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Sample records for antigen-1 ama-1 administered

  1. In Vitro Studies with Recombinant Plasmodium falciparum Apical Membrane Antigen 1 (AMA1): Production and Activity of an AMA1 Vaccine and Generation of a Multiallelic Response

    PubMed Central

    Kennedy, Michael C.; Wang, Jin; Zhang, Yanling; Miles, Aaron P.; Chitsaz, Farideh; Saul, Allan; Long, Carole A.; Miller, Louis H.; Stowers, Anthony W.

    2002-01-01

    Apical membrane antigen 1 (AMA1) is regarded as a leading malaria blood-stage vaccine candidate. While the overall structure of AMA1 is conserved in Plasmodium spp., numerous AMA1 allelic variants of P. falciparum have been described. The effect of AMA1 allelic diversity on the ability of a recombinant AMA1 vaccine to protect against human infection by different P. falciparum strains is unknown. We characterize two allelic forms of AMA1 that were both produced in Pichia pastoris at a sufficient economy of scale to be usable for clinical vaccine studies. Both proteins were used to immunize rabbits, singly and in combination, in order to evaluate their immunogenicity and the ability of elicited antibodies to block the growth of different P. falciparum clones. Both antigens, when used alone, elicited high homologous anti-AMA1 titers, with reduced strain cross-reactivity. Similarly, sera from rabbits immunized with a single antigen were capable of blocking the growth of homologous parasite strains at levels theoretically sufficient to clear parasite infections. However, heterologous inhibition was significantly reduced, providing experimental evidence that AMA1 allelic diversity is a result of immune pressure. Encouragingly, rabbits immunized with a combination of both antigens exhibited titers and levels of parasite inhibition as good as those of the single-antigen-immunized rabbits for each of the homologous parasite lines, and consequently exhibited a broadening of allelic diversity coverage. PMID:12438374

  2. Identification of a Highly Antigenic Linear B Cell Epitope within Plasmodium vivax Apical Membrane Antigen 1 (AMA-1)

    PubMed Central

    Bueno, Lilian Lacerda; Lobo, Francisco Pereira; Morais, Cristiane Guimarães; Mourão, Luíza Carvalho; de Ávila, Ricardo Andrez Machado; Soares, Irene Silva; Fontes, Cor Jesus; Lacerda, Marcus Vinícius; Olórtegui, Carlos Chavez; Bartholomeu, Daniella Castanheira; Fujiwara, Ricardo Toshio; Braga, Érika Martins

    2011-01-01

    Apical membrane antigen 1 (AMA-1) is considered to be a major candidate antigen for a malaria vaccine. Previous immunoepidemiological studies of naturally acquired immunity to Plasmodium vivax AMA-1 (PvAMA-1) have shown a higher prevalence of specific antibodies to domain II (DII) of AMA-1. In the present study, we confirmed that specific antibody responses from naturally infected individuals were highly reactive to both full-length AMA-1 and DII. Also, we demonstrated a strong association between AMA-1 and DII IgG and IgG subclass responses. We analyzed the primary sequence of PvAMA-1 for B cell linear epitopes co-occurring with intrinsically unstructured/disordered regions (IURs). The B cell epitope comprising the amino acid sequence 290–307 of PvAMA-1 (SASDQPTQYEEEMTDYQK), with the highest prediction scores, was identified in domain II and further selected for chemical synthesis and immunological testing. The antigenicity of the synthetic peptide was identified by serological analysis using sera from P. vivax-infected individuals who were knowingly reactive to the PvAMA-1 ectodomain only, domain II only, or reactive to both antigens. Although the synthetic peptide was recognized by all serum samples specific to domain II, serum with reactivity only to the full-length protein presented 58.3% positivity. Moreover, IgG reactivity against PvAMA-1 and domain II after depletion of specific synthetic peptide antibodies was reduced by 18% and 33% (P = 0.0001 for both), respectively. These results suggest that the linear epitope SASDQPTQYEEEMTDYQK is highly antigenic during natural human infections and is an important antigenic region of the domain II of PvAMA-1, suggesting its possible future use in pre-clinical studies. PMID:21713006

  3. Polymorphism in the gene encoding the apical membrane antigen-1 (AMA-1) of Plasmodium falciparum. X. Asembo Bay Cohort Project.

    PubMed

    Escalante, A A; Grebert, H M; Chaiyaroj, S C; Magris, M; Biswas, S; Nahlen, B L; Lal, A A

    2001-04-01

    We have investigated the genetic diversity of the gene encoding the apical membrane antigen-1 (AMA-1) in natural populations of Plasmodium falciparum from western Kenya and compared it with parasite populations from other geographic regions. A total of 28 complete sequences from Kenya, Thailand, India, and Venezuela field isolates were obtained. The genetic polymorphism is not evenly distributed across the gene, which is in agreement with the pattern reported in earlier studies. The alleles from Kenya exhibit 20 and 30% more polymorphism than that found in Southeast Asia and Venezuelan alleles, respectively. Based on the gene genealogies derived from sequencing data, no evidence for allele families was found. We have found evidence supporting limited gene flow between the parasite populations, specifically, between the Southeast Asian and Venezuelan isolates; however, no alleles could be linked to a specific geographic region. This study reveals that positive natural selection is an important factor in the maintenance of genetic diversity for AMA-1. We did not find conclusive evidence indicating intragenic recombination is important in the generation of the AMA-1 allelic diversity. The study provides information on the genetic diversity of the AMA-1 gene that would be useful in vaccine development and testing, as well as in assessing factors that are involved in the generation and maintenance of the genetic diversity in P. falciparum. PMID:11295182

  4. Babesia divergens apical membrane antigen-1 (BdAMA-1): A poorly polymorphic protein that induces a weak and late immune response.

    PubMed

    Moreau, E; Bonsergent, C; Al Dybiat, I; Gonzalez, L M; Lobo, C A; Montero, E; Malandrin, L

    2015-08-01

    Babesiosis is an important veterinary and zoonotic tick borne disease caused by the hemoprotozoan Babesia spp. which infects red blood cell of its vertebrate host. In order to control the infection, vaccination that targets molecules involved in the invasion process of red blood cells could provide a good alternative to chemotherapy. Among these molecules, Apical Membrane Antigen-1 (AMA-1) has been described as an excellent vaccine candidate in Plasmodium spp. In this paper, we have investigated AMA-1 of Babesia divergens (BdAMA-1) as vaccine candidate by evaluating its polymorphism and by studying the humoral response against BdAMA-1 of sheep experimentally infected with B. divergens. Polymorphism of BdAMA-1 was investigated by sequencing the corresponding gene of 9 B. divergens isolates from different geographical areas in France. Two Bdama-1 haplotypes (A and B) could be defined based on 2 non-synonymous point mutations. In silico prediction of linear epitopes revealed that the antigenicity of the 2 haplotypes is very similar. Antibody production against the extracellular domain of BdAMA-1 is weak and late, between 1 and 5 months after the inoculation of parasites. Both IgG1 and IgG2 are components of the anti-BdAMA-1 response. These results indicate that while BdAMA-1 may not be an immuno-dominant antigen, it could induce a mixed type 1 and type 2 immune response. In light of these results, the potential of BdAMA-1 as vaccine candidate is discussed. PMID:25956948

  5. An Extended Surface Loop on Toxoplasma gondii Apical Membrane Antigen 1 (AMA1) Governs Ligand Binding Selectivity

    PubMed Central

    Parker, Michelle L.; Boulanger, Martin J.

    2015-01-01

    Apicomplexan parasites are the causative agents of globally prevalent diseases including malaria and toxoplasmosis. These obligate intracellular pathogens have evolved a sophisticated host cell invasion strategy that relies on a parasite-host cell junction anchored by interactions between apical membrane antigens (AMAs) on the parasite surface and rhoptry neck 2 (RON2) proteins discharged from the parasite and embedded in the host cell membrane. Key to formation of the AMA1-RON2 complex is displacement of an extended surface loop on AMA1 called the DII loop. While conformational flexibility of the DII loop is required to expose the mature RON2 binding groove, a definitive role of this substructure has not been elucidated. To establish a role of the DII loop in Toxoplasma gondii AMA1, we engineered a form of the protein where the mobile portion of the loop was replaced with a short Gly-Ser linker (TgAMA1ΔDIIloop). Isothermal titration calorimetry measurements with a panel of RON2 peptides revealed an influential role for the DII loop in governing selectivity. Most notably, an Eimeria tenella RON2 (EtRON2) peptide that showed only weak binding to TgAMA1 bound with high affinity to TgAMA1ΔDIIloop. To define the molecular basis for the differential binding, we determined the crystal structure of TgAMA1ΔDIIloop in complex with the EtRON2 peptide. When analyzed in the context of existing AMA1-RON2 structures, spatially distinct anchor points in the AMA1 groove were identified that, when engaged, appear to provide the necessary traction to outcompete the DII loop. Collectively, these data support a model where the AMA1 DII loop serves as a structural gatekeeper to selectively filter out ligands otherwise capable of binding with high affinity in the AMA1 apical groove. These data also highlight the importance of considering the functional implications of the DII loop in the ongoing development of therapeutic intervention strategies targeting the AMA1-RON2 invasion

  6. Multilevel Precision-Based Rational Design of Chemical Inhibitors Targeting the Hydrophobic Cleft of Toxoplasma gondii Apical Membrane Antigen 1 (AMA1)

    PubMed Central

    Muralikumar, Shalini; Mahalakshmi, B; Lily Therese, K; Madhavan, HN; Alameen, Mohamed; Thirumudi, Indhuja

    2016-01-01

    Toxoplasma gondii is an intracellular Apicomplexan parasite and a causative agent of toxoplasmosis in human. It causes encephalitis, uveitis, chorioretinitis, and congenital infection. T. gondii invades the host cell by forming a moving junction (MJ) complex. This complex formation is initiated by intermolecular interactions between the two secretory parasitic proteins—namely, apical membrane antigen 1 (AMA1) and rhoptry neck protein 2 (RON2) and is critically essential for the host invasion process. By this study, we propose two potential leads, NSC95522 and NSC179676 that can efficiently target the AMA1 hydrophobic cleft, which is a hotspot for targeting MJ complex formation. The proposed leads are the result of an exhaustive conformational search-based virtual screen with multilevel precision scoring of the docking affinities. These two compounds surpassed all the precision levels of docking and also the stringent post docking and cumulative molecular dynamics evaluations. Moreover, the backbone flexibility of hotspot residues in the hydrophobic cleft, which has been previously reported to be essential for accommodative binding of RON2 to AMA1, was also highly perturbed by these compounds. Furthermore, binding free energy calculations of these two compounds also revealed a significant affinity to AMA1. Machine learning approaches also predicted these two compounds to possess more relevant activities. Hence, these two leads, NSC95522 and NSC179676, may prove to be potential inhibitors targeting AMA1-RON2 complex formation towards combating toxoplasmosis. PMID:27445648

  7. Multilevel Precision-Based Rational Design of Chemical Inhibitors Targeting the Hydrophobic Cleft of Toxoplasma gondii Apical Membrane Antigen 1 (AMA1).

    PubMed

    Vetrivel, Umashankar; Muralikumar, Shalini; Mahalakshmi, B; Lily Therese, K; Madhavan, H N; Alameen, Mohamed; Thirumudi, Indhuja

    2016-06-01

    Toxoplasma gondii is an intracellular Apicomplexan parasite and a causative agent of toxoplasmosis in human. It causes encephalitis, uveitis, chorioretinitis, and congenital infection. T. gondii invades the host cell by forming a moving junction (MJ) complex. This complex formation is initiated by intermolecular interactions between the two secretory parasitic proteins-namely, apical membrane antigen 1 (AMA1) and rhoptry neck protein 2 (RON2) and is critically essential for the host invasion process. By this study, we propose two potential leads, NSC95522 and NSC179676 that can efficiently target the AMA1 hydrophobic cleft, which is a hotspot for targeting MJ complex formation. The proposed leads are the result of an exhaustive conformational search-based virtual screen with multilevel precision scoring of the docking affinities. These two compounds surpassed all the precision levels of docking and also the stringent post docking and cumulative molecular dynamics evaluations. Moreover, the backbone flexibility of hotspot residues in the hydrophobic cleft, which has been previously reported to be essential for accommodative binding of RON2 to AMA1, was also highly perturbed by these compounds. Furthermore, binding free energy calculations of these two compounds also revealed a significant affinity to AMA1. Machine learning approaches also predicted these two compounds to possess more relevant activities. Hence, these two leads, NSC95522 and NSC179676, may prove to be potential inhibitors targeting AMA1-RON2 complex formation towards combating toxoplasmosis. PMID:27445648

  8. Vaccination with Plasmodium knowlesi AMA1 formulated in the novel adjuvant co-vaccine HT™ protects against blood-stage challenge in rhesus macaques.

    PubMed

    Mahdi Abdel Hamid, Muzamil; Remarque, Edmond J; van Duivenvoorde, Leonie M; van der Werff, Nicole; Walraven, Vanessa; Faber, Bart W; Kocken, Clemens H M; Thomas, Alan W

    2011-01-01

    Plasmodium falciparum apical membrane antigen 1 (PfAMA1) is a leading blood stage vaccine candidate. Plasmodium knowlesi AMA1 (PkAMA1) was produced and purified using similar methodology as for clinical grade PfAMA1 yielding a pure, conformational intact protein. Combined with the adjuvant CoVaccine HT™, PkAMA1 was found to be highly immunogenic in rabbits and the efficacy of the PkAMA1 was subsequently tested in a rhesus macaque blood-stage challenge model. Six rhesus monkeys were vaccinated with PkAMA1 and a control group of 6 were vaccinated with PfAMA1. A total of 50 µg AMA1 was administered intramuscularly three times at 4 week intervals. One of six rhesus monkeys vaccinated with PkAMA1 was able to control parasitaemia, upon blood stage challenge with P. knowlesi H-strain. Four out of the remaining five showed a delay in parasite onset that correlated with functional antibody titres. In the PfAMA1 vaccinated control group, five out of six animals had to be treated with antimalarials 8 days after challenge; one animal did not become patent during the challenge period. Following a rest period, animals were boosted and challenged again. Four of the six rhesus monkeys vaccinated with PkAMA1 were able to control the parasitaemia, one had a delayed onset of parasitaemia and one animal was not protected, while all control animals required treatment. To confirm that the control of parasitaemia was AMA1-related, animals were allowed to recover, boosted and re-challenged with P. knowlesi Nuri strain. All control animals had to be treated with antimalarials by day 8, while five out of six PkAMA1 vaccinated animals were able to control parasitaemia. This study shows that: i) Yeast-expressed PkAMA1 can protect against blood stage challenge; ii) Functional antibody levels as measured by GIA correlated inversely with the day of onset and iii) GIA IC(50) values correlated with estimated in vivo growth rates. PMID:21655233

  9. A comparative study of natural immune responses against Plasmodium vivax C-terminal merozoite surface protein-1 (PvMSP-1) and apical membrane antigen-1 (PvAMA-1) in two endemic settings

    PubMed Central

    Xia, Hui; Fang, Qiang; Jangpatarapongsa, Kulachart; Zhiyong, Tao; Cui, Liwang; Li, Baiqing; Udomsangpetch, Rachanee

    2015-01-01

    The mechanisms of cellular and humoral immune responses against P. vivax parasite remain poorly understood. Several malaria immunological studies have been conducted in endemic regions where both P. falciparum and P. vivax parasites co-exist. In this study, a comparative analysis of immunity to Plasmodium vivax antigens in different geography and incidence of Plasmodium spp. infection was performed. We characterised antibodies against two P. vivax antigens, PvMSP-1 and PvAMA-1, and the cross-reactivity between these antigens using plasma from acute malaria infected patients living in the central region of China and in the western border of Thailand. P. vivax endemicity is found in central China whereas both P. vivax and P. falciparum are endemic in Thailand. There was an increased level of anti-PvMSP-1/anti-PvAMA-1 in both populations. An elevated level of antibodies to total P. vivax proteins and low level of antibodies to total P. falciparum proteins was found in acute P. vivax infected Chinese, suggesting antibody cross-reactivity between the two species. P. vivax infected Thai patients had both anti-P. vivax and anti-P. falciparum antibodies as expected since both species are present in Thailand. More information on humoral and cell mediated immunity during acute P. vivax-infection in the area where only single P. vivax species existed is of great interest in the relation of building up anti-disease severity caused by P. falciparum. This knowledge will support vaccine development in the future. PMID:26713085

  10. Identification and localization of minimal MHC-restricted CD8+ T cell epitopes within the Plasmodium falciparum AMA1 protein

    PubMed Central

    2010-01-01

    Background Plasmodium falciparum apical membrane antigen-1 (AMA1) is a leading malaria vaccine candidate antigen that is expressed by sporozoite, liver and blood stage parasites. Since CD8+ T cell responses have been implicated in protection against pre-erythrocytic stage malaria, this study was designed to identify MHC class I-restricted epitopes within AMA1. Methods A recombinant adenovirus serotype 5 vector expressing P. falciparum AMA1 was highly immunogenic when administered to healthy, malaria-naive adult volunteers as determined by IFN-γ ELISpot responses to peptide pools containing overlapping 15-mer peptides spanning full-length AMA1. Computerized algorithms (NetMHC software) were used to predict minimal MHC-restricted 8-10-mer epitope sequences within AMA1 15-mer peptides active in ELISpot. A subset of epitopes was synthesized and tested for induction of CD8+ T cell IFN-γ responses by ELISpot depletion and ICS assays. A 3-dimensional model combining Domains I + II of P. falciparum AMA1 and Domain III of P. vivax AMA1 was used to map these epitopes. Results Fourteen 8-10-mer epitopes were predicted to bind to HLA supertypes A01 (3 epitopes), A02 (4 epitopes), B08 (2 epitopes) and B44 (5 epitopes). Nine of the 14 predicted epitopes were recognized in ELISpot or ELISpot and ICS assays by one or more volunteers. Depletion of T cell subsets confirmed that these epitopes were CD8+ T cell-dependent. A mixture of the 14 minimal epitopes was capable of recalling CD8+ T cell IFN-γ responses from PBMC of immunized volunteers. Thirteen of the 14 predicted epitopes were polymorphic and the majority localized to the more conserved front surface of the AMA1 model structure. Conclusions This study predicted 14 and confirmed nine MHC class I-restricted CD8+ T cell epitopes on AMA1 recognized in the context of seven HLA alleles. These HLA alleles belong to four HLA supertypes that have a phenotypic frequency between 23% - 100% in different human populations. PMID

  11. ChAd63-MVA–vectored Blood-stage Malaria Vaccines Targeting MSP1 and AMA1: Assessment of Efficacy Against Mosquito Bite Challenge in Humans

    PubMed Central

    Sheehy, Susanne H; Duncan, Christopher JA; Elias, Sean C; Choudhary, Prateek; Biswas, Sumi; Halstead, Fenella D; Collins, Katharine A; Edwards, Nick J; Douglas, Alexander D; Anagnostou, Nicholas A; Ewer, Katie J; Havelock, Tom; Mahungu, Tabitha; Bliss, Carly M; Miura, Kazutoyo; Poulton, Ian D; Lillie, Patrick J; Antrobus, Richard D; Berrie, Eleanor; Moyle, Sarah; Gantlett, Katherine; Colloca, Stefano; Cortese, Riccardo; Long, Carole A; Sinden, Robert E; Gilbert, Sarah C; Lawrie, Alison M; Doherty, Tom; Faust, Saul N; Nicosia, Alfredo; Hill, Adrian VS; Draper, Simon J

    2012-01-01

    The induction of cellular immunity, in conjunction with antibodies, may be essential for vaccines to protect against blood-stage infection with the human malaria parasite Plasmodium falciparum. We have shown that prime-boost delivery of P. falciparum blood-stage antigens by chimpanzee adenovirus 63 (ChAd63) followed by the attenuated orthopoxvirus MVA is safe and immunogenic in healthy adults. Here, we report on vaccine efficacy against controlled human malaria infection delivered by mosquito bites. The blood-stage malaria vaccines were administered alone, or together (MSP1+AMA1), or with a pre-erythrocytic malaria vaccine candidate (MSP1+ME-TRAP). In this first human use of coadministered ChAd63-MVA regimes, we demonstrate immune interference whereby responses against merozoite surface protein 1 (MSP1) are dominant over apical membrane antigen 1 (AMA1) and ME-TRAP. We also show that induction of strong cellular immunity against MSP1 and AMA1 is safe, but does not impact on parasite growth rates in the blood. In a subset of vaccinated volunteers, a delay in time to diagnosis was observed and sterilizing protection was observed in one volunteer coimmunized with MSP1+AMA1—results consistent with vaccine-induced pre-erythrocytic, rather than blood-stage, immunity. These data call into question the utility of T cell-inducing blood-stage malaria vaccines and suggest that the focus should remain on high-titer antibody induction against susceptible antigen targets. PMID:23089736

  12. Structure of the Malaria Antigen AMA1 in Complex with a Growth-Inhibitory Antibody

    PubMed Central

    Bai, Tao; Kim, Hanna; Anders, Robin F; Foley, Michael; Batchelor, Adrian H

    2007-01-01

    Identifying functionally critical regions of the malaria antigen AMA1 (apical membrane antigen 1) is necessary to understand the significance of the polymorphisms within this antigen for vaccine development. The crystal structure of AMA1 in complex with the Fab fragment of inhibitory monoclonal antibody 1F9 reveals that 1F9 binds to the AMA1 solvent-exposed hydrophobic trough, confirming its importance. 1F9 uses the heavy and light chain complementarity-determining regions (CDRs) to wrap around the polymorphic loops adjacent to the trough, but uses a ridge of framework residues to bind to the hydrophobic trough. The resulting 1F9-AMA1–combined buried surface of 2,470 Å2 is considerably larger than previously reported Fab–antigen interfaces. Mutations of polymorphic AMA1 residues within the 1F9 epitope disrupt 1F9 binding and dramatically reduce the binding of affinity-purified human antibodies. Moreover, 1F9 binding to AMA1 is competed by naturally acquired human antibodies, confirming that the 1F9 epitope is a frequent target of immunological attack. PMID:17907804

  13. Functional Analysis of the Leading Malaria Vaccine Candidate AMA-1 Reveals an Essential Role for the Cytoplasmic Domain in the Invasion Process

    PubMed Central

    Treeck, Moritz; Zacherl, Sonja; Herrmann, Susann; Cabrera, Ana; Kono, Maya; Struck, Nicole S.; Engelberg, Klemens; Haase, Silvia; Frischknecht, Friedrich; Miura, Kota; Spielmann, Tobias; Gilberger, Tim W.

    2009-01-01

    A key process in the lifecycle of the malaria parasite Plasmodium falciparum is the fast invasion of human erythrocytes. Entry into the host cell requires the apical membrane antigen 1 (AMA-1), a type I transmembrane protein located in the micronemes of the merozoite. Although AMA-1 is evolving into the leading blood-stage malaria vaccine candidate, its precise role in invasion is still unclear. We investigate AMA-1 function using live video microscopy in the absence and presence of an AMA-1 inhibitory peptide. This data reveals a crucial function of AMA-1 during the primary contact period upstream of the entry process at around the time of moving junction formation. We generate a Plasmodium falciparum cell line that expresses a functional GFP-tagged AMA-1. This allows the visualization of the dynamics of AMA-1 in live parasites. We functionally validate the ectopically expressed AMA-1 by establishing a complementation assay based on strain-specific inhibition. This method provides the basis for the functional analysis of essential genes that are refractory to any genetic manipulation. Using the complementation assay, we show that the cytoplasmic domain of AMA-1 is not required for correct trafficking and surface translocation but is essential for AMA-1 function. Although this function can be mimicked by the highly conserved cytoplasmic domains of P. vivax and P. berghei, the exchange with the heterologous domain of the microneme protein EBA-175 or the rhoptry protein Rh2b leads to a loss of function. We identify several residues in the cytoplasmic tail that are essential for AMA-1 function. We validate this data using additional transgenic parasite lines expressing AMA-1 mutants with TY1 epitopes. We show that the cytoplasmic domain of AMA-1 is phosphorylated. Mutational analysis suggests an important role for the phosphorylation in the invasion process, which might translate into novel therapeutic strategies. PMID:19283086

  14. Human adenovirus 5-vectored Plasmodium falciparum NMRC-M3V-Ad-PfCA vaccine encoding CSP and AMA1 is safe, well-tolerated and immunogenic but does not protect against controlled human malaria infection

    PubMed Central

    Tamminga, Cindy; Sedegah, Martha; Maiolatesi, Santina; Fedders, Charlotte; Reyes, Sharina; Reyes, Anatalio; Vasquez, Carlos; Alcorta, Yolanda; Chuang, Ilin; Spring, Michele; Kavanaugh, Michael; Ganeshan, Harini; Huang, Jun; Belmonte, Maria; Abot, Esteban; Belmonte, Arnel; Banania, JoGlenna; Farooq, Fouzia; Murphy, Jittawadee; Komisar, Jack; Richie, Nancy O; Bennett, Jason; Limbach, Keith; Patterson, Noelle B; Bruder, Joseph T; Shi, Meng; Miller, Edward; Dutta, Sheetij; Diggs, Carter; Soisson, Lorraine A; Hollingdale, Michael R; Epstein, Judith E; Richie, Thomas L

    2013-01-01

    Background: In a prior study, a DNA prime / adenovirus boost vaccine (DNA/Ad) expressing P. falciparum circumsporozoite protein (CSP) and apical membrane antigen-1 (AMA1) (NMRC-M3V-D/Ad-PfCA Vaccine) induced 27% protection against controlled human malaria infection (CHMI). To investigate the contribution of DNA priming, we tested the efficacy of adenovirus vaccine alone (NMRC-M3V-Ad-PfCA ) in a Phase 1 clinical trial. Methodology/Principal Findings: The regimen was a single intramuscular injection with two non-replicating human serotype 5 adenovectors encoding CSP and AMA1, respectively. One x 1010 particle units of each construct were combined prior to administration. The regimen was safe and well-tolerated. Four weeks later, 18 study subjects received P. falciparum CHMI administered by mosquito bite. None were fully protected although one showed delayed onset of parasitemia. Antibody responses were low, with geometric mean CSP ELISA titer of 381 (range < 50–1626) and AMA1 ELISA of 4.95 µg/mL (range 0.2–38). Summed ex vivo IFN-γ ELISpot responses to overlapping peptides were robust, with geometric mean spot forming cells/million peripheral blood mononuclear cells [sfc/m] for CSP of 273 (range 38–2550) and for AMA1 of 1303 (range 435–4594). CD4+ and CD8+ T cell IFN-γ responses to CSP were positive by flow cytometry in 25% and 56% of the research subjects, respectively, and to AMA1 in 94% and 100%, respectively. Significance: In contrast to DNA/Ad, Ad alone did not protect against CHMI despite inducing broad, cell-mediated immunity, indicating that DNA priming is required for protection by the adenovirus-vectored vaccine. ClinicalTrials.gov Identifier: NCT00392015. PMID:23899517

  15. AMA1-Deficient Toxoplasma gondii Parasites Transiently Colonize Mice and Trigger an Innate Immune Response That Leads to Long-Lasting Protective Immunity

    PubMed Central

    Lagal, Vanessa; Dinis, Márcia; Cannella, Dominique; Bargieri, Daniel; Gonzalez, Virginie; Andenmatten, Nicole; Meissner, Markus

    2015-01-01

    The apical membrane antigen 1 (AMA1) protein was believed to be essential for the perpetuation of two Apicomplexa parasite genera, Plasmodium and Toxoplasma, until we genetically engineered viable parasites lacking AMA1. The reduction in invasiveness of the Toxoplasma gondii RH-AMA1 knockout (RH-AMA1KO) tachyzoite population, in vitro, raised key questions about the outcome associated with these tachyzoites once inoculated in the peritoneal cavity of mice. In this study, we used AMNIS technology to simultaneously quantify and image the parasitic process driven by AMA1KO tachyzoites. We report their ability to colonize and multiply in mesothelial cells and in both resident and recruited leukocytes. While the RH-AMA1KO population amplification is rapidly lethal in immunocompromised mice, it is controlled in immunocompetent hosts, where immune cells in combination sense parasites and secrete proinflammatory cytokines. This innate response further leads to a long-lasting status immunoprotective against a secondary challenge by high inocula of the homologous type I or a distinct type II T. gondii genotypes. While AMA1 is definitively not an essential protein for tachyzoite entry and multiplication in host cells, it clearly assists the expansion of parasite population in vivo. PMID:25847964

  16. Stability of the Plasmodium falciparum AMA1-RON2 Complex Is Governed by the Domain II (DII) Loop

    PubMed Central

    Delgadillo, Roberto F.; Parker, Michelle L.; Lebrun, Maryse; Boulanger, Martin J.; Douguet, Dominique

    2016-01-01

    Plasmodium falciparum is an obligate intracellular protozoan parasite that employs a highly sophisticated mechanism to access the protective environment of the host cells. Key to this mechanism is the formation of an electron dense ring at the parasite-host cell interface called the Moving Junction (MJ) through which the parasite invades. The MJ incorporates two key parasite components: the surface protein Apical Membrane Antigen 1 (AMA1) and its receptor, the Rhoptry Neck Protein (RON) complex, the latter one being targeted to the host cell membrane during invasion. Crystal structures of AMA1 have shown that a partially mobile loop, termed the DII loop, forms part of a deep groove in domain I and overlaps with the RON2 binding site. To investigate the mechanism by which the DII loop influences RON2 binding, we measured the kinetics of association and dissociation and binding equilibria of a PfRON2sp1 peptide with both PfAMA1 and an engineered form of PfAMA1 where the flexible region of the DII loop was replaced by a short Gly-Ser linker (ΔDII-PfAMA1). The reactions were tracked by fluorescence anisotropy as a function of temperature and concentration and globally fitted to acquire the rate constants and corresponding thermodynamic profiles. Our results indicate that both PfAMA1 constructs bound to the PfRON2sp1 peptide with the formation of one intermediate in a sequential reversible reaction: A↔B↔C. Consistent with Isothermal Titration Calorimetry measurements, final complex formation was enthalpically driven and slightly entropically unfavorable. Importantly, our experimental data shows that the DII loop lengthened the complex half-life time by 18-fold (900 s and 48 s at 25°C for Pf and ΔDII-Pf complex, respectively). The longer half-life of the Pf complex appeared to be driven by a slower dissociation process. These data highlight a new influential role for the DII loop in kinetically locking the functional binary complex to enable host cell invasion

  17. Detailed functional characterization of glycosylated and nonglycosylated variants of malaria vaccine candidate PfAMA1 produced in Nicotiana benthamiana and analysis of growth inhibitory responses in rabbits.

    PubMed

    Boes, Alexander; Spiegel, Holger; Edgue, Gueven; Kapelski, Stephanie; Scheuermayer, Matthias; Fendel, Rolf; Remarque, Edmond; Altmann, Friedrich; Maresch, Daniel; Reimann, Andreas; Pradel, Gabriele; Schillberg, Stefan; Fischer, Rainer

    2015-02-01

    One of the most promising malaria vaccine candidate antigens is the Plasmodium falciparum apical membrane antigen 1 (PfAMA1). Several studies have shown that this blood-stage antigen can induce strong parasite growth inhibitory antibody responses. PfAMA1 contains up to six recognition sites for N-linked glycosylation, a post-translational modification that is absent in P. falciparum. To prevent any potential negative impact of N-glycosylation, the recognition sites have been knocked out in most PfAMA1 variants expressed in eukaryotic hosts. However, N-linked glycosylation may increase efficacy by improving immunogenicity and/or focusing the response towards relevant epitopes by glycan masking. We describe the production of glycosylated and nonglycosylated PfAMA1 in Nicotiana benthamiana and its detailed characterization in terms of yield, integrity and protective efficacy. Both PfAMA1 variants accumulated to high levels (>510 μg/g fresh leaf weight) after transient expression, and high-mannose-type N-glycans were confirmed for the glycosylated variant. No significant differences between the N. benthamiana and Pichia pastoris PfAMA1 variants were detected in conformation-sensitive ligand-binding studies. Specific titres of >2 × 10(6) were induced in rabbits, and strong reactivity with P. falciparum schizonts was observed in immunofluorescence assays, as well as up to 100% parasite growth inhibition for both variants, with IC₅₀ values of ~35 μg/mL. Competition assays indicated that a number of epitopes were shielded from immune recognition by N-glycans, warranting further studies to determine how glycosylation can be used for the directed targeting of immune responses. These results highlight the potential of plant transient expression systems as a production platform for vaccine candidates. PMID:25236489

  18. Adenovirus 5-Vectored P. falciparum Vaccine Expressing CSP and AMA1. Part A: Safety and Immunogenicity in Seronegative Adults

    PubMed Central

    Sedegah, Martha; Tamminga, Cindy; McGrath, Shannon; House, Brent; Ganeshan, Harini; Lejano, Jennylynn; Abot, Esteban; Banania, Glenna J.; Sayo, Renato; Farooq, Fouzia; Belmonte, Maria; Manohar, Nalini; Richie, Nancy O.; Wood, Chloe; Long, Carole A.; Regis, David; Williams, Francis T.; Shi, Meng; Chuang, Ilin; Spring, Michele; Epstein, Judith E.; Mendoza-Silveiras, Jose; Limbach, Keith; Patterson, Noelle B.; Bruder, Joseph T.; Doolan, Denise L.; King, C. Richter; Soisson, Lorraine; Diggs, Carter; Carucci, Daniel; Dutta, Sheetij; Hollingdale, Michael R.; Ockenhouse, Christian F.; Richie, Thomas L.

    2011-01-01

    Background Models of immunity to malaria indicate the importance of CD8+ T cell responses for targeting intrahepatic stages and antibodies for targeting sporozoite and blood stages. We designed a multistage adenovirus 5 (Ad5)-vectored Plasmodium falciparum malaria vaccine, aiming to induce both types of responses in humans, that was tested for safety and immunogenicity in a Phase 1 dose escalation trial in Ad5-seronegative volunteers. Methodology/Principal Findings The NMRC-M3V-Ad-PfCA vaccine combines two adenovectors encoding circumsporozoite protein (CSP) and apical membrane antigen-1 (AMA1). Group 1 (n = 6) healthy volunteers received one intramuscular injection of 2×10∧10 particle units (1×10∧10 each construct) and Group 2 (n = 6) a five-fold higher dose. Transient, mild to moderate adverse events were more pronounced with the higher dose. ELISpot responses to CSP and AMA1 peaked at 1 month, were higher in the low dose (geomean CSP = 422, AMA1 = 862 spot forming cells/million) than in the high dose (CSP = 154, p = 0.049, AMA1 = 423, p = 0.045) group and were still positive at 12 months in a number of volunteers. ELISpot depletion assays identified dependence on CD4+ or on both CD4+ and CD8+ T cells, with few responses dependent only on CD8+ T cells. Intracellular cytokine staining detected stronger CD8+ than CD4+ T cell IFN-γ responses (CSP p = 0.0001, AMA1 p = 0.003), but similar frequencies of multifunctional CD4+ and CD8+ T cells secreting two or more of IFN-γ, TNF-α or IL-2. Median fluorescence intensities were 7–10 fold higher in triple than single secreting cells. Antibody responses were low but trended higher in the high dose group and did not inhibit growth of cultured P. falciparum blood stage parasites. Significance As found in other trials, adenovectored vaccines appeared safe and well-tolerated at doses up to 1×10∧11 particle units. This is the first demonstration in humans of a malaria vaccine

  19. Low Levels of Polymorphisms and No Evidence for Diversifying Selection on the Plasmodium knowlesi Apical Membrane Antigen 1 Gene

    PubMed Central

    Faber, Bart W.; Abdul Kadir, Khamisah; Rodriguez-Garcia, Roberto; Remarque, Edmond J; Saul, Frederick A.; Vulliez-Le Normand, Brigitte; Bentley, Graham A.; Kocken, Clemens H. M.; Singh, Balbir

    2015-01-01

    Infection with Plasmodium knowlesi, a zoonotic primate malaria, is a growing human health problem in Southeast Asia. P. knowlesi is being used in malaria vaccine studies, and a number of proteins are being considered as candidate malaria vaccine antigens, including the Apical Membrane Antigen 1 (AMA1). In order to determine genetic diversity of the ama1 gene and to identify epitopes of AMA1 under strongest immune selection, the ama1 gene of 52 P. knowlesi isolates derived from human infections was sequenced. Sequence analysis of isolates from two geographically isolated regions in Sarawak showed that polymorphism in the protein is low compared to that of AMA1 of the major human malaria parasites, P. falciparum and P. vivax. Although the number of haplotypes was 27, the frequency of mutations at the majority of the polymorphic positions was low, and only six positions had a variance frequency higher than 10%. Only two positions had more than one alternative amino acid. Interestingly, three of the high-frequency polymorphic sites correspond to invariant sites in PfAMA1 or PvAMA1. Statistically significant differences in the quantity of three of the six high frequency mutations were observed between the two regions. These analyses suggest that the pkama1 gene is not under balancing selection, as observed for pfama1 and pvama1, and that the PkAMA1 protein is not a primary target for protective humoral immune responses in their reservoir macaque hosts, unlike PfAMA1 and PvAMA1 in humans. The low level of polymorphism justifies the development of a single allele PkAMA1-based vaccine. PMID:25881166

  20. DNA Prime/Adenovirus Boost Malaria Vaccine Encoding P. falciparum CSP and AMA1 Induces Sterile Protection Associated with Cell-Mediated Immunity

    PubMed Central

    Chuang, Ilin; Sedegah, Martha; Cicatelli, Susan; Spring, Michele; Polhemus, Mark; Tamminga, Cindy; Patterson, Noelle; Guerrero, Melanie; Bennett, Jason W.; McGrath, Shannon; Ganeshan, Harini; Belmonte, Maria; Farooq, Fouzia; Abot, Esteban; Banania, Jo Glenna; Huang, Jun; Newcomer, Rhonda; Rein, Lisa; Litilit, Dianne; Richie, Nancy O.; Wood, Chloe; Murphy, Jittawadee; Sauerwein, Robert; Hermsen, Cornelus C.; McCoy, Andrea J.; Kamau, Edwin; Cummings, James; Komisar, Jack; Sutamihardja, Awalludin; Shi, Meng; Epstein, Judith E.; Maiolatesi, Santina; Tosh, Donna; Limbach, Keith; Angov, Evelina; Bergmann-Leitner, Elke; Bruder, Joseph T.; Doolan, Denise L.; King, C. Richter; Carucci, Daniel; Dutta, Sheetij; Soisson, Lorraine; Diggs, Carter; Hollingdale, Michael R.; Ockenhouse, Christian F.; Richie, Thomas L.

    2013-01-01

    Background Gene-based vaccination using prime/boost regimens protects animals and humans against malaria, inducing cell-mediated responses that in animal models target liver stage malaria parasites. We tested a DNA prime/adenovirus boost malaria vaccine in a Phase 1 clinical trial with controlled human malaria infection. Methodology/Principal Findings The vaccine regimen was three monthly doses of two DNA plasmids (DNA) followed four months later by a single boost with two non-replicating human serotype 5 adenovirus vectors (Ad). The constructs encoded genes expressing P. falciparum circumsporozoite protein (CSP) and apical membrane antigen-1 (AMA1). The regimen was safe and well-tolerated, with mostly mild adverse events that occurred at the site of injection. Only one AE (diarrhea), possibly related to immunization, was severe (Grade 3), preventing daily activities. Four weeks after the Ad boost, 15 study subjects were challenged with P. falciparum sporozoites by mosquito bite, and four (27%) were sterilely protected. Antibody responses by ELISA rose after Ad boost but were low (CSP geometric mean titer 210, range 44–817; AMA1 geometric mean micrograms/milliliter 11.9, range 1.5–102) and were not associated with protection. Ex vivo IFN-γ ELISpot responses after Ad boost were modest (CSP geometric mean spot forming cells/million peripheral blood mononuclear cells 86, range 13–408; AMA1 348, range 88–1270) and were highest in three protected subjects. ELISpot responses to AMA1 were significantly associated with protection (p = 0.019). Flow cytometry identified predominant IFN-γ mono-secreting CD8+ T cell responses in three protected subjects. No subjects with high pre-existing anti-Ad5 neutralizing antibodies were protected but the association was not statistically significant. Significance The DNA/Ad regimen provided the highest sterile immunity achieved against malaria following immunization with a gene-based subunit vaccine (27%). Protection was

  1. Solution NMR characterization of apical membrane antigen 1 and small molecule interactions as a basis for designing new antimalarials.

    PubMed

    Krishnarjuna, Bankala; Lim, San Sui; Devine, Shane M; Debono, Cael O; Lam, Raymond; Chandrashekaran, Indu R; Jaipuria, Garima; Yagi, Hiromasa; Atreya, Hanudatta S; Scanlon, Martin J; MacRaild, Christopher A; Scammells, Peter J; Norton, Raymond S

    2016-06-01

    Plasmodium falciparum apical membrane antigen 1 (PfAMA1) plays an important role in the invasion by merozoites of human red blood cells during a malaria infection. A key region of PfAMA1 is a conserved hydrophobic cleft formed by 12 hydrophobic residues. As anti-apical membrane antigen 1 antibodies and other inhibitory molecules that target this hydrophobic cleft are able to block the invasion process, PfAMA1 is an attractive target for the development of strain-transcending antimalarial agents. As solution nuclear magnetic resonance spectroscopy is a valuable technique for the rapid characterization of protein-ligand interactions, we have determined the sequence-specific backbone assignments for PfAMA1 from two P. falciparum strains, FVO and 3D7. Both selective labelling and unlabelling strategies were used to complement triple-resonance experiments in order to facilitate the assignment process. We have then used these assignments for mapping the binding sites for small molecules, including benzimidazoles, pyrazoles and 2-aminothiazoles, which were selected on the basis of their affinities measured from surface plasmon resonance binding experiments. Among the compounds tested, benzimidazoles showed binding to a similar region on both FVO and 3D7 PfAMA1, suggesting that these compounds are promising scaffolds for the development of novel PfAMA1 inhibitors. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26804042

  2. Immunization with Apical Membrane Antigen 1 Confers Sterile Infection-Blocking Immunity against Plasmodium Sporozoite Challenge in a Rodent Model

    PubMed Central

    Schussek, Sophie; Trieu, Angela; Apte, Simon H.; Sidney, John; Sette, Alessandro

    2013-01-01

    Apical membrane antigen 1 (AMA-1) is a leading blood-stage malaria vaccine candidate. Consistent with a key role in erythrocytic invasion, AMA-1-specific antibodies have been implicated in AMA-1-induced protective immunity. AMA-1 is also expressed in sporozoites and in mature liver schizonts where it may be a target of protective cell-mediated immunity. Here, we demonstrate for the first time that immunization with AMA-1 can induce sterile infection-blocking immunity against Plasmodium sporozoite challenge in 80% of immunized mice. Significantly higher levels of gamma interferon (IFN-γ)/interleukin-2 (IL-2)/tumor necrosis factor (TNF) multifunctional T cells were noted in immunized mice than in control mice. We also report the first identification of minimal CD8+ and CD4+ T cell epitopes on Plasmodium yoelii AMA-1. These data establish AMA-1 as a target of both preerythrocytic- and erythrocytic-stage protective immune responses and validate vaccine approaches designed to induce both cellular and humoral immunity. PMID:23836827

  3. Lethal and Amanitin-Resistance Mutations in the Caenorhabditis Elegans Ama-1 and Ama-2 Genes

    PubMed Central

    Rogalski, T. M.; Bullerjahn, AME.; Riddle, D. L.

    1988-01-01

    Mutants of Caenorhabditis elegans resistant to α-amanitin have been isolated at a frequency of about 1.6 X 10(-6) after EMS mutagenesis of the wild-type strain, N2. Four new dominant resistance mutations have been studied genetically. Three are alleles of a previously identified gene, ama-1 IV, encoding the largest subunit of RNA polymerase II. The fourth mutation defines a new gene, ama-2 V. Unlike the ama-1 alleles, the ama-2 mutation exhibits a recessive-lethal phenotype. Growth and reproduction of N2 was inhibited at a concentration of 10 μg/ml amanitin, whereas ama-2/+ animals were inhibited at 100 μg/ml, and 800 μg/ml was required to inhibit growth of ama-1/+ larvae. We have also determined that two reference strains used for genetic mapping, dpy-11(e224)V and sma-1(e30)V, are at least four-fold more sensitive to amanitin that the wild-type strain. Using an amanitin-resistant ama-1(m118) or ama-1(m322) strain as a parent, we have isolated amanitin-sensitive mutants that carry recessive-lethal ama-1 alleles. The frequency of EMS-induced lethal ama-1 mutations is approximately 1.7 X 10(-3), 1000-fold higher than the frequency of amanitin-resistance alleles. Nine of the lethal alleles are apparent null mutations, and they exhibit L1-lethal phenotypes at both 20° and 25°. Six alleles result in partial loss of RNA polymerase II function as determined by their sterile phenotypes at 20°. All but one of these latter mutations exhibit a more severe phenotype at 25°C. We have also selected seven EMS-induced revertants of three different ama-1 lethals. These revertants restore dominant resistance to amanitin. The selection for revertants also produced eight new dominant amanitin resistance alleles on the balancer chromosome, nT1. PMID:3197954

  4. A Caenorhabditis Elegans RNA Polymerase II Gene, Ama-1 Iv, and Nearby Essential Genes

    PubMed Central

    Rogalski, T. M.; Riddle, D. L.

