Science.gov

Sample records for 80s initiation complex

  1. Role of Pre-rRNA Base Pairing and 80S Complex Formation in Subnucleolar Localization of the U3 snoRNP

    PubMed Central

    Granneman, Sander; Vogelzangs, Judith; Lührmann, Reinhard; van Venrooij, Walther J.; Pruijn, Ger J. M.; Watkins, Nicholas J.

    2004-01-01

    In the nucleolus the U3 snoRNA is recruited to the 80S pre-rRNA processing complex in the dense fibrillar component (DFC). The U3 snoRNA is found throughout the nucleolus and has been proposed to move with the preribosomes to the granular component (GC). In contrast, the localization of other RNAs, such as the U8 snoRNA, is restricted to the DFC. Here we show that the incorporation of the U3 snoRNA into the 80S processing complex is not dependent on pre-rRNA base pairing sequences but requires the B/C motif, a U3-specific protein-binding element. We also show that the binding of Mpp10 to the 80S U3 complex is dependent on sequences within the U3 snoRNA that base pair with the pre-rRNA adjacent to the initial cleavage site. Furthermore, mutations that inhibit 80S complex formation and/or the association of Mpp10 result in retention of the U3 snoRNA in the DFC. From this we propose that the GC localization of the U3 snoRNA is a direct result of its active involvement in the initial steps of ribosome biogenesis. PMID:15367679

  2. Capillary electrophoresis of affinity complexes between subviral 80S particles of human rhinovirus and monoclonal antibody 2G2.

    PubMed

    Kremser, Leopold; Petsch, Martina; Blaas, Dieter; Kenndler, Ernst

    2006-07-01

    Human rhinoviruses (HRVs), the main etiologic agents of the common cold, transform into subviral B- or 80S particles (they sediment at 80S upon sucrose density gradient centrifugation) during infection and, in vitro, upon exposure to a temperature between 50 and 56 degrees C. With respect to the native virion they lack the genomic RNA and the viral capsid protein VP4. 80S particles are unstable and easily disintegrate into their components, VP1, VP2, and VP3 in buffers containing SDS. However, this detergent was found to be a necessary constituent of the BGE for the analysis of these viruses and their complexes with receptors and antibodies by CE. We here demonstrate that dodecylpoly(ethyleneglycol ether) (D-PEG) a nonionic detergent, is suitable for analysis of subviral particles as it preserves their integrity, in contrast to SDS. Electrophoresis of the 80S particles in borate buffer (pH 8.3, 100 mM) containing 10 mM D-PEG resulted in a well-defined electrophoretic peak. The identity of the peak was confirmed, among other means, by complexation with mAb 2G2, which recognizes a structural epitope exclusively present on subviral particles but not on native virus. Upon incubation of the 80S particles with mAb 2G2 the peak disappeared, but a new peak, attributed to the antibody complex emerged. The separation system allowed following the time course of the transformation of intact HRV serotype 2 into 80S particles upon incubation at temperatures between 40 and 65 degrees C. We also demonstrate that subviral particles derived from HRV2 labeled with the fluorescence dyes FITC or Cy3.5 were stable in the separation system containing D-PEG. Dye-modified particles were still recognized by mAb 2G2, suggesting that the exposed lysines that are derivatized by the reagent do not form part of the epitope of the antibody.

  3. Initial '80s Development of Inflated Antennas

    NASA Technical Reports Server (NTRS)

    Friese, G. J.; Bilyeu, G. D.; Thomas, M.

    1983-01-01

    State of the art technology was considered in the definition and documentation of a membrane surface suitable for use in a space reflector system for long durations in orbit. Requirements for a metal foil-plastic laminate structural element were determined and a laboratory model of a rigidized element to test for strength characteristics was constructed. Characteristics of antennas ranging from 10 meters to 1000 meters were determined. The basic antenna configuration studied consists of (1) a thin film reflector, (2) a thin film cone, (3) a self-rigidizing structural torus at the interface of the cone and reflector; and (4) an inflation system. The reflector is metallized and, when inflated, has a parabolic shape. The cone not only completes the enclosure of the inflatant, but also holds the antenna feed at its apex. The torus keeps the inflated cone-reflector from collapsing inward. Laser test equipment determined the accuracy of the inflated paraboloids.

  4. Structure of the no-go mRNA decay complex Dom34-Hbs1 bound to a stalled 80S ribosome.

    PubMed

    Becker, Thomas; Armache, Jean-Paul; Jarasch, Alexander; Anger, Andreas M; Villa, Elizabeth; Sieber, Heidemarie; Motaal, Basma Abdel; Mielke, Thorsten; Berninghausen, Otto; Beckmann, Roland

    2011-06-01

    No-go decay (NGD) is a mRNA quality-control mechanism in eukaryotic cells that leads to degradation of mRNAs stalled during translational elongation. The key factors triggering NGD are Dom34 and Hbs1. We used cryo-EM to visualize NGD intermediates resulting from binding of the Dom34-Hbs1 complex to stalled ribosomes. At subnanometer resolution, all domains of Dom34 and Hbs1 were identified, allowing the docking of crystal structures and homology models. Moreover, the close structural similarity of Dom34 and Hbs1 to eukaryotic release factors (eRFs) enabled us to propose a model for the ribosome-bound eRF1-eRF3 complex. Collectively, our data provide structural insights into how stalled mRNA is recognized on the ribosome and how the eRF complex can simultaneously recognize stop codons and catalyze peptide release.

  5. Education in the 80's: Science.

    ERIC Educational Resources Information Center

    Rowe, Mary Budd, Ed.

    Designed to serve as a resource for science teachers, kindergarten through college, this publication contains 10 chapters, each focused on a topic of interest to science teachers working in the 1980's. Chapter titles and their authors are: (1) Understanding Science as a Cultural Phenomenon - Mission for the 80's, Drew Christianson; (2) What…

  6. Purification, characterization and crystallization of the human 80S ribosome

    PubMed Central

    Khatter, Heena; Myasnikov, Alexander G.; Mastio, Leslie; Billas, Isabelle M. L.; Birck, Catherine; Stella, Stefano; Klaholz, Bruno P.

    2014-01-01

    Ribosomes are key macromolecular protein synthesis machineries in the cell. Human ribosomes have so far not been studied to atomic resolution because of their particularly complex structure as compared with other eukaryotic or prokaryotic ribosomes, and they are difficult to prepare to high homogeneity, which is a key requisite for high-resolution structural work. We established a purification protocol for human 80S ribosomes isolated from HeLa cells that allows obtaining large quantities of homogenous samples as characterized by biophysical methods using analytical ultracentrifugation and multiangle laser light scattering. Samples prepared under different conditions were characterized by direct single particle imaging using cryo electron microscopy, which helped optimizing the preparation protocol. From a small data set, a 3D reconstruction at subnanometric resolution was obtained showing all prominent structural features of the human ribosome, and revealing a salt concentration dependence of the presence of the exit site tRNA, which we show is critical for obtaining crystals. With these well-characterized samples first human 80S ribosome crystals were obtained from several crystallization conditions in capillaries and sitting drops, which diffract to 26 Å resolution at cryo temperatures and for which the crystallographic parameters were determined, paving the way for future high-resolution work. PMID:24452798

  7. Education in the 80's: Physical Education.

    ERIC Educational Resources Information Center

    Ulrich, Celeste, Ed.; And Others

    In this collection of essays, theories are presented on the present and future status of physical education instruction. The essay in the first chapter explores the idea that, to function or survive in a complex society, individuals must work to unify the mind and body. The second chapter emphasizes that physical education provides people with…

  8. Prenatal Care for the 80s

    PubMed Central

    Mohide, P. T.

    1981-01-01

    Despite improvements in the last decade, Canada's perinatal mortality rate is still higher than those of many other developed countries. Consumer expectations have increased not only for a good outcome, but also a more personal and humane process. The physician has to make a decision to be involved in prenatal care. Appropriate steps are suggested for initial assessment, genetic evaluation, and ongoing prenatal care. PMID:21289752

  9. Transcription initiation complex structures elucidate DNA opening.

    PubMed

    Plaschka, C; Hantsche, M; Dienemann, C; Burzinski, C; Plitzko, J; Cramer, P

    2016-05-19

    Transcription of eukaryotic protein-coding genes begins with assembly of the RNA polymerase (Pol) II initiation complex and promoter DNA opening. Here we report cryo-electron microscopy (cryo-EM) structures of yeast initiation complexes containing closed and open DNA at resolutions of 8.8 Å and 3.6 Å, respectively. DNA is positioned and retained over the Pol II cleft by a network of interactions between the TATA-box-binding protein TBP and transcription factors TFIIA, TFIIB, TFIIE, and TFIIF. DNA opening occurs around the tip of the Pol II clamp and the TFIIE 'extended winged helix' domain, and can occur in the absence of TFIIH. Loading of the DNA template strand into the active centre may be facilitated by movements of obstructing protein elements triggered by allosteric binding of the TFIIE 'E-ribbon' domain. The results suggest a unified model for transcription initiation with a key event, the trapping of open promoter DNA by extended protein-protein and protein-DNA contacts.

  10. Ribosomal Initiation Complex Assembly within the Wild-Strain of Coxsackievirus B3 and Live-Attenuated Sabin3-like IRESes during the Initiation of Translation

    PubMed Central

    Souii, Amira; M’hadheb-Gharbi, Manel Ben; Sargueil, Bruno; Brossard, Audrey; Chamond, Nathalie; Aouni, Mahjoub; Gharbi, Jawhar

    2013-01-01

    Coxsackievirus B3 (CVB3) is an enterovirus of the family of Picornaviridae. The Group B coxsackieviruses include six serotypes (B1 to B6) that cause a variety of human diseases, including myocarditis, meningitis, and diabetes. Among the group B, the B3 strain is mostly studied for its cardiovirulence and its ability to cause acute and persistent infections. Translation initiation of CVB3 RNA has been shown to be mediated by a highly ordered structure of the 5′-untranslated region (5′UTR), which harbors an internal ribosome entry site (IRES). Translation initiation is a complex process in which initiator tRNA, 40S and 60S ribosomal subunits are assembled by eukaryotic initiation factors (eIFs) into an 80S ribosome at the initiation codon of the mRNA. We have previously addressed the question of whether the attenuating mutations of domain V of the poliovirus IRES were specific for a given genomic context or whether they could be transposed and extrapolated to a genomic related virus, i.e., CVB3 wild-type strain. In this context, we have described that Sabin3-like mutation (U473→C) introduced in CVB3 genome led to a defective mutant with a serious reduction in translation efficiency. In this study, we analyzed the efficiency of formation of ribosomal initiation complexes 48S and 80S through 10%–30% and 10%–50% sucrose gradients using rabbit reticulocyte lysates (RRLs) and stage-specific translation inhibitors: 5′-Guanylyl-imidodiphosphate (GMP-PNP) and Cycloheximide (CHX), respectively. We demonstrated that the interaction of 48S and 80S ribosomal complexes within the mutant CVB3 RNA was abolished compared with the wild-type RNA by ribosome assembly analysis. Taken together, it is possible that the mutant RNA was unable to interact with some trans-acting factors critical for enhanced IRES function. PMID:23439549

  11. Energy in the '80s: a call for leadership

    SciTech Connect

    Not Available

    1981-07-01

    The theme of this conference - Energy in the '80s: A Call for Leadership - was selected to focus attention on what was believed to be what America needs now - to get on with the tasks at hand. This proceedings of the Public Awareness Symposium, held on February 19, featured six speakers; the address of Senator Jackson at the banquet on February 20, which concluded the conference is also included; a separate abstract was prepared for each of these seven presentations. Also, the society-sponsored technical session papers are listed in Appendix A, and the Engineering/Communication scholarships are noted in Appendix B.

  12. In vitro synthesis of human protein synthesis initiation factor 4 gamma and its localization on 43 and 48 S initiation complexes.

