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Sample records for antigen-1 ama-1 administered

  1. Plasmodium vivax: genetic diversity of the apical membrane antigen-1 (AMA-1) in isolates from India.

    PubMed

    Rajesh, Vidya; Elamaran, M; Vidya, S; Gowrishankar, M; Kochar, Dhanpat; Das, Ashis

    2007-07-01

    Malaria parasites exhibit sequence diversity for a number of stage specific antigens. Several studies have proved that apical membrane antigen-1 (AMA-1) is an effective target for eliciting a protective immune response in humans and other experimental animals. We have investigated the sequence variation in Plasmodium vivax AMA-1 (Pv AMA-1) from different Indian isolates. This is the first study of its kind for the nearly full length Pv AMA-1 from India. Our analysis reveals greater degree of genetic diversity in Pv AMA-1 than reported so far and identifies five novel haplotypes. This is significant to establish the antigenic repertoire of isolates in a malaria endemic country like India. PMID:17336299

  2. Polymorphism at the apical membrane antigen 1 gene (AMA1) of the malaria parasite Plasmodium falciparum in a Vietnamese population.

    PubMed

    Quang, Nguyen Duc; Hoa, Phan Thi Phuong; Tuan, Mai Sy; Viet, Nguyen Xuan; Jalloh, Amadu; Matsuoka, Hiroyuki

    2009-06-01

    The patterns of molecular evolution of the most diverse region of the apical membrane antigen 1 (AMA1) gene in Plasmodium falciparum from a Vietnamese subpopulation (Bao Loc) were investigated. Within the Bao Loc population, the sequenced gene region showed relatively high allelic and nucleotide diversity (0.985 and 0.02694, respectively). Further, the level of population recombination was substantial, resulting in a significant decay of linkage disequilibrium along the gene region. The results suggest that AMA1 is a useful genetic marker for studying the relationships between adaptation of parasite populations (to the human host immune system) and malaria epidemiology.

  3. Genetic diversity and natural selection at the domain I of apical membrane antigen-1 (AMA-1) of Plasmodium falciparum in isolates from Iran.

    PubMed

    Mardani, Ahmad; Keshavarz, Hossein; Heidari, Aliehsan; Hajjaran, Homa; Raeisi, Ahmad; Khorramizadeh, Mohammad Reza

    2012-04-01

    The apical membrane antigen-1 (AMA-1) of Plasmodium falciparum is a prime malaria asexual blood-stage vaccine candidate. Antigenic variation is one of the main obstacles in the development of a universal effective malaria vaccine. The extracellular region of P. falciparum AMA-1 (PfAMA-1) consists of three domains (I-III), of which the domain I is the most diverse region of this antigen. The objective of our study was to investigate and analyze the extent of genetic diversity and the effectiveness of natural selection at the AMA-1 domain I of P. falciparum in isolates from Iran. A fragment of ama-1 gene spanning domain I was amplified by nested PCR from 48 P. falciparum isolates collected from two major malaria endemic areas of Iran during 2009 to August 2010 and sequenced. Genetic polymorphism and statistical analyses were performed using DnaSP and MEGA software packages. Analysis of intrapopulation diversity revealed relatively high nucleotide and haplotype diversity at the PfAMA-1 domain I of Iranian isolates. Neutrality tests provided strong evidence of positive natural selection acting on the sequenced gene region. The findings also demonstrated that, in addition to natural selection, intragenic recombination may contribute to the diversity observed at the domain I. The results obtained will have significant implications in the design and the development of an AMA-1-based vaccine against falciparum malaria.

  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.

  5. 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

  6. 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.

  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. Genetic polymorphism and effect of natural selection at domain I of apical membrane antigen-1 (AMA-1) in Plasmodium vivax isolates from Myanmar.

    PubMed

    Moon, Sung-Ung; Na, Byoung-Kuk; Kang, Jung-Mi; Kim, Jung-Yeon; Cho, Shin-Hyeong; Park, Yun-Kyu; Sohn, Woon-Mok; Lin, Khin; Kim, Tong-Soo

    2010-05-01

    Malaria is endemic or hypoendemic in Myanmar and the country still contributes to the high level of malaria deaths in South-East Asia. Although information on the nature and extent of population diversity within malaria parasites in the country is essential not only for understanding the epidemic situation but also to establish a proper control strategy, very little data is currently available on the extent of genetic polymorphisms of the malaria parasites in Myanmar. In this study, we analyzed the genetic polymorphism and natural selection at domain I of the apical membrane antigen-1 (AMA-1) among Plasmodium vivax Myanmar isolates. A total of 34 distinguishable haplotypes were identified among the 76 isolates sequenced. Comparison with the previously available PvAMA-1 sequences in the GenBank database revealed that 21 of them were new haplotypes that have never been reported till date. The difference between the rate of nonsynonymous (dN) and synonymous (dS) mutations was positive (dN-dS, 0.013+/-0.005), suggesting the domain I is under positive natural selection. The Tajima's D statistics was found to be -0.74652, suggesting that the gene has evolved under population size expansion and/or positive selection. The minimum recombination events were also high, indicating that recombination may occur within the domain I resulting in allelic diversity of PvAMA-1. Our results collectively suggest that PvAMA-1 displays high genetic polymorphism among Myanmar P. vivax isolates with highly diversifying selection at domain I. These results have significant implications in understanding the nature of P. vivax population circulating in Myanmar as well as providing useful information for malaria vaccine development based on this antigen.

  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. Not a Simple Tether: Binding of Toxoplasma gondii AMA1 to RON2 during Invasion Protects AMA1 from Rhomboid-Mediated Cleavage and Leads to Dephosphorylation of Its Cytosolic Tail

    PubMed Central

    Krishnamurthy, Shruthi; Deng, Bin; del Rio, Roxana; Buchholz, Kerry R.; Treeck, Moritz; Urban, Siniša; Boothroyd, John; Lam, Ying-Wai

    2016-01-01

    ABSTRACT Apical membrane antigen 1 (AMA1) is a receptor protein on the surface of Toxoplasma gondii that plays a critical role in host cell invasion. The ligand to which T. gondii AMA1 (TgAMA1) binds, TgRON2, is secreted into the host cell membrane by the parasite during the early stages of invasion. The TgAMA1-TgRON2 complex forms the core of the “moving junction,” a ring-shaped zone of tight contact between the parasite and host cell membranes, through which the parasite pushes itself during invasion. Paradoxically, the parasite also expresses rhomboid proteases that constitutively cleave the TgAMA1 transmembrane domain. How can TgAMA1 function effectively in host cell binding if its extracellular domain is constantly shed from the parasite surface? We show here that when TgAMA1 binds the domain 3 (D3) peptide of TgRON2, its susceptibility to cleavage by rhomboid protease(s) is greatly reduced. This likely serves to maintain parasite-host cell binding at the moving junction, a hypothesis supported by data showing that parasites expressing a hypercleavable version of TgAMA1 invade less efficiently than wild-type parasites do. Treatment of parasites with the D3 peptide was also found to reduce phosphorylation of S527 on the cytoplasmic tail of TgAMA1, and parasites expressing a phosphomimetic S527D allele of TgAMA1 showed an invasion defect. Taken together, these data suggest that TgAMA1-TgRON2 interaction at the moving junction protects TgAMA1 molecules that are actively engaged in host cell penetration from rhomboid-mediated cleavage and generates an outside-in signal that leads to dephosphorylation of the TgAMA1 cytosolic tail. Both of these effects are required for maximally efficient host cell invasion. PMID:27624124

  11. 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

  12. 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

  13. 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

  14. [Humoral immune anti-Plasmodium falciparum AMA1 and MSP1 response in two ethnic groups living in sympatry in Mali].

    PubMed

    Dolo, A; Coulibaly, M; Maïga, B; Daou, M; Arama, C; Troye-Blomberg, M; Doumbo, O

    2012-12-01

    Fulani of Mali are known for their lower susceptibility to Plasmodium falciparum malaria than their neighbours, the Dogon, despite similar transmission conditions. However, the mechanisms underlying these differences are poorly understood, particularly those concerning antigenspecific immune responses. The Apical Membrane Antigen 1 (AMA1) and the Merozoite Surface Antigen 1 (MSP1) are two malaria vaccine candidates, which play a pivotal role during the invasion of parasites into erythrocytes, and in the case of AMA1, of hepatocytes. Therefore, we analyzed the level of anti-AMA1 and anti-MSP1 antibodies (FVO and 3D7 alleles), by using ELISA (Enzyme Linked Immuno Sorbent Assay) to investigate whether there are differences between the two ethnic groups. Our results show that the splenic rate, the level of anti-AMA1 and anti-MSP1 were significantly higher in Fulani compared to Dogon; while the parasite rate was lower in Fulani group compared to Dogon. Our results suggest that the lower susceptibility of Fulani to malaria could be due to the higher specific humoral responses against AMA1 and MSP 1 in Fulani's ethnic group compared to Dogon.

  15. Long term stability of a recombinant Plasmodium falciparum AMA1 malaria vaccine adjuvanted with Montanide® ISA 720 and stabilized with Glycine

    PubMed Central

    Zhu, Daming; McClellan, Holly; Dai, Weili; Gebregeorgis, Elizabeth; Kidwell, Mary Anne; Aebig, Joan; Rausch, Kelly M.; Martin, Laura B.; Ellis, Ruth D.; Miller, Louis; Wu, Yimin

    2011-01-01

    Plasmodium falciparum apical membrane antigen 1 (AMA1) is an asexual blood-stage vaccine candidate against the malaria parasite. AMA1-C1/ISA720 refers to a mixture of recombinant AMA1 proteins representing the FVO and 3D7 alleles in 1:1 mass ratio, formulated with Montanide® ISA 720 as a water-in oil emulsion. In order to develop the AMA1-C1/ISA720 vaccine for human use, it was important to determine the shelf life of this formulation. Previously it was found 267mM glycine stabilized the proteins in Montanide® ISA 720 formulations for a short period of time at 2-8°C[25], we now test the long term stability of AMA1-C1 at 10 and 40 μg/ml formulated with Montanide® ISA 720 with 50 mM glycine as a stabilizer. Stability of AMA1-C1/ISA720 at different time points following formulation (0, 5, 12 or 18 months) was evaluated by determining the mean particle size (diameter of the mean droplet volume), total protein content by a Modified Lowry assay, identity and integrity using western blot and SDS-PAGE. Our results showed that the mean particle size of these emulsions increased over time, whereas protein content, as determined by an ELISA method using a monoclonal antibody against penta-his, decreased over time. For the 10 μg/ml AMA1-C1/ISA720 vaccine, the protein content with was 6.5 ± 2.2 μg/ml, and for the 40 μg/ml AMA1-C1/ISA720 vaccine, the protein content was only 8.2 ± 2.3 μg/ml after 18 months of storage at 2-8°C. These results suggest that the integrity of the protein was affected by long-term storage. The results of the present study indicate that the AMA1-C1/ISA720 emulsion was unstable after 12 months of storage, after which AMA1-C1 proteins were partially degraded. PMID:21440641

  16. Plasmodium falciparum: genetic polymorphism in apical membrane antigen-1 gene from Indian isolates.

    PubMed

    Rajesh, Vidya; Singamsetti, Vijay Kumar; Vidya, S; Gowrishankar, M; Elamaran, M; Tripathi, Jyotsna; Radhika, N B; Kochar, Dhanpat; Ranjan, Akash; Roy, S K; Das, Ashis

    2008-05-01

    A number of stage-specific antigens have been characterized for vaccine development against Plasmodium falciparum malaria. This study presents a comprehensive analysis of the sequence polymorphism in Plasmodium falciparum apical membrane antigen-1 (PfAMA-1) in population samples from the eastern and western parts of India. This is the first study of its kind for the nearly full length PfAMA-1 gene from these regions in India. Our observations confirmed that sequence diversity of PfAMA-1 confines only to point mutations and shows 4-8% variation as compared to the prototypes. As opposed to the previous studies on PfAMA-1, our study revealed a greater degree of polymorphism in the Domain II region of PfAMA-1 protein, though signature for diversifying selection is seen throughout the gene. Our present investigation also indicates a very high degree of variation in the reported T- and B-cell epitopes of PfAMA-1. Few noteworthy and unique observations made in this study are the substitution of Cysteine residues responsible for the disulfide bond structure of the protein and the presence of premature termination after 595 amino acids in 3 of the 13 isolates under consideration. These crucial findings add new perspectives to the future of AMA-1 research and could have major implications in establishing AMA-1 as a vaccine candidate. PMID:18343371

  17. Production, Quality Control, Stability and Pharmacotoxicity of a Malaria Vaccine Comprising Three Highly Similar PfAMA1 Protein Molecules to Overcome Antigenic Variation

    PubMed Central

    Houard, Sophie; Havelange, Nicolas; Drossard, Jürgen; Mertens, Hubert; Croon, Alexander; Kastilan, Robin; Byrne, Richard; van der Werff, Nicole; van der Eijk, Marjolein; Thomas, Alan W.; Kocken, Clemens H. M.; Remarque, Edmond J.

    2016-01-01

    Plasmodium falciparum apical membrane antigen 1 (PfAMA1) is a leading asexual blood stage vaccine candidate for malaria. In preparation for clinical trials, three Diversity Covering (DiCo) PfAMA1 ectodomain proteins, designed to overcome the intrinsic polymorphism that is present in PfAMA1, were produced under Good Manufacturing Practice (GMP) in Pichia pastoris. Using identical methodology, the 3 strains were cultivated in 70-L scale fed-batch fermentations and PfAMA1-DiCos were purified by two chromatography steps, an ultrafiltration/diafiltration procedure and size exclusion chromatography, resulting in highly pure (>95%) PfAMA1-DiCo1, PfAMA1 DiCo2 and PfAMA1 DiCo3, with final yields of 1.8, 1.9 and 1.3 gram, respectively. N-terminal determinations showed that approximately 50% of each of the proteins lost 12 residues from their N-terminus, in accordance with SDS-PAGE (2 main bands) and MS-data. Under reducing conditions a site of limited proteolytic cleavage within a disulphide bonded region became evident. The three proteins quantitatively bound to the mAb 4G2 that recognizes a conformational epitope, suggesting proper folding of the proteins. The lyophilized Drug Product (1:1:1 mixture of PfAMA1-DiCo1, DiCo2, DiCo3) fulfilled all pre-set release criteria (appearance, dissolution rate, identity, purity, protein content, moisture content, sub-visible particles, immuno-potency (after reconstitution with adjuvant), abnormal toxicity, sterility and endotoxin), was stable in accelerated and real-time stability studies at -20°C for over 24 months. When formulated with adjuvants selected for clinical phase I evaluation, the Drug Product did not show adverse effect in a repeated-dose toxicity study in rabbits. The Drug Product has entered a phase Ia/Ib clinical trial. PMID:27695087

  18. Generation of humoral immune responses to multi-allele PfAMA1 vaccines; effect of adjuvant and number of component alleles on the breadth of response.

    PubMed

    Kusi, Kwadwo A; Faber, Bart W; Riasat, Vanessa; Thomas, Alan W; Kocken, Clemens H M; Remarque, Edmond J

    2010-11-03

    There is increasing interest in multi-allele vaccines to overcome strain-specificity against polymorphic vaccine targets such as Apical Membrane Antigen 1 (AMA1). These have been shown to induce broad inhibitory antibodies in vitro and formed the basis for the design of three Diversity-Covering (DiCo) proteins with similar immunological effects. The antibodies produced are to epitopes that are shared between vaccine alleles and theoretically, increasing the number of component AMA1 alleles is expected to broaden the antibody response. A plateau effect could however impose a limit on the number of alleles needed to achieve the broadest specificity. Moreover, production cost and the vaccine formulation process would limit the number of component alleles. In this paper, we compare rabbit antibody responses elicited with multi-allele vaccines incorporating seven (three DiCos and four natural AMA1 alleles) and three (DiCo mix) antigens for gains in broadened specificity. We also investigate the effect of three adjuvant platforms on antigen specificity and antibody functionality. Our data confirms a broadened response after immunisation with DiCo mix in all three adjuvants. Higher antibody titres were elicited with either CoVaccine HT™ or Montanide ISA 51, resulting in similar in vitro inhibition (65-82%) of five out of six culture-adapted P. falciparum strains. The antigen binding specificities of elicited antibodies were also similar and independent of the adjuvant used or the number of vaccine component alleles. Thus neither the four extra antigens nor adjuvant had any observable benefits with respect to specificity broadening, although adjuvant choice influenced the absolute antibody levels and thus the extent of parasite inhibition. Our data confirms the feasibility and potential of multi-allele PfAMA1 formulations, and highlights the need for adjuvants with improved antibody potentiation properties for AMA1-based vaccines.

  19. 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

  20. 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

  1. 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

  2. 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

  3. Invasion-inhibitory antibodies elicited by immunization with Plasmodium vivax apical membrane antigen-1 expressed in Pichia pastoris yeast.

    PubMed

    Vicentin, Elaine C; Françoso, Kátia S; Rocha, Mariana V; Iourtov, Dmitri; Dos Santos, Fernanda L; Kubrusly, Flávia S; Sakauchi, Maria A; Raw, Isaias; Nosten, Francois; Rénia, Laurent; Rodrigues, Mauricio M; Russell, Bruce; Soares, Irene S

    2014-03-01

    In a recent vaccine trial performed with African children, immunization with a recombinant protein based on Plasmodium falciparum apical membrane antigen 1 (AMA-1) conferred a significant degree of strain-specific resistance against malaria. To contribute to the efforts of generating a vaccine against Plasmodium vivax malaria, we expressed the ectodomain of P. vivax AMA-1 (PvAMA-1) as a secreted soluble protein in the methylotrophic yeast Pichia pastoris. Recognized by a high percentage of sera from individuals infected by P. vivax, this recombinant protein was found to have maintained its antigenicity. The immunogenicity of this protein was evaluated in mice using immunization protocols that included homologous and heterologous prime-boost strategies with plasmid DNA and recombinant protein. We used the following formulations containing different adjuvants: aluminum salts (Alum), Bordetella pertussis monophosphoryl lipid A (MPLA), flagellin FliC from Salmonella enterica serovar Typhimurium, saponin Quil A, or incomplete Freund's adjuvant (IFA). The formulations containing the adjuvants Quil A or IFA elicited the highest IgG antibody titers. Significant antibody titers were also obtained using a formulation developed for human use containing MPLA or Alum plus MPLA. Recombinant PvAMA-1 produced under "conditions of good laboratory practice" provided a good yield, high purity, low endotoxin levels, and no microbial contaminants and reproduced the experimental immunizations. Most relevant for vaccine development was the fact that immunization with PvAMA-1 elicited invasion-inhibitory antibodies against different Asian isolates of P. vivax. Our results show that AMA-1 expressed in P. pastoris is a promising antigen for use in future preclinical and clinical studies.

  4. 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.

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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.

  10. 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

  11. 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

  12. Human Leukocyte Antigen Class II Alleles Influence Levels of Antibodies to the Plasmodium falciparum Asexual-Stage Apical Membrane Antigen 1 but Not to Merozoite Surface Antigen 2 and Merozoite Surface Protein 1

    PubMed Central

    Johnson, Armead H.; Leke, Rose G. F.; Mendell, Nancy R.; Shon, Dewon; Suh, Young Ju; Bomba-Nkolo, Dennis; Tchinda, Viviane; Kouontchou, Samuel; Thuita, Lucy W.; van der Wel, Anne Marie; Thomas, Alan; Stowers, Anthony; Saul, Allan; Zhou, Ainong; Taylor, Diane W.; Quakyi, Isabella A.

    2004-01-01

    The apical membrane antigen 1 (AMA1), merozoite surface antigen 2 (MSA2), and merozoite surface protein 1 (MSP1) are asexual-stage proteins currently being evaluated for inclusion in a vaccine for Plasmodium falciparum. Accordingly, it is important to understand factors that control antibody responses to these antigens. Antibody levels in plasma from residents of Etoa, Cameroon, between the ages of 5 and 70 years, were determined using recombinant AMA1, MSA2, and the N-terminal region of MSP1 (MSP1-190L). In addition, antibody responses to four variants of the C-terminal region of MSP1 (MSP119) were assessed. Results showed that all individuals produced antibodies to AMA1, MSA2, and MSP1-190L; however, a proportion of individuals never produced antibodies to the MSP119 variants, although the percentage of nonresponders decreased with age. The influence of age and human leukocyte antigen (HLA)-DRB1/DQB1 alleles on antibody levels was evaluated using two-way analysis of variance. Age was correlated with levels of antibodies to AMA1 and MSP119 but not with levels of antibodies to MSA2 and MSP1-190L. No association was found between a single HLA allele and levels of antibodies to MSA2, MSP1-190L, or any of the MSP119 variants. However, individuals positive for DRB1*1201 had higher levels of antibodies to the variant of recombinant AMA1 tested than did individuals of all other HLA types. Since the effect was seen across all age groups, HLA influenced the level but not the rate of antibody acquisition. This association for AMA1, combined with the previously reported association between HLA class II alleles and levels of antibodies to rhoptry-associated protein 1 (RAP1) and RAP2, indicates that HLA influences the levels of antibodies to three of the five vaccine candidate antigens that we have evaluated. PMID:15102786

  13. Potential Impact of Seasonal Malaria Chemoprevention on the Acquisition of Antibodies against Glutamate-Rich Protein and Apical Membrane Antigen 1 in Children Living in Southern Senegal

    PubMed Central

    Ndiaye, Magatte; Sylla, Khadime; Sow, Doudou; Tine, Roger; Faye, Babacar; Ndiaye, Jean Louis; Dieng, Yemou; Lo, Aminata Collé; Abiola, Annie; Cisse, Badara; Ndiaye, Daouda; Theisen, Michael; Gaye, Oumar; Alifrangis, Michael

    2015-01-01

    Seasonal malaria chemoprevention (SMC) is defined as the intermittent administration of full treatment courses of an antimalarial drug to children during the peak of malaria transmission season with the aim of preventing malaria-associated mortality and morbidity. SMC using sulfadoxine–pyrimethamine (SP) combined with amodiaquine (AQ) is a promising strategy to control malaria morbidity in areas of highly seasonal malaria transmission. However, a concern is whether SMC can delay the natural acquisition of immunity toward malaria parasites in areas with intense SMC delivery. To investigate this, total IgG antibody (Ab) responses to Plasmodium falciparum antigens glutamate-rich protein R0 (GLURP-R0) and apical membrane antigen 1 (AMA-1) were measured by enzyme-linked immunosorbent assay in Senegalese children under the age of 10 years in 2010 living in Saraya and Velingara districts (with SMC using SP+AQ [SMC+] since 2007) and Tambacounda district (without SMC (SMC−)). For both P. falciparum antigens, total IgG response were significantly higher in the SMC− compared with the SMC+ group (for GLURP-R0, P < 0.001 and for AMA-1, P = 0.001). There was as well a nonsignificant tendency for higher percentage of positive responders in the SMC− compared with the SMC+ group (for GLURP-R0: 22.2% versus 14.4%, respectively [P = 0.06]; for AMA-1: 45.6% versus 40.0%, respectively [P = 0.24]). Results suggest that long-term malaria chemoprevention by SMC/SP+AQ have limited impact on the development of acquired immunity, as tested using the P. falciparum antigens GLURP-R0 and AMA-1. However, other factors, not measured in this study, may interfere as well. PMID:26283746

  14. Hierarchical phosphorylation of apical membrane antigen 1 is required for efficient red blood cell invasion by malaria parasites

    PubMed Central

    Prinz, Boris; Harvey, Katherine L.; Wilcke, Louisa; Ruch, Ulrike; Engelberg, Klemens; Biller, Laura; Lucet, Isabelle; Erkelenz, Steffen; Heincke, Dorothee; Spielmann, Tobias; Doerig, Christian; Kunick, Conrad; Crabb, Brendan S.; Gilson, Paul R.; Gilberger, Tim W.