    1988-01-01

    The amanitin-binding subunit of RNA polymerase II in Caenorhabditis elegans is encoded by the ama-1 gene, located approximately 0.05 map unit to the right of dpy-13 IV. Using the amanitin-resistant ama-1(m118) strain as a parent, we have isolated amanitin-sensitive mutants that carry recessive-lethal ama-1 alleles. Of the six ethyl methanesulfonate-induced mutants examined, two are arrested late in embryogenesis. One of these is a large deficiency, mDf9, but the second may be a novel point mutation. The four other mutants are hypomorphs, and presumably produce altered RNA polymerase II enzymes with some residual function. Two of these mutants develop into sterile adults at 20° but are arrested as larvae at 25°, and two others are fertile at 20° and sterile at 25°. Temperature-shift experiments performed with the adult sterile mutant, ama-1(m118m238ts), have revealed a temperature-sensitive period that begins late in gonadogenesis and is centered around the initiation of egg-laying. Postembryonic development at 25° is slowed by 30%. By contrast, the amanitin-resistant allele of ama-1 has very little effect on developmental rate or fertility. We have identified 15 essential genes in an interval of 4.5 map units surrounding ama-1, as well as four γ-ray-induced deficiencies and two duplications that include the ama-1 gene. The larger duplication, mDp1, may include the entire left arm of chromosome IV, and it recombines with the normal homologue at a low frequency. The smallest deficiency, mDf10, complements all but three identified genes: let-278, dpy-13 and ama-1, which define an interval of only 0.1 map unit. The terminal phenotype of mDf10 homozygotes is developmental arrest during the first larval stage, suggesting that there is sufficient maternal RNA polymerase II to complete embryonic development. PMID:8608933

  5. Molecular Insights into the Interaction between Plasmodium falciparum Apical Membrane Antigen 1 and an Invasion-Inhibitory Peptide

    PubMed Central

    Wang, Geqing; MacRaild, Christopher A.; Mohanty, Biswaranjan; Mobli, Mehdi; Cowieson, Nathan P.; Anders, Robin F.; Simpson, Jamie S.; McGowan, Sheena; Norton, Raymond S.; Scanlon, Martin J.

    2014-01-01

    Apical membrane antigen 1 (AMA1) of the human malaria parasite Plasmodium falciparum has been implicated in invasion of the host erythrocyte. It interacts with malarial rhoptry neck (RON) proteins in the moving junction that forms between the host cell and the invading parasite. Agents that block this interaction inhibit invasion and may serve as promising leads for anti-malarial drug development. The invasion-inhibitory peptide R1 binds to a hydrophobic cleft on AMA1, which is an attractive target site for small molecules that block parasite invasion. In this work, truncation and mutational analyses show that Phe5-Phe9, Phe12 and Arg15 in R1 are the most important residues for high affinity binding to AMA1. These residues interact with two well-defined binding hot spots on AMA1. Computational solvent mapping reveals that one of these hot spots is suitable for small molecule targeting. We also confirm that R1 in solution binds to AMA1 with 1∶1 stoichiometry and adopts a secondary structure consistent with the major form of R1 observed in the crystal structure of the complex. Our results provide a basis for designing high affinity inhibitors of the AMA1-RON2 interaction. PMID:25343578

  6. A promising new ELISA diagnostic test for cattle babesiosis based on Babesia bigemina Apical Membrane Antigen-1.

    PubMed

    Torina, Alessandra; Cordaro, Antonio; Blanda, Valeria; D'Agostino, Rosalia; Scimeca, Salvatore; Scariano, Maria E; Sireci, Guido; Lelli, Rossella

    2016-01-01

    Babesiosis due to Babesia bigemina is a relevant tick-borne disease, affecting cattle worldwide. Many surface proteins of the pathogen including the Apical Membrane Antigen 1 (AMA-1) - have been analysed for vaccine and diagnostic purposes. This study focused on B. bigemina AMA-1 and on its use for the assessment of diagnostic tests. After bioinformatic analyses, AMA-1 codifying region was amplified and cloned into an expression vector used to induce protein synthesis in Escherichia coli cells. AMA-1 was purified by affinity chromatography and used to set up the best condition for an ELISA protocol. Bovine field sera positive to B. bigemina were used to evaluate the presence of anti-AMA-1 antibodies. In order to verify the assay specificity, sera positive to Babesia bovis or to the piroplasm Theileria annulata were also included. Significant differences were obtained between sera negative to both B. bigemina and B. bovis and samples positive to B. bigemina, to B. bovis or to both pathogens. No significant reaction was observed with T. annulata positive sera. The results showed that AMA-1 protein is suitable to be used as antigen in diagnostic assays for babesiosis diagnosis in cattle, as it does not show any cross reaction with anti-T. annulata antibodies. PMID:27033532

  7. A randomized and controlled Phase 1 study of the safety and immunogenicity of the AMA1-C1/Alhydrogel + CPG 7909 vaccine for Plasmodium falciparum malaria in semi-immune Malian adults.

    PubMed

    Sagara, Issaka; Ellis, Ruth D; Dicko, Alassane; Niambele, Mohamed B; Kamate, Beh; Guindo, Ousmane; Sissoko, Mahamadou S; Fay, Michael P; Guindo, Merepen A; Kante, Ousmane; Saye, Renion; Miura, Kazutoyo; Long, Carole; Mullen, Gregory E D; Pierce, Mark; Martin, Laura B; Rausch, Kelly; Dolo, Amagana; Diallo, Dapa A; Miller, Louis H; Doumbo, Ogobara K

    2009-12-01

    A double blind, randomized and controlled Phase 1 clinical trial was conducted to assess the safety and immunogenicity in malaria-exposed adults of the Plasmodium falciparum blood stage vaccine candidate Apical Membrane Antigen 1-Combination 1 (AMA1-C1)/Alhydrogel with and without the novel adjuvant CPG 7909. Participants were healthy adults 18-45 years old living in the village of Donéguébougou, Mali. A total of 24 participants received 2 doses one month apart of either 80 microg AMA1-C1/Alhydrogel or 80 microg AMA1-C1/Alhydrogel + 564 microg CPG 7909. The study started in October 2007 and completed follow up in May 2008. Both vaccines were well tolerated, with only mild local adverse events and no systemic adverse events judged related to vaccination. The difference in antibody responses were over 2-fold higher in the group receiving CPG 7909 for all time points after second vaccination and the differences are statistically significant (all p<0.05). This is the first use of the novel adjuvant CPG 7909 in a malaria-exposed population. PMID:19874925

  8. Crystal Structure of Plasmodium knowlesi Apical Membrane Antigen 1 and Its Complex with an Invasion-Inhibitory Monoclonal Antibody

    PubMed Central

    van der Eijk, Marjolein; Thomas, Alan W.; Singh, Balbir; Kocken, Clemens H. M.

    2015-01-01

    The malaria parasite Plasmodium knowlesi, previously associated only with infection of macaques, is now known to infect humans as well and has become a significant public health problem in Southeast Asia. This species should therefore be targeted in vaccine and therapeutic strategies against human malaria. Apical Membrane Antigen 1 (AMA1), which plays a role in Plasmodium merozoite invasion of the erythrocyte, is currently being pursued in human vaccine trials against P. falciparum. Recent vaccine trials in macaques using the P. knowlesi orthologue PkAMA1 have shown that it protects against infection by this parasite species and thus should be developed for human vaccination as well. Here, we present the crystal structure of Domains 1 and 2 of the PkAMA1 ectodomain, and of its complex with the invasion-inhibitory monoclonal antibody R31C2. The Domain 2 (D2) loop, which is displaced upon binding the Rhoptry Neck Protein 2 (RON2) receptor, makes significant contacts with the antibody. R31C2 inhibits binding of the Rhoptry Neck Protein 2 (RON2) receptor by steric blocking of the hydrophobic groove and by preventing the displacement of the D2 loop which is essential for exposing the complete binding site on AMA1. R31C2 recognizes a non-polymorphic epitope and should thus be cross-strain reactive. PkAMA1 is much less polymorphic than the P. falciparum and P. vivax orthologues. Unlike these two latter species, there are no polymorphic sites close to the RON2-binding site of PkAMA1, suggesting that P. knowlesi has not developed a mechanism of immune escape from the host’s humoral response to AMA1. PMID:25886591

  9. Overcoming Antigenic Diversity by Enhancing the Immunogenicity of Conserved Epitopes on the Malaria Vaccine Candidate Apical Membrane Antigen-1

    PubMed Central

    Dutta, Sheetij; Dlugosz, Lisa S.; Drew, Damien R.; Ge, Xiopeng; Ababacar, Diouf; Rovira, Yazmin I.; Moch, J. Kathleen; Shi, Meng; Long, Carole A.; Foley, Michael; Beeson, James G.; Anders, Robin F.; Miura, Kazutoyo; Haynes, J. David; Batchelor, Adrian H.

    2013-01-01

    Malaria vaccine candidate Apical Membrane Antigen-1 (AMA1) induces protection, but only against parasite strains that are closely related to the vaccine. Overcoming the AMA1 diversity problem will require an understanding of the structural basis of cross-strain invasion inhibition. A vaccine containing four diverse allelic proteins 3D7, FVO, HB3 and W2mef (AMA1 Quadvax or QV) elicited polyclonal rabbit antibodies that similarly inhibited the invasion of four vaccine and 22 non-vaccine strains of P. falciparum. Comparing polyclonal anti-QV with antibodies against a strain-specific, monovalent, 3D7 AMA1 vaccine revealed that QV induced higher levels of broadly inhibitory antibodies which were associated with increased conserved face and domain-3 responses and reduced domain-2 response. Inhibitory monoclonal antibodies (mAb) raised against the QV reacted with a novel cross-reactive epitope at the rim of the hydrophobic trough on domain-1; this epitope mapped to the conserved face of AMA1 and it encompassed the 1e-loop. MAbs binding to the 1e-loop region (1B10, 4E8 and 4E11) were ∼10-fold more potent than previously characterized AMA1-inhibitory mAbs and a mode of action of these 1e-loop mAbs was the inhibition of AMA1 binding to its ligand RON2. Unlike the epitope of a previously characterized 3D7-specific mAb, 1F9, the 1e-loop inhibitory epitope was partially conserved across strains. Another novel mAb, 1E10, which bound to domain-3, was broadly inhibitory and it blocked the proteolytic processing of AMA1. By itself mAb 1E10 was weakly inhibitory but it synergized with a previously characterized, strain-transcending mAb, 4G2, which binds close to the hydrophobic trough on the conserved face and inhibits RON2 binding to AMA1. Novel inhibition susceptible regions and epitopes, identified here, can form the basis for improving the antigenic breadth and inhibitory response of AMA1 vaccines. Vaccination with a few diverse antigenic proteins could provide universal

  10. Analysis of human B-cell responses following ChAd63-MVA MSP1 and AMA1 immunization and controlled malaria infection

    PubMed Central

    Elias, Sean C; Choudhary, Prateek; de Cassan, Simone C; Biswas, Sumi; Collins, Katharine A; Halstead, Fenella D; Bliss, Carly M; Ewer, Katie J; Hodgson, Susanne H; Duncan, Christopher J A; Hill, Adrian V S; Draper, Simon J

    2014-01-01

    Acquisition of non-sterilizing natural immunity to Plasmodium falciparum malaria has been shown in low transmission areas following multiple exposures. However, conflicting data from endemic areas suggest that the parasite may interfere with the induction of effective B-cell responses. To date, the impact of blood-stage parasite exposure on antigen-specific B cells has not been reported following controlled human malaria infection (CHMI). Here we analysed human B-cell responses in a series of Phase I/IIa clinical trials, which include CHMI, using candidate virus-vectored vaccines encoding two blood-stage antigens: merozoite surface protein 1 (MSP1) and apical membrane antigen 1 (AMA1). Previously vaccinated volunteers show boosting of pre-existing antigen-specific memory B-cell (mBC) responses following CHMI. In contrast, unvaccinated malaria-naive control volunteers developed an mBC response against MSP1 but not AMA1. Serum IgG correlated with the mBC response after booster vaccination but this relationship was less well maintained following CHMI. A significant reduction in peripheral MSP1-specific mBC was observed at the point of diagnosis of blood-stage infection. This was coincident with a reduction in peripheral blood B-cell subsets expressing CXCR3 and elevated serum levels of interferon-γ and CXCL9, suggesting migration away from the periphery. These CHMI data confirm that mBC and antibody responses can be induced and boosted by blood-stage parasite exposure, in support of epidemiological studies on low-level parasite exposure. PMID:24303947

  11. Genetic detection of Babesia bigemina from Mongolian cattle using apical membrane antigen-1 gene-based PCR assay.

    PubMed

    Sivakumar, Thillaiampalam; Altangerel, Khukhuu; Battsetseg, Badgar; Battur, Banzragch; Aboulaila, Mahmoud; Munkhjargal, Tserendorj; Yoshinari, Takeshi; Yokoyama, Naoaki; Igarashi, Ikuo

    2012-06-01

    We developed a new nested PCR (nPCR) assay based on the Babesia bigemina apical membrane antigen-1 (AMA-1) gene sequence for parasite-specific detection. The primers were designed to amplify 738-bp and 211-bp fragments of the AMA-1 gene by primary and nested PCRs, respectively. The assay was proven to be specific for the B. bigemina, whereas the previously established SpeI-AvaI nPCR assay amplified not only the target fragment of B. bigemina but also a homologous one from Babesia ovata. The AMA-1 nPCR assay was also evaluated using field DNA samples extracted from 266 bovine blood samples collected from Mongolia in 2010. In a comparative evaluation, 90 (33.8%) and 25 (9.4%) of the blood samples showed positive reactions for B. bigemina by the SpeI-AvaI nPCR and AMA-1 nPCR assays, respectively. The sequencing analysis of the nPCR products confirmed that the AMA-1 nPCR method had specifically detected the target B. bigemina DNA. However, 4 different kinds of sequences were determined among the SpeI-AvaI nPCR amplicons. Two of them were derived from B. bigemina and B. ovata, while the origins of the others were unknown. In the current study, the presence of B. bigemina was clearly demonstrated among Mongolian cattle populations by the current nPCR assay for the first time. Furthermore, our findings also indicate that the AMA-1 nPCR assay may be a useful diagnostic tool for the specific detection of B. bigemina. PMID:22284301

  12. Localisation-based imaging of malarial antigens during erythrocyte entry reaffirms a role for AMA1 but not MTRAP in invasion

    PubMed Central

    Riglar, David T.; Whitehead, Lachlan; Cowman, Alan F.; Rogers, Kelly L.; Baum, Jake

    2016-01-01

    ABSTRACT Microscopy-based localisation of proteins during malaria parasite (Plasmodium) invasion of the erythrocyte is widely used for tentative assignment of protein function. To date, however, imaging has been limited by the rarity of invasion events and the poor resolution available, given the micron size of the parasite, which leads to a lack of quantitative measures for definitive localisation. Here, using computational image analysis we have attempted to assign relative protein localisation during invasion using wide-field deconvolution microscopy. By incorporating three-dimensional information we present a detailed assessment of known parasite effectors predicted to function during entry but as yet untested or for which data are equivocal. Our method, termed longitudinal intensity profiling, resolves confusion surrounding the localisation of apical membrane antigen 1 (AMA1) at the merozoite–erythrocyte junction and predicts that the merozoite thrombospondin-related anonymous protein (MTRAP) is unlikely to play a direct role in the mechanics of entry, an observation supported with additional biochemical evidence. This approach sets a benchmark for imaging of complex micron-scale events and cautions against simplistic interpretations of small numbers of representative images for the assignment of protein function or prioritisation of candidates as therapeutic targets. PMID:26604223

  13. A Phase 1 study of the blood-stage malaria vaccine candidate AMA1-C1/Alhydrogel with CPG 7909, using two different formulations and dosing intervals.

    PubMed

    Ellis, Ruth D; Mullen, Gregory E D; Pierce, Mark; Martin, Laura B; Miura, Kazutoyo; Fay, Michael P; Long, Carole A; Shaffer, Donna; Saul, Allan; Miller, Louis H; Durbin, Anna P

    2009-06-24

    A Phase 1 study was conducted in 24 malaria naïve adults to assess the safety and immunogenicity of the recombinant protein vaccine apical membrane antigen 1-Combination 1 (AMA1-C1)/Alhydrogel with CPG 7909 in two different formulations (phosphate buffer and saline), and given at two different dosing schedules, 0 and 1 month or 0 and 2 months. Both formulations were well tolerated and frequency of local reactions and solicited adverse events was similar among the groups. Peak antibody levels in the groups receiving CPG 7909 in saline were not significantly different than those receiving CPG 7909 in phosphate. Peak antibody levels in the groups vaccinated at a 0,2 month interval were 2.52-fold higher than those vaccinated at a 0,1 month interval (p=0.037, 95% CI 1.03, 4.28). In vitro growth inhibition followed the antibody level: median inhibition was 51% (0,1 month interval) versus 85% (0,2 month interval) in antibody from samples taken 2 weeks post-second vaccination (p=0.056). PMID:19410624

  14. High-Level Expression, Purification and Characterization of A Recombinant Plasmodium vivax Apical Membrane Antigen 1: Implication for vivax Malaria Vaccine Development

    PubMed Central

    Salavatifar, Maryam; Zakeri, Sedigheh; Hayati Roodbari, Nasim; Djadid, Navid Dinparast

    2015-01-01

    Objective The apical membrane antigen-1 (AMA-1) is considered as a promising candidate for development of a malaria vaccine against Plasmodium parasites. The correct conformation of this protein appears to be necessary for the stimulation of parasite-inhibitory responses, and these responses, in turn, seem to be antibody-mediated. Therefore, in the present investigation, we expressed the Plasmodium vivax AMA-1 (PvAMA-1) ectodomain in Escherichia coli (E. coli), purified it using standard procedures and characterized it to determine its biological activities for it to be used as a potential target for developing a protective and safe vivax malaria vaccine. Materials and Methods In this experimental investigation, the ectodomain of PvAMA-1 antigen (GenBank accession no. JX624741) was expressed in the E. coli M15pQE30 expression system and purified with immobilized-metal affinity chromatography. The correct conformation of the recombinant protein was evaluated by Western blotting and indirect immunofluorescence antibody (IFA) test. In addition, the immunogenic properties of PvAMA-1 were evaluated in BALB/c mice with the purified protein emulsified in Freund’s adjuvant. Results In the present study, the PvAMA-1 ectodomain was expressed at a high-level (65 mg/L) using a bacterial system. Reduced and non-reduced sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) as well as Western blot analysis confirmed the appropriate conformation and folding of PvAMA-1. The evaluation of immunogenic properties of PvAMA-1 showed that both T helper-1 and 2 cells (Th1 and Th2) responses were present in mice after three immunizations and persisted up to one year after the first immunization. Moreover, the antibodies raised against the recombinant PvAMA-1 in injected mice could recognize the native protein localized on P. vivax parasites. Conclusion We demonstrate that our recombinant protein had proper conformation and folding. Also, there were common epitopes in the

  15. Amino Acid Substitutions in the Caenorhabditis elegans RNA Polymerase II Large Subunit AMA-1/RPB-1 that Result in α-Amanitin Resistance and/or Reduced Function.

    PubMed

    Bowman, Elizabeth Anne; Riddle, Donald L; Kelly, William

    2011-11-01

    Mutations in the Caenorhabditis elegans RNA polymerase II AMA-1/RPB-1 subunit that cause α-amanitin resistance and/or developmental defects were isolated previously. We identified 12 of these mutations and mapped them onto the Saccharomyces cerevisiae RPB1 structure to provide insight into AMA-1 regions that are essential for development in a multicellular organism. PMID:22384351

  16. ama1 Genes of Sympatric Plasmodium vivax and P. falciparum from Venezuela Differ Significantly in Genetic Diversity and Recombination Frequency

    PubMed Central

    Ord, Rosalynn L.; Tami, Adriana; Sutherland, Colin J.

    2008-01-01

    Background We present the first population genetic analysis of homologous loci from two sympatric human malaria parasite populations sharing the same human hosts, using full-length sequences of ama1 genes from Plasmodium vivax and P. falciparum collected in the Venezuelan Amazon. Methodology/Principal Findings Significant differences between the two species were found in genetic diversity at the ama1 locus, with 18 distinct haplotypes identified among the 73 Pvama1 sequences obtained, compared to 6 unique haplotypes from 30 Pfama1 sequences, giving overall diversity estimates of h = 0.9091, and h = 0.538 respectively. Levels of recombination were also found to differ between the species, with P. falciparum exhibiting very little recombination across the 1.77kb sequence. In contrast, analysis of patterns of nucleotide substitutions provided evidence that polymorphisms in the ama1 gene of both species are maintained by balancing selection, particularly in domain I. The two distinct population structures observed are unlikely to result from different selective forces acting upon the two species, which share both human and mosquito hosts in this setting. Rather, the highly structured P. falciparum population appears to be the result of a population bottleneck, while the much less structured P. vivax population is likely to be derived from an ancient pool of diversity, as reflected in a larger estimate of effective population size for this species. Greatly reduced mosquito transmission in 1997, due to low rainfall prior to the second survey, was associated with far fewer P. falciparum infections, but an increase in P. vivax infections, probably due to hypnozoite activation. Conclusions/Significance The relevance of these findings to putative competitive interactions between these two important human pathogen species is discussed. These results highlight the need for future control interventions to employ strategies targeting each of the parasite species present

  17. Comparative sequence analysis of domain I of Plasmodium falciparum apical membrane antigen 1 from Saudi Arabia and worldwide isolates.

    PubMed

    Al-Qahtani, Ahmed A; Abdel-Muhsin, Abdel-Muhsin A; Bin Dajem, Saad M; AlSheikh, Adel Ali H; Bohol, Marie Fe F; Al-Ahdal, Mohammed N; Putaporntip, Chaturong; Jongwutiwes, Somchai

    2016-04-01

    The apical membrane antigen 1 of Plasmodium falciparum (PfAMA1) plays a crucial role in erythrocyte invasion and is a target of protective antibodies. Although domain I of PfAMA1 has been considered a promising vaccine component, extensive sequence diversity in this domain could compromise an effective vaccine design. To explore the extent of sequence diversity in domain I of PfAMA1, P. falciparum-infected blood samples from Saudi Arabia collected between 2007 and 2009 were analyzed and compared with those from worldwide parasite populations. Forty-six haplotypes and a novel codon change (M190V) were found among Saudi Arabian isolates. The haplotype diversity (0.948±0.004) and nucleotide diversity (0.0191±0.0008) were comparable to those from African hyperendemic countries. Positive selection in domain I of PfAMA1 among Saudi Arabian parasite population was observed because nonsynonymous nucleotide substitutions per nonsynonymous site (dN) significantly exceeded synonymous nucleotide substitutions per synonymous site (dS) and Tajima's D and its related statistics significantly deviated from neutrality in the positive direction. Despite a relatively low prevalence of malaria in Saudi Arabia, a minimum of 17 recombination events occurred in domain I. Genetic differentiation was significant between P. falciparum in Saudi Arabia and parasites from other geographic origins. Several shared or closely related haplotypes were found among parasites from different geographic areas, suggesting that vaccine derived from multiple shared epitopes could be effective across endemic countries. PMID:26867816

  18. Cheminformatics Based Machine Learning Models for AMA1-RON2 Abrogators for Inhibiting Plasmodium falciparum Erythrocyte Invasion.

    PubMed

    Maindola, Priyank; Jamal, Salma; Grover, Abhinav

    2015-10-01

    Malaria remains a dreadful disease by putting every year about 3.4 billion people at risk and resulting into mortality of 627 thousand people worldwide. Existing therapies based upon Quinines and Artemisinin-based combination therapies have started showing resistance, pressing the need for search of anti-malarials with different mechanisms of action. In this respect erythrocyte invasion by Plasmodium is immensely crucial, as being obligate intracellular parasite it must invade host cells. This process is mediated by interaction between conserved Apical Membrane Antigen (AMA1) and Rhoptry Neck (RON2) protein, which is compulsory for successful invasion of erythrocyte by Plasmodium and manifestation of the disease Malaria. Here, using the physicochemical properties of the compounds available from a confirmatory high throughput screening, which were tested for their disruption capability of this crucial molecular interaction, we trained supervised classifiers and validated their robustness by various statistical parameters. Best model was used for screening new compounds from Traditional Chinese Medicine Database. Some of the best hits already find their use as anti-malarials and the model predicts that an essential part of their effectiveness is likely due to inhibition of AMA1-RON2 interaction. Pharmacophoric features have also been identified to ease further designing of possible leads in an effective way. PMID:27490966

  19. Clinical Variation of Plasmodium falciparum eba-175, ama-1, and msp-3 Genotypes in Young Children Living in a Seasonally High Malaria Transmission Setting in Burkina Faso

    PubMed Central

    Soulama, Issiaka; Sermé, Samuel S.; Bougouma, Edith C.; Diarra, Amidou; Tiono, Alfred B.; Ouedraogo, Alphonse; Konate, Amadou T.; Nebie, Issa; Sirima, Sodiomon B.

    2015-01-01

    The association between P. falciparum eba-175, ama-1, and msp-3 polymorphism in the pathogenicity of malaria disease was investigated. We therefore compared the prevalence of different alleles between symptomatic and asymptomatic malarial children under five years of age living in Burkina Faso. Blood filter papers were collected during the 2008 malaria transmission season from 228 symptomatic and 199 asymptomatic children under five years of age. All patients were living in the rural area of Saponé at about 50 km from Ouagadougou, the capital city of Burkina Faso. P. falciparum parasite DNA was extracted using QIAGEN kits and the alleles diversity was assessed by a nested PCR. PCR products were then digested by restriction enzymes based on already described polymorphic regions of the eba-175, ama-1, and msp-3 genes. The individual alleles eba-175_FCR3 and msp-3_K1 frequencies were statistically higher (p < 0.0001) in the asymptomatic group compared to the symptomatic ones. No statistically significant difference was noted in the prevalence of ama-1-3D7, ama-1-K1, and ama-1-HB3 genotypes between the two groups (p > 0.05). The comparative analysis of P. falciparum genotypes indicated that the polymorphism in eba-175 and msp-3 genotypes varied between asymptomatic and symptomatic clinical groups and may contribute to the pathogenesis of malaria. PMID:26634149

  20. Clinical Variation of Plasmodium falciparum eba-175, ama-1, and msp-3 Genotypes in Young Children Living in a Seasonally High Malaria Transmission Setting in Burkina Faso.

    PubMed

    Soulama, Issiaka; Sermé, Samuel S; Bougouma, Edith C; Diarra, Amidou; Tiono, Alfred B; Ouedraogo, Alphonse; Konate, Amadou T; Nebie, Issa; Sirima, Sodiomon B

    2015-01-01

    The association between P. falciparum eba-175, ama-1, and msp-3 polymorphism in the pathogenicity of malaria disease was investigated. We therefore compared the prevalence of different alleles between symptomatic and asymptomatic malarial children under five years of age living in Burkina Faso. Blood filter papers were collected during the 2008 malaria transmission season from 228 symptomatic and 199 asymptomatic children under five years of age. All patients were living in the rural area of Saponé at about 50 km from Ouagadougou, the capital city of Burkina Faso. P. falciparum parasite DNA was extracted using QIAGEN kits and the alleles diversity was assessed by a nested PCR. PCR products were then digested by restriction enzymes based on already described polymorphic regions of the eba-175, ama-1, and msp-3 genes. The individual alleles eba-175_FCR3 and msp-3_K1 frequencies were statistically higher (p < 0.0001) in the asymptomatic group compared to the symptomatic ones. No statistically significant difference was noted in the prevalence of ama-1-3D7, ama-1-K1, and ama-1-HB3 genotypes between the two groups (p > 0.05). The comparative analysis of P. falciparum genotypes indicated that the polymorphism in eba-175 and msp-3 genotypes varied between asymptomatic and symptomatic clinical groups and may contribute to the pathogenesis of malaria. PMID:26634149

  1. Enhanced antibody production in mice to the malaria antigen AMA1 by CPG 7909 requires physical association of CpG and antigen

    PubMed Central

    Mullen, Gregory E. D.; Aebig, Joan A.; Dobrescu, Gelu; Rausch, Kelly; Lambert, Lynn; Long, Carole A.; Miles, Aaron P.; Saul, Allan

    2007-01-01

    CpG oligodeoxynucleotides are potent immunostimulants. In this study, CPG 7909 was formulated with the recombinant Plasmodium falciparum protein AMA1-C1 adsorbed to Alhydrogel (aluminum hydroxide) and used to immunize mice. Mice receiving free CPG 7909 in a separate same site injection to the AMA1-C1/Alhydrogel had the same antibody responses as mice receiving AMA1-C1/Alhydrogel alone. For mice immunized with CPG 7909 bound to the AMA1-C1/Alhydrogel formulation, there was a bell shaped CPG 7909 dose response curve with the highest antibody response co-incident with the concentration of CPG 7909 that saturated binding to the Alhydrogel. At a higher CPG 7909 dose where 74% was unbound, there was no enhancement of response over AMA1-C1/Alhydrogel alone. Our results suggest that the adjuvant effects of CpGs are optimal when adsorbed to Alhydrogel and highlight the need for careful characterization of the vaccine formulation. PMID:17566616

  2. Conditional expression of apical membrane antigen 1 in Plasmodium falciparum shows it is required for erythrocyte invasion by merozoites

    PubMed Central

    Yap, Alan; Azevedo, Mauro F; Gilson, Paul R; Weiss, Greta E; O’Neill, Matthew T; Wilson, Danny W; Crabb, Brendan S; Cowman, Alan F

    2014-01-01

    Summary Malaria is caused by obligate intracellular parasites, of which Plasmodium falciparum is the most lethal species. In humans, P. falciparum merozoites (invasive forms of the parasite) employ a host of parasite proteins to rapidly invade erythrocytes. One of these is the P. falciparum apical membrane antigen 1 (PfAMA1) which forms a complex with rhoptry neck proteins at the tight junction. Here, we have placed the Pfama1 gene under conditional control using dimerizable Cre recombinase (DiCre) in P. falciparum. DiCre-mediated excision of the loxP-flanked Pfama1 gene results in approximately 80% decreased expression of the protein within one intraerythrocytic growth cycle. This reduces growth by 40%, due to decreased invasion efficiency characterized by a post-invasion defect in sealing of the parasitophorous vacuole. These results show that PfAMA1 is an essential protein for merozoite invasion in P. falciparum and either directly or indirectly plays a role in resealing of the red blood cell at the posterior end of the invasion event. PMID:24571085

  3. Combining Viral Vectored and Protein-in-adjuvant Vaccines Against the Blood-stage Malaria Antigen AMA1: Report on a Phase 1a Clinical Trial

    PubMed Central

    Hodgson, Susanne H; Choudhary, Prateek; Elias, Sean C; Milne, Kathryn H; Rampling, Thomas W; Biswas, Sumi; Poulton, Ian D; Miura, Kazutoyo; Douglas, Alexander D; Alanine, Daniel GW; Illingworth, Joseph J; de Cassan, Simone C; Zhu, Daming; Nicosia, Alfredo; Long, Carole A; Moyle, Sarah; Berrie, Eleanor; Lawrie, Alison M; Wu, Yimin; Ellis, Ruth D; Hill, Adrian V S; Draper, Simon J

    2014-01-01

    The development of effective vaccines against difficult disease targets will require the identification of new subunit vaccination strategies that can induce and maintain effective immune responses in humans. Here we report on a phase 1a clinical trial using the AMA1 antigen from the blood-stage Plasmodium falciparum malaria parasite delivered either as recombinant protein formulated with Alhydrogel adjuvant with and without CPG 7909, or using recombinant vectored vaccines—chimpanzee adenovirus ChAd63 and the orthopoxvirus MVA. A variety of promising “mixed-modality” regimens were tested. All volunteers were primed with ChAd63, and then subsequently boosted with MVA and/or protein-in-adjuvant using either an 8- or 16-week prime-boost interval. We report on the safety of these regimens, as well as the T cell, B cell, and serum antibody responses. Notably, IgG antibody responses primed by ChAd63 were comparably boosted by AMA1 protein vaccine, irrespective of whether CPG 7909 was included in the Alhydrogel adjuvant. The ability to improve the potency of a relatively weak aluminium-based adjuvant in humans, by previously priming with an adenoviral vaccine vector encoding the same antigen, thus offers a novel vaccination strategy for difficult or neglected disease targets when access to more potent adjuvants is not possible. PMID:25156127

  4. Next-generation protein-rich potato expressing the seed protein gene AmA1 is a result of proteome rebalancing in transgenic tuber

    PubMed Central

    Chakraborty, Subhra; Chakraborty, Niranjan; Agrawal, Lalit; Ghosh, Sudip; Narula, Kanika; Shekhar, Shubhendu; Naik, Prakash S.; Pande, P. C.; Chakrborti, Swarup Kumar; Datta, Asis

    2010-01-01

    Protein deficiency is the most crucial factor that affects physical growth and development and that increases morbidity and mortality especially in developing countries. Efforts have been made to improve protein quality and quantity in crop plants but with limited success. Here, we report the development of transgenic potatoes with enhanced nutritive value by tuber-specific expression of a seed protein, AmA1 (Amaranth Albumin 1), in seven genotypic backgrounds suitable for cultivation in different agro-climatic regions. Analyses of the transgenic tubers revealed up to 60% increase in total protein content. In addition, the concentrations of several essential amino acids were increased significantly in transgenic tubers, which are otherwise limited in potato. Moreover, the transgenics also exhibited enhanced photosynthetic activity with a concomitant increase in total biomass. These results are striking because this genetic manipulation also resulted in a moderate increase in tuber yield. The comparative protein profiling suggests that the proteome rebalancing might cause increased protein content in transgenic tubers. Furthermore, the data on field performance and safety evaluation indicate that the transgenic potatoes are suitable for commercial cultivation. In vitro and in vivo studies on experimental animals demonstrate that the transgenic tubers are also safe for human consumption. Altogether, these results emphasize that the expression of AmA1 is a potential strategy for the nutritional improvement of food crops. PMID:20855595

  5. Combining viral vectored and protein-in-adjuvant vaccines against the blood-stage malaria antigen AMA1: report on a phase 1a clinical trial.

    PubMed

    Hodgson, Susanne H; Choudhary, Prateek; Elias, Sean C; Milne, Kathryn H; Rampling, Thomas W; Biswas, Sumi; Poulton, Ian D; Miura, Kazutoyo; Douglas, Alexander D; Alanine, Daniel Gw; Illingworth, Joseph J; de Cassan, Simone C; Zhu, Daming; Nicosia, Alfredo; Long, Carole A; Moyle, Sarah; Berrie, Eleanor; Lawrie, Alison M; Wu, Yimin; Ellis, Ruth D; Hill, Adrian V S; Draper, Simon J

    2014-12-01

    The development of effective vaccines against difficult disease targets will require the identification of new subunit vaccination strategies that can induce and maintain effective immune responses in humans. Here we report on a phase 1a clinical trial using the AMA1 antigen from the blood-stage Plasmodium falciparum malaria parasite delivered either as recombinant protein formulated with Alhydrogel adjuvant with and without CPG 7909, or using recombinant vectored vaccines--chimpanzee adenovirus ChAd63 and the orthopoxvirus MVA. A variety of promising "mixed-modality" regimens were tested. All volunteers were primed with ChAd63, and then subsequently boosted with MVA and/or protein-in-adjuvant using either an 8- or 16-week prime-boost interval. We report on the safety of these regimens, as well as the T cell, B cell, and serum antibody responses. Notably, IgG antibody responses primed by ChAd63 were comparably boosted by AMA1 protein vaccine, irrespective of whether CPG 7909 was included in the Alhydrogel adjuvant. The ability to improve the potency of a relatively weak aluminium-based adjuvant in humans, by previously priming with an adenoviral vaccine vector encoding the same antigen, thus offers a novel vaccination strategy for difficult or neglected disease targets when access to more potent adjuvants is not possible. PMID:25156127

  6. Administering Eye Medications.

    ERIC Educational Resources Information Center

    Morris, Sara; Michael, Nancy, Ed.

    This module on administering eye medications is intended for use in inservice or continuing education programs for persons who administer medications in long-term care facilities. Instructor information, including teaching suggestions, and a listing of recommended audiovisual materials and their sources appear first. A brief discussion follows of…

  7. Apical membrane antigen 1 mediates apicomplexan parasite attachment but is dispensable for host cell invasion

    PubMed Central

    Bargieri, Daniel Y.; Andenmatten, Nicole; Lagal, Vanessa; Thiberge, Sabine; Whitelaw, Jamie A.; Tardieux, Isabelle; Meissner, Markus; Ménard, Robert

    2013-01-01

    Apicomplexan parasites invade host cells by forming a ring-like junction with the cell surface and actively sliding through the junction inside an intracellular vacuole. Apical membrane antigen 1 is conserved in apicomplexans and a long-standing malaria vaccine candidate. It is considered to have multiple important roles during host cell penetration, primarily in structuring the junction by interacting with the rhoptry neck 2 protein and transducing the force generated by the parasite motor during internalization. Here, we generate Plasmodium sporozoites and merozoites and Toxoplasma tachyzoites lacking apical membrane antigen 1, and find that the latter two are impaired in host cell attachment but the three display normal host cell penetration through the junction. Therefore, apical membrane antigen 1, rather than an essential invasin, is a dispensable adhesin of apicomplexan zoites. These genetic data have implications on the use of apical membrane antigen 1 or the apical membrane antigen 1–rhoptry neck 2 interaction as targets of intervention strategies against malaria or other diseases caused by apicomplexans. PMID:24108241

  8. Transcription factor Fos-related antigen 1 is an effective target for a breast cancer vaccine

    NASA Astrophysics Data System (ADS)

    Luo, Yunping; Zhou, He; Mizutani, Masato; Mizutani, Noriko; Reisfeld, Ralph A.; Xiang, Rong

    2003-07-01

    Protection against breast cancer was achieved with a DNA vaccine against murine transcription factor Fos-related antigen 1, which is overexpressed in aggressively proliferating D2F2 murine breast carcinoma. Growth of primary s.c. tumor and dissemination of pulmonary metastases was markedly suppressed by this oral DNA vaccine, carried by attenuated Salmonella typhimurium, encoding murine Fos-related antigen 1, fused with mutant polyubiquitin, and cotransformed with secretory murine IL-18. The life span of 60% of vaccinated mice was tripled in the absence of detectable tumor growth after lethal tumor cell challenge. Immunological mechanisms involved activation of T, natural killer, and dendritic cells, as indicated by up-regulation of their activation markers and costimulatory molecules. Markedly increased specific target cell lysis was mediated by both MHC class I-restricted CD8+ T cells and natural killer cells isolated from splenocytes of vaccinated mice, including a significant release of proinflammatory cytokines IFN- and IL-2. Importantly, fluorescence analysis of fibroblast growth factor 2 and tumor cell-induced vessel growth in Matrigel plugs demonstrated marked suppression of angiogenesis only in vaccinated animals. Taken together, this multifunctional DNA vaccine proved effective in protecting against growth and metastases of breast cancer by combining the action of immune effector cells with suppression of tumor angiogenesis. vaccine | tumor | metastases | antiangiogenesis

  9. Transcriptional activation by EBV nuclear antigen 1 is essential for the expression of EBV's transforming genes

    PubMed Central

    Altmann, Markus; Pich, Dagmar; Ruiss, Romana; Wang, Jindong; Sugden, Bill; Hammerschmidt, Wolfgang

    2006-01-01

    EBV is a paradigm for human tumor viruses because, although it infects most people benignly, it also can cause a variety of cancers. Both in vivo and in vitro, EBV infects B lymphocytes in G0, induces them to become blasts, and can maintain their proliferation in cell culture or in vivo as tumors. How EBV succeeds in these contrasting cellular environments in expressing its genes that control the host has not been explained. We have genetically dissected the EBV nuclear antigen 1 (EBNA1) gene that is required for replication of the viral genome, to elucidate its possible role in the transcription of viral genes. Strikingly, EBNA1 is essential to drive transcription of EBV's transforming genes after infection of primary B lymphocytes. PMID:16966603

  10. FRET detection of lymphocyte function–associated antigen-1 conformational extension

    PubMed Central

    Chigaev, Alexandre; Smagley, Yelena; Haynes, Mark K.; Ursu, Oleg; Bologa, Cristian G.; Halip, Liliana; Oprea, Tudor; Waller, Anna; Carter, Mark B.; Zhang, Yinan; Wang, Wei; Buranda, Tione; Sklar, Larry A.