    PubMed

    Joshi, B; Yan, R; Rhoads, R E

    1994-01-21

    The rate of protein synthesis is controlled in a large number of physiological situations at the stage of 48 S initiation complex formation, a phase that involves the recruitment of mRNA to the 40 S ribosomal subunit. This process is mediated by the eukaryotic initiation factor-4 (eIF-4) group of translation initiation factors consisting of eIF-4E, eIF-4A, eIF-4B, and eIF-4 gamma. In order to develop a new tool to study this process, we have produced radiolabeled eIF-4 gamma by in vitro transcription and translation. Despite the fact that eIF-4 gamma is predicted from the cDNA sequence to be 154 kDa, the major synthetic product migrated on SDS-polyacrylamide gel electrophoresis at 205 kDa. Although this is similar to the migration of the fastest polypeptide of authentic eIF-4 gamma (approximately 206 kDa), no products were found to co-migrate with the slowest forms of authentic eIF-4 gamma (210-220 kDa), suggesting that these forms derive from extensive modification of the initial polypeptide. The in vitro product also formed a complex with eIF-4E, as judged by its ability to bind to m7GTP-Sepharose. Sucrose gradient sedimentation studies demonstrated that eIF-4 gamma was present on both 43 and 48 S initiation complexes but not 80 S complexes. This supports a model in which free eIF-4E binds to mRNA followed by binding of the eIF-4E.mRNA complex to a 43 S initiation complex already containing eIF-4 gamma.

  13. Organization of the human mitochondrial transcription initiation complex

    PubMed Central

    Yakubovskaya, Elena; Guja, Kip E.; Eng, Edward T.; Choi, Woo Suk; Mejia, Edison; Beglov, Dmitri; Lukin, Mark; Kozakov, Dima; Garcia-Diaz, Miguel

    2014-01-01

    Initiation of transcription in human mitochondria involves two factors, TFAM and TFB2M, in addition to the mitochondrial RNA polymerase, POLRMT. We have investigated the organization of the human mitochondrial transcription initiation complex on the light-strand promoter (LSP) through solution X-ray scattering, electron microscopy (EM) and biochemical studies. Our EM results demonstrate a compact organization of the initiation complex, suggesting that protein–protein interactions might help mediate initiation. We demonstrate that, in the absence of DNA, only POLRMT and TFAM form a stable interaction, albeit one with low affinity. This is consistent with the expected transient nature of the interactions necessary for initiation and implies that the promoter DNA acts as a scaffold that enables formation of the full initiation complex. Docking of known crystal structures into our EM maps results in a model for transcriptional initiation that strongly correlates with new and existing biochemical observations. Our results reveal the organization of TFAM, POLRMT and TFB2M around the LSP and represent the first structural characterization of the entire mitochondrial transcriptional initiation complex. PMID:24413562

  14. Converting PSO dynamics into complex network - Initial study

    NASA Astrophysics Data System (ADS)

    Pluhacek, Michal; Janostik, Jakub; Senkerik, Roman; Zelinka, Ivan

    2016-06-01

    In this paper it is presented the initial study on the possibility of capturing the inner dynamic of Particle Swarm Optimization algorithm into a complex network structure. Inspired in previous works there are two different approaches for creating the complex network presented in this paper. Visualizations of the networks are presented and commented. The possibilities for future applications of the proposed design are given in detail.

  15. Crystal structure of the 80S yeast ribosome.

    PubMed

    Jenner, Lasse; Melnikov, Sergey; Garreau de Loubresse, Nicolas; Ben-Shem, Adam; Iskakova, Madina; Urzhumtsev, Alexandre; Meskauskas, Arturas; Dinman, Jonathan; Yusupova, Gulnara; Yusupov, Marat

    2012-12-01

    The first X-ray structure of the eukaryotic ribosome at 3.0Å resolution was determined using ribosomes isolated and crystallized from the yeast Saccharomyces cerevisiae (Ben-Shem A, Garreau de Loubresse N, Melnikov S, Jenner L, Yusupova G, Yusupov M: The structure of the eukaryotic ribosome at 3.0 A resolution. Science 2011, 334:1524-1529). This accomplishment was possible due to progress in yeast ribosome biochemistry as well as recent advances in crystallographic methods developed for structure determination of prokaryotic ribosomes isolated from Thermus thermophilus and Escherichia coli. In this review we will focus on the development of isolation procedures that allowed structure determination (both cryo-EM and X-ray crystallography) to be successful for the yeast S. cerevisiae. Additionally we will introduce a new nomenclature that facilitates comparison of ribosomes from different species and kingdoms of life. Finally we will discuss the impact of the yeast 80S ribosome crystal structure on perspectives for future investigations.

  16. The Complexities of Creativity within Initial Teacher Education

    ERIC Educational Resources Information Center

    Ludhra, Geeta

    2008-01-01

    This research explores beginning teachers' perceptions of creative practice and investigates the complexities of developing creative processes within Initial Teacher Education (ITE) and the primary classroom (pupils aged 5-11 years of age). The term "beginning teachers" refers to trainees within the first few months of their teacher training…

  17. Voices of Chinese Post-­80s Students in English Academic Writing

    ERIC Educational Resources Information Center

    Que, Hua; Li, Xuemei

    2015-01-01

    This study looks into the changing voice of Chinese Post-80s' students in English academic writing. Data were collected qualitatively through interviews with four Chinese Post-80s overseas graduate students and through an examination of their English essays with a focus on discursive features. Findings indicate that Chinese Post-80s' voice is…

  18. [Study of molecular mechanisms of translation initiation in mammals using in vitro reconstruction of initiation complexes].

    PubMed

    Shatskiĭ, I N

    2001-01-01

    Papers on the mechanisms of translation initiation in mammals studied by reconstruction of initiation complexes from individual components are reviewed. The author points to the constraints of this approach and to the pitfalls ignoring which one might come to erroneous conclusions and even artifacts. In addition, some methods employed in the field as well as some technical problems are discussed in the paper, together with the means of obviating them. The review could be a guidebook for newcomers into this quite labor-consuming field.

  19. Composition and structure of the 80S ribosome from the green alga Chlamydomonas reinhardtii: 80S ribosomes are conserved in plants and animals.

    PubMed

    Manuell, Andrea L; Yamaguchi, Kenichi; Haynes, Paul A; Milligan, Ronald A; Mayfield, Stephen P

    2005-08-12

    We have conducted a proteomic analysis of the 80S cytosolic ribosome from the eukaryotic green alga Chlamydomonas reinhardtii, and accompany this with a cryo-electron microscopy structure of the ribosome. Proteins homologous to all but one rat 40S subunit protein, including a homolog of RACK1, and all but three rat 60S subunit proteins were identified as components of the C. reinhardtii ribosome. Expressed Sequence Tag (EST) evidence and annotation of the completed C. reinhardtii genome identified genes for each of the four proteins not identified by proteomic analysis, showing that algae potentially have a complete set of orthologs to mammalian 80S ribosomal proteins. Presented at 25A, the algal 80S ribosome is very similar in structure to the yeast 80S ribosome, with only minor distinguishable differences. These data show that, although separated by billions of years of evolution, cytosolic ribosomes from photosynthetic organisms are highly conserved with their yeast and animal counterparts.

  20. Subseabed radioactive waste disposal feasibility program: ocean engineering challenges for the 80's

    SciTech Connect

    Talbert, D. M.

    1980-11-01

    The objective of the Subseabed Disposal Program is to assess the feasibility of disposing of high-level radioactive wastes or spent fuel in suitable geologic formations beneath the deep ocean floor. The program is entering a phase which will address engineering feasibility. While the current phase of the program to determine the scientific and environmental feasibility of the concept is not yet complete, activities to assess the engineering aspects are being initiated in parallel to facilitate the development of the concept on a time scale commensurate with related programs both in the United States and abroad. It is anticipated that engineering aspects will become the central focus of the program during the early 80's and will continue so through the establishment of a pilot-plant level activity which could occur by the mid-90's.

  1. Subseabed Radioactive Waste Disposal Feasibility Program: ocean engineering challenges for the 80's

    SciTech Connect

    Talbert, D. M.

    1980-01-01

    The objective of the Subseabed Disposal Program is to assess the feasibility of disposing of high-level radioactive wastes or spent fuel in suitable geologic formations beneath the deep ocean floor. The program is entering a phase which will address engineering feasibility. While the current phase of the program to determine the scientific and environmental feasibility of the concept is not yet complete, activities to assess the engineering aspects are being initiated in parallel to facilitate the development of the concept on a time scale commensurate with other related programs both in the United States and abroad. It is anticipated that engineering aspects will become the central focus of the program during the early 80's and will continue so through the establishment of a pilot-plant level activity which could occur by the mid-90's.

  2. The mammalian autophagy initiator complex contains 2 HORMA domain proteins

    PubMed Central

    Michel, Max; Schwarten, Melanie; Decker, Christina; Nagel-Steger, Luitgard; Willbold, Dieter; Weiergräber, Oliver H

    2015-01-01

    ATG101 is an essential component of the ULK complex responsible for initiating cellular autophagy in mammalian cells; its 3-dimensional structure and molecular function, however, are currently unclear. Here we present the X-ray structure of human ATG101. The protein displays an open HORMA domain fold. Both structural properties and biophysical evidence indicate that ATG101 is locked in this conformation, in contrast to the prototypical HORMA domain protein MAD2. Moreover, we discuss a potential mode of dimerization with ATG13 as a fundamental aspect of ATG101 function. PMID:26236954

  3. Reservoir fisheries management: Strategies for the 80's

    SciTech Connect

    Hall, G.E.; Van Den Avyle, M.J.

    1986-01-01

    Reservoirs constitute one of our most valuable fishery resources - a resource that is exceedingly complex, poorly understood, and crudely managed. As such, reservoirs continue to provide major fishery management problems, and consequently, offer tremendous opportunities for improvement. A symposium was held in Lexington, Kentucky, on June 13-16, 1983 to explore management of reservoir fisheries. Specific objectives of the symposium were (1) to provide a critical assessment of current practices for managing reservoir fisheries; (2) to provide a forum for the exchange of information and ideas among users and managers of reservoir fishery resources; (3) to stimulate new ideas and approaches for managing reservoir fishery resources; (4) to identify critical research and management needs; and (5) to clarify the role of fishery management relative to reservoir planning, operation, and other recreational uses. This compilation from the symposium includes technical papers on development of management programs and measurement of economic values, assessment of fish populations and measurement of angler harvest, management of the physical and chemical environment, management of reservoir fish communities by influencing species interactions and by harvest regulation, management implications of energy development and management of reservoir releases. Abstracts of poster presentation focus on harvest regulation and reservoir stocking.

  4. Microplastics in the Solent estuarine complex, UK: An initial assessment.

    PubMed

    Gallagher, Anthony; Rees, Aldous; Rowe, Rob; Stevens, John; Wright, Paul

    2016-01-30

    Microplastics are known to be an increasing component found within both marine sediments and the water column. This study carried out an initial assessment of the levels of microplastics present within the Solent estuarine complex, focusing specifically on the water column. A plankton net trawl survey was carried out, with samples analysed using visual observation and Fourier Transform Infrared Spectroscopy (FT-IR). The study identified significant quantities of plastics, ranging in shape, with hot spots found at confluence points within the estuary. Though the FT-IR analysis was inconclusive, the nature of the samples indicates the effect of oceanographic conditions on the prevalent types of microplastics found, which in turn identifies key local sources such as wastewater treatment plants and the plastics industry as being the dominant inputs.

  5. Exstrophy epispadias complex- Issues beyond the initial repair

    PubMed Central

    Mahajan, Jai K.; Rao, Kattragadda L. N.

    2012-01-01

    Despite advances in the management of exstrophy epispadias complex (EEC), the quality of life of these patients is far from good. The post-operative period is complicated by numerous and variable events - infection, dehiscence, upper tract dilatation with deterioration, fistulas, stone formation and incontinence to name a few of the major complications. Redo surgery for bladder closure, bladder neck reconstruction, epispadias repair and closure of fistulas are frequently required. The current focus is on limiting the frequency and morbidity of the reconstructive procedures. A successful initial closure and early satisfactory cosmetic and functional results are gratifying for the family and the health care team, but this is only the beginning of the lifelong care necessary for bladder exstrophy (BE) patients. In this article, the long-term outcome of various treatment options and the continent procedures in BE has been reviewed, tracing the journey of these patients into adolescence and adulthood. PMID:23450435

  6. Initial soils of heaps of Mikhailovsky mining complex, Kurskiy region

    NASA Astrophysics Data System (ADS)

    Tatyana, Pigareva

    2014-05-01

    Soil forming processes were investigated on the spoil heaps of one of the biggest mines of Russian European part - Mikhailovsky mining complex. Soils formed on the different heaps were classified as Lithosols or Sod Lithosols and some soil-like bodies with essential features of surface erosion. The heaps physical parameters play a critical role in initial soil formation by regulation of soil thickness increasing rate and biogenic processes intensity. Important indicator for the research of young soils were pH, C, N values and Cha/Cfa ratios. Humification degree in all soils investigated was lower than in natural Luvisols and Luvic Chernozems . The rate of humus accumulation decreases with increasing age of the soil. The humus content where rapidly increases in soil chronosequence. Morphology, soil chemical composition and texture classes described in details in presentation with special reference to the reclamation procedures and ecosystem management.