    2016-01-01

    Central to the pathogenesis of malaria is the proliferation of Plasmodium falciparum parasites within human erythrocytes. Parasites invade erythrocytes via a coordinated sequence of receptor-ligand interactions between the parasite and host cell. One key ligand, Apical Membrane Antigen 1 (AMA1), is a leading blood-stage vaccine and previous work indicates that phosphorylation of its cytoplasmic domain (CPD) is important to its function during invasion. Here we investigate the significance of each of the six available phospho-sites in the CPD. We confirm that the cyclic AMP/protein kinase A (PKA) signalling pathway elicits a phospho-priming step upon serine 610 (S610), which enables subsequent phosphorylation in vitro of a conserved, downstream threonine residue (T613) by glycogen synthase kinase 3 (GSK3). Both phosphorylation steps are required for AMA1 to function efficiently during invasion. This provides the first evidence that the functions of key invasion ligands of the malaria parasite are regulated by sequential phosphorylation steps. PMID:27698395

  15. Genetic polymorphism in domain I of the apical membrane antigen-1 among Plasmodium knowlesi clinical isolates from Peninsular Malaysia.

    PubMed

    Fong, Mun Yik; Wong, Shen Siang; Silva, Jeremy Ryan De; Lau, Yee Ling

    2015-12-01

    The simian malaria parasite Plasmodium knowlesi is now recognized as a species that can cause human malaria. The first report of large scale human knowlesi malaria was in 2004 in Malaysia Borneo. Since then, hundreds of human knowlesi malaria cases have been reported in Southeast Asia. The present study investigates the genetic polymorphism of P. knowlesi DI domain of the apical membrane antigen-1 (AMA-1), a protein considered as a promising vaccine candidate for malaria. The DI domain of AMA-1 gene of P. knowlesi clinical isolates from Peninsular Malaysia was amplified by PCR, cloned into Escherichia coli, then sequenced and analysed. Ninety-seven DI domain sequences were obtained. Comparison at the nucleotide level against P. knowlesi strain H as reference sequence showed 21 synonymous and 25 nonsynonymous mutations. Nonetheless, nucleotide sequence analysis revealed low genetic diversity of the DI domain, and it was under purifying (negative) selection. At the amino acid level, 26 different haplotypes were identified and 2 were predominant haplotypes (H1, H2) with high frequencies. Phylogenetic analysis revealed that the 26 haplotypes could be clustered into 2 distinct groups (I and II). Members of the groups were basically derived from haplotypes H1 and H2, respectively.

  16. 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

  17. 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

  18. 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

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

    PubMed

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

    2010-10-12

    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.

  20. Seroreactivity to a Large Panel of Field-Derived Plasmodium falciparum Apical Membrane Antigen 1 and Merozoite Surface Protein 1 Variants Reflects Seasonal and Lifetime Acquired Responses to Malaria

    PubMed Central

    Bailey, Jason A.; Pablo, Jozelyn; Niangaly, Amadou; Travassos, Mark A.; Ouattara, Amed; Coulibaly, Drissa; Laurens, Matthew B.; Takala-Harrison, Shannon L.; Lyke, Kirsten E.; Skinner, Jeff; Berry, Andrea A.; Jasinskas, Algis; Nakajima-Sasaki, Rie; Kouriba, Bourema; Thera, Mahamadou A.; Felgner, Philip L.; Doumbo, Ogobara K.; Plowe, Christopher V.

    2015-01-01

    Parasite antigen diversity poses an obstacle to developing an effective malaria vaccine. A protein microarray containing Plasmodium falciparum apical membrane antigen 1 (AMA1, n = 57) and merozoite surface protein 1 19-kD (MSP119, n = 10) variants prevalent at a malaria vaccine testing site in Bandiagara, Mali, was used to assess changes in seroreactivity caused by seasonal and lifetime exposure to malaria. Malian adults had significantly higher magnitude and breadth of seroreactivity to variants of both antigens than did Malian children. Seroreactivity increased over the course of the malaria season in children and adults, but the difference was more dramatic in children. These results help to validate diversity-covering protein microarrays as a promising tool for measuring the breadth of antibody responses to highly variant proteins, and demonstrate the potential of this new tool to help guide the development of malaria vaccines with strain-transcending efficacy. PMID:25294612

  1. Seroreactivity to a large panel of field-derived Plasmodium falciparum apical membrane antigen 1 and merozoite surface protein 1 variants reflects seasonal and lifetime acquired responses to malaria.

    PubMed

    Bailey, Jason A; Pablo, Jozelyn; Niangaly, Amadou; Travassos, Mark A; Ouattara, Amed; Coulibaly, Drissa; Laurens, Matthew B; Takala-Harrison, Shannon L; Lyke, Kirsten E; Skinner, Jeff; Berry, Andrea A; Jasinskas, Algis; Nakajima-Sasaki, Rie; Kouriba, Bourema; Thera, Mahamadou A; Felgner, Philip L; Doumbo, Ogobara K; Plowe, Christopher V

    2015-01-01

    Parasite antigen diversity poses an obstacle to developing an effective malaria vaccine. A protein microarray containing Plasmodium falciparum apical membrane antigen 1 (AMA1, n = 57) and merozoite surface protein 1 19-kD (MSP119, n = 10) variants prevalent at a malaria vaccine testing site in Bandiagara, Mali, was used to assess changes in seroreactivity caused by seasonal and lifetime exposure to malaria. Malian adults had significantly higher magnitude and breadth of seroreactivity to variants of both antigens than did Malian children. Seroreactivity increased over the course of the malaria season in children and adults, but the difference was more dramatic in children. These results help to validate diversity-covering protein microarrays as a promising tool for measuring the breadth of antibody responses to highly variant proteins, and demonstrate the potential of this new tool to help guide the development of malaria vaccines with strain-transcending efficacy.

  2. Stem Cell Antigen-1 in Skeletal Muscle Function

    PubMed Central

    Bernstein, Harold S.; Samad, Tahmina; Cholsiripunlert, Sompob; Khalifian, Saami; Gong, Wenhui; Ritner, Carissa; Aurigui, Julian; Ling, Vivian; Wilschut, Karlijn J.; Bennett, Stephen; Hoffman, Julien; Oishi, Peter

    2013-01-01

    Stem cell antigen-1 (Sca-1) is a member of the Ly-6 multigene family encoding highly homologous, glycosyl-phosphatidylinositol-anchored membrane proteins. Sca-1 is expressed on muscle-derived stem cells and myogenic precursors recruited to sites of muscle injury. We previously reported that inhibition of Sca-1 expression stimulated myoblast proliferation in vitro and regulated the tempo of muscle repair in vivo. Despite its function in myoblast expansion during muscle repair, a role for Sca-1 in normal, post-natal muscle has not been thoroughly investigated. We systematically compared Sca-1-/- (KO) and Sca-1+/+ (WT) mice and hindlimb muscles to elucidate the tissue, contractile, and functional effects of Sca-1 in young and aging animals. Comparison of muscle volume, fibrosis, myofiber cross-sectional area, and Pax7+ myoblast number showed little differences between ages or genotypes. Exercise protocols, however, demonstrated decreased stamina in KO versus WT mice, with young KO mice achieving results similar to aging WT animals. In addition, KO mice did not improve with practice, while WT animals demonstrated conditioning over time. Surprisingly, myomechanical analysis of isolated muscles showed that KO young muscle generated more force and experienced less fatigue. However, KO muscle also demonstrated incomplete relaxation with fatigue. These findings suggest that Sca-1 is necessary for muscle conditioning with exercise, and that deficient conditioning in Sca-1 KO animals becomes more pronounced with age. PMID:24042315

  3. Orally administered grass pollen.

    PubMed

    Taudorf, E; Weeke, B

    1983-11-01

    In 1900 it was claimed that oral administration of ragweed could be used for the hyposensitization of hay fever patients. Several uncontrolled trials have been published, all showing an effect of oral hyposensitization. Only one study was controlled and showed no effect of oral hyposensitization. It was decided to undertake controlled clinical trials to determine the safety and effectiveness of orally administered enteric-coated grass pollen tablets in patients with hay fever. The actual grass pollen dose in the first trial was 30 times the dose that is normally recommended for preseasonal oral pollen hyposensitization using pollen aqueous solution or pollen powder. The safety study will be described here. Twelve young adults with a history of grass pollen hay fever positive skin prick test and positive nasal provocation test with extracts of timothy grass pollen were randomly allocated to one of the treatment groups with four patients in each group taking enteric-coated Conjuvac Timothy tablets or enteric-coated Whole Timothy pollen tablets or enteric-coated placebo tablets. The study was double blind. Preseasonally, the patients received 342,500 PNU and in total they received 4,500,000 PNU during 6 months. The patients receiving active treatment did not have any side effects. No significant changes were shown in the skin and nasal reactivity to grass pollen during the study. Neither were there any changes in timothy-specific IgE, IgG, total IgE nor histamine liberation from basophils.

  4. 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

  5. Evidence that measles virus hemagglutinin initiates modulation of leukocyte function-associated antigen 1 expression.

    PubMed

    Nagendra, A R; Smith, C W; Wyde, P R

    1995-07-01

    Measles virus (MV), human immunodeficiency virus, Epstein-Barr virus, and other leukotropic viruses can modulate the expression of leukocyte function antigen 1 (LFA-1) on the surface of infected and nearby leukocytes. This ability to induce changes in LFA-1 expression may play an important role in the pathogenesis of these viruses. However, the mechanism(s) involved in virus-mediated regulation of LFA-1 is unknown. Evidence is presented in this report that it is the MV hemagglutinin (H) protein that initiates up-regulation of LFA-1 expression in leukocyte cultures infected with this virus. Indeed, comparison of the abilities of different MV strains to modulate LFA-1 expression, examination of published nucleotide sequences for the H proteins of different vaccine strains, and competitive inhibition assays using oligopeptides homologous or heterologous to a region of the H protein gene encompassing amino acid 116 (from the amino terminus) all suggest that it is this portion of the H protein that is responsible for MV-induced alteration of LFA-1. These comparisons also support the hypothesis that there is a relationship between the abilities of different MV strains to alter LFA-1 expression and their pathogenic potentials.

  6. Control of leucocyte function-associated antigen-1-dependent cellular conjugation by divalent cations.

    PubMed Central

    Jackson, A M; Alexandroff, A B; Lappin, M B; Esuvaranathan, K; James, K; Chisholm, G D

    1994-01-01

    The control of integrin activation is fundamental to an understanding of the integrin-dependent cellular adhesion thought to be important for a plethora of basic cellular functions. Using a cell-cell conjugation assay the role of divalent cations in leucocyte function-associated antigen-1 (LFA-1)-dependent cellular adhesion was further investigated. The conjugation of interleukin-2 (IL-2)-activated lymphocytes to tumour cells was found to be energy dependent and required the presence of various divalent cations, removal of which decreased the level of conjugation. Increased concentrations of calcium, magnesium and manganese ions resulted in a corresponding increase in levels of conjugation. This increase in conjugation was LFA-1 dependent. Interestingly, when calcium ions were first removed from LFA-1, treatment of lymphocytes with magnesium and manganese ions gave significantly higher levels of conjugation than in the presence of calcium. Using a simple displacement study, calcium ions were shown to displace magnesium ions resulting in decreased conjugation. However, calcium ions were unable to displace manganese ions for binding to LFA-1. That manganese was exerting its effect via an LFA-1-dependent mechanism was confirmed using monoclonal antibodies to CD11a which negated the increased conjugation frequency due to manganese. PMID:7907574

  7. Leukocyte function-associated antigen-1 deficiency impairs responses to polymicrobial sepsis

    PubMed Central

    Liu, Jia-Ren; Han, Xiaohui; Soriano, Sulpicio G; Yuki, Koichi

    2015-01-01

    AIM: To determine the role of leukocyte function-associated antigen-1 (LFA-1) in polymicrobial sepsis model in mice. METHODS: Cecal ligation and puncture model was used to study polymicrobial sepsis in wild type and LFA-1 knockout (KO) (= CD11a KO) mice. Their survivals were examined. Neutrophil recruitment to the abdominal cavity, bacterial tissue load and bacterial killing by neutrophils, tissue cytokine profiles, and serum cytokines were examined. Apoptosis of tissues was assessed using cleaved-caspase 3 and TUNNEL staining. The recruitment of neutrophils to various tissues was assessed using myeloperoxidase staining or measuring myeloperoxidase activity. RESULTS: LFA-1 deficiency significantly decreased survival (P = 0.0024) with the reduction of neutrophil recruitment to the abdominal cavity and higher bacterial load in blood. It was also associated with increased apoptosis in spleen and more organ injuries probed by interleukin-6 mRNA level. However, the deficiency of LFA-1 did not prevent neutrophil recruitment to lung, liver, spleen or kidney, which suggested the existence of LFA-1 independent recruitment mechanism in these organs. CONCLUSION: LFA-1 deficiency did not attenuate neutrophil recruitment to various organs to adequately mitigate secondary tissue injury in sepsis. It was associated with decreased neutrophil recruitment to the abdominal cavity, higher bacterial load, leading to increased mortality in an abdominal, polymicrobial sepsis. PMID:26380827

  8. Stereoselectivity of Isoflurane in Adhesion Molecule Leukocyte Function-Associated Antigen-1

    PubMed Central

    Bu, Weiming; Pereira, Luis M.; Eckenhoff, Roderic G.; Yuki, Koichi

    2014-01-01

    Background Isoflurane in clinical use is a racemate of S- and R-isoflurane. Previous studies have demonstrated that the effects of S-isoflurane on relevant anesthetic targets might be modestly stronger (less than 2-fold) than R-isoflurane. The X-ray crystallographic structure of the immunological target, leukocyte function-associated antigen-1 (LFA-1) with racemic isoflurane suggested that only S-isoflurane bound specifically to this protein. If so, the use of specific isoflurane enantiomers may have advantage in the surgical settings where a wide range of inflammatory responses is expected to occur. Here, we have further tested the hypothesis that isoflurane enantioselectivity is apparent in solution binding and functional studies. Methods First, binding of isoflurane enantiomers to LFA-1 was studied using 1-aminoanthracene (1-AMA) displacement assays. The binding site of each enantiomer on LFA-1 was studied using the docking program GLIDE. Functional studies employed the flow-cytometry based ICAM binding assay. Results Both enantiomers decreased 1-AMA fluorescence signal (at 520 nm), indicating that both competed with 1-AMA and bound to the αL I domain. The docking simulation demonstrated that both enantiomers bound to the LFA-1 “lovastatin site.” ICAM binding assays showed that S-isoflurane inhibited more potently than R-isoflurane, consistent with the result of 1-AMA competition assay. Conclusions In contrast with the x-ray crystallography, both enantiomers bound to and inhibited LFA-1. S-isoflurane showed slight preference over R-isoflurane. PMID:24801074

  9. 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

  10. 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

  11. Measles virus-induced changes in leukocyte function antigen 1 expression and leukocyte aggregation: possible role in measles virus pathogenesis.

    PubMed

    Attibele, N; Wyde, P R; Trial, J; Smole, S C; Smith, C W; Rossen, R D

    1993-02-01

    Measles virus (MV) infection of U937 cell or peripheral blood leukocyte cultures was shown to induce changes in the expression of leukocyte function antigen 1 (LFA-1) and cause marked aggregation of these cells. Addition of selected monoclonal antibodies specific for LFA-1 epitopes that did not neutralize MV in standard neutralization assays were found to block both virus-induced leukocyte aggregation and virus dissemination. These data suggest that MV modulation of LFA-1 expression on leukocytes may be an important step in MV pathogenesis.

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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.

  18. 22 CFR 196.4 - Administering office.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 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...

  19. 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...

  20. 22 CFR 196.4 - Administering office.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 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...

  1. 22 CFR 196.4 - Administering office.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 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...

  2. 22 CFR 196.4 - Administering office.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 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...

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

    PubMed Central

    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

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

    PubMed Central

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

    2015-01-01

    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

  5. Epstein-Barr nuclear antigen 1 mediates a DNA loop within the latent replication origin of Epstein-Barr virus.

    PubMed

    Frappier, L; O'Donnell, M

    1991-12-01

    Epstein-Barr virus-encoded nuclear antigen 1 (EBNA-1) binds and activates the viral latent origin of DNA replication, oriP. We have used electron microscopy to examine the assembly of EBNA-1 onto oriP. The oriP region consists of two essential elements separated by approximately 1 kilobase pair of DNA. One element contains 20 tandom EBNA-1 binding sites [called the family of repeats (FR)] and serves to activate initiation of replication at the dyad symmetry (DS) element, which contains 4 EBNA-1 binding sites. Titration of homogeneous EBNA-1 produced in baculovirus (bEBNA-1) onto oriP DNA showed an order to the assembly of bEBNA-1 onto oriP. At low concentrations, bEBNA-1 was located exclusively on the FR element. As the level of bEBNA-1 was raised, a loop between the FR and DS elements became the most prevalent DNA-protein complex. These data suggest protein-mediated DNA looping may play a role in activating latent-phase replication of the Epstein-Barr virus.

  6. Thymus cell antigen 1 (Thy1, CD90) is expressed by lymphatic vessels and mediates cell adhesion to lymphatic endothelium.

    PubMed

    Jurisic, Giorgia; Iolyeva, Maria; Proulx, Steven T; Halin, Cornelia; Detmar, Michael

    2010-10-15

    The lymphatic vascular system plays an important role in inflammation and cancer progression, although the molecular mechanisms involved are poorly understood. As determined by comparative transcriptional profiling studies of ex vivo isolated mouse intestinal lymphatic endothelial cells versus blood vascular endothelial cells, thymus cell antigen 1 (Thy1, CD90) was expressed at much higher levels in lymphatic endothelial cells than in blood vascular endothelial cells. These findings were confirmed by quantitative PCR, and at the protein level by FACS and immunofluorescence analyses. Thy1 was also strongly expressed by tumor-associated lymphatic vessels, as evaluated in a B16 melanoma footpad model in mice. Blockade of Thy1 inhibited tumor cell adhesion to cultured mouse lymphatic endothelial cells. Importantly, treatment of human dermal microvascular endothelial cells with tumor necrosis factor or phorbol 12-myristate 13-acetate resulted in Thy1 upregulation in podoplanin-expressing lymphatic endothelial cells, but not in podoplanin-negative blood vascular endothelial cells. Moreover, adhesion of human polymorphonuclear and mononuclear leukocytes to human lymphatic endothelial cells was Thy1-dependent. Together, these results identify Thy1 as a novel lymphatic vessel expressed gene and suggest its potential role in the cell adhesion processes required for tumor progression and inflammation.

  7. 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.

  8. 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

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

    PubMed

    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

  10. Expression of epstein-barr virus encoded nuclear antigen 1 in benign and malignant tissues harbouring EBV.

    PubMed Central

    Oudejans, J J; Dukers, D F; Jiwa, N M; van den Brule, A J; Grässer, F A; de Bruin, P C; Horstman, A; Vos, W; van Gorp, J; Middeldorp, J M; Meijer, C J

    1996-01-01

    AIMS: To determine levels of expression of Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) in benign and malignant tissues harbouring EBV in relation to EBNA1 promoter usage. METHODS: Expression of EBNA1 was investigated by means of immunohistochemistry using a mixture of two EBNA1 specific monoclonal antibodies, 1H4-1 and 2B4-1. The presence of EBV was detected by EBER1/2 RNA in situ hybridisation. Detection of promoter specific EBNA1 transcripts was by RT-PCR analysis. RESULTS: EBNA1 positive cells were detected in all 20 EBV associated B cell lymphomas, 18 of which had arisen in immunocompromised patients; in eight of nine EBV associated T cell lymphomas; in 11 of 27 EBV positive cases of Hodgkin's disease; and in reactive lymphoid tissue harbouring EBV, including four cases of infectious mononucleosis. A diffuse EBNA1 staining pattern was observed in most of the EBV associated B cell lymphomas and was comparable with the EBER1/2 staining pattern. In the T cell lymphomas the number of EBNA1 positive cells was usually considerably less than the number of EBER1/2 positive ones. RT-PCR analysis revealed that in tumours with restricted EBNA1 expression-that is, T cell lymphomas and Hodgkin's disease lesions, EBNA1 transcripts were usually generated only by the F/Q promoter, whereas in B cell lymphomas EBNA1 transcripts were usually generated by both the C/W and F/Q promoters. CONCLUSIONS: EBNA1 is expressed in all types of tissue harbouring EBV, but the level of expression varies greatly. This may be the result of differential promoter usage. Images PMID:8944608

  11. 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

  12. 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

  13. 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…

  14. 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…

  15. Trials of intranasally administered rubella vaccine.

    PubMed

    Hillary, I B

    1971-12-01

    No evidence of vaccine virus transmission was found in two studies where Wistar RA 27/3 rubella vaccine was administered intranasally. Vaccine was immunogenic in all of 23 vaccinated children in one study, while in the other only 5 of the 11 vaccinees developed antibody. The reduced seroconversion rate in the latter study appears to have been caused by one or a combination of factors, including the vaccination technique, the presence of infective nasal conditions in vaccinees and the titre of vaccine used.