    2015-01-01

    Lymphocyte function–associated antigen 1 (LFA-1, CD11a/CD18, αLβ2-integrin) and its ligands are essential for adhesion between T-cells and antigen-presenting cells, formation of the immunological synapse, and other immune cell interactions. LFA-1 function is regulated through conformational changes that include the modulation of ligand binding affinity and molecular extension. However, the relationship between molecular conformation and function is unclear. Here fluorescence resonance energy transfer (FRET) with new LFA-1–specific fluorescent probes showed that triggering of the pathway used for T-cell activation induced rapid unquenching of the FRET signal consistent with extension of the molecule. Analysis of the FRET quenching at rest revealed an unexpected result that can be interpreted as a previously unknown LFA-1 conformation. PMID:25378583

  11. Ribosome Protein L4 is essential for Epstein–Barr Virus Nuclear Antigen 1 function

    PubMed Central

    Shen, Chih-Lung; Liu, Cheng-Der; You, Ren-In; Ching, Yung-Hao; Liang, Jun; Ke, Liangru; Chen, Ya-Lin; Chen, Hong-Chi; Hsu, Hao-Jen; Liou, Je-Wen; Kieff, Elliott; Peng, Chih-Wen

    2016-01-01

    Epstein–Barr Virus (EBV) Nuclear Antigen 1 (EBNA1)-mediated origin of plasmid replication (oriP) DNA episome maintenance is essential for EBV-mediated tumorigenesis. We have now found that EBNA1 binds to Ribosome Protein L4 (RPL4). RPL4 shRNA knockdown decreased EBNA1 activation of an oriP luciferase reporter, EBNA1 DNA binding in lymphoblastoid cell lines, and EBV genome number per lymphoblastoid cell line. EBV infection increased RPL4 expression and redistributed RPL4 to cell nuclei. RPL4 and Nucleolin (NCL) were a scaffold for an EBNA1-induced oriP complex. The RPL4 N terminus cooperated with NCL-K429 to support EBNA1 and oriP-mediated episome binding and maintenance, whereas the NCL C-terminal K380 and K393 induced oriP DNA H3K4me2 modification and promoted EBNA1 activation of oriP-dependent transcription. These observations provide new insights into the mechanisms by which EBV uses NCL and RPL4 to establish persistent B-lymphoblastoid cell infection. PMID:26858444

  12. Ribosome Protein L4 is essential for Epstein-Barr Virus Nuclear Antigen 1 function.

    PubMed

    Shen, Chih-Lung; Liu, Cheng-Der; You, Ren-In; Ching, Yung-Hao; Liang, Jun; Ke, Liangru; Chen, Ya-Lin; Chen, Hong-Chi; Hsu, Hao-Jen; Liou, Je-Wen; Kieff, Elliott; Peng, Chih-Wen

    2016-02-23

    Epstein-Barr Virus (EBV) Nuclear Antigen 1 (EBNA1)-mediated origin of plasmid replication (oriP) DNA episome maintenance is essential for EBV-mediated tumorigenesis. We have now found that EBNA1 binds to Ribosome Protein L4 (RPL4). RPL4 shRNA knockdown decreased EBNA1 activation of an oriP luciferase reporter, EBNA1 DNA binding in lymphoblastoid cell lines, and EBV genome number per lymphoblastoid cell line. EBV infection increased RPL4 expression and redistributed RPL4 to cell nuclei. RPL4 and Nucleolin (NCL) were a scaffold for an EBNA1-induced oriP complex. The RPL4 N terminus cooperated with NCL-K429 to support EBNA1 and oriP-mediated episome binding and maintenance, whereas the NCL C-terminal K380 and K393 induced oriP DNA H3K4me2 modification and promoted EBNA1 activation of oriP-dependent transcription. These observations provide new insights into the mechanisms by which EBV uses NCL and RPL4 to establish persistent B-lymphoblastoid cell infection. PMID:26858444

  13. Modelling the structure of full-length Epstein-Barr virus nuclear antigen 1.

    PubMed

    Hussain, Mushtaq; Gatherer, Derek; Wilson, Joanna B

    2014-12-01

    Epstein-Barr virus is a clinically important human virus associated with several cancers and is the etiologic agent of infectious mononucleosis. The viral nuclear antigen-1 (EBNA1) is central to the replication and propagation of the viral genome and likely contributes to tumourigenesis. We have compared EBNA1 homologues from other primate lymphocryptoviruses and found that the central glycine/alanine repeat (GAr) domain as well as predicted cellular protein (USP7 and CK2) binding sites are present in homologues in the Old World primates, but not the marmoset, suggesting that these motifs may have co-evolved. Using the resolved structure of the C-terminal one-third of EBNA1 (homodimerization and DNA binding domain), we have gone on to develop monomeric and dimeric models in silico of the full-length protein. The C-terminal domain is predicted to be structurally highly similar between homologues, indicating conserved function. Zinc could be stably incorporated into the model, bonding with two N-terminal cysteines predicted to facilitate multimerisation. The GAr contains secondary structural elements in the models, while the protein binding regions are unstructured, irrespective of the prediction approach used and sequence origin. These intrinsically disordered regions may facilitate the diversity observed in partner interactions. We hypothesize that the structured GAr could mask the disordered regions, thereby protecting the protein from default degradation. In the dimer conformation, the C-terminal tails of each monomer wrap around a proline-rich protruding loop of the partner monomer, providing dimer stability, a feature which could be exploited in therapeutic design. PMID:25011696

  14. Genetic diversity and antigenicity variation of Babesia bovis merozoite surface antigen-1 (MSA-1) in Thailand.

    PubMed

    Tattiyapong, Muncharee; Sivakumar, Thillaiampalam; Takemae, Hitoshi; Simking, Pacharathon; Jittapalapong, Sathaporn; Igarashi, Ikuo; Yokoyama, Naoaki

    2016-07-01

    Babesia bovis, an intraerythrocytic protozoan parasite, causes severe clinical disease in cattle worldwide. The genetic diversity of parasite antigens often results in different immune profiles in infected animals, hindering efforts to develop immune control methodologies against the B. bovis infection. In this study, we analyzed the genetic diversity of the merozoite surface antigen-1 (msa-1) gene using 162 B. bovis-positive blood DNA samples sourced from cattle populations reared in different geographical regions of Thailand. The identity scores shared among 93 msa-1 gene sequences isolated by PCR amplification were 43.5-100%, and the similarity values among the translated amino acid sequences were 42.8-100%. Of 23 total clades detected in our phylogenetic analysis, Thai msa-1 gene sequences occurred in 18 clades; seven among them were composed of sequences exclusively from Thailand. To investigate differential antigenicity of isolated MSA-1 proteins, we expressed and purified eight recombinant MSA-1 (rMSA-1) proteins, including an rMSA-1 from B. bovis Texas (T2Bo) strain and seven rMSA-1 proteins based on the Thai msa-1 sequences. When these antigens were analyzed in a western blot assay, anti-T2Bo cattle serum strongly reacted with the rMSA-1 from T2Bo, as well as with three other rMSA-1 proteins that shared 54.9-68.4% sequence similarity with T2Bo MSA-1. In contrast, no or weak reactivity was observed for the remaining rMSA-1 proteins, which shared low sequence similarity (35.0-39.7%) with T2Bo MSA-1. While demonstrating the high genetic diversity of the B. bovis msa-1 gene in Thailand, the present findings suggest that the genetic diversity results in antigenicity variations among the MSA-1 antigens of B. bovis in Thailand. PMID:27101782

  15. Plasmodium falciparum liver stage antigen-1 is cross-linked by tissue transglutaminase

    PubMed Central

    2011-01-01

    Background Plasmodium falciparum sporozoites injected by mosquitoes into the blood rapidly enter liver hepatocytes and undergo pre-erythrocytic developmental schizogony forming tens of thousands of merozoites per hepatocyte. Shortly after hepatocyte invasion, the parasite starts to produce Liver Stage Antigen-1 (LSA-1), which accumulates within the parasitophorous vacuole surrounding the mass of developing merozoites. The LSA-1 protein has been described as a flocculent mass, but its role in parasite development has not been determined. Methods Recombinant N-terminal, C-terminal or a construct containing both the N- and C- terminal regions flanking two 17 amino acid residue central repeat sequences (LSA-NRC) were subjected to in vitro modification by tissue transglutaminase-2 (TG2) to determine if cross-linking occurred. In addition, tissue sections of P. falciparum-infected human hepatocytes were probed with monoclonal antibodies to the isopeptide ε-(γ-glutamyl)lysine cross-bridge formed by TG2 enzymatic activity to determine if these antibodies co-localized with antibodies to LSA-1 in the growing liver schizonts. Results This study identified a substrate motif for (TG2) and a putative casein kinase 2 phosphorylation site within the central repeat region of LSA-1. The function of TG2 is the post-translational modification of proteins by the formation of a unique isopeptide ε-(γ-glutamyl)lysine cross-bridge between glutamine and lysine residues. When recombinant LSA-1 protein was crosslinked in vitro by purified TG2 in a calcium dependent reaction, a flocculent mass of protein was formed that was highly resistant to degradation. The cross-linking was not detectably affected by phosphorylation with plasmodial CK2 in vitro. Monoclonal antibodies specific to the very unique TG2 catalyzed ε- lysine cross-bridge co-localized with antibodies to LSA-1 in infected human hepatocytes providing visual evidence that LSA-1 was cross-linked in vivo. Conclusions While the

  16. Lymphocyte function-associated antigen 1 is a receptor for Pasteurella haemolytica leukotoxin in bovine leukocytes.

    PubMed

    Jeyaseelan, S; Hsuan, S L; Kannan, M S; Walcheck, B; Wang, J F; Kehrli, M E; Lally, E T; Sieck, G C; Maheswaran, S K

    2000-01-01

    Pasteurella (Mannheimia) haemolytica leukotoxin (Lkt) causes cell type- and species-specific effects in ruminant leukocytes. Recent studies indicate that P. haemolytica Lkt binds to bovine CD18, the common subunit of all beta2 integrins. We designed experiments with the following objectives: to identify which member of the beta2 integrins is a receptor for Lkt; to determine whether Lkt binding to the receptor is target cell (bovine leukocytes) specific; to define the relationships between Lkt binding to the receptor, calcium elevation, and cytolysis; and to determine whether a correlation exists between Lkt receptor expression and the magnitude of target cell cytolysis. We compared Lkt-induced cytolysis in neutrophils from control calves and from calves with bovine leukocyte adhesion deficiency (BLAD), because neutrophils from BLAD-homozygous calves exhibit reduced beta2 integrin expression. The results demonstrate for the first time that Lkt binds to bovine CD11a and CD18 (lymphocyte function-associated antigen 1 [LFA-1]). The binding was abolished by anti-CD11a or anti-CD18 monoclonal antibody (MAb). Lkt-induced calcium elevation in bovine alveolar macrophages (BAMs) was inhibited by anti-CD11a or anti-CD18 MAb (65 to 94% and 37 to 98%, respectively, at 5 and 50 Lkt units per ml; P < 0.05). Lkt-induced cytolysis in neutrophils and BAMs was also inhibited by anti-CD11a or anti-CD18 MAb in a concentration-dependent manner. Lkt bound to porcine LFA-1 but did not induce calcium elevation or cytolysis. In neutrophils from BLAD calves, Lkt-induced cytolysis was decreased by 44% compared to that of neutrophils from control calves (P < 0.05). These results indicate that LFA-1 is a Lkt receptor, Lkt binding to LFA-1 is not target cell specific, Lkt binding to bovine LFA-1 correlates with calcium elevation and cytolysis, and bovine LFA-1 expression correlates with the magnitude of Lkt-induced target cell cytolysis. PMID:10603370

  17. Small molecule and peptide-mediated inhibition of Epstein-Barr virus nuclear antigen 1 dimerization

    SciTech Connect

    Kim, Sun Young; Song, Kyung-A; Kieff, Elliott; Kang, Myung-Soo

    2012-07-27

    Highlights: Black-Right-Pointing-Pointer Evidence that targeting EBNA1 dimer, an EBV onco-antigen, can be achievable. Black-Right-Pointing-Pointer A small molecule and a peptide as EBNA1 dimerization inhibitors identified. Black-Right-Pointing-Pointer Both inhibitors associated with EBNA1 and blocked EBNA1 DNA binding activity. Black-Right-Pointing-Pointer Also, prevented its dimerization, and repressed viral gene transcription. -- Abstract: Latent Epstein-Barr virus (EBV) infection is associated with human B cell lymphomas and certain carcinomas. EBV episome persistence, replication, and gene expression are dependent on EBV-encoded nuclear antigen 1 (EBNA1)'s DNA binding domain (DBD)/dimerization domain (DD)-mediated sequence-specific DNA binding activity. Homodimerization of EBNA1 is essential for EBNA1 DNA binding and transactivation. In this study, we characterized a novel small molecule EBNA1 inhibitor EiK1, screened from the previous high throughput screening (HTS). The EiK1 compound specifically inhibited the EBNA1-dependent, OriP-enhanced transcription, but not EBNA1-independent transcription. A Surface Plasmon Resonance Biacore assay revealed that EiK1 associates with EBNA1 amino acid 459-607 DBD/DD. Consistent with the SPR data, in vitro gel shift assays showed that EiK1 suppressed the activity of EBNA1 binding to the cognate familial repeats (FR) sequence, but not control RBP-J{kappa} binding to the J{kappa} site. Subsequently, a cross-linker-mediated in vitro multimerization assay and EBNA1 homodimerization-dependent yeast two-hybrid assay showed that EiK1 significantly inhibited EBNA1 dimerization. In an attempt to identify more highly specific peptide inhibitors, small peptides encompassing the EBNA1 DBD/DD were screened for inhibition of EBNA1 DBD-mediated DNA binding function. The small peptide P85, covering EBNA1 a.a. 560-574, significantly blocked EBNA1 DNA binding activity in vitro, prevented dimerization in vitro and in vivo, associated with

  18. Bioavailability of intramuscularly administered tenoxicam.

    PubMed

    Stebler, T; Guentert, T W

    1993-08-01

    Bioavailability of intramuscularly administered tenoxicam relative to single oral and relative to intravenous doses was determined in two separate randomized crossover studies. Twelve healthy volunteers (12 males, age 20-30 years) received a rapid intravenous injection and a single intramuscular dose and 12 other subjects (11 males, 1 female, age 21-25 years) a single oral and a single intramuscular dose of 20 mg of tenoxicam on two different occasions. The wash-out period between the two consecutive treatments was 4 weeks. Plasma concentrations after dosing were determined by a specific HPLC method. Differences in tenoxicam concentration-time profiles after the different routes of administration were limited to the first 2 h after dosing. Later, plasma concentrations were almost superimposable within and across the two studies. The extent of absorption of intramuscularly administered tenoxicam was complete (mean +/- CV per cent: F(abs) 0.99 +/- 20 per cent) with no difference between the two extravascular administrations (F(rel) 0.95 +/- 10 per cent, intramuscular vs oral). After intramuscular administration tenoxicam was more rapidly absorbed compared to the oral dose (Tmax 0.71 h +/- 80 per cent vs 1.4 h +/- 62 per cent; p > 0.05). Peak concentrations after oral and intramuscular administration (Cmax 2.5 mg l-1 +/- 19 per cent vs 2.7 mg l-1 +/- 14 per cent; p < 0.05) were very similar. PMID:8218966

  19. 16 CFR 1000.2 - Laws administered.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Laws administered. 1000.2 Section 1000.2 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION GENERAL COMMISSION ORGANIZATION AND FUNCTIONS § 1000.2 Laws administered. The Commission administers five acts: (a) The Consumer Product Safety Act...

  20. 16 CFR 1000.2 - Laws administered.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 2 2013-01-01 2013-01-01 false Laws administered. 1000.2 Section 1000.2 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION GENERAL COMMISSION ORGANIZATION AND FUNCTIONS § 1000.2 Laws administered. The Commission administers five acts: (a) The Consumer Product Safety Act...

  1. 16 CFR 1000.2 - Laws administered.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Laws administered. 1000.2 Section 1000.2 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION GENERAL COMMISSION ORGANIZATION AND FUNCTIONS § 1000.2 Laws administered. The Commission administers five acts: (a) The Consumer Product Safety Act...

  2. 16 CFR 1000.2 - Laws administered.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 2 2014-01-01 2014-01-01 false Laws administered. 1000.2 Section 1000.2 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION GENERAL COMMISSION ORGANIZATION AND FUNCTIONS § 1000.2 Laws administered. The Commission administers five acts: (a) The Consumer Product Safety Act...

  3. 16 CFR 1000.2 - Laws administered.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Laws administered. 1000.2 Section 1000.2 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION GENERAL COMMISSION ORGANIZATION AND FUNCTIONS § 1000.2 Laws administered. The Commission administers five acts: (a) The Consumer Product Safety Act...

  4. Association of serum Epstein-Barr nuclear antigen-1 antibodies and intrathecal immunoglobulin synthesis in early multiple sclerosis.

    PubMed

    Pfuhl, Catherina; Oechtering, Johanna; Rasche, Ludwig; Gieß, René M; Behrens, Janina R; Wakonig, Katharina; Freitag, Erik; Pache, Florence C; Otto, Carolin; Hofmann, Jörg; Eberspächer, Bettina; Bellmann-Strobl, Judith; Paul, Friedemann; Ruprecht, Klemens

    2015-08-15

    Multiple sclerosis (MS) is associated with Epstein-Barr virus (EBV) infection. A characteristic feature of MS is an intrathecal synthesis of immunoglobulin (Ig)G. In 90 patients with clinically isolated syndromes/early relapsing-remitting MS, serum antibodies to Epstein-Barr nuclear antigen-1, but not to EBV viral capsid antigen, rubella, or varicella zoster virus, were higher (p=0.03) in those with than those without a calculated intrathecal IgG synthesis >0% and correlated with the percentage (r=0.27, p=0.009) and concentration (r=0.27, p=0.012) of intrathecally produced IgG. These findings suggest a link between EBV infection and the events leading to intrathecal IgG synthesis in patients with MS. PMID:26198934

  5. 22 CFR 196.4 - Administering office.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Administering office. 196.4 Section 196.4 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL COMMERCIAL ARBITRATION THOMAS R. PICKERING FOREIGN AFFAIRS/GRADUATE FOREIGN AFFAIRS FELLOWSHIP PROGRAM § 196.4 Administering office. The Department of...

  6. 16 CFR 0.4 - Laws administered.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Laws administered. 0.4 Section 0.4 Commercial Practices FEDERAL TRADE COMMISSION ORGANIZATION, PROCEDURES AND RULES OF PRACTICE ORGANIZATION § 0.4 Laws administered. The Commission exercises enforcement and administrative authority under the Federal Trade Commission Act (15 U.S.C....

  7. 16 CFR 0.4 - Laws administered.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 1 2011-01-01 2011-01-01 false Laws administered. 0.4 Section 0.4 Commercial Practices FEDERAL TRADE COMMISSION ORGANIZATION, PROCEDURES AND RULES OF PRACTICE ORGANIZATION § 0.4 Laws administered. The Commission exercises enforcement and administrative authority under the Federal Trade Commission Act (15 U.S.C....

  8. 7 CFR 247.3 - Administering agencies.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 4 2010-01-01 2010-01-01 false Administering agencies. 247.3 Section 247.3 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE CHILD NUTRITION PROGRAMS COMMODITY SUPPLEMENTAL FOOD PROGRAM § 247.3 Administering agencies....

  9. Relaxation processes in administered-rate pricing

    NASA Astrophysics Data System (ADS)

    Hawkins, Raymond J.; Arnold, Michael R.

    2000-10-01

    We show how the theory of anelasticity unifies the observed dynamics and proposed models of administered-rate products. This theory yields a straightforward approach to rate model construction that we illustrate by simulating the observed relaxation dynamics of two administered rate products. We also demonstrate how the use of this formalism leads to a natural definition of market friction.

  10. Comparison and Equating of Paper-Administered, Computer-Administered and Computerized Adaptive Tests of Achievement.

    ERIC Educational Resources Information Center

    Olsen, James B.; And Others

    Student achievement test scores were compared and equated, using three different testing methods: paper-administered, computer-administered, and computerized adaptive testing. The tests were developed from third and sixth grade mathematics item banks of the California Assessment Program. The paper and the computer-administered tests were identical…

  11. Antibodies specific for Epstein-Barr virus nuclear antigen-1 cross-react with human heterogeneous nuclear ribonucleoprotein L.

    PubMed

    Lindsey, J William; deGannes, Samantha L; Pate, Kimberly A; Zhao, Xiurong

    2016-01-01

    Epstein-Barr virus (EBV) is associated with multiple sclerosis (MS), and antibodies to the EBV nuclear antigen-1 (EBNA-1) are consistently increased in MS patients. The hypothesis of this study is that anti-EBNA-1 antibodies cross-react with a self antigen in MS patients. We affinity purified anti-EBNA-1 antibodies from human plasma, used the anti-EBNA-1 to immunoprecipitate antigens from human brain, and identified bound antigens with mass spectrometry. Anti-EBNA-1 consistently bound heterogeneous nuclear ribonucleoprotein L (HNRNPL). We expressed both the long and short isoforms of this protein, and verified with Western blots and ELISA that the long isoform cross-reacts with EBNA-1. Immunohistochemistry demonstrated that anti-EBNA-1 bound to an antigen in the nucleus of cultured rat central nervous system cells. ELISA demonstrated the presence of antibodies to HNRNPL in the plasma of both healthy controls and MS patients, but anti-HNRNPL was not increased in MS patients. We conclude that HNRNPL is an autoantigen which cross-reacts with EBNA-1. The relevance of this autoantigen to MS and other autoimmune diseases remains to be investigated. PMID:26637929

  12. Nucleolin is important for Epstein-Barr virus nuclear antigen 1-mediated episome binding, maintenance, and transcription.

    PubMed

    Chen, Ya-Lin; Liu, Cheng-Der; Cheng, Chi-Ping; Zhao, Bo; Hsu, Hao-Jen; Shen, Chih-Long; Chiu, Shu-Jun; Kieff, Elliott; Peng, Chih-wen

    2014-01-01

    Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) is essential for EBV episome maintenance, replication, and transcription. These effects are mediated by EBNA1 binding to cognate oriP DNA, which comprise 20 imperfect copies of a 30-bp dyad symmetry enhancer and an origin for DNA replication. To identify cell proteins essential for these EBNA1 functions, EBNA1 associated cell proteins were immune precipitated and analyzed by liquid chromatography-tandem mass spectrometry. Nucleolin (NCL) was identified to be EBNA1 associated. EBNA1's N-terminal 100 aa and NCL's RNA-binding domains were critical for EBNA1/NCL interaction. Lentivirus shRNA-mediated NCL depletion substantially reduced EBNA1 recruitment to oriP DNA, EBNA1-dependent transcription of an EBV oriP luciferase reporter, and EBV genome maintenance in lymphoblastoid cell lines. NCL RNA-binding domain K429 was critical for ATP and EBNA1 binding. NCL overexpression increased EBNA1 binding to oriP and transcription, whereas NCL K429A was deficient. Moreover, NCL silencing impaired lymphoblastoid cell line growth. These experiments reveal a surprisingly critical role for NCL K429 in EBNA1 episome maintenance and transcription, which may be a target for therapeutic intervention. PMID:24344309

  13. Proteome Based Construction of the Lymphocyte Function-Associated Antigen 1 (LFA-1) Interactome in Human Dendritic Cells

    PubMed Central

    Eich, Christina; Lasonder, Edwin; Cruz, Luis J.; Reinieren-Beeren, Inge; Cambi, Alessandra; Figdor, Carl G.; Buschow, Sonja I.

    2016-01-01

    The β2-integrin lymphocyte function-associated antigen 1 (LFA-1) plays an important role in the migration, adhesion and intercellular communication of dendritic cells (DCs). During the differentiation of human DCs from monocyte precursors, LFA-1 ligand binding capacity is completely lost, even though its expression levels were remained constant. Yet LFA-1-mediated adhesive capacity on DCs can be regained by exposing DCs to the chemokine CCL21, suggesting a high degree of regulation of LFA-1 activity during the course of DC differentiation. The molecular mechanisms underlying this regulation of LFA-1 function in DCs, however, remain elusive. To get more insight we attempted to identify specific LFA-1 binding partners that may play a role in regulating LFA-1 activity in DCs. We used highly sensitive label free quantitative mass-spectrometry to identify proteins co-immunoprecipitated (co-IP) with LFA-1 from ex vivo generated DCs. Among the potential binding partners we identified not only established components of integrin signalling pathways and cytoskeletal proteins, but also several novel LFA-1 binding partners including CD13, galectin-3, thrombospondin-1 and CD44. Further comparison to the LFA-1 interaction partners in monocytes indicated that DC differentiation was accompanied by an overall increase in LFA-1 associated proteins, in particular cytoskeletal, signalling and plasma membrane (PM) proteins. The here presented LFA-1 interactome composed of 78 proteins thus represents a valuable resource of potential regulators of LFA-1 function during the DC lifecycle. PMID:26889827

  14. Decitabine enhances stem cell antigen-1 expression in cigarette smoke extract-induced emphysema in animal model.

    PubMed

    He, Zhi-Hui; Chen, Yan; Chen, Ping; He, Sheng-Dong; Ye, Ji-Ru; Liu, Da

    2016-01-01

    Stem cell antigen-1 (Sca-1) is a mouse glycosyl phosphatidylinositol-anchored protein and a cell surface marker found on hematopoietic stem cells (HSCs). Despite decades of study, its biological functions remain little known. Sca-1 is a typical marker of bone marrow-derived HSCs, it is also expressed by a mixture of tissue-resident stem, progenitor cells in nonhematopoietic organs. Endothelial progenitor cell (EPC) is a subtype of HSC and contributes to endothelial repair by homing in on locations of injury. Abnormal genetic methylation has been detected in smoking-related diseases. The present study aimed to investigate the lung function and histomorphology, the expression of Sca-1 gene in lung tissues, and bone marrow-derived EPCs in cigarette smoke extract (CSE)-induced emphysema mice, and to further determine whether Decitabine (Dec), the most widely used inhibitor of DNA methylation, could protect against the damages caused by CSE. The results of the present study demonstrated that Dec could partly protect against CSE-induced emphysema in mice, enhance Sca-1 expression in lung tissue, and bone marrow-derived EPCs. The results suggested that the depletion of the progenitor cell pool and DNA methylation of Sca-1 gene may be involved in the progression of emphysema in mice. PMID:26264445

  15. Myeloid-specific Fos-related antigen-1 regulates cigarette smoke-induced lung inflammation, not emphysema, in mice.

    PubMed

    Vaz, Michelle; Rajasekaran, Subbiah; Potteti, Haranatha R; Reddy, Sekhar P

    2015-07-01

    Heightened lung inflammation is a cardinal feature of chronic obstructive pulmonary disease (COPD). Cigarette smoke (CS)-induced macrophage recruitment and activation, accompanied by abnormal secretion of a number of inflammatory cytokines and matrix metalloproteinases, play a major role in the pathophysiology of COPD. The Fos-related antigen-1 (Fra-1) transcription factor differentially regulates several cellular processes that are implicated in COPD, such as inflammation and immune responses, cell proliferation and death, and extracellular remodeling. Although CS stimulates Fra-1 expression in the lung, the precise role of this transcription factor in the regulation of CS-induced lung inflammation in vivo is poorly understood. Here, we report that myeloid-specific Fra-1 signaling is important for CS-induced lung macrophagic inflammatory response. In response to chronic CS exposure, mice with Fra-1 specifically deleted in myeloid cells showed reduced levels of CS-induced lung macrophagic inflammation, accompanied by decreased expression levels of proinflammatory cytokines compared with their wild-type counterparts. Consistent with this result, bone marrow-derived Fra-1-null macrophages treated with CS showed decreased levels of proinflammatory mediators and matrix metalloproteinases. Interestingly, deletion of Fra-1 in myeloid cells did not affect the severity of emphysema. We propose that Fra-1 plays a key role in promoting chronic CS-induced lung macrophagic inflammation in vivo, and that targeting this transcription factor may be useful in dampening persistent lung inflammation in patients with COPD. PMID:25489966

  16. The Epstein-Barr virus nuclear antigen-1 reprograms transcription by mimicry of high mobility group A proteins.

    PubMed

    Coppotelli, Giuseppe; Mughal, Nouman; Callegari, Simone; Sompallae, Ramakrishna; Caja, Laia; Luijsterburg, Martijn S; Dantuma, Nico P; Moustakas, Aristidis; Masucci, Maria G

    2013-03-01

    Viral proteins reprogram their host cells by hijacking regulatory components of protein networks. Here we describe a novel property of the Epstein-Barr virus (EBV) nuclear antigen-1 (EBNA1) that may underlie the capacity of the virus to promote a global remodeling of chromatin architecture and cellular transcription. We found that the expression of EBNA1 in transfected human and mouse cells is associated with decreased prevalence of heterochromatin foci, enhanced accessibility of cellular DNA to micrococcal nuclease digestion and decreased average length of nucleosome repeats, suggesting de-protection of the nucleosome linker regions. This is a direct effect of EBNA1 because targeting the viral protein to heterochromatin promotes large-scale chromatin decondensation with slow kinetics and independent of the recruitment of adenosine triphosphate-dependent chromatin remodelers. The remodeling function is mediated by a bipartite Gly-Arg rich domain of EBNA1 that resembles the AT-hook of High Mobility Group A (HMGA) architectural transcription factors. Similar to HMGAs, EBNA1 is highly mobile in interphase nuclei and promotes the mobility of linker histone H1, which counteracts chromatin condensation and alters the transcription of numerous cellular genes. Thus, by regulating chromatin compaction, EBNA1 may reset cellular transcription during infection and prime the infected cells for malignant transformation. PMID:23358825

  17. Self-administered treatment for smoking cessation.

    PubMed

    Curry, Susan J; Ludman, Evette J; McClure, Jennifer

    2003-03-01

    Self-administered treatment for smoking cessation has the potential to reach a broad spectrum of the population of smokers. This article focuses on self-administration of behavioral and pharmacological treatments for smoking cessation. Evidence for the effectiveness of written manuals to self-administer behavioral treatment is mixed. There is no evidence that self-help manuals alone are effective. However, they do increase quit rates when combined with personalized adjuncts such as written feedback and outreach telephone counseling. Efficacy trials of first-line pharmacotherapies (nicotine gum, nicotine patch, and bupropion) result in doubling of cessation rates compared to placebo. It is difficult to evaluate the effectiveness of pharmacotherapies when self-administered under real-world conditions. The general consensus is that they improve quit rates, although poor compliance and early discontinuation reduce their effectiveness. Areas for further research include randomized trials of the use of new technologies (e.g., hand-held computers and the Internet) to disseminate self-administered treatments as well as improved surveillance of the use of self-administered treatment in population-based health surveys. PMID:12579547

  18. IL-13 Production by Regulatory T Cells Protects Against Experimental Autoimmune Encephalomyelitis (EAE) Independent of Auto-Antigen1

    PubMed Central

    Ochoa-Repáraz, Javier; Rynda, Agnieszka; Ascón, Miguel A.; Yang, Xinghong; Kochetkova, Irina; Riccardi, Carol; Callis, Gayle; Trunkle, Theresa; Pascual, David W.

    2008-01-01

    Treatment with an anti-inflammatory Salmonella vaccine expressing enterotoxigenic E. coli colonization factor antigen 1 (CFA/I) proved effective in stimulating protective, potent CD25+ CD4+ T (Treg) cells in susceptible mice challenged with experimental autoimmune encephalomyelitis (EAE). Since the Salmonella vector was considerably less protective, we questioned whether altering the fimbrial subunit expression to resemble conventional Salmonella expression may impact Treg cell potency. The Salmonella-CFA/I vaccine was modified to limit the fimbrial subunit expression to the intracellular compartment (Salmonella-CFA/IIC). SJL mice were challenged with proteolipid protein (PLP)139–151 to induce EAE and orally treated with one of three Salmonella vaccines six days post-challenge. Treatment with Salmonella-CFA/IIC greatly reduced clinical disease, similar to Salmonella-CFA/I, by subduing IL-17 and IL-21; however, mechanisms of protection differed, as evident by increased IL-13 and IFN-γ, but diminished TGF-β production by Treg cells from Salmonella-CFA/IIC-treated mice. Adoptive transfer of Treg cells from both CFA/I-expressing constructs was equivalent in protecting against EAE, showing minimal disease. While not as potent in its protection, CD25−CD4+ T cells from Salmonella-CFA/IIC showed minimal Th2 cells, but this vaccine did prime for Th2 cells subsequent EAE challenge. In vivo IL-13, but not IFN-γ neutralization, compromised protection conferred by adoptive transfer with Salmonella-CFA/IIC-induced Treg cells. Thus, the Salmonella-CFA/IIC vaccine elicits Treg cells with attributes from both the Salmonella vector and Salmonella-CFA/I vaccines. Importantly, these Treg cells can be induced to high potency by simply vaccinating against irrelevant Ags, offering a novel approach to treat autoimmune diseases independently of the auto-Ag. PMID:18606647

  19. NMR characterization of the conformational fluctuations of the human lymphocyte function-associated antigen-1 I-domain

    PubMed Central

    Leung, Hoi Tik Alvin; Kukic, Predrag; Camilloni, Carlo; Bemporad, Francesco; De Simone, Alfonso; Aprile, Francesco A; Kumita, Janet R; Vendruscolo, Michele

    2014-01-01

    Lymphocyte function-associated antigen-1 (LFA-1) is an integrin protein that transmits information across the plasma membrane through the so-called inside-out and outside-in signaling mechanisms. To investigate these mechanisms, we carried out an NMR analysis of the dynamics of the LFA-1 I-domain, which has enabled us to characterize the motions of this domain on a broad range of timescales. We studied first the internal motions on the nanosecond timescale by spin relaxation measurements and model-free analysis. We then extended this analysis to the millisecond timescale motions by measuring 15N-1H residual dipolar couplings of the backbone amide groups. We analyzed these results in the context of the three major conformational states of the I-domain using their corresponding X-ray crystallographic structures. Our results highlight the importance of the low-frequency motions of the LFA-1 I-domain in the inactive apo-state. We found in particular that α-helix 7 is in a position in the apo-closed state that cannot be fully described by any of the existing X-ray structures, as it appears to be in dynamic exchange between different conformations. This type of motion seems to represent an inherent property of the LFA-1 I-domain and might be relevant for controlling the access to the allosteric binding pocket, as well as for the downward displacement of α-helix 7 that is required for the activation of LFA-1. PMID:25147050

  20. Changes in Medications Administered in Schools

    ERIC Educational Resources Information Center

    McCarthy, Ann Marie; Kelly, Michael W.; Johnson, Shella; Roman, Jaclyn; Zimmerman, M. Bridget

    2006-01-01

    The purpose of this descriptive, cross-sectional study was to determine if there have been changes in the type and number of attention deficit/hyperactivity disorder (AD/HD) medications administered in schools since the introduction of long-acting stimulants. A survey was sent to 1,000 school nurses randomly selected from the National Association…

  1. Teaching Students to Administer the WISC

    ERIC Educational Resources Information Center

    Ritter, Kathleen Yost

    1977-01-01

    A college level psychology course is described in which students were trained by both traditional and experimental methods to administer individual intelligence tests. Comparative analysis of performance by each group indicates that student motivation and performance is not greatly influenced by teaching method and that videotape demonstrations…

  2. Genome-wide analysis of host-chromosome binding sites for Epstein-Barr Virus Nuclear Antigen 1 (EBNA1)

    PubMed Central

    2010-01-01

    The Epstein-Barr Virus (EBV) Nuclear Antigen 1 (EBNA1) protein is required for the establishment of EBV latent infection in proliferating B-lymphocytes. EBNA1 is a multifunctional DNA-binding protein that stimulates DNA replication at the viral origin of plasmid replication (OriP), regulates transcription of viral and cellular genes, and tethers the viral episome to the cellular chromosome. EBNA1 also provides a survival function to B-lymphocytes, potentially through its ability to alter cellular gene expression. To better understand these various functions of EBNA1, we performed a genome-wide analysis of the viral and cellular DNA sites associated with EBNA1 protein in a latently infected Burkitt lymphoma B-cell line. Chromatin-immunoprecipitation (ChIP) combined with massively parallel deep-sequencing (ChIP-Seq) was used to identify cellular sites bound by EBNA1. Sites identified by ChIP-Seq were validated by conventional real-time PCR, and ChIP-Seq provided quantitative, high-resolution detection of the known EBNA1 binding sites on the EBV genome at OriP and Qp. We identified at least one cluster of unusually high-affinity EBNA1 binding sites on chromosome 11, between the divergent FAM55 D and FAM55B genes. A consensus for all cellular EBNA1 binding sites is distinct from those derived from the known viral binding sites, suggesting that some of these sites are indirectly bound by EBNA1. EBNA1 also bound close to the transcriptional start sites of a large number of cellular genes, including HDAC3, CDC7, and MAP3K1, which we show are positively regulated by EBNA1. EBNA1 binding sites were enriched in some repetitive elements, especially LINE 1 retrotransposons, and had weak correlations with histone modifications and ORC binding. We conclude that EBNA1 can interact with a large number of cellular genes and chromosomal loci in latently infected cells, but that these sites are likely to represent a complex ensemble of direct and indirect EBNA1 binding sites. PMID

  3. Stem Cells Antigen-1 Enriches for a Cancer Stem Cell-Like Subpopulation in Mouse Gastric Cancer.

    PubMed

    Park, Jun Won; Park, Jung Min; Park, Dong Min; Kim, Dae-Yong; Kim, Hark Kyun

    2016-05-01

    There is a strong need to identify markers to enrich gastric cancer stem cells (CSCs). However, CSC enrichment markers for mouse gastric cancers have not yet been determined. In our previous study, we generated primary mouse gastric cancer cell line NCC-S1 (S1) established from a Villin-cre;Smad4(F/F) ;Trp53(F/F) ;Cdh1(F/wt) mouse and its metastatic variant cell line NCC-S1M (S1M). Interestingly, S1M cells exhibited CSC-like features, such as increased tumorigenic potential and chemoresistance. By comparing gene expression profiles between S1 and S1M cells, we identified Stem Cells Antigen-1 (Sca-1) as a cell surface marker, which was mostly upregulated in S1M. Sca-1 was upregulated in tumorspheres from S1 cells or after cisplatin treatment in S1 cells. Immunofluorescence (IF) analysis showed that approximately 7% of cancer cells exhibited positivity for Sca-1 in primary mouse gastric cancer tissues. An in vivo-limiting dilution assay showed that Sca-1(high) mouse gastric cancer cells demonstrated increased tumorigenicity compared with Sca-1(negative) cells. The Sca-1 expression was downregulated by TGF-β pathway activation and Wnt pathway inhibition in mouse gastric cancer cells. Sca-1(high) cells showed relatively low TGF-β reporter activity and high TCF/LEF1 reporter activity compared with Sca-1(negative) cells. A chromatin immunoprecipitation analysis demonstrated that Sca-1 was a β-catenin/LEF1 target gene. Sca-1(high) allografts were more resistant to cisplatin/fluorouracil chemotherapy than Sca-1(negative) allografts, and overexpressed Bcl-xL. Eighty-five mouse genes overexpressed in Sca-1(high) S1 cells compared with Sca-1(negative) cells clustered 123 pretreatment gastric cancer patient samples according to survival following chemotherapy. Taken together, Sca-1 is a novel CSC enrichment marker that mediates TGF-β and Wnt/β-catenin signaling in mouse gastric cancer. Stem Cells 2016;34:1177-1187. PMID:26869189

  4. Sequence Variation Analysis of Epstein-Barr Virus Nuclear Antigen 1 Gene in the Virus Associated Lymphomas of Northern China

    PubMed Central

    Sun, Lingling; Zhao, Zhenzhen; Liu, Song; Liu, Xia; Sun, Zhifu; Luo, Bing

    2015-01-01

    Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) is the only viral protein expressed in all EBV-positive tumors as it is essential for the maintenance, replication and transcription of the virus genome. According to the polymorphism of residue 487 in EBNA1 gene, EBV isolates can be classified into five subtypes: P-ala, P-thr, V-val, V-leu and V-pro. Whether these EBNA1 subtypes contribute to different tissue tropism of EBV and are consequently associated with certain malignancies remain to be determined. To elucidate the relationship, one hundred and ten EBV-positive lymphoma tissues of different types from Northern China, a non-NPC endemic area, were tested for the five subtypes by nested-PCR and DNA sequencing. In addition, EBV type 1 and type 2 classification was typed by using standard PCR assays across type-specific regions of the EBNA3C genes. Four EBNA1 subtypes were identified: V-val (68.2%, 75/110), P-thrV (15.5%, 17/110), V-leuV (3.6%, 4/110) and P-ala (10.9%, 12/110). The distribution of the EBNA1 subtypes in the four lymphoma groups was not significantly different (p = 0.075), neither was that of the EBV type 1/type 2 (p = 0.089). Compared with the previous data of gastric carcinoma (GC), nasopharyngeal carcinoma (NPC) and throat washing (TW) from healthy donors, the distribution of EBNA1 subtypes in lymphoma differed significantly (p = 0.016), with a little higher frequency of P-ala subtype. The EBV type distribution between lymphoma and the other three groups was significantly different (p = 0.000, p = 0.000, p = 0.001, respectively). The proportion of type 1 and type 2 mixed infections was higher in lymphoma than that in GC, NPC and TW. In lymphomas, the distribution of EBNA1 subtypes in the three EBV types was not significantly different (p = 0.546). These data suggested that the variation patterns of EBNA1 gene may be geographic-associated rather than tumor-specific and the role of EBNA1 gene variations in tumorigenesis needs more extensive and

  5. Administering social security: challenges yesterday and today.

    PubMed

    Puckett, Carolyn

    2010-01-01

    In 2010, the Social Security Administration (SSA) celebrates the 75th anniversary of the passage of the Social Security Act. In those 75 years, SSA has been responsible for programs providing unemployment insurance, child welfare, and supervision of credit unions, among other duties. This article focuses on the administration of the Old-Age, Survivors, and Disability Insurance program, although it also covers some of the other major programs SSA has been tasked with administering over the years-in particular, Medicare, Black Lung benefits, and Supplemental Security Income. The article depicts some of the challenges that have accompanied administering these programs and the steps that SSA has taken to meet those challenges. Whether implementing complex legislation in short timeframes or coping with natural disasters, SSA has found innovative ways to overcome problems and has evolved to meet society's changing needs. PMID:20737858

  6. Ocular toxicity from systemically administered xenobiotics

    PubMed Central

    Gokulgandhi, Mitan R; Vadlapudi, Aswani Dutt; Mitra, Ashim K

    2015-01-01

    Introduction The eye is considered as the most privileged organ because of the blood–ocular barrier that acts as a barrier to systemically administered xenobiotics. However, there has been a significant increase in the number of reports on systemic drug-induced ocular complications. If such complications are left untreated, then it may cause permanent damage to vision. Hence, knowledge of most recent updates on ever-increasing reports of such toxicities has become imperative to develop better therapy while minimizing toxicities. Areas covered The article is mainly divided into anterior and posterior segment manifestations caused by systemically administered drugs. The anterior segment is further elaborated on corneal complications where as the posterior segment is focused on optic nerve, retinal and vitreous complications. Furthermore, this article includes recent updates on acute and chronic ocular predicaments, in addition to discussing various associated symptoms caused by drugs. Expert opinion Direct correlation of ocular toxicities due to systemic drug therapy is evident from current literature. Therefore, it is necessary to have detailed documentation of these complications to improve understanding and predict toxicities. We made an attempt to ensure that the reader is aware of the characteristic ocular complications, the potential for irreversible drug toxicity and indications for cessation. PMID:22803583

  7. The radiation dosimetry of intrathecally administered radionuclides

    SciTech Connect

    Stabin, M.G.; Evans, J.F.

    1999-01-01

    The radiation dose to the spine, spinal cord, marrow, and other organs of the body from intrathecal administration of several radiopharmaceuticals was studied. Anatomic models were developed for the spine, spinal cerebrospinal fluid (CSF), spinal cord, spinal skeleton, cranial skeleton, and cranial CSF. A kinetic model for the transport of CSF was used to determine residence times in the CSF; material leaving the CSF was thereafter assumed to enter the bloodstream and follow the kinetics of the radiopharmaceutical as if intravenously administered. The radiation transport codes MCNP and ALGAMP were used to model the electron and photon transport and energy deposition. The dosimetry of Tc-99m DTPA and HSA, In-111 DTPA, I-131 HSA, and Yb-169 DTPA was studied. Radiation dose profiles for the spinal cord and marrow in the spine were developed and average doses to all other organs were estimated, including dose distributions within the bone and marrow.

  8. Epstein-Barr virus-induced autoimmune responses. I. Immunoglobulin M autoantibodies to proteins mimicking and not mimicking Epstein-Barr virus nuclear antigen-1.

    PubMed

    Vaughan, J H; Valbracht, J R; Nguyen, M D; Handley, H H; Smith, R S; Patrick, K; Rhodes, G H

    1995-03-01

    In previous studies of infectious mononucleosis, we found IgM autoantibodies which react with hematopoietic cell antigens. Many of these were inhibited by synthetic glycine/alanine peptides representing the glycine/alanine repeat of Epstein-Barr virus nuclear antigen-1. We have cloned and expressed fragments of genes encoding two of these autoantigens. One gene (p542) encodes a protein containing a glycine-rich 28-mer, which is its chief autoantigenic epitope and which represents a newly identified class of evolutionarily conserved autoepitopes. The other gene (p554) encodes a protein that is not demonstrably cross-reactive with Epstein-Barr virus nuclear antigen-1 or with any other EBV protein, but forms complexes with other proteins. Immunoaffinity-purified anti-p542 and anti-p554 have relatively high binding affinities, as evidenced by inhibition at 10(6)-10(8) M-1, and neither autoantibody showed polyreactivity with other common antigens. The data thus suggest that neither autoantibody is simply an expression of polyclonal B cell activation. We conclude that the two autoantigens stimulate autoantibody synthesis by different mechanisms. One autoantigen shares homology to a viral protein which generates cross-reacting antibodies to the autoantigenic epitope. The other has no recognizable cross-reaction with the infecting pathogen and may become immunogenic through complexing with other proteins. PMID:7533788

  9. Effects of cytokines and periodontopathic bacteria on the leukocyte function-associated antigen 1/intercellular adhesion molecule 1 pathway in gingival fibroblasts in adult periodontitis.

    PubMed

    Hayashi, J; Saito, I; Ishikawa, I; Miyasaka, N

    1994-12-01

    We investigated the effects of inflammatory cytokines and periodontopathic bacteria on expression of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1, and E-selectin (endothelial leukocyte adhesion molecule 1) in cultured human gingival fibroblasts (HGF). Cell surface ICAM-1 was upregulated on HGF under transcriptional control by exposure not only to interleukin-1 beta, tumor necrosis factor alpha, and gamma interferon but also to sonic extracts prepared from Porphyromonas gingivalis and Prevotella intermedia (nigrescens) and lipopolysaccharides from Escherichia coli. However, these stimuli induced only minimal expression of vascular cell adhesion molecule 1 and E-selectin on HGF. Binding assays using HGF and Molt 4, the human T-cell leukemia cell line, showed induced ICAM-1 to be functional, and the increased binding was blocked by a combination of monoclonal antibodies against ICAM-1 and leukocyte function-associated antigen 1. Furthermore, gingival tissues from adult periodontitis patients showed increased mRNA expression of ICAM-1 compared with that in tissues from normal healthy donors. In immunohistological analysis, we also observed in vivo that the expression of ICAM-1 on fibroblasts in adult periodontitis tissues was greater than that in normal gingiva. Thus, the overexpression of ICAM-1 on gingival fibroblasts induced by cytokines and periodontopathic bacteria is speculated to be deeply involved in the accumulation and retention of leukocyte function-associated antigen 1-bearing leukocytes in adult periodontitis lesions. PMID:7525481

  10. [Pharmacokinetics of cefatrizine administered in repeated doses].