  7. Calcium-dependent interaction of calmodulin with human 80S ribosomes and polyribosomes.

    PubMed

    Behnen, Petra; Davis, Elizabeth; Delaney, Erin; Frohm, Birgitta; Bauer, Mikael; Cedervall, Tommy; O'Connell, David; Åkerfeldt, Karin S; Linse, Sara

    2012-08-28

    Ribosomes are the protein factories of every living cell. The process of protein translation is highly complex and tightly regulated by a large number of diverse RNAs and proteins. Earlier studies indicate that Ca(2+) plays a role in protein translation. Calmodulin (CaM), a ubiquitous Ca(2+)-binding protein, regulates a large number of proteins participating in many signaling pathways. Several 40S and 60S ribosomal proteins have been identified to interact with CaM, and here, we report that CaM binds with high affinity to 80S ribosomes and polyribosomes in a Ca(2+)-dependent manner. No binding is observed in buffer with 6 mM Mg(2+) and 1 mM EGTA that chelates Ca(2+), suggesting high specificity of the CaM-ribosome interaction dependent on the Ca(2+) induced conformational change of CaM. The interactions between CaM and ribosomes are inhibited by synthetic peptides comprising putative CaM-binding sites in ribosomal proteins S2 and L14. Using a cell-free in vitro translation system, we further found that these synthetic peptides are potent inhibitors of protein synthesis. Our results identify an involvement of CaM in the translational activity of ribosomes.

  8. Evaluation of a Complex, Multisite, Multilevel Grants Initiative

    ERIC Educational Resources Information Center

    Rollison, Julia; Hill, Gary; Yu, Ping; Murray, Stephen; Mannix, Danyelle; Mathews-Younes, Anne; Wells, Michael E.

    2012-01-01

    The Safe Schools/Healthy Students (SS/HS) national evaluation seeks to assess both the implementation process and the results of the SS/HS initiative, exploring factors that have contributed to or detracted from grantee success. Each site is required to forge partnerships with representatives from education, mental health, juvenile justice, and…

  9. Evaluating Complex Systems-Building Initiatives: A Work in Progress

    ERIC Educational Resources Information Center

    Walker, Gary; Kubisch, Anne C.

    2008-01-01

    In April 2007, more than 60 people--practitioners, advocates, funders, and evaluators--met for 2 days in Pittsburgh, Pennsylvania, to discuss the challenges that arise in evaluating systems change or systems-building initiatives and to suggest approaches to resolving those challenges. The symposium was convened by the partners of BUILD, a…

  10. Mechanisms initiating deep convection over complex terrain during COPS.

    SciTech Connect

    Kottmeier, C.; Kalthoff, N.; Barthlott, C.; Corsmeier, U.; Van Baelen, J.; Coulter, R.; Environmental Science Division; Inst. for Meteorology and Climate Research; Lab. de Meteorologie Physique; Inst. of Physics and Meteorology

    2008-12-01

    Precipitating convection in a mountain region of moderate topography is investigated, with particular emphasis on its initiation in response to boundary-layer and mid- and upper-tropospheric forcing mechanisms. The data used in the study are from COPS (Convective and Orographically-induced Precipitation Study) that took place in southwestern Germany and eastern France in the summer of 2007. It is found that the initiation of precipitating convection can be roughly classified as being due to either: (i) surface heating and low-level flow convergence; (ii) surface heating and moisture supply overcoming convective inhibition during latent and/or potential instability; or (iii) mid-tropospheric dynamical processes due to mesoscale convergence lines and forced mean vertical motion. These phenomena have to be adequately represented in models in order to improve quantitative precipitation forecast. Selected COPS cases are analyzed and classified into these initiation categories. Although only a subset of COPS data (mainly radiosondes, surface weather stations, radar and satellite data) are used here, it is shown that convective systems are captured in considerable detail by sensor synergy. Convergence lines were observed by Doppler radar in the location where deep convection is triggered several hours later. The results suggest that in many situations, observations of the location and timing of convergence lines will facilitate the nowcasting of convection. Further on, forecasting of the initiation of convection is significantly complicated if advection of potentially convective air masses over changing terrain features plays a major role. The passage of a frontal structure over the Vosges - Rhine valley - Black Forest orography was accompanied by an intermediate suppression of convection over the wide Rhine valley. Further downstream, an intensification of convection was observed over the Black Forest due to differential surface heating, a convergence line, and the flow

  11. A DNA topoisomerase VI-like complex initiates meiotic recombination.

    PubMed

    Vrielynck, Nathalie; Chambon, Aurélie; Vezon, Daniel; Pereira, Lucie; Chelysheva, Liudmila; De Muyt, Arnaud; Mézard, Christine; Mayer, Claudine; Grelon, Mathilde

    2016-02-26

    The SPO11 protein catalyzes the formation of meiotic DNA double strand breaks (DSBs) and is homologous to the A subunit of an archaeal topoisomerase (topo VI). Topo VI are heterotetrameric enzymes comprising two A and two B subunits; however, no topo VIB involved in meiotic recombination had been identified. We characterized a structural homolog of the archaeal topo VIB subunit [meiotic topoisomerase VIB-like (MTOPVIB)], which is essential for meiotic DSB formation. It forms a complex with the two Arabidopsis thaliana SPO11 orthologs required for meiotic DSB formation (SPO11-1 and SPO11-2) and is absolutely required for the formation of the SPO11-1/SPO11-2 heterodimer. These findings suggest that the catalytic core complex responsible for meiotic DSB formation in eukaryotes adopts a topo VI-like structure.

  12. Futurism in the Education of the Deaf: Directions and Alternatives for the 80's.

    ERIC Educational Resources Information Center

    Marshall, William J. A.

    The author presents a rationale for the study of futurism in education and analyzes the effects of significant future changes upon deaf education in the 80s. The roles that change agents play in influencing the permanence of innovations within the school are examined: advocacy, information sharing, and organizational development training.…

  13. Therapeutic Discourse and ACOA Films of the '80s and '90s.

    ERIC Educational Resources Information Center

    Lynch, Joan Driscoll

    2000-01-01

    Argues that many family melodramas in films of the '80s and '90s focus their narrative on the negative dynamics of the parental relationship. Identifies underlying generic patterns and ideas found in these films. Explores representations of mothers, fathers, and children; gender representation and codependency; and familial dysfunction. Broadens…

  14. Ribosomal Protein Rps26 Influences 80S Ribosome Assembly in Saccharomyces cerevisiae

    PubMed Central

    Belyy, Alexander; Levanova, Nadezhda; Tabakova, Irina; Rospert, Sabine

    2016-01-01

    ABSTRACT The eukaryotic ribosome consists of a small (40S) and a large (60S) subunit. Rps26 is one of the essential ribosomal proteins of the 40S subunit and is encoded by two almost identical genes, RPS26a and RPS26b. Previous studies demonstrated that Rps26 interacts with the 5′ untranslated region of mRNA via the eukaryote-specific 62-YXXPKXYXK-70 (Y62–K70) motif. Those observations suggested that this peptide within Rps26 might play an important and specific role during translation initiation. By using alanine-scanning mutagenesis and engineered strains of the yeast Saccharomyces cerevisiae, we found that single amino acid substitutions within the Y62–K70 motif of Rps26 did not affect the in vivo function of the protein. In contrast, complete deletion of the Y62–K70 segment was lethal. The simultaneous replacement of five conserved residues within the Y62–K70 segment by alanines resulted in growth defects under stress conditions and produced distinct changes in polysome profiles that were indicative of the accumulation of free 60S subunits. Human Rps26 (Rps26-Hs), which displays significant homology with yeast Rps26, supported the growth of an S. cerevisiae Δrps26a Δrps26b strain. However, the Δrps26a Δrps26b double deletion strain expressing Rps26-Hs displayed substantial growth defects and an altered ratio of 40S/60S ribosomal subunits. The combined data strongly suggest that the eukaryote-specific motif within Rps26 does not play a specific role in translation initiation. Rather, the data indicate that Rps26 as a whole is necessary for proper assembly of the 40S subunit and the 80S ribosome in yeast. IMPORTANCE Rps26 is an essential protein of the eukaryotic small ribosomal subunit. Previous experiments demonstrated an interaction between the eukaryote-specific Y62–K70 segment of Rps26 and the 5′ untranslated region of mRNA. The data suggested a specific role of the Y62–K70 motif during translation initiation. Here, we report that single

  15. Dynamic regulation of the translation initiation helicase complex by mitogenic signal transduction to eukaryotic translation initiation factor 4G.

    PubMed

    Dobrikov, Mikhail I; Dobrikova, Elena Y; Gromeier, Matthias

    2013-03-01

    Eukaryotic translation initiation factor 4F (eIF4F), comprising the cap-binding protein eIF4E, the helicase eIF4A, and the central scaffold eIF4G, is a convergence node for a complex signaling network that controls protein synthesis. Together with eIF3 and eIF4A/4B, eIF4G recruits ribosomal subunits to mRNAs and facilitates 5' untranslated region unwinding. Mammalian eIF4G contains three HEAT domains and unstructured regions involved in protein-protein interactions. Despite detailed eIF4G structure data, the mechanisms controlling initiation scaffold formation remain obscure. We found a new, highly regulated eIF4B/-3 binding site within the HEAT-1/-2 interdomain linker, harboring two phosphorylation sites that we identified as substrates for Erk1/2 and casein kinase 2. Phorbol ester-induced sequential phosphorylation of both sites detached HEAT-2 from the complex with eIF4A/-4B/-3 and stimulated the association of HEAT-3 with the mitogen-activated protein kinase signal integrating kinase Mnk1. Our results provide a mechanistic link between intracellular signal transduction and dynamic initiation complex formation coordinated by flexible eIF4G structure.

  16. A joint experimental/theoretical investigation of the MMA polymerization initiated by yttrium phenoxyamine complexes.

    PubMed

    Fang, Jian; Tschan, Mathieu J-L; Brulé, E; Robert, Carine; Thomas, Christophe M; Maron, Laurent

    2013-07-01

    A joint experimental/theoretical study has been carried out on the putative MMA polymerization catalyzed by an yttrium isopropyloxide complex. Despite its high activity in lactone polymerization, this catalyst is found to be unreactive on methyl methacrylate (MMA) polymerization. This surprising result is rationalized using a computational approach at the DFT level. Indeed, the endothermicity of the initiation step explains this lack of reactivity. The theoretical proposal of yttrium amido complexes as catalysts allows overcoming this initiation problem.

  17. Biochemical Analysis of Initiator Caspase-Activating Complexes: The Apoptosome and the Death-Inducing Signaling Complex.

    PubMed

    Langlais, Claudia; Hughes, Michelle A; Cain, Kelvin; MacFarlane, Marion

    2015-12-02

    Apoptosis is a highly regulated process that can be initiated by activation of death receptors or perturbation of mitochondria causing the release of apoptogenic proteins. This results in the activation of caspases, which are responsible for many of the biochemical and morphological changes associated with apoptosis. Caspases are normally inactive and require activation in a cascade emanating from an "initiator" or activating caspase, which in turn activates a downstream or "effector" caspase. Activation of initiator caspases is tightly regulated and requires the assembly of caspase-9 (via mitochondrial perturbation) or caspase-8/10 (via death receptor ligation) activating complexes, which are termed the apoptosome and the death-inducing signaling complex (DISC), respectively. These large multiprotein complexes can initially be separated according to size by gel filtration chromatography and subsequently analyzed by affinity purification or immunoprecipitation. The advantage of combining these techniques is one can first assess the assembly of individual components into a multiprotein complex, and then assess the size and composition of the native functional signaling platform within a particular cell type alongside a biochemical analysis of the enriched/purified complex. Here, we describe various methods currently used for characterization of the apoptosome and DISC.