  16. 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

  17. Absorption of orally administered amphotericin B lozenges.

    PubMed

    Ching, M S; Raymond, K; Bury, R W; Mashford, M L; Morgan, D J

    1983-07-01

    The systemic absorption of amphotericin B, administered as a 10 mg lozenge, was investigated in 14 patients with malignancies, who received three or four doses daily during chronic administration. The mean plasma amphotericin B concentration, measured 3 h after the morning dose on from 1-20 occasions over a 1-80 day period, ranged among subjects from 46 +/- 13 ng/ml (s.d., n = 20) to 136 +/- 25 ng/ml (n = 19). Using the previously reported intravenous clearance of the drug, the fraction of the dose absorbed was estimated at 8.3-9.9%. This is considerably greater than that estimated from earlier reports (0.2-0.9%), which used much higher oral doses (2-10 g/day). PMID:6882617

  18. 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.

  19. 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 Central

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

    1994-01-01

    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. Images PMID:7525481

  20. 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

  1. Efficacy of intravenously administered ibandronate in postmenopausal Korean women with insufficient response to orally administered bisphosphonates.

    PubMed

    Bae, Sung Jin; Kim, Beom-Jun; Lim, Kyeong Hye; Lee, Seung Hun; Kim, Hong Kyu; Kim, Ghi Su; Koh, Jung-Min

    2012-09-01

    We investigated rates of insufficient and over-responsiveness to orally administered bisphosphonates in postmenopausal women, and tested the efficacy of intravenous ibandronate in patients with insufficient response to orally administered bisphosphonates. Postmenopausal women were treated with either alendronate (70 mg/week; n = 88) or risedronate (35 mg/week; n = 84) for 1 year, and their response to orally administered bisphosphonates was assessed using serum C-telopeptide (CTX) levels. Insufficient responders were changed to once-quarterly intravenous ibandronate 3 mg injection (n = 13) or maintained on orally administered bisphosphonates (n = 19), according to patients' preference, for an additional 1 year. There was no significant difference in baseline characteristics between two orally administered bisphosphonate groups except the bone mineral density values at the lumbar spine. Insufficient rate was higher in the risedronate group (19.0 %) than in the alendronate group (8.0 %), using the premenopausal serum CTX median as a cut-off (P = 0.043). The over-response rate among the alendronate group (59.1 %) was significantly higher than that in the risedronate group (38.1 %), based on a serum CTX cut-off value of 0.100 ng/ml (P = 0.006). Intravenous ibandronate suppressed serum CTX levels to a significantly greater degree at 7 days after the second dosing (0.191 ± 0.110 ng/mL; P < 0.001) and 3 months after the fourth dosing (0.274 ± 0.159 ng/mL; P = 0.004) among insufficient responders, compared with post-oral/pre-intravenous levels (0.450 ± 0.134 ng/mL). Rates of insufficient and over-responsiveness to orally administered bisphosphonates were considerable, and a change to intravenous bisphosphonates may be considered in patients showing an insufficient response to orally administered bisphosphonates.

  2. 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

  3. 40 CFR 147.1201 - EPA-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... (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 147.1201 - 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...

  5. 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...

  6. 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...

  7. 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...

  8. 47 CFR 97.509 - Administering VE requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...) Each examination for an amateur operator license must be administered by a team of at least 3 VEs at an... examination. The administering VEs are responsible for the proper conduct and necessary supervision of each examination. The administering VEs must immediately terminate the examination upon failure of the examinee...

  9. 47 CFR 97.509 - Administering VE requirements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...) Each examination for an amateur operator license must be administered by a team of at least 3 VEs at an... administering VEs are responsible for the proper conduct and necessary supervision of each examination. The administering VEs must immediately terminate the examination upon failure of the examinee to comply with...

  10. 47 CFR 97.509 - Administering VE requirements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...) Each examination for an amateur operator license must be administered by a team of at least 3 VEs at an... examination. The administering VEs are responsible for the proper conduct and necessary supervision of each examination. The administering VEs must immediately terminate the examination upon failure of the examinee...

  11. 47 CFR 97.509 - Administering VE requirements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...) Each examination for an amateur operator license must be administered by a team of at least 3 VEs at an... examination. The administering VEs are responsible for the proper conduct and necessary supervision of each examination. The administering VEs must immediately terminate the examination upon failure of the examinee...

  12. 47 CFR 97.509 - Administering VE requirements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...) Each examination for an amateur operator license must be administered by a team of at least 3 VEs at an... examination. The administering VEs are responsible for the proper conduct and necessary supervision of each examination. The administering VEs must immediately terminate the examination upon failure of the examinee...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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

  18. Reaction of antibodies to rheumatoid arthritis nuclear antigen with a synthetic peptide corresponding to part of Epstein-Barr nuclear antigen 1.

    PubMed Central

    Venables, P J; Pawlowski, T; Mumford, P A; Brown, C; Crawford, D H; Maini, R N

    1988-01-01

    Antibodies to rheumatoid arthritis nuclear antigen (RANA) are detected by immunodiffusion (ID) and immunofluorescence (IF), though reports of the identity of the antigen(s) have been conflicting. In this study it is shown conclusively that ID and IF anti-RANA react with epitopes on Epstein-Barr nuclear antigen 1 (EBNA-1) and that the major epitope detected by immunofluorescence is represented by a synthetic peptide, P62, corresponding to part of EBNA-1. In an enzyme linked immunosorbent assay (ELISA) anti-P62 antibodies in 35 rheumatoid arthritis sera were threefold higher than those of 35 age and sex matched controls, with the highest levels occurring in young patients with active joint disease. Images PMID:2452607

  19. 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

  20. 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.

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. Acquired and congenital cholesteatoma: determination of tumor necrosis factor-alpha, intercellular adhesion molecule-1, interleukin-1-alpha and lymphocyte functional antigen-1 in the inflammatory process.

    PubMed

    Akimoto, R; Pawankar, R; Yagi, T; Baba, S

    2000-01-01

    The molecular and cellular factors resulting in the pathologic features of acquired and congenital cholesteatomas are not completely known. Recently, proinflammatory cytokines like interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor-alpha (TNF-alpha) have been shown to induce bone resorption, in vitro. To elucidate the key molecules involved in bone resorption and cell infiltration associated with cholesteatoma, we examined the in vivo levels of IL-1 alpha and TNF-alpha, intercellular adhesion molecule-1 (ICAM-1) and lymphocyte functional antigen-1 (LFA-1) in acquired and congenital cholesteatomas, by reverse transcriptase-polymerase chain reaction, immunohistochemistry, and ELISA. Increased levels of IL-1 and TNF-alpha were detected in both types of cholesteatomas as compared to normal skin. Increased ICAM-1 expression and LFA-1+ cells were detected in acquired but not congenital cholesteatoma. Strong correlation was detected between TNF-alpha and bone resorption in both types of cholesteatoma, and between TNF-alpha and ICAM, TNF-alpha and severity of infection, or cell infiltration in acquired cholesteatoma. No correlation existed between various parameters and IL-1 alpha. These results suggest that TNF-alpha may play a crucial role in the pathogenesis of both acquired and congenital cholesteatomas by regulating bone resorption and cell infiltration.

  6. 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

  7. Lymphocyte function-associated antigen-1 binding residues in intercellular adhesion molecule-2 (ICAM-2) and the integrin binding surface in the ICAM subfamily

    PubMed Central

    Casasnovas, José M.; Pieroni, Cristiana; Springer, Timothy A.

    1999-01-01

    The crystal structure of intercellular adhesion molecule-2 (ICAM-2) revealed significant differences in the presentation of the critical acidic residue important for integrin binding between I and non-I-domain integrin ligands. Based on this crystal structure, we mutagenized ICAM-2 to localize the binding site for the integrin lymphocyte function-associated antigen-1 (LFA-1). The integrin binding site runs diagonally across the GFC β-sheet and includes residues on the CD edge of the β-sandwich. The site is oblong and runs along a flat ridge on the upper half of domain 1, which is proposed to dock to a groove in the I domain of LFA-1, with the critical Glu-37 residue ligating the Mg2+ in the I domain. Previous mutagenesis of ICAM-1 and ICAM-3, interpreted in light of the recently determined ICAM-1 and ICAM-2 structures, suggests similar binding sites. By contrast, major differences are seen with vascular cell adhesion molecule-1 (VCAM-1), which binds α4 integrins that lack an I domain. The binding site on VCAM-1 includes the lower portion of domain 1 and the upper part of domain 2, whereas the LFA-1 binding site on ICAM is confined to the upper part of domain 1. PMID:10077629

  8. Mechanisms of drug-induced lupus. II. T cells overexpressing lymphocyte function-associated antigen 1 become autoreactive and cause a lupuslike disease in syngeneic mice.

    PubMed

    Yung, R; Powers, D; Johnson, K; Amento, E; Carr, D; Laing, T; Yang, J; Chang, S; Hemati, N; Richardson, B

    1996-06-15

    Current theories propose that systemic lupus erythematosus develops when genetically predisposed individuals are exposed to certain environmental agents, although how these agents trigger lupus is uncertain. Some of these agents, such as procainamide, hydralazine, and UV-light inhibit T cell DNA methylation, increase lymphocyte function-associated antigen 1 (LFA-1) (CD11a/CD18) expression, and induce autoreactivity in vitro, and adoptive transfer of T cells that are made autoreactive by this mechanism causes a lupuslike disease. The mechanism by which these cells cause autoimmunity is unknown. In this report, we present evidence that LFA-1 overexpression is sufficient to induce autoimmunity. LFA-1 overexpression was induced on cloned murine Th2 cells by transfection, resulting in autoreactivity. Adoptive transfer of the transfected, autoreactive cells into syngeneic recipients caused a lupuslike disease with anti-DNA antibodies, an immune complex glomerulonephritis and pulmonary alveolitis, similar to that caused by cells treated with procainamide. These results indicate that agents or events which modify T cell DNA methylation may induce autoimmunity by causing T cell LFA-1 overexpression. Since T cells from patients with active lupus have hypomethylated DNA and overexpressed LFA-1, this mechanism could be important in the development of human autoimmunity.

  9. Lymphocyte function-associated antigen-1 binding residues in intercellular adhesion molecule-2 (ICAM-2) and the integrin binding surface in the ICAM subfamily.

    PubMed

    Casasnovas, J M; Pieroni, C; Springer, T A

    1999-03-16

    The crystal structure of intercellular adhesion molecule-2 (ICAM-2) revealed significant differences in the presentation of the critical acidic residue important for integrin binding between I and non-I-domain integrin ligands. Based on this crystal structure, we mutagenized ICAM-2 to localize the binding site for the integrin lymphocyte function-associated antigen-1 (LFA-1). The integrin binding site runs diagonally across the GFC beta-sheet and includes residues on the CD edge of the beta-sandwich. The site is oblong and runs along a flat ridge on the upper half of domain 1, which is proposed to dock to a groove in the I domain of LFA-1, with the critical Glu-37 residue ligating the Mg2+ in the I domain. Previous mutagenesis of ICAM-1 and ICAM-3, interpreted in light of the recently determined ICAM-1 and ICAM-2 structures, suggests similar binding sites. By contrast, major differences are seen with vascular cell adhesion molecule-1 (VCAM-1), which binds alpha4 integrins that lack an I domain. The binding site on VCAM-1 includes the lower portion of domain 1 and the upper part of domain 2, whereas the LFA-1 binding site on ICAM is confined to the upper part of domain 1. PMID:10077629

  10. The genetic diversity of merozoite surface antigen 1 (MSA-1) among Babesia bovis detected from cattle populations in Thailand, Brazil and Ghana.

    PubMed

    Nagano, Daisuke; Sivakumar, Thillaiampalam; De De Macedo, Alane Caine Costa; Inpankaew, Tawin; Alhassan, Andy; Igarashi, Ikuo; Yokoyama, Naoaki

    2013-11-01

    In the present study, we screened blood DNA samples obtained from cattle bred in Brazil (n=164) and Ghana (n=80) for Babesia bovis using a diagnostic PCR assay and found prevalences of 14.6% and 46.3%, respectively. Subsequently, the genetic diversity of B. bovis in Thailand, Brazil and Ghana was analyzed, based on the DNA sequence of merozoite surface antigen-1 (MSA-1). In Thailand, MSA-1 sequences were relatively conserved and found in a single clade of the phylogram, while Brazilian MSA-1 sequences showed high genetic diversity and were dispersed across three different clades. In contrast, the sequences from Ghanaian samples were detected in two different clades, one of which contained only a single Ghanaian sequence. The identities among the MSA-1 sequences from Thailand, Brazil and Ghana were 99.0-100%, 57.5-99.4% and 60.3-100%, respectively, while the similarities among the deduced MSA-1 amino acid sequences within the respective countries were 98.4-100%, 59.4-99.7% and 58.7-100%, respectively. These observations suggested that the genetic diversity of B. bovis based on MSA-1 sequences was higher in Brazil and Ghana than in Thailand. The current data highlight the importance of conducting extensive studies on the genetic diversity of B. bovis before designing immune control strategies in each surveyed country.

  11. 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...

  12. 40 CFR 147.150 - 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. 147.150 Section 147.150 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Arizona §...

  13. 40 CFR 147.150 - 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. 147.150 Section 147.150 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Arizona §...

  14. 40 CFR 147.150 - 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. 147.150 Section 147.150 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Arizona §...

  15. 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 §...

  16. 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 §...

  17. 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 §...

  18. 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 §...

  19. 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 §...

  20. 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 §...

  1. 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... RCWP Contracts § 634.30 Appeals in USDA administered projects. The participant in a...

  2. 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... RCWP Contracts § 634.30 Appeals in USDA administered projects. The participant in a...

  3. 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... RCWP Contracts § 634.30 Appeals in USDA administered projects. The participant in a...

  4. 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... RCWP Contracts § 634.30 Appeals in USDA administered projects. The participant in a...

  5. 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... RCWP Contracts § 634.30 Appeals in USDA administered projects. The participant in a...

  6. 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 §...

  7. 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 §...

  8. 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 §...

  9. 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 §...

  10. 49 CFR 7.22 - Who administers this subpart?

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 1 2014-10-01 2014-10-01 false Who administers this subpart? 7.22 Section 7.22 Transportation Office of the Secretary of Transportation PUBLIC AVAILABILITY OF INFORMATION Availability of Reasonably Described Records Under the Freedom of Information Act § 7.22 Who administers this subpart? (a) A Chief FOIA Officer is appointed...

  11. 40 CFR 147.3000 - EPA-administered program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 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)...

  12. 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..., Ute Mountain Ute, and All Other New Mexico Tribes § 147.3000 EPA-administered program. (a)...

  13. 40 CFR 147.1550 - State-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Director of the Federal Register on June 25, 1984. (1) Water Pollution Control Act, New Jersey Statutes... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS New Jersey § 147.1550 State-administered program. The UIC program for all classes of wells in the State of New Jersey,...

  14. Plasmid-encoded production of coli surface-associated antigen 1 (CS1) in a strain of Escherichia coli serotype O139.H28.

    PubMed

    Willshaw, G A; Smith, H R; McConnell, M M; Gaastra, W; Thomas, A; Hibberd, M; Rowe, B

    1990-07-01

    Production of coli surface-associated antigen 1 (CS1) by Escherichia coli strain E24377 of serotype O139.H28 was controlled by a plasmid that also encoded heat stable and heat labile enterotoxins and CS3. The presence of a regulatory sequence was detected on this plasmid by hybridization with the cfaD gene that regulates expression of colonization factor antigen I fimbriae and is at least 96% homologous with the rns sequence controlling production of CS1 or CS2 fimbriae by strains of serotype O6.H16 of appropriate biotype. A separate plasmid, pDEP20, carrying the structural genes for CS1 synthesis was identified and transformed into E. coli strain HB101 or a derivative of strain E24377 without large plasmids. Transformants carrying pDEP20 did not produce CS1 fimbrial antigen, but antigen expression was obtained when a cloned cfaD gene or a wild-type plasmid carrying the rns sequence was introduced. Transposon mutagenesis with Tn1000 identified a 3.7 kbp region of pDEP20 essential for production of CS1 fimbriae. Genes encoding production of CS1 fimbriae were cloned on a 9.9 kbp BamHI fragment and were expressed in the presence of the cfaD sequence. A strain producing both CS1 and CS2 antigens was constructed by introduction of the cloned cfaD gene into a strain of serotype O6.H16 biotype C carrying plasmid pDEP20.

  15. T-cell immunity to peptide epitopes of liver-stage antigen 1 in an area of Papua New Guinea in which malaria is holoendemic.

    PubMed Central

    Connelly, M; King, C L; Bucci, K; Walters, S; Genton, B; Alpers, M P; Hollingdale, M; Kazura, J W

    1997-01-01

    Liver-stage antigen 1 (LSA1) is one of several pre-erythrocytic antigens considered for inclusion in a multiantigen, multistage subunit vaccine against falciparum malaria. We examined T-cell proliferation and cytokine responses to peptides corresponding to amino acids 84 to 107, 1813 to 1835, and 1888 to 1909 of LSA1 in asymptomatic adults living in an area of Papua New Guinea where malaria is holoendemic. Whereas T cells from North Americans never exposed to malaria did not respond to any of the peptides, those from 52 of 55 adults from the area where malaria is endemic had vigorous proliferation responses to one or more of the LSA1 peptides (mean stimulation indices of 6.8 to 7.2). Gamma interferon (IFN-gamma) production driven by LSA1 peptides ranged from 34 to more than 3,500 pg/2 x 10(6) cells, was derived primarily from CD8+ cells, and was dissociated from T-cell proliferation. The frequencies of IFN-gamma response to the amino acid 1819 to 1835 and 1888 to 1909 peptides were significantly greater than that to the amino acid 84 to 107 peptide (87 and 88% versus 33% of subjects; P < 0.0001). In contrast to proliferation and IFN-gamma, interleukin 4 (IL-4) and/or IL-5 responses to LSA1 peptides were detected in only 18% of the subjects. These data show that T-cell immunity to epitopes in the N- and C-terminal regions of LSA1 are common in persons living in this area of Papua New Guinea where malaria is endemic. The dominance of type 1 CD8 cell IFN-gamma responses is consistent with a role for this T-cell population in immunity to liver-stage Plasmodium falciparum in humans. PMID:9393799

  16. A randomized multicenter trial comparing leukocyte function-associated antigen-1 monoclonal antibody with rabbit antithymocyte globulin as induction treatment in first kidney transplantations.

    PubMed

    Hourmant, M; Bedrossian, J; Durand, D; Lebranchu, Y; Renoult, E; Caudrelier, P; Buffet, R; Soulillou, J P

    1996-12-15

    Adhesion molecules are involved in several steps in the immune response: leukocyte adhesion to the endothelium, transendothelial migration, cooperation between immunocompetent cells, and cytotoxicity. Leukocyte function-associated antigen-1 plays a central role among adhesion molecules. In a multicenter randomized open trial, we compared a monoclonal antibody directed against the alpha chain of LFA-1 (Oduli-momab; IMTIX/Pasteur Mérieux Sérums et Vaccins) with rabbit antithymocyte globulin (rATG; IMTIX/Pasteur Mérieux Sérums et Vaccins), as part of a quadruple sequential protocol in 101 patients receiving a first kidney transplant. Clinical tolerance of anti-LFA-1 mAb was better than that of rATG. Short-term rejection rates (< 15 days) were not significantly different (15% and 16% for anti-LFA-1 mAb and rATG, respectively). However, 11% of the anti-LFA-1 mAb patients experienced rejection during the first 10 days of the treatment course compared with none of the patients treated with rATG. The incidence and severity of acute rejection in the first 3 months was not significantly different between groups. Of the LFA-1 and rATG patients, 96% and 92% of the grafts, respectively, were functioning at 12 months. The incidence and severity of infection, whatever the origin, were comparable in both groups. In addition, it was observed that fewer patients required posttransplantation dialysis in the anti-LFA-1 mAb group (19%, vs. 35% for rATG), although the difference was not statistically significant. Altogether, the beneficial action of this monoclonal antibody on short-term renal function recovery makes it a useful tool in the management of renal patients undergoing kidney transplantation.

  17. A Genome-Wide Integrative Genomic Study Localizes Genetic Factors Influencing Antibodies against Epstein-Barr Virus Nuclear Antigen 1 (EBNA-1)

    PubMed Central

    Rubicz, Rohina; Yolken, Robert; Drigalenko, Eugene; Carless, Melanie A.; Dyer, Thomas D.; Bauman, Lara; Melton, Phillip E.; Kent, Jack W.; Harley, John B.; Curran, Joanne E.; Johnson, Matthew P.; Cole, Shelley A.; Almasy, Laura; Moses, Eric K.; Dhurandhar, Nikhil V.; Kraig, Ellen; Blangero, John; Leach, Charles T.; Göring, Harald H. H.

    2013-01-01

    Infection with Epstein-Barr virus (EBV) is highly prevalent worldwide, and it has been associated with infectious mononucleosis and severe diseases including Burkitt lymphoma, Hodgkin lymphoma, nasopharyngeal lymphoma, and lymphoproliferative disorders. Although EBV has been the focus of extensive research, much still remains unknown concerning what makes some individuals more sensitive to infection and to adverse outcomes as a result of infection. Here we use an integrative genomics approach in order to localize genetic factors influencing levels of Epstein Barr virus (EBV) nuclear antigen-1 (EBNA-1) IgG antibodies, as a measure of history of infection with this pathogen, in large Mexican American families. Genome-wide evidence of both significant linkage and association was obtained on chromosome 6 in the human leukocyte antigen (HLA) region and replicated in an independent Mexican American sample of large families (minimum p-value in combined analysis of both datasets is 1.4×10−15 for SNPs rs477515 and rs2516049). Conditional association analyses indicate the presence of at least two separate loci within MHC class II, and along with lymphocyte expression data suggest genes HLA-DRB1 and HLA-DQB1 as the best candidates. The association signals are specific to EBV and are not found with IgG antibodies to 12 other pathogens examined, and therefore do not simply reveal a general HLA effect. We investigated whether SNPs significantly associated with diseases in which EBV is known or suspected to play a role (namely nasopharyngeal lymphoma, Hodgkin lymphoma, systemic lupus erythematosus, and multiple sclerosis) also show evidence of associated with EBNA-1 antibody levels, finding an overlap only for the HLA locus, but none elsewhere in the genome. The significance of this work is that a major locus related to EBV infection has been identified, which may ultimately reveal the underlying mechanisms by which the immune system regulates infection with this pathogen

  18. Delta-like 1/Fetal Antigen-1 (Dlk1/FA1) Is a Novel Regulator of Chondrogenic Cell Differentiation via Inhibition of the Akt Kinase-dependent Pathway*

    PubMed Central

    Chen, Li; Qanie, Diyako; Jafari, Abbas; Taipaleenmaki, Hanna; Jensen, Charlotte H.; Säämänen, Anna-Marja; Sanz, Maria Luisa Nueda; Laborda, Jorge; Abdallah, Basem M.; Kassem, Moustapha

    2011-01-01

    Delta-like 1 (Dlk1, also known as fetal antigen-1, FA1) is a member of Notch/Delta family that inhibits adipocyte and osteoblast differentiation; however, its role in chondrogenesis is still not clear. Thus, we overexpressed Dlk1/FA1 in mouse embryonic ATDC5 cells and tested its effects on chondrogenic differentiation. Dlk1/FA1 inhibited insulin-induced chondrogenic differentiation as evidenced by reduction of cartilage nodule formation and gene expression of aggrecan, collagen Type II and X. Similar effects were obtained either by using Dlk1/FA1-conditioned medium or by addition of a purified, secreted, form of Dlk1 (FA1) directly to the induction medium. The inhibitory effects of Dlk1/FA1 were dose-dependent and occurred irrespective of the chondrogenic differentiation stage: proliferation, differentiation, maturation, or hypertrophic conversion. Overexpression or addition of the Dlk1/FA1 protein to the medium strongly inhibited the activation of Akt, but not the ERK1/2, or p38 MAPK pathways, and the inhibition of Akt by Dlk1/FA1 was mediated through PI3K activation. Interestingly, inhibition of fibronectin expression by siRNA rescued the Dlk1/FA1-mediated inhibition of Akt, suggesting interaction of Dlk1/FA1 and fibronectin in chondrogenic cells. Our results identify Dlk1/FA1 as a novel regulator of chondrogenesis and suggest Dlk1/FA1 acts as an inhibitor of the PI3K/Akt pathways that leads to its inhibitory effects on chondrogenesis. PMID:21724852

  19. Differential regulation of leukocyte function-associated antigen-1/ intercellular adhesion molecules-1-dependent adhesion and aggregation in HL-60 cells.