    PubMed

    Couet, W; Reigner, B G; Lefebvre, M A; Bizouard, J; Fourtillan, J B

    1988-05-01

    Twelve healthy volunteers received cefatrizine orally at doses equal to 500 mg every 12 h for 5 days. Cefatrizine was assayed by high performance liquid chromatography in plasma and urines collected after the first and/or the last administration. Cefatrizine absorption was rapid; its peak plasma level was reached at time 1.79 +/- 0.07 h following the first dose, it was equal to 7.37 +/- 0.31 micrograms.ml-1. Its apparent elimination half-life was equal to 1.50 +/- 0.05 h, it explains the lack of accumulation with time during multiple administrations every 12 hours. Comparisons between peak plasma concentration and area under curves following the first and last dosing showed significant (p less than 0.01) but weak (close to 15%) reduction of these 2 parameters with time which could be explained by a slight reduction of cefatrizine absorption with time. In conclusion, cefatrizine does not accumulate when administered repeatedly at a dose equal to 500 mg every 12 h in young adult, and its pharmacokinetics is virtually linear with time. PMID:3043350

  11. 40 CFR 147.1700 - State-administered program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 24 2012-07-01 2012-07-01 false State-administered program. 147.1700 Section 147.1700 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS North Carolina § 147.1700 State-administered program. The...

  12. 40 CFR 147.2500 - State-administered program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 24 2012-07-01 2012-07-01 false State-administered program. 147.2500 Section 147.2500 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Wisconsin § 147.2500 State-administered program. The...

  13. 40 CFR 147.1450 - State-administered program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 23 2011-07-01 2011-07-01 false State-administered program. 147.1450 Section 147.1450 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Nevada § 147.1450 State-administered program. The UIC...

  14. 40 CFR 147.2351 - EPA-administered program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Virginia § 147.2351 EPA-administered program. (a) Contents. The UIC program for the State of Virginia, including all Indian lands, is administered by EPA. This program consists of the UIC program requirements of 40...

  15. 40 CFR 147.2351 - EPA-administered program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Virginia § 147.2351 EPA-administered program. (a) Contents. The UIC program for the State of Virginia, including all Indian lands, is administered by EPA. This program consists of the UIC program requirements of 40...

  16. 40 CFR 147.2351 - EPA-administered program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Virginia § 147.2351 EPA-administered program. (a) Contents. The UIC program for the State of Virginia, including all Indian lands, is administered by EPA. This program consists of the UIC program requirements of 40...

  17. 40 CFR 147.2351 - EPA-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Virginia § 147.2351 EPA-administered program. (a) Contents. The UIC program for the State of Virginia, including all Indian lands, is administered by EPA. This program consists of the UIC program requirements of 40...

  18. 40 CFR 147.1651 - EPA-administered program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS New York § 147.1651 EPA-administered program. (a) Contents. The UIC program for the State of New York, including all Indian lands, is administered by EPA. The program consists of the UIC program requirements of 40...

  19. 40 CFR 147.1651 - EPA-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS New York § 147.1651 EPA-administered program. (a) Contents. The UIC program for the State of New York, including all Indian lands, is administered by EPA. The program consists of the UIC program requirements of 40...

  20. 40 CFR 147.1201 - EPA-administered program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Minnesota § 147.1201 EPA-administered program. (a) Contents. The UIC program for the State of Minnesota is administered by EPA. This program consists of the UIC program requirements of 40 CFR parts 124, 144, 146, 148, and...

  1. 40 CFR 147.1201 - EPA-administered program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Minnesota § 147.1201 EPA-administered program. (a) Contents. The UIC program for the State of Minnesota is administered by EPA. This program consists of the UIC program requirements of 40 CFR parts 124, 144, 146, 148, and...

  2. 40 CFR 147.1201 - EPA-administered program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Minnesota § 147.1201 EPA-administered program. (a) Contents. The UIC program for the State of Minnesota is administered by EPA. This program consists of the UIC program requirements of 40 CFR parts 124, 144, 146, 148, and...

  3. 40 CFR 147.1201 - EPA-administered program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Minnesota § 147.1201 EPA-administered program. (a) Contents. The UIC program for the State of Minnesota is administered by EPA. This program consists of the UIC program requirements of 40 CFR parts 124, 144, 146, 148, and...

  4. 40 CFR 147.2751 - EPA-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... lands, is administered by EPA. This program consists of the UIC program requirements of 40 CFR parts 124... 40 Protection of Environment 22 2010-07-01 2010-07-01 false EPA-administered program. 147.2751... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS American Samoa §...

  5. 40 CFR 147.2701 - EPA-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Indian lands, is administered by EPA. This program consists of the UIC program requirements of 40 CFR... 40 Protection of Environment 22 2010-07-01 2010-07-01 false EPA-administered program. 147.2701... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Virgin Islands §...

  6. 40 CFR 147.601 - EPA-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... administered by EPA. This program consists of the UIC program requirements of 40 CFR parts 124, 144, 146, 148... 40 Protection of Environment 22 2010-07-01 2010-07-01 false EPA-administered program. 147.601... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Hawaii § 147.601...

  7. 40 CFR 147.1151 - EPA-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Indian lands, is administered by EPA. This program consists of the UIC program requirements of 40 CFR... 40 Protection of Environment 22 2010-07-01 2010-07-01 false EPA-administered program. 147.1151... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Michigan §...

  8. 40 CFR 147.801 - EPA-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... administered by EPA. This program consists of the UIC program requirements of 40 CFR parts 124, 144, 146, 148... 40 Protection of Environment 22 2010-07-01 2010-07-01 false EPA-administered program. 147.801... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Iowa § 147.801...

  9. 40 CFR 147.901 - EPA-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... lands, is administered by EPA. This program consists of the UIC program requirements of 40 CFR parts 124... 40 Protection of Environment 22 2010-07-01 2010-07-01 false EPA-administered program. 147.901... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Kentucky § 147.901...

  10. 40 CFR 147.2151 - EPA-administered program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Tennessee § 147.2151 EPA-administered program. (a) Contents. The UIC program for the State of Tennessee, including all Indian lands, is administered by EPA. This program consists of the UIC program requirements of 40...

  11. 40 CFR 147.2151 - EPA-administered program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Tennessee § 147.2151 EPA-administered program. (a) Contents. The UIC program for the State of Tennessee, including all Indian lands, is administered by EPA. This program consists of the UIC program requirements of 40...

  12. 40 CFR 147.2151 - EPA-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Tennessee § 147.2151 EPA-administered program. (a) Contents. The UIC program for the State of Tennessee, including all Indian lands, is administered by EPA. This program consists of the UIC program requirements of 40...

  13. Cloning and Expression of Major Surface Antigen 1 Gene of Toxoplasma gondii RH Strain Using the Expression Vector pVAX1 in Chinese Hamster Ovary Cells

    PubMed Central

    Abdizadeh, Rahman; Maraghi, Sharif; Ghadiri, Ata A.; Tavalla, Mehdi; Shojaee, Saeedeh

    2015-01-01

    Background: Toxoplasmosis is an opportunistic protozoan infection with a high prevalence in a broad range of hosts infecting up to one-third of the world human population. Toxoplasmosis leads to serious medical problems in immunocompromised individuals and fetuses and also induces abortion and mortality in domestic animals. Therefore, there is a huge demand for the development of an effective vaccine. Surface Antigen 1 (SAG1) is one of the important immunodominant surface antigens of Toxoplasma gondii, which interacts with host cells and primarily involved in adhesion, invasion and stimulation of host immune response. Surface antigen 1 is considered as the leading candidate for development of an effective vaccine against toxoplasmosis. Objectives: The purpose of this study was to clone the major surface antigen1 gene (SAG1) from the genotype 1 of T. gondii, RH strain into the eukaryotic expression vector pVAX1 in order to use for a DNA vaccine. Materials and Methods: Genomic DNA was extracted from tachyzoite of the parasite using the QIAamp DNA mini kit. After designing the specific primers, SAG1 gene was amplified by Polymerase Chain Reaction (PCR). The purified PCR products were then cloned into a pPrime plasmid vector. The aforementioned product was subcloned into the pVAX1 eukaryotic expression vector. The recombinant pVAX1-SAG1 was then transfected into Chinese Hamster Ovary (CHO) cells and expression of SAG1 antigen was evaluated using Reverse Transcriptase Polymerase Chain Reaction (RT-PCR), Immunofluorescence Assay (IFA) and Western Blotting (WB). Results: The cloning and subcloning products (pPrime-SAG1 and pVAX1-SAG1 plasmid vectors) of SAG1 gene were verified and confirmed by enzyme digestion and sequencing. A 30 kDa recombinant protein was expressed in CHO cells as shown by IFA and WB methods. Conclusions: The pVAX1 expression vector and CHO cells are a suitable system for high-level recombinant protein production for SAG1 gene from T. gondii parasites

  14. Targeted Lung Delivery of Nasally Administered Aerosols

    PubMed Central

    Tian, Geng; Hindle, Michael; Longest, P. Worth

    2014-01-01

    Using the nasal route to deliver pharmaceutical aerosols to the lungs has a number of advantages including co-administration during non-invasive ventilation. The objective of this study was to evaluate the growth and deposition characteristics of nasally administered aerosol throughout the conducting airways based on delivery with streamlined interfaces implementing two forms of controlled condensational growth technology. Characteristic conducting airways were considered including a nose-mouth-throat (NMT) geometry, complete upper tracheobronchial (TB) model through the third bifurcation (B3), and stochastic individual path (SIP) model to the terminal bronchioles (B15). Previously developed streamlined nasal cannula interfaces were used for the delivery of submicrometer particles using either enhanced condensational growth (ECG) or excipient enhanced growth (EEG) techniques. Computational fluid dynamics (CFD) simulations predicted aerosol transport, growth and deposition for a control (4.7 μm) and three submicrometer condensational aerosols with budesonide as a model insoluble drug. Depositional losses with condensational aerosols in the cannula and NMT were less than 5% of the initial dose, which represents an order-of-magnitude reduction compared to the control. The condensational growth techniques increased the TB dose by a factor of 1.1–2.6x, delivered at least 70% of the dose to the alveolar region, and produced final aerosol sizes ≥2.5 μm. Compared to multiple commercial orally inhaled products, the nose-to-lung delivery approach increased dose to the biologically important lower TB region by factors as large as 35x. In conclusion, nose-to-lung delivery with streamlined nasal cannulas and condensational aerosols was highly efficient and targeted deposition to the lower TB and alveolar regions. PMID:24932058

  15. Who Should Administer Energy-Efficiency Programs?

    SciTech Connect

    Blumstein, Carl; Goldman, Charles; Barbose, Galen L.

    2003-05-01

    The restructuring of the electric utility industry in the US created a crisis in the administration of ratepayer-funded energy-efficiency programs. Before restructuring, nearly all energy-efficiency programs in the US were administered by utilities and funded from utility rates. Restructuring called these arrangements into question in two ways. First, the separation of generation from transmission and distribution undermined a key rationale for utility administration. This was the Integrated Resource Planning approach in which the vertically integrated utility was given incentives to provide energy services at least cost. Second, questions were raised as to whether funding through utility rates could be sustained in a competitive environment and most states that restructured their electricity industry adopted a system benefits charge. The crisis in administration of energy-efficiency programs produced a variety of responses in the eight years since restructuring in the US began in earn est. These responses have included new rationales for energy-efficiency programs, new mechanisms for funding programs, and new mechanisms for program administration and governance. This paper focuses on issues related to program administration. It describes the administrative functions and some of the options for accomplishing them. Then it discusses criteria for choosing among the options. Examples are given that highlight some of the states that have made successful transitions to new governance and/or administration structures. Attention is also given to California where large-scale energy-efficiency programs have continued to operate, despite the fact that many of the key governance/administration issues remain unresolved. The conclusion attempts to summarize lessons learned.

  16. RNA Binding of T-cell Intracellular Antigen-1 (TIA-1) C-terminal RNA Recognition Motif Is Modified by pH Conditions*

    PubMed Central

    Cruz-Gallardo, Isabel; Aroca, Ángeles; Persson, Cecilia; Karlsson, B. Göran; Díaz-Moreno, Irene

    2013-01-01

    T-cell intracellular antigen-1 (TIA-1) is a DNA/RNA-binding protein that regulates critical events in cell physiology by the regulation of pre-mRNA splicing and mRNA translation. TIA-1 is composed of three RNA recognition motifs (RRMs) and a glutamine-rich domain and binds to uridine-rich RNA sequences through its C-terminal RRM2 and RRM3 domains. Here, we show that RNA binding mediated by either isolated RRM3 or the RRM23 construct is controlled by slight environmental pH changes due to the protonation/deprotonation of TIA-1 RRM3 histidine residues. The auxiliary role of the C-terminal RRM3 domain in TIA-1 RNA recognition is poorly understood, and this work provides insight into its binding mechanisms. PMID:23902765

  17. In Vitro Differentiation of Insulin Secreting Cells from Mouse Bone Marrow Derived Stage-Specific Embryonic Antigen 1 Positive Stem Cells

    PubMed Central

    Abouzaripour, Morteza; Pasbakhsh, Parichehr; Atlasi, Nader; Shahverdi, Abdol Hossein; Mahmoudi, Reza; Kashani, Iraj Ragerdi

    2016-01-01

    Objective Bone marrow has recently been recognized as a novel source of stem cells for the treatment of wide range of diseases. A number of studies on murine bone mar- row have shown a homogenous population of rare stage-specific embryonic antigen 1 (SSEA-1) positive cells that express markers of pluripotent stem cells. This study focuses on SSEA-1 positive cells isolated from murine bone marrow in an attempt to differentiate them into insulin-secreting cells (ISCs) in order to investigate their differentiation potential for future use in cell therapy. Materials and Methods This study is an experimental research. Mouse SSEA-1 positive cells were isolated by Magnetic-activated cell sorting (MACS) followed by characteriza- tion with flow cytometry. Induced SSEA-1 positive cells were differentiated into ISCs with specific differentiation media. In order to evaluate differentiation quality and analysis, dithizone (DTZ) staining was use, followed by reverse transcription polymerase chain reaction (RT-PCR), immunocytochemistry and insulin secretion assay. Statistical results were analyzed by one-way ANOVA. Results The results achieved in this study reveal that mouse bone marrow contains a population of SSEA-1 positive cells that expresses pluripotent stem cells markers such as SSEA-1, octamer-binding transcription factor 4 (OCT-4) detected by immunocytochem- istry and C-X-C chemokine receptor type 4 (CXCR4) and stem cell antigen-1 (SCA-1) detected by flow cytometric analysis. SSEA-1 positive cells can differentiate into ISCs cell clusters as evidenced by their DTZ positive staining and expression of genes such as Pdx1 (pancreatic transcription factors), Ngn3 (endocrine progenitor marker), Insulin1 and Insulin2 (pancreaticβ-cell markers). Additionally, our results demonstrate expression of Pdx1 and Glut2 protein and insulin secretion in response to a glucose challenge in the differentiated cells. Conclusion Our study clearly demonstrates the potential of SSEA-1 positive

  18. Noninvasive Imaging of Administered Progenitor Cells

    SciTech Connect

    Steven R Bergmann, M.D., Ph.D.

    2012-12-03

    -99% pure population of leukocytes. Viability was assessed using Trypan blue histological analysis. We successfully isolated and labeled ~25-30 x 10{sup 7} CD34+ lymphocytes in cytokine mobilized progenitor cell apharesis harvests. Cells were also subjected to a stat gram stain to look for bacterial contamination, stat endotoxin LAL to look for endotoxin contamination, flow cytometry for evaluation of the purity of the cells and 14-day sterility culture. Colony forming assays confirm the capacity of these cells to proliferate and function ex-vivo with CFU-GM values of 26 colonies/ 1 x 10{sup 4} cells plated and 97% viability in cytokine augmented methylcellulose at 10-14 days in CO{sub 2} incubation. We developed a closed-processing system for the product labeling prior to infusion to maintain autologous cell integrity and sterility. Release criteria for the labeled product were documented for viability, cell count and differential, and measured radiolabel. We were successful in labeling the cells with up to 500 uCi/10{sup 8} cells, with viability of >98%. However, due to delays in getting the protocol approved by the FDA, the cells were not infused in humans in this location (although we did successfully use CD34+ cells in humans in a study in Australia). The approach developed should permit labeling of progenitor cells that can be administered to human subjects for tracking. The labeling approach should be useful for all progenitor cell types, although this would need to be verified since different cell lines may have differential radiosensitivity.

  19. An Inhibitory Antibody Blocks Interactions between Components of the Malarial Invasion Machinery

    PubMed Central

    Collins, Christine R.; Withers-Martinez, Chrislaine; Hackett, Fiona; Blackman, Michael J.

    2009-01-01

    Host cell invasion by apicomplexan pathogens such as the malaria parasite Plasmodium spp. and Toxoplasma gondii involves discharge of proteins from secretory organelles called micronemes and rhoptries. In Toxoplasma a protein complex comprising the microneme apical membrane antigen 1 (AMA1), two rhoptry neck proteins, and a protein called Ts4705, localises to the moving junction, a region of close apposition between parasite and host cell during invasion. Antibodies against AMA1 prevent invasion and are protective in vivo, and so AMA1 is of widespread interest as a malaria vaccine candidate. Here we report that the AMA1 complex identified in Toxoplasma is conserved in Plasmodium falciparum. We demonstrate that the invasion-inhibitory monoclonal antibody (mAb) 4G2, which recognises P. falciparum AMA1 (PfAMA1), cannot bind when PfAMA1 is in a complex with its partner proteins. We further show that a single completely conserved PfAMA1 residue, Tyr251, lying within a conserved hydrophobic groove adjacent to the mAb 4G2 epitope, is required for complex formation. We propose that mAb 4G2 inhibits invasion by preventing PfAMA1 from interacting with other components of the invasion complex. Our findings should aid the rational design of subunit malaria vaccines based on PfAMA1. PMID:19165323

  20. 40 CFR 282.56 - Connecticut State-Administered Program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 28 2012-07-01 2012-07-01 false Connecticut State-Administered Program. 282.56 Section 282.56 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.56 Connecticut State-Administered Program. (a) The...

  1. 40 CFR 282.56 - Connecticut State-Administered Program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 27 2011-07-01 2011-07-01 false Connecticut State-Administered Program. 282.56 Section 282.56 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.56 Connecticut State-Administered Program. (a) The...

  2. 47 CFR 97.509 - Administering VE requirements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... SERVICES AMATEUR RADIO SERVICE Qualifying Examination Systems § 97.509 Administering VE requirements. (a) Each examination for an amateur operator license must be administered by a team of at least 3 VEs at an... person who holds an amateur operator license of the class specified below: (i) Amateur Extra, Advanced...

  3. 47 CFR 97.509 - Administering VE requirements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... SERVICES AMATEUR RADIO SERVICE Qualifying Examination Systems § 97.509 Administering VE requirements. (a) Each examination for an amateur operator license must be administered by a team of at least 3 VEs at an... person who holds an amateur operator license of the class specified below: (i) Amateur Extra, Advanced...

  4. 47 CFR 97.509 - Administering VE requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... SERVICES AMATEUR RADIO SERVICE Qualifying Examination Systems § 97.509 Administering VE requirements. (a) Each examination for an amateur operator license must be administered by a team of at least 3 VEs at an... person who holds an amateur operator license of the class specified below: (i) Amateur Extra, Advanced...

  5. 47 CFR 97.509 - Administering VE requirements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... SERVICES AMATEUR RADIO SERVICE Qualifying Examination Systems § 97.509 Administering VE requirements. (a) Each examination for an amateur operator license must be administered by a team of at least 3 VEs at an... person who holds an amateur operator license of the class specified below: (i) Amateur Extra, Advanced...

  6. 47 CFR 97.509 - Administering VE requirements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... SERVICES AMATEUR RADIO SERVICE Qualifying Examination Systems § 97.509 Administering VE requirements. (a) Each examination for an amateur operator license must be administered by a team of at least 3 VEs at an... person who holds an amateur operator license of the class specified below: (i) Amateur Extra, Advanced...

  7. 40 CFR 282.66 - Kansas State-Administered Program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 28 2012-07-01 2012-07-01 false Kansas State-Administered Program. 282.66 Section 282.66 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.66 Kansas State-Administered Program. (a) The State of...

  8. 40 CFR 282.88 - Pennsylvania State-Administered Program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 28 2012-07-01 2012-07-01 false Pennsylvania State-Administered Program. 282.88 Section 282.88 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.88 Pennsylvania State-Administered Program. (a)...

  9. 40 CFR 282.96 - Virginia State-Administered Program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 28 2012-07-01 2012-07-01 false Virginia State-Administered Program. 282.96 Section 282.96 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.96 Virginia State-Administered Program. (a) The State...

  10. 40 CFR 147.2350 - State-administered program. [Reserved

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 23 2014-07-01 2014-07-01 false State-administered program. 147.2350 Section 147.2350 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Virginia §...

  11. 40 CFR 147.2350 - State-administered program. [Reserved

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 24 2012-07-01 2012-07-01 false State-administered program. 147.2350 Section 147.2350 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Virginia §...

  12. 40 CFR 147.2350 - State-administered program. [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 23 2011-07-01 2011-07-01 false State-administered program. 147.2350 Section 147.2350 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Virginia §...

  13. 40 CFR 147.2350 - State-administered program. [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program. 147.2350 Section 147.2350 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Virginia §...

  14. 24 CFR 982.51 - PHA authority to administer program.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 24 Housing and Urban Development 4 2013-04-01 2013-04-01 false PHA authority to administer program. 982.51 Section 982.51 Housing and Urban Development REGULATIONS RELATING TO HOUSING AND URBAN... PHA Plan for Administration of Program § 982.51 PHA authority to administer program. (a) The PHA...

  15. 40 CFR 147.3000 - EPA-administered program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... administered by EPA. (The term “Indian lands” is defined at 40 CFR 144.3.) The Navajo Indian lands are in the... Utah. This program consists of the UIC program requirements of 40 CFR parts 124, 144, 146, 148, and..., Ute Mountain Ute, and All Other New Mexico Tribes § 147.3000 EPA-administered program. (a)...

  16. 40 CFR 147.3000 - EPA-administered program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., Ute Mountain Ute, and All Other New Mexico Tribes § 147.3000 EPA-administered program. (a) Contents... Mountain Ute lands in Utah and New Mexico), and all wells on other Indian lands in New Mexico is administered by EPA. (The term “Indian lands” is defined at 40 CFR 144.3.) The Navajo Indian lands are in...

  17. 40 CFR 147.3000 - EPA-administered program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., Ute Mountain Ute, and All Other New Mexico Tribes § 147.3000 EPA-administered program. (a) Contents... Mountain Ute lands in Utah and New Mexico), and all wells on other Indian lands in New Mexico is administered by EPA. (The term “Indian lands” is defined at 40 CFR 144.3.) The Navajo Indian lands are in...

  18. 39 CFR 222.1 - Authority to administer postal affairs.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 39 Postal Service 1 2014-07-01 2014-07-01 false Authority to administer postal affairs. 222.1 Section 222.1 Postal Service UNITED STATES POSTAL SERVICE ORGANIZATION AND ADMINISTRATION DELEGATIONS OF AUTHORITY § 222.1 Authority to administer postal affairs. (a) The Postmaster General. The postmaster...

  19. 39 CFR 222.1 - Authority to administer postal affairs.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 39 Postal Service 1 2012-07-01 2012-07-01 false Authority to administer postal affairs. 222.1 Section 222.1 Postal Service UNITED STATES POSTAL SERVICE ORGANIZATION AND ADMINISTRATION DELEGATIONS OF AUTHORITY § 222.1 Authority to administer postal affairs. (a) The Postmaster General. The postmaster...

  20. 39 CFR 222.1 - Authority to administer postal affairs.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Authority to administer postal affairs. 222.1 Section 222.1 Postal Service UNITED STATES POSTAL SERVICE ORGANIZATION AND ADMINISTRATION DELEGATIONS OF AUTHORITY § 222.1 Authority to administer postal affairs. (a) The Postmaster General. The postmaster...

  1. 39 CFR 222.1 - Authority to administer postal affairs.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 39 Postal Service 1 2011-07-01 2011-07-01 false Authority to administer postal affairs. 222.1 Section 222.1 Postal Service UNITED STATES POSTAL SERVICE ORGANIZATION AND ADMINISTRATION DELEGATIONS OF AUTHORITY § 222.1 Authority to administer postal affairs. (a) The Postmaster General. The postmaster...

  2. 39 CFR 222.1 - Authority to administer postal affairs.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 39 Postal Service 1 2013-07-01 2013-07-01 false Authority to administer postal affairs. 222.1 Section 222.1 Postal Service UNITED STATES POSTAL SERVICE ORGANIZATION AND ADMINISTRATION DELEGATIONS OF AUTHORITY § 222.1 Authority to administer postal affairs. (a) The Postmaster General. The postmaster...

  3. 40 CFR 147.1650 - State-administered program. [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program. 147.1650 Section 147.1650 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS New York §...

  4. 40 CFR 147.1650 - State-administered program. [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 23 2011-07-01 2011-07-01 false State-administered program. 147.1650 Section 147.1650 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS New York §...

  5. 40 CFR 147.3000 - EPA-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... administered by EPA. (The term “Indian lands” is defined at 40 CFR 144.3.) The Navajo Indian lands are in the... Utah. This program consists of the UIC program requirements of 40 CFR parts 124, 144, 146, 148, and... 40 Protection of Environment 22 2010-07-01 2010-07-01 false EPA-administered program....

  6. 40 CFR 147.1200 - State-administered program. [Reserved

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 24 2013-07-01 2013-07-01 false State-administered program. 147.1200 Section 147.1200 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Minnesota §...

  7. 40 CFR 147.1200 - State-administered program. [Reserved

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 23 2014-07-01 2014-07-01 false State-administered program. 147.1200 Section 147.1200 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Minnesota §...

  8. 40 CFR 147.1200 - State-administered program. [Reserved

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 24 2012-07-01 2012-07-01 false State-administered program. 147.1200 Section 147.1200 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Minnesota §...

  9. 40 CFR 147.1200 - State-administered program. [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 23 2011-07-01 2011-07-01 false State-administered program. 147.1200 Section 147.1200 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Minnesota §...

  10. 40 CFR 147.1200 - State-administered program. [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program. 147.1200 Section 147.1200 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Minnesota §...

  11. 40 CFR 147.451 - EPA-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth in the remainder of... 40 Protection of Environment 22 2010-07-01 2010-07-01 false EPA-administered program. 147.451... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS District of...

  12. 40 CFR 147.151 - EPA-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Navajo Indian lands consists of the UIC program requirements of 40 CFR parts 124, 144, 146, 148, and any... 40 Protection of Environment 22 2010-07-01 2010-07-01 false EPA-administered program. 147.151... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Arizona § 147.151...

  13. 40 CFR 147.1951 - EPA-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... CFR parts 124, 144, 146, 148, and any additional requirements set forth in the remainder of this... 40 Protection of Environment 22 2010-07-01 2010-07-01 false EPA-administered program. 147.1951... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Pennsylvania §...

  14. 40 CFR 147.101 - EPA-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... program requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth in the... 40 Protection of Environment 22 2010-07-01 2010-07-01 false EPA-administered program. 147.101... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Alaska § 147.101...

  15. 40 CFR 147.2851 - EPA-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... UIC program requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth... 40 Protection of Environment 22 2010-07-01 2010-07-01 false EPA-administered program. 147.2851... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Trust Territory of...

  16. 40 CFR 147.751 - EPA-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... program consists of the UIC program requirements of 40 CFR parts 124, 144, 146, and 148 and the additional... 40 Protection of Environment 22 2010-07-01 2010-07-01 false EPA-administered program. 147.751... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Indiana § 147.751...

  17. 40 CFR 147.1201 - EPA-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... EPA. This program consists of the UIC program requirements of 40 CFR parts 124, 144, 146, 148, and any... 40 Protection of Environment 22 2010-07-01 2010-07-01 false EPA-administered program. 147.1201... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Minnesota §...

  18. 40 CFR 147.2801 - EPA-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... of the UIC program requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements... 40 Protection of Environment 22 2010-07-01 2010-07-01 false EPA-administered program. 147.2801... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Commonwealth of...

  19. 40 CFR 147.1351 - EPA-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... consists of the UIC program requirements of 40 CFR parts 124, 144, 146, 148, and any additional... 40 Protection of Environment 22 2010-07-01 2010-07-01 false EPA-administered program. 147.1351... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Montana § 147.1351...

  20. 40 CFR 147.2150 - State-administered program. [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program. 147.2150 Section 147.2150 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Tennessee §...

  1. 40 CFR 147.2150 - State-administered program. [Reserved

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 23 2014-07-01 2014-07-01 false State-administered program. 147.2150 Section 147.2150 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Tennessee §...

  2. 40 CFR 147.2150 - State-administered program. [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 23 2011-07-01 2011-07-01 false State-administered program. 147.2150 Section 147.2150 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Tennessee §...

  3. Stem cell antigen-1 regulates the tempo of muscle repair through effects on proliferation of {alpha}7 integrin-expressing myoblasts

    SciTech Connect

    Epting, Conrad L.; Lopez, Javier E.; Pedersen, Anissa; Brown, Courtney; Spitz, Paul; Ursell, Philip C.; Bernstein, Harold S.

    2008-03-10

    Skeletal muscle repair occurs through a programmed series of events including myogenic precursor activation, myoblast proliferation, and differentiation into new myofibers. We previously identified a role for Stem cell antigen-1 (Sca-1) in myoblast proliferation and differentiation in vitro. We demonstrated that blocking Sca-1 expression resulted in sustained myoblast cell division. Others have since demonstrated that Sca-1-null myoblasts display a similar phenotype when cultured ex vivo. To test the importance of Sca-1 during myogenesis in vivo, we employed a myonecrotic injury model in Sca-1{sup -/-} and Sca-1{sup +/+} mice. Our results demonstrate that Sca-1{sup -/-} myoblasts exhibit a hyperproliferative response consisting of prolonged and accelerated cell division in response to injury. This leads to delayed myogenic differentiation and muscle repair. These data provide the first in vivo evidence for Sca-1 as a regulator of myoblast proliferation during muscle regeneration. These studies also suggest that the balance between myogenic precursor proliferation and differentiation is critical to normal muscle repair.

  4. Effects of Intermittent Administration of Parathyroid Hormone (1-34) on Bone Differentiation in Stromal Precursor Antigen-1 Positive Human Periodontal Ligament Stem Cells

    PubMed Central

    Wang, Xiaoxiao; Wang, Yanlan; Dai, Xubin; Chen, Tianyu; Yang, Fanqiao; Dai, Shuangye; Ou, Qianmin; Wang, Yan; Lin, Xuefeng

    2016-01-01

    Periodontitis is the most common cause of tooth loss and bone destruction in adults worldwide. Human periodontal ligament stem cells (hPDLSCs) may represent promising new therapeutic biomaterials for tissue engineering applications. Stromal precursor antigen-1 (STRO-1) has been shown to have roles in adherence, proliferation, and multipotency. Parathyroid hormone (PTH) has been shown to enhance proliferation in osteoblasts. Therefore, in this study, we aimed to compare the functions of STRO-1(+) and STRO-1(−) hPDLSCs and to investigate the effects of PTH on the osteogenic capacity of STRO-1(+) hPDLSCs in order to evaluate their potential applications in the treatment of periodontitis. Our data showed that STRO-1(+) hPDLSCs expressed higher levels of the PTH-1 receptor (PTH1R) than STRO-1(−) hPDLSCs. In addition, intermittent PTH treatment enhanced the expression of PTH1R and osteogenesis-related genes in STRO-1(+) hPDLSCs. PTH-treated cells also exhibited increased alkaline phosphatase activity and mineralization ability. Therefore, STRO-1(+) hPDLSCs represented a more promising cell resource for biomaterials and tissue engineering applications. Intermittent PTH treatment improved the capacity for STRO-1(+) hPDLSCs to repair damaged tissue and ameliorate the symptoms of periodontitis. PMID:27069479

  5. FRET Based Quantification and Screening Technology Platform for the Interactions of Leukocyte Function-Associated Antigen-1 (LFA-1) with InterCellular Adhesion Molecule-1 (ICAM-1)

    PubMed Central

    Chakraborty, Sandeep; Núñez, David; Hu, Shih-Yang; Domingo, María Pilar; Pardo, Julian; Karmenyan, Artashes; Chiou, Arthur

    2014-01-01

    The interaction between leukocyte function-associated antigen-1(LFA-1) and intercellular adhesion molecule-1 (ICAM-1) plays a pivotal role in cellular adhesion including the extravasation and inflammatory response of leukocytes, and also in the formation of immunological synapse. However, irregular expressions of LFA-1 or ICAM-1 or both may lead to autoimmune diseases, metastasis cancer, etc. Thus, the LFA-1/ICAM-1 interaction may serve as a potential therapeutic target for the treatment of these diseases. Here, we developed one simple ‘in solution’ steady state fluorescence resonance energy transfer (FRET) technique to obtain the dissociation constant (Kd) of the interaction between LFA-1 and ICAM-1. Moreover, we developed the assay into a screening platform to identify peptides and small molecules that inhibit the LFA-1/ICAM-1 interaction. For the FRET pair, we used Alexa Fluor 488-LFA-1 conjugate as donor and Alexa Fluor 555-human recombinant ICAM-1 (D1-D2-Fc) as acceptor. From our quantitative FRET analysis, the Kd between LFA-1 and D1-D2-Fc was determined to be 17.93±1.34 nM. Both the Kd determination and screening assay were performed in a 96-well plate platform, providing the opportunity to develop it into a high-throughput assay. This is the first reported work which applies FRET based technique to determine Kd as well as classifying inhibitors of the LFA-1/ICAM-1 interaction. PMID:25032811

  6. Anti-early endosome antigen 1 autoantibodies were detected in a pemphigus-like patient but not in the majority of pemphigus diseases.

    PubMed

    Nishikawa, Ryuhei; Takahashi, Hitoshi; Matsuda, Mitsuhiro; Imaoka, Kaoru; Ogawa, Masahiro; Teye, Kwesi; Tsuchisaka, Atsunari; Koga, Hiroshi; Komorowski, Lars; Probst, Christian; Hachiya, Takahisa; Fritzler, Marvin J; Ishii, Norito; Ohata, Chika; Furumura, Minao; Krol, Rafal P; Muro, Yoshinao; Morita, Eishin; Hashimoto, Takashi

    2016-05-01

    Although the major autoantigens in classic pemphigus are desmogleins, sera from various types of pemphigus react with a number of other molecules, including desmocollins and plakin proteins. However, other novel pemphigus-related autoantigens remain to be identified. In this study, immunoblotting for serum from an atypical autoimmune bullous disease patient identified an unknown 175 kDa protein. Subsequent studies using two-dimensional gel electrophoresis, immunoblotting and mass-spectrometry identified the 175 kDa protein as early endosome antigen 1 (EEA1). This finding was confirmed by subsequent immunological studies, including indirect immunofluorescence of skin and cultured keratinocytes, two-dimensional gel electrophoresis and immunoblotting with anti-EEA1 polyclonal antibody, and preabsorption with EEA1 recombinant protein. Finally, we developed a novel BIOCHIP assay using full-length EEA1 recombinant protein to detect anti-EEA1 antibodies. However, none of 35 sera from various types of pemphigus showed anti-EEA1 antibodies in the BIOCHIP assay, with the exception of the serum from the index case. In addition, various findings in the index case did not suggest pathogenic role of anti-EEA1 autoantibodies. Therefore, although we successfully identified the 175 kDa protein reacted by a serum of an atypical pemphigus-like patient as EEA1, novel BIOCHIP study for other pemphigus sera indicated that EEA1 is not a common and pathogenic autoantigen in pemphigus. PMID:26909655

  7. Dual role for mitogen-activated protein kinase (Erk) in insulin-dependent regulation of Fra-1 (fos-related antigen-1) transcription and phosphorylation.

    PubMed Central

    Hurd, Toby W; Culbert, Ainsley A; Webster, Kenneth J; Tavaré, Jeremy M

    2002-01-01

    Insulin regulates the activity of the AP-1 (activator protein-1) transcriptional complex in several cell types. One component of the AP-1 complex is the transcription factor Fra-1 (fos-related antigen-1), and we have demonstrated previously that insulin stimulates the expression of Fra-1 mRNA in CHO.T cells [Griffiths, Black, Culbert, Dickens, Shaw, Gillespie and Tavaré (1998) Biochem. J. 335, 19-26]. Here we demonstrate that insulin stimulates the activity of a fra-1 promoter linked to a luciferase reporter gene, indicating that the ability of insulin to induce expression of Fra-1 mRNA is due, at least in part, to an increase in gene transcription. Furthermore, we found that insulin induces the serine phosphorylation of Fra-1 and reduces its mobility during SDS/PAGE as a result of phosphorylation. The ability of insulin to induce the accumulation of Fra-1 mRNA, stimulate the fra-1 promoter and stimulate phosphorylation of Fra-1 all require the mitogen-activated protein (MAP) kinase cascade, which leads to the activation of extracellular-signal-regulated kinase (Erk) 1/2. Consequently, our results demonstrate that the Erk cascade plays a dual role in the co-ordinated regulation of the transcription and the phosphorylation of Fra-1 by insulin. PMID:12197835

  8. Tumor-promoting function and prognostic significance of the RNA-binding protein T-cell intracellular antigen-1 in esophageal squamous cell carcinoma

    PubMed Central

    Fujita, Yuji; Naruto, Takuya; Kohmoto, Tomohiro; Miyakami, Yuko; Watanabe, Miki; Kudo, Yasusei; Fujiwara, Hitoshi; Ichikawa, Daisuke; Otsuji, Eigo; Imoto, Issei

    2016-01-01

    T-cell intracellular antigen-1 (TIA1) is an RNA-binding protein involved in many regulatory aspects of mRNA metabolism. Here, we report previously unknown tumor-promoting activity of TIA1, which seems to be associated with its isoform-specific molecular distribution and regulation of a set of cancer-related transcripts, in esophageal squamous cell carcinoma (ESCC). Immunohistochemical overexpression of TIA1 ectopically localized in the cytoplasm of tumor cells was an independent prognosticator for worse overall survival in a cohort of 143 ESCC patients. Knockdown of TIA1 inhibited proliferation of ESCC cells. By exogenously introducing each of two major isoforms, TIA1a and TIA1b, only TIA1a, which was localized to both the nucleus and cytoplasm, promoted anchorage-dependent and anchorage-independent ESCC cell proliferation. Ribonucleoprotein immunoprecipitation, followed by microarray analysis or massive-parallel sequencing, identified a set of TIA1-binding mRNAs, including SKP2 and CCNA2. TIA1 increased SKP2 and CCNA2 protein levels through the suppression of mRNA decay and translational induction, respectively. Our findings uncover a novel oncogenic function of TIA1 in esophageal tumorigenesis, and implicate its use as a marker for prognostic evaluation and as a therapeutic target in ESCC. PMID:26958940

  9. Improved EBV-based shuttle vector system: dicistronic mRNA couples the synthesis of the Epstein-Barr nuclear antigen-1 protein to neomycin resistance.

    PubMed

    Ramage, A D; Clark, A J; Smith, A G; Mountford, P S; Burt, D W

    1997-09-15

    Use of EBV-based vector systems has been limited by the requirement to generate EBNA+ cells which are 'permissive' for replication of an oriP-vector. In current constructs, selectable marker and EBNA-1 are not always co-expressed. This is a significant problem since the EBNA-1 gene product can be toxic in some cell types and may be selected against. In this paper, we describe a gene construct that overcomes this limitation. We have exploited the piconaviral internal ribosome entry site to allow the genes for Epstein-Barr nuclear antigen-1 and G-418 resistance to be transcribed as a dicistronic fusion mRNA under the control of the phosphoglucokinase promoter. This construct can be routinely integrated into human cell lines. The presence of EBNA-1 protein was reflected by a large increase in transfection frequencies (1000-fold) using an oriP-based vector which was shown to replicate stably in these cells with no apparent gross rearrangements detected after 8 weeks in culture. Using this system, G-418 resistance should directly reflect integration, as well as expression of the EBNA-1 gene, which, in turn, increases transfection frequencies and stability of EBV-based vector systems and should result in its increased use. PMID:9332352

  10. Heat shock factor 1 upregulates transcription of Epstein-Barr Virus nuclear antigen 1 by binding to a heat shock element within the BamHI-Q promoter

    SciTech Connect

    Wang, Feng-Wei; Wu, Xian-Rui; Liu, Wen-Ju; Liao, Yi-Ji; Lin, Sheng; Zong, Yong-Sheng; Zeng, Mu-Sheng; Zeng, Yi-Xin; Mai, Shi-Juan; Xie, Dan

    2011-12-20

    Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) is essential for maintenance of the episome and establishment of latency. In this study, we observed that heat treatment effectively induced EBNA1 transcription in EBV-transformed B95-8 and human LCL cell lines. Although Cp is considered as the sole promoter used for the expression of EBNA1 transcripts in the lymphoblastoid cell lines, the RT-PCR results showed that the EBNA1 transcripts induced by heat treatment arise from Qp-initiated transcripts. Using bioinformatics, a high affinity and functional heat shock factor 1 (HSF1)-binding element within the - 17/+4 oligonucleotide of the Qp was found, and was determined by electrophoretic mobility shift assay and chromatin immunoprecipitation assay. Moreover, heat shock and exogenous HSF1 expression induced Qp activity in reporter assays. Further, RNA interference-mediated HSF1 gene silencing attenuated heat-induced EBNA1 expression in B95-8 cells. These results provide evidence that EBNA1 is a new target for the transcription factor HSF1.

  11. Anti-Leukocyte Function-Associated Antigen 1 Therapy in a Nonhuman Primate Renal Transplant Model of Costimulation Blockade-Resistant Rejection.

    PubMed

    Anderson, D J; Lo, D J; Leopardi, F; Song, M; Turgeon, N A; Strobert, E A; Jenkins, J B; Wang, R; Reimann, K A; Larsen, C P; Kirk, A D

    2016-05-01

    Costimulation blockade with the fusion protein belatacept provides a desirable side effect profile and improvement in renal function compared with calcineurin inhibition in renal transplantation. This comes at the cost of increased rates of early acute rejection. Blockade of the integrin molecule leukocyte function-associated antigen 1 (LFA-1) has been shown to be an effective adjuvant to costimulation blockade in a rigorous nonhuman primate (NHP) model of islet transplantation; therefore, we sought to test this combination in an NHP renal transplant model. Rhesus macaques received belatacept maintenance therapy with or without the addition of LFA-1 blockade, which was achieved using a murine-derived LFA-1-specific antibody TS1/22. Additional experiments were performed using chimeric rhesus IgG1 (TS1/22R1) or IgG4 (TS1/22R4) variants, each engineered to limit antibody clearance. Despite evidence of proper binding to the target molecule and impaired cellular egress from the intravascular space indicative of a therapeutic effect similar to prior islet studies, LFA-1 blockade failed to significantly prolong graft survival. Furthermore, evidence of impaired protective immunity against cytomegalovirus was observed. These data highlight the difficulties in translating treatment regimens between organ models and suggest that the primarily vascularized renal model is more robust with regard to belatacept-resistant rejection than the islet model. PMID:26602755

  12. Association analysis of anti-Epstein-Barr nuclear antigen-1 antibodies, anti-cyclic citrullinated peptide antibodies, the shared epitope and smoking status in Brazilian patients with rheumatoid arthritis

    PubMed Central

    Yazbek, Michel Alexandre; de Barros-Mazon, Silvia; Rossi, Cláudio Lúcio; Londe, Ana Carolina; Costallat, Lilian Tereza Lavras; Bértolo, Manoel Barros

    2011-01-01

    INTRODUCTION: Epstein-Barr virus exposure appears to be an environmental trigger for rheumatoid arthritis that interacts with other risk factors. Relationships among anti-cyclic citrullinated peptide antibodies, the shared epitope, and smoking status have been observed in patients with rheumatoid arthritis from different populations. OBJECTIVE: To perform an association analysis of anti-Epstein-Barr nuclear antigen-1 antibodies, anti-cyclic citrullinated peptide antibodies, the shared epitope, and smoking status in Brazilian patients with rheumatoid arthritis. METHODS: In a case-control study, 140 rheumatoid arthritis patients and 143 healthy volunteers who were matched for age, sex, and ethnicity were recruited. Anti-Epstein-Barr nuclear antigen-1 antibodies and anti-cyclic citrullinated peptide antibodies were examined using an enzyme-linked immunosorbent assay, and shared epitope alleles were identified by genotyping. Smoking information was collected from all subjects. A comparative analysis of anti-Epstein-Barr nuclear antigen-1 antibodies, anti-cyclic citrullinated peptide antibodies, the shared epitope, and smoking status was performed in the patient group. Logistic regression analysis models were used to analyze the risk of rheumatoid arthritis. RESULTS: Anti-Epstein-Barr nuclear antigen-1 antibodies were not associated with anti-cyclic citrullinated peptide antibodies, shared epitope alleles, or smoking status. Anti-cyclic citrullinated peptide antibody positivity was significantly higher in smoking patients with shared epitope alleles (OR = 3.82). In a multivariate logistic regression analysis using stepwise selection, only anti-cyclic citrullinated peptide antibodies were found to be independently associated with rheumatoid arthritis (OR = 247.9). CONCLUSION: Anti-Epstein-Barr nuclear antigen-1 antibodies did not increase the risk of rheumatoid arthritis and were not associated with the rheumatoid arthritis risk factors studied. Smoking and

  13. The bioavailability of an orally administered medroxyprogesterone acetate suspension.

    PubMed

    Antal, E J; Gillespie, W R; Albert, K S

    1983-05-01

    The relative bioavailability of an orally administered aqueous suspension of medroxyprogesterone acetate (MPA) intended for intramuscular injection (Depo-Provera) was determined in relation to orally administered tablets. Serum levels of MPA were determined by radioimmunoassay following the administration of 400-mg doses to 19 adult male volunteers in a crossover design after an overnight fast. The two treatments were judged bioequivalent based upon a comparison of the resultant MPA serum levels and the derived bioavailability parameters. Hence, the intramuscular suspension administered orally offers an alternative means of achieving optimal serum levels of MPA in patients requiring high dose therapy. PMID:6222996

  14. Findings from Survey Administered to Weatherization Training Centers

    SciTech Connect

    Conlon, Brian; Tonn, Bruce Edward

    2015-03-01

    This report summarizes results of a survey administered to directors of weatherization training centers that receive funding from the U.S. Department of Energy. The survey presents results related to questions on training offered and future plans.