  18. Coupling of downstream RNA polymerase-promoter interactions with formation of catalytically competent transcription initiation complex

    PubMed Central

    Mekler, Vladimir; Minakhin, Leonid; Borukhov, Sergei; Mustaev, Arkady; Severinov, Konstantin

    2014-01-01

    Bacterial RNA polymerase (RNAP) makes extensive contacts with duplex DNA downstream of the transcription bubble in initiation and elongation complexes. We investigated the role of downstream interactions in formation of catalytically competent transcription initiation complex by measuring initiation activity of stable RNAP complexes with model promoter DNA fragments whose downstream ends extend from +3 to +21 relative to the transcription start site at +1. We found that DNA downstream of position +6 does not play a significant role in transcription initiation when RNAP-promoter interactions upstream of the transcription start site are strong and promoter melting region is AT-rich. Further shortening of downstream DNA dramatically reduces efficiency of transcription initiation. The boundary of minimal downstream DNA duplex needed for efficient transcription initiation shifted further away from the catalytic center upon increasing the GC content of promoter melting region or in the presence of bacterial stringent response regulators DksA and ppGpp. These results indicate that the strength of RNAP-downstream DNA interactions has to reach a certain threshold to retain the catalytically competent conformation of the initiation complex and that establishment of contacts between RNAP and downstream DNA can be coupled with promoter melting. The data further suggest that RNAP interactions with DNA immediately downstream of the transcription bubble are particularly important for initiation of transcription. We hypothesize that these active center-proximal contacts stabilize the DNA template strand in the active center cleft and/or position the RNAP clamp domain to allow RNA synthesis. PMID:25311862

  19. Scandium and yttrium phosphasalen complexes as initiators for ring-opening polymerization of cyclic esters.

    PubMed

    Bakewell, Clare; White, Andrew J P; Long, Nicholas J; Williams, Charlotte K

    2015-03-01

    The synthesis and characterization of novel scandium and yttrium phosphasalen complexes is reported, where phosphasalen refers to two different bis(iminophosphorane) derivatives of the more ubiquitous salen ligands. The activity of the complexes as initiators for the ring-opening polymerization of cyclic esters is presented. The scandium complexes are inactive for lactide polymerization but slow and controlled initiators for ε-caprolactone polymerization. The lack of activity toward lactide exhibited by these compounds is probed, and a rare example of single-monomer insertion product, unable to undergo further reactions with lactide, is identified. In contrast, the analogous yttrium phosphasalen complex is a very active initiator for the ring-opening polymerization of rac-lactide (kobs = 1.5 × 10(-3) s(-1) at 1:500 [yttrium initiator]:[rac-lactide], 1 M overall concentration of lactide in THF at 298 K). In addition to being a very fast initiator, the yttrium complex also maintains excellent levels of polymerization control and a high degree of isoselectivity, with the probability of isotactic enchainment being Pi = 0.78 at 298 K.

  20. Assembly, purification and crystallization of an active HIV-1 reverse transcriptase initiation complex

    PubMed Central

    Pata, Janice D.; King, Bradford R.; Steitz, Thomas A.

    2002-01-01

    Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) initiates DNA synthesis from the 3′ end of human tRNALys3. We have used cis-acting hammerhead ribozymes to produce homogeneous-length transcribed tRNALys3 and have developed conditions for purifying highly structured RNAs on a modified tube-gel apparatus. Titration experiments show that this RNA can assemble into an initiation complex that contains equimolar amounts of HIV-1 RT, transcribed tRNALys3, and chemically synthesized template RNA. We have purified this complex using gel-filtration chromatography and have found that it is homogeneous with respect to molecular weight, demonstrating that the initiation complex forms a single discrete species at micromolar concentrations. When this initiation complex is supplied with deoxynucleotides, essentially all of the tRNA is used as a primer by HIV-1 RT and is fully extended to the 5′ end of the template. Thus, in vitro transcribed tRNA can be used efficiently as a primer by HIV-1 RT. We have also obtained crystals of the HIV-1 initiation complex that require the precisely defined ends of this in vitro transcribed tRNALys3 to grow. PMID:12433988

  1. Dom34-Hbs1 mediated dissociation of inactive 80S ribosomes promotes restart of translation after stress.

    PubMed

    van den Elzen, Antonia M G; Schuller, Anthony; Green, Rachel; Séraphin, Bertrand

    2014-02-01

    Following translation termination, ribosomal subunits dissociate to become available for subsequent rounds of protein synthesis. In many translation-inhibiting stress conditions, e.g. glucose starvation in yeast, free ribosomal subunits reassociate to form a large pool of non-translating 80S ribosomes stabilized by the 'clamping' Stm1 factor. The subunits of these inactive ribosomes need to be mobilized for translation restart upon stress relief. The Dom34-Hbs1 complex, together with the Rli1 NTPase (also known as ABCE1), have been shown to split ribosomes stuck on mRNAs in the context of RNA quality control mechanisms. Here, using in vitro and in vivo methods, we report a new role for the Dom34-Hbs1 complex and Rli1 in dissociating inactive ribosomes, thereby facilitating translation restart in yeast recovering from glucose starvation stress. Interestingly, we found that this new role is not restricted to stress conditions, indicating that in growing yeast there is a dynamic pool of inactive ribosomes that needs to be split by Dom34-Hbs1 and Rli1 to participate in protein synthesis. We propose that this provides a new level of translation regulation.

  2. Breakdown by Streptomycin of Initiation Complexes Formed on Ribosomes of Escherichia coli*

    PubMed Central

    Modolell, Juan; Davis, Bernard D.

    1970-01-01

    Streptomycin induces breakdown of the completed 70S initiation complex on ribosomes of Escherichia coli, but it does not interfere with any step in the formation of the complex. Moreover, it does not appear to interact with the ribosome in any special way during initiation, since the kinetics of breakdown are the same whether streptomycin is added before formation of the initiation complex, or after its completion, or (as previously observed) after formation of a polypeptide. fMet-tRNA is released as such, without chain elongation; it is released from a puromycin-reactive („P”) site. Streptomycin thus appears to distort not only the A site of the ribosome (as suggested earlier) but also the P site. PMID:4922285

  3. Requirement of the eukaryotic translation initiation factor 4F complex in hepatitis E virus replication.

    PubMed

    Zhou, Xinying; Xu, Lei; Wang, Yijin; Wang, Wenshi; Sprengers, Dave; Metselaar, Herold J; Peppelenbosch, Maikel P; Pan, Qiuwei

    2015-12-01

    Hepatitis E virus (HEV) infection, one of the foremost causes of acute hepatitis, is becoming a health problem of increasing magnitude. As other viruses, HEV exploits elements from host cell biochemistry, but we understand little as to which components of the human hepatocellular machinery are perverted for HEV multiplication. It is, however, known that the eukaryotic translation initiation factors 4F (eIF4F) complex, the key regulator of the mRNA-ribosome recruitment phase of translation initiation, serves as an important component for the translation and replication of many viruses. Here we aim to investigate the role of three subunits of the eIF4F complex: eukaryotic translation initiation factor 4A (eIF4A), eukaryotic translation initiation factor 4G (eIF4G) and eukaryotic translation initiation factor 4E (eIF4E) in HEV replication. We found that efficient replication of HEV requires eIF4A, eIF4G and eIF4E. Consistently, the negative regulatory factors of this complex: programmed cell death 4 (PDCD4) and eIF4E-binding protein 1 (4E-BP1) exert anti-HEV activities, which further illustrates the requirement for eIF4A and eIF4E in supporting HEV replication. Notably, phosphorylation of eIF4E induced by MNK1/2 activation is not involved in HEV replication. Although ribavirin and interferon-α (IFN-α), the most often-used off-label drugs for treating hepatitis E, interact with this complex, their antiviral activities are independent of eIF4E. In contrast, eIF4E silencing provokes enhanced anti-HEV activity of these compounds. Thus, HEV replication requires eIF4F complex and targeting essential elements of this complex provides important clues for the development of novel antiviral therapy against HEV.

  4. Sequential initiation of lagging and leading strand synthesis by two different polymerase complexes at the SV40 DNA replication origin.

    PubMed

    Tsurimoto, T; Melendy, T; Stillman, B

    1990-08-01

    Enzymatic synthesis of DNA from the simian virus 40 origin of DNA replication has been reconstituted in vitro with eight purified components. DNA polymerase alpha-primase complex first initiates DNA synthesis at the replication origin and continues as the lagging strand polymerase. Subsequently, the DNA polymerase delta complex initiates replication on the leading strand template. Some prokaryotic DNA polymerase complexes can replace the eukaryotic polymerase delta complex. A model for polymerase switching during initiation of DNA replication is presented.

  5. The Intrinsically Disordered Protein Atg13 Mediates Supramolecular Assembly of Autophagy Initiation Complexes.

    PubMed

    Yamamoto, Hayashi; Fujioka, Yuko; Suzuki, Sho W; Noshiro, Daisuke; Suzuki, Hironori; Kondo-Kakuta, Chika; Kimura, Yayoi; Hirano, Hisashi; Ando, Toshio; Noda, Nobuo N; Ohsumi, Yoshinori

    2016-07-11

    Autophagosome formation in yeast entails starvation-induced assembly of the pre-autophagosomal structure (PAS), in which multiple Atg1 complexes (composed of Atg1, Atg13, and the Atg17-Atg29-Atg31 subcomplex) are initially engaged. However, the molecular mechanisms underlying the multimeric assembly of these complexes remain unclear. Using structural and biological techniques, we herein demonstrate that Atg13 has a large intrinsically disordered region (IDR) and interacts with two distinct Atg17 molecules using two binding regions in the IDR. We further reveal that these two binding regions are essential not only for Atg1 complex assembly in vitro, but also for PAS organization in vivo. These findings underscore the structural and functional significance of the IDR of Atg13 in autophagy initiation: Atg13 provides intercomplex linkages between Atg17-Atg29-Atg31 complexes, thereby leading to supramolecular self-assembly of Atg1 complexes, in turn accelerating the initial events of autophagy, including autophosphorylation of Atg1, recruitment of Atg9 vesicles, and phosphorylation of Atg9 by Atg1. PMID:27404361

  6. Initiating Molecular Growth in the Interstellar Medium via Dimeric Complexes of Observed Ions and Molecules

    NASA Technical Reports Server (NTRS)

    Bera, Partha P.; Head-Gordon, Martin; Lee, Timothy J.

    2011-01-01

    A feasible initiation step for particle growth in the interstellar medium (ISM) is simulated by means of ab quantum chemistry methods. The systems studied are dimer ions formed by pairing nitrogen containing small molecules known to exist in the ISM with ions of unsaturated hydrocarbons or vice versa. Complexation energies, structures of ensuing complexes and electronic excitation spectra of the encounter complexes are estimated using various quantum chemistry methods. Moller-Plesset perturbation theory (MP2, Z-averaged perturbation theory (ZAP2), coupled cluster singles and doubles with perturbative triples corrections (CCSD(T)), and density functional theory (DFT) methods (B3LYP) were employed along with the correlation consistent cc-pVTZ and aug-cc-pVTZ basis sets. Two types of complexes are predicted. One type of complex has electrostatic binding with moderate (7-20 kcal per mol) binding energies, that are nonetheless significantly stronger than typical van der Waals interactions between molecules of this size. The other type of complex develops strong covalent bonds between the fragments. Cyclic isomers of the nitrogen containing complexes are produced very easily by ion-molecule reactions. Some of these complexes show intense ultraviolet visible spectra for electronic transitions with large oscillator strengths at the B3LYP, omegaB97, and equations of motion coupled cluster (EOM-CCSD) levels. The open shell nitrogen containing carbonaceous complexes especially exhibit a large oscillator strength electronic transition in the visible region of the electromagnetic spectrum.

  7. Implications for Evaluating Multi-Component, Complex Prevention Initiatives: Taking Guidance from the Safe Schools/Healthy Students Initiative

    ERIC Educational Resources Information Center

    Felix, Erika; Furlong, Michael; Sharkey, Jill; Osher, David

    2007-01-01

    The Safe Schools/Healthy Students (SS/HS) Initiative is an ambitious and comprehensive prevention initiative to promote evidence-based practice to address school safety and the reduction of substance abuse. This article describes the history of the SS/HS initiative and the national evaluation efforts to monitor the success of the initiative. To…

  8. Structure of a Complete Mediator-RNA Polymerase II Pre-Initiation Complex.

    PubMed

    Robinson, Philip J; Trnka, Michael J; Bushnell, David A; Davis, Ralph E; Mattei, Pierre-Jean; Burlingame, Alma L; Kornberg, Roger D

    2016-09-01

    A complete, 52-protein, 2.5 million dalton, Mediator-RNA polymerase II pre-initiation complex (Med-PIC) was assembled and analyzed by cryo-electron microscopy and by chemical cross-linking and mass spectrometry. The resulting complete Med-PIC structure reveals two components of functional significance, absent from previous structures, a protein kinase complex and the Mediator-activator interaction region. It thereby shows how the kinase and its target, the C-terminal domain of the polymerase, control Med-PIC interaction and transcription. PMID:27610567

  9. Backarc Oceanic Core Complexes Formed During Initial Spreading in the Southern Shikoku Basin

    NASA Astrophysics Data System (ADS)

    Miura, R.; Coffin, M. F.; Nakamura, Y.; Nishizawa, A.; Koda, K.; Tokuyama, H.