    PubMed

    Katagiri, K; Kinashi, T; Irie, S; Katagiri, T

    1996-05-15

    Activation of integrin and organization of cytoskeletal proteins are highly regulated in cell adhesion and aggregation. The interaction of leukocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecules-1 (ICAM-1) mediates cell adhesion and aggregation, which facilitate leukocyte trafficking to inflamed tissues and augment effector functions. We investigated how LFA-1/ICAM-1-mediated adhesion and aggregation are regulated in HL-60 cells induced to differentiate into neutrophils by retinoic acid (RA). Uninduced HL-60 cells did not bind to ICAM-1 even with stimulation by 12-0-tetradecanoyl phorbol-13-acetate, although they express LFA-1 on the cell surface. When cultured with RA for 24 hours, HL-60 cells were able to adhere to ICAM-1 constitutively. The induction of adhesion did not accompany any change in surface density of LFA-1, indicating that the avidity of LFA-1 was increased. The change in its avidity required de novo synthesis of proteins. Although ICAM-1 was intensely expressed on RA-induced HL-60 cells, these cells did not show any cellular aggregation. The HL-60 cells transfected with the active form of Ras (Val12) exhibited LFA-1/ICAM-1-dependent aggregation by RA stimulation without change in the avidity of LFA-1. In these Ras-transfectants, a cytoskeletal protein, paxillin, was tyrosine-phosphorylated, and the level of F-actin increased. Transforming growth factor (TGF) beta, as well as cytochalasin D, prevented both the tyrosine phosphorylation of paxillin and the aggregation without any effects on the avidity of LFA-1. Thus, an increase in the avidity of LFA-1 was not sufficient for the induction of aggregation, which required activation of Ras and reorganization of cytoskeletal proteins. These results suggest that distinct regulatory mechanisms control LFA-1/ICAM-1-dependent adhesion and aggregation in HL-60 cells differentiating into neutrophils.

  20. 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

  1. 40 CFR 147.1651 - EPA-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Indian lands, is administered by EPA. The program consists of the UIC program requirements of 40 CFR... Seneca Indian Tribe is June 25, 1984. The effective date for the UIC program for the lands of the...

  2. 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.

  3. 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

  4. Characterization of Fetal Antigen 1/Delta-Like 1 Homologue Expressing Cells in the Rat Nigrostriatal System: Effects of a Unilateral 6-Hydroxydopamine Lesion

    PubMed Central

    Liechti, Rémy; Ducray, Angélique D.; Jensen, Pia; Di Santo, Stefano; Seiler, Stefanie; Jensen, Charlotte H.; Meyer, Morten; Widmer, Hans Rudolf

    2015-01-01

    Fetal antigen 1/delta-like 1 homologue (FA1/dlk1) belongs to the epidermal growth factor superfamily and is considered to be a non-canonical ligand for the Notch receptor. Interactions between Notch and its ligands are crucial for the development of various tissues. Moreover, FA1/dlk1 has been suggested as a potential supplementary marker of dopaminergic neurons. The present study aimed at investigating the distribution of FA1/dlk1-immunoreactive (-ir) cells in the early postnatal and adult midbrain as well as in the nigrostriatal system of 6-hydroxydopamine (6-OHDA)-lesioned hemiparkinsonian adult rats. FA1/dlk1-ir cells were predominantly distributed in the substantia nigra (SN) pars compacta (SNc) and in the ventral tegmental area. Interestingly, the expression of FA1/dlk1 significantly increased in tyrosine hydroxylase (TH)-ir cells during early postnatal development. Co-localization and tracing studies demonstrated that FA1/dlk1-ir cells in the SNc were nigrostriatal dopaminergic neurons, and unilateral 6-OHDA lesions resulted in loss of both FA1/dlk1-ir and TH-ir cells in the SNc. Surprisingly, increased numbers of FA1/dlk1-ir cells (by 70%) were detected in dopamine-depleted striata as compared to unlesioned controls. The higher number of FA1/dlk1-ir cells was likely not due to neurogenesis as colocalization studies for proliferation markers were negative. This suggests that FA1/dlk1 was up-regulated in intrinsic cells in response to the 6-OHDA-mediated loss of FA1/dlk1-expressing SNc dopaminergic neurons and/or due to the stab wound. Our findings hint to a significant role of FA1/dlk1 in the SNc during early postnatal development. The differential expression of FA1/dlk1 in the SNc and the striatum of dopamine-depleted rats could indicate a potential involvement of FA1/dlk1 in the cellular response to the degenerative processes. PMID:25723595

  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. Application of encoded library technology (ELT) to a protein-protein interaction target: discovery of a potent class of integrin lymphocyte function-associated antigen 1 (LFA-1) antagonists.

    PubMed

    Kollmann, Christopher S; Bai, Xiaopeng; Tsai, Ching-Hsuan; Yang, Hongfang; Lind, Kenneth E; Skinner, Steven R; Zhu, Zhengrong; Israel, David I; Cuozzo, John W; Morgan, Barry A; Yuki, Koichi; Xie, Can; Springer, Timothy A; Shimaoka, Motomu; Evindar, Ghotas

    2014-04-01

    The inhibition of protein-protein interactions remains a challenge for traditional small molecule drug discovery. Here we describe the use of DNA-encoded library technology for the discovery of small molecules that are potent inhibitors of the interaction between lymphocyte function-associated antigen 1 and its ligand intercellular adhesion molecule 1. A DNA-encoded library with a potential complexity of 4.1 billion compounds was exposed to the I-domain of the target protein and the bound ligands were affinity selected, yielding an enriched small-molecule hit family. Compounds representing this family were synthesized without their DNA encoding moiety and found to inhibit the lymphocyte function-associated antigen 1/intercellular adhesion molecule-1 interaction with submicromolar potency in both ELISA and cell adhesion assays. Re-synthesized compounds conjugated to DNA or a fluorophore were demonstrated to bind to cells expressing the target protein. PMID:24593905

  7. Determinants of nurses' intention to administer opioids for pain relief.

    PubMed

    Edwards, H E; Nash, R E; Najman, J M; Yates, P M; Fentiman, B J; Dewar, A; Walsh, A M; McDowell, J K; Skerman, H M

    2001-09-01

    A statewide cross-sectional survey was conducted in Australia to identify the determinants of registered nurses' intention to administer opioids to patients with pain. Attitudes, subjective norms and perceived control, the key determinants of the Theory of Planned Behavior, were found to independently predict nurses' intention to administer opioids to these patients. Perceived control was the strongest predictor. Nurses reported positive overall attitudes towards opioids and their use in pain management. However, many negative attitudes were identified; for example, administering the least amount of opioid and encouraging patients to have non-opioids rather than opioids for pain relief. The findings related to specific attitudes and normative pressures provide insight into registered nurses' management of pain for hospitalized patients and the direction for educational interventions to improve registered nurses' administration of opioids for pain management.

  8. 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

  9. Systemic Effects of Vaginally Administered Estrogen Therapy: A Review

    PubMed Central

    Krause, Megan; Wheeler, Thomas L.; Richter, Holly E.; Snyder, Thomas E.

    2015-01-01

    Hormone Therapy (HT) was considered the standard of care prior to the publication of the Women’s Health Initiative (WHI). After the study was published, the use of systemic HT dramatically decreased resulting in an increased incidence of menopausal symptoms such as hot flashes, vaginal dryness and dyspareunia experienced by women. Use of vaginal estrogen offers women a unique alternative for relief of these symptoms. This article reviews the systemic effects of vaginally administered estrogen. Effects on serum hormone levels, vasomotor symptoms, lipid profiles and use in women with breast cancer are reviewed. An accompanying review examines the local effects of vaginally administered estrogen. PMID:22453284

  10. 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…

  11. 40 CFR 282.88 - Pennsylvania State-Administered Program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., Bureau of Land Recycling and Waste Management, Storage Tank Program, Rachel Carson State Office Building... WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.88 Pennsylvania State-Administered Program. (a) The Commonwealth of Pennsylvania's underground storage...

  12. 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...

  13. 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...

  14. 40 CFR 282.73 - Minnesota 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 Minnesota obtains... 40 Protection of Environment 27 2014-07-01 2014-07-01 false Minnesota State-Administered Program... WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.73...

  15. 40 CFR 282.73 - Minnesota 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 Minnesota obtains... 40 Protection of Environment 27 2011-07-01 2011-07-01 false Minnesota State-Administered Program... WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.73...

  16. 40 CFR 282.73 - Minnesota 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 Minnesota obtains... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Minnesota State-Administered Program... WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.73...

  17. 40 CFR 282.66 - Kansas State-Administered Program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    .... 6991c, and 40 CFR part 281, subpart E. If Kansas obtains approval for the revised requirements pursuant... 1976 (RCRA), as amended, 42 U.S.C. 6991 et seq. The State's program, as administered by the Kansas... subtitle I of RCRA, 42 U.S.C. 6991d and 6991e, as well as under other statutory and regulatory...

  18. 40 CFR 282.78 - Nevada State-Administered Program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., 42 U.S.C. 6991c, and 40 CFR part 281, subpart E. If Nevada obtains approval for the revised... 1976 (RCRA), as amended, 42 U.S.C. 6991 et seq. The state's program, as administered by the Nevada... of Subtitle I of RCRA, 42 U.S.C. 6991d and 6991e, as well as under other statutory and...

  19. 40 CFR 282.78 - Nevada State-Administered Program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., 42 U.S.C. 6991c, and 40 CFR part 281, subpart E. If Nevada obtains approval for the revised... 1976 (RCRA), as amended, 42 U.S.C. 6991 et seq. The state's program, as administered by the Nevada... of Subtitle I of RCRA, 42 U.S.C. 6991d and 6991e, as well as under other statutory and...

  20. 40 CFR 282.66 - Kansas State-Administered Program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    .... 6991c, and 40 CFR part 281, subpart E. If Kansas obtains approval for the revised requirements pursuant... 1976 (RCRA), as amended, 42 U.S.C. 6991 et seq. The State's program, as administered by the Kansas... subtitle I of RCRA, 42 U.S.C. 6991d and 6991e, as well as under other statutory and regulatory...

  1. 40 CFR 282.66 - Kansas State-Administered Program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    .... 6991c, and 40 CFR part 281, subpart E. If Kansas obtains approval for the revised requirements pursuant... 1976 (RCRA), as amended, 42 U.S.C. 6991 et seq. The State's program, as administered by the Kansas... subtitle I of RCRA, 42 U.S.C. 6991d and 6991e, as well as under other statutory and regulatory...

  2. 40 CFR 282.78 - Nevada State-Administered Program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., 42 U.S.C. 6991c, and 40 CFR part 281, subpart E. If Nevada obtains approval for the revised... 1976 (RCRA), as amended, 42 U.S.C. 6991 et seq. The state's program, as administered by the Nevada... of Subtitle I of RCRA, 42 U.S.C. 6991d and 6991e, as well as under other statutory and...

  3. 40 CFR 282.78 - Nevada State-Administered Program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., 42 U.S.C. 6991c, and 40 CFR part 281, subpart E. If Nevada obtains approval for the revised... 1976 (RCRA), as amended, 42 U.S.C. 6991 et seq. The state's program, as administered by the Nevada... of Subtitle I of RCRA, 42 U.S.C. 6991d and 6991e, as well as under other statutory and...

  4. 40 CFR 282.66 - Kansas State-Administered Program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    .... 6991c, and 40 CFR part 281, subpart E. If Kansas obtains approval for the revised requirements pursuant... 1976 (RCRA), as amended, 42 U.S.C. 6991 et seq. The State's program, as administered by the Kansas... subtitle I of RCRA, 42 U.S.C. 6991d and 6991e, as well as under other statutory and regulatory...

  5. 40 CFR 282.66 - Kansas State-Administered Program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    .... 6991c, and 40 CFR part 281, subpart E. If Kansas obtains approval for the revised requirements pursuant... 1976 (RCRA), as amended, 42 U.S.C. 6991 et seq. The State's program, as administered by the Kansas... subtitle I of RCRA, 42 U.S.C. 6991d and 6991e, as well as under other statutory and regulatory...

  6. 40 CFR 282.78 - Nevada State-Administered Program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., 42 U.S.C. 6991c, and 40 CFR part 281, subpart E. If Nevada obtains approval for the revised... 1976 (RCRA), as amended, 42 U.S.C. 6991 et seq. The state's program, as administered by the Nevada... of Subtitle I of RCRA, 42 U.S.C. 6991d and 6991e, as well as under other statutory and...

  7. Microcomputer-Administered Research: What it Means for Educational Researchers.

    ERIC Educational Resources Information Center

    Johnson, Craig W.

    1982-01-01

    The development of the microcomputer offers advantages for behavioral science and educational research. Among the potentials of microcomputer use are enhanced capacities for precise replication and extension, measurement, and experimental control and randomization, and the relative economy that microcomputer-administered experimental treatments…

  8. 40 CFR 282.94 - Utah State-Administered Program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    .... 6991c, and 40 CFR part 281, subpart E. If Utah obtains approval for the revised requirements pursuant to... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Utah State-Administered Program. 282.94 Section 282.94 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID...

  9. 40 CFR 282.61 - Hawaii State-Administered Program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    .... 6991c, and 40 CFR part 281, subpart E. If Hawaii obtains approval for the revised requirements pursuant... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Hawaii State-Administered Program. 282.61 Section 282.61 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID...

  10. 40 CFR 282.61 - Hawaii State-Administered Program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    .... 6991c, and 40 CFR part 281, subpart E. If Hawaii obtains approval for the revised requirements pursuant... 40 Protection of Environment 27 2011-07-01 2011-07-01 false Hawaii State-Administered Program. 282.61 Section 282.61 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID...

  11. 40 CFR 147.1100 - State-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Section 147.1100 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS..., except those on Indian lands, is the program administered by the Massachusetts Department of... Department of Environmental Quality Engineering, signed by the EPA Regional Administrator on August 18,...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  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. 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...

  3. 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...

  4. 40 CFR 147.3000 - EPA-administered program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... administered by EPA. (The term “Indian lands” is defined at 40 CFR 144.3.) The Navajo Indian lands are in the.... The UIC program for Navajo Indian lands, except for Class II wells on Navajo Indian lands for which..., except for Class II wells on Navajo Indian lands for which EPA has granted the Navajo Nation primacy......

  5. 40 CFR 147.3000 - EPA-administered program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... administered by EPA. (The term “Indian lands” is defined at 40 CFR 144.3.) The Navajo Indian lands are in the.... The UIC program for Navajo Indian lands, except for Class II wells on Navajo Indian lands for which..., except for Class II wells on Navajo Indian lands for which EPA has granted the Navajo Nation primacy......

  6. 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.... The UIC program for Navajo Indian lands, except for Class II wells on Navajo Indian lands for which..., except for Class II wells on Navajo Indian lands for which EPA has granted the Navajo Nation primacy......

  7. 40 CFR 147.151 - EPA-administered program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Navajo Indian lands consists of the UIC program requirements of 40 CFR parts 124, 144, 146, 148, and any..., including those on Indian lands, except for Class II wells on Navajo Indian lands for which EPA has granted... administered by EPA. The UIC program for Navajo Indian lands, except for Class II wells on Navajo Indian......

  8. 40 CFR 147.151 - EPA-administered program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Navajo Indian lands consists of the UIC program requirements of 40 CFR parts 124, 144, 146, 148, and any..., including those on Indian lands, except for Class II wells on Navajo Indian lands for which EPA has granted... administered by EPA. The UIC program for Navajo Indian lands, except for Class II wells on Navajo Indian......

  9. 40 CFR 147.151 - EPA-administered program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Navajo Indian lands consists of the UIC program requirements of 40 CFR parts 124, 144, 146, 148, and any..., including those on Indian lands, except for Class II wells on Navajo Indian lands for which EPA has granted... administered by EPA. The UIC program for Navajo Indian lands, except for Class II wells on Navajo Indian......

  10. 40 CFR 147.151 - EPA-administered program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Navajo Indian lands consists of the UIC program requirements of 40 CFR parts 124, 144, 146, 148, and any..., including those on Indian lands, except for Class II wells on Navajo Indian lands for which EPA has granted... administered by EPA. The UIC program for Navajo Indian lands, except for Class II wells on Navajo Indian......

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 40 CFR 147.1450 - State-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Director of the Federal Register in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. Copies may be... of Nevada, other than those on Indian lands, is the program administered by the Nevada Division of... Protection Agency, Region IX, 215 Fremont Street, San Francisco, California 99105, or at the...

  17. 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…

  18. 40 CFR 147.1300 - State-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program. 147.1300...) Opinion Letter No. 63 and attached Memorandum Opinion, signed by Attorney General of Missouri, March 16, 1982; (2) Addendum to Opinion Letter No. 63 (1982), signed by Attorney General of Missouri, October...

  19. Evaluation of coagulation via thromboelastography in healthy horses administered dexamethasone

    PubMed Central

    Woodman, Jenna; Wagg, Catherine R.; Boysen, Søren R.; Leguillette, Renaud; Mizen, Kyle; Roy, Marie-France

    2015-01-01

    Dexamethasone was administered to healthy horses daily for 7 days. Blood samples were collected at 3 time points from both treatment and non-treatment groups, and analyzed via thromboelastography (TEG). There were no significant differences in TEG parameters between treated and untreated horses, or within treatment groups over time. PMID:26677262

  20. 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......

  1. 40 CFR 147.950 - State-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... of Drilling Mud and Salt Water Generated from Drilling and Production of Oil and Gas Wells..., 1985 and January 20, 1986; (3)(i) Statewide Order Governing the Drilling for and Producing of Oil and... State-administered program. The UIC program for Class I, II, III, IV, and V wells in the State...

  2. Molecular Mechanisms of Taste Disorder in Oxaliplatin-administered Rats.

    PubMed

    Nishida, Kentaro

    2016-01-01

    Taste disorder is one of the adverse effects of cancer chemotherapy resulting in a loss of appetite, leading to malnutrition and a decrease in the quality of life of the patient. Oxaliplatin, a platinum anticancer drug, has a critical role in colon cancer chemotherapy and is known to induce taste disorder. Here, we evaluated the taste functions in oxaliplatin-administered rats. Among the taste receptors, expression levels of T1R2, one of the sweet receptor subunits, increased in the circumvallate papillae of the oxaliplatin-administered rats. In a brief-access test, i.e., behavioral analysis of the taste response, oxaliplatin-administered rats showed a decreased response to sweet taste. However, we did not detect any differences in the plasma levels of zinc, number of taste cells, or morphology of taste buds between control and oxaliplatin-administered rats. In conclusion, the decreased response to sweet taste by oxaliplatin administration may be due to the upregulation of T1R2 expression. PMID:27374965

  3. 40 CFR 147.151 - EPA-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Arizona § 147.151 EPA... the Navajo Nation primacy for the SDWA Class II UIC program (as defined in § 147.3400), is... for which EPA has granted the Navajo Nation primacy for the SDWA Class II UIC program, consists of...

  4. 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...

  5. 40 CFR 147.1700 - State-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 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...

  6. 40 CFR 147.1700 - State-administered program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 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. 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,...

  8. 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

  9. 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

  10. Analgesic efficacy of orally administered buprenorphine in rats.

    PubMed

    Martin, L B; Thompson, A C; Martin, T; Kristal, M B

    2001-02-01

    The analgesic effect of orally administered buprenorphine was compared with that induced by a standard therapeutic injected dose (0.05 mg/kg of body weight, s.c.) in male Long-Evans rats. Analgesia was assessed by measuring pain threshold, using the hot-water tail-flick assay before and after administration of buprenorphine. The results suggest that a commonly used formula for oral buprenorphine in flavored gelatin, at a dose of 0.5 mg/kg, does not increase pain threshold in rats. Instead, oral buprenorphine doses of 5 and 10 mg/kg were necessary to induce significant increases in pain threshold. However, these doses had to be administered by orogastric infusion because the rats would not voluntarily eat flavored gelatin containing this much buprenorphine. The depth of analgesia induced by these infused doses was comparable to that induced by the clinically effective s.c. treatment (0.05 mg/kg).

  11. 40 CFR 282.69 - Maine State-Administered Program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... section 9004 of RCRA, 42 U.S.C. 6991c, and 40 CFR part 281, subpart E. If Maine obtains approval for the... 1976 (RCRA), as amended, 42 U.S.C. 6991 et seq. The State's program, as administered by the Maine..., 7003, 9005 and 9006 of RCRA, 42 U.S.C. 6927, 6973, 6991d and 6991e, as well as under other...

  12. 40 CFR 282.69 - Maine State-Administered Program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... section 9004 of RCRA, 42 U.S.C. 6991c, and 40 CFR part 281, subpart E. If Maine obtains approval for the... 1976 (RCRA), as amended, 42 U.S.C. 6991 et seq. The State's program, as administered by the Maine..., 7003, 9005 and 9006 of RCRA, 42 U.S.C. 6927, 6973, 6991d and 6991e, as well as under other...