  15. Prion Protein and Stage Specific Embryo Antigen 1 as Selection Markers to Enrich the Fraction of Murine Embryonic Stem Cell-Derived Cardiomyocytes

    PubMed Central

    Ikeda, Nobuhito; Nakayama, Yuji; Nakazawa, Natsumi; Yoshida, Akio; Ninomiya, Haruaki; Shirayoshi, Yasuaki

    2016-01-01

    Background The prion protein (PrP) might be useful as a tool to collect cardiac progenitor cells derived from embryonic stem (ES) cells. It is also possible that PrP+ cells include undifferentiated cells with a capacity to develop into tumors. Methods PrP+ cells isolated from embryoid bodies (EB) formed by mouse AB1 ES cells were examined using RT–PCR analysis and clonogeneic cell assay. To assess their potential to differentiate into cardiomyocytes, Nkx2.5GFP/+ (hcgp7) cells, another ES cell line that carries the GFP reporter gene in the Nkx2.5 loci, were used. Results PrP+ cells isolated from EB of day 7 and 14 did not express pluripotency markers, but expressed cardiac cell markers, while PrP+ cells isolated from EB of day 21 expressed pluripotency markers. Cultured PrP+ cells isolated from EB of day 21 expressed pluripotency markers to form colonies, whereas those isolated from EB of day 7 and 14 did not. To exclude proliferating cells from PrP+ cells, stage specific embryo antigen 1 (SSEA1) was employed as a second marker. PrP+/SSEA1– cells did not proliferate and expressed cardiac cell markers, while PrP+/SSEA1+ did proliferate. Conclusion PrP+ cells isolated from EB included undifferentiated cells in day 21. PrP+/SSEA1– cells included cardiomyoctes, suggesting PrP and SSEA1 may be useful as markers to enrich the fraction of cardiomyocytes. PMID:27493483

  16. Sequence Variation and Immunologic Cross-Reactivity among Babesia bovis Merozoite Surface Antigen 1 Proteins from Vaccine Strains and Vaccine Breakthrough Isolates

    PubMed Central

    LeRoith, Tanya; Brayton, Kelly A.; Molloy, John B.; Bock, Russell E.; Hines, Stephen A.; Lew, Ala E.; McElwain, Terry F.

    2005-01-01

    The Babesia bovis merozoite surface antigen 1 (MSA-1) is an immunodominant membrane glycoprotein that is the target of invasion-blocking antibodies. While antigenic variation has been demonstrated in MSA-1 among strains from distinct geographical areas, the extent of sequence variation within a region where it is endemic and the effect of variation on immunologic cross-reactivity have not been assessed. In this study, sequencing of MSA-1 from two Australian B. bovis vaccine strains and 14 breakthrough isolates from vaccinated animals demonstrated low sequence identity in the extracellular region of the molecule, ranging from 19.8 to 46.7% between the T vaccine strain and eight T vaccine breakthrough isolates, and from 18.7 to 99% between the K vaccine strain and six K vaccine breakthrough isolates. Although MSA-1 amino acid sequence varied substantially among strains, overall predicted regions of hydrophilicity and hydrophobicity in the extracellular domain were conserved in all strains examined, suggesting a conserved functional role for MSA-1 despite sequence polymorphism. Importantly, the antigenic variation created by sequence differences resulted in a lack of immunologic cross-reactivity among outbreak strains using sera from animals infected with the B. bovis vaccine strains. Additionally, sera from cattle hyperinfected with the Mexico strain of B. bovis and shown to be clinically immune did not cross-react with MSA-1 from any other isolate tested. The results indicate that isolates of B. bovis capable of evading vaccine-induced immunity contain an msa-1 gene that is significantly different from the msa-1 of the vaccine strain, and that the difference can result in a complete lack of cross-reactivity between MSA-1 from vaccine and breakthrough strains in immunized animals. PMID:16113254

  17. Identification and expression of Babesia ovis secreted antigen 1 and evaluation of its diagnostic potential in an enzyme-linked immunosorbent assay.

    PubMed

    Sevinc, Ferda; Cao, Shinuo; Xuan, Xuenan; Sevinc, Mutlu; Ceylan, Onur

    2015-05-01

    In order to identify immunoreactive proteins that are usable for the immunological diagnosis of Babesia ovis infections, a phage lambda cDNA expression library was constructed and screened using parasite-specific immune serum. Immunoscreening resulted in the identification of a full-length cDNA clone encoding a secreted protein designated Babesia ovis secreted antigen 1 (BoSA1). The full-length BoSA1 cDNA contained a 1,137-bp open reading frame that encoded a protein of 378 amino acids, with a signal peptide and 2 internal repeat domains. The theoretical molecular mass of the mature protein was 42.5 kDa. Recombinant BoSA1 (rBoSA1) protein was expressed in Escherichia coli strain DH5α cells as a glutathione S-transferase (GST) fusion protein and was purified by affinity chromatography. Purified rBoSA1 was tested for reactivity with sera from animals experimentally or naturally infected with B. ovis, in an indirect enzyme-linked immunosorbent assay (ELISA). The results showed that specific antibodies against rBoSA1 were detectable on days 7 and 8 of the experimental infection and were maintained during the sampling period. Additionally, 38 field sera taken from sheep naturally infected with B. ovis gave strong positive reactions in the ELISA between day 20 and day 30 of treatment. As a result, the identified recombinant BoSA1 protein seems to be a promising diagnostic antigen that is usable for the development of serological assays for the diagnosis of ovine babesiosis. This is the first report on the molecular cloning, expression, and potential use of a recombinant antigen for the diagnosis of ovine babesiosis. PMID:25694531

  18. Early Endosomal Antigen 1 (EEA1) Is an Obligate Scaffold for Angiotensin II-induced, PKC-α-dependent Akt Activation in Endosomes*

    PubMed Central

    Nazarewicz, Rafal Robert; Salazar, Gloria; Patrushev, Nikolay; Martin, Alejandra San; Hilenski, Lula; Xiong, Shiqin; Alexander, R. Wayne

    2011-01-01

    Akt/protein kinase B (PKB) activation/phosphorylation by angiotensin II (Ang II) is a critical signaling event in hypertrophy of vascular smooth muscle cells (VSMCs). Conventional wisdom asserts that Akt activation occurs mainly in plasma membrane domains. Recent evidence that Akt activation may take place within intracellular compartments challenges this dogma. The spatial identity and mechanistic features of these putative signaling domains have not been defined. Using cell fractionation and fluorescence methods, we demonstrate that the early endosomal antigen-1 (EEA1)-positive endosomes are a major site of Ang II-induced Akt activation. Akt moves to and is activated in EEA1 endosomes. The expression of EEA1 is required for phosphorylation of Akt at both Thr-308 and Ser-473 as well as for phosphorylation of its downstream targets mTOR and S6 kinase, but not for Erk1/2 activation. Both Akt and phosphorylated Akt (p-Akt) interact with EEA1. We also found that PKC-α is required for organizing Ang II-induced, EEA1-dependent Akt phosphorylation in VSMC early endosomes. EEA1 expression enables PKC-α phosphorylation, which in turn regulates Akt upstream signaling kinases, PDK1 and p38 MAPK. Our results indicate that PKC-α is a necessary regulator of EEA1-dependent Akt signaling in early endosomes. Finally, EEA1 down-regulation or expression of a dominant negative mutant of PKC-α blunts Ang II-induced leucine incorporation in VSMCs. Thus, EEA1 serves a novel function as an obligate scaffold for Ang II-induced Akt activation in early endosomes. PMID:21097843

  19. Upregulated Neuro-oncological Ventral Antigen 1 (NOVA1) Expression Is Specific to Mature and Immature T- and NK-Cell Lymphomas

    PubMed Central

    Kim, Eun Kyung; Yoon, Sun Och; Kim, Soo Hee; Yang, Woo Ick; Cho, Yoon Ah; Kim, Soo Jeong

    2016-01-01

    Background: Recent studies have revealed that the splicing factor neuro-oncological ventral antigen 1 (NOVA1) is enriched in fibroblasts and accumulated T cells of tertiary lymphoid structures. In the present study, we investigated NOVA1 expression in various subtypes of mature and immature T- and natural killer (NK)-cell lymphomas as well as in various B-cell lymphoma subtypes. Methods: NOVA1 immunoexpression was evaluated in hyperplastic palatine tonsils (n = 20), T- and NK-cell lymphomas (n = 177), diffuse large B-cell lymphomas (n = 151), and other types of B cell lymphomas (n = 31). Nuclear staining intensity and percentage of positive tumor cells were graded. NOVA1 mRNA expression was analyzed in various lymphoma cell lines. Results: Tumor cells of T- and NK-cell lymphomas showed higher expression levels of NOVA1 than did normal paracortical T cells, and 56.5% of T- and NK-cell lymphoma cases showed diffuse and strong expression. The NOVA1 expression level varied according to the subtype; it was higher in angioimmunoblastic T-cell lymphoma, anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCL), and T lymphoblastic leukemia/lymphoma (T-LBL), but it was lower in ALK-positive ALCL. In almost all B-cell lymphomas, NOVA1 expression was very low or negative. NOVA1 mRNA was also expressed in Jurkat, a T-LBL cell line. Conclusions: The present findings suggest that NOVA1 upregulation may be involved in certain subtypes of T- and NK-cell lymphomas, but not in B-cell lymphomas. Upregulated NOVA1 expression seems to be a specific biological feature of activated T cells such as T- and NK-cell lymphomas. PMID:26922803

  20. Identification and Expression of Babesia ovis Secreted Antigen 1 and Evaluation of Its Diagnostic Potential in an Enzyme-Linked Immunosorbent Assay

    PubMed Central

    Cao, Shinuo; Xuan, Xuenan; Sevinc, Mutlu; Ceylan, Onur

    2015-01-01

    In order to identify immunoreactive proteins that are usable for the immunological diagnosis of Babesia ovis infections, a phage lambda cDNA expression library was constructed and screened using parasite-specific immune serum. Immunoscreening resulted in the identification of a full-length cDNA clone encoding a secreted protein designated Babesia ovis secreted antigen 1 (BoSA1). The full-length BoSA1 cDNA contained a 1,137-bp open reading frame that encoded a protein of 378 amino acids, with a signal peptide and 2 internal repeat domains. The theoretical molecular mass of the mature protein was 42.5 kDa. Recombinant BoSA1 (rBoSA1) protein was expressed in Escherichia coli strain DH5α cells as a glutathione S-transferase (GST) fusion protein and was purified by affinity chromatography. Purified rBoSA1 was tested for reactivity with sera from animals experimentally or naturally infected with B. ovis, in an indirect enzyme-linked immunosorbent assay (ELISA). The results showed that specific antibodies against rBoSA1 were detectable on days 7 and 8 of the experimental infection and were maintained during the sampling period. Additionally, 38 field sera taken from sheep naturally infected with B. ovis gave strong positive reactions in the ELISA between day 20 and day 30 of treatment. As a result, the identified recombinant BoSA1 protein seems to be a promising diagnostic antigen that is usable for the development of serological assays for the diagnosis of ovine babesiosis. This is the first report on the molecular cloning, expression, and potential use of a recombinant antigen for the diagnosis of ovine babesiosis. PMID:25694531

  1. Comparison of quality of induction of anaesthesia between intramuscularly administered ketamine, intravenously administered ketamine and intravenously administered propofol in xylazine premedicated cats.

    PubMed

    Dzikiti, T B; Chanaiwa, S; Mponda, P; Sigauke, C; Dzikiti, L N

    2007-12-01

    The quality of induction of general anesthesia produced by ketamine and propofol, 2 of the most commonly used anaesthetic agents in cats, was assessed. Eighteen cats admitted for elective procedures were randomly assigned to 3 groups and then premedicated with xylazine 0.75 mg/kg intramuscularly before anaesthesia was induced with ketamine 15 mg/kg intramuscularly (KetIM group), ketamine 10 mg/kg intravenously (KetIV group) or propofol 4 mg/kg intravenously (PropIV group). Quality of induction of general anaesthesia was determined by scoring ease of intubation, degree of struggling, and vocalisation during the induction period. The quality of induction of anaesthesia of intramuscularly administered ketamine was inferior to that of intravenously administered ketamine, while intravenously administered propofol showed little difference in quality of induction from ketamine administered by both the intramuscular and intravenous routes. There were no significant differences between groups in the ease of intubation scores, while vocalisation and struggling were more common in cats that received ketamine intramuscularly than in those that received intravenously administered ketamine or propofol for induction of anaesthesia. Laryngospasms occurred in 2 cats that received propofol. The heart rates and respiratory rates decreased after xylazine premedication and either remained the same or decreased further after induction for all 3 groups, but remained within normal acceptable limits. This study indicates that the 3 regimens are associated with acceptable induction characteristics, but administration of ketamine intravenously is superior to its administration intramuscularly and laryngeal desensitisation is recommended to avoid laryngospasms. PMID:18507218

  2. Identifying Patient-Specific Epstein-Barr Nuclear Antigen-1 Genetic Variation and Potential Autoreactive Targets Relevant to Multiple Sclerosis Pathogenesis

    PubMed Central

    Tschochner, Monika; Leary, Shay; Cooper, Don; Strautins, Kaija; Chopra, Abha; Clark, Hayley; Choo, Linda; Dunn, David; James, Ian; Carroll, William M.; Kermode, Allan G.; Nolan, David

    2016-01-01

    Background Epstein-Barr virus (EBV) infection represents a major environmental risk factor for multiple sclerosis (MS), with evidence of selective expansion of Epstein-Barr Nuclear Antigen-1 (EBNA1)-specific CD4+ T cells that cross-recognize MS-associated myelin antigens in MS patients. HLA-DRB1*15-restricted antigen presentation also appears to determine susceptibility given its role as a dominant risk allele. In this study, we have utilised standard and next-generation sequencing techniques to investigate EBNA-1 sequence variation and its relationship to HLA-DR15 binding affinity, as well as examining potential cross-reactive immune targets within the central nervous system proteome. Methods Sanger sequencing was performed on DNA isolated from peripheral blood samples from 73 Western Australian MS cases, without requirement for primary culture, with additional FLX 454 Roche sequencing in 23 samples to identify low-frequency variants. Patient-derived viral sequences were used to predict HLA-DRB1*1501 epitopes (NetMHCII, NetMHCIIpan) and candidates were evaluated for cross recognition with human brain proteins. Results EBNA-1 sequence variation was limited, with no evidence of multiple viral strains and only low levels of variation identified by FLX technology (8.3% nucleotide positions at a 1% cut-off). In silico epitope mapping revealed two known HLA-DRB1*1501-restricted epitopes (‘AEG’: aa 481–496 and ‘MVF’: aa 562–577), and two putative epitopes between positions 502–543. We identified potential cross-reactive targets involving a number of major myelin antigens including experimentally confirmed HLA-DRB1*15-restricted epitopes as well as novel candidate antigens within myelin and paranodal assembly proteins that may be relevant to MS pathogenesis. Conclusions This study demonstrates the feasibility of obtaining autologous EBNA-1 sequences directly from buffy coat samples, and confirms divergence of these sequences from standard laboratory strains

  3. Tumor cell lysis by activated human neutrophils: analysis of neutrophil-delivered oxidative attack and role of leukocyte function-associated antigen 1.

    PubMed

    Dallegri, F; Ottonello, L; Ballestrero, A; Dapino, P; Ferrando, F; Patrone, F; Sacchetti, C

    1991-02-01

    The lysis of tumor cells, and other nucleated mammalian cells, by neutrophilic polymorphonuclear leukocytes (PMNs) triggered by phorbol myristate acetate (PMA) represents a widely used model system to dissect the PMN cytolytic armamentarium, potentially responsible for the cell damage at tissue sites of PMN activation. Although oxidants are generally considered to be instrumental in the target lysis by PMNs, the mediators actually involved remain a matter of controversy. Moreover, other factors potentially crucial to the lysis have not been clearly identified. In order to reexamine the determinants of the cytolytic process, we studied the events underlying the PMA-triggered PMN-delivered attack against two different targets, selected on the basis of preliminary experiments (B lymphoblastoid Daudi cells and erythroleukemic K 562 cells). The results suggest that the lysis is promoted by hypochlorous acid (HOCl) or a compound with characteristics very similar to HOCl itself. No evidence was obtained for the intervention or contribution of hydrogen peroxide (H2O2), hydroxyl (OH.) radicals, and the major HOCl-derived chloramines. PMNs appeared to use 35% of the generated H2O2 to produce HOCl, while the remainder appears to be consumed by PMNs themselves and target cells as well. Moreover, PMNs and target cells coaggregated at an early step of the cytolytic reaction, through a process efficiently prevented by a monoclonal antibody (MoAb J-90) directed against leukocyte function-associated antigen-1 (LFA-1). The inhibition of the PMN-target aggregation by the MoAb J-90 resulted in the impairment of the lysis, despite a normal generation of HOCl. Thus, the data demonstrate that the PMA-triggered lysis of tumor target cells by PMNs requires at least two events, occurring simultaneously: the LFA-1-mediated effector-target adherence and the PMN production of HOCl. The intervention of the LFA-1-mediated PMN-target adherence in the PMA-triggered lysis is likely to allow PMNs to

  4. Specific acceptance of fetal bowel allograft in mice after combined treatment with anti-intercellular adhesion molecule-1 and leukocyte function-associated antigen-1 antibodies.

    PubMed Central

    Kato, Y; Yamataka, A; Yagita, H; Okumura, K; Fujiwara, T; Miyano, T

    1996-01-01

    OBJECTIVE: The aim of this study was to see whether tolerance could be induced by simultaneous administration of monoclonal antibodies (MoAbs) to intercellular adhesion molecule-1 (ICAM-1) and leukocyte function-associated antigen-1 (LFA-1) after transplantation of fetal small bowel between fully incompatible mice strains. METHODS: Fetal small bowel from either BALB/c (H-2d) or C3H/He (H-2k) mice was transplanted into the space between the peritoneum and rectus abdominis of adult C3H/He recipient mice. Syngeneic (n = 6) and two allogeneic transplant groups were made. In one of the allogeneic groups (n = 8), no immunosuppressant was given. In the other allogeneic group (n = 13), both anti-LFA-1 and anti-ICAM-1 MoAbs (50 micrograms each/mouse/day) were given intraperitoneally after transplantation for the first 4 weeks. In the syngeneic and untreated allogeneic groups, all mice were killed 4 weeks after transplantation. In the treated allogeneic group, eight mice were killed 6 weeks after cessation of the MoAb treatment. At the time the mice were killed, the bowel graft as well as the recipient spleen were taken for histologic analysis and cytotoxic T-lymphocyte (CTL) assay, respectively. Each mouse in the remaining treated five mice was transplanted with BALB/c and C57BL/6 (as third-party) full-thickness skin simultaneously 8 weeks after cessation of the MoAb treatment. RESULTS: All grafts in the syngeneic group survived with normally developing villi, whereas all grafts in the untreated allogeneic group disappeared. In the treated allogeneic group, all allografts developed normal mucosa without any sign of rejection. Splenocytes from the recipient mice in the untreated allogeneic group showed increased CTL induction against donor-type alloantigen (p < 0.005), compared with that in the syngeneic group. Suppressed CTL induction against donor-type alloantigen was observed in the treated allografted recipient (p < 0.001), whereas CTL induction against third

  5. Isolation of functionally distinct mesenchymal stem cell subsets using antibodies against CD56, CD271, and mesenchymal stem cell antigen-1

    PubMed Central

    Battula, Venkata Lokesh; Treml, Sabrina; Bareiss, Petra M.; Gieseke, Friederike; Roelofs, Helene; de Zwart, Peter; Müller, Ingo; Schewe, Bernhard; Skutella, Thomas; Fibbe, Willem E.; Kanz, Lothar; Bühring, Hans-Jörg

    2009-01-01

    Background Conventionally, mesenchymal stem cells are functionally isolated from primary tissue based on their capacity to adhere to a plastic surface. This isolation procedure is hampered by the unpredictable influence of co-cultured hematopoietic and/or other unrelated cells and/or by the elimination of a late adhering mesenchymal stem cells subset during removal of undesired cells. To circumvent these limitations, several antibodies have been developed to facilitate the prospective isolation of mesenchymal stem cells. Recently, we described a panel of monoclonal antibodies with superior selectivity for mesenchymal stem cells, including the monoclonal antibodies W8B2 against human mesenchymal stem cell antigen-1 (MSCA-1) and 39D5 against a CD56 epitope, which is not expressed on natural killer cells. Design and Methods Bone marrow derived mesenchymal stem cells from healthy donors were analyzed and isolated by flow cytometry using a large panel of antibodies against surface antigens including CD271, MSCA-1, and CD56. The growth of mesenchymal stem cells was monitored by colony formation unit fibroblast (CFU-F) assays. The differentiation of mesenchymal stem cells into defined lineages was induced by culture in appropriate media and verified by immunostaining. Results Multicolor cell sorting and CFU-F assays showed that mesenchymal stem cells were ~90-fold enriched in the MSCA-1+CD56− fraction and ~180-fold in the MSCA-1+CD56+ fraction. Phenotype analysis revealed that the expression of CD10, CD26, CD106, and CD146 was restricted to the MSCA-1+CD56− mesenchymal stem cells subset and CD166 to MSCA-1+CD56± mesenchymal stem cells. Further differentiation of these subsets showed that chondrocytes and pancreatic-like islets were predominantly derived from MSCA-1+CD56± cells whereas adipocytes emerged exclusively from MSCA-1+CD56− cells. The culture of single sorted MSCA-1+CD56+ cells resulted in the appearance of phenotypically heterogeneous clones with

  6. Pediatric nurses' thinking in response to vignettes on administering analgesics.

    PubMed

    Van Hulle Vincent, Catherine; Gaddy, Erica J

    2009-10-01

    Pediatric nurses are not administering available and recommended analgesics to hospitalized children after surgery. This descriptive study was conducted to examine 30 pediatric nurses' thinking-in response to case study vignettes-about pain assessment and morphine administration for children experiencing postoperative pain. Nurses considered numerous factors when assessing and managing children's pain, including pain level, vital signs, and facial expression. Nurses frequently relied, however, on behavioral and physiological manifestations, as opposed to self-report, when choosing whether to administer morphine. Nurses demonstrated misconceptions about pharmacokinetics and unwarranted concerns about the adverse effects of morphine. These findings partly explain why children continue to report high levels of pain after surgery and why nurses may not administer adequate analgesics to relieve children's pain. PMID:19504564

  7. Self-administered electroconvulsive treatment with a homemade device.

    PubMed

    Adachi, Takuya; Masumura, Toshiaki; Arai, Minoru; Adachi, Naoto; Akazawa, Shigeru; Arai, Heii

    2006-09-01

    Two patients with personality disorder and depression attempted to self-administer electroconvulsive therapy with a homemade device. The patients showed no proper psychopathological improvement after these attempts. Both of the patients' temples were seriously burned, and one of them required skin grafting. Both patients rejected to have reasonable psychosocial support, and followed a cult mental health manual in attempting to self-administer electroconvulsive therapy. To our knowledge, this is only the second report of its kind. The intractable psychopathology, poor interpersonal skills, and misleading information seemed to lead to the self-harm behaviors of our 2 patients. PMID:16957542

  8. 40 CFR 282.56 - Connecticut State-Administered Program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ....C. 6991c and 40 CFR part 281. EPA approved the Connecticut program on June 27, 1995, and the... stringent, in accordance with Section 9004 of RCRA, 42 U.S.C. 6991c, and 40 CFR part 281, subpart E. If... 40 Protection of Environment 27 2014-07-01 2014-07-01 false Connecticut State-Administered...

  9. 40 CFR 282.56 - Connecticut State-Administered Program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ....C. 6991c and 40 CFR part 281. EPA approved the Connecticut program on June 27, 1995, and the... stringent, in accordance with Section 9004 of RCRA, 42 U.S.C. 6991c, and 40 CFR part 281, subpart E. If... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Connecticut State-Administered...

  10. 40 CFR 282.56 - Connecticut State-Administered Program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ....C. 6991c and 40 CFR part 281. EPA approved the Connecticut program on June 27, 1995, and the... stringent, in accordance with Section 9004 of RCRA, 42 U.S.C. 6991c, and 40 CFR part 281, subpart E. If... 40 Protection of Environment 28 2013-07-01 2013-07-01 false Connecticut State-Administered...

  11. A Mobile Platform for Administering Questionnaires and Synchronizing Their Answers

    ERIC Educational Resources Information Center

    Ginardi, Maria Germana; Lanzola, Giordano

    2013-01-01

    This paper describes a platform for administering questionnaires on smart-phones and tablets. The project arises from the need of acquiring data for monitoring the outcomes of different homecare interventions. First a model has been defined for representing questionnaires, able to support adaptivity in the dialog with the user and enforce some…

  12. 40 CFR 282.86 - Oklahoma State-Administered Program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... with section 9004 of RCRA, 42 U.S.C. 6991c, and 40 CFR part 281, subpart E. If Oklahoma obtains... 40 Protection of Environment 27 2014-07-01 2014-07-01 false Oklahoma State-Administered Program... WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.86...

  13. 40 CFR 282.86 - Oklahoma State-Administered Program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... with section 9004 of RCRA, 42 U.S.C. 6991c, and 40 CFR part 281, subpart E. If Oklahoma obtains... 40 Protection of Environment 28 2012-07-01 2012-07-01 false Oklahoma State-Administered Program... WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.86...

  14. 40 CFR 282.86 - Oklahoma State-Administered Program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... with section 9004 of RCRA, 42 U.S.C. 6991c, and 40 CFR part 281, subpart E. If Oklahoma obtains... 40 Protection of Environment 28 2013-07-01 2013-07-01 false Oklahoma State-Administered Program... WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.86...

  15. 40 CFR 282.86 - Oklahoma State-Administered Program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... with section 9004 of RCRA, 42 U.S.C. 6991c, and 40 CFR part 281, subpart E. If Oklahoma obtains... 40 Protection of Environment 27 2011-07-01 2011-07-01 false Oklahoma State-Administered Program... WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.86...

  16. 40 CFR 147.3100 - EPA-administered program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Osage Mineral Reserve (found at 40 CFR part 147, Subpart GGG) and the Class II program for the Five Civilized Tribes, consists of the UIC program requirements of 40 CFR parts 124, 144, 146, 148, and... Oklahoma Indian Tribes § 147.3100 EPA-administered program. (a) Contents. The UIC program for the...

  17. 40 CFR 147.3100 - EPA-administered program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Osage Mineral Reserve (found at 40 CFR part 147, Subpart GGG) and the Class II program for the Five Civilized Tribes, consists of the UIC program requirements of 40 CFR parts 124, 144, 146, 148, and... Oklahoma Indian Tribes § 147.3100 EPA-administered program. (a) Contents. The UIC program for the...

  18. 40 CFR 147.3100 - EPA-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Osage Mineral Reserve (found at 40 CFR part 147, Subpart GGG) and the Class II program for the Five Civilized Tribes, consists of the UIC program requirements of 40 CFR parts 124, 144, 146, 148, and... Oklahoma Indian Tribes § 147.3100 EPA-administered program. (a) Contents. The UIC program for the...

  19. 40 CFR 282.86 - Oklahoma State-Administered Program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... with section 9004 of RCRA, 42 U.S.C. 6991c, and 40 CFR part 281, subpart E. If Oklahoma obtains... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Oklahoma State-Administered Program... WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.86...

  20. Teaching Auction Strategy Using Experiments Administered Via the Internet

    ERIC Educational Resources Information Center

    Asker, John; Grosskopf, Brit; McKinney, C. Nicholas; Niederle, Muriel; Roth, Alvin E.; Weizsacker, Georg

    2004-01-01

    The authors present an experimental design used to teach concepts in the economics of auctions and implications for e-Business procurement. The experiment is easily administered and can be adapted to many different treatments. The chief innovation is that it does not require the use of a lab or class time. Instead, the design can be implemented on…

  1. 40 CFR 147.2500 - State-administered program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... reference was approved by the Director of the OFR in accordance with 5 U.S.C. 552(a) and 1 CFR part 51... State-administered program: (1) Chapter 144, Water, Sewage, Refuse, Mining and Air Pollution, Wisconsin... Section 147.2500 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER...

  2. 40 CFR 147.2500 - State-administered program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... reference was approved by the Director of the OFR in accordance with 5 U.S.C. 552(a) and 1 CFR part 51... State-administered program: (1) Chapter 144, Water, Sewage, Refuse, Mining and Air Pollution, Wisconsin... Section 147.2500 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER...

  3. 25 CFR 170.471 - How are projects administered?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Construction Monitoring § 170.471 How are projects administered? (a) When a tribe carries out an IRR project under ISDEAA, BIA will monitor performance under the requirements of 25 CFR 900.130 and 900.131(b)(9) or 25 CFR 1000.243 and 1000.249(c) and (e), as appropriate. If BIA discovers a problem during an...

  4. 25 CFR 170.471 - How are projects administered?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false How are projects administered? 170.471 Section 170.471 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER INDIAN RESERVATION ROADS PROGRAM Planning, Design, and Construction of Indian Reservation Roads Program Facilities Construction and Construction Monitoring § 170.471 How...

  5. 40 CFR 282.92 - Tennessee State-Administered Program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., and 40 CFR part 281, subpart E. If Tennessee obtains approval for the revised requirements pursuant to... Storage Tanks, 4th Floor, L&C Tower, 401 Church Street, Nashville, Tennessee 37243-1541. (1) State... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Tennessee State-Administered...

  6. 40 CFR 282.60 - Georgia State-Administered Program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... it more stringent, in accordance with section 9004 of RCRA, 42 U.S.C. 6991c, and 40 CFR part 281... 40 Protection of Environment 28 2013-07-01 2013-07-01 false Georgia State-Administered Program... WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.60...

  7. 40 CFR 282.60 - Georgia State-Administered Program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... it more stringent, in accordance with section 9004 of RCRA, 42 U.S.C. 6991c, and 40 CFR part 281... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Georgia State-Administered Program... WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.60...

  8. 40 CFR 282.60 - Georgia State-Administered Program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... it more stringent, in accordance with section 9004 of RCRA, 42 U.S.C. 6991c, and 40 CFR part 281... 40 Protection of Environment 27 2014-07-01 2014-07-01 false Georgia State-Administered Program... WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.60...

  9. 40 CFR 282.60 - Georgia State-Administered Program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... it more stringent, in accordance with section 9004 of RCRA, 42 U.S.C. 6991c, and 40 CFR part 281... 40 Protection of Environment 28 2012-07-01 2012-07-01 false Georgia State-Administered Program... WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.60...

  10. 40 CFR 282.60 - Georgia State-Administered Program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... it more stringent, in accordance with section 9004 of RCRA, 42 U.S.C. 6991c, and 40 CFR part 281... 40 Protection of Environment 27 2011-07-01 2011-07-01 false Georgia State-Administered Program... WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.60...

  11. 40 CFR 282.96 - Virginia State-Administered Program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... stringent, in accordance with section 9004 of RCRA, 42 U.S.C. 6991c, and 40 CFR part 281, subpart E. If... 40 Protection of Environment 27 2014-07-01 2014-07-01 false Virginia State-Administered Program... WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.96...

  12. 40 CFR 282.96 - Virginia State-Administered Program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... stringent, in accordance with section 9004 of RCRA, 42 U.S.C. 6991c, and 40 CFR part 281, subpart E. If... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Virginia State-Administered Program... WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.96...

  13. 40 CFR 282.96 - Virginia State-Administered Program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... stringent, in accordance with section 9004 of RCRA, 42 U.S.C. 6991c, and 40 CFR part 281, subpart E. If... 40 Protection of Environment 28 2013-07-01 2013-07-01 false Virginia State-Administered Program... WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.96...

  14. 40 CFR 282.96 - Virginia State-Administered Program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... stringent, in accordance with section 9004 of RCRA, 42 U.S.C. 6991c, and 40 CFR part 281, subpart E. If... 40 Protection of Environment 27 2011-07-01 2011-07-01 false Virginia State-Administered Program... WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.96...

  15. 7 CFR 634.30 - Appeals in USDA administered projects.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Appeals in USDA administered projects. 634.30 Section 634.30 Agriculture Regulations of the Department of Agriculture (Continued) NATURAL RESOURCES CONSERVATION SERVICE, DEPARTMENT OF AGRICULTURE LONG TERM CONTRACTING RURAL CLEAN WATER PROGRAM...

  16. 7 CFR 634.30 - Appeals in USDA administered projects.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 6 2012-01-01 2012-01-01 false Appeals in USDA administered projects. 634.30 Section 634.30 Agriculture Regulations of the Department of Agriculture (Continued) NATURAL RESOURCES CONSERVATION SERVICE, DEPARTMENT OF AGRICULTURE LONG TERM CONTRACTING RURAL CLEAN WATER PROGRAM...

  17. 7 CFR 634.30 - Appeals in USDA administered projects.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 6 2013-01-01 2013-01-01 false Appeals in USDA administered projects. 634.30 Section 634.30 Agriculture Regulations of the Department of Agriculture (Continued) NATURAL RESOURCES CONSERVATION SERVICE, DEPARTMENT OF AGRICULTURE LONG TERM CONTRACTING RURAL CLEAN WATER PROGRAM...

  18. 7 CFR 634.30 - Appeals in USDA administered projects.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 6 2011-01-01 2011-01-01 false Appeals in USDA administered projects. 634.30 Section 634.30 Agriculture Regulations of the Department of Agriculture (Continued) NATURAL RESOURCES CONSERVATION SERVICE, DEPARTMENT OF AGRICULTURE LONG TERM CONTRACTING RURAL CLEAN WATER PROGRAM...

  19. 7 CFR 634.30 - Appeals in USDA administered projects.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 6 2014-01-01 2014-01-01 false Appeals in USDA administered projects. 634.30 Section 634.30 Agriculture Regulations of the Department of Agriculture (Continued) NATURAL RESOURCES CONSERVATION SERVICE, DEPARTMENT OF AGRICULTURE LONG TERM CONTRACTING RURAL CLEAN WATER PROGRAM...

  20. 24 CFR 511.51 - State-administered program.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... URBAN DEVELOPMENT SLUM CLEARANCE AND URBAN RENEWAL RENTAL REHABILITATION GRANT PROGRAM State Program... 24 Housing and Urban Development 3 2013-04-01 2013-04-01 false State-administered program. 511.51 Section 511.51 Housing and Urban Development Regulations Relating to Housing and Urban...

  1. 24 CFR 511.51 - State-administered program.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... URBAN DEVELOPMENT SLUM CLEARANCE AND URBAN RENEWAL RENTAL REHABILITATION GRANT PROGRAM State Program... 24 Housing and Urban Development 3 2014-04-01 2013-04-01 true State-administered program. 511.51 Section 511.51 Housing and Urban Development Regulations Relating to Housing and Urban...

  2. 24 CFR 511.51 - State-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... URBAN DEVELOPMENT SLUM CLEARANCE AND URBAN RENEWAL RENTAL REHABILITATON GRANT PROGRAM State Program... 24 Housing and Urban Development 3 2010-04-01 2010-04-01 false State-administered program. 511.51 Section 511.51 Housing and Urban Development Regulations Relating to Housing and Urban...

  3. 24 CFR 511.51 - State-administered program.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... URBAN DEVELOPMENT SLUM CLEARANCE AND URBAN RENEWAL RENTAL REHABILITATON GRANT PROGRAM State Program... 24 Housing and Urban Development 3 2011-04-01 2010-04-01 true State-administered program. 511.51 Section 511.51 Housing and Urban Development Regulations Relating to Housing and Urban...

  4. 24 CFR 511.51 - State-administered program.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... URBAN DEVELOPMENT SLUM CLEARANCE AND URBAN RENEWAL RENTAL REHABILITATION GRANT PROGRAM State Program... 24 Housing and Urban Development 3 2012-04-01 2012-04-01 false State-administered program. 511.51 Section 511.51 Housing and Urban Development Regulations Relating to Housing and Urban...

  5. 40 CFR 282.92 - Tennessee State-Administered Program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... administered by the Tennessee Department of Environment and Conservation, Division of Underground Storage Tanks... Underground Storage Tanks, signed by the EPA Regional Administrator on July 1, 1998, though not incorporated... Storage Tanks, 4th Floor, L&C Tower, 401 Church Street, Nashville, Tennessee 37243-1541. (1)...

  6. 40 CFR 147.1700 - State-administered program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... incorporation by reference was approved by the Director of the OFR in accordance with 5 U.S.C. 552(a) and 1 CFR...-administered program: (1) N.C. ADMIN. CODE, Title 15, r. 02L.0100 et seq. Groundwater Classification...

  7. 32 CFR 637.11 - Authority to administer oaths.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 4 2012-07-01 2011-07-01 true Authority to administer oaths. 637.11 Section 637.11 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) LAW ENFORCEMENT AND CRIMINAL INVESTIGATIONS MILITARY POLICE INVESTIGATION Investigations § 637.11 Authority...

  8. 32 CFR 637.11 - Authority to administer oaths.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 4 2013-07-01 2013-07-01 false Authority to administer oaths. 637.11 Section 637.11 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) LAW ENFORCEMENT AND CRIMINAL INVESTIGATIONS MILITARY POLICE INVESTIGATION Investigations § 637.11 Authority...

  9. 32 CFR 637.11 - Authority to administer oaths.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 4 2014-07-01 2013-07-01 true Authority to administer oaths. 637.11 Section 637.11 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) LAW ENFORCEMENT AND CRIMINAL INVESTIGATIONS MILITARY POLICE INVESTIGATION Investigations § 637.11 Authority...

  10. 32 CFR 637.11 - Authority to administer oaths.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Authority to administer oaths. 637.11 Section 637.11 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) LAW ENFORCEMENT AND CRIMINAL INVESTIGATIONS MILITARY POLICE INVESTIGATION Investigations § 637.11 Authority...

  11. 32 CFR 637.11 - Authority to administer oaths.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 4 2011-07-01 2011-07-01 false Authority to administer oaths. 637.11 Section 637.11 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) LAW ENFORCEMENT AND CRIMINAL INVESTIGATIONS MILITARY POLICE INVESTIGATION Investigations § 637.11 Authority...

  12. Baseline Geography Competency Test Administered in Indiana Universities.

    ERIC Educational Resources Information Center

    Bein, Frederick L.

    A baseline geography skills test was administered during 1987 to over 3,000 students who were enrolled in freshmen geography courses at 18 Indiana universities. Known as the National Council for Geographic Education Competency-Based Geography Test, Secondary Level, Form D, this test was used to measure the students' level of geographic ability in:…

  13. 40 CFR 282.53 - Arkansas State-Administered Program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... stringent, in accordance with section 9004 of RCRA, 42 U.S.C. 6991c, and 40 CFR part 281, subpart E. If... administered by the Arkansas Department of Pollution Control and Ecology, was approved by EPA pursuant to 42 U... Pollution Control and Ecology, 8001 National Drive, Little Rock, AR 72219-8913. (1) State statutes...

  14. 40 CFR 282.53 - Arkansas State-Administered Program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... stringent, in accordance with section 9004 of RCRA, 42 U.S.C. 6991c, and 40 CFR part 281, subpart E. If... administered by the Arkansas Department of Pollution Control and Ecology, was approved by EPA pursuant to 42 U... Pollution Control and Ecology, 8001 National Drive, Little Rock, AR 72219-8913. (1) State statutes...

  15. 40 CFR 282.53 - Arkansas State-Administered Program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... stringent, in accordance with section 9004 of RCRA, 42 U.S.C. 6991c, and 40 CFR part 281, subpart E. If... administered by the Arkansas Department of Pollution Control and Ecology, was approved by EPA pursuant to 42 U... Pollution Control and Ecology, 8001 National Drive, Little Rock, AR 72219-8913. (1) State statutes...

  16. 40 CFR 282.53 - Arkansas State-Administered Program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... stringent, in accordance with section 9004 of RCRA, 42 U.S.C. 6991c, and 40 CFR part 281, subpart E. If... administered by the Arkansas Department of Pollution Control and Ecology, was approved by EPA pursuant to 42 U... Pollution Control and Ecology, 8001 National Drive, Little Rock, AR 72219-8913. (1) State statutes...

  17. 40 CFR 282.53 - Arkansas State-Administered Program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... stringent, in accordance with section 9004 of RCRA, 42 U.S.C. 6991c, and 40 CFR part 281, subpart E. If... administered by the Arkansas Department of Pollution Control and Ecology, was approved by EPA pursuant to 42 U... Pollution Control and Ecology, 8001 National Drive, Little Rock, AR 72219-8913. (1) State statutes...

  18. 40 CFR 147.2300 - State-administered program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... the Underground Water Source Protection Program Pursuant to the Safe Drinking Water Act and 40 CFR 145... was approved by the Director of the Federal Register July 6, 1984. (1) Vt. Stat. Ann. tit. 10... are part of the approved State-administered program: (1) Vt. Stat. Ann. tit. 10, sections 1251...

  19. 40 CFR 147.2300 - State-administered program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... the Underground Water Source Protection Program Pursuant to the Safe Drinking Water Act and 40 CFR 145... was approved by the Director of the Federal Register July 6, 1984. (1) Vt. Stat. Ann. tit. 10... are part of the approved State-administered program: (1) Vt. Stat. Ann. tit. 10, sections 1251...

  20. 40 CFR 147.2300 - State-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... the Underground Water Source Protection Program Pursuant to the Safe Drinking Water Act and 40 CFR 145... was approved by the Director of the Federal Register July 6, 1984. (1) Vt. Stat. Ann. tit. 10... are part of the approved State-administered program: (1) Vt. Stat. Ann. tit. 10, sections 1251...

  1. 40 CFR 147.2300 - State-administered program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... the Underground Water Source Protection Program Pursuant to the Safe Drinking Water Act and 40 CFR 145... was approved by the Director of the Federal Register July 6, 1984. (1) Vt. Stat. Ann. tit. 10... are part of the approved State-administered program: (1) Vt. Stat. Ann. tit. 10, sections 1251...

  2. 40 CFR 147.2300 - State-administered program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... the Underground Water Source Protection Program Pursuant to the Safe Drinking Water Act and 40 CFR 145... was approved by the Director of the Federal Register July 6, 1984. (1) Vt. Stat. Ann. tit. 10... are part of the approved State-administered program: (1) Vt. Stat. Ann. tit. 10, sections 1251...

  3. 8 CFR 337.8 - Oath administered by the courts.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... naturalization not subject to the exclusive jurisdiction of 8 CFR 310.2(d) must notify USCIS at the time of the... from the list of eligible persons as provided in 8 CFR 335.5 and the court will not administer the oath... naturalization not subject to the exclusive jurisdiction of 8 CFR 310.3(d) who has elected to have......