    2007-12-01

    Seafloor spreading occurs in two distinct geodynamic environments, major ocean basins and backarc basins. Unusual magma-poor seafloor spreading has been identified at slow- and intermediate-rate spreading centers in major ocean basins, e.g., Mid-Atlantic Ridge, Southwest Indian Ridge, and Australia-Antarctica Discordance. Some of these spreading centers are characterized by corrugated bathymetry known as megamullions, and some by chaotic bathymetry. Serpentinized peridotite and altered gabbro have been sampled from megamullions, and the three-dimensional geological structures that form megamullions are known as oceanic core complexes. Oceanic core complexes have also been identified at extinct backarc spreading centers, e.g., Parece Vela Basin and Shikoku Basin. The Shikoku Basin formed in conjunction with subduction along the Izu- Bonin arc at the eastern edge of the Philippine Sea plate. Although the general spreading history of the basin is known from identification of magnetic lineations, the early tectonic history of Proto-Izu-Bonin arc breakup and subsequent initial backarc spreading is uncertain. We identify, describe, and interpret oceanic core complexes amid chaotic bathymetry of the southern Shikoku Basin just east of the Kyushu-Palau Ridge, the remnant arc of the Proto-Izu-Bonin arc, on the basis of marine geological and geophysical data including multichannel seismic reflection, seismic refraction, swath bathymetry, and gravity. Just west of the core complexes, the Kyushu-Palau Ridge has been dated as Oligocene in age (~25 Ma), and just to the east lies magnetic anomaly 6B (~23 Ma). Crustal structure derived from seismic and gravity data indicates that anomalously thin -less than 5 km thick- crust is located in the arc-ocean transition between the central Kyushu-Palau Ridge and southern Shikoku Basin, which suggests rift-related crustal thinning and low magma productivity during backarc spreading initiation. Near the core complexes, seamount fragments

  10. Dirac's formalism combined with complex Fourier operational matrices to solve initial and boundary value problems

    NASA Astrophysics Data System (ADS)

    Labecca, William; Guimarães, Osvaldo; Piqueira, José Roberto C.

    2014-08-01

    Approximations of functions in terms of orthogonal polynomials have been used to develop and implement numerical approaches to solve spectrally initial and boundary value problems. The main idea behind these approaches is to express differential and integral operators by using matrices, and this, in turn, makes the numerical implementation easier to be expressed in computational algebraic languages. In this paper, the application of the methodology is enlarged by using Dirac's formalism, combined with complex Fourier series.

  11. Multiplex method for initial complex testing of antibodies to blood transmitted diseases agents.

    PubMed

    Poltavchenko, Alexander G; Nechitaylo, Oleg V; Filatov, Pavel V; Ersh, Anna V; Gureyev, Vadim N

    2016-10-01

    Initial screening of donors and population at high risk of infection with blood transmitted diseases involves a number of analyses using monospesific diagnostic systems, and therefore is expensive labor- and time-consuming process. The goal of this work is to construct a multiplex test enabling to carry out rapid initial complex testing at a low price. The paper describes a kit making it possible to detect simultaneously antibodies to six agents of the most significant blood transmitted diseases: HIV virus, hepatitis B and C viruses, cytomegalovirus, T. pallidum and T. gondii in blood products. The kit comprises multiplex dot-immunoassay based on plane protein arrays (immune chips) using colloidal gold conjugates and silver development. It provides an opportunity to carry out complex analysis within 70min at room temperature, and there is no need of well-qualified personnel. We compared laboratory findings of the kit with monospecific kits for ELISA produced by two Russian commercial companies. Dot-assay results correlate well with data obtained using commercial kits for ELISA. Furthermore, multiplex analysis is quicker and cheaper in comparison with ELISA and can be carried out in non-laboratory conditions. The kit for multiplex dot-immunoassay of antibodies to blood transmitted agents can significantly simplify initial complex testing. PMID:27497868

  12. Initial formation of an indigenous crop complex in eastern North America at 3800 B.P.

    PubMed

    Smith, Bruce D; Yarnell, Richard A

    2009-04-21

    Although geneticists and archaeologists continue to make progress world-wide in documenting the time and place of the initial domestication of a growing number of plants and animals, far less is known regarding the critically important context of coalescence of various species into distinctive sets or complexes of domesticates in each of the world's 10 or more independent centers of agricultural origin. In this article, the initial emergence of a crop complex is described for one of the best-documented of these independent centers, eastern North America (ENA). Before 4000 B.P. there is no indication of a crop complex in ENA, only isolated evidence for single indigenous domesticate species. By 3800 B.P., however, at least 5 domesticated seed-bearing plants formed a coherent complex in the river valley corridors of ENA. Accelerator mass spectrometer radiocarbon dates and reanalysis of archaeobotanical assemblages from a short occupation of the Riverton Site in Illinois documents the contemporary cultivation at 3800 B.P. of domesticated bottle gourd (Lagenaria siceraria), marshelder (Iva annua var. macrocarpa), sunflower (Helianthus annuus var. macrocarpus), and 2 cultivated varieties of chenopod (Chenopodium berlandieri), as well as the possible cultivation of Cucurbita pepo squash and little barley (Hordeum pusillum). Rather than marking either an abrupt developmental break or a necessary response to population-packing or compressed resource catchments, the coalescence of an initial crop complex in ENA appears to reflect an integrated expansion and enhancement of preexisting hunting and gathering economies that took place within a context of stable long-term adaptation to resource-rich river valley settings.

  13. Critical initial-slip scaling for the noisy complex Ginzburg–Landau equation

    NASA Astrophysics Data System (ADS)

    Liu, Weigang; Täuber, Uwe C.

    2016-10-01

    We employ the perturbative fieldtheoretic renormalization group method to investigate the universal critical behavior near the continuous non-equilibrium phase transition in the complex Ginzburg–Landau equation with additive white noise. This stochastic partial differential describes a remarkably wide range of physical systems: coupled nonlinear oscillators subject to external noise near a Hopf bifurcation instability; spontaneous structure formation in non-equilibrium systems, e.g., in cyclically competing populations; and driven-dissipative Bose–Einstein condensation, realized in open systems on the interface of quantum optics and many-body physics, such as cold atomic gases and exciton-polaritons in pumped semiconductor quantum wells in optical cavities. Our starting point is a noisy, dissipative Gross–Pitaevski or nonlinear Schrödinger equation, or equivalently purely relaxational kinetics originating from a complex-valued Landau–Ginzburg functional, which generalizes the standard equilibrium model A critical dynamics of a non-conserved complex order parameter field. We study the universal critical behavior of this system in the early stages of its relaxation from a Gaussian-weighted fully randomized initial state. In this critical aging regime, time translation invariance is broken, and the dynamics is characterized by the stationary static and dynamic critical exponents, as well as an independent ‘initial-slip’ exponent. We show that to first order in the dimensional expansion about the upper critical dimension, this initial-slip exponent in the complex Ginzburg–Landau equation is identical to its equilibrium model A counterpart. We furthermore employ the renormalization group flow equations as well as construct a suitable complex spherical model extension to argue that this conclusion likely remains true to all orders in the perturbation expansion.

  14. Energetic Chromophores: Low-Energy Laser Initiation in Explosive Fe(II) Tetrazine Complexes.

    PubMed

    Myers, Thomas W; Bjorgaard, Josiah A; Brown, Kathryn E; Chavez, David E; Hanson, Susan K; Scharff, R Jason; Tretiak, Sergei; Veauthier, Jacqueline M

    2016-04-01

    The synthesis and characterization of air stable Fe(II) coordination complexes with tetrazine and triazolo-tetrazine ligands and perchlorate counteranions have been achieved. Time-dependent density functional theory (TD-DFT) was used to model the structural, electrochemical, and optical properties of these materials. These compounds are secondary explosives that can be initiated with Nd:YAG laser light at lower energy thresholds than those of PETN. Furthermore, these Fe(II) tetrazine complexes have significantly lower sensitivity than PETN toward mechanical stimuli such as impact and friction. The lower threshold for laser initiation was achieved by altering the electronic properties of the ligand scaffold to tune the metal ligand charge transfer (MLCT) bands of these materials from the visible into the near-infrared region of the electromagnetic spectrum. Unprecedented decrease in both the laser initiation threshold and the mechanical sensitivity makes these materials the first explosives that are both safer to handle and easier to initiate than PETN with NIR lasers. PMID:26986744

  15. Energetic Chromophores: Low-Energy Laser Initiation in Explosive Fe(II) Tetrazine Complexes.

    PubMed

    Myers, Thomas W; Bjorgaard, Josiah A; Brown, Kathryn E; Chavez, David E; Hanson, Susan K; Scharff, R Jason; Tretiak, Sergei; Veauthier, Jacqueline M

    2016-04-01

    The synthesis and characterization of air stable Fe(II) coordination complexes with tetrazine and triazolo-tetrazine ligands and perchlorate counteranions have been achieved. Time-dependent density functional theory (TD-DFT) was used to model the structural, electrochemical, and optical properties of these materials. These compounds are secondary explosives that can be initiated with Nd:YAG laser light at lower energy thresholds than those of PETN. Furthermore, these Fe(II) tetrazine complexes have significantly lower sensitivity than PETN toward mechanical stimuli such as impact and friction. The lower threshold for laser initiation was achieved by altering the electronic properties of the ligand scaffold to tune the metal ligand charge transfer (MLCT) bands of these materials from the visible into the near-infrared region of the electromagnetic spectrum. Unprecedented decrease in both the laser initiation threshold and the mechanical sensitivity makes these materials the first explosives that are both safer to handle and easier to initiate than PETN with NIR lasers.

  16. Diverged composition and regulation of the Trypanosoma brucei origin recognition complex that mediates DNA replication initiation

    PubMed Central

    Marques, Catarina A.; Tiengwe, Calvin; Lemgruber, Leandro; Damasceno, Jeziel D.; Scott, Alan; Paape, Daniel; Marcello, Lucio; McCulloch, Richard

    2016-01-01

    Initiation of DNA replication depends upon recognition of genomic sites, termed origins, by AAA+ ATPases. In prokaryotes a single factor binds each origin, whereas in eukaryotes this role is played by a six-protein origin recognition complex (ORC). Why eukaryotes evolved a multisubunit initiator, and the roles of each component, remains unclear. In Trypanosoma brucei, an ancient unicellular eukaryote, only one ORC-related initiator, TbORC1/CDC6, has been identified by sequence homology. Here we show that three TbORC1/CDC6-interacting factors also act in T. brucei nuclear DNA replication and demonstrate that TbORC1/CDC6 interacts in a high molecular complex in which a diverged Orc4 homologue and one replicative helicase subunit can also be found. Analysing the subcellular localization of four TbORC1/CDC6-interacting factors during the cell cycle reveals that one factor, TbORC1B, is not a static constituent of ORC but displays S-phase restricted nuclear localization and expression, suggesting it positively regulates replication. This work shows that ORC architecture and regulation are diverged features of DNA replication initiation in T. brucei, providing new insight into this key stage of eukaryotic genome copying. PMID:26951375

  17. Arterio-Venous Fistula: Is it Critical for Prolonged Survival in the over 80's Starting Haemodialysis?

    PubMed Central

    Jakes, Adam D.; Jani, Poonam; Allgar, Victoria; Lamplugh, Archie; Zeidan, Ahmed; Bhandari, Sunil

    2016-01-01

    Background Dialysis in elderly patients (>80-years-old) carries a poor prognosis, but little is known about the most effective vascular access method in this age group. An arteriovenous fistula (AVF) is both time-consuming and initially expensive, requiring surgical insertion. A central venous catheter (CVC) is initially a cheaper alternative, but carries a higher risk of infection. We examined whether vascular access affected 1-year and 2-year mortality in elderly patients commencing haemodialysis. Methods Initial vascular access, demographic and survival data for elective haemodialysis patients >80-years was collated using regional databases. A cohort of conservatively managed patients was included for comparison. A log-rank test was used to compare survival between groups and a chi-square test was used to compare 1-year and 2-year survival. Results 167 patients (61% male) were included: CVC (101), AVF (25) and conservative management (41). Mean age (median) of starting haemodialysis (eGFR ≤10mL/min/1.73m2): CVC; 83.4 (2.3) and AVF; 82.3 (1.8). Mean age of conservatively managed patients reaching an eGFR ≤10mL/min/1.73m2 was 85.8 (3.6). Mean (median) survival on dialysis was 2.2 (1.8) years for AVF patients, 2.1 (1.2) for CVC patients, and 1.5 (0.9) for conservatively managed patients (p = 0.107, controlling for age/sex p = 0.519). 1-year and 2-year mortality: AVF (28%/52%); CVC (49%/57%), and conservative management (54%/68%). There was no significant difference between the groups at 1-year (p = 0.108) or 2-years (p = 0.355). Conclusion These results suggest that there is no significant survival benefit over a 2-year period when comparing vascular access methods. In comparison to conservative management, survival benefit was marginal. The decision of whether and how (choice of their vascular access method) to dialysis the over 80s is multifaceted and requires a tailored, multidisciplinary approach. PMID:27684071

  18. Complex Oncogenic Translocations with Gene Amplification are Initiated by Specific DNA Breaks in Lymphocytes

    PubMed Central

    Wright, Sarah M.; Woo, Yong H.; Alley, Travis L.; Shirley, Bobbi-Jo; Akeson, Ellen C.; Snow, Kathy J.; Maas, Sarah A.; Elwell, Rachel L.; Foreman, Oded; Mills, Kevin D.