  13. 40 CFR 282.69 - Maine State-Administered Program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... section 9004 of RCRA, 42 U.S.C. 6991c, and 40 CFR part 281, subpart E. If Maine obtains approval for the... 1976 (RCRA), as amended, 42 U.S.C. 6991 et seq. The State's program, as administered by the Maine..., 7003, 9005 and 9006 of RCRA, 42 U.S.C. 6927, 6973, 6991d and 6991e, as well as under other...

  14. 40 CFR 282.69 - Maine State-Administered Program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... section 9004 of RCRA, 42 U.S.C. 6991c, and 40 CFR part 281, subpart E. If Maine obtains approval for the... 1976 (RCRA), as amended, 42 U.S.C. 6991 et seq. The State's program, as administered by the Maine..., 7003, 9005 and 9006 of RCRA, 42 U.S.C. 6927, 6973, 6991d and 6991e, as well as under other...

  15. 40 CFR 282.69 - Maine State-Administered Program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... section 9004 of RCRA, 42 U.S.C. 6991c, and 40 CFR part 281, subpart E. If Maine obtains approval for the... 1976 (RCRA), as amended, 42 U.S.C. 6991 et seq. The State's program, as administered by the Maine..., 7003, 9005 and 9006 of RCRA, 42 U.S.C. 6927, 6973, 6991d and 6991e, as well as under other...

  16. Nursing takes time: workload associated with administering cancer protocols.

    PubMed

    de Raad, Johan; van Gool, Kees; Haas, Marion; Haywood, Philip; Faedo, Margaret; Gallego, Gisselle; Pearson, Sallie; Ward, Robyn

    2010-12-01

    New medicines and therapeutic combinations are tested and marketed every year. Healthcare decision makers have to make explicit choices about adopting new treatments and deal with the resource consequences of their choices. The aim of this article is to examine the nursing workload of administering alternative chemotherapy protocols as a driver of costs. Data collection (focus groups with chemotherapy nurses and a survey of nurse unit managers) was conducted to ascertain the time required to undertake chemotherapy-related tasks and the sources of variability in six chemotherapy centers in New South Wales, Australia. Four task types (patient education, patient assessment, administration, and patient communication) were identified as being associated with administering chemotherapy. On average, patient education required 48 minutes during the first visit and 18.5 minutes thereafter, patient assessment took 20.3 minutes, administration averaged 23 minutes, and patient communication required 24.2 minutes. Each center treated an average of 14 patients per day. Each patient received 3.3 hours of staff time (1.7 hours of direct contact time and 1.6 hours of noncontact time). The result of this research will allow healthcare decision makers and evaluators to predict the amount of nursing time required to administer chemotherapy based on the characteristics of a wide range of chemotherapy protocols.

  17. 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.

  18. Pharmacokinetics of tetraplatin administered intraperitoneally with reduced glutathione in mice.

    PubMed

    Kido, Y; Khokhar, A R; Yoshida, M; Thai, G W; Siddik, Z H

    1994-01-01

    Tetraplatin (Ormaplatin) has been developed as a second generation platinum complex because of its good antitumor activity against some cisplatin-resistant tumor cell lines. It is currently in clinical trials. Its reduction to diaminocyclohexane (DACH)-dichloroplatinum(II) [DACH-Pt(II)Cl2] or closely similar species is essential for binding to DNA to produce the desired antitumor effects. We have studied the pharmacokinetics of tetraplatin in mice after intraperitoneal administration with the reducing agent glutathione (GSH). The systemic absorption of tetraplatin (5 mg/kg) with GSH (31 mg/kg) was faster than of tetraplatin alone. Peak plasma platinum (Pt) levels of 0.89 and 1.44 micrograms Pt/ml were observed at 15 min and 2 hr after administration of tetraplatin with and without GSH, respectively, and the Pt then decayed biphasically when administered with GSH and monophasically when administered alone. The plasma Pt level was 4-fold lower (0.17 vs. 0.71 micrograms Pt/ml) by 24 hr when tetraplatin was administered with GSH compared with its administration alone. DACH-Pt(II)Cl2 (4.21 mg/kg, ip) gave similar plasma Pt kinetics to that seen with the combination of tetraplatin and GSH. Pt levels in kidney 24 hr after administration of tetraplatin+GSH or of DACH-Pt(II)Cl2 were lower (1.6-fold) than after tetraplatin alone. Plasma and ascitic fluid from tumor-bearing mice demonstrated equivalent abilities to reduce tetraplatin rapidly. However, tetraplatin treatment of intraperitoneal-inoculated L1210/0 (parent) or L1210/DDP (cisplatin-resistant) tumor cells was unaffected by GSH. As GSH lowered systemic tetraplatin exposure in vivo without compromising antitumor activity against peritoneal tumor models, the combination of thiol and tetraplatin may be clinically useful in the treatment of intraperitoneal disseminated cancers. PMID:8013287

  19. Administering an epoch initiated for remote memory access

    DOEpatents

    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.

  20. 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.

  1. 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.

  2. Absorption and distribution of orally administered jojoba wax in mice.

    PubMed

    Yaron, A; Samoiloff, V; Benzioni, A

    1982-03-01

    The liquid wax obtained from the seeds of the arid-land shrub jojoba (Simmondsia chinensis) is finding increasing use in skin treatment preparations. The fate of this wax upon reaching the digestive tract was studied. 14C-Labeled wax was administered intragastrically to mice, and the distribution of the label in the body was determined as a function of time. Most of the wax was excreted, but a small amount was absorbed, as was indicated by the distribution of label in the internal organs and the epididymal fat. The label was incorporated into the body lipids and was found to diminish with time.

  3. 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.

  4. Administering truncated receive functions in a parallel messaging interface

    DOEpatents

    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.

  5. Analgesic and cardiovascular effects of centrally administered substance P.

    PubMed

    Clint, B D; Lipton, J M; Giesecke, A H

    1988-01-01

    Substance P (SP) injected intracerebroventricularly (ICV) into rabbits caused dose-related thermal analgesia with the maximum effect after 2 micrograms. The analgesia was measured by timing the withdrawal of the rabbit's ear from an infrared beam. Equimolar amounts of the related peptides physalaemin and eledoisin-related peptide also caused analgesia, but the SP N-terminal fragment (1-9) was inactive. This suggests that the analgesic message of SP resides within the C-terminal fragment. The analgesia caused by each peptide developed more rapidly but did not last as long as that after central injection of beta-endorphin. In separate experiments, 2 micrograms SP injected ICV increased blood pressure and decreased heart rate. The analgesic, bradycardic and pressor responses to central administration of SP were opposite to effects of peripherally administered SP, described previously. These results indicate that the effect induced by SP depends upon its specific neuroanatomical site of action.

  6. [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

  7. Human metabolism of orally administered radioactive cobalt chloride.

    PubMed

    Holstein, H; Ranebo, Y; Rääf, C L

    2015-05-01

    This study investigated the human gastrointestinal uptake (f1) and subsequent whole-body retention of orally administered inorganic radioactive cobalt. Of eight adult volunteers aged between 24 and 68 years, seven were given solutions of (57)Co (T1/2 = 272 d) containing a stable cobalt carrier, and six were given carrier-free (58)Co (T1/2 = 71 d). The administered activities ranged between 25 and 103 kBq. The observed mean f1, based on 6 days accumulated urinary excretion sampling and whole-body counting, was 0.028 ± 0.0048 for carrier-free (58)Co, and 0.016 ± 0.0021 for carrier-associated (57)Co. These values were in reasonable agreement with values reported from previous studies involving a single intake of inorganic cobalt. The time pattern of the total retention (including residual cobalt in the GI tract) included a short-term component with a biological half-time of 0.71 ± 0.03 d (average ± 1 standard error of the mean for the two nuclides), an intermediate component with a mean half-time of 32 ± 8.5 d, and a long-term component (observed in two volunteers) with half-times ranging from 80 to 720 d for the two isotopes. From the present data we conclude that for the short-lived (57)Co and (58)Co, more than 95% of the internal absorbed dose was delivered within 7 days following oral intake, with a high individual variation influenced by the transit time of the unabsorbed cobalt through the gastro-intestinal tract.

  8. Opponent process properties of self-administered cocaine.

    PubMed

    Ettenberg, Aaron

    2004-01-01

    Over the past decade, data collected in our laboratory have demonstrated that self-administered cocaine produces Opponent-Process-like behavioral effects. Animals running a straight alley once each day for IV cocaine develop over trials an approach-avoidance conflict about re-entering the goal box. This conflict behavior is characterized by a stop in forward locomotion (usually at the very mouth of the goal box) followed by a turn and 'retreat' back toward the goal box. The results of a series of studies conducted over the past decade collectively suggest that the behavioral ambivalence exemplified by rats running the alley for IV cocaine stems from concurrent and opponent positive (rewarding) and negative (anxiogenic) properties of the drug--both of which are associated with the goal box. These opponent properties of cocaine have been shown to result from temporally distinct affective states. Using a conditioned place preference test, we have been able to demonstrate that while the initial immediate effects of IV cocaine are reinforcing, the state present 15 min post-injection is aversive. In our most recent work, the co-administration of IV cocaine with either oral ethanol or IV heroin was found to greatly diminish the development and occurrence of retreat behaviors in the runway. It may therefore be that the high incidence of co-abuse of cocaine with either ethanol or heroin, stems from the users' motivation to alleviate some of the negative side effects of cocaine. It would seem then that the Opponent Process Theory has provided a useful conceptual framework for the study of the behavioral consequences of self-administered cocaine including the notion that both positive and negative reinforcement mechanisms are involved in the development and maintenance of cocaine abuse.

  9. 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.

  10. Opponent process properties of self-administered cocaine.

    PubMed

    Ettenberg, Aaron

    2004-01-01

    Over the past decade, data collected in our laboratory have demonstrated that self-administered cocaine produces Opponent-Process-like behavioral effects. Animals running a straight alley once each day for IV cocaine develop over trials an approach-avoidance conflict about re-entering the goal box. This conflict behavior is characterized by a stop in forward locomotion (usually at the very mouth of the goal box) followed by a turn and 'retreat' back toward the goal box. The results of a series of studies conducted over the past decade collectively suggest that the behavioral ambivalence exemplified by rats running the alley for IV cocaine stems from concurrent and opponent positive (rewarding) and negative (anxiogenic) properties of the drug--both of which are associated with the goal box. These opponent properties of cocaine have been shown to result from temporally distinct affective states. Using a conditioned place preference test, we have been able to demonstrate that while the initial immediate effects of IV cocaine are reinforcing, the state present 15 min post-injection is aversive. In our most recent work, the co-administration of IV cocaine with either oral ethanol or IV heroin was found to greatly diminish the development and occurrence of retreat behaviors in the runway. It may therefore be that the high incidence of co-abuse of cocaine with either ethanol or heroin, stems from the users' motivation to alleviate some of the negative side effects of cocaine. It would seem then that the Opponent Process Theory has provided a useful conceptual framework for the study of the behavioral consequences of self-administered cocaine including the notion that both positive and negative reinforcement mechanisms are involved in the development and maintenance of cocaine abuse. PMID:15019422

  11. Evaluation of a Self-Administered Oral Glucose Tolerance Test

    PubMed Central

    Bethel, M. Angelyn; Price, Hermione C.; Sourij, Harald; White, Sarah; Coleman, Ruth L.; Ring, Arne; Kennedy, Irene E.C.; Tucker, Lynne; Holman, Rury R.

    2013-01-01

    OBJECTIVE To assess the feasibility of using a disposable, self-administered, capillary blood sampling oral glucose tolerance test (OGTT) device in a community setting. RESEARCH DESIGN AND METHODS Eighteen healthy and 12 type 2 diabetic volunteers underwent six 75-g OGTTs using a prototype device in the following three settings: unaided at home (twice); unaided but observed in clinic (twice); and performed by a nurse with simultaneous laboratory glucose assays of 0- and 120-min venous plasma samples (twice). The device displayed no results. A detachable data recorder returned to the clinic provided plasma-equivalent 0- and 120-min glucose values and key parameters, including test date, start and end times, and time taken to consume the glucose drink. RESULTS The device was universally popular with participants and was perceived as easy to use, and the ability to test at home was well liked. Device failures meant that 0- and 120-min glucose values were obtained for only 141 (78%) of the 180 OGTTs performed, independent of setting. Device glucose measurements showed a mean bias compared with laboratory-measured values of +0.9 at 5.0 mmol/L increasing to +4.4 at 15.0 mmol/L. Paired device glucose values were equally reproducible across settings, with repeat testing showing no training effect regardless of setting order. CONCLUSIONS Self-administered OGTTs can be performed successfully by untrained individuals in a community setting. With improved device reliability and appropriate calibration, this novel technology could be used in routine practice to screen people who might need a formal OGTT to confirm the presence of impaired glucose tolerance or diabetes. PMID:23321216

  12. 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...

  13. 43 CFR 420.25 - Reclamation lands administered by other agencies.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... RECLAMATION, DEPARTMENT OF THE INTERIOR OFF-ROAD VEHICLE USE Designated Areas and Permitted Events § 420.25 Reclamation lands administered by other agencies. (a) Off-road vehicle use will be administered in...

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

    PubMed

    Hagler, James R; Machtley, Scott A

    2016-01-28

    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.

  15. A non-specific effect of orally administered Escherichia coli.

    PubMed

    Gardlik, Roman

    2011-01-01

    A number of genetically modified bacteria able to deliver a therapeutic gene into target cells has already been tested. Apart from the expected effects of bacterial therapy, the therapeutic bacterial strain also mediates a non-specific effect independent of the gene to be delivered. In this regard, we have recently shown that oral administration of the bacterial strain Escherichia coli XL1-Blue via gastric gavage to rats leads to a non-specific decrease in expression of vascular endothelial growth factor (VEGF) in intestinal wall without corresponding changes in other parameters. We tried to adopt a model of intestinal ischemia and to treat the subsequent hypoxic condition using a strain carrying the effector plasmid encoding hypoxia-inducible factor 1 alpha (HIF-1alpha), as well as the helper plasmid encoding invasion and listeriolysin O. However, the model was ineffective, as obvious from macroscopic and molecular observations. We hypothesize that a competitive behavior of the administered strain in the intestinal microbiota leads to a decrease in activity of HIF-1alpha and reduction in expression of VEGF. Also, a functional disease model would be necessary for the invasion-expressing therapeutic strain to be effective. A different approach using bacterial protein delivery would possibly circumvent these bactofection-related problems.

  16. Hemodynamic effects of centrally administered, norcocaine in the rat.

    PubMed

    Barber, D A; Tackett, R L

    1992-01-01

    Norcocaine is the N-demethylated metabolite of cocaine. It is present in the CNS and is reported to be pharmacologically active. The present study was designed to evaluate the cardiovascular actions of norcocaine following central administration. Wistar Kyoto (WKY) rats were anesthetized with pentobarbital and instrumented for measurement of blood pressure and renal and hindlimb blood flow (via Doppler flowprobes). A cerebroventricular cannula was placed in the lateral ventricle for drug administration. Cocaine or norcocaine was administered centrally in a dose range of 0.025 to 4.0 mg/kg. Under the above experimental conditions, 4.0 mg/kg of norcocaine decreased blood pressure without a significant change in either hind limb or renal blood flow. Central administration of cocaine also produced a similar depressor response. In conscious, unrestrained rats, cocaine produced a pressor response while norcocaine did not significantly alter blood pressure. The depressor response to both cocaine and norcocaine in the anesthetized animal is speculated to be due to the local anesthetic properties of the drugs.

  17. 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

  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. Experiences of administering and receiving therapeutic touch in intensive care.

    PubMed

    Cox, C; Hayes, J

    1998-10-01

    This article describes the experiences of a practitioner who administered therapeutic touch (TT) to two patients in an intensive care unit and the experiences of the two patients who received TT. The experiences are presented as two case studies. Each of the patients presented in the case studies received either five or ten treatments of TT lasting five minutes each. Following each administration of TT the practitioner described what she sensed verbally and in writing. However, owing to the medical conditions of the patients, only brief interviews were conducted in which the patients were asked to describe their experiences of receiving TT. The experiences, which have been reflected in the case studies, indicate TT assists patients to relax, brings comfort and a sense of peace. Much like meditation, TT helps patients become more in touch with themselves. They come to understand more about themselves and reality. TT is recommended as a practice which could contribute to the psychological well-being of patients in intensive care as it promotes relaxation, comfort and a sense of peace.

  20. Nicotine elicits methamphetamine-seeking in rats previously administered nicotine.

    PubMed

    Neugebauer, N M; Harrod, S B; Bardo, M T

    2010-01-01

    Research has indicated a high correlation between psychostimulant use and tobacco cigarette smoking in human substance abusers. The objective of the current study was to examine the effects of acute and repeated nicotine administration on responding for intravenous methamphetamine (0.03 mg/kg/infusion) in a rodent model of self-administration, as well as the potential of nicotine to induce reinstatement of previously extinguished drug-taking behavior in male Sprague-Dawley rats. In addition, it was assessed whether nicotine-induced reinstatement of methamphetamine-seeking behavior and nicotine-induced locomotor sensitization require that nicotine be temporally paired with the methamphetamine self-administration session or the locomotor activity chamber. Nicotine acutely decreased methamphetamine self-administration, but did not persistently alter responding during the maintenance of methamphetamine self-administration. However, following extinction of methamphetamine self-administration, nicotine administration reinstated methamphetamine-seeking behavior only in rats that had previously been administered nicotine. Nicotine-induced reinstatement and expression of locomotor sensitization were not dependent on a temporal pairing of nicotine with either the methamphetamine self-administration session or the locomotor activity chamber, respectively. These results indicate that nicotine may be acting, at least in part, through a non-associative mechanism to reinstate methamphetamine-seeking behavior.

  1. 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).

  2. Suppression of reagin synthesis in rabbits by passively administered antibody

    PubMed Central

    Strannegård, Ö.; Belin, L.

    1970-01-01

    The formation of rabbit antibodies, capable of sensitizing homologous skin, (reagins), was completely inhibited by passive administration of serum containing large quantities of 7S antibody 24 hours before or after antigen injection. No evident effect on reagin formation was noted when passive antibody was administered 8 days after antigen injection although some suppression of agglutinating antibody synthesis was observed. In rabbits not treated with passive antibody the injection of haemocyanin resulted in the formation of reagins reaching maximum serum concentrations 1 and 3 weeks following antigen injection. Both the `early' and `late' reagins persisted for a long time in the skin of injected rabbits, they appeared to have similar molecular size and both were devoid of PCA activity when injected into decomplemented rabbits. There was some indication that the `early' reagins may be more heat-labile than the `late' ones. A secondary reagin response was obtained in several animals which had shown a primary reagin response, but not in rabbits with inhibited primary response. The reagins formed in response to secondary antigen stimulation disappeared rapidly from the circulation, simultaneously with the rise in agglutinating antibody titres. The possible implications of the findings for the immunological treatment of allergic disorders is discussed. PMID:5420728

  3. 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

  4. 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

  5. [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

  6. 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.

  7. 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...

  8. 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...

  9. 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...

  10. 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... 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, 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...

  12. 40 CFR 147.2601 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ....2601 EPA-administered program—Indian lands. (a) Contents. The UIC program for Indian lands in the territory of Guam is administered by EPA. This program consists of the UIC program requirements of 40 CFR... 40 Protection of Environment 23 2011-07-01 2011-07-01 false EPA-administered program-Indian...

  13. 40 CFR 147.2510 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... § 147.2510 EPA-administered program—Indian lands. (a) Contents. The UIC program for Indian lands in the State of Wisconsin is administered by EPA. This program consists of 40 CFR parts 144 and 146 and... 40 Protection of Environment 22 2010-07-01 2010-07-01 false EPA-administered program-Indian...

  14. 40 CFR 147.2601 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ....2601 EPA-administered program—Indian lands. (a) Contents. The UIC program for Indian lands in the territory of Guam 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-Indian...

  15. 40 CFR 147.2510 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... § 147.2510 EPA-administered program—Indian lands. (a) Contents. The UIC program for Indian lands in the State of Wisconsin is administered by EPA. This program consists of 40 CFR parts 144 and 146 and... 40 Protection of Environment 23 2011-07-01 2011-07-01 false EPA-administered program-Indian...

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

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 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. 77 FR 19425 - Prescription Drugs Not Administered During Treatment; Update to Administrative Cost for Calendar...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-30

    ... AFFAIRS Prescription Drugs Not Administered During Treatment; Update to Administrative Cost for Calendar... purposes of calculating VA's charges for prescription drugs that were not administered during treatment but... administered during treatment for: (1) A nonservice-connected disability for which the veteran is entitled...

  18. 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...

  19. 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...

  20. 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...

  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, 2010 CFR

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 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. 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

  4. Liver regeneration in rats administered high levels of carbohydrates.

    PubMed

    Gershbein, L L

    1976-01-01

    Partially hepatectomized male rats were administered high levels of carbohydrates by drinker, in a casein-cellulose synthetic medium and in a commercial meal over a period of 10 days after surgery and the amount of liver regenerating or the increment ascertained; representative hepatic glycogen changes were also followed. Of the carbohydrate solutions, 5% levulose, 5% levulose+5% glucose and 10% sucrose increased the extent of liver regeneration as was also the case with the synthetic diet suplemented with 30 and 60% glucose, 30 and 60% levulose, 30% levulose+30% glucose, 30% each of galactose and the arabinoglactan, Stractan and 60% each of sucrose, honey and unsulphured molasses. The liver increments and glycogen contents were in the control range for animals fed the synthetic diet containing 30% each of lactose, sorbitol, corn starch and raffinose pentahydrate, 5% ascorbic acid and 15% L-arabinose but the liver glycogen was depressed with 30% xylose, a diet which was poorly tolerated; 15% mannitol caused a decrease inthe increment. The incorporation of several sugars into the commercial rat meal, including xylose (11%), raffinose (15%), L-arabinose (8%), D-arabinose (5%), L-sorbose (17%), galactosamine (0.20%) and galactono-gamma-lactone (10%), led to little change over the control increments. In intact rats fed the synthetic diet containing 30% each of glucose, lactose, galactose, sucrose and levulose for an interval of 10 days, the wet and dry liver--body weight ratios were significantly elevated only with the last two sugars but liver glycogen was increased in each instance.