  4. 40 CFR 147.2500 - State-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... reference was approved by the Director of the OFR in accordance with 5 U.S.C. 552(a) and 1 CFR part 51... Disposal of Liquid Industrial Wastes and By-Products, Wisconsin Administrative Code §§ 214.03 and 214.08... State-administered program: (1) Chapter 144, Water, Sewage, Refuse, Mining and Air Pollution,...

  5. 40 CFR 282.73 - Minnesota State-Administered Program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., Chapter 7150—Minnesota Pollution Control Agency, Water Quality Division, Underground Storage Tanks Program... WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.73 Minnesota State-Administered Program. (a) The State of Minnesota's underground storage tank program is approved...

  6. 40 CFR 282.73 - Minnesota State-Administered Program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., Chapter 7150—Minnesota Pollution Control Agency, Water Quality Division, Underground Storage Tanks Program... WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.73 Minnesota State-Administered Program. (a) The State of Minnesota's underground storage tank program is approved...

  7. 40 CFR 282.73 - Minnesota State-Administered Program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., Chapter 7150—Minnesota Pollution Control Agency, Water Quality Division, Underground Storage Tanks Program... WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.73 Minnesota State-Administered Program. (a) The State of Minnesota's underground storage tank program is approved...

  8. 40 CFR 282.73 - Minnesota State-Administered Program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., Chapter 7150—Minnesota Pollution Control Agency, Water Quality Division, Underground Storage Tanks Program... WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.73 Minnesota State-Administered Program. (a) The State of Minnesota's underground storage tank program is approved...

  9. 40 CFR 282.50 - Alabama State-Administered Program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... administered by the Alabama Department of Environmental Management, was approved by EPA pursuant to 42 U.S.C... RCRA, 42 U.S.C. 6991c, and 40 CFR part 281, subpart E. If Alabama obtains approval for the revised... obtained from the Ground Water Branch, Alabama Department of Environmental Management, 1751 W.L....

  10. Systemically Administered, Target Organ-Specific Therapies for Regenerative Medicine

    PubMed Central

    Järvinen, Tero A. H.; May, Ulrike; Prince, Stuart

    2015-01-01

    Growth factors and other agents that could potentially enhance tissue regeneration have been identified, but their therapeutic value in clinical medicine has been limited for reasons such as difficulty to maintain bioactivity of locally applied therapeutics in the protease-rich environment of regenerating tissues. Although human diseases are treated with systemically administered drugs in general, all current efforts aimed at enhancing tissue repair with biological drugs have been based on their local application. The systemic administration of growth factors has been ruled out due to concerns about their safety. These concerns are warranted. In addition, only a small proportion of systemically administered drugs reach their intended target. Selective delivery of the drug to the target tissue and use of functional protein domains capable of penetrating cells and tissues could alleviate these problems in certain circumstances. We will present in this review a novel approach utilizing unique molecular fingerprints (“Zip/postal codes”) in the vasculature of regenerating tissues that allows target organ-specific delivery of systemically administered therapeutic molecules by affinity-based physical targeting (using peptides or antibodies as an “address tag”) to injured tissues undergoing repair. The desired outcome of targeted therapies is increased local accumulation and lower systemic concentration of the therapeutic payload. We believe that the physical targeting of systemically administered therapeutic molecules could be rapidly adapted in the field of regenerative medicine. PMID:26437400

  11. 40 CFR 147.2500 - State-administered program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... reference was approved by the Director of the OFR in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. Copies may be obtained at the Wisconsin Department of Natural Resources, Box 7921, Madison, Wisconsin... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Wisconsin §...

  12. 40 CFR 282.92 - Tennessee State-Administered Program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., and 40 CFR part 281, subpart E. If Tennessee obtains approval for the revised requirements pursuant to... 40 Protection of Environment 27 2014-07-01 2014-07-01 false Tennessee State-Administered Program... WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.92...

  13. 40 CFR 282.92 - Tennessee State-Administered Program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., and 40 CFR part 281, subpart E. If Tennessee obtains approval for the revised requirements pursuant to... 40 Protection of Environment 27 2011-07-01 2011-07-01 false Tennessee State-Administered Program... WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.92...

  14. 40 CFR 282.92 - Tennessee State-Administered Program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., and 40 CFR part 281, subpart E. If Tennessee obtains approval for the revised requirements pursuant to... 40 Protection of Environment 28 2012-07-01 2012-07-01 false Tennessee State-Administered Program... WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.92...

  15. Topically administered corticosteroids: effect on antibiotic-treated bacterial keratitis.

    PubMed

    Leibowitz, H M; Kupferman, A

    1980-07-01

    The effect of a topically administered corticosteroid, 1.0% prednisolone acetate, on bacterial replication in rabbit cornea receiving adequate antibiotic therapy was determined. Staphylococcus aureus keratitis was treated either with neomycin sulfate or gentamicin sulfate, while Pseudomonas aeruginosa keratitis was treated either with gentamicin or polymyxin B sulfate. Each antibiotic was administered topically at hourly intervals in both the commercially available concentration and as a formulation containing four times the quantity of drug found in the commercial preparations. In each instance, the antibiotic regimen sharply reduced the number of viable organisms in the cornea, although the concentrated preparations did so more rapidly and effectively. The addition of 1.0% prednisolone acetate had no measurable effect on outcome. In no instance was there a statistically significant difference between number of residual viable organisms in antibiotic-treated corneas and antibiotic/corticosteroid-treated corneas. PMID:7396786

  16. Registered nurse-administered sedation for gastrointestinal endoscopic procedure

    PubMed Central

    Amornyotin, Somchai

    2015-01-01

    The rising use of nonanesthesiologist-administered sedation for gastrointestinal endoscopy has clinical significances. Most endoscopic patients require some forms of sedation and/or anesthesia. The goals of this sedation are to guard the patient’s safety, minimize physical discomfort, to control behavior and to diminish psychological responses. Generally, moderate sedation for these procedures has been offered by the non-anesthesiologist by using benzodiazepines and/or opioids. Anesthesiologists and non-anesthesiologist personnel will need to work together for these challenges and for safety of the patients. The sedation training courses including clinical skills and knowledge are necessary for the registered nurses to facilitate the patient safety and the successful procedure. However, appropriate patient selection and preparation, adequate monitoring and regular training will ensure that the use of nurse-administered sedation is a feasible and safe technique for gastrointestinal endoscopic procedures. PMID:26191341

  17. Intravenously administered nanoparticles increase survival following blast trauma

    PubMed Central

    Lashof-Sullivan, Margaret M.; Shoffstall, Erin; Atkins, Kristyn T.; Keane, Nickolas; Bir, Cynthia; VandeVord, Pamela; Lavik, Erin B.

    2014-01-01

    Explosions account for 79% of combat-related injuries, leading to multiorgan hemorrhage and uncontrolled bleeding. Uncontrolled bleeding is the leading cause of death in battlefield traumas as well as in civilian life. We need to stop the bleeding quickly to save lives, but, shockingly, there are no treatments to stop internal bleeding. A therapy that halts bleeding in a site-specific manner and is safe, stable at room temperature, and easily administered is critical for the advancement of trauma care. To address this need, we have developed hemostatic nanoparticles that are administered intravenously. When tested in a model of blast trauma with multiorgan hemorrhaging, i.v. administration of the hemostatic nanoparticles led to a significant improvement in survival over the short term (1 h postblast). No complications from this treatment were apparent out to 3 wk. This work demonstrates that these particles have the potential to save lives and fundamentally change trauma care. PMID:24982180

  18. Paradata: a new data source from web-administered measures.

    PubMed

    Sowan, Azizeh K; Jenkins, Louise S

    2010-01-01

    Web administration of measures offers numerous advantages as well as some drawbacks; the efficiency of collecting data in this way is dramatic. An important by-product of Web administration of measures is the option of creating paradata that offer information about how respondents access a measure (server-side paradata) and navigate within the online environment (client-side paradata) to complete the measure. Paradata can play a critical role in developing and piloting measures as well as refining the measurement process. Uses of paradata in Web-administered measures include (1) informing the choice of response formats, (2) examining the extent of changing response options, (3) examining the extent of following a prescribed sequence in completing a measure, (4) tracking the response process, (5) aiding in designing a Web-administered measure and its layout, and (6) assisting in determining the most appropriate log-in procedure. Because of the potential value of this new type of useful data to researchers in nursing and health, this article focuses on paradata within the context of Web-administered measures. More specifically, the article focuses on the definition, generation, and uses of paradata, as well as the ethical issues and other concerns in obtaining and using paradata. Uses of paradata to test the usability of information systems used in nursing and health practices are also included. PMID:20978403

  19. A self administered reliable questionnaire to assess lower bowel symptoms

    PubMed Central

    Adelstein, Barbara-Ann; Irwig, Les; Macaskill, Petra; Katelaris, Peter H; Jones, David B; Bokey, Les

    2008-01-01

    Background Bowel symptoms are considered indicators of the presence of colorectal cancer and other bowel diseases. Self administered questionnaires that elicit information about lower bowel symptoms have not been assessed for reliability, although this has been done for upper bowel symptoms. Our aim was to develop a self administered questionnaire for eliciting the presence, nature and severity of lower bowel symptoms potentially related to colorectal cancer, and assess its reliability. Methods Immediately before consulting a gastroenterologist or colorectal surgeon, 263 patients likely to have a colonoscopy completed the questionnaire. Reliability was assessed in two ways: by assessing agreement between patient responses and (a) responses given by the doctor at the consultation; and (b) responses given by patients two weeks later. Results There was more than 75% agreement for 78% of the questions for the patient-doctor comparison and for 92% of the questions for the patient-patient comparison. Agreement for the length of time a symptom was present, its severity, duration, frequency of occurrence and whether or not medical consultation had been sought, all had agreement of greater than 70%. Over all questions, the chance corrected agreement for the patient-doctor comparison had a median kappa of 65% (which represents substantial agreement), interquartile range 57–72%. The patient-patient comparison also showed substantial agreement with a median kappa of 75%, interquartile range 68–81%. Conclusion This self administered questionnaire about lower bowel symptoms is a useful way of eliciting details of bowel symptoms. It is a reliable instrument that is acceptable to patients and easily completed. Its use could guide the clinical consultation, allowing a more efficient, comprehensive and useful interaction, ensuring that all symptoms are assessed. It will also be a useful tool in research studies on bowel symptoms and their predictive value for colorectal cancer

  20. Patient biodistribution of intraperitoneally administered yttrium-90-labeled antibody.

    PubMed

    Hnatowich, D J; Chinol, M; Siebecker, D A; Gionet, M; Griffin, T; Doherty, P W; Hunter, R; Kase, K R

    1988-08-01

    Although 90Y is one of the best radionuclides for radioimmunotherapeutic applications, the lack of gamma rays in its decay complicates the estimation of radiation dose since its biodistribution cannot be accurately determined by external imaging. A limited clinical trial has been conducted with tracer doses (1 mCi) of 90Y in five patients who then received second-look surgery such that tissue samples were obtained for accurate radioactivity quantitation by in vitro counting. The anti-ovarian antibody OC-125 as the F(ab')2 fragment was coupled with diethylenetriaminepentaacetic acid, radiolabeled with 90Y and administered intraperitoneally to patients with suspected or documented ovarian cancer. Size exclusion and ion exchange high performance liquid chromatography analysis of patient ascitic fluid and serum samples showed no evidence of radiolabel instability although a high molecular weight species (presumably immune complex) was observed in three patients. Total urinary excretion of radioactivity prior to surgery averaged 7% of the administered radioactivity while at surgery the mean organ accumulation was 8% of the administered radioactivity in serum, 10% in liver, 7% in bone marrow, and 19% in bone with large patient to patient variation. The mean tumor/normal tissue radioactivity ratio varied between 3 and 25. On the assumption that the above radioactivity levels were achieved immediately following administration, that the radioactivity remained in situ until decayed and that the dimensions of tumor were sufficient to completely attenuate the emissions of 90Y, the dose to tumor for a 1-mCi administration would be approximately 50 rad with normal tissues receiving approximately 8 rad. PMID:3404257

  1. 40 CFR 282.102 - Puerto Rico State-Administered Program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Puerto Rico State-Administered Program... Rico State-Administered Program. (a) The Commonwealth of Puerto Rico is approved to administer and...'s program, as administered by the Commonwealth of Puerto Rico Environmental Quality Board,...

  2. Self-Administered Behavioral Family Intervention for Parents of Toddlers: Part 1. Efficacy

    ERIC Educational Resources Information Center

    Morawska, Alina; Sanders, Matthew R.

    2006-01-01

    This study examined the efficacy of a self-administered behavioral family intervention for 126 parents of toddlers. The effects of 2 different levels of intensity of the self-administered intervention were contrasted (self-administered alone or self-administered plus brief therapist telephone assistance). The results provide support for the…

  3. 40 CFR 282.91 - South Dakota State-Administered Program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 27 2011-07-01 2011-07-01 false South Dakota State-Administered... Dakota State-Administered Program. (a) The State of South Dakota is approved to administer and enforce an... administered by the South Dakota Department of Environment and Natural Resources, was approved by EPA...

  4. 40 CFR 282.91 - South Dakota State-Administered Program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 27 2014-07-01 2014-07-01 false South Dakota State-Administered... Dakota State-Administered Program. (a) The State of South Dakota is approved to administer and enforce an... administered by the South Dakota Department of Environment and Natural Resources, was approved by EPA...

  5. 40 CFR 282.91 - South Dakota State-Administered Program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 28 2013-07-01 2013-07-01 false South Dakota State-Administered... Dakota State-Administered Program. (a) The State of South Dakota is approved to administer and enforce an... administered by the South Dakota Department of Environment and Natural Resources, was approved by EPA...

  6. 40 CFR 282.91 - South Dakota State-Administered Program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 28 2012-07-01 2012-07-01 false South Dakota State-Administered... Dakota State-Administered Program. (a) The State of South Dakota is approved to administer and enforce an... administered by the South Dakota Department of Environment and Natural Resources, was approved by EPA...

  7. 34 CFR 461.1 - What is the Adult Education State-administered Basic Grant Program?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false What is the Adult Education State-administered Basic...-ADMINISTERED BASIC GRANT PROGRAM General § 461.1 What is the Adult Education State-administered Basic Grant Program? The Adult Education State-administered basic Grant Program (the program) is a cooperative...

  8. Administering an epoch initiated for remote memory access

    SciTech Connect

    Blocksome, Michael A; Miller, Douglas R

    2014-03-18

    Methods, systems, and products are disclosed for administering an epoch initiated for remote memory access that include: initiating, by an origin application messaging module on an origin compute node, one or more data transfers to a target compute node for the epoch; initiating, by the origin application messaging module after initiating the data transfers, a closing stage for the epoch, including rejecting any new data transfers after initiating the closing stage for the epoch; determining, by the origin application messaging module, whether the data transfers have completed; and closing, by the origin application messaging module, the epoch if the data transfers have completed.

  9. Disposition of disodium cromoglycate administered in three particle sizes.

    PubMed Central

    Curry, S H; Taylor, A J; Evans, S; Godfrey, S; Zeidifard, E

    1975-01-01

    1 Disodium cromoglycate (DSCG) was administered in three particle sizes to five human subjects. 2 Urinary excretion of DSCG, as a proportion of the dose, was highest following small particles; the lower values recorded following intermediate-sized and large particles were similar. 3 DSCG deposited in the mouth was highest following large particles; the lower values recorded following intermediate-sized and small particles were similar. 4 The data were examined in relation to the recent observation that the protective effect of small particles of DSCG is dramatically superior to that of large particles. PMID:825134

  10. Self-administered treatments for depression: a review.

    PubMed

    McKendree-Smith, Nancy L; Floyd, Mark; Scogin, Forrest R

    2003-03-01

    Although there are numerous self-help books for depression, relatively few have been empirically tested. However, those that have been used in clinical trials have fared well, with an average effect size roughly equivalent to the average effect size obtained in psychotherapy studies. Computer-based treatments are being developed and appear promising as an alternative to bibliotherapy for those interested in self-administered treatments. This article provides a summary of the depression bibliotherapy literature and discusses several remaining questions such as effectiveness versus efficacy, practice applications, ethics, and future research. PMID:12579545

  11. Key safety considerations when administering epidural steroid injections.

    PubMed

    Manchikanti, Laxmaiah; Benyamin, Ramsin M

    2015-01-01

    Neurological and other complications of epidural steroid injections have been widely discussed in recent years. Consequently, the US FDA issued a warning about serious neurological events, some resulting in death, and consequently is requiring label changes. Neurological adverse events numbering 131, including 41 cases of arachnoiditis, have been identified by the FDA, and 700 cases of fungal meningitis following injection of contaminated steroids. A review of the literature reveals an overwhelming proportion of the complications are related to transforaminal epidural injections, with the majority of them to cervical transforaminal epidural injections. This perspective describes the prevalence of administering epidural injections, complications, pathoanatomy, mechanism of injury and various preventive strategies. PMID:26059467

  12. Administering an epoch initiated for remote memory access

    DOEpatents

    Blocksome, Michael A; Miller, Douglas R

    2012-10-23

    Methods, systems, and products are disclosed for administering an epoch initiated for remote memory access that include: initiating, by an origin application messaging module on an origin compute node, one or more data transfers to a target compute node for the epoch; initiating, by the origin application messaging module after initiating the data transfers, a closing stage for the epoch, including rejecting any new data transfers after initiating the closing stage for the epoch; determining, by the origin application messaging module, whether the data transfers have completed; and closing, by the origin application messaging module, the epoch if the data transfers have completed.

  13. Administering an epoch initiated for remote memory access

    DOEpatents

    Blocksome, Michael A.; Miller, Douglas R.

    2013-01-01

    Methods, systems, and products are disclosed for administering an epoch initiated for remote memory access that include: initiating, by an origin application messaging module on an origin compute node, one or more data transfers to a target compute node for the epoch; initiating, by the origin application messaging module after initiating the data transfers, a closing stage for the epoch, including rejecting any new data transfers after initiating the closing stage for the epoch; determining, by the origin application messaging module, whether the data transfers have completed; and closing, by the origin application messaging module, the epoch if the data transfers have completed.

  14. Characterisation of a Babesia orientalis apical membrane antigen, and comparison of its orthologues among selected apicomplexans.

    PubMed

    He, Lan; Fan, Lizhe; Hu, Jinfang; Miao, Xiaoyan; Huang, Yuan; Zhou, Yanqin; Hu, Min; Zhao, Junlong

    2015-04-01

    In the present study, we identified and characterised the complete coding sequence of Babesia orientalis apical membrane antigen 1 (designated Bo-ama1); it is 1803bp in length and encodes a polypeptide of 601 amino acids (aa). The Bo-ama-1 gene product (Bo-AMA1) is predicted to be 67kDa in size and contains a signal peptide. Mature Bo-AMA1 is predicted to have one transmembrane region and a short cytoplasmic tail (C-terminal domain). The extracellular part of Bo-AMA1 has three functional domains (DI, DII and DIII) with 14 conserved cysteine residues. A Bo-AMA1 fragment containing all three of these domains (designated Bo-AMA1-DI/II/III) was cloned into the plasmid vector pET-28a and expressed as a recombinant (His-fusion) protein of 53kDa. Antibodies in the serum from a B. orientalis-infected water buffalo specifically recognised this protein in immunoblotting analysis. Rabbit antibodies raised against the recombinant protein were able to detect native Bo-AMA1 (67kDa) from erythrocytes of B. orientalis-infected water buffalo. Bo-AMA1 is a new member of the AMA1 family and might be a good antigen for the specific detection of antibodies produced in B. orientalis infected cattle. This protein is likely to play critical roles during host cell adherence and invasion by B. orientalis, as the AMA1s reported in other organisms such as Plasmodium falciparum and Toxoplasma gondii. Further research is required to explore the biological functions of this protein and to determine whether its immunisation can induce protective effects in water buffalo against B. orientalis infection. PMID:25732411

  15. Functional dissection of latency-associated nuclear antigen 1 of Kaposi's sarcoma-associated herpesvirus involved in latent DNA replication and transcription of terminal repeats of the viral genome.

    PubMed

    Lim, Chunghun; Sohn, Hekwang; Lee, Daeyoup; Gwack, Yousang; Choe, Joonho

    2002-10-01

    Latency-associated nuclear antigen 1 (LANA1) of Kaposi's sarcoma-associated herpesvirus (KSHV) is implicated in the maintenance of the viral genome during latent infection. LANA1 colocalizes with KSHV episomes on the host chromosome and mediates their maintenance by attaching these viral structures to host chromosomes. Data from long-term selection of drug resistance in cells conferred by plasmids containing the terminal repeat (TR) sequence of KSHV revealed that KSHV TRs and LANA1 act as cis and trans elements of viral latent replication, respectively. In this study, we further characterized the cis- and trans-acting elements of KSHV latent replication by using a transient replication assay with a methylation-sensitive restriction enzyme, DpnI. Transient reporter and replication assays disclosed that the orientation and basal transcriptional activity of TR constructs did not significantly affect the efficiency of replication. However, at least two TR units were necessary for efficient replication. The N-terminal 90 amino acids comprising the chromosome-binding domain of LANA1 were required for the mediation of LANA1 C-terminal DNA-binding and dimerization domains to support the transient replication of KSHV TRs. LANA1 interacted with components of the origin recognition complexes (ORCs), similar to Epstein-Barr virus nuclear antigen 1. Our data suggest that LANA1 recruits ORCs to KSHV TRs for latent replication of the viral genome. PMID:12239308

  16. Comparison of Interviewer-Administered and Automated Self-Administered 24-Hour Dietary Recalls in 3 Diverse Integrated Health Systems.

    PubMed

    Thompson, Frances E; Dixit-Joshi, Sujata; Potischman, Nancy; Dodd, Kevin W; Kirkpatrick, Sharon I; Kushi, Lawrence H; Alexander, Gwen L; Coleman, Laura A; Zimmerman, Thea P; Sundaram, Maria E; Clancy, Heather A; Groesbeck, Michelle; Douglass, Deirdre; George, Stephanie M; Schap, TusaRebecca E; Subar, Amy F

    2015-06-15

    Twenty-four-hour dietary recalls provide high-quality intake data but have been prohibitively expensive for large epidemiologic studies. This study's goal was to assess whether the web-based Automated Self-Administered 24-Hour Recall (ASA24) performs similarly enough to the standard interviewer-administered, Automated Multiple-Pass Method (AMPM) 24-hour dietary recall to be considered a viable alternative. In 2010-2011, 1,081 adults from 3 integrated health systems in Detroit, Michigan; Marshfield, Wisconsin; and Kaiser-Permanente Northern California participated in a field trial. A quota design ensured a diverse sample by sex, age, and race/ethnicity. Each participant was asked to complete 2 recalls and was randomly assigned to 1 of 4 protocols differing by type of recall and administration order. For energy, the mean intakes were 2,425 versus 2,374 kcal for men and 1,876 versus 1,906 kcal for women by AMPM and ASA24, respectively. Of 20 nutrients/food groups analyzed and controlling for false discovery rate, 87% were judged equivalent at the 20% bound. ASA24 was preferred over AMPM by 70% of the respondents. Attrition was lower in the ASA24/AMPM study group than in the AMPM/ASA24 group, and it was lower in the ASA24/ASA24 group than in the AMPM/AMPM group. ASA24 offers the potential to collect high-quality dietary intake information at low cost with less attrition. PMID:25964261

  17. [Spontaneous reporting system data analysis of parenterally administered Shenmai].

    PubMed

    Wang, Lian-Xin; Xiang, Yong-Yang; Xie, Yan-Ming; Shen, Hao; Ai, Qing-Hua

    2013-09-01

    Spontaneous reporting system (SRS) datais currently an important source of monitoring and finding ADRs signals throughout the world. This method can promptly and effectively discover ADR signals, thus preventing and avoiding ADRs effectively. Parenterally administered Shenmai has the functions of benefiting vital energy, nourishing Yin and generating body fluids, and activating the pulse. Clinically it is used in various diseases including shock, coronary heart disease, viral myocarditis, chronic pulmonary heart disease, and granulocytopenia. The large, national SRS database of ADRs needs effective evaluation methods. We report on the use of Bayesian confidence propagation neural network method (BCPNN) and proportional reporting ration (PRR) with propensity score to control for confounding variables. Early warning signs of an ADR are, a feeling of suffocation (difficulty exhaling), anaphylactoid reactions and flushing. Furthermore, relevant relationships between the different factors is analysed by association rules (AR). It is found that there is a close relationship between past history of ADRs, a family history of ADRs and itching. PMID:24471317

  18. Web administered pre/post assessment: reliability, compliance and security

    NASA Astrophysics Data System (ADS)

    Bonham, Scott W.

    2006-12-01

    Pre/post assessment measures learning by comparing assessment performance before and after instruction. Usually it is administered on paper during class, needing to be distributed, collected, graded and analyzed. Administration on the web outside class frees up class time and automates many steps. However, this switch to unproctored web administration raises questions. Will the results be as reliable? Will students take it? Will test questions leak to fraternity files? An experiment using two different assessments pre/post test was carried out in introductory astronomy classes. Each section took one assessment on line and one in class. Comparing performance on paper vs. web provides information on reliability. Numbers of students completing in each mode give information on compliance and factors influencing it. Browser events that could indicate copying, saving or printing of questions were recorded to identify possible loss of security.

  19. Administering truncated receive functions in a parallel messaging interface

    SciTech Connect

    Archer, Charles J; Blocksome, Michael A; Ratterman, Joseph D; Smith, Brian E

    2014-12-09

    Administering truncated receive functions in a parallel messaging interface (`PMI`) of a parallel computer comprising a plurality of compute nodes coupled for data communications through the PMI and through a data communications network, including: sending, through the PMI on a source compute node, a quantity of data from the source compute node to a destination compute node; specifying, by an application on the destination compute node, a portion of the quantity of data to be received by the application on the destination compute node and a portion of the quantity of data to be discarded; receiving, by the PMI on the destination compute node, all of the quantity of data; providing, by the PMI on the destination compute node to the application on the destination compute node, only the portion of the quantity of data to be received by the application; and discarding, by the PMI on the destination compute node, the portion of the quantity of data to be discarded.

  20. Interactions of conjugate vaccines and co-administered vaccines.

    PubMed

    Findlow, H; Borrow, R

    2016-01-01

    Conjugate vaccines play an important role in the prevention of infectious diseases such as those caused by the bacteria Haemophilus influenzae (Hi) type b (Hib), Neisseria meningitidis, and Streptococcus pneumoniae. Vaccines developed against these 3 pathogens utilize 3 main carrier proteins, non-toxic mutant of diphtheria toxin (CRM197), diphtheria toxoid (DT) and tetanus toxoid (TT). Current pediatric immunisation schedules include the administration of several vaccines simultaneously, therefore increasing the potential for immune interference (both positively and negatively) to the antigens administered. Knowledge of vaccine interactions is principally derived from clinical trials, these are reviewed here to explore immune interference which may result of from carrier-specific T-cell helper interactions, bystander interference and carrier induced epitopic suppression. PMID:26619353

  1. An Overview of Self-Administered Health Literacy Instruments

    PubMed Central

    O′Neill, Braden; Gonçalves, Daniela; Ricci-Cabello, Ignacio; Ziebland, Sue; Valderas, Jose

    2014-01-01

    With the increasing recognition of health literacy as a worldwide research priority, the development and refinement of indices to measure the construct is an important area of inquiry. Furthermore, the proliferation of online resources and research means that there is a growing need for self-administered instruments. We undertook a systematic overview to identify all published self-administered health literacy assessment indices to report their content and considerations associated with their administration. A primary aim of this study was to assist those seeking to employ a self-reported health literacy index to select one that has been developed and validated for an appropriate context, as well as with desired administration characteristics. Systematic searches were carried out in four electronic databases, and studies were included if they reported the development and/or validation of a novel health literacy assessment measure. Data were systematically extracted on key characteristics of the instruments: breadth of construct (“generic” vs. “content- or context- specific” health literacy), whether it was an original instrument or a derivative, country of origin, administration characteristics, age of target population (adult vs. pediatric), and evidence for validity. 35 articles met the inclusion criteria. There were 27 original instruments (27/35; 77.1%) and 8 derivative instruments (8/35; 22.9%). 22 indices measured “general” health literacy (22/35; 62.9%) while the remainder measured condition- or context- specific health literacy (13/35; 37.1%). Most health literacy measures were developed in the United States (22/35; 62.9%), and about half had adequate face, content, and construct validity (16/35; 45.7%). Given the number of measures available for many specific conditions and contexts, and that several have acceptable validity, our findings suggest that the research agenda should shift towards the investigation and elaboration of health literacy

  2. Safety of florfenicol administered in feed to tilapia (Oreochromis sp.)

    USGS Publications Warehouse

    Gaikowski, Mark P.; Wolf, Jeffrey C.; Schleis, Susan M.; Tuomari, Darrell; Endris, Richard G.

    2013-01-01

    The safety of Aquaflor® (50% w/w florfenicol [FFC]) incorporated in feed then administered to tilapia for 20 days (2x the recommended duration) at 0, 15, 45, or 75 mg/kg body weight/day (0, 1, 3, or 5x the recommended dose of 15 mg FFC/kg BW/d) was investigated. Mortality, behavioral change, feed consumption, body size, and gross and microscopic lesions were determined. Estimated delivered doses were >96.9% of target. Three unscheduled mortalities occurred but were considered incidental since FFC-related findings were not identified. Feed consumption was only affected during the last 10 dosing days when the 45 and 75 mg/kg groups consumed only 62.5% and 55.3% of the feed offered, respectively. There were significant, dose-dependent reductions in body size in the FFC-dose groups relative to the controls. Treatment-related histopathological findings included increased severity of lamellar epithelial hyperplasia, increased incidence of lamellar adhesions, decreased incidence of lamellar telangiectasis in the gills, increased glycogen-type and lipid-type hepatocellular vacuolation in the liver, decreased lymphocytes, increased blast cells, and increased individual cell necrosis in the anterior kidney, and tubular epithelial degeneration and mineralization in the posterior kidney. These changes are likely to be of minimal clinical relevance, given the lack of mortality or morbidity observed. This study has shown that FFC, when administered in feed to tilapia at the recommended dose (15 mg FFC/kg BW/day) for 10 days would be well tolerated.

  3. The FlyBar: Administering Alcohol to Flies

    PubMed Central

    van der Linde, Kim; Fumagalli, Emiliano; Roman, Gregg; Lyons, Lisa C.

    2014-01-01

    Fruit flies (Drosophila melanogaster) are an established model for both alcohol research and circadian biology. Recently, we showed that the circadian clock modulates alcohol sensitivity, but not the formation of tolerance. Here, we describe our protocol in detail. Alcohol is administered to the flies using the FlyBar. In this setup, saturated alcohol vapor is mixed with humidified air in set proportions, and administered to the flies in four tubes simultaneously. Flies are reared under standardized conditions in order to minimize variation between the replicates. Three-day old flies of different genotypes or treatments are used for the experiments, preferably by matching flies of two different time points (e.g., CT 5 and CT 17) making direct comparisons possible. During the experiment, flies are exposed for 1 hr to the pre-determined percentage of alcohol vapor and the number of flies that exhibit the Loss of Righting reflex (LoRR) or sedation are counted every 5 min. The data can be analyzed using three different statistical approaches. The first is to determine the time at which 50% of the flies have lost their righting reflex and use an Analysis of the Variance (ANOVA) to determine whether significant differences exist between time points. The second is to determine the percentage flies that show LoRR after a specified number of minutes, followed by an ANOVA analysis. The last method is to analyze the whole times series using multivariate statistics. The protocol can also be used for non-circadian experiments or comparisons between genotypes. PMID:24895004

  4. Acute Lymphoid Leukemia Cells with Greater Stem Cell Antigen-1 (Ly6a/Sca-1) Expression Exhibit Higher Levels of Metalloproteinase Activity and Are More Aggressive In Vivo

    PubMed Central

    Hsu, Yu-Chiao; Mildenstein, Kurt; Hunter, Kordell; Tkachenko, Olena; Mullen, Craig A.

    2014-01-01

    Stem cell antigen-1 (Ly6a/Sca-1) is a gene that is expressed in activated lymphocytes, hematopoietic stem cells and stem cells of a variety of tissues in mice. Despite decades of study its functions remain poorly defined. These studies explored the impact of expression of this stem cell associated gene in acute lymphoid leukemia. Higher levels of Ly6a/Sca-1 expression led to more aggressive leukemia growth in vivo and earlier death of hosts. Leukemias expressing higher levels of Ly6a/Sca-1 exhibited higher levels of matrix metalloproteinases. The results suggest the hypothesis that the more aggressive behavior of Ly6a/Sca-1 expressing leukemias is due at least in part to greater capacity to degrade microenvironmental stroma and invade tissues. PMID:24586463

  5. 40 CFR 147.1852 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Oklahoma... lands in Oklahoma, except Class II wells on the lands of the Five Civilized Tribes, is administered...

  6. 40 CFR 147.1852 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Oklahoma... lands in Oklahoma, except Class II wells on the lands of the Five Civilized Tribes, is administered...

  7. 40 CFR 147.1852 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Oklahoma... lands in Oklahoma, except Class II wells on the lands of the Five Civilized Tribes, is administered...

  8. Effects of Systemically Administered Hydrocortisone on the Human Immunome.

    PubMed

    Olnes, Matthew J; Kotliarov, Yuri; Biancotto, Angélique; Cheung, Foo; Chen, Jinguo; Shi, Rongye; Zhou, Huizhi; Wang, Ena; Tsang, John S; Nussenblatt, Robert

    2016-01-01

    Corticosteroids have been used for decades to modulate inflammation therapeutically, yet there is a paucity of data on their effects in humans. We examined the changes in cellular and molecular immune system parameters, or "immunome", in healthy humans after systemic corticosteroid administration. We used multiplexed techniques to query the immunome in 20 volunteers at baseline, and after intravenous hydrocortisone (HC) administered at moderate (250 mg) and low (50 mg) doses, to provide insight into how corticosteroids exert their effects. We performed comprehensive phenotyping of 120 lymphocyte subsets by high dimensional flow cytometry, and observed a decline in circulating specific B and T cell subsets, which reached their nadir 4-8 hours after administration of HC. However, B and T cells rebounded above baseline 24 hours after HC infusion, while NK cell numbers remained stable. Whole transcriptome profiling revealed down regulation of NF-κB signaling, apoptosis, and cell death signaling transcripts that preceded lymphocyte population changes, with activation of NK cell and glucocorticoid receptor signaling transcripts. Our study is the first to systematically characterize the effects of corticosteroids on the human immunome, and we demonstrate that HC exerts differential effects on B and T lymphocytes and natural killer cells in humans. PMID:26972611

  9. Pharmacokinetics of Paradol Analogues Orally Administered to Rats.

    PubMed

    Setoguchi, Shuichi; Watase, Daisuke; Nagata-Akaho, Nami; Haratake, Akinori; Matsunaga, Kazuhisa; Takata, Jiro

    2016-03-01

    The kinetics parameters of paradols with different acyl chain lengths have been evaluated to determine their antiobesity site of action. Rats were orally administered olive oil containing 0-, 6-, 8-, or 12-paradol, and blood samples were collected at different time points. The concentrations of the paradols in the plasma were analyzed both with and without β-glucuronidase treatment. The area under the plasma concentration-time curve from 0 to 24 h (AUC0-24h) of the parent compounds decreased with increasing acyl chain length. Whereas 12-paradol showed the largest AUC0-24h with the longest time to reach its maximum plasma concentration of all of the compounds tested, the AUC0-24h values of the metabolites decreased with increasing acyl chain length. These results indicate that increasing acyl chain length leads to a decrease in the absorption of paradols via the intestinal tract, the wall of which was estimated to be their antiobesity site of action. PMID:26868188

  10. Inducing and Administering Tregs to Treat Human Disease

    PubMed Central

    Perdigoto, Ana Luisa; Chatenoud, Lucienne; Bluestone, Jeffrey A.; Herold, Kevan C.

    2016-01-01

    Regulatory T cells (Tregs) control unwanted immune responses, including those that mediate tolerance to self as well as to foreign antigens. Their mechanisms of action include direct and indirect effects on effector T cells and important functions in tissue repair and homeostasis. Tregs express a number of cell surface markers and transcriptional factors that have been instrumental in defining their origins and potentially their function. A number of immune therapies, such as rapamycin, IL-2, and anti-T cell antibodies, are able to induce Tregs and are being tested for their efficacy in diverse clinical settings with exciting preliminary results. However, a balance exists with the use of some, such as IL-2, that may have effects on unwanted populations as well as promoting expansion and survival of Tregs requiring careful selection of dose for clinical use. The use of cell surface markers has enabled investigators to isolate and expand ex vivo Tregs more than 500-fold routinely. Clinical trials have begun, administering these expanded Tregs to patients as a means of suppressing autoimmune and alloimmune responses and potentially inducing immune tolerance. Studies in the future are likely to build on these initial technical achievements and use combinations of agents to improve the survival and functional capacity of Tregs. PMID:26834735

  11. Recovery of cholinesterase activity in mallard ducklings administered organophosphorus pesticides

    USGS Publications Warehouse

    Fleming, W.J.; Bradbury, S.P.

    1981-01-01

    Oral doses of the organophosphorus pesticides acephate, dicrotophos, fensulfothion, fonofos, malathion, and parathion were administered to mallard ducklings (Anas platyrhynchos), and brain and plasma cholinesterase (ChE) activities were determined for up to 77 d after dosing. In vivo recovery of brain ChE activity to within 2 standard deviations of the mean activity of undosed birds occurred within 8 d, after being depressed an average of 25-58% at 24 h after dosing. In vivo recovery of plasma ChE appeared as fast as or faster than that of brain, but the pattern of recovery was more erratic and therefore statistical comparison with brain ChE recovery was not attempted. In vitro tests indicated that the potential for dephosphorylation to contribute to in vivo recovery of inhibited brain ChE differed among chemical treatments. Some ducklings died as a result of organophosphate dosing. In an experiment in which ducklings within each treatment group received the same dose (mg/kg), the brain ChE activity in birds that died was less than that in birds that survived. Brain ChE activities in ducklings that died were significantly different among pesticide treatments: fensulfothion > parathion> acephate > malathion (p < 0.05).

  12. Administering and Detecting Protein Marks on Arthropods for Dispersal Research.

    PubMed

    Hagler, James R; Machtley, Scott A

    2016-01-01

    Monitoring arthropod movement is often required to better understand associated population dynamics, dispersal patterns, host plant preferences, and other ecological interactions. Arthropods are usually tracked in nature by tagging them with a unique mark and then re-collecting them over time and space to determine their dispersal capabilities. In addition to actual physical tags, such as colored dust or paint, various types of proteins have proven very effective for marking arthropods for ecological research. Proteins can be administered internally and/or externally. The proteins can then be detected on recaptured arthropods with a protein-specific enzyme-linked immunosorbent assay (ELISA). Here we describe protocols for externally and internally tagging arthropods with protein. Two simple experimental examples are demonstrated: (1) an internal protein mark introduced to an insect by providing a protein-enriched diet and (2) an external protein mark topically applied to an insect using a medical nebulizer. We then relate a step-by-step guide of the sandwich and indirect ELISA methods used to detect protein marks on the insects. In this demonstration, various aspects of the acquisition and detection of protein markers on arthropods for mark-release-recapture, mark-capture, and self-mark-capture types of research are discussed, along with the various ways that the immunomarking procedure has been adapted to suit a wide variety of research objectives. PMID:26863574

  13. Macroscopic and microscopic biodistribution of intravenously administered iron oxide nanoparticles

    NASA Astrophysics Data System (ADS)

    Misra, Adwiteeya; Petryk, Alicia A.; Strawbridge, Rendall R.; Hoopes, P. Jack

    2015-03-01

    Iron oxide nanoparticles (IONP) are being developed for use as a cancer treatment. They have demonstrated efficacy when used either as a monotherapy or in conjunction with conventional chemotherapy and radiation. The success of IONP as a therapeutic tool depends on the delivery of a safe and controlled cytotoxic thermal dose to tumor tissue following activation with an alternating magnetic field (AMF). Prior to clinical approval, knowledge of IONP toxicity, biodistribution and physiological clearance is essential. This preliminary time-course study determines the acute toxicity and biodistribution of 110 nm dextran-coated IONP (iron) in mice, 7 days post systemic, at doses of 0.4, 0.6, and 1.0 mg Fe/ g mouse bodyweight. Acute toxicity, manifested as changes in the behavior of mice, was only observed temporarily at 1.0 mg Fe/ g mouse bodyweight, the highest dose administered. Regardless of dose, mass spectrometry and histological analysis demonstrated over 3 mg Fe/g tissue in organs within the reticuloendotheilial system (i.e. liver, spleen, and lymph nodes). Other organs (brain, heart, lungs, and kidney) had less than 0.5 mg Fe/g tissue with iron predominantly confined to the organ vasculature.

  14. Effects of Systemically Administered Hydrocortisone on the Human Immunome

    PubMed Central

    Olnes, Matthew J.; Kotliarov, Yuri; Biancotto, Angélique; Cheung, Foo; Chen, Jinguo; Shi, Rongye; Zhou, Huizhi; Wang, Ena; Tsang, John S.; Nussenblatt, Robert; Dickler, Howard B.; Hourigan, Christopher S.; Marincola, Francesco M.; McCoy, J. Phillip; Perl, Shira; Schum, Paula; Schwartzberg, Pamela L.; Trinchieri, Giorgio; Valdez, Janet; Young, Neal S.

    2016-01-01

    Corticosteroids have been used for decades to modulate inflammation therapeutically, yet there is a paucity of data on their effects in humans. We examined the changes in cellular and molecular immune system parameters, or “immunome”, in healthy humans after systemic corticosteroid administration. We used multiplexed techniques to query the immunome in 20 volunteers at baseline, and after intravenous hydrocortisone (HC) administered at moderate (250 mg) and low (50 mg) doses, to provide insight into how corticosteroids exert their effects. We performed comprehensive phenotyping of 120 lymphocyte subsets by high dimensional flow cytometry, and observed a decline in circulating specific B and T cell subsets, which reached their nadir 4–8 hours after administration of HC. However, B and T cells rebounded above baseline 24 hours after HC infusion, while NK cell numbers remained stable. Whole transcriptome profiling revealed down regulation of NF-κB signaling, apoptosis, and cell death signaling transcripts that preceded lymphocyte population changes, with activation of NK cell and glucocorticoid receptor signaling transcripts. Our study is the first to systematically characterize the effects of corticosteroids on the human immunome, and we demonstrate that HC exerts differential effects on B and T lymphocytes and natural killer cells in humans. PMID:26972611

  15. Correlation between administered treatment and patient’s living will

    PubMed Central

    Andreoni, B; Goldhirsch, A; Orecchia, R; Venturino, M; Spirito, R; Tadini, L; Corbellini, C; Bertani, E; Veronesi, U

    2009-01-01

    Respecting the wishes of an adequately informed patient should be a priority in any health structure. A patient with advanced or terminal cancer should be allowed to express their will during the most important phases of their illness. Unfortunately, this is seldom the case, and in general instructions regarding an individual’s medical care preferences, i.e., their ‘living will’, expressed when healthy, often change with the onset of a serious illness. At the European Institute of Oncology (IEO), a clinical study is ongoing to verify whether, during clinical practice, the patient is adequately informed to sign an ‘informed consent’, in a fully aware manner, that will allow the patient and doctor to share in the decisions regarding complex treatment strategies (living will). A further aim of the study is to verify if health workers, both in hospital and at home, respect the patient’s will. The observational study ‘Respecting the patient’s wishes: Correlation between administered treatment and that accepted by the patient in their Living Will’ was approved by the IEO Ethical Committee in April 2008. PMID:22276019

  16. [What lipid emulsion should be administered to ICU patients?].