    2009-01-01

    Chromosomal instability is a hallmark of many tumor types. Complex chromosomal rearrangements with associated gene amplification, known as complicons, characterize many hematologic and solid cancers. While chromosomal aberrations, including complicons, are useful diagnostic and prognostic cancer markers, their molecular origins are not known. Although accumulating evidence has implicated DNA double strand break repair in suppression of oncogenic genome instability, the genomic elements required for chromosome rearrangements, especially complex lesions, have not been elucidated. Using a mouse model of B-lineage lymphoma, characterized by complicon formation involving the immunoglobulin heavy chain (Igh) locus and the c-myc oncogene, we have now investigated the requirement for specific genomic segments as donors for complex rearrangements. We now demonstrate that specific DNA double strand breaks, occurring within a narrow segment of Igh are necessary to initiate complicon formation. By contrast, neither specific DNA breaks nor the powerful intronic enhancer Eμ are required for complicon-independent oncogenesis. This study is the first to delineate mechanisms of complex versus simple instability, and the first to identify specific chromosomal elements required for complex chromosomal aberrations. These findings will illuminate genomic cancer susceptibility and risk factors. PMID:19435904

  19. Complex oncogenic translocations with gene amplification are initiated by specific DNA breaks in lymphocytes.

    PubMed

    Wright, Sarah M; Woo, Yong H; Alley, Travis L; Shirley, Bobbi-Jo; Akeson, Ellen C; Snow, Kathy J; Maas, Sarah A; Elwell, Rachel L; Foreman, Oded; Mills, Kevin D

    2009-05-15

    Chromosomal instability is a hallmark of many tumor types. Complex chromosomal rearrangements with associated gene amplification, known as complicons, characterize many hematologic and solid cancers. Whereas chromosomal aberrations, including complicons, are useful diagnostic and prognostic cancer markers, their molecular origins are not known. Although accumulating evidence has implicated DNA double-strand break repair in suppression of oncogenic genome instability, the genomic elements required for chromosome rearrangements, especially complex lesions, have not been elucidated. Using a mouse model of B-lineage lymphoma, characterized by complicon formation involving the immunoglobulin heavy chain (Igh) locus and the c-myc oncogene, we have now investigated the requirement for specific genomic segments as donors for complex rearrangements. We now show that specific DNA double-strand breaks, occurring within a narrow segment of Igh, are necessary to initiate complicon formation. By contrast, neither specific DNA breaks nor the powerful intronic enhancer Emu are required for complicon-independent oncogenesis. This study is the first to delineate mechanisms of complex versus simple instability and the first to identify specific chromosomal elements required for complex chromosomal aberrations. These findings will illuminate genomic cancer susceptibility and risk factors.

  20. Nonlinear dynamics of initially imperfect functionally graded circular cylindrical shell under complex loads

    NASA Astrophysics Data System (ADS)

    Liu, Y. Z.; Hao, Y. X.; Zhang, W.; Chen, J.; Li, S. B.

    2015-07-01

    The nonlinear vibration of a simply supported FGM cylindrical shell with small initial geometric imperfection under complex loads is studied. The effects of radial harmonic excitation, compressive in-plane force combined with supersonic aerodynamic and thermal loads are considered. The small initial geometric imperfection of the cylindrical shell is characterized in the form of the sine-type trigonometric functions. The effective material properties of this FGM cylindrical shell are graded in the radial direction according to a simple power law in terms of the volume fractions. Based on Reddy's third-order shear deformation theory, von Karman-type nonlinear kinematics and Hamilton's principle, the nonlinear partial differential equation that controls the shell dynamics is derived. Both axial symmetric and driven modes of the cylindrical shell deflection pattern are included. Furthermore, the equations of motion can be reduced into a set of coupled nonlinear ordinary differential equations by applying Galerkin's method. In the study of the nonlinear dynamics responses of small initial geometric imperfect FGM cylindrical shell under complex loads, the 4th order Runge-Kutta method is used to obtain time history, phase portraits, bifurcation diagrams and Poincare maps with different parameters. The effects of external loads, geometric imperfections and volume fractions on the nonlinear dynamics of the system are discussed.

  1. Crystal structure of the eukaryotic 60S ribosomal subunit in complex with initiation factor 6.

    PubMed

    Klinge, Sebastian; Voigts-Hoffmann, Felix; Leibundgut, Marc; Arpagaus, Sofia; Ban, Nenad

    2011-11-18

    Protein synthesis in all organisms is catalyzed by ribosomes. In comparison to their prokaryotic counterparts, eukaryotic ribosomes are considerably larger and are subject to more complex regulation. The large ribosomal subunit (60S) catalyzes peptide bond formation and contains the nascent polypeptide exit tunnel. We present the structure of the 60S ribosomal subunit from Tetrahymena thermophila in complex with eukaryotic initiation factor 6 (eIF6), cocrystallized with the antibiotic cycloheximide (a eukaryotic-specific inhibitor of protein synthesis), at a resolution of 3.5 angstroms. The structure illustrates the complex functional architecture of the eukaryotic 60S subunit, which comprises an intricate network of interactions between eukaryotic-specific ribosomal protein features and RNA expansion segments. It reveals the roles of eukaryotic ribosomal protein elements in the stabilization of the active site and the extent of eukaryotic-specific differences in other functional regions of the subunit. Furthermore, it elucidates the molecular basis of the interaction with eIF6 and provides a structural framework for further studies of ribosome-associated diseases and the role of the 60S subunit in the initiation of protein synthesis.

  2. Conformational Differences between Open and Closed States of the Eukaryotic Translation Initiation Complex.

    PubMed

    Llácer, Jose L; Hussain, Tanweer; Marler, Laura; Aitken, Colin Echeverría; Thakur, Anil; Lorsch, Jon R; Hinnebusch, Alan G; Ramakrishnan, V

    2015-08-01

    Translation initiation in eukaryotes begins with the formation of a pre-initiation complex (PIC) containing the 40S ribosomal subunit, eIF1, eIF1A, eIF3, ternary complex (eIF2-GTP-Met-tRNAi), and eIF5. The PIC, in an open conformation, attaches to the 5' end of the mRNA and scans to locate the start codon, whereupon it closes to arrest scanning. We present single particle cryo-electron microscopy (cryo-EM) reconstructions of 48S PICs from yeast in these open and closed states, at 6.0 Å and 4.9 Å, respectively. These reconstructions show eIF2β as well as a configuration of eIF3 that appears to encircle the 40S, occupying part of the subunit interface. Comparison of the complexes reveals a large conformational change in the 40S head from an open mRNA latch conformation to a closed one that constricts the mRNA entry channel and narrows the P site to enclose tRNAi, thus elucidating key events in start codon recognition.

  3. The Atg1-kinase complex tethers Atg9-vesicles to initiate autophagy

    NASA Astrophysics Data System (ADS)

    Rao, Yijian; Perna, Marco G.; Hofmann, Benjamin; Beier, Viola; Wollert, Thomas

    2016-01-01

    Autophagosomes are double-membrane vesicles that sequester cytoplasmic material for lysosomal degradation. Their biogenesis is initiated by recruitment of Atg9-vesicles to the phagophore assembly site. This process depends on the regulated activation of the Atg1-kinase complex. However, the underlying molecular mechanism remains unclear. Here we reconstitute this early step in autophagy from purified components in vitro. We find that on assembly from its cytoplasmic subcomplexes, the Atg1-kinase complex becomes activated, enabling it to recruit and tether Atg9-vesicles. The scaffolding protein Atg17 targets the Atg1-kinase complex to autophagic membranes by specifically recognizing the membrane protein Atg9. This interaction is inhibited by the two regulatory subunits Atg31 and Atg29. Engagement of the Atg1-Atg13 subcomplex restores the Atg9-binding and membrane-tethering activity of Atg17. Our data help to unravel the mechanism that controls Atg17-mediated tethering of Atg9-vesicles, providing the molecular basis to understand initiation of autophagosome-biogenesis.

  4. The Atg1–kinase complex tethers Atg9-vesicles to initiate autophagy

    PubMed Central

    Rao, Yijian; Perna, Marco G.; Hofmann, Benjamin; Beier, Viola; Wollert, Thomas

    2016-01-01

    Autophagosomes are double-membrane vesicles that sequester cytoplasmic material for lysosomal degradation. Their biogenesis is initiated by recruitment of Atg9-vesicles to the phagophore assembly site. This process depends on the regulated activation of the Atg1–kinase complex. However, the underlying molecular mechanism remains unclear. Here we reconstitute this early step in autophagy from purified components in vitro. We find that on assembly from its cytoplasmic subcomplexes, the Atg1–kinase complex becomes activated, enabling it to recruit and tether Atg9-vesicles. The scaffolding protein Atg17 targets the Atg1–kinase complex to autophagic membranes by specifically recognizing the membrane protein Atg9. This interaction is inhibited by the two regulatory subunits Atg31 and Atg29. Engagement of the Atg1–Atg13 subcomplex restores the Atg9-binding and membrane-tethering activity of Atg17. Our data help to unravel the mechanism that controls Atg17-mediated tethering of Atg9-vesicles, providing the molecular basis to understand initiation of autophagosome-biogenesis. PMID:26753620

  5. Initiator-integrated 3D printing enables the formation of complex metallic architectures.

    PubMed

    Wang, Xiaolong; Guo, Qiuquan; Cai, Xiaobing; Zhou, Shaolin; Kobe, Brad; Yang, Jun

    2014-02-26

    Three-dimensional printing was used to fabricate various metallic structures by directly integrating a Br-containing vinyl-terminated initiator into the 3D resin followed by surface-initiated atomic-transfer radical polymerization (ATRP) and subsequent electroless plating. Cu- and Ni-coated complex structures, such as microlattices, hollow balls, and even Eiffel towers, were prepared. Moreover, the method is also capable of fabricating ultralight cellular metals with desired structures by simply etching the polymer template away. By combining the merits of 3D printing in structure design with those of ATRP in surface modification and polymer-assisted ELP of metals, this universal, robust, and cost-effective approach has largely extended the capability of 3D printing and will make 3D printing technology more practical in areas of electronics, acoustic absorption, thermal insulation, catalyst supports, and others. PMID:24328276

  6. Fast IIR isotropic 2-D complex Gabor filters with boundary initialization.

    PubMed

    Bernardino, Alexandre; Santos-Victor, José

    2006-11-01

    Gabor filters are widely applied in image analysis and computer vision applications. This paper describes a fast algorithm for isotropic complex Gabor filtering that outperforms existing implementations. The main computational improvement arises from the decomposition of Gabor filtering into more efficient Gaussian filtering and sinusoidal modulations. Appropriate filter initial conditions are derived to avoid boundary transients, without requiring explicit image border extension. Our proposal reduces up to 39% the number of required operations with respect to state-of-the-art approaches. A full C++ implementation of the method is publicly available.