  5. Maternal Satisfaction with Administering Infant Interventions in the NICU

    PubMed Central

    Holditch-Davis, Diane; White-Traut, Rosemary; Levy, Janet; Williams, Kristi L.; Ryan, Donna; Vonderheid, Susan

    2015-01-01

    Objective To examine mothers’ satisfaction with administering interventions for their preterm infants and with the helpfulness of the study nurse by comparing the ATVV intervention (massage with auditory, tactile, visual, and vestibular stimulation), kangaroo care, and education about equipment needed at home. Secondarily, to explore whether mother and infant characteristics affected maternal satisfaction ratings. Design Three-group experimental design. Setting Four NICUs (two in North Carolina, two in Illinois). Participants 208 preterm infants and their mothers. Methods When the infant was no longer critically ill, mother-infant dyads were randomly assigned to ATVV, kangaroo care, or the education group, all taught by study nurses. At discharge and 2 months corrected age, mothers completed questionnaires. Results All groups were satisfied with the intervention and with nurse helpfulness, and the degree of satisfaction did not differ among them. Intervention satisfaction, but not nurse helpfulness, was related to recruitment site. Older, married, and minority mothers were less satisfied with the intervention but only at 2 months. Higher anxiety was related to lower intervention satisfaction at discharge and lower ratings of nurse helpfulness at discharge and 2 months. More depressive symptoms were related to lower nurse helpfulness ratings at 2 months. Conclusions Mothers were satisfied with providing interventions for their infants regardless of the intervention performed. Maternal satisfaction with the intervention was related to recruitment site, maternal demographic characteristics, and maternal psychological distress, especially at 2 months. Thus, nursing interventions that provide mothers with a role to play in the infant’s care during hospitalization are particularly likely to be appreciated by mothers. PMID:25803213

  6. The accuracy of a patient or parent-administered bleeding assessment tool administered in a paediatric haematology clinic.

    PubMed

    Lang, A T; Sturm, M S; Koch, T; Walsh, M; Grooms, L P; O'Brien, S H

    2014-11-01

    Classifying and describing bleeding symptoms is essential in the diagnosis and management of patients with mild bleeding disorders (MBDs). There has been increased interest in the use of bleeding assessment tools (BATs) to more objectively quantify the presence and severity of bleeding symptoms. To date, the administration of BATs has been performed almost exclusively by clinicians; the accuracy of a parent-proxy BAT has not been studied. Our objective was to determine the accuracy of a parent-administered BAT by measuring the level of agreement between parent and clinician responses to the Condensed MCMDM-1VWD Bleeding Questionnaire. Our cross-sectional study included children 0-21 years presenting to a haematology clinic for initial evaluation of a suspected MBD or follow-up evaluation of a previously diagnosed MBD. The parent/caregiver completed a modified version of the BAT; the clinician separately completed the BAT through interview. The mean parent-report bleeding score (BS) was 6.09 (range: -2 to 25); the mean clinician report BS was 4.54 (range: -1 to 17). The mean percentage of agreement across all bleeding symptoms was 78% (mean κ = 0.40; Gwet's AC1 = 0.74). Eighty percent of the population had an abnormal BS (defined as ≥2) when rated by parents and 76% had an abnormal score when rated by clinicians (86% agreement, κ = 0.59, Gwet's AC1 = 0.79). While parents tended to over-report bleeding as compared to clinicians, overall, BSs were similar between groups. These results lend support for further study of a modified proxy-report BAT as a clinical and research tool.

  7. Influence of intravenously administered ciprofloxacin on aerobic intestinal microflora and fecal drug levels when administered simultaneously with sucralfate.

    PubMed Central

    Krueger, W A; Ruckdeschel, G; Unertl, K

    1997-01-01

    Ciprofloxacin, when given intravenously (i.v.), is secreted in significant amounts via the mucosa into the intestinal lumen. Sucralfate inhibits the antimicrobial activity of ciprofloxacin. The effect of combined therapy on the intestinal flora was investigated in 16 healthy volunteers. They were randomly assigned to two groups. Group A received 2 g of sucralfate orally three times a day for 7 days and 400 mg of ciprofloxacin i.v. twice a day (b.i.d.) starting 3 days after the sucralfate administration began. Group B was given only 400 mg of ciprofloxacin i.v. b.i.d. for 4 days. A total of 9 stool samples were collected from each subject beginning the week before ciprofloxacin was administered and on days -1, 1, 2, 3, 4, 7, 9, and 10 or 11 after commencement of the infusion period. The aerobic fecal flora was determined by standard microbiological methods. Measurements of fecal ciprofloxacin levels were based on high-performance liquid chromatography. Counts of bacteria of the family Enterobacteriaceae decreased in all subjects and were below 10(2) CFU/g in eight of eight subjects (group A) and six of eight subjects (group B) on day 4, but they returned to normal in all but one subject (group A) 10 days after the last infusion. The decreases in levels of bacteria of the family Enterobacteriaceae were not significantly different in groups A and B (Kaplan-Meier test). Staphylococci and nonfermenters responded variably, enterococci and lactobacilli remained unchanged, and candida levels increased transiently in four subjects (two in each group). Maximum fecal drug levels ranged from 251 to 811 microg/g. No significant difference could be found between the two groups. The i.v. application of ciprofloxacin eliminates intestinal bacteria of the family Enterobacteriaceae in a rapid and selective manner. This effect is not affected by simultaneous oral application of sucralfate. PMID:9257749

  8. Global Analysis of Palmitoylated Proteins in Toxoplasma gondii.

    PubMed

    Foe, Ian T; Child, Matthew A; Majmudar, Jaimeen D; Krishnamurthy, Shruthi; van der Linden, Wouter A; Ward, Gary E; Martin, Brent R; Bogyo, Matthew

    2015-10-14

    Post-translational modifications (PTMs) such as palmitoylation are critical for the lytic cycle of the protozoan parasite Toxoplasma gondii. While palmitoylation is involved in invasion, motility, and cell morphology, the proteins that utilize this PTM remain largely unknown. Using a chemical proteomic approach, we report a comprehensive analysis of palmitoylated proteins in T. gondii, identifying a total of 282 proteins, including cytosolic, membrane-associated, and transmembrane proteins. From this large set of palmitoylated targets, we validate palmitoylation of proteins involved in motility (myosin light chain 1, myosin A), cell morphology (PhIL1), and host cell invasion (apical membrane antigen 1, AMA1). Further studies reveal that blocking AMA1 palmitoylation enhances the release of AMA1 and other invasion-related proteins from apical secretory organelles, suggesting a previously unrecognized role for AMA1. These findings suggest that palmitoylation is ubiquitous throughout the T. gondii proteome and reveal insights into the biology of this important human pathogen.

  9. Comparison of total costs of administering calcium polycarbophil and psyllium mucilloid in an institutional setting.

    PubMed

    Mamtani, R; Cimino, J A; Cooperman, J M; Kugel, R

    1990-01-01

    The total cost of administering calcium polycarbophil per unit dose (two tablets) was compared with that of administering psyllium mucilloid (one packet dissolved in 8 oz of water) in 20 elderly nursing-home residents. Times for printing labels, checking and initialing labels, gathering materials needed, and preparing and administering the medications were recorded during at least 50 observations in each treatment group. Total cost included nurses' and pharmacists' time, materials, and medications. Calcium polycarbophil doses were prepared and administered more quickly (mean, 49.5 sec) than psyllium mucilloid (105.3 sec). The mean cost of preparing and administering a unit dose was 28.2 for calcium polycarbophil tablets and 59.9 for psyllium mucilloid. The results suggest that the use of calcium polycarbophil tablets would save time and money in institutions in which laxatives are frequently administered.

  10. Engagement of the small GTPase Rab31 protein and its effector, early endosome antigen 1, is important for trafficking of the ligand-bound epidermal growth factor receptor from the early to the late endosome.

    PubMed

    Chua, Christelle En Lin; Tang, Bor Luen

    2014-05-01

    Rab31 is a member of the Rab5 subfamily of Rab GTPases. Although localized largely to the trans-Golgi network, it shares common guanine nucleotide exchange factors and effectors with other Rab5 subfamily members that have been implicated in endocytic membrane traffic. We investigated whether Rab31 also has a role in the trafficking of the ligand-bound EGF receptor (EGFR) internalized through receptor-mediated endocytosis. We found that loss of Rab31 inhibits, but overexpression enhances, EGFR trafficking to the late endosomes and that the effect of Rab31 silencing could be specifically rescued by overexpression of a silencing-resistant form of Rab31. Rab31 was found to interact with the EGFR by coimmunoprecipitation and affinity pulldown analyses, and the primarily trans-Golgi network-localized Rab31 has increased colocalization with the EGFR in A431 cells 30 min after pulsing with EGF. A glycerol gradient sedimentation assay suggested that Rab31 is sequestered into a high molecular weight complex after stimulation with EGF, as was early endosome antigen 1 (EEA1), a factor responsible for endosomal tethering and fusion events. We found that loss of EEA1 reduced the interaction between Rab31 and the EGFR and abrogated the effect of Rab31 overexpression on the trafficking of the EGFR. Likewise, loss of GAPex5, a Rab31 guanine nucleotide exchange factor that has a role in ubiquitination and degradation of the EGFR, reduced the interaction of Rab31 with the EGFR and its effect on EGFR trafficking. Taken together, our results suggest that Rab31 is an important regulator of endocytic trafficking of the EGFR and functions in an EGFR trafficking complex that includes EEA1 and GAPex5.

  11. Bombyx mori nucleopolyhedrovirus nucleic acid binding proteins BRO-B and BRO-E associate with host T-cell intracellular antigen 1 homologue BmTRN-1 to influence protein synthesis during infection.

    PubMed

    Kotani, Eiji; Muto, Sayaka; Ijiri, Hiroshi; Mori, Hajime

    2015-07-01

    Previous reports have indicated that the Bombyx mori nucleopolyhedrovirus (BmNPV) nucleic acid binding proteins BRO-B and BRO-E are expressed during the early stage of infection and that the BRO family likely supports the regulation of mRNA; however, no study has directly examined the function of BRO family proteins in virus-permissive cells. Here, we show that BRO-B and BRO-E associate with cellular T-cell intracellular antigen 1 homologue (BmTRN-1), a translational regulator, and other cellular translation-related proteins in silkworm cells during viral infection. We created BM-N cells that expressed BRO-B/E to study molecular interactions between BmTRN-1 and BRO-B/E and how they influenced protein synthesis. Fluorescent microscopy revealed that BmTRN-1 was localized in cytoplasmic foci during BmNPV infection. Immunofluorescence studies confirmed that BmTRN-1 and BRO-B/E were colocalized in the amorphous conspicuous cytoplasmic foci. Reporter gene studies revealed that co-expression of BRO-B/E synergistically led to a significant decrease in protein synthesis from a designed transcript carrying the 5'untranslated region of a cellular mRNA with no significant change of transcript abundance. Additionally, RNA interference-mediated knockdown of BmTRN-1 resulted in a marked inhibition of the ability of BRO-B/E to regulate the transcript. These results suggested that the association of BmTRN-1 with BRO-B/E is responsible for the inhibitory regulation of certain mRNAs at the post-transcriptional level and add an additional mechanism for how baculoviruses control protein synthesis during infection. PMID:25834094

  12. Fusion of Epstein-Barr virus nuclear antigen-1-derived glycine-alanine repeat to trans-dominant HIV-1 Gag increases inhibitory activities and survival of transduced cells in vivo.

    PubMed

    Hammer, Diana; Wild, Jens; Ludwig, Christine; Asbach, Benedikt; Notka, Frank; Wagner, Ralf

    2008-06-01

    Trans-dominant human immunodeficiency virus type 1 (HIV-1) Gag derivatives have been shown to efficiently inhibit late steps of HIV-1 replication in vitro by interfering with Gag precursor assembly, thus ranking among the interesting candidates for gene therapy approaches. However, efficient antiviral activities of corresponding transgenes are likely to be counteracted in particular by cell-mediated host immune responses toward the transgene-expressing cells. To decrease this potential immunogenicity, a 24-amino acid Gly-Ala (GA) stretch derived from Epstein-Barr virus nuclear antigen-1 (EBNA1) and known to overcome proteasomal degradation was fused to a trans-dominant Gag variant (sgD1). To determine the capacity of this fusion polypeptide to repress viral replication, PM-1 cells were transduced with sgD1 and GAsgD1 transgenes, using retroviral gene transfer. Challenge of stably transfected permissive cell lines with various viral strains indicated that N-terminal GA fusion even enhanced the inhibitory properties of sgD1. Further studies revealed that the GA stretch increased protein stability by blocking proteasomal degradation of Gag proteins. Immunization of BALB/c mice with a DNA vaccine vector expressing sgD1 induced substantial Gag-specific immune responses that were, however, clearly diminished in the presence of GA. Furthermore, recognition of cells expressing the GA-fused transgene by CD8(+) T cells was drastically reduced, both in vitro and in vivo, resulting in prolonged survival of the transduced cells in recipient mice.

  13. Bombyx mori nucleopolyhedrovirus nucleic acid binding proteins BRO-B and BRO-E associate with host T-cell intracellular antigen 1 homologue BmTRN-1 to influence protein synthesis during infection.

    PubMed

    Kotani, Eiji; Muto, Sayaka; Ijiri, Hiroshi; Mori, Hajime

    2015-07-01

    Previous reports have indicated that the Bombyx mori nucleopolyhedrovirus (BmNPV) nucleic acid binding proteins BRO-B and BRO-E are expressed during the early stage of infection and that the BRO family likely supports the regulation of mRNA; however, no study has directly examined the function of BRO family proteins in virus-permissive cells. Here, we show that BRO-B and BRO-E associate with cellular T-cell intracellular antigen 1 homologue (BmTRN-1), a translational regulator, and other cellular translation-related proteins in silkworm cells during viral infection. We created BM-N cells that expressed BRO-B/E to study molecular interactions between BmTRN-1 and BRO-B/E and how they influenced protein synthesis. Fluorescent microscopy revealed that BmTRN-1 was localized in cytoplasmic foci during BmNPV infection. Immunofluorescence studies confirmed that BmTRN-1 and BRO-B/E were colocalized in the amorphous conspicuous cytoplasmic foci. Reporter gene studies revealed that co-expression of BRO-B/E synergistically led to a significant decrease in protein synthesis from a designed transcript carrying the 5'untranslated region of a cellular mRNA with no significant change of transcript abundance. Additionally, RNA interference-mediated knockdown of BmTRN-1 resulted in a marked inhibition of the ability of BRO-B/E to regulate the transcript. These results suggested that the association of BmTRN-1 with BRO-B/E is responsible for the inhibitory regulation of certain mRNAs at the post-transcriptional level and add an additional mechanism for how baculoviruses control protein synthesis during infection.

  14. 34 CFR 406.1 - What is the State-Administered Tech-Prep Education Program?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 34 Education 3 2014-07-01 2014-07-01 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...

  15. 34 CFR 406.1 - What is the State-Administered Tech-Prep Education Program?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 34 Education 3 2013-07-01 2013-07-01 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...

  16. 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 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...

  17. 34 CFR 406.1 - What is the State-Administered Tech-Prep Education Program?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 34 Education 3 2012-07-01 2012-07-01 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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)...

  6. 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)...

  7. 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...

  8. 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...

  9. 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...

  10. 40 CFR 272.151 - Arizona State-administered program: Final authorization.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Arizona State-administered program... (CONTINUED) SOLID WASTES (CONTINUED) APPROVED STATE HAZARDOUS WASTE MANAGEMENT PROGRAMS Arizona § 272.151 Arizona State-administered program: Final authorization. (a) Pursuant to section 3006(b) of RCRA, 42...

  11. 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... (CONTINUED) SOLID WASTES (CONTINUED) APPROVED STATE HAZARDOUS WASTE MANAGEMENT PROGRAMS Arizona § 272.151 Arizona State-administered program: Final authorization. (a) Pursuant to section 3006(b) of RCRA, 42...

  12. 40 CFR 272.151 - Arizona State-administered program: Final authorization.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 27 2011-07-01 2011-07-01 false Arizona State-administered program... (CONTINUED) SOLID WASTES (CONTINUED) APPROVED STATE HAZARDOUS WASTE MANAGEMENT PROGRAMS Arizona § 272.151 Arizona State-administered program: Final authorization. (a) Pursuant to section 3006(b) of RCRA, 42...

  13. 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... (CONTINUED) SOLID WASTES (CONTINUED) APPROVED STATE HAZARDOUS WASTE MANAGEMENT PROGRAMS Minnesota § 272.1201 Minnesota State-administered program; Final authorization. Pursuant to section 3006(b) of RCRA, 42...

  14. 40 CFR 272.1201 - Minnesota 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 Minnesota State-administered program... (CONTINUED) SOLID WASTES (CONTINUED) APPROVED STATE HAZARDOUS WASTE MANAGEMENT PROGRAMS Minnesota § 272.1201 Minnesota State-administered program; Final authorization. Pursuant to section 3006(b) of RCRA, 42...

  15. 40 CFR 272.1201 - Minnesota State-administered program; Final authorization.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 27 2011-07-01 2011-07-01 false Minnesota State-administered program... (CONTINUED) SOLID WASTES (CONTINUED) APPROVED STATE HAZARDOUS WASTE MANAGEMENT PROGRAMS Minnesota § 272.1201 Minnesota State-administered program; Final authorization. Pursuant to section 3006(b) of RCRA, 42...

  16. 40 CFR 272.1201 - Minnesota State-administered program; Final authorization.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Minnesota State-administered program... (CONTINUED) SOLID WASTES (CONTINUED) APPROVED STATE HAZARDOUS WASTE MANAGEMENT PROGRAMS Minnesota § 272.1201 Minnesota State-administered program; Final authorization. Pursuant to section 3006(b) of RCRA, 42...

  17. 40 CFR 272.1201 - Minnesota 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 Minnesota State-administered program... (CONTINUED) SOLID WASTES (CONTINUED) APPROVED STATE HAZARDOUS WASTE MANAGEMENT PROGRAMS Minnesota § 272.1201 Minnesota State-administered program; Final authorization. Pursuant to section 3006(b) of RCRA, 42...

  18. 40 CFR 147.1451 - 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... § 147.1451 EPA administered program—Indian lands. (a) Contents. The UIC program for all classes of...

  19. 40 CFR 147.1703 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... the UIC program requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set... 40 Protection of Environment 22 2010-07-01 2010-07-01 false EPA-administered program-Indian lands... Carolina § 147.1703 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes...

  20. 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... 40 Protection of Environment 23 2011-07-01 2011-07-01 false EPA-administered program-Indian lands... Island § 147.2001 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes...

  1. 40 CFR 147.1053 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... program requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth in the... 40 Protection of Environment 23 2011-07-01 2011-07-01 false EPA-administered program-Indian lands... § 147.1053 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of...

  2. 40 CFR 147.2253 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... wells on Indian lands consists of the UIC program requirements of 40 CFR parts 124, 144, 146, 148, and... 40 Protection of Environment 23 2011-07-01 2011-07-01 false EPA-administered program-Indian lands....2253 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of wells...

  3. 40 CFR 147.60 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... requirements of 40 CFR parts 124, 144, 146, 148 and any additional requirements set forth in the remainder of... 40 Protection of Environment 23 2011-07-01 2011-07-01 false EPA-administered program-Indian lands... § 147.60 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of...

  4. 40 CFR 147.1752 - 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... 40 Protection of Environment 22 2010-07-01 2010-07-01 false EPA-administered program-Indian lands... Dakota § 147.1752 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes...

  5. 40 CFR 147.2651 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... the UIC program requirements of 40 CFR parts 124, 144, 146, 148 and any additional requirements set... 40 Protection of Environment 22 2010-07-01 2010-07-01 false EPA-administered program-Indian lands... § 147.2651 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of...

  6. 40 CFR 147.1703 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... the UIC program requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set... 40 Protection of Environment 23 2011-07-01 2011-07-01 false EPA-administered program-Indian lands... Carolina § 147.1703 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes...

  7. 40 CFR 147.1403 - 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... § 147.1403 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of...

  8. 40 CFR 147.2553 - 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... § 147.2553 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of...

  9. 40 CFR 147.2453 - 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... 40 Protection of Environment 22 2010-07-01 2010-07-01 false EPA-administered program-Indian lands... Virginia § 147.2453 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes...

  10. 40 CFR 147.2403 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... except those of the Colville Tribe, consists of the UIC program requirements of 40 CFR parts 124, 144... 40 Protection of Environment 22 2010-07-01 2010-07-01 false EPA-administered program-Indian lands... § 147.2403 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of...

  11. 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... 40 Protection of Environment 22 2010-07-01 2010-07-01 false EPA-administered program-Indian lands... Island § 147.2001 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes...

  12. 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....651 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of wells...

  13. 40 CFR 147.1551 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... program requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth in the... 40 Protection of Environment 23 2011-07-01 2011-07-01 false EPA-administered program-Indian lands... § 147.1551 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of...

  14. 40 CFR 147.1303 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... program requirements of 40 CFR parts 124, 144, 145, 146, 148, and any additional requirements set forth in... 40 Protection of Environment 22 2010-07-01 2010-07-01 false EPA-administered program-Indian lands... § 147.1303 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of...

  15. 40 CFR 147.2253 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... wells on Indian lands 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-Indian lands....2253 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of wells...

  16. 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... § 147.205 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of...

  17. 40 CFR 147.860 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... program requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth in the... 40 Protection of Environment 23 2011-07-01 2011-07-01 false EPA-administered program-Indian lands... § 147.860 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of...

  18. 40 CFR 147.2403 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... except those of the Colville Tribe, consists of the UIC program requirements of 40 CFR parts 124, 144... 40 Protection of Environment 23 2011-07-01 2011-07-01 false EPA-administered program-Indian lands... § 147.2403 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of...

  19. 40 CFR 147.1805 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth in the remainder of... 40 Protection of Environment 23 2011-07-01 2011-07-01 false EPA-administered program-Indian lands....1805 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of wells...

  20. 40 CFR 147.205 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... requirements of 40 CFR parts 124, 144, 146, 148 and any additional requirements set forth in this subpart... 40 Protection of Environment 23 2011-07-01 2011-07-01 false EPA-administered program-Indian lands... § 147.205 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of...

  1. 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... § 147.60 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of...

  2. 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... § 147.703 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of...

  3. 40 CFR 147.1752 - 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... 40 Protection of Environment 23 2011-07-01 2011-07-01 false EPA-administered program-Indian lands... Dakota § 147.1752 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes...

  4. 40 CFR 147.553 - 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... § 147.553 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of...

  5. 40 CFR 147.1805 - 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....1805 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of wells...

  6. 40 CFR 147.1901 - 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... § 147.1901 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of...