    PubMed

    Kreymann, G

    2014-01-01

    The review deals with a question what lipid emulsion should be administered to ICU patients according to recently published official parenteral and enteral nutrition guidelines. Classic lipid emulsions based on omega-6 fatty acids are immunosuppressive and should not be used with ICU patients. The olive/soy emulsion is immunoneutral and can be used for most patients. Many ICU patients are in an inflammatory state (e.g. sepsis, ARDS, pancreatitis). A common belief is that this "hyperinflammed patient population" would profit from an anti-inflammatory lipid component of their parenteral nutrition solution, such as fish oil. On the other hand, every anti-inflammatory therapy has the disadvantage of also being immunosuppressive. Inflammation is a necessary part of the host defense against infection and any correct anti-inflammatory medication presupposes the exact immunologic knowledge that there is too much inflammation for a given situation. This "too much" is certainly not fulfilled in every patient with sepsis, ARDS or pancreatitis. At the bedside it is nearly impossible to determine the degree of "hyper" inflammation. In reality, a number of these patients may be adequately inflamed or, in fact, even hypoinflammed. Specific emulsions which can be used in hyper- or hypoinflammation should be developed in the future. As long as these difficulties in the immunologic diagnosis prevail, the clinician might be best advised to use an immunoneutral lipid emulsion when choosing a lipid preparation for the ICU patients. PMID:25306684

  17. Improving child compliance on a computer administered nonword repetition task.

    PubMed

    Polišenská, Kamila; Kapalková, Svetlana

    2014-06-01

    Purpose: A range of nonword repetition (NWR) tasks are used in research and clinical applications, but compliance rates among young children remain low. Live presentation is usually used to improve compliance rates, but this lacks the consistency of recorded stimuli. In this study, the authors examined whether a novel delivery of NWR stimuli based on recorded material could provide improved compliance rates in young children, thereby reducing research bias.Method: The novel NWR task with 26 recorded items was administered to 391 typically developing children ages 2–6 years. The children were presented with a story that they could influence by repeating “magic” words. Results: From the 384 children who completed the task, the authors found a noncompliance rate related to age. In line with previous research, no effect of demographic factors was found,but there was a significant main effect of age, syllable length,and phonological complexity on repetition accuracy. Test–retest and interrater scoring showed high levels of reliability.Conclusion: The task described in this study offers an objective delivery of recorded stimuli that engages young children and provides high compliance rates. The task is inexpensive, requires minimal training, and can be adapted to other languages. PMID:25667943

  18. Absorption Kinetics of Subcutaneously Administered Ceftazidime in Hypoperfused Guinea Pigs

    PubMed Central

    Ebihara, Tsuyoshi; Oshima, Shinji; Okita, Mitsuyoshi; Shiina, Sayumi; Negishi, Akio; Ohara, Kousuke; Ohshima, Shigeru; Iwasaki, Hiroyuki; Yoneyama, Akira; Kitazumi, Eiji; Kobayashi, Daisuke

    2014-01-01

    Background Pneumonia is the most common cause of death in patients with severe motor and intellectual disabilities (SMID), and intravenous ceftazidime (CAZ) is a widely used treatment for such infections. However, intravenous administration in patients with SMID may be difficult because of insufficient vascular development. Objectives The aim of our study was to determine the feasibility of subcutaneous drug administration by mentholated warm compresses (WMCs) as an alternative delivery method for ceftazidime in patients with SMID. Methods CAZ was subcutaneously administered to the abdominal region of naphazoline-treated hypoperfused guinea pigs, which were used as a hemodynamic model of patients with SMID. MWCs or warm compresses (WCs) were applied to the injection site to increase blood flow. We calculated the cumulative CAZ absorption over time by using the deconvolution method. Results Application of MWCs or WCs increased blood flow at the administration site and increased CAZ plasma levels. Application of MWCs or WCs after subcutaneous CAZ injection led to higher CAZ plasma levels than the mutant prevention concentration for a longer period than was observed for CAZ administration without the application of MWCs or WCs. Conclusions The application of MWCs or WCs enhanced subcutaneous CAZ absorption by increasing blood flow. MWCs and WCs are considered to be safe and routine methods to induce defecation after surgery on the digestive system; thus, the combination of these methods and subcutaneous CAZ administration is a potential method for treating pneumonia in patients with SMID. PMID:26649076

  19. 34 CFR 461.1 - What is the Adult Education State-administered Basic Grant Program?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 3 2011-07-01 2011-07-01 false What is the Adult Education State-administered Basic... (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION ADULT EDUCATION STATE-ADMINISTERED BASIC GRANT PROGRAM General § 461.1 What is the Adult Education State-administered Basic...

  20. 34 CFR 461.1 - What is the Adult Education State-administered Basic Grant Program?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 34 Education 3 2013-07-01 2013-07-01 false What is the Adult Education State-administered Basic... (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION ADULT EDUCATION STATE-ADMINISTERED BASIC GRANT PROGRAM General § 461.1 What is the Adult Education State-administered Basic...

  1. 34 CFR 461.1 - What is the Adult Education State-administered Basic Grant Program?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 34 Education 3 2012-07-01 2012-07-01 false What is the Adult Education State-administered Basic... (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION ADULT EDUCATION STATE-ADMINISTERED BASIC GRANT PROGRAM General § 461.1 What is the Adult Education State-administered Basic...

  2. 34 CFR 461.1 - What is the Adult Education State-administered Basic Grant Program?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 34 Education 3 2014-07-01 2014-07-01 false What is the Adult Education State-administered Basic... (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION ADULT EDUCATION STATE-ADMINISTERED BASIC GRANT PROGRAM General § 461.1 What is the Adult Education State-administered Basic...

  3. 25 CFR 26.4 - Who administers the Job Placement and Training Program?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Who administers the Job Placement and Training Program... PLACEMENT AND TRAINING PROGRAM General Applicability § 26.4 Who administers the Job Placement and Training Program? The Job Placement and Training Program is administered by the Bureau of Indian Affairs or...

  4. 45 CFR 400.66 - Eligibility and payment levels in a publicly-administered RCA program.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... REFUGEE RESETTLEMENT, ADMINISTRATION FOR CHILDREN AND FAMILIES, DEPARTMENT OF HEALTH AND HUMAN SERVICES REFUGEE RESETTLEMENT PROGRAM Refugee Cash Assistance § 400.66 Eligibility and payment levels in a publicly-administered RCA program. (a) In administering a publicly-administered refugee cash assistance program,...

  5. 34 CFR 406.1 - What is the State-Administered Tech-Prep Education Program?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 3 2011-07-01 2011-07-01 false What is the State-Administered Tech-Prep Education... (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION STATE-ADMINISTERED TECH-PREP EDUCATION PROGRAM General § 406.1 What is the State-Administered Tech-Prep Education Program? If the...

  6. 25 CFR 171.110 - How does BIA administer its irrigation facilities?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 1 2014-04-01 2014-04-01 false How does BIA administer its irrigation facilities? 171... IRRIGATION OPERATION AND MAINTENANCE General Provisions § 171.110 How does BIA administer its irrigation facilities? (a) We administer our irrigation facilities by enforcing the applicable statutes,...

  7. 25 CFR 171.110 - How does BIA administer its irrigation facilities?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 1 2011-04-01 2011-04-01 false How does BIA administer its irrigation facilities? 171... IRRIGATION OPERATION AND MAINTENANCE General Provisions § 171.110 How does BIA administer its irrigation facilities? (a) We administer our irrigation facilities by enforcing the applicable statutes,...

  8. 25 CFR 171.110 - How does BIA administer its irrigation facilities?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 1 2013-04-01 2013-04-01 false How does BIA administer its irrigation facilities? 171... IRRIGATION OPERATION AND MAINTENANCE General Provisions § 171.110 How does BIA administer its irrigation facilities? (a) We administer our irrigation facilities by enforcing the applicable statutes,...

  9. 21 CFR 1306.07 - Administering or dispensing of narcotic drugs.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 9 2012-04-01 2012-04-01 false Administering or dispensing of narcotic drugs... PRESCRIPTIONS General Information § 1306.07 Administering or dispensing of narcotic drugs. (a) A practitioner may administer or dispense directly (but not prescribe) a narcotic drug listed in any schedule to...

  10. 21 CFR 1306.07 - Administering or dispensing of narcotic drugs.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 9 2011-04-01 2011-04-01 false Administering or dispensing of narcotic drugs... PRESCRIPTIONS General Information § 1306.07 Administering or dispensing of narcotic drugs. (a) A practitioner may administer or dispense directly (but not prescribe) a narcotic drug listed in any schedule to...

  11. 21 CFR 1306.07 - Administering or dispensing of narcotic drugs.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 9 2014-04-01 2014-04-01 false Administering or dispensing of narcotic drugs... PRESCRIPTIONS General Information § 1306.07 Administering or dispensing of narcotic drugs. (a) A practitioner may administer or dispense directly (but not prescribe) a narcotic drug listed in any schedule to...

  12. 21 CFR 1306.07 - Administering or dispensing of narcotic drugs.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Administering or dispensing of narcotic drugs... PRESCRIPTIONS General Information § 1306.07 Administering or dispensing of narcotic drugs. (a) A practitioner may administer or dispense directly (but not prescribe) a narcotic drug listed in any schedule to...

  13. 45 CFR 400.66 - Eligibility and payment levels in a publicly-administered RCA program.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... REFUGEE RESETTLEMENT, ADMINISTRATION FOR CHILDREN AND FAMILIES, DEPARTMENT OF HEALTH AND HUMAN SERVICES REFUGEE RESETTLEMENT PROGRAM Refugee Cash Assistance § 400.66 Eligibility and payment levels in a publicly-administered RCA program. (a) In administering a publicly-administered refugee cash assistance program,...

  14. 25 CFR 518.2 - Who will administer the self-regulation program for the Commission?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 2 2014-04-01 2014-04-01 false Who will administer the self-regulation program for the... PROVISIONS SELF-REGULATION OF CLASS II GAMING § 518.2 Who will administer the self-regulation program for the Commission? The self-regulation program will be administered by the Office of Self-Regulation. The...

  15. 45 CFR 400.66 - Eligibility and payment levels in a publicly-administered RCA program.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... REFUGEE RESETTLEMENT, ADMINISTRATION FOR CHILDREN AND FAMILIES, DEPARTMENT OF HEALTH AND HUMAN SERVICES REFUGEE RESETTLEMENT PROGRAM Refugee Cash Assistance § 400.66 Eligibility and payment levels in a publicly-administered RCA program. (a) In administering a publicly-administered refugee cash assistance program,...

  16. 45 CFR 400.66 - Eligibility and payment levels in a publicly-administered RCA program.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... REFUGEE RESETTLEMENT, ADMINISTRATION FOR CHILDREN AND FAMILIES, DEPARTMENT OF HEALTH AND HUMAN SERVICES REFUGEE RESETTLEMENT PROGRAM Refugee Cash Assistance § 400.66 Eligibility and payment levels in a publicly-administered RCA program. (a) In administering a publicly-administered refugee cash assistance program,...

  17. 25 CFR 171.110 - How does BIA administer its irrigation facilities?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false How does BIA administer its irrigation facilities? 171... IRRIGATION OPERATION AND MAINTENANCE General Provisions § 171.110 How does BIA administer its irrigation facilities? (a) We administer our irrigation facilities by enforcing the applicable statutes,...

  18. Structural and functional insights into the malaria parasite moving junction complex.

    PubMed

    Vulliez-Le Normand, Brigitte; Tonkin, Michelle L; Lamarque, Mauld H; Langer, Susann; Hoos, Sylviane; Roques, Magali; Saul, Frederick A; Faber, Bart W; Bentley, Graham A; Boulanger, Martin J; Lebrun, Maryse

    2012-01-01

    Members of the phylum Apicomplexa, which include the malaria parasite Plasmodium, share many features in their invasion mechanism in spite of their diverse host cell specificities and life cycle characteristics. The formation of a moving junction (MJ) between the membranes of the invading apicomplexan parasite and the host cell is common to these intracellular pathogens. The MJ contains two key parasite components: the surface protein Apical Membrane Antigen 1 (AMA1) and its receptor, the Rhoptry Neck Protein (RON) complex, which is targeted to the host cell membrane during invasion. In particular, RON2, a transmembrane component of the RON complex, interacts directly with AMA1. Here, we report the crystal structure of AMA1 from Plasmodium falciparum in complex with a peptide derived from the extracellular region of PfRON2, highlighting clear specificities of the P. falciparum RON2-AMA1 interaction. The receptor-binding site of PfAMA1 comprises the hydrophobic groove and a region that becomes exposed by displacement of the flexible Domain II loop. Mutations of key contact residues of PfRON2 and PfAMA1 abrogate binding between the recombinant proteins. Although PfRON2 contacts some polymorphic residues, binding studies with PfAMA1 from different strains show that these have little effect on affinity. Moreover, we demonstrate that the PfRON2 peptide inhibits erythrocyte invasion by P. falciparum merozoites and that this strong inhibitory potency is not affected by AMA1 polymorphisms. In parallel, we have determined the crystal structure of PfAMA1 in complex with the invasion-inhibitory peptide R1 derived by phage display, revealing an unexpected structural mimicry of the PfRON2 peptide. These results identify the key residues governing the interactions between AMA1 and RON2 in P. falciparum and suggest novel approaches to antimalarial therapeutics. PMID:22737069

  19. Validation of a cognitive assessment battery administered by telephone

    PubMed Central

    Rapp, Stephen R.; Legault, Claudine; Espeland, Mark A.; Resnick, Susan M.; Hogan, Patricia E.; Coker, Laura H.; Dailey, Maggie; Shumaker, Sally A.

    2012-01-01

    Background While the gold standard method of cognitive assessment is a face-to-face administration, telephone-based assessments offer several advantages if they demonstrate reliability and validity. Design Observational study; 110 participants randomly assigned to receive two administrations of the same cognitive test battery 6 months apart in one of four combinations (1st administration/2nd administration): telephone/telephone; telephone/face-to-face; face-to-face/telephone; or face-to-face/face-to-face. Setting Academic medical center Participants 110 non-demented women between the ages of 65 and 90 years. Measures The battery included tests of attention, verbal learning and memory, verbal fluency, executive function, working memory and global cognitive functioning plus self-report measures of perceived memory problems, depressive symptoms, sleep disturbance and health-related quality of life. Test-retest reliability, concurrent validity, relative bias associated with telephone administration, and change scores were evaluated. Results There were no statistically significant differences in scores on any of the cognitive tests or questionnaires between randomly assigned modes of administration at baseline indicating equivalence across modes. There was no significant bias for tests or questionnaires administered by telephone (ps>0.01). Nor was there a difference in mean change scores between administration modes except for the Category Fluency (p = 0.01) and the California Verbal Learning Test long delay-free recall (p < 0.01). Mean test-retest coefficients for the battery were not significantly different across groups though individual test-retest correlation coefficients were generally higher within mode than across mode. Conclusions Telephone administration of cognitive tests and questionnaires to older women is both reliable and valid. Use of telephone batteries can substantially reduce the economic cost and burden of cognitive assessments and increase

  20. Centrally administered naloxone blocks reflex natriuresis after acute unilateral nephrectomy.

    PubMed

    Lin, S Y; Humphreys, M H

    1985-09-01

    Acute unilateral nephrectomy (AUN) leads to a natriuresis and kaliuresis by the remaining kidney through reflex mechanisms involving opiate receptors. To determine whether the opiate receptors mediating these responses are located in the central nervous system, we carried out AUN in anesthetized rats undergoing continuous ventriculocisternal perfusion (VCP) with artificial cerebrospinal fluid (CSF). AUN caused large increases in both Na (UNaV) and K (UKV) excretion without changes in glomerular filtration rate or arterial blood pressure. When the opiate receptor antagonist naloxone was added to the perfusate to achieve a perfusion rate of 32 micrograms X kg-1 X h-1, AUN failed to increase either UNaV or UKV by the remaining kidney. This dose of naloxone, however, was without effect when infused intravenously. Addition of thyrotropin-releasing hormone (TRH) to the artificial CSF to achieve a VCP rate of 50 micrograms X kg-1 X h-1 also blocked the expected increase in UNaV and UKV by the remaining kidney after AUN. Infusion of TRH intravenously at the same rate did not interfere with the postnephrectomy natriuresis or kaliuresis. Higher intravenous infusion rates of TRH (1 and 2 mg X kg-1h-1) prevented the postnephrectomy natriuresis without affecting the kaliuresis. These results indicate that the effect of naloxone to block the reflex natriuresis and kaliuresis after AUN resides largely in the central nervous system. The blockade by naloxone of the postnephrectomy natriuresis is duplicated by centrally administered TRH, providing another example of the interaction of this hormone with the endogenous opioid system. Large intravenous infusions of TRH also block the postnephrectomy natriuresis but not the kaliuresis. PMID:3929623

  1. Safety of Intravitreally Administered Recombinant Erythropoietin (An AOS Thesis)

    PubMed Central

    Tsai, James C.

    2008-01-01

    Purpose This study investigated the safety and potential retinal toxicity of intravitreally administered erythropoietin (EPO) in a rodent animal model. Methods Forty-two healthy Sprague-Dawley rats were divided into one of 7 groups (N = 6 per group): control, sham injection, vehicle injection, and EPO injections of 50 ng (5 U), 100 ng (10 U), 250 ng (25 U), and 625 ng (62.5 U). Only the right eye was treated in each animal. Standard full-field dark- and light-adapted electroretinography (ERG) was obtained at 1 day prior to injection and then on postinjection days 3, 7, 14, and 21. Intraocular pressure (IOP) was measured at the conclusion of each ERG recording. Animals were sacrificed and the eyes underwent histologic examination with light microscopy and hematoxylin-eosin staining. Results Rod peak, scotopic, and photopic responses (amplitude and latency) were not statistically different in the animals receiving 50 to 100 ng EPO. In the 250-ng group, the photopic b-wave amplitude at day 21 was elevated (P <.05), whereas in the 625-ng group, the scotopic OP3 latency ratio was higher at baseline (P <.05). No significant histologic abnormalities were noted except for one animal (625-ng group) with qualitative differences in retinal layer thickness and cellular density. Conclusions Intravitreal administration of EPO (at doses up to 625 ng) does not cause adverse effects on retinal function as assessed by ERG. Moreover, single intravitreal dosing does not appear to elicit retinal neovascularization. Further investigation is warranted to assess fully the potential of this neuroprotective cytokine as a treatment for glaucoma. PMID:19277250

  2. Strain-specific Plasmodium falciparum multifunctional CD4(+) T cell cytokine expression in Malian children immunized with the FMP2.1/AS02A vaccine candidate.

    PubMed

    Graves, Shawna F; Kouriba, Bourema; Diarra, Issa; Daou, Modibo; Niangaly, Amadou; Coulibaly, Drissa; Keita, Yamoussa; Laurens, Matthew B; Berry, Andrea A; Vekemans, Johan; Ripley Ballou, W; Lanar, David E; Dutta, Sheetij; Gray Heppner, D; Soisson, Lorraine; Diggs, Carter L; Thera, Mahamadou A; Doumbo, Ogobara K; Plowe, Christopher V; Sztein, Marcelo B; Lyke, Kirsten E

    2016-05-17

    Based on Plasmodium falciparum (Pf) apical membrane antigen 1 (AMA1) from strain 3D7, the malaria vaccine candidate FMP2.1/AS02A showed strain-specific efficacy in a Phase 2 clinical trial in 400 Malian children randomized to 3 doses of the AMA1 vaccine candidate or control rabies vaccine on days 0, 30 and 60. A subset of 10 Pf(-) (i.e., no clinical malaria episodes) AMA1 recipients, 11 Pf(+) (clinical malaria episodes with parasites with 3D7 or Fab9-type AMA1 cluster 1 loop [c1L]) AMA1 recipients, and 10 controls were randomly chosen for analysis. Peripheral blood mononuclear cells (PBMCs) isolated on days 0, 90 and 150 were stimulated with full-length 3D7 AMA1 and c1L from strains 3D7 (c3D7) and Fab9 (cFab9). Production of IFN-γ, TNF-α, IL-2, and/or IL-17A was analyzed by flow cytometry. Among AMA1 recipients, 18/21 evaluable samples stimulated with AMA1 demonstrated increased IFN-γ, TNF-α, and IL-2 derived from CD4(+) T cells by day 150 compared to 0/10 in the control group (p<0.0001). Among AMA1 vaccines, CD4(+) cells expressing both TNF-α and IL-2 were increased in Pf(-) children compared to Pf(+) children. When PBMCs were stimulated with c3D7 and cFab9 separately, 4/18 AMA1 recipients with an AMA1-specific CD4(+) response had a significant response to one or both c1L. This suggests that recognition of the AMA1 antigen is not dependent upon c1L alone. In summary, AMA1-specific T cell responses were notably increased in children immunized with an AMA1-based vaccine candidate. The role of CD4(+)TNF-α(+)IL-2(+)-expressing T cells in vaccine-induced strain-specific protection against clinical malaria requires further exploration. Clinicaltrials.gov Identifier: NCT00460525. PMID:27087149

  3. Transcription of Epstein-Barr virus-encoded nuclear antigen 1 promoter Qp is repressed by transforming growth factor-beta via Smad4 binding element in human BL cells.

    PubMed

    Liang, C L; Tsai, C N; Chung, P J; Chen, J L; Sun, C M; Chen, R H; Hong, J H; Chang, Y S

    2000-11-10

    In Epstein-Barr virus (EBV)-infected BL cells, the oncogenic EBV-encoded nuclear antigen 1 (EBNA 1) gene is directed from the latent promoter Qp. Yeast one-hybrid screen analysis using the -50 to -37 sequence of Qp as the bait was carried out to identify transcriptional factors that may control Qp activity. Results showed that Smad4 binds the -50 to -37 sequence of Qp, indicating that this promoter is potentially regulated by TGF-beta. The association of Smad4 with Qp was further confirmed by supershift of EMSA complexes using Smad4-specific antibody. The transfection of a Qp reporter construct in two EBV(+) BL cell lines, Rael and WW2, showed that Qp activity is repressed in response to the TGF-beta treatment. This repression involves the interaction of a Smad3/Smad4 complex and the transcriptional repressor TGIF, as determined by cotransfection assay and coimmunoprecipitation analysis. Results suggest that TGF-beta may transcriptionally repress Qp through the Smad4-binding site in human BL cells. PMID:11062049

  4. 40 CFR 147.1851 - State-administered program-Class II wells.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Oklahoma § 147.1851 State-administered program—Class II wells. The UIC program for Class II wells in the State of Oklahoma, including the lands of the Five Civilized Tribes, but not including those on other Indian lands, is the program administered by the Oklahoma Corporation Commission approved by EPA...

  5. 40 CFR 147.1851 - State-administered program-Class II wells.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Oklahoma § 147.1851 State-administered program—Class II wells. The UIC program for Class II wells in the State of Oklahoma, including the lands of the Five Civilized Tribes, but not including those on other Indian lands, is the program administered by the Oklahoma Corporation Commission approved by EPA...

  6. 40 CFR 147.1851 - State-administered program-Class II wells.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Oklahoma § 147.1851 State-administered program—Class II wells. The UIC program for Class II wells in the State of Oklahoma, including the lands of the Five Civilized Tribes, but not including those on other Indian lands, is the program administered by the Oklahoma Corporation Commission approved by EPA...

  7. 40 CFR 147.1851 - State-administered program-Class II wells.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Oklahoma § 147.1851 State-administered program—Class II wells. The UIC program for Class II wells in the State of Oklahoma, including the lands of the Five Civilized Tribes, but not including those on other Indian lands, is the program administered by the Oklahoma Corporation Commission approved by EPA...

  8. 30 CFR 250.1508 - What must I do when BSEE administers written or oral tests?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Control and Production Safety Training § 250.1508 What must I do when BSEE administers written or oral... 30 Mineral Resources 2 2012-07-01 2012-07-01 false What must I do when BSEE administers written or oral tests? 250.1508 Section 250.1508 Mineral Resources BUREAU OF SAFETY AND ENVIRONMENTAL...

  9. 30 CFR 250.1508 - What must I do when BSEE administers written or oral tests?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Control and Production Safety Training § 250.1508 What must I do when BSEE administers written or oral... 30 Mineral Resources 2 2013-07-01 2013-07-01 false What must I do when BSEE administers written or oral tests? 250.1508 Section 250.1508 Mineral Resources BUREAU OF SAFETY AND ENVIRONMENTAL...

  10. 30 CFR 250.1508 - What must I do when BSEE administers written or oral tests?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Control and Production Safety Training § 250.1508 What must I do when BSEE administers written or oral... 30 Mineral Resources 2 2014-07-01 2014-07-01 false What must I do when BSEE administers written or oral tests? 250.1508 Section 250.1508 Mineral Resources BUREAU OF SAFETY AND ENVIRONMENTAL...

  11. 25 CFR 26.4 - Who administers the Job Placement and Training Program?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 1 2014-04-01 2014-04-01 false Who administers the Job Placement and Training Program? 26.4 Section 26.4 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR HUMAN SERVICES JOB PLACEMENT AND TRAINING PROGRAM General Applicability § 26.4 Who administers the Job Placement and...

  12. 25 CFR 26.4 - Who administers the Job Placement and Training Program?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 1 2013-04-01 2013-04-01 false Who administers the Job Placement and Training Program? 26.4 Section 26.4 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR HUMAN SERVICES JOB PLACEMENT AND TRAINING PROGRAM General Applicability § 26.4 Who administers the Job Placement and...

  13. 25 CFR 26.4 - Who administers the Job Placement and Training Program?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 1 2011-04-01 2011-04-01 false Who administers the Job Placement and Training Program? 26.4 Section 26.4 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR HUMAN SERVICES JOB PLACEMENT AND TRAINING PROGRAM General Applicability § 26.4 Who administers the Job Placement and...

  14. Alliance in Two Telephone-Administered Treatments: Relationship with Depression and Health Outcomes

    ERIC Educational Resources Information Center

    Beckner, Victoria; Vella, Lea; Howard, Isa; Mohr, David C.

    2007-01-01

    The present study examined the relationship between therapeutic alliance and both depression and health outcomes in a randomized clinical trial of 2 telephone-administered treatments with 97 clients with multiple sclerosis (MS). The 16-week, manualized treatments compared were telephone-administered cognitive-behavioral therapy (T-CBT) and…

  15. Development of Teacher-Administered Tests for the SWRL Reading Programs.

    ERIC Educational Resources Information Center

    Niedermeyer, Fred C.; Sullivan, Howard J.

    To investigate the type of classroom testing format most appropriate for the Southwest Regional Laboratory (SWRL) Mod 2 Reading Program, three types of teacher-administered tests for the SWRL Second-Year Communication Skills Program were developed and tried out during the 1970-71 school year. The tests were administered by the classroom teacher as…

  16. 40 CFR 147.2651 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Puerto Rico... on Indian lands in the Commonwealth of Puerto Rico is administered by EPA. This program consists of the UIC program requirements of 40 CFR parts 124, 144, 146, 148 and any additional requirements...

  17. 19 CFR 207.13 - Cooperation with administering authority; preliminary phase of investigation.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 19 Customs Duties 3 2014-04-01 2014-04-01 false Cooperation with administering authority; preliminary phase of investigation. 207.13 Section 207.13 Customs Duties UNITED STATES INTERNATIONAL TRADE... Determinations § 207.13 Cooperation with administering authority; preliminary phase of investigation....

  18. 40 CFR 282.81 - New Mexico State-Administered Program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 28 2012-07-01 2012-07-01 false New Mexico State-Administered Program. 282.81 Section 282.81 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.81 New Mexico State-Administered Program. (a) The State...

  19. 40 CFR 282.83 - North Carolina State-Administered Program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 28 2012-07-01 2012-07-01 false North Carolina State-Administered Program. 282.83 Section 282.83 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.83 North Carolina State-Administered Program. (a)...

  20. 40 CFR 282.98 - West Virginia State-Administered Program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 28 2012-07-01 2012-07-01 false West Virginia State-Administered Program. 282.98 Section 282.98 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.98 West Virginia State-Administered Program. (a)...

  1. 40 CFR 272.1651 - New York State-Administered Program: Final authorization.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 28 2012-07-01 2012-07-01 false New York State-Administered Program: Final authorization. 272.1651 Section 272.1651 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) APPROVED STATE HAZARDOUS WASTE MANAGEMENT PROGRAMS New York § 272.1651 New York State-Administered...

  2. 7 CFR 4280.195 - Awarding and administering energy audit and renewable energy development assistance grants.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 15 2014-01-01 2014-01-01 false Awarding and administering energy audit and renewable... OF AGRICULTURE LOANS AND GRANTS Rural Energy for America Program General Energy Audit and Renewable Energy Development Assistance Grants § 4280.195 Awarding and administering energy audit and...

  3. 7 CFR 4280.195 - Awarding and administering energy audit and renewable energy development assistance grants.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 15 2012-01-01 2012-01-01 false Awarding and administering energy audit and renewable... OF AGRICULTURE LOANS AND GRANTS Rural Energy for America Program General Energy Audit and Renewable Energy Development Assistance Grants § 4280.195 Awarding and administering energy audit and...

  4. 7 CFR 4280.195 - Awarding and administering energy audit and renewable energy development assistance grants.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 15 2013-01-01 2013-01-01 false Awarding and administering energy audit and renewable... OF AGRICULTURE LOANS AND GRANTS Rural Energy for America Program General Energy Audit and Renewable Energy Development Assistance Grants § 4280.195 Awarding and administering energy audit and...

  5. 42 CFR 2a.5 - Contents of application; research projects in which drugs will be administered.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Contents of application; research projects in which... application; research projects in which drugs will be administered. (a) In addition to the information... for an authorization of confidentiality for a research project which involves the administering of...

  6. 42 CFR 2a.5 - Contents of application; research projects in which drugs will be administered.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 1 2013-10-01 2013-10-01 false Contents of application; research projects in which... application; research projects in which drugs will be administered. (a) In addition to the information... for an authorization of confidentiality for a research project which involves the administering of...

  7. 42 CFR 2a.5 - Contents of application; research projects in which drugs will be administered.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 1 2014-10-01 2014-10-01 false Contents of application; research projects in which... application; research projects in which drugs will be administered. (a) In addition to the information... for an authorization of confidentiality for a research project which involves the administering of...

  8. 42 CFR 2a.5 - Contents of application; research projects in which drugs will be administered.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Contents of application; research projects in which... application; research projects in which drugs will be administered. (a) In addition to the information... for an authorization of confidentiality for a research project which involves the administering of...

  9. 42 CFR 2a.5 - Contents of application; research projects in which drugs will be administered.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false Contents of application; research projects in which... application; research projects in which drugs will be administered. (a) In addition to the information... for an authorization of confidentiality for a research project which involves the administering of...

  10. 20 CFR 672.200 - How are YouthBuild grants funded and administered?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 4 2014-04-01 2014-04-01 false How are YouthBuild grants funded and... How are YouthBuild grants funded and administered? The Secretary uses funds authorized for appropriation under sec. 173A of the Workforce Investment Act (WIA) to administer YouthBuild as a...

  11. 20 CFR 672.200 - How are YouthBuild grants funded and administered?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 4 2012-04-01 2012-04-01 false How are YouthBuild grants funded and... How are YouthBuild grants funded and administered? The Secretary uses funds authorized for appropriation under sec. 173A of the Workforce Investment Act (WIA) to administer YouthBuild as a...

  12. 20 CFR 672.200 - How are YouthBuild grants funded and administered?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 4 2013-04-01 2013-04-01 false How are YouthBuild grants funded and... How are YouthBuild grants funded and administered? The Secretary uses funds authorized for appropriation under sec. 173A of the Workforce Investment Act (WIA) to administer YouthBuild as a...

  13. 7 CFR 4280.181 - Awarding and administering feasibility study grants.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 15 2012-01-01 2012-01-01 false Awarding and administering feasibility study grants... Energy for America Program General Renewable Energy System Feasibility Study Grants § 4280.181 Awarding and administering feasibility study grants. Renewable energy system feasibility study grants will...

  14. 7 CFR 4280.181 - Awarding and administering feasibility study grants.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 15 2014-01-01 2014-01-01 false Awarding and administering feasibility study grants... Energy for America Program General Renewable Energy System Feasibility Study Grants § 4280.181 Awarding and administering feasibility study grants. Renewable energy system feasibility study grants will...

  15. 7 CFR 4280.181 - Awarding and administering feasibility study grants.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 15 2013-01-01 2013-01-01 false Awarding and administering feasibility study grants... Energy for America Program General Renewable Energy System Feasibility Study Grants § 4280.181 Awarding and administering feasibility study grants. Renewable energy system feasibility study grants will...

  16. 20 CFR 669.120 - How do we administer the NFJP program?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 4 2014-04-01 2014-04-01 false How do we administer the NFJP program? 669.120 Section 669.120 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) NATIONAL FARMWORKER JOBS PROGRAM UNDER TITLE I OF THE WORKFORCE INVESTMENT ACT Purpose and Definitions § 669.120 How do we administer...

  17. 20 CFR 669.120 - How do we administer the NFJP program?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false How do we administer the NFJP program? 669.120 Section 669.120 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR NATIONAL FARMWORKER JOBS PROGRAM UNDER TITLE I OF THE WORKFORCE INVESTMENT ACT Purpose and Definitions § 669.120 How do we administer the NFJP...

  18. 40 CFR 147.553 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... on Indian lands in the State of Georgia is administered by EPA. This program consists of the UIC program requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth in the... PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS...

  19. 40 CFR 147.553 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... on Indian lands in the State of Georgia is administered by EPA. This program consists of the UIC program requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth in the... PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS...

  20. 30 CFR 250.1508 - What must I do when MMS administers written or oral tests?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 2 2011-07-01 2011-07-01 false What must I do when MMS administers written or oral tests? 250.1508 Section 250.1508 Mineral Resources BUREAU OF OCEAN ENERGY MANAGEMENT, REGULATION... authorized representative to administer written or oral tests; and (b) Identify personnel by current...

  1. 25 CFR 171.110 - How does BIA administer its irrigation facilities?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 1 2012-04-01 2011-04-01 true How does BIA administer its irrigation facilities? 171.110 Section 171.110 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER IRRIGATION OPERATION AND MAINTENANCE General Provisions § 171.110 How does BIA administer its irrigation facilities?...

  2. 40 CFR 282.98 - West Virginia State-Administered Program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... it more stringent, in accordance with section 9004 of RCRA, 42 U.S.C. 6991c, and 40 CFR part 281... 40 Protection of Environment 27 2014-07-01 2014-07-01 false West Virginia State-Administered... Virginia State-Administered Program. (a) The State of West Virginia's underground storage tank program...

  3. 40 CFR 147.2453 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Virginia § 147.2453 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of wells on Indian lands in the State of West Virginia is administered by EPA. This program consists of the UIC program requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set...

  4. 40 CFR 282.98 - West Virginia State-Administered Program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... it more stringent, in accordance with section 9004 of RCRA, 42 U.S.C. 6991c, and 40 CFR part 281... 40 Protection of Environment 27 2011-07-01 2011-07-01 false West Virginia State-Administered... Virginia State-Administered Program. (a) The State of West Virginia's underground storage tank program...

  5. 40 CFR 282.98 - West Virginia State-Administered Program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... it more stringent, in accordance with section 9004 of RCRA, 42 U.S.C. 6991c, and 40 CFR part 281... 40 Protection of Environment 26 2010-07-01 2010-07-01 false West Virginia State-Administered... Virginia State-Administered Program. (a) The State of West Virginia's underground storage tank program...

  6. 40 CFR 147.2453 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Virginia § 147.2453 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of wells on Indian lands in the State of West Virginia is administered by EPA. This program consists of the UIC program requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set...

  7. 40 CFR 147.2453 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Virginia § 147.2453 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of wells on Indian lands in the State of West Virginia is administered by EPA. This program consists of the UIC program requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set...

  8. 40 CFR 282.98 - West Virginia State-Administered Program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... it more stringent, in accordance with section 9004 of RCRA, 42 U.S.C. 6991c, and 40 CFR part 281... 40 Protection of Environment 28 2013-07-01 2013-07-01 false West Virginia State-Administered... Virginia State-Administered Program. (a) The State of West Virginia's underground storage tank program...

  9. 40 CFR 147.2453 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Virginia § 147.2453 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of wells on Indian lands in the State of West Virginia is administered by EPA. This program consists of the UIC program requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set...

  10. 40 CFR 147.1703 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... wells on Indian lands in the State of North Carolina is administered by EPA. This program consists of the UIC program requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set... PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS...

  11. 40 CFR 147.1703 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... wells on Indian lands in the State of North Carolina is administered by EPA. This program consists of the UIC program requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set... PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS...

  12. 25 CFR 166.603 - If cash is submitted as a bond, how is it administered?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false If cash is submitted as a bond, how is it administered... GRAZING PERMITS Bonding and Insurance Requirements § 166.603 If cash is submitted as a bond, how is it administered? If cash is submitted as a bond, we will establish an account in the name of the permittee...

  13. 41 CFR 302-6.300 - How should we administer the TQSE allowance?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 41 Public Contracts and Property Management 4 2010-07-01 2010-07-01 false How should we administer the TQSE allowance? 302-6.300 Section 302-6.300 Public Contracts and Property Management Federal... Responsibilities § 302-6.300 How should we administer the TQSE allowance? Temporary quarters should be used only...

  14. 40 CFR 147.860 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... on Indian lands in the State of Kansas is administered by EPA. This program consists of the UIC program requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth in the... PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS...

  15. 40 CFR 147.851 - State-administered program-Class II wells.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Kansas § 147.851 State-administered program—Class II wells. The UIC program for Class II wells in the State of Kansas, except those on Indian lands as described in § 147.860, is the program administered by the Kansas Corporation Commission and the Kansas Department of Health and Environment, approved by...

  16. 40 CFR 131.8 - Requirements for Indian Tribes to administer a water quality standards program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... administer a water quality standards program. 131.8 Section 131.8 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS WATER QUALITY STANDARDS General Provisions § 131.8 Requirements for Indian Tribes to administer a water quality standards program. (a) The Regional Administrator,...

  17. 40 CFR 131.8 - Requirements for Indian Tribes to administer a water quality standards program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... administer a water quality standards program. 131.8 Section 131.8 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS WATER QUALITY STANDARDS General Provisions § 131.8 Requirements for Indian Tribes to administer a water quality standards program. (a) The Regional Administrator,...

  18. 40 CFR 131.8 - Requirements for Indian Tribes to administer a water quality standards program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... administer a water quality standards program. 131.8 Section 131.8 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS WATER QUALITY STANDARDS General Provisions § 131.8 Requirements for Indian Tribes to administer a water quality standards program. (a) The Regional Administrator,...

  19. 40 CFR 131.8 - Requirements for Indian Tribes to administer a water quality standards program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... administer a water quality standards program. 131.8 Section 131.8 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS WATER QUALITY STANDARDS General Provisions § 131.8 Requirements for Indian Tribes to administer a water quality standards program. (a) The Regional Administrator,...

  20. 40 CFR 131.8 - Requirements for Indian Tribes to administer a water quality standards program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... administer a water quality standards program. 131.8 Section 131.8 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS WATER QUALITY STANDARDS General Provisions § 131.8 Requirements for Indian Tribes to administer a water quality standards program. (a) The Regional Administrator,...

  1. 40 CFR 147.1401 - State administered program-Class I, III, IV and V wells.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 23 2014-07-01 2014-07-01 false State administered program-Class I, III, IV and V wells. 147.1401 Section 147.1401 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Nebraska § 147.1401...

  2. 40 CFR 147.1401 - State administered program-Class I, III, IV and V wells.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State administered program-Class I, III, IV and V wells. 147.1401 Section 147.1401 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Nebraska § 147.1401...

  3. 40 CFR 147.2100 - State-administered program-Class II wells.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... South Dakota § 147.2100 State-administered program—Class II wells. The UIC program for Class II wells in the State of South Dakota, except those on Indian lands, is the program administered by the South... part of the applicable UIC program under the SDWA for the State of South Dakota. This incorporation...

  4. 40 CFR 147.2100 - State-administered program-Class II wells.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... South Dakota § 147.2100 State-administered program—Class II wells. The UIC program for Class II wells in the State of South Dakota, except those on Indian lands, is the program administered by the South... part of the applicable UIC program under the SDWA for the State of South Dakota. This incorporation...

  5. 40 CFR 147.2100 - State-administered program-Class II wells.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... South Dakota § 147.2100 State-administered program—Class II wells. The UIC program for Class II wells in the State of South Dakota, except those on Indian lands, is the program administered by the South... part of the applicable UIC program under the SDWA for the State of South Dakota. This incorporation...

  6. 40 CFR 272.2101 - South Dakota State-Administered Program: Final Authorization.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... accordance with 5 U.S.C. 552(a) and 1 CFR part 51. Copies of the South Dakota regulations that are... 40 Protection of Environment 28 2013-07-01 2013-07-01 false South Dakota State-Administered... Dakota § 272.2101 South Dakota State-Administered Program: Final Authorization. (a) Pursuant to...

  7. 40 CFR 147.2100 - State-administered program-Class II wells.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... South Dakota § 147.2100 State-administered program—Class II wells. The UIC program for Class II wells in the State of South Dakota, except those on Indian lands, is the program administered by the South... part of the applicable UIC program under the SDWA for the State of South Dakota. This incorporation...

  8. 40 CFR 147.2100 - State-administered program-Class II wells.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 23 2011-07-01 2011-07-01 false State-administered program-Class II wells. 147.2100 Section 147.2100 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS South Dakota § 147.2100...

  9. 40 CFR 272.1301 - State-administered program; Final authorization.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 27 2014-07-01 2014-07-01 false State-administered program; Final authorization. 272.1301 Section 272.1301 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) APPROVED STATE HAZARDOUS WASTE MANAGEMENT PROGRAMS Missouri § 272.1301 State-administered program; Final...

  10. 40 CFR 272.151 - Arizona State-administered program: Final authorization.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 27 2014-07-01 2014-07-01 false Arizona State-administered program: Final authorization. 272.151 Section 272.151 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) APPROVED STATE HAZARDOUS WASTE MANAGEMENT PROGRAMS Arizona § 272.151 Arizona State-administered program:...

  11. 40 CFR 272.1201 - Minnesota State-administered program; Final authorization.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 27 2014-07-01 2014-07-01 false Minnesota State-administered program; Final authorization. 272.1201 Section 272.1201 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) APPROVED STATE HAZARDOUS WASTE MANAGEMENT PROGRAMS Minnesota § 272.1201 Minnesota State-administered...

  12. 40 CFR 272.401 - State-administered program: Final authorization.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 27 2014-07-01 2014-07-01 false State-administered program: Final authorization. 272.401 Section 272.401 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) APPROVED STATE HAZARDOUS WASTE MANAGEMENT PROGRAMS Delaware § 272.401 State-administered program: Final...

  13. 40 CFR 272.1151 - State-administered program: Final authorization.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 27 2014-07-01 2014-07-01 false State-administered program: Final authorization. 272.1151 Section 272.1151 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) APPROVED STATE HAZARDOUS WASTE MANAGEMENT PROGRAMS Michigan § 272.1151 State-administered program: Final...

  14. 40 CFR 272.651 - Idaho State-Administered Program: Final Authorization.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 27 2014-07-01 2014-07-01 false Idaho State-Administered Program: Final Authorization. 272.651 Section 272.651 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) APPROVED STATE HAZARDOUS WASTE MANAGEMENT PROGRAMS Idaho § 272.651 Idaho State-Administered Program:...

  15. 40 CFR 272.701 - State-administered program: Final authorization.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 27 2014-07-01 2014-07-01 false State-administered program: Final authorization. 272.701 Section 272.701 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) APPROVED STATE HAZARDOUS WASTE MANAGEMENT PROGRAMS Illinois § 272.701 State-administered program: Final...

  16. 40 CFR 147.2205 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Indian lands in the State of Texas is administered by EPA. This program consists of the UIC program requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth in the remainder of... PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Texas §...

  17. 40 CFR 147.2205 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Indian lands in the State of Texas is administered by EPA. This program consists of the UIC program requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth in the remainder of... PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Texas §...

  18. 40 CFR 147.2205 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Indian lands in the State of Texas is administered by EPA. This program consists of the UIC program requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth in the remainder of... PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Texas §...

  19. 40 CFR 147.2205 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Indian lands in the State of Texas is administered by EPA. This program consists of the UIC program requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth in the remainder of... PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Texas §...

  20. Test-Retest Reliability of Psychological and Neurobehavioral Tests Self-Administered by Computer.

    ERIC Educational Resources Information Center

    Campbell, Keith A.; Rohlman, Diane S.; Storzbach, Daniel; Binder, Laurence M.; Anger, W. Kent; Kovera, Craig A.; Davis, Kelly L.; Grossman, Sandra J.

    1999-01-01

    Administered 12 psychological and 7 neurobehavioral performance tests twice to nonclinical normative samples of 30 adults (computer format only) and 30 adults (computer and conventional administration) with one week between administrations. Results suggest that individual test-retest reliability is not affected when tests are administered as part…

  1. 40 CFR 147.1600 - State-administered program-Class II wells.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... New Mexico § 147.1600 State-administered program—Class II wells. The UIC program for Class II wells in the State of New Mexico, except for those on Indian lands, is the program administered by the New... reference and made a part of the applicable UIC program under the SDWA for the State of New Mexico....