  7. Structure of an RNA Polymerase II-TFIIB Complex and the Transcription Initiation Mechanism

    SciTech Connect

    Liu, Xin; Bushnell, David A; Wang, Dong; Calero, Guillermo; Kornberg, Roger D

    2010-01-14

    Previous x-ray crystal structures have given insight into the mechanism of transcription and the role of general transcription factors in the initiation of the process. A structure of an RNA polymerase II-general transcription factor TFIIB complex at 4.5 angstrom resolution revealed the amino-terminal region of TFIIB, including a loop termed the 'B finger,' reaching into the active center of the polymerase where it may interact with both DNA and RNA, but this structure showed little of the carboxyl-terminal region. A new crystal structure of the same complex at 3.8 angstrom resolution obtained under different solution conditions is complementary with the previous one, revealing the carboxyl-terminal region of TFIIB, located above the polymerase active center cleft, but showing none of the B finger. In the new structure, the linker between the amino- and carboxyl-terminal regions can also be seen, snaking down from above the cleft toward the active center. The two structures, taken together with others previously obtained, dispel long-standing mysteries of the transcription initiation process.

  8. Architecture of TFIIIC and its role in RNA polymerase III pre-initiation complex assembly

    NASA Astrophysics Data System (ADS)

    Male, Gary; von Appen, Alexander; Glatt, Sebastian; Taylor, Nicholas M. I.; Cristovao, Michele; Groetsch, Helga; Beck, Martin; Müller, Christoph W.

    2015-06-01

    In eukaryotes, RNA Polymerase III (Pol III) is specifically responsible for transcribing genes encoding tRNAs and other short non-coding RNAs. The recruitment of Pol III to tRNA-encoding genes requires the transcription factors (TF) IIIB and IIIC. TFIIIC has been described as a conserved, multi-subunit protein complex composed of two subcomplexes, called τA and τB. How these two subcomplexes are linked and how their interaction affects the formation of the Pol III pre-initiation complex (PIC) is poorly understood. Here we use chemical crosslinking mass spectrometry and determine the molecular architecture of TFIIIC. We further report the crystal structure of the essential TPR array from τA subunit τ131 and characterize its interaction with a central region of τB subunit τ138. The identified τ131-τ138 interacting region is essential in vivo and overlaps with TFIIIB-binding sites, revealing a crucial interaction platform for the regulation of tRNA transcription initiation.

  9. Architecture of TFIIIC and its role in RNA polymerase III pre-initiation complex assembly

    PubMed Central

    Male, Gary; von Appen, Alexander; Glatt, Sebastian; Taylor, Nicholas M. I.; Cristovao, Michele; Groetsch, Helga; Beck, Martin; Müller, Christoph W.

    2015-01-01

    In eukaryotes, RNA Polymerase III (Pol III) is specifically responsible for transcribing genes encoding tRNAs and other short non-coding RNAs. The recruitment of Pol III to tRNA-encoding genes requires the transcription factors (TF) IIIB and IIIC. TFIIIC has been described as a conserved, multi-subunit protein complex composed of two subcomplexes, called τA and τB. How these two subcomplexes are linked and how their interaction affects the formation of the Pol III pre-initiation complex (PIC) is poorly understood. Here we use chemical crosslinking mass spectrometry and determine the molecular architecture of TFIIIC. We further report the crystal structure of the essential TPR array from τA subunit τ131 and characterize its interaction with a central region of τB subunit τ138. The identified τ131–τ138 interacting region is essential in vivo and overlaps with TFIIIB-binding sites, revealing a crucial interaction platform for the regulation of tRNA transcription initiation. PMID:26060179

  10. Structures of E. coli σS-transcription initiation complexes provide new insights into polymerase mechanism

    PubMed Central

    Liu, Bin; Zuo, Yuhong; Steitz, Thomas A.

    2016-01-01

    In bacteria, multiple σ factors compete to associate with the RNA polymerase (RNAP) core enzyme to form a holoenzyme that is required for promoter recognition. During transcription initiation RNAP remains associated with the upstream promoter DNA via sequence-specific interactions between the σ factor and the promoter DNA while moving downstream for RNA synthesis. As RNA polymerase repetitively adds nucleotides to the 3′-end of the RNA, a pyrophosphate ion is generated after each nucleotide incorporation. It is currently unknown how the release of pyrophosphate affects transcription. Here we report the crystal structures of E. coli transcription initiation complexes (TICs) containing the stress-responsive σS factor, a de novo synthesized RNA oligonucleotide, and a complete transcription bubble (σS-TIC) at about 3.9-Å resolution. The structures show the 3D topology of the σS factor and how it recognizes the promoter DNA, including likely specific interactions with the template-strand residues of the −10 element. In addition, σS-TIC structures display a highly stressed pretranslocated initiation complex that traps a pyrophosphate at the active site that remains closed. The position of the pyrophosphate and the unusual phosphodiester linkage between the two terminal RNA residues suggest an unfinished nucleotide-addition reaction that is likely at equilibrium between nucleotide addition and pyrophosphorolysis. Although these σS-TIC crystals are enzymatically active, they are slow in nucleotide addition, as suggested by an NTP soaking experiment. Pyrophosphate release completes the nucleotide addition reaction and is associated with extensive conformational changes around the secondary channel but causes neither active site opening nor transcript translocation. PMID:27035955

  11. Three-dimensional EM Structure of an Intact Activator-dependent Transcription Initiation Complex

    SciTech Connect

    Hudson, B.; Quispe, J; Lara-González, S; Kim, Y; Berman, H; Arnold, E; Ebright, R; Lawson, C

    2009-01-01

    We present the experimentally determined 3D structure of an intact activator-dependent transcription initiation complex comprising the Escherichia coli catabolite activator protein (CAP), RNA polymerase holoenzyme (RNAP), and a DNA fragment containing positions -78 to +20 of a Class I CAP-dependent promoter with a CAP site at position -61.5 and a premelted transcription bubble. A 20-{angstrom} electron microscopy reconstruction was obtained by iterative projection-based matching of single particles visualized in carbon-sandwich negative stain and was fitted using atomic coordinate sets for CAP, RNAP, and DNA. The structure defines the organization of a Class I CAP-RNAP-promoter complex and supports previously proposed interactions of CAP with RNAP {alpha} subunit C-terminal domain ({alpha}CTD), interactions of {alpha}CTD with {sigma}70 region 4, interactions of CAP and RNAP with promoter DNA, and phased-DNA-bend-dependent partial wrapping of DNA around the complex. The structure also reveals the positions and shapes of species-specific domains within the RNAP {beta}{prime}, {beta}, and {sigma}70 subunits.

  12. Initial characterization of the FlgE hook high molecular weight complex of Borrelia burgdorferi.

    PubMed

    Miller, Kelly A; Motaleb, Md A; Liu, Jun; Hu, Bo; Caimano, Melissa J; Miller, Michael R; Charon, Nyles W

    2014-01-01

    The spirochete periplasmic flagellum has many unique attributes. One unusual characteristic is the flagellar hook. This structure serves as a universal joint coupling rotation of the membrane-bound motor to the flagellar filament. The hook is comprised of about 120 FlgE monomers, and in most bacteria these structures readily dissociate to monomers (∼ 50 kDa) when treated with heat and detergent. However, in spirochetes the FlgE monomers form a large mass of over 250 kDa [referred to as a high molecular weight complex (HMWC)] that is stable to these and other denaturing conditions. In this communication, we examined specific aspects with respect to the formation and structure of this complex. We found that the Lyme disease spirochete Borrelia burgdorferi synthesized the HMWC throughout the in vitro growth cycle, and also in vivo when implanted in dialysis membrane chambers in rats. The HMWC was stable to formic acid, which supports the concept that the stability of the HMWC is dependent on covalent cross-linking of individual FlgE subunits. Mass spectrometry analysis of the HMWC from both wild type periplasmic flagella and polyhooks from a newly constructed ΔfliK mutant indicated that other proteins besides FlgE were not covalently joined to the complex, and that FlgE was the sole component of the complex. In addition, mass spectrometry analysis also indicated that the HMWC was composed of a polymer of the FlgE protein with both the N- and C-terminal regions remaining intact. These initial studies set the stage for a detailed characterization of the HMWC. Covalent cross-linking of FlgE with the accompanying formation of the HMWC we propose strengthens the hook structure for optimal spirochete motility. PMID:24859001

  13. Initial characterization of the FlgE hook high molecular weight complex of Borrelia burgdorferi.

    PubMed

    Miller, Kelly A; Motaleb, Md A; Liu, Jun; Hu, Bo; Caimano, Melissa J; Miller, Michael R; Charon, Nyles W

    2014-01-01

    The spirochete periplasmic flagellum has many unique attributes. One unusual characteristic is the flagellar hook. This structure serves as a universal joint coupling rotation of the membrane-bound motor to the flagellar filament. The hook is comprised of about 120 FlgE monomers, and in most bacteria these structures readily dissociate to monomers (∼ 50 kDa) when treated with heat and detergent. However, in spirochetes the FlgE monomers form a large mass of over 250 kDa [referred to as a high molecular weight complex (HMWC)] that is stable to these and other denaturing conditions. In this communication, we examined specific aspects with respect to the formation and structure of this complex. We found that the Lyme disease spirochete Borrelia burgdorferi synthesized the HMWC throughout the in vitro growth cycle, and also in vivo when implanted in dialysis membrane chambers in rats. The HMWC was stable to formic acid, which supports the concept that the stability of the HMWC is dependent on covalent cross-linking of individual FlgE subunits. Mass spectrometry analysis of the HMWC from both wild type periplasmic flagella and polyhooks from a newly constructed ΔfliK mutant indicated that other proteins besides FlgE were not covalently joined to the complex, and that FlgE was the sole component of the complex. In addition, mass spectrometry analysis also indicated that the HMWC was composed of a polymer of the FlgE protein with both the N- and C-terminal regions remaining intact. These initial studies set the stage for a detailed characterization of the HMWC. Covalent cross-linking of FlgE with the accompanying formation of the HMWC we propose strengthens the hook structure for optimal spirochete motility.

  14. The product definition initiative in the Department of Energy Nuclear Weapons Complex

    SciTech Connect

    Wapman, P.D.

    1988-08-17

    The US Department of Energy Nuclear Weapons Complex (NWC) formed the Product Definition initiative (PDI) to identify, using information modeling techniques, the NWC product data to be implemented in a computer environment. Information modeling techniques are used to assemble the product data required by a specific problem domain into a logical form. The resulting model may be used to generate a complete, accurate, and unambiguous database for the electronic exchange and utilization of product data. This reduces the need for human interpretation of product definition data and can serve as the foundation for the automation of many manufacturing applications. The PDI project is developing application or resource information models for five domains of interest to the NWC: Drafting, Numerical Control, Inspection, Tooling, and Form Features. Additionally, the project is working closely with vendors, other NWC computer integrated manufacturing initiatives, and the National Bureau of Standards Product Data Exchange Specification (PDES) project to ensure the NWC's product data needs will be met by future exchange protocols and CADD/CAM systems. 1 ref., 1 fig.

  15. Reconfiguration of yeast 40S ribosomal subunit domains by the translation initiation multifactor complex.

    PubMed

    Gilbert, Robert J C; Gordiyenko, Yulya; von der Haar, Tobias; Sonnen, Andreas F-P; Hofmann, Gregor; Nardelli, Maria; Stuart, David I; McCarthy, John E G

    2007-04-01

    In the process of protein synthesis, the small (40S) subunit of the eukaryotic ribosome is recruited to the capped 5' end of the mRNA, from which point it scans along the 5' untranslated region in search of a start codon. However, the 40S subunit alone is not capable of functional association with cellular mRNA species; it has to be prepared for the recruitment and scanning steps by interactions with a group of eukaryotic initiation factors (eIFs). In budding yeast, an important subset of these factors (1, 2, 3, and 5) can form a multifactor complex (MFC). Here, we describe cryo-EM reconstructions of the 40S subunit, of the MFC, and of 40S complexes with MFC factors plus eIF1A. These studies reveal the positioning of the core MFC on the 40S subunit, and show how eIF-binding induces mobility in the head and platform and reconfigures the head-platform-body relationship. This is expected to increase the accessibility of the mRNA channel, thus enabling the 40S subunit to convert to a recruitment-competent state.

  16. Guide to export crude for the 80s: Columbia's Cano Limon crude ready for export

    SciTech Connect

    Corbett, R.