  7. 40 CFR 147.2205 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth in the remainder of... 40 Protection of Environment 23 2011-07-01 2011-07-01 false EPA-administered program-Indian lands....2205 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of wells...

  8. 40 CFR 147.2303 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... program requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth in the... 40 Protection of Environment 23 2011-07-01 2011-07-01 false EPA-administered program-Indian lands... § 147.2303 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of...

  9. 40 CFR 147.1053 - 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... § 147.1053 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of...

  10. 40 CFR 147.1252 - 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... § 147.1252 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of...

  11. 40 CFR 147.1001 - 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....1001 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of wells...

  12. 40 CFR 147.403 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth in the remainder of... 40 Protection of Environment 23 2011-07-01 2011-07-01 false EPA-administered program-Indian lands... § 147.403 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of...

  13. 40 CFR 147.2051 - 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... 40 Protection of Environment 23 2011-07-01 2011-07-01 false EPA-administered program-Indian lands... Carolina § 147.2051 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes...

  14. 40 CFR 147.1852 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 23 2011-07-01 2011-07-01 false EPA-administered program-Indian lands... § 147.1852 EPA-administered program—Indian lands. (a) Contents. The UIC program for all wells on Indian... forth in subpart GGG of this part. The UIC program for all other wells on Indian lands consists of...

  15. 40 CFR 147.2651 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... the UIC program requirements of 40 CFR parts 124, 144, 146, 148 and any additional requirements set... 40 Protection of Environment 23 2011-07-01 2011-07-01 false EPA-administered program-Indian lands... § 147.2651 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of...

  16. 40 CFR 147.2303 - 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... § 147.2303 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of...

  17. 40 CFR 147.1101 - 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... 40 Protection of Environment 23 2011-07-01 2011-07-01 false EPA-administered program-Indian lands... Massachusetts § 147.1101 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes...

  18. 40 CFR 147.703 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... program requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth in the... 40 Protection of Environment 23 2011-07-01 2011-07-01 false EPA-administered program-Indian lands... § 147.703 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of...

  19. 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... § 147.353 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of...

  20. 40 CFR 147.1403 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... program requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth in the... 40 Protection of Environment 23 2011-07-01 2011-07-01 false EPA-administered program-Indian lands... § 147.1403 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of...

  1. 40 CFR 147.1501 - 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... 40 Protection of Environment 23 2011-07-01 2011-07-01 false EPA-administered program-Indian lands... Hampshire § 147.1501 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes...

  2. 40 CFR 147.2051 - 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... 40 Protection of Environment 22 2010-07-01 2010-07-01 false EPA-administered program-Indian lands... Carolina § 147.2051 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes...

  3. 40 CFR 147.1303 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... program requirements of 40 CFR parts 124, 144, 145, 146, 148, and any additional requirements set forth in... 40 Protection of Environment 23 2011-07-01 2011-07-01 false EPA-administered program-Indian lands... § 147.1303 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of...

  4. 40 CFR 147.1101 - 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... 40 Protection of Environment 22 2010-07-01 2010-07-01 false EPA-administered program-Indian lands... Massachusetts § 147.1101 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes...

  5. 40 CFR 147.1451 - EPA administered program-Indian lands.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... program requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth in the... 40 Protection of Environment 23 2011-07-01 2011-07-01 false EPA administered program-Indian lands... § 147.1451 EPA administered program—Indian lands. (a) Contents. The UIC program for all classes of...

  6. 40 CFR 147.860 - 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... § 147.860 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of...

  7. 40 CFR 147.1252 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... program requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth in the... 40 Protection of Environment 23 2011-07-01 2011-07-01 false EPA-administered program-Indian lands... § 147.1252 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of...

  8. 40 CFR 147.1001 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth in the remainder of... 40 Protection of Environment 23 2011-07-01 2011-07-01 false EPA-administered program-Indian lands....1001 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of wells...

  9. 40 CFR 147.2205 - 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....2205 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of wells...

  10. 40 CFR 147.951 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... program requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth in the... 40 Protection of Environment 23 2011-07-01 2011-07-01 false EPA-administered program-Indian lands... § 147.951 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of...

  11. 40 CFR 147.2453 - 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... 40 Protection of Environment 23 2011-07-01 2011-07-01 false EPA-administered program-Indian lands... Virginia § 147.2453 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes...

  12. 40 CFR 147.1603 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 23 2011-07-01 2011-07-01 false EPA-administered program-Indian lands... § 147.1603 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of wells on Indian lands in New Mexico, except for Class II wells on Navajo Indian lands for which EPA...

  13. 40 CFR 147.553 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... program requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth in the... 40 Protection of Environment 23 2011-07-01 2011-07-01 false EPA-administered program-Indian lands... § 147.553 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of...

  14. 40 CFR 147.651 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth in the remainder of... 40 Protection of Environment 23 2011-07-01 2011-07-01 false EPA-administered program-Indian lands....651 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of wells...

  15. 40 CFR 147.353 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth in the remainder of... 40 Protection of Environment 23 2011-07-01 2011-07-01 false EPA-administered program-Indian lands... § 147.353 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of...

  16. 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... § 147.403 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of...

  17. 40 CFR 147.1551 - 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... § 147.1551 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of...

  18. 40 CFR 147.1501 - 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... 40 Protection of Environment 22 2010-07-01 2010-07-01 false EPA-administered program-Indian lands... Hampshire § 147.1501 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes...

  19. 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... § 147.951 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of...

  20. 40 CFR 147.1901 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... program requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth in the... 40 Protection of Environment 23 2011-07-01 2011-07-01 false EPA-administered program-Indian lands... § 147.1901 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of...

  1. 40 CFR 147.2553 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... program requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth in the... 40 Protection of Environment 23 2011-07-01 2011-07-01 false EPA-administered program-Indian lands... § 147.2553 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of...

  2. 40 CFR 147.1852 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false EPA-administered program-Indian lands... § 147.1852 EPA-administered program—Indian lands. (a) Contents. The UIC program for all wells on Indian... forth in subpart GGG of this part. The UIC program for all other wells on Indian lands consists of...

  3. 47 CFR 64.1110 - State notification of election to administer FCC rules.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false State notification of election to administer FCC rules. 64.1110 Section 64.1110 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED... Telecommunications Service Providers § 64.1110 State notification of election to administer FCC rules. (a)...

  4. 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...

  5. 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...

  6. 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...

  7. 40 CFR 272.501 - Florida 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 Florida State-administered program... (CONTINUED) SOLID WASTES (CONTINUED) APPROVED STATE HAZARDOUS WASTE MANAGEMENT PROGRAMS Florida § 272.501 Florida State-administered program: Final authorization. (a) Pursuant to section 3006(b) of RCRA, 42...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 39 CFR 222.2 - Authority to administer oaths or function as notaries public.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Authority to administer oaths or function as notaries public. 222.2 Section 222.2 Postal Service UNITED STATES POSTAL SERVICE ORGANIZATION AND ADMINISTRATION DELEGATIONS OF AUTHORITY § 222.2 Authority to administer oaths or function as notaries public. (a) Authority to approve personnel actions...

  18. 48 CFR 3004.804-1 - Closeout by the office administering the contract.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Closeout by the office administering the contract. 3004.804-1 Section 3004.804-1 Federal Acquisition Regulations System DEPARTMENT OF... Government Contract Files 3004.804-1 Closeout by the office administering the contract. (b) The...

  19. Comparing Social Desirability Responding on World Wide Web and Paper-Administered Surveys.

    ERIC Educational Resources Information Center

    Hancock, Dawson R.; Flowers, Claudia P.

    2001-01-01

    Examines social desirability responding (SDR) on surveys administered on the World Wide Web and on paper to graduate and undergraduate students. Discusses response bias; describes use of the Balanced Inventory of Desirable Responding; and reports findings that reveal no differences in SDR between the Web-administered and paper-administered…

  20. 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…

  1. 40 CFR 147.2201 - State-administered program-Class II wells

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Texas § 147.2201 State-administered program—Class II wells The UIC program for Class II wells in the State of Texas, except for those wells on Indian lands, is the program administered by the Railroad Commission of Texas, approved by EPA pursuant to section 1425 of the SDWA. Notice of this approval...

  2. 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 §...

  3. 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 §...

  4. 40 CFR 147.2201 - State-administered program-Class II wells.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Texas § 147.2201 State-administered program—Class II wells. The UIC program for Class II wells in the State of Texas, except for those wells on Indian lands, is the program administered by the Railroad Commission of Texas, approved by EPA pursuant to section 1425 of the SDWA. Notice of this approval...

  5. 40 CFR 147.2201 - State-administered program-Class II wells.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Texas § 147.2201 State-administered program—Class II wells. The UIC program for Class II wells in the State of Texas, except for those wells on Indian lands, is the program administered by the Railroad Commission of Texas, approved by EPA pursuant to section 1425 of the SDWA. Notice of this approval...

  6. 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,...

  7. 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,...

  8. 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,...

  9. 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,...

  10. 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? 171.110 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...

  11. 48 CFR 904.804-1 - Closeout by the office administering the contract.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... administering the contract. 904.804-1 Section 904.804-1 Federal Acquisition Regulations System DEPARTMENT OF ENERGY GENERAL ADMINISTRATIVE MATTERS Government Contract Files 904.804-1 Closeout by the office administering the contract. (a) The Head of the Contracting Activity (HCA) shall ensure that...

  12. 48 CFR 4.804-1 - Closeout by the office administering the contract.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... administering the contract. 4.804-1 Section 4.804-1 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION GENERAL ADMINISTRATIVE MATTERS Government Contract Files 4.804-1 Closeout by the office administering the contract. (a) Except as provided in paragraph (c) below, time standards for closing...

  13. 48 CFR 3004.804-1 - Closeout by the office administering the contract.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Government Contract Files 3004.804-1 Closeout by the office administering the contract. (b) The quick closeout procedures under (FAR) 48 CFR 42.708 may be used for the settlement of indirect costs under... administering the contract. 3004.804-1 Section 3004.804-1 Federal Acquisition Regulations System DEPARTMENT...

  14. 48 CFR 904.804-1 - Closeout by the office administering the contract.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... administering the contract. 904.804-1 Section 904.804-1 Federal Acquisition Regulations System DEPARTMENT OF ENERGY GENERAL ADMINISTRATIVE MATTERS Government Contract Files 904.804-1 Closeout by the office administering the contract. (a) The Head of the Contracting Activity (HCA) shall ensure that...

  15. 48 CFR 4.804-1 - Closeout by the office administering the contract.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... administering the contract. 4.804-1 Section 4.804-1 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION GENERAL ADMINISTRATIVE MATTERS Government Contract Files 4.804-1 Closeout by the office administering the contract. (a) Except as provided in paragraph (c) below, time standards for closing...

  16. 48 CFR 4.804-1 - Closeout by the office administering the contract.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... administering the contract. 4.804-1 Section 4.804-1 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION GENERAL ADMINISTRATIVE MATTERS Government Contract Files 4.804-1 Closeout by the office administering the contract. (a) Except as provided in paragraph (c) below, time standards for closing...

  17. 48 CFR 904.804-1 - Closeout by the office administering the contract.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... administering the contract. 904.804-1 Section 904.804-1 Federal Acquisition Regulations System DEPARTMENT OF ENERGY GENERAL ADMINISTRATIVE MATTERS Government Contract Files 904.804-1 Closeout by the office administering the contract. (a) The Head of the Contracting Activity (HCA) shall ensure that...

  18. 48 CFR 904.804-1 - Closeout by the office administering the contract.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... administering the contract. 904.804-1 Section 904.804-1 Federal Acquisition Regulations System DEPARTMENT OF ENERGY GENERAL ADMINISTRATIVE MATTERS Government Contract Files 904.804-1 Closeout by the office administering the contract. (a) The Head of the Contracting Activity (HCA) shall ensure that...

  19. 48 CFR 4.804-1 - Closeout by the office administering the contract.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... administering the contract. 4.804-1 Section 4.804-1 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION GENERAL ADMINISTRATIVE MATTERS Government Contract Files 4.804-1 Closeout by the office administering the contract. (a) Except as provided in paragraph (c) below, time standards for closing...

  20. 48 CFR 4.804-1 - Closeout by the office administering the contract.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... administering the contract. 4.804-1 Section 4.804-1 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION GENERAL ADMINISTRATIVE MATTERS Government Contract Files 4.804-1 Closeout by the office administering the contract. (a) Except as provided in paragraph (c) below, time standards for closing...

  1. 48 CFR 904.804-1 - Closeout by the office administering the contract.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... administering the contract. 904.804-1 Section 904.804-1 Federal Acquisition Regulations System DEPARTMENT OF ENERGY GENERAL ADMINISTRATIVE MATTERS Government Contract Files 904.804-1 Closeout by the office administering the contract. (a) The Head of the Contracting Activity (HCA) shall ensure that...

  2. 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?...

  3. 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? 171.110 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...

  4. 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? 171.110 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...

  5. 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? 171.110 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...

  6. 40 CFR 147.1053 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... on Indian lands in the State of Maryland 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...

  7. 40 CFR 147.1053 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... on Indian lands in the State of Maryland 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...

  8. 40 CFR 147.1053 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... on Indian lands in the State of Maryland 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...

  9. 40 CFR 147.2551 - State-administered program-Class II wells.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS... State of Wyoming, except those on Indian lands, is the program administered by the Wyoming Oil and Gas... Director of the OFR in accordance with 5 U.S.C. 552(a) and 1 CFR Part 51. Copies may be obtained at...

  10. 40 CFR 147.2551 - State-administered program-Class II wells.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS... State of Wyoming, except those on Indian lands, is the program administered by the Wyoming Oil and Gas... Director of the OFR in accordance with 5 U.S.C. 552(a) and 1 CFR Part 51. Copies may be obtained at...

  11. Effects of Teacher- and Self-Administered Procedures on the Spelling Performance of Learning-Handicapped Children.

    ERIC Educational Resources Information Center

    Kapadia, E. Shireen; Fantuzzo, John W.

    1988-01-01

    Compared the relative effectiveness of teacher-administered and self-administered procedures on spelling for four educationally handicapped children using a modified reversal design. Found teacher- and self-administered interventions resulted in gains in performance, although self-administered procedures during treatment phases produced greater…

  12. Utilization of orally administered D-[14C]mannitol via fermentation by intestinal microbes in rats.

    PubMed

    Hongo, Ryoko; Nakamura, Sadako; Oku, Tsuneyuki

    2010-01-01

    To investigate the available energy of orally administered [(14)C]mannitol via intestinal microbes, [(14)C]mannitol (222 kBq, 105 mg) or [(14)C]glucose (222 kBq, 105 mg) was administered to conventional rats and antibiotics-treated rats whose intestinal microbes were depleted by drinking water containing antibiotics, respectively. The exhausted CO(2), feces and urine were then separately collected at 2, 4, 6, 8, 10, 12 and 24 h after administration of the test solution. In the conventional rats, 45% of administered radioactivity was recovered as (14)CO(2) in the administration of [(14)C]mannitol, while 57% of administered radioactivity was recovered as (14)CO(2) following the administration of [(14)C]glucose for 24 h. The time sequence for the (14)CO(2) excretion from [(14)C]mannitol was delayed as compared to [(14)C]glucose by about 4-6 h (p<0.05). However, when [(14)C]mannitol was orally administered to antibiotics-treated rats, only 3% of administered radioactivity was excreted as (14)CO(2) for 24 h. The total radioactivity of the gastrointestinal contents and feces for 24 h after administration was over 70%, much higher than those of the conventional rats (p<0.05). When a half dose (222 kBq, 52.5 mg) of [(14)C]mannitol was administered to conventional rats, the recovery as (14)CO(2) for 24 h (%) was significantly higher than that of a regular dose of [(14)C]mannitol (105 mg). When cold mannitol (105 mg) was orally administered to the antibiotics-treated rats, about 9% of intact mannitol was excreted in feces within 48 h after administration. However, no intact mannitol was detected in the conventional rats. These results demonstrate that more than 95% of mannitol administered orally is utilized via fermentation by intestinal microbes.

  13. The CC chemokine thymus-derived chemotactic agent 4 (TCA-4, secondary lymphoid tissue chemokine, 6Ckine, exodus-2) triggers lymphocyte function-associated antigen 1-mediated arrest of rolling T lymphocytes in peripheral lymph node high endothelial venules.

    PubMed

    Stein, J V; Rot, A; Luo, Y; Narasimhaswamy, M; Nakano, H; Gunn, M D; Matsuzawa, A; Quackenbush, E J; Dorf, M E; von Andrian, U H

    2000-01-01

    T cell homing to peripheral lymph nodes (PLNs) is defined by a multistep sequence of interactions between lymphocytes and endothelial cells in high endothelial venules (HEVs). After initial tethering and rolling via L-selectin, firm adhesion of T cells requires rapid upregulation of lymphocyte function-associated antigen 1 (LFA-1) adhesiveness by a previously unknown pathway that activates a Galpha(i)-linked receptor. Here, we used intravital microscopy of murine PLNs to study the role of thymus-derived chemotactic agent (TCA)-4 (secondary lymphoid tissue chemokine, 6Ckine, Exodus-2) in homing of adoptively transferred T cells from T-GFP mice, a transgenic strain that expresses green fluorescent protein (GFP) selectively in naive T lymphocytes (T(GFP) cells). TCA-4 was constitutively presented on the luminal surface of HEVs, where it was required for LFA-1 activation on rolling T(GFP) cells. Desensitization of the TCA-4 receptor, CC chemokine receptor 7 (CCR7), blocked T(GFP) cell adherence in wild-type HEVs, whereas desensitization to stromal cell-derived factor (SDF)-1alpha (the ligand for CXC chemokine receptor 4 [CXCR4]) did not affect T(GFP) cell behavior. TCA-4 protein was not detected on the luminal surface of PLN HEVs in plt/plt mice, which have a congenital defect in T cell homing to PLNs. Accordingly, T(GFP) cells rolled but did not arrest in plt/plt HEVs. When TCA-4 was injected intracutaneously into plt/plt mice, the chemokine entered afferent lymph vessels and accumulated in draining PLNs. 2 h after intracutaneous injection, luminal presentation of TCA-4 was detectable in a subset of HEVs, and LFA-1-mediated T(GFP) cell adhesion was restored in these vessels. We conclude that TCA-4 is both required and sufficient for LFA-1 activation on rolling T cells in PLN HEVs. This study also highlights a hitherto undocumented role for chemokines contained in afferent lymph, which may modulate leukocyte recruitment in draining PLNs.

  14. Induction of long-lasting protective immunity against Toxoplasma gondii in BALB/c mice by recombinant surface antigen 1 protein encapsulated in poly (lactide-co-glycolide) microparticles

    PubMed Central

    2013-01-01

    Background Current development efforts of subunit vaccines against Toxoplasma gondii, the etiological agent of toxoplasmosis, have been focused mainly on tachyzoite surface antigen 1 (SAG1). Since microparticles made from poly (lactide-co-glycolide) (PLG) polymers have been developed as safe, potent adjuvants or delivery systems, we aimed to encapsulate recombinant SAG1 (rSAG1) with the PLG polymers to prepare PLG-encapsulated rSAG1 (PLG-rSAG1) microparticles that would sustain rSAG1 release and generate long-lasting protective immunity against T. gondii in BALB/c mice. Methods In the present study, rSAG1 was encapsulated into PLG microparticles by the double emulsion method. PLG-rSAG1 microparticles were then intraperitoneally injected twice at a 14-day interval into BALB/c mice. We examined the ability of PLG-rSAG1 microparticles to induce and prolong effective anti-Toxoplasma immune responses, in comparison with rSAG1 formulated with a Vet L-10 adjuvant (rSAG1 (Vet L-10)). Eight weeks after the last immunization, protective activities were also evaluated after a lethal subcutaneous challenge of 1x104 live T. gondii tachyzoites. Results PLG-rSAG1 microparticles, 4.25~6.58 micrometers in diameter, showed 69%~81% entrapment efficiency. The amount of released rSAG1 protein from microparticles increased gradually over a 35-day period and the protein still retained native SAG1 antigenicity. Intraperitoneal vaccination of mice with the microparticles resulted in enhanced SAG1-specific IgG titers as well as lymphocyte proliferation and, more importantly, these enhanced activities were maintained for 10 weeks. In addition, eight weeks after the last immunization, maximum production of gamma interferon was detected in mice immunized with PLG-rSAG1 microparticles. Furthermore, 80% (8/10) of mice immunized with PLG-rSAG1 microparticles survived at least 28 days after a lethal subcutaneous tachyzoite challenge. Conclusions Encapsulation of rSAG1 into PLG microparticles

  15. 20 CFR 668.120 - How must INA programs be administered?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... WIA section 166(h)(1). (e) We will establish and maintain administrative procedures for the selection... this Act. We will utilize staff who have a particular competence in this field to administer...

  16. 30 CFR 250.1508 - What must I do when BSEE administers written or oral tests?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., DEPARTMENT OF THE INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Well Control and Production Safety Training § 250.1508 What must I do when BSEE administers written or...

  17. 30 CFR 250.1508 - What must I do when BSEE administers written or oral tests?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., DEPARTMENT OF THE INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Well Control and Production Safety Training § 250.1508 What must I do when BSEE administers written or...

  18. 30 CFR 250.1508 - What must I do when MMS administers written or oral tests?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Well Control and Production Safety Training § 250.1508 What must I do when MMS administers written or oral tests? MMS or...

  19. 30 CFR 250.1508 - What must I do when BSEE administers written or oral tests?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., DEPARTMENT OF THE INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Well Control and Production Safety Training § 250.1508 What must I do when BSEE administers written or...

  20. Effects of orally administered bovine lactoperoxidase on dextran sulfate sodium-induced colitis in mice.

    PubMed

    Shin, Kouichirou; Horigome, Ayako; Yamauchi, Koji; Takase, Mitsunori; Yaeshima, Tomoko; Iwatsuki, Keiji

    2008-07-01

    The effect of lactoperoxidase (LPO) on dextran sulfate sodium-induced colitis was examined in mice. After 9 d of colitis induction, weight loss, colon shortening, and the histological score were significantly suppressed in mice orally administered LPO (62.5 mg/body/d) as compared to a group administered bovine serum albumin. These results suggest that LPO exhibits anti-inflammatory effects in the gastrointestinal tract.

  1. 25 CFR 166.603 - If cash is submitted as a bond, how is it administered?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 1 2014-04-01 2014-04-01 false If cash is submitted as a bond, how is it administered? 166.603 Section 166.603 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER 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,...

  2. Validation of a self-administered questionnaire for assessing occupational and environmental exposures of pregnant women

    SciTech Connect

    Eskenazi, B.; Pearson, K.