  2. 40 CFR 147.1600 - State-administered program-Class II wells.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... New Mexico § 147.1600 State-administered program—Class II wells. The UIC program for Class II wells in the State of New Mexico, except for those on Indian lands, is the program administered by the New... reference and made a part of the applicable UIC program under the SDWA for the State of New Mexico....

  3. 40 CFR 147.1600 - State-administered program-Class II wells.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... New Mexico § 147.1600 State-administered program—Class II wells. The UIC program for Class II wells in the State of New Mexico, except for those on Indian lands, is the program administered by the New... reference and made a part of the applicable UIC program under the SDWA for the State of New Mexico....

  4. 40 CFR 147.1600 - State-administered program-Class II wells.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... New Mexico § 147.1600 State-administered program—Class II wells. The UIC program for Class II wells in the State of New Mexico, except for those on Indian lands, is the program administered by the New... reference and made a part of the applicable UIC program under the SDWA for the State of New Mexico....

  5. 40 CFR 147.300 - State-administered program-Class II wells.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program-Class II wells. 147.300 Section 147.300 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Colorado § 147.300...

  6. 40 CFR 147.2251 - State-administered program-Class II wells.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 23 2011-07-01 2011-07-01 false State-administered program-Class II wells. 147.2251 Section 147.2251 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Utah § 147.2251...

  7. 40 CFR 147.1401 - State administered program-Class I, III, IV and V wells.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 24 2012-07-01 2012-07-01 false State administered program-Class I, III, IV and V wells. 147.1401 Section 147.1401 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Nebraska § 147.1401...

  8. 40 CFR 147.1401 - State administered program-Class I, III, IV and V wells.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 24 2013-07-01 2013-07-01 false State administered program-Class I, III, IV and V wells. 147.1401 Section 147.1401 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Nebraska § 147.1401...

  9. 40 CFR 147.353 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth in the remainder of... 40 Protection of Environment 22 2010-07-01 2010-07-01 false EPA-administered program-Indian lands... PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS...

  10. 40 CFR 147.403 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth in the remainder of... 40 Protection of Environment 22 2010-07-01 2010-07-01 false EPA-administered program-Indian lands... PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS...

  11. 40 CFR 147.951 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... program requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth in the... 40 Protection of Environment 22 2010-07-01 2010-07-01 false EPA-administered program-Indian lands... PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS...

  12. 40 CFR 147.60 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... requirements of 40 CFR parts 124, 144, 146, 148 and any additional requirements set forth in the remainder of... 40 Protection of Environment 22 2010-07-01 2010-07-01 false EPA-administered program-Indian lands... PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS...

  13. 40 CFR 147.703 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... program requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth in the... 40 Protection of Environment 22 2010-07-01 2010-07-01 false EPA-administered program-Indian lands... PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS...

  14. 40 CFR 147.205 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... requirements of 40 CFR parts 124, 144, 146, 148 and any additional requirements set forth in this subpart... 40 Protection of Environment 22 2010-07-01 2010-07-01 false EPA-administered program-Indian lands... PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS...

  15. 40 CFR 147.651 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth in the remainder of... 40 Protection of Environment 22 2010-07-01 2010-07-01 false EPA-administered program-Indian lands... PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Idaho §...

  16. 40 CFR 147.1401 - State administered program-Class I, III, IV and V wells.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 23 2011-07-01 2011-07-01 false State administered program-Class I, III, IV and V wells. 147.1401 Section 147.1401 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Nebraska § 147.1401...

  17. 40 CFR 147.1600 - State-administered program-Class II wells.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... New Mexico § 147.1600 State-administered program—Class II wells. The UIC program for Class II wells in the State of New Mexico, except for those on Indian lands, is the program administered by the New Mexico Energy and Minerals Department, Oil Conservation Division, approved by EPA pursuant to...

  18. Epstein-Barr Virus-Encoded Latent Membrane Protein 2A Promotes the Epithelial-Mesenchymal Transition in Nasopharyngeal Carcinoma via Metastatic Tumor Antigen 1 and Mechanistic Target of Rapamycin Signaling Induction

    PubMed Central

    Lin, Zhe; Wan, Xin; Jiang, Runqiu; Deng, Lei; Gao, Yun; Tang, Junwei; Yang, Yu; Zhao, Wei; Yan, Xin; Yao, Kun

    2014-01-01

    ABSTRACT Epstein-Barr virus-encoded latent membrane protein 2A (LMP2A) promotes the epithelial-mesenchymal transition (EMT) of nasopharyngeal carcinoma (NPC), thereby increasing tumor invasion. Recently, the dysregulation of metastatic tumor antigen 1 (MTA1) was found to enhance tumor metastasis in a variety of cancers. A molecular connection between these two proteins has been proposed but not firmly established. In this study, we reported the overexpression of MTA1 in 29/60 (48.3%) NPC patients, and the overexpression of MTA1 significantly correlated with tumor metastasis. The overexpression of MTA1 promoted EMT via the Wnt1 pathway and β-catenin activation. We demonstrated that LMP2A reinforces the expression of MTA1 via the mechanistic target of rapamycin (mTOR) pathway to promote EMT in NPC. Furthermore, by knocking down 4EBP1 in combination with the new mTOR inhibitor INK-128 treatment, we discovered that LMP2A expression activates the 4EBP1-eIF4E axis and increases the expression of MTA1 at the translational level partially independent of c-myc. These findings provided novel insights into the correlation between the LMP2A and MTA1 proteins and reveal a novel function of the 4EBP1-eIF4E axis in EMT of nasopharyngeal carcinoma. IMPORTANCE Prevention of the recurrence and metastasis of NPC is critical to achieving a successful NPC treatment. As we all know, EMT has a vital role in metastasis of malignancies. LMP2A, an oncoprotein of Epstein-Barr virus, a well-known NPC activator, induces EMT and has been proved to exert a promoting effect in tumor metastasis. Our study demonstrated that LMP2A could induce EMT by activating MTA1 at the translational level via activating mTOR signaling and the 4EBP1-eIF4E axis. Taken together, our findings bridge the gap between the NPC-specific cell surface molecule and the final phenotype of the NPC cells. Additionally, our findings indicate that LMP2A and mTOR will serve as targets for NPC therapy in the future. PMID:25100829

  19. 78 FR 23777 - Notice of Proposed Information Collection: Comment Request: HUD-Administered Small Cities Program...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-22

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT Notice of Proposed Information Collection: Comment Request: HUD- Administered Small... INFORMATION CONTACT: Colette Pollard, Reports Management Officer, QDAM, Department of Housing and...

  20. 9 CFR 103.2 - Disposition of animals administered experimental biological products or live organisms.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... live organisms. Safeguards as herein provided shall be established by the research investigator or research sponsor to control disposition of all animals administered experimental biological products or... Regulations). (c) Except as otherwise provided in this paragraph, the research investigator or...

  1. 9 CFR 103.2 - Disposition of animals administered experimental biological products or live organisms.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... live organisms. Safeguards as herein provided shall be established by the research investigator or research sponsor to control disposition of all animals administered experimental biological products or... Regulations). (c) Except as otherwise provided in this paragraph, the research investigator or...

  2. Test-retest reliability of psychological and neurobehavioral tests self-administered by computer.

    PubMed

    Campbell, K A; Rohlman, D S; Storzbach, D; Binder, L M; Anger, W K; Kovera, C A; Davis, K L; Grossmann, S J

    1999-03-01

    A series of 12 psychological and 7 neurobehavioral performance tests were administered twice to a nonclinical normative sample with 1 week between administrations. The tests were presented in a self-administered computerized format. One week test-retest reliabilities were comparable to conventional administration formats. The results suggest that individual test reliability is not affected when tests are administered as part of an extensive multi-measure battery. Computer administered test reliability coefficients also were compared to a Mixed Format (computer-conventional) administration with mixed format reliabilities generally similar to the reliabilities of published conventional tests but also generally lower than same format testing. Compared to psychological test reliability, neurobehavioral test reliability appeared more vulnerable to decreases with mixed format testing. These conclusions should not be generalized to all computer implemented tests as the qualities of the test implementation will affect the outcome. PMID:9971880

  3. 20 CFR 668.120 - How must INA programs be administered?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ..., administration, monitoring, and evaluation of Native American employment and training programs authorized under this Act. We will utilize staff who have a particular competence in this field to administer...

  4. 34 CFR 406.1 - What is the State-Administered Tech-Prep Education Program?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false What is the State-Administered Tech-Prep Education Program? 406.1 Section 406.1 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION STATE-ADMINISTERED TECH-PREP EDUCATION PROGRAM General § 406.1 What is...

  5. Dose Dependence of the Anticoagulant Effect of Intravenously Administered Cellulose Sulfate.

    PubMed

    Drozd, N N; Kuznetsova, S A; Kalinina, T B; Vasilieva, N Yu

    2016-04-01

    Experiments on rabbits showed that increasing the dose of intravenously administered cellulose sulfate from wheat straw (dynamic viscosity 3.4 cP, sulfur content 14.1%) increased plasma clotting time in some coagulation tests and plasma anticoagulant activity. When cellulose sulfate was administered in the dose of 1 mg/kg, plasma clotting time in the presence of the anticoagulant (5 min after administration) was ~3-fold higher than after saline administration. PMID:27165079

  6. Effects of microcomputer-administered diagnostic testing on immediate and continuing science achievement and attitudes

    NASA Astrophysics Data System (ADS)

    Waugh, Michael Leonard

    This investigation had three purposes: (1) to document any immediate and continuing benefits associated with the use of microcomputer-administered testing; (2) to determine what type of student might benefit most from microcomputer-administered diagnostic testing; and (3) to document the feasibility of microcomputer-administered diagnostic testing. The subjects of the study were enrolled in a biology course based on the BSCS Blue text. A random half of the students received behaviorally-stated performance objectives, while the remaining half received behaviorally-stated performance objectives in conjunction with microcomputer-administered diagnostic testing. The results of this study indicate that microcomputer-administered diagnostic testing can positively influence the immediate, but not the continuing, achievement of students in science. In addition, neither student aptitude nor achievement motivation level were found to interact with treatment or influence achievement. Affective data indicate that students react favorably to the use of objectives, computers, and diagnostic testing. Cost summary data reveal that when the expense of administering diagnostic testing by microcomputer is prorated over a five-year period, the cost of a diagnostic test is reduced to approximately three cents.

  7. 34 CFR 462.41 - How must tests be administered in order to accurately measure educational gain?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... assessment policy; (3)(i) Administer post-tests with a secure, parallel, equated form of the same test—either traditional paper and pencil or computer-administered instruments—for which forms are constructed prior...

  8. Internet- vs. telephone-administered questionnaires in a randomized trial of smoking cessation.

    PubMed

    Graham, Amanda L; Papandonatos, George D; Bock, Beth C; Cobb, Nathan K; Baskin-Sommers, Arielle; Niaura, Raymond; Abrams, David B

    2006-12-01

    The Internet offers a promising channel to conduct smoking cessation research. Among the advantages of Internet research are the ability to access large numbers of participants who might not otherwise participate in a cessation trial, and the ability to conduct research efficiently and cost-effectively. To leverage the opportunity of the Internet in clinical research, it is necessary to establish that measures of known validity used in research trials are reliable when administered via the Internet. To date, no published studies examine the psychometric properties of measures administered via the Internet to assess smoking variables and psychosocial constructs related to cessation (e.g., stress, social support, quit methods). The purpose of the present study was to examine the reliability of measures of previous quit methods, perceived stress, depression, social support for cessation, smoking temptations, alcohol use, perceived health status, and income when administered via the Internet. Participants in the present study were enrolled in a randomized controlled trial of the efficacy of Internet smoking cessation. Following baseline telephone assessment and randomization into the parent trial, participants were recruited to the reliability substudy. An email was sent 2 days after the telephone assessment with a link to the Internet survey and instructions to complete the survey that day. Of the 297 individuals invited to participate, 213 completed the survey within 1 week. Results indicate that the internal consistency and test-retest reliability of the measures examined are comparable when self-administered via the Internet or when interviewer-administered via telephone. PMID:17491171

  9. Pharmacokinetics of dolutegravir when administered with mineral supplements in healthy adult subjects.

    PubMed

    Song, Ivy; Borland, Julie; Arya, Niki; Wynne, Brian; Piscitelli, Stephen

    2015-05-01

    All commercially available integrase inhibitors are 2-metal binders and may be affected by co-administration with metal cations. The purpose of this study was to evaluate the effect of calcium and iron supplements on dolutegravir pharmacokinetics and strategies (dose separation and food) to attenuate the effects if significant reductions in dolutegravir exposure were observed. This was an open-label, crossover study that randomized 24 healthy subjects into 1 of 2 cohorts to receive 4 treatments: (1) dolutegravir alone, fasting; (2) dolutegravir with calcium carbonate or ferrous fumarate, fasting; (3) dolutegravir with calcium carbonate or ferrous fumarate with a moderate-fat meal; (4) dolutegravir administered 2 hours before calcium carbonate or ferrous fumarate, fasting. Plasma dolutegravir AUC(0-∞), Cmax , and C24 were reduced by 39%, 37%, and 39%, respectively, when co-administered with calcium carbonate while fasting and were reduced by 54%, 57%, and 56%, respectively, when co-administered with ferrous fumarate while fasting. Dolutegravir administration 2 hours before calcium or iron supplement administration (fasted), as well as administration with a meal, counteracted the effect. Dolutegravir and calcium or iron supplements can be co-administered if taken with a meal. Under fasted conditions, dolutegravir should be administered 2 hours before or 6 hours after calcium or iron supplements. PMID:25449994

  10. Safety Evaluation of CNS Administered Biologics-Study Design, Data Interpretation, and Translation to the Clinic.

    PubMed

    Vuillemenot, Brian R; Korte, Sven; Wright, Teresa L; Adams, Eric L; Boyd, Robert B; Butt, Mark T

    2016-07-01

    Many central nervous system (CNS) diseases are inadequately treated by systemically administered therapies due to the blood brain barrier (BBB), which prevents achieving adequate drug concentrations at sites of action. Due to the increasing prevalence of neurodegenerative diseases and the inability of most systemically administered therapies to cross the BBB, direct CNS delivery will likely play an increasing role in treatment. Administration of large molecules, cells, viral vectors, oligonucleotides, and other novel therapies directly to the CNS via the subarachnoid space, ventricular system, or parenchyma overcomes this obstacle. Clinical experience with direct CNS administration of small molecule therapies suggests that this approach may be efficacious for the treatment of neurodegenerative disorders using biological therapies. Risks of administration into the brain tissue or cerebrospinal fluid include local damage from implantation of the delivery system and/or administration of the therapeutic and reactions affecting the CNS. Preclinical safety studies on CNS administered compounds must differentiate between the effects of the test article, the delivery device, and/or the vehicle, and assess exacerbations of reactions due to combinations of effects. Animal models characterized for safety assessment of CNS administered therapeutics have enabled human trials, but interpretation can be challenging. This manuscript outlines the challenges of preclinical intrathecal/intracerebroventricular/intraparenchymal studies, evaluation of results, considerations for special endpoints, and translation of preclinical findings to enable first-in-human trials. Recommendations will be made based on the authors' collective experience with conducting these studies to enable clinical development of CNS-administered biologics. PMID:27354708

  11. 43 CFR 5.1 - Areas administered by U.S. Fish and Wildlife Service or National Park Service.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Areas administered by U.S. Fish and... JURISDICTION OF THE DEPARTMENT OF THE INTERIOR § 5.1 Areas administered by U.S. Fish and Wildlife Service or... track made on any area administered by the U.S. Fish and Wildlife Service or the National Park...

  12. 43 CFR 5.1 - Areas administered by U.S. Fish and Wildlife Service or National Park Service.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 1 2011-10-01 2011-10-01 false Areas administered by U.S. Fish and... JURISDICTION OF THE DEPARTMENT OF THE INTERIOR § 5.1 Areas administered by U.S. Fish and Wildlife Service or... track made on any area administered by the U.S. Fish and Wildlife Service or the National Park...

  13. 43 CFR 5.1 - Areas administered by U.S. Fish and Wildlife Service or National Park Service.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 43 Public Lands: Interior 1 2012-10-01 2011-10-01 true Areas administered by U.S. Fish and... JURISDICTION OF THE DEPARTMENT OF THE INTERIOR § 5.1 Areas administered by U.S. Fish and Wildlife Service or... track made on any area administered by the U.S. Fish and Wildlife Service or the National Park...

  14. Genetic diversity of the Plasmodium falciparum apical membrane antigen I gene in parasite population from the China-Myanmar border area.

    PubMed

    Zhu, Xiaotong; Zhao, Zhenjun; Feng, Yonghui; Li, Peipei; Liu, Fei; Liu, Jun; Yang, Zhaoqing; Yan, Guiyun; Fan, Qi; Cao, Yaming; Cui, Liwang

    2016-04-01

    To investigate the genetic diversity of the Plasmodium falciparum apical membrane antigen 1 (PfAMA1) gene in Southeast Asia, we determined PfAMA1 sequences from 135 field isolates collected from the China-Myanmar border area and compared them with 956 publically available PfAMA1 sequences from seven global P. falciparum populations. This analysis revealed high genetic diversity of PfAMA1 in global P. falciparum populations with a total of 229 haplotypes identified. The genetic diversity of PfAMA1 gene from the China-Myanmar border is not evenly distributed in the different domains of this gene. Sequence diversity in PfAMA1 from the China-Myanmar border is lower than that observed in Thai, African and Oceanian populations, but higher than that in the South American population. This appeared to correlate well with the levels of endemicity of different malaria-endemic regions, where hyperendemic regions favor genetic cross of the parasite isolates and generation of higher genetic diversity. Neutrality tests show significant departure from neutrality in the entire ectodomain and Domain I of PfAMA1 in the China-Myanmar border parasite population. We found evidence supporting a substantial continent-wise genetic structure among P. falciparum populations, with the highest genetic differentiation detected between the China-Myanmar border and the South American populations. Whereas no alleles were unique to a specific region, there were considerable geographical differences in major alleles and their frequencies, highlighting further necessity to include more PfAMA1 alleles in vaccine designs. PMID:26825252

  15. Comparative Discussion on Psychophysiological Effect of Self-administered Facial Massage by Treatment Method

    NASA Astrophysics Data System (ADS)

    Nozawa, Akio; Takei, Yuya

    The aim of study was to quantitatively evaluate the effects of self-administered facial massage, which was done by hand or facial roller. In this study, the psychophysiological effects of facial massage were evaluated. The central nerves system and the autonomic nervous system were administered to evaluate physiological system. The central nerves system was assessed by Electroencephalogram (EEG). The autonomic nervous system were assessed by peripheral skin temperature(PST) and heart rate variability (HRV) with spectral analysis. In the spectral analysis of HRV, the high-frequency components (HF) were evaluated. State-Trait Anxiety Inventory (STAI), Profile of Mood Status (POMS) and subjective sensory amount with Visual Analog Scale (VAS) were administered to evaluate psychological status. These results suggest that kept brain activity and had strong effects on stress alleviation.

  16. Enhanced glucose tolerance by intravascularly administered piceatannol in freely moving healthy rats.

    PubMed

    Oritani, Yukihiro; Okitsu, Teru; Nishimura, Eisaku; Sai, Masahiko; Ito, Tatsuhiko; Takeuchi, Shoji

    2016-02-12

    Piceatannol is a phytochemical in the seeds of passion fruit that has a hypoglycemic effect when orally administered. To elucidate the contribution of intact and metabolites of piceatannol after gastro-intestinal absorption to hypoglycemic effect, we examined the influence of piceatannol and isorhapontigenin on blood glucose concentrations during fasting and glucose tolerance tests by administering them intravascularly to freely moving healthy rats. We found that intravascularly administered piceatannol reduced the blood glucose concentrations during both fasting and glucose tolerance tests, but isorhapontigenin did not during either of them. Furthermore, we found that piceatannol increased the insulinogenic index during glucose tolerance tests and that piceatannol had no influence on insulin sensitivity by performing hyperinsulinemic euglycemic clamping tests. These results suggest that piceatannol orally intaken may enhance glucose tolerance by the effect of intact piceatannol through enhanced early-phase secretion of insulin. Therefore, oral intake of piceatannol might contribute to proper control of postprandial glycemic excursions in healthy subjects. PMID:26773506

  17. [Technical specifications for rational clinical use of parenterally administered Chinese medicine (draft version for comments)].

    PubMed

    Xie, Yan-Ming; Li, Ming-Quan; Zhang, Yun-Ling; Ma, Rong; Xian, Shao-Xiang; Liu, Jian; Li, Su-Yun; Zhao, Yu-Bin

    2013-09-01

    The regulations on basic clinical use of parenterally administered Chinese medicine, issued jointly in 2008, by the ministry of health (MOH), China food and drug administration (SFDA) and the state administration of traditional Chinese medicine (SATCM). Integrating actual clinical practice, these presented doctors and nurses with detailed specifications for the safe use of parenterally administered Chinese medicine. The regulations emphasize the use of Chinese medicine pattern differentiation, use in strict accordance with instructions, and they prohibit use combined with other medicines. The emphasis of the regulations are practicality and operability, and provide meaningful guidance to doctors and nurses for the rational and safe use of parenterally administered Chinese medicine, to reduce adverse reactions/adverse events caused by improper use. PMID:24471306

  18. Comparing administered and market-based water allocation systems using an agent-based modeling approach

    NASA Astrophysics Data System (ADS)

    Zhao, J.; Cai, X.; Wang, Z.

    2009-12-01

    It also has been well recognized that market-based systems can have significant advantages over administered systems for water allocation. However there are not many successful water markets around the world yet and administered systems exist commonly in water allocation management practice. This paradox has been under discussion for decades and still calls for attention for both research and practice. This paper explores some insights for the paradox and tries to address why market systems have not been widely implemented for water allocation. Adopting the theory of agent-based system we develop a consistent analytical model to interpret both systems. First we derive some theorems based on the analytical model, with respect to the necessary conditions for economic efficiency of water allocation. Following that the agent-based model is used to illustrate the coherence and difference between administered and market-based systems. The two systems are compared from three aspects: 1) the driving forces acting on the system state, 2) system efficiency, and 3) equity. Regarding economic efficiency, penalty on the violation of water use permits (or rights) under an administered system can lead to system-wide economic efficiency, as well as being acceptable by some agents, which follows the theory of the so-call rational violation. Ideal equity will be realized if penalty equals incentive with an administered system and if transaction costs are zero with a market system. The performances of both agents and the over system are explained with an administered system and market system, respectively. The performances of agents are subject to different mechanisms of interactions between agents under the two systems. The system emergency (i.e., system benefit, equilibrium market price, etc), resulting from the performance at the agent level, reflects the different mechanism of the two systems, the “invisible hand” with the market system and administrative measures (penalty

  19. BIOAVAILABILITY AND BIOLOGICAL RESPONSE OF PBDES ADMINISTERED TO RATS IN HOUSEHOLD DUST

    EPA Science Inventory

    Abstract Household dust has recently been implicated as a source of PBDE exposure. This study investigated the bioavailability of PBDEs in house dust administered through the diet as compared to PBDEs in oil via the diet. PBDEs in household dust were just as bioavailabl...

  20. 24 CFR 570.497 - Condition of State election to administer State CDBG Program.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 24 Housing and Urban Development 3 2013-04-01 2013-04-01 false Condition of State election to administer State CDBG Program. 570.497 Section 570.497 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued) OFFICE OF ASSISTANT SECRETARY FOR COMMUNITY PLANNING...

  1. 24 CFR 570.497 - Condition of State election to administer State CDBG Program.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 24 Housing and Urban Development 3 2014-04-01 2013-04-01 true Condition of State election to administer State CDBG Program. 570.497 Section 570.497 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued) OFFICE OF ASSISTANT SECRETARY FOR COMMUNITY PLANNING...

  2. 43 CFR 420.25 - Reclamation lands administered by other agencies.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... for management of Reclamation lands for recreation purposes. Specifically: (1) Reclamation lands managed by the National Park Service, the Bureau of Sport Fisheries and Wildlife, the Bureau of Land Management, the Forest Service, and other Federal agencies will be administered in accordance...

  3. 40 CFR 282.83 - North Carolina State-Administered Program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.83 North... administered by the North Carolina Department of Environment and Natural Resources, Division of Waste... RCRA, 42 U.S.C. 6991c, and 40 CFR part 281, subpart E. If North Carolina obtains approval for...

  4. 40 CFR 282.83 - North Carolina State-Administered Program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.83 North... administered by the North Carolina Department of Environment and Natural Resources, Division of Waste... RCRA, 42 U.S.C. 6991c, and 40 CFR part 281, subpart E. If North Carolina obtains approval for...

  5. 21 CFR 1306.07 - Administering or dispensing of narcotic drugs.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 9 2013-04-01 2013-04-01 false Administering or dispensing of narcotic drugs. 1306.07 Section 1306.07 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE... qualifications, security, records, and unsupervised use of the drugs pursuant to the Act. (b) Nothing in...

  6. 32 CFR 37.120 - Can my organization award or administer TIAs?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 1 2010-07-01 2010-07-01 false Can my organization award or administer TIAs? 37.120 Section 37.120 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DoD GRANT AND AGREEMENT REGULATIONS TECHNOLOGY INVESTMENT AGREEMENTS General § 37.120 Can my organization...

  7. Cataloging, Processing, Administering AV Materials. A Model for Wisconsin Schools. Revised, 1974.

    ERIC Educational Resources Information Center

    Little, Robert David, Ed.; And Others

    The Wisconsin Association of School Librarians has produced a manual for standardized processing of all nonprint media, based on two principles: (1) the media should be centralized, organized, and administered for maximum access; and (2) content is more important than form. Definitions, cataloging, processing, housing, circulation, and care are…

  8. 50 CFR 86.115 - How should I administer the survey?

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 50 Wildlife and Fisheries 9 2012-10-01 2012-10-01 false How should I administer the survey? 86.115 Section 86.115 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM BOATING INFRASTRUCTURE GRANT...

  9. 20 CFR 641.610 - How are section 502(e) activities administered?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false How are section 502(e) activities administered? 641.610 Section 641.610 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR PROVISIONS GOVERNING THE SENIOR COMMUNITY SERVICE EMPLOYMENT PROGRAM Private Sector Training Projects Under Section 502(e) of the OAA §...

  10. Employing Computer-Administered Exams in General Psychology: Student Anxiety and Expectations

    ERIC Educational Resources Information Center

    Schult, Carolyn A.; McIntosh, John L.

    2004-01-01

    Computer-administered exams offer many advantages, but instructors may be reluctant to use them due to concerns that computer anxiety may increase student test anxiety. Introductory psychology students (N = 265) completed surveys prior to their first exam about their anxiety related to the upcoming exam, computers in general, and taking exams on…

  11. 45 CFR 1180.52 - The grantee administers or supervises the grant.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 3 2011-10-01 2011-10-01 false The grantee administers or supervises the grant. 1180.52 Section 1180.52 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL FOUNDATION ON THE ARTS AND THE HUMANITIES INSTITUTE OF MUSEUM AND LIBRARY SERVICES GRANTS REGULATIONS...

  12. 45 CFR 1180.52 - The grantee administers or supervises the grant.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false The grantee administers or supervises the grant. 1180.52 Section 1180.52 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL FOUNDATION ON THE ARTS AND THE HUMANITIES INSTITUTE OF MUSEUM AND LIBRARY SERVICES GRANTS REGULATIONS...

  13. 40 CFR 272.2101 - South Dakota State-Administered Program: Final Authorization.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 28 2012-07-01 2012-07-01 false South Dakota State-Administered Program: Final Authorization. 272.2101 Section 272.2101 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) APPROVED STATE HAZARDOUS WASTE MANAGEMENT PROGRAMS South Dakota § 272.2101 South...

  14. 40 CFR 272.1751 - North Dakota State-administered program: Final authorization.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 28 2012-07-01 2012-07-01 false North Dakota State-administered program: Final authorization. 272.1751 Section 272.1751 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) APPROVED STATE HAZARDOUS WASTE MANAGEMENT PROGRAMS North Dakota § 272.1751 North...

  15. 40 CFR 272.1601 - New Mexico State-Administered Program: Final Authorization.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 28 2012-07-01 2012-07-01 false New Mexico State-Administered Program: Final Authorization. 272.1601 Section 272.1601 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) APPROVED STATE HAZARDOUS WASTE MANAGEMENT PROGRAMS New Mexico § 272.1601 New Mexico...

  16. 24 CFR 570.497 - Condition of State election to administer State CDBG Program.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 3 2010-04-01 2010-04-01 false Condition of State election to administer State CDBG Program. 570.497 Section 570.497 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued) OFFICE OF ASSISTANT SECRETARY FOR COMMUNITY PLANNING...

  17. 24 CFR 570.497 - Condition of State election to administer State CDBG Program.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 3 2011-04-01 2010-04-01 true Condition of State election to administer State CDBG Program. 570.497 Section 570.497 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued) OFFICE OF ASSISTANT SECRETARY FOR COMMUNITY PLANNING...

  18. Preliminary Reliability and Validity of the Clinician-Administered PTSD Scale for Schizophrenia

    ERIC Educational Resources Information Center

    Gearon, Jean S.; Bellack, Alan S.; Tenhula, Wendy N.

    2004-01-01

    This study provides preliminary psychometric support for a version of the Clinician-Administered Posttraumatic Stress Disorder (PTSD) Scale (CAPS; D. D. Blake et al., 1990) adapted for use with patients with schizophrenia (CAPS-S; J. S. Gearon. S. Thomas-Lohrman, & A. S. Bellack, 2001). Nineteen women with schizophrenia and co-occurring illicit…

  19. 45 CFR 400.65 - Continuation of a publicly-administered RCA program.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... program. 400.65 Section 400.65 Public Welfare Regulations Relating to Public Welfare OFFICE OF REFUGEE RESETTLEMENT, ADMINISTRATION FOR CHILDREN AND FAMILIES, DEPARTMENT OF HEALTH AND HUMAN SERVICES REFUGEE RESETTLEMENT PROGRAM Refugee Cash Assistance § 400.65 Continuation of a publicly-administered RCA...

  20. 45 CFR 400.65 - Continuation of a publicly-administered RCA program.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    .... 400.65 Section 400.65 Public Welfare Regulations Relating to Public Welfare OFFICE OF REFUGEE RESETTLEMENT, ADMINISTRATION FOR CHILDREN AND FAMILIES, DEPARTMENT OF HEALTH AND HUMAN SERVICES REFUGEE RESETTLEMENT PROGRAM Refugee Cash Assistance § 400.65 Continuation of a publicly-administered RCA...

  1. 20 CFR 408.1220 - How do we pay Federally administered State recognition payments?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false How do we pay Federally administered State recognition payments? 408.1220 Section 408.1220 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SPECIAL BENEFITS FOR CERTAIN WORLD WAR II VETERANS Federal Administration of State Recognition Payments §...

  2. 45 CFR 1180.52 - The grantee administers or supervises the grant.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 45 Public Welfare 3 2012-10-01 2012-10-01 false The grantee administers or supervises the grant. 1180.52 Section 1180.52 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL FOUNDATION ON THE ARTS AND THE HUMANITIES INSTITUTE OF MUSEUM AND LIBRARY SERVICES GRANTS REGULATIONS...

  3. 45 CFR 1180.52 - The grantee administers or supervises the grant.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 45 Public Welfare 3 2013-10-01 2013-10-01 false The grantee administers or supervises the grant. 1180.52 Section 1180.52 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL FOUNDATION ON THE ARTS AND THE HUMANITIES INSTITUTE OF MUSEUM AND LIBRARY SERVICES GRANTS REGULATIONS...

  4. 45 CFR 1180.52 - The grantee administers or supervises the grant.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 45 Public Welfare 3 2014-10-01 2014-10-01 false The grantee administers or supervises the grant. 1180.52 Section 1180.52 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL FOUNDATION ON THE ARTS AND THE HUMANITIES INSTITUTE OF MUSEUM AND LIBRARY SERVICES GRANTS REGULATIONS...

  5. 40 CFR 147.2404 - EPA-administered program-Colville Reservation.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... CFR part 124, 144 and 146 and any additional requirements set forth in the remainder of this subpart... Reservation. 147.2404 Section 147.2404 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Washington § 147.2404 EPA-administered program—Colville Reservation. (a) The UIC program for the...

  6. 22 CFR 196.2 - How is the Fellowship Program administered?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false How is the Fellowship Program administered? 196.2 Section 196.2 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL COMMERCIAL ARBITRATION THOMAS R. PICKERING FOREIGN AFFAIRS/GRADUATE FOREIGN AFFAIRS FELLOWSHIP PROGRAM § 196.2 How is the Fellowship...

  7. 22 CFR 196.2 - How is the Fellowship Program administered?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false How is the Fellowship Program administered? 196.2 Section 196.2 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL COMMERCIAL ARBITRATION THOMAS R. PICKERING FOREIGN AFFAIRS/GRADUATE FOREIGN AFFAIRS FELLOWSHIP PROGRAM § 196.2 How is the Fellowship...

  8. 22 CFR 196.2 - How is the Fellowship Program administered?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false How is the Fellowship Program administered? 196.2 Section 196.2 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL COMMERCIAL ARBITRATION THOMAS R. PICKERING FOREIGN AFFAIRS/GRADUATE FOREIGN AFFAIRS FELLOWSHIP PROGRAM § 196.2 How is the Fellowship...

  9. 22 CFR 196.2 - How is the Fellowship Program administered?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false How is the Fellowship Program administered? 196.2 Section 196.2 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL COMMERCIAL ARBITRATION THOMAS R. PICKERING FOREIGN AFFAIRS/GRADUATE FOREIGN AFFAIRS FELLOWSHIP PROGRAM § 196.2 How is the Fellowship...

  10. 22 CFR 196.2 - How is the Fellowship Program administered?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false How is the Fellowship Program administered? 196.2 Section 196.2 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL COMMERCIAL ARBITRATION THOMAS R. PICKERING FOREIGN AFFAIRS/GRADUATE FOREIGN AFFAIRS FELLOWSHIP PROGRAM § 196.2 How is the Fellowship...

  11. Psychomotor and Motor Speed in Power Athletes Self-Administering Testosterone and Anabolic Steroids.

    ERIC Educational Resources Information Center

    Era, Pertti; And Others

    1988-01-01

    Self-administered testosterone and anabolic steroids resulted in insignificant improvement in psychomotor and motor speed tests of power athletes. This study is part of a larger study on the effects of such drugs on endocrinology, metabolism and neuromuscular functions. Methodolgy and results are discussed. (Author/JL)

  12. 42 CFR 447.520 - FFP: Conditions relating to physician-administered drugs.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 4 2011-10-01 2011-10-01 false FFP: Conditions relating to physician-administered drugs. 447.520 Section 447.520 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL ASSISTANCE PROGRAMS PAYMENTS FOR SERVICES Payment for Drugs § 447.520 FFP: Conditions relating...

  13. 40 CFR 147.1800 - State-administered program-Class II wells.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., Environmental Law Section, for the Attorney General of Ohio, September 30, 1982. (d) The Program Description and... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program-Class II wells. 147.1800 Section 147.1800 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY...

  14. Case Management Agency Systems of Administering Long-Term Care: Evidence from the Channeling Demonstration.

    ERIC Educational Resources Information Center

    Kemper, Peter

    1990-01-01

    Examines what was learned from channeling demonstration about potential of case management agency systems for administering home care benefits. Considers both advantages (substitution of lower cost for higher cost services, negotiation of lower prices for services, quality assurance) and disadvantages (difficulty controlling participation rates,…

  15. 20 CFR 664.610 - How is the summer employment opportunities element administered?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false How is the summer employment opportunities... Opportunities § 664.610 How is the summer employment opportunities element administered? Chief elected officials... used to provide summer youth employment opportunities, these providers must be selected by awarding...

  16. 40 CFR 272.951 - Louisiana state-administered program: Final authorization.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 28 2013-07-01 2013-07-01 false Louisiana state-administered program: Final authorization. 272.951 Section 272.951 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) APPROVED STATE HAZARDOUS WASTE MANAGEMENT PROGRAMS Louisiana §...

  17. 7 CFR 46.45 - Procedure in administering section 2(5) of the Act.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Procedure in administering section 2(5) of the Act. 46.45 Section 46.45 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE MARKETING OF PERISHABLE AGRICULTURAL COMMODITIES REGULATIONS...

  18. 9 CFR 103.2 - Disposition of animals administered experimental biological products or live organisms.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... experimental biological products or live organisms. 103.2 Section 103.2 Animals and Animal Products ANIMAL AND... PRODUCTS; ORGANISMS AND VECTORS EXPERIMENTAL PRODUCTION, DISTRIBUTION, AND EVALUATION OF BIOLOGICAL PRODUCTS PRIOR TO LICENSING § 103.2 Disposition of animals administered experimental biological products...

  19. 9 CFR 103.2 - Disposition of animals administered experimental biological products or live organisms.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... experimental biological products or live organisms. 103.2 Section 103.2 Animals and Animal Products ANIMAL AND... PRODUCTS; ORGANISMS AND VECTORS EXPERIMENTAL PRODUCTION, DISTRIBUTION, AND EVALUATION OF BIOLOGICAL PRODUCTS PRIOR TO LICENSING § 103.2 Disposition of animals administered experimental biological products...

  20. 9 CFR 103.2 - Disposition of animals administered experimental biological products or live organisms.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... experimental biological products or live organisms. 103.2 Section 103.2 Animals and Animal Products ANIMAL AND... PRODUCTS; ORGANISMS AND VECTORS EXPERIMENTAL PRODUCTION, DISTRIBUTION, AND EVALUATION OF BIOLOGICAL PRODUCTS PRIOR TO LICENSING § 103.2 Disposition of animals administered experimental biological products...

  1. 24 CFR 982.160 - HUD determination to administer a local program.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false HUD determination to administer a local program. 982.160 Section 982.160 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued) OFFICE OF ASSISTANT SECRETARY FOR PUBLIC AND INDIAN HOUSING, DEPARTMENT...

  2. 40 CFR 147.2001 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... UIC program requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth.... 147.2001 Section 147.2001 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER... Island § 147.2001 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes...

  3. 40 CFR 147.2001 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... UIC program requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth.... 147.2001 Section 147.2001 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER... Island § 147.2001 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes...

  4. The Impact of Schools Self-Administering Substance Abuse Surveys: An Evaluation

    ERIC Educational Resources Information Center

    Van Valey, Thomas L.; Hartmann, David; Post, William

    2005-01-01

    The literature suggests that administering drug surveys to public school students is best done by persons outside of the school system (or at least unfamiliar to the students). This is the approach used by the long-time "Monitoring the Future" project. Because of the increased costs that administration by outside research associates requires (both…

  5. Should Creativity Tests Be Administered under Testlike Conditions? An Empirical Study of Three Alternative Conditions.

    ERIC Educational Resources Information Center

    Hattie, John

    1980-01-01

    Three conditions for administering creativity tests by Torrance and by Wallach and Kogan were compared: (1) untimed, gamelike; (2) conventional testlike; and (3) administration of measures under testlike conditions on two adjacent days, using the second testing as the predictor. The conventional testlike condition seems optimal. (Author/CP)

  6. 50 CFR 86.115 - How should I administer the survey?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 8 2011-10-01 2011-10-01 false How should I administer the survey? 86.115 Section 86.115 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM BOATING INFRASTRUCTURE GRANT (BIG) PROGRAM How States Will...

  7. 50 CFR 86.115 - How should I administer the survey?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 false How should I administer the survey? 86.115 Section 86.115 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM BOATING INFRASTRUCTURE GRANT (BIG) PROGRAM How States Will...

  8. 34 CFR 650.41 - How are institutional payments to be administered?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Consumer Price Index for the previous calendar year. (b) If the institution of higher education charges and... 34 Education 3 2010-07-01 2010-07-01 false How are institutional payments to be administered? 650.41 Section 650.41 Education Regulations of the Offices of the Department of Education...

  9. Validity of a Self-Administered 3-Day Physical Activity Recall in Young Adults

    ERIC Educational Resources Information Center

    Han, Jennifer L.; Dinger, Mary K.

    2009-01-01

    Background: Most physical activity recall questionnaires assess activity over a 7-day period. However, questionnaires have been validated in adolescents and adults using shorter recall timeframes. Purpose: The purpose of this study was to assess the validity of a self-administered 3-day physical activity recall instrument (3DR) in young adults.…

  10. Stress Management for Special Educators: The Self-Administered Tool for Awareness and Relaxation (STAR)

    ERIC Educational Resources Information Center

    Williams, Krista; Poel, Elissa Wolfe

    2006-01-01

    The Self-Administered Tool for Awareness and Relaxation (STAR) is a stress management strategy designed to facilitate awareness of the physical, mental, emotional, and physiological effects of stress through the interconnectedness of the brain, body, and emotions. The purpose of this article is to present a stress-management model for teachers,…

  11. 41 CFR 302-14.100 - How should we administer our home marketing incentive payment program?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 41 Public Contracts and Property Management 4 2011-07-01 2011-07-01 false How should we administer our home marketing incentive payment program? 302-14.100 Section 302-14.100 Public Contracts and Property Management Federal Travel Regulation System RELOCATION ALLOWANCES RESIDENCE TRANSACTION...

  12. 41 CFR 302-14.100 - How should we administer our home marketing incentive payment program?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 41 Public Contracts and Property Management 4 2010-07-01 2010-07-01 false How should we administer our home marketing incentive payment program? 302-14.100 Section 302-14.100 Public Contracts and Property Management Federal Travel Regulation System RELOCATION ALLOWANCES RESIDENCE TRANSACTION...

  13. 41 CFR 302-14.100 - How should we administer our home marketing incentive payment program?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 41 Public Contracts and Property Management 4 2012-07-01 2012-07-01 false How should we administer our home marketing incentive payment program? 302-14.100 Section 302-14.100 Public Contracts and Property Management Federal Travel Regulation System RELOCATION ALLOWANCES RESIDENCE TRANSACTION...

  14. 41 CFR 302-14.100 - How should we administer our home marketing incentive payment program?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 41 Public Contracts and Property Management 4 2013-07-01 2012-07-01 true How should we administer our home marketing incentive payment program? 302-14.100 Section 302-14.100 Public Contracts and Property Management Federal Travel Regulation System RELOCATION ALLOWANCES RESIDENCE TRANSACTION...

  15. 41 CFR 302-14.100 - How should we administer our home marketing incentive payment program?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 41 Public Contracts and Property Management 4 2014-07-01 2014-07-01 false How should we administer our home marketing incentive payment program? 302-14.100 Section 302-14.100 Public Contracts and Property Management Federal Travel Regulation System RELOCATION ALLOWANCES RESIDENCE TRANSACTION...

  16. Depression in People with Intellectual Disability: An Evaluation of a Staff-Administered Treatment Program

    ERIC Educational Resources Information Center

    McGillivray, Jane A.; McCabe, Marita P.; Kershaw, Mavis M.

    2008-01-01

    The prevalence of co-morbid depression in people with intellectual disability (ID) provides a strong rationale for the early identification and treatment of individuals at risk. The aim of this study was to evaluate a staff-administered group CBT program for the treatment of depression in people with mild ID. A sample of 13 staff employed at two…

  17. 24 CFR 511.50 - State election to administer a rental rehabilitation program.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... DEVELOPMENT, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT SLUM CLEARANCE AND URBAN RENEWAL RENTAL REHABILITATON... 24 Housing and Urban Development 3 2011-04-01 2010-04-01 true State election to administer a rental rehabilitation program. 511.50 Section 511.50 Housing and Urban Development Regulations...

  18. 24 CFR 511.50 - State election to administer a rental rehabilitation program.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... DEVELOPMENT, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT SLUM CLEARANCE AND URBAN RENEWAL RENTAL... 24 Housing and Urban Development 3 2012-04-01 2012-04-01 false State election to administer a rental rehabilitation program. 511.50 Section 511.50 Housing and Urban Development Regulations...

  19. 24 CFR 511.50 - State election to administer a rental rehabilitation program.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... DEVELOPMENT, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT SLUM CLEARANCE AND URBAN RENEWAL RENTAL... 24 Housing and Urban Development 3 2013-04-01 2013-04-01 false State election to administer a rental rehabilitation program. 511.50 Section 511.50 Housing and Urban Development Regulations...

  20. 24 CFR 511.50 - State election to administer a rental rehabilitation program.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... DEVELOPMENT, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT SLUM CLEARANCE AND URBAN RENEWAL RENTAL... 24 Housing and Urban Development 3 2014-04-01 2013-04-01 true State election to administer a rental rehabilitation program. 511.50 Section 511.50 Housing and Urban Development Regulations...