    1988-11-01

    The present investigation sought to determine whether a self-administered questionnaire could be used to obtain occupational information from pregnant women attending the obstetrical clinics at the University of California, San Francisco from July to November 1986. The authors compared the accuracy of responses of 57 women on the self-administered questionnaire with those obtained on a detailed clinical interview by an occupational health professional. The self-administered questionnaire and the clinical interview included information on the woman's job title, the type of company she worked for, the level of physical activity, her exposures on the job and at home, and her partner's occupation. The authors also examined whether the validity of the self-administered questionnaire could be improved on review by an industrial hygienist. The questionnaire took less than 20 minutes to complete, with over 90% of the women answering three-quarters of it. It was substantially accurate in obtaining information on number of hours worked during pregnancy, type of shift worked, and stress level in the workplace; exposure to radiation, video display terminals, fumes, gases, and cigarette smoke in the workplace; and exposure to pesticides, paint, and cigarette smoke at home. On those variables for which the responses on the self-administered questionnaire were less accurate, review by the industrial hygienist improved the level of accuracy considerably. These findings suggest that a self-administered questionnaire can be used to obtain valid information from pregnant women attending a prenatal clinic.

  3. Genetic diversity of the Plasmodium falciparum apical membrane antigen I gene in parasite population from the China-Myanmar border area

    PubMed Central

    Zhu, Xiaotong; Zhao, Zhenjun; Feng, Yonghui; Li, Peipei; Liu, Fei; Liu, Jun; Yang, Zhaoqing; Yan, Guiyun; Fan, Qi; Cao, Yaming; Cui, Liwang

    2016-01-01

    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

  4. 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.

  5. Validation of interviewer- and self-administered physical activity checklists for fifth grade students.

    PubMed

    Sallis, J F; Strikmiller, P K; Harsha, D W; Feldman, H A; Ehlinger, S; Stone, E J; Williston, J; Woods, S

    1996-07-01

    The purpose of the study was to evaluate two physical activity recall instruments appropriate for use in epidemiologic studies of fifth grade children. The instruments were similar, except one (PACI) was administered in a personal interview, and the other (SAPAC) was self-completed in a group setting. Both forms required children to report the minutes during the previous day they spent in 21 common physical activities that represented a range of intensities, plus sedentary pursuits. To validate the recalls, children simultaneously wore an accelerometer (motion sensor) and a heart rate monitor for at least 8 h the day before the interview. Subjects were 55 boys and 70 girls from four regions of the United States. The Pearson correlation between the self- and interviewer-administered forms was 0.76 (P < 0.001). The interviewer-administered form correlated 0.51 (P < 0.001) with the heart rate index and 0.33 (P < 0.001) with the accelerometer score. The self-administered form correlated 0.57 (P < 0.001) with the heart rate index and 0.30 (P < 0.001) with the accelerometer score. It is concluded that both self-report forms received moderate support for their validity in all gender and ethnic subgroups. The self-administered format is more cost-effective. PMID:8832538

  6. 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

  7. 26 CFR 1.457-9 - Effect on eligible plans when not administered in accordance with eligibility requirements.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 6 2010-04-01 2010-04-01 false Effect on eligible plans when not administered... for Which Items of Gross Income Included § 1.457-9 Effect on eligible plans when not administered in... date on which the Commissioner notifies the State in writing that the plan is being administered in...

  8. 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...

  9. 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...

  10. 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.

  11. 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.

  12. Disclosure of sensitive behaviors across self-administered survey modes: a meta-analysis.

    PubMed

    Gnambs, Timo; Kaspar, Kai

    2015-12-01

    In surveys, individuals tend to misreport behaviors that are in contrast to prevalent social norms or regulations. Several design features of the survey procedure have been suggested to counteract this problem; particularly, computerized surveys are supposed to elicit more truthful responding. This assumption was tested in a meta-analysis of survey experiments reporting 460 effect sizes (total N =125,672). Self-reported prevalence rates of several sensitive behaviors for which motivated misreporting has been frequently observed were compared across self-administered paper-and-pencil versus computerized surveys. The results revealed that computerized surveys led to significantly more reporting of socially undesirable behaviors than comparable surveys administered on paper. This effect was strongest for highly sensitive behaviors and surveys administered individually to respondents. Moderator analyses did not identify interviewer effects or benefits of audio-enhanced computer surveys. The meta-analysis highlighted the advantages of computerized survey modes for the assessment of sensitive topics.

  13. Progesterone, administered prior to kainic acid, reduces decrements in cognitive performance in the Morris Water Maze

    PubMed Central

    Frye, Cheryl A.; Walf, Alicia

    2013-01-01

    The nature of progesterone (P4)’s neuroprotective effects is of interest. We investigated effects of P4 when administered prior to, or following, kainic acid, which produces ictal activity and damage to the hippocampus, to mediate effects on spatial performance. The hypothesis was that P4, compared to vehicle, would reduce decrements in Morris Water Maze performance induced by kainic acid. Experiment 1: We examined the effects of kainic acid on plasma stress hormone, corticosterone, and progestogen (P4 and its metabolites) levels in plasma and the hippocampus following subcutaneous (s.c.) P4 administration to ovariectomized rats. Rats administered kainic acid had the highest corticosterone levels immediately following injection. P4 is 5α-reduced to dihydroprogesterone (DHP) and subsequently metabolized to 5α-pregnan-3α-ol-20-one (3α,5α-THP) by 3α-hydroxysteroid dehydrogenase. The regimen of P4 utilized produced circulating and hippocampal levels of P4, DHP, and 3α,5α-THP within a physiological range, which decline at 14 hours post-injection, and were not altered by kainic acid. Experiment 2: The physiological P4 regimen was administered to rats before, or following, kainic acid-induced seizures, and later effects on water maze performance were compared to that of rats administered vehicle. Rats administered kainic acid had significantly poorer performance in the water maze (i.e. increased latencies and distances to the hidden platform) than did rats administered vehicle. Administration of P4 before, but not after, kainic acid prevented these performance deficits. Thus, these data suggest that a physiological regimen of P4 can prevent some of the deficits in water maze performance produced by kainic acid. PMID:20715152

  14. Pharmacokinetics of posaconazole administered orally or by nasogastric tube in healthy volunteers.

    PubMed

    Dodds Ashley, Elizabeth S; Varkey, Jay B; Krishna, Gopal; Vickery, Donna; Ma, Lei; Yu, Xin; Malavade, Darshana; Goodwin, Megan; Perfect, John R; Power, Eddie

    2009-07-01

    The use of a nasogastric tube is one means of administering antifungal therapy to critically ill patients unable to receive medication via the oral route. This was a phase 1, open-label, single-center, randomized, crossover study of posaconazole administered via nasogastric tube in healthy volunteers. Each subject received two 400-mg single doses of posaconazole, one administered orally and one administered by nasogastric tube, with a 7-day washout period between each dose. Posaconazole was administered 5 to 10 min after subjects received a nutritional supplement. Blood samples for pharmacokinetic analysis were obtained up to 120 h postdose. The analysis of variance estimate of the study population suggests that the posaconazole nasogastric tube administration least-square mean values of observed maximum concentration (C(max)), area under the plasma concentration-time curve (AUC) to the last measurable concentration, and AUC to time infinity were 81%, 76%, and 77%, respectively, of the corresponding oral administration values. The reason for lower C(max) and AUC values when posaconazole is administered via the nasogastric tube route is not known. Oral and nasogastric tube administration of a single 400-mg dose of posaconazole suspension was safe and well tolerated in healthy adult subjects. The incidence and nature of treatment-emergent adverse events were similar with both administration routes, and no serious adverse events or clinically significant laboratory test or vital sign abnormalities were reported. Obtaining plasma posaconazole concentrations may be warranted when posaconazole is given to patients via a nasogastric tube to ensure adequate posaconazole exposure. Strategies that have been shown to enhance posaconazole exposure (such as splitting the dose and minimizing the use of proton pump inhibitors) may also be used.

  15. 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

  16. 20 CFR 641.610 - How are pilot, demonstration, and evaluation projects administered?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 3 2012-04-01 2012-04-01 false How are pilot, demonstration, and evaluation projects administered? 641.610 Section 641.610 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION..., and Evaluation Projects § 641.610 How are pilot, demonstration, and evaluation projects...

  17. 20 CFR 641.610 - How are pilot, demonstration, and evaluation projects administered?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 3 2013-04-01 2013-04-01 false How are pilot, demonstration, and evaluation projects administered? 641.610 Section 641.610 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION..., and Evaluation Projects § 641.610 How are pilot, demonstration, and evaluation projects...

  18. 20 CFR 641.610 - How are pilot, demonstration, and evaluation projects administered?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false How are pilot, demonstration, and evaluation projects administered? 641.610 Section 641.610 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION..., and Evaluation Projects § 641.610 How are pilot, demonstration, and evaluation projects...

  19. 20 CFR 641.610 - How are pilot, demonstration, and evaluation projects administered?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 3 2014-04-01 2014-04-01 false How are pilot, demonstration, and evaluation projects administered? 641.610 Section 641.610 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION..., and Evaluation Projects § 641.610 How are pilot, demonstration, and evaluation projects...

  20. 40 CFR 272.701 - State-administered program: Final authorization.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Register in accordance with 5 U.S.C. 552(a) and 1 CFR part 51 as part of the hazardous waste management... 40 Protection of Environment 28 2013-07-01 2013-07-01 false State-administered program: Final authorization. 272.701 Section 272.701 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY...

  1. 40 CFR 272.1301 - 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 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...

  2. 40 CFR 272.2501 - Wisconsin 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 Wisconsin State-administered program: Final authorization. 272.2501 Section 272.2501 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) APPROVED STATE HAZARDOUS WASTE MANAGEMENT PROGRAMS Wisconsin §...

  3. 40 CFR 272.151 - Arizona 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 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 §...

  4. 40 CFR 272.651 - Idaho 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 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...

  5. 40 CFR 272.401 - 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 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...

  6. 40 CFR 272.2251 - Utah 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 Utah State-Administered program: Final authorization. 272.2251 Section 272.2251 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) APPROVED STATE HAZARDOUS WASTE MANAGEMENT PROGRAMS Utah § 272.2251 Utah...

  7. 40 CFR 272.1301 - 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 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...

  8. 40 CFR 272.501 - Florida State-administered program: Final authorization.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    .../92 Recycled Used Oil Management Standards (Checklist 112) 57 FR 41566: Amendments to 40 CFR Parts 260... 40 Protection of Environment 28 2013-07-01 2013-07-01 false Florida State-administered program: Final authorization. 272.501 Section 272.501 Protection of Environment ENVIRONMENTAL PROTECTION...

  9. 40 CFR 272.1351 - Montana 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 Montana State-Administered Program: Final Authorization. 272.1351 Section 272.1351 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) APPROVED STATE HAZARDOUS WASTE MANAGEMENT PROGRAMS Montana §...

  10. 40 CFR 272.1801 - 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 State-administered program: Final authorization. 272.1801 Section 272.1801 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) APPROVED STATE HAZARDOUS WASTE MANAGEMENT PROGRAMS Ohio § 272.1801...

  11. 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 §...

  12. 40 CFR 272.701 - State-administered program: Final authorization.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Register in accordance with 5 U.S.C. 552(a) and 1 CFR part 51 as part of the hazardous waste management... 40 Protection of Environment 28 2012-07-01 2012-07-01 false State-administered program: Final authorization. 272.701 Section 272.701 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY...

  13. 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 §...

  14. 40 CFR 272.401 - 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 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...

  15. 40 CFR 272.1801 - 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 State-administered program: Final authorization. 272.1801 Section 272.1801 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) APPROVED STATE HAZARDOUS WASTE MANAGEMENT PROGRAMS Ohio § 272.1801...

  16. 40 CFR 272.151 - Arizona 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 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 §...

  17. 50 CFR 86.115 - How should I administer the survey?

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... (BIG) PROGRAM How States Will Complete Access Needs Surveys § 86.115 How should I administer the survey... methodology to collect data, which may include telephone, mail, fax, or other inventory means. We do not expect you to use automated, electronic, mechanical, or similar means of information collection. (d)...

  18. 50 CFR 86.115 - How should I administer the survey?

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... (BIG) PROGRAM How States Will Complete Access Needs Surveys § 86.115 How should I administer the survey... methodology to collect data, which may include telephone, mail, fax, or other inventory means. We do not expect you to use automated, electronic, mechanical, or similar means of information collection. (d)...

  19. 45 CFR 400.65 - Continuation of a publicly-administered RCA program.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 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. [Distribution of orally administered aflatoxin B 1 in the tissues and organs of the goat (Capra)].

    PubMed

    Veselý, D; Veselá, D; Kusák, V; Nesnídal, P

    1978-09-01

    In the experiment the goat was administered an amount of 450 mg aflatoxin B1. The milk taken during the experiment was lyophilized and aflatoxins B1 and M1 were isolated. After the death of the goat some tissues, blood and bile of the experimental animal were analyzed to find out the aflatoxin content.

  1. 40 CFR 147.2205 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... requirements of 40 CFR parts 124, 144, 146, 148, and any additional requirements set forth in the remainder of.... 147.2205 Section 147.2205 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER....2205 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of wells...

  2. DEVELOPMENTAL EFFECTS OF TRICHLOROACETONITRILE ADMINISTERED IN CORN OIL TO PREGNANT LONG-EVANS RATS

    EPA Science Inventory

    Trichloroacetonitrile (TCAN) is a by-product of the chlorine disinfection of water containing natural organic material. When administered by gavage to pregnant Long-Evans rats in a medium-chain triglyceride vehicle, tricaprylin oil (Tricap), at a volume of 10 ml/kg, TCAN induced ...

  3. 40 CFR 147.52 - State-administered program-Hydraulic Fracturing of Coal Beds.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...) The Program Description for the Regulation of Hydraulic Fracturing of Coal Beds As required by 40 CFR... PROGRAMS Alabama § 147.52 State-administered program—Hydraulic Fracturing of Coal Beds. The UIC program for hydraulic fracturing of coal beds in the State of Alabama, except those on Indian lands, is the...

  4. 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...) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS... shall plug and abandon the well according to the approved plan and schedule....

  5. 40 CFR 147.2404 - EPA-administered program-Colville Reservation.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... CFR part 124, 144 and 146 and any additional requirements set forth in the remainder of this subpart...) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS... shall plug and abandon the well according to the approved plan and schedule....

  6. 40 CFR 147.2404 - EPA-administered program-Colville Reservation.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... CFR part 124, 144 and 146 and any additional requirements set forth in the remainder of this subpart...) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS... shall plug and abandon the well according to the approved plan and schedule....

  7. 40 CFR 147.2404 - EPA-administered program-Colville Reservation.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... CFR part 124, 144 and 146 and any additional requirements set forth in the remainder of this subpart...) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS... shall plug and abandon the well according to the approved plan and schedule....

  8. 40 CFR 147.2404 - EPA-administered program-Colville Reservation.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... CFR part 124, 144 and 146 and any additional requirements set forth in the remainder of this subpart...) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS... shall plug and abandon the well according to the approved plan and schedule....

  9. 40 CFR 147.1400 - State-administered program-Class II wells.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... State of Nebraska, except those on Indian lands, is the program administered by the Nebraska Oil and Gas..., 1984. (1) Rules and Regulations of the Nebraska Oil and Gas Conservation Commission, Rules 1 through 6...-906 (Reissue 1988). (b) Other laws. The following statutes and regulations, although not...

  10. 40 CFR 147.1400 - State-administered program-Class II wells.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... State of Nebraska, except those on Indian lands, is the program administered by the Nebraska Oil and Gas..., 1984. (1) Rules and Regulations of the Nebraska Oil and Gas Conservation Commission, Rules 1 through 6...-906 (Reissue 1988). (b) Other laws. The following statutes and regulations, although not...

  11. Testing Adult Basic Education Students for Reading Ability and Progress: How Many Tests to Administer?

    ERIC Educational Resources Information Center

    Greenberg, Daphne; Levy, Susan R.; Rasher, Sue; Kim, Yoonsang; Carter, Sarah Deardorff; Berbaum, Michael L.

    2010-01-01

    This study examines the relationship between TABE-R performance and performance on selected, more focused reading component tests after 42 hours of adult education classroom instruction. Specifically, measures of expressive vocabulary, reading fluency, sight word reading, and decoding were administered to 98 participants along with the TABE-R.…

  12. 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…

  13. 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

    ... recipients participating in the HUD administered CDBG program provides HUD with financial and physical... technology, e.g., permitting electronic submission of responses. This notice also lists the following... program provides HUD with financial and physical development status of each activity funded. These...

  14. 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…

  15. 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... WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.98...

  16. 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,…

  17. The Assessment of Role Identity: Problems of Administering the Instrumental Activities Inventory to Inuit Children.

    ERIC Educational Resources Information Center

    McElroy, Ann

    A modified version of the Instrumental Activities Inventory (IAI) was administered to a sample of Canadian Inuit children (41 girls and 37 boys aged 9 to 17 from Frobisher Bay and 40 boys and 35 girls aged 8 to 16 from Pangnirtung) for purposes of assessing role model preferences relative to the socialization process. Consisting of 12 female and…

  18. 9 CFR 103.2 - Disposition of animals administered experimental biological products or live organisms.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Disposition of animals administered experimental biological products or live organisms. 103.2 Section 103.2 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND...

  19. 9 CFR 103.2 - Disposition of animals administered experimental biological products or live organisms.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Disposition of animals administered experimental biological products or live organisms. 103.2 Section 103.2 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND...

  20. 9 CFR 103.2 - Disposition of animals administered experimental biological products or live organisms.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Disposition of animals administered experimental biological products or live organisms. 103.2 Section 103.2 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND...

  1. 9 CFR 103.2 - Disposition of animals administered experimental biological products or live organisms.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Disposition of animals administered experimental biological products or live organisms. 103.2 Section 103.2 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND...

  2. 24 CFR 511.50 - State election to administer a rental rehabilitation program.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... rental rehabilitation program. 511.50 Section 511.50 Housing and Urban Development Regulations Relating... GRANT PROGRAM State Program § 511.50 State election to administer a rental rehabilitation program. (a) State allocations may be used to carry out eligible rehabilitation activities in accordance with...

  3. 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...

  4. 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...

  5. 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...

  6. 76 FR 72211 - Notice of Proposed Information Collection: Comment Request, HUD-Administered Small Cities Program...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-22

    ... URBAN DEVELOPMENT Notice of Proposed Information Collection: Comment Request, HUD- Administered Small... be sent to: William Kelleher, Reports Liaison Officer, Department of Housing and Urban Development... previously approved collection for which approval has expired, and a request for OMB renewal for three...

  7. 24 CFR 511.50 - State election to administer a rental rehabilitation program.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... DEVELOPMENT, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT SLUM CLEARANCE AND URBAN RENEWAL RENTAL REHABILITATON... 24 Housing and Urban Development 3 2010-04-01 2010-04-01 false State election to administer a rental rehabilitation program. 511.50 Section 511.50 Housing and Urban Development Regulations...

  8. 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...

  9. 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…

  10. 43 CFR 420.25 - Reclamation lands administered by other agencies.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 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...

  11. 76 FR 71830 - Defense Federal Acquisition Regulation Supplement: Administering Trafficking in Persons...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-18

    ... Regulation Supplement: Administering Trafficking in Persons Regulations (DFARS Case 2011-D051) AGENCY... compliance with duties and responsibilities pertaining to trafficking in persons when they are incorporated... Trafficking in Persons, in all solicitations and contracts. When the contract will be performed outside...

  12. 40 CFR 282.102 - Puerto Rico State-Administered Program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... program which make it more stringent, in accordance with section 9004 of RCRA, 42 U.S.C. 6991c, and 40 CFR... 40 Protection of Environment 28 2012-07-01 2012-07-01 false Puerto Rico State-Administered Program... WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.102...

  13. 40 CFR 272.2101 - South Dakota State-Administered Program: Final Authorization.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 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 Dakota State-Administered Program: Final Authorization. (a) Pursuant to...

  14. Telephone-Administered Cognitive Behavioral Therapy for Veterans Served by Community-Based Outpatient Clinics

    ERIC Educational Resources Information Center

    Mohr, David C.; Carmody, Timothy; Erickson, Lauren; Jin, Ling; Leader, Julie

    2011-01-01

    Objective: Multiple trials have found telephone-administered cognitive behavioral therapy (T-CBT) to be effective for the treatment of depression. The aim of this study was to evaluate T-CBT for the treatment of depression among veterans served by community-based outpatient clinics (CBOCs) outside of major urban areas. Method: Eighty-five veterans…

  15. 40 CFR 147.1603 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... on Indian lands in New Mexico, except for Class II wells on Navajo Indian lands for which EPA has... effective date for the UIC program on Indian lands in New Mexico, except for Class II wells on Navajo Indian... 40 Protection of Environment 24 2013-07-01 2013-07-01 false EPA-administered program-Indian...

  16. 40 CFR 147.2253 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Indian lands in the State of Utah, except for Class II wells on Navajo Indian lands for which EPA has... administered by EPA. The program for wells on Navajo Indian lands, except for Class II wells on Navajo Indian... wells on Indian lands consists of the UIC program requirements of 40 CFR parts 124, 144, 146, 148,...

  17. 40 CFR 147.1603 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... on Indian lands in New Mexico, except for Class II wells on Navajo Indian lands for which EPA has... effective date for the UIC program on Indian lands in New Mexico, except for Class II wells on Navajo Indian... 40 Protection of Environment 24 2012-07-01 2012-07-01 false EPA-administered program-Indian...

  18. 40 CFR 147.2253 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Indian lands in the State of Utah, except for Class II wells on Navajo Indian lands for which EPA has... administered by EPA. The program for wells on Navajo Indian lands, except for Class II wells on Navajo Indian... wells on Indian lands consists of the UIC program requirements of 40 CFR parts 124, 144, 146, 148,...

  19. 40 CFR 147.1603 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... on Indian lands in New Mexico, except for Class II wells on Navajo Indian lands for which EPA has... effective date for the UIC program on Indian lands in New Mexico, except for Class II wells on Navajo Indian... 40 Protection of Environment 23 2014-07-01 2014-07-01 false EPA-administered program-Indian...

  20. 40 CFR 147.2253 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Indian lands in the State of Utah, except for Class II wells on Navajo Indian lands for which EPA has... administered by EPA. The program for wells on Navajo Indian lands, except for Class II wells on Navajo Indian... wells on Indian lands consists of the UIC program requirements of 40 CFR parts 124, 144, 146, 148,...