    1986-05-12

    The completion of the Cano Limon pipeline and offshore loading facilities last month put Colombia's new Cano Limon crude into the world crude oil trade. Operators of the field, Empresa Colombia de Petroleos (Ecopetrol), Occidental de Colombia Inc., and Shell de Colombia Inc., expect an initial tanker loading capability of 90,000 b/d with total capacity reaching 250,000 b/d in by July. The crude oil will be loaded from a tanker-loading facility and a floating storage unit located offshore in the Caribbean Sea at the Covenas marine terminal. The loading facility will have two CALM buoys each capable of handling 40,000 bbl/hr, and will be able to handle two shuttle tankers at once.

  17. The Nevada Rural Ozone Initiative (NVROI): Insights to understanding air pollution in complex terrain.

    PubMed

    Gustin, Mae Sexauer; Fine, Rebekka; Miller, Matthieu; Jaffe, Dan; Burley, Joel

    2015-10-15

    The Nevada Rural Ozone Initiative (NVROI) was established to better understand O3 concentrations in the Western United States (US). The major working hypothesis for development of the sampling network was that the sources of O3 to Nevada are regional and global. Within the framework of this overarching hypothesis, we specifically address two conceptual meteorological hypotheses: (1) The high elevation, complex terrain, and deep convective mixing that characterize Nevada, make this state ideally located to intercept polluted parcels of air transported into the US from the free troposphere; and (2) site specific terrain features will influence O3 concentrations observed at surface sites. Here, the impact of complex terrain and site location on observations are discussed. Data collected in Nevada at 6 sites (1385 to 2082 m above sea level (asl)) are compared with that collected at high elevation sites in Yosemite National Park and the White Mountains, California. Average daily maximum 1-hour concentrations of O3 during the first year of the NVROI ranged from 58 to 69 ppbv (spring), 53 to 62 ppbv (summer), 44 to 49 ppbv (fall), and 37 to 45 ppbv (winter). These were similar to those measured at 3 sites in Yosemite National Park (2022 to 3031 m asl), and at 4 sites in the White Mountains (1237 to 4342 m asl) (58 to 67 ppbv (summer) and 47 to 58 ppbv (fall)). Results show, that in complex terrain, collection of data should occur at high and low elevation sites to capture surface impacts, and site location with respect to topography should be considered. Additionally, concentrations measured are above the threshold reported for causing a reduction in growth and visible injury for plants (40 ppbv), and sustained exposure at high elevation locations in the Western USA may be detrimental for ecosystems.

  18. Two-dimensional organic molecules for two-photon absorption, aluminum alkyl complexes initiated polymerizations, and unimolecular living radical polymerization initiators

    NASA Astrophysics Data System (ADS)

    Bi, Xiangdong

    A study of structure-property relationship on two-photon absorbing chromophores showed that highly symmetric and conjugated molecular structures exhibited larger two-photon absorption cross-section in comparison to their counterparts with lower symmetry. A number of symmetric two-photon absorbing chromophores were developed. Measurements of their optical properties showed that cross-sections were further enhanced upon (i) attachment of electron donating groups, such as substituted amino groups, to the symmetric structures; (ii) extension of the conjugation length; and (iii) replacement of conjugated pi center with an sp3 hybridized nitrogen atom. Two-photon absorbing polymers and a dendritic structure of symmetric molecules were also synthesized and characterized. A series of bulky aluminum complexes were synthesized and characterized. For the first time, they were found to be active initiators towards the polymerization of acrylates. Coordination of methyl acrylate to aluminum complexes was observed by variable-temperature nuclear magnetic resonance spectroscopy. Adducts of methyl acrylate to aluminum complexes were isolated and characterized by both 1H and 13C nuclear magnetic resonance spectroscopy. The proposed mechanism involved a radical process where the radicals were produced by an assisted homolysis of the Al-alkyl bond. A kinetic study of the methyl acrylate polymerization initiated by bulky aluminum complex showed that the rate of polymerization was first-order with respect to the monomer concentration and half-order with respect to the concentration of aluminum initiator. Further investigation showed bulky aluminum complexes were also active in the initiation of the polymerization of styrene and some other monomers. A facile one-step synthesis of an unimolecular initiator, 2,3-dimethyl-4-phenyl-4-(2 ',2',6',6' -tetramethylpiperidinoxy)butanitrile, was developed for "living" radical polymerization study. A "living" polymerization of styrene was observed

  19. Effects of additional iron-chelators on Fe(2+)-initiated lipid peroxidation: evidence to support the Fe2+ ... Fe3+ complex as the initiator.

    PubMed

    Tang, L X; Yang, J L; Shen, X

    1997-12-01

    The addition of chelated Fe2+ ions in a liposomal system often results in a short lag period before peroxidation starts. The addition of a second chelator at the end of the lag period results in an inhibition of the lipid peroxidation. The degree of inhibition depends on the stability constants of the chelator in ligating Fe2+ and/or Fe3+. A more striking inhibitory effect was observed for the chelators with higher stability constant for either or both Fe(2+)- and Fe(3+)-complex, but much less inhibition was found for those with lower stability constants for both complexes. Assuming that the "initiator" for iron-dependent lipid peroxidation is formed through the redox process of iron ion and finally emerged at the end of the latent period, the inhibitory effect of the second chelator may be explained as the abstraction of either Fe2+ or Fe3+ from the initiator by an additional free chelator, which results in the decomposition of the initiator. This study supports the hypothesis that a Fe2+ ... Fe3+ complex is responsible for iron-initiated lipid peroxidation. PMID:9397574

  20. Initial diameter of the polar body contractile ring is minimized by the centralspindlin complex

    PubMed Central

    Fabritius, Amy S.; Flynn, Jonathan R.; McNally, Francis J.

    2011-01-01

    Polar body formation is an essential step in forming haploid eggs from diploid oocytes. This process involves completion of a highly asymmetric cytokinesis that results in a large egg and two small polar bodies. Unlike mitotic contractile rings, polar body contractile rings assemble over one spindle pole so that the spindle must move through the contractile ring before cytokinesis. During time-lapse imaging of C. elegans meiosis, the contractile ring moved downward along the length of the spindle and completed scission at the midpoint of the spindle, even when spindle length or rate of ring movement was increased. Patches of myosin heavy chain and dynamic furrowing of the plasma membrane over the entire embryo suggested that global cortical contraction forces the meiotic spindle and overlying membrane out through the contractile ring center. Consistent with this model, depletion of myosin phosphatase increased the velocity of ring movement along the length of the spindle. Global dynamic furrowing, which was restricted to anaphase I and II, was dependent on myosin II, the anaphase promoting complex and separase, but did not require cortical contact by the spindle. Large cortical patches of myosin during metaphase I and II indicated that myosin was already in the active form before activation of separase. To identify the signal at the midpoint of the anaphase spindle that induces scission, we depleted two proteins that mark the exact midpoint of the spindle during late anaphase, CYK-4 and ZEN-4. Depletion of either protein resulted in the unexpected phenotype of initial ingression of a polar body ring with twice the diameter of wild type. This phenotype revealed a novel mechanism for minimizing polar body size. Proteins at the spindle midpoint are required for initial ring ingression to occur close to the membrane-proximal spindle pole. PMID:21889938

  1. Iron-molybdenum-oxo complexes as initiators for olefin autoxidation with O2.

    PubMed

    Falkenhagen, Jan P; Limberg, Christian; Demeshko, Serhiy; Horn, Sebastian; Haumann, Michael; Braun, Beatrice; Mebs, Stefan

    2014-01-14

    The reaction between [(TPA)Fe(MeCN)2](OTf)2 and [nBu4N](Cp*MoO3) yields the novel tetranuclear complex [(TPA)Fe(μ-Cp*MoO3)]2(OTf)2, 1, with a rectangular [Mo-O-Fe-O-]2 core containing high-spin iron(ii) centres. 1 proved to be an efficient initiator/(pre)catalyst for the autoxidation of cis-cyclooctene with O2 to give cyclooctene epoxide. To test, which features of 1 are essential in this regard, analogues with zinc(ii) and cobalt(ii) central atoms, namely [(TPA)Zn(Cp*MoO3)](OTf), 3, and [(TPA)Co(Cp*MoO3)](OTf), 4, were prepared, which proved to be inactive. The precursor compounds of 1, [(TPA)Fe(MeCN)2](OTf)2 and [nBu4N](Cp*MoO3) as well as Cp2*Mo2O5, were found to be inactive, too. Reactivity studies in the absence of cyclooctene revealed that 1 reacts both with O2 and PhIO via loss of the Cp* ligands to give the triflate salt 2 of the known cation [((TPA)Fe)2(μ-O)(μ-MoO4)](2+). The cobalt analogue 4 reacts with O2 in a different way yielding [((TPA)Co)2(μ-Mo2O8)](OTf)2, 5, featuring a Mo2O8(4-) structural unit which is novel in coordination chemistry. The compound [(TPA)Fe(μ-MoO4)]2, 6, being related to 1, but lacking Cp* ligands failed to trigger autoxidation of cyclooctene. However, initiation of autoxidation by Cp* radicals was excluded via experiments including thermal dissociation of Cp2*.

  2. Bis(phosphinic)diamido yttrium amide, alkoxide, and aryloxide complexes: an evaluation of lactide ring-opening polymerization initiator efficiency.

    PubMed

    Platel, Rachel H; White, Andrew J P; Williams, Charlotte K

    2011-08-15

    The synthesis and characterization of a series of bis(phosphinic)diamido yttrium alkoxide, amide, and aryloxide initiators are reported. The new complexes are characterized using multinuclear nuclear magnetic resonance (NMR) spectroscopy, elemental analysis, and, in some cases, X-ray crystallography. The alkoxide complexes are all dimeric in both the solid state and in solution, as are the amide complexes substituted with iso-propyl or phenyl groups on the phosphorus atoms. On the other hand, increasing the steric hindrance of the phosphorus substituents (tert-butyl), enables isolation of mononuclear yttrium amide complexes with either 2,2-dimethylpropylene or ethylene diamido ligand backbones. The complex of 2,6-di-tert-butyl-4-methylphenoxide is also mononuclear. All the new complexes are efficient initiators for rac-lactide ring-opening polymerization. The polymerization kinetics are compared and pseudo first order rate constants, k(obs), determined. The polymerization control is also discussed, by monitoring the number-averaged molecular weight, M(n), and polydispersity index, PDI, obtained using gel permeation chromatography (GPC). The alkoxide complexes are the most efficient initiators, showing very high rates and good polymerization control, behavior consistent with rapid rates of initiation. The phenoxide and amide complexes are less efficient as manifest by nonlinear regions in the kinetic plots, lower values for k(obs), and reduced polymerization control. One of the mononuclear yttrium amide complexes shows heteroselectivity in the polymerization of rac-lactide; however, this effect is reduced on changing the initiating group to phenoxide or on changing the ancillary ligand diamido backbone group.

  3. [SWI/SNF Protein Complexes Participate in the Initiation and Elongation Stages of Drosophila hsp70 Gene Transcription].

    PubMed

    Mazina, M Yu; Nikolenko, Yu V; Krasnov, A N; Vorobyeva, N E

    2016-02-01

    The participation of the SWI/SNF chromatin remodeling complex in the stimulation of the RNA polymerase II binding to gene promotors was demonstrated in all model eukaryotic organisms. It was shown eight years ago that the SWI/SNF complex influence on transcription is not limited to its role in initiation but also includes participation in elongation and alternative splicing. In the current work, we describe the subunit composition of the SWI/SNF complexes participating in initiation, preparing for the elongation and elongation of hsp70 gene transcription in Drosophila melanogaster. The data reveal the high mobility of the SWI/SNF complex composition during the hsp 70 gene transcription process. We suggest a model describing the process of sequential SWI/SNF complex formation during heat-shock induced transcription of the hsp 70 gene. PMID:27215030

  4. [SWI/SNF Protein Complexes Participate in the Initiation and Elongation Stages of Drosophila hsp70 Gene Transcription].

    PubMed

    Mazina, M Yu; Nikolenko, Yu V; Krasnov, A N; Vorobyeva, N E

    2016-02-01

    The participation of the SWI/SNF chromatin remodeling complex in the stimulation of the RNA polymerase II binding to gene promotors was demonstrated in all model eukaryotic organisms. It was shown eight years ago that the SWI/SNF complex influence on transcription is not limited to its role in initiation but also includes participation in elongation and alternative splicing. In the current work, we describe the subunit composition of the SWI/SNF complexes participating in initiation, preparing for the elongation and elongation of hsp70 gene transcription in Drosophila melanogaster. The data reveal the high mobility of the SWI/SNF complex composition during the hsp 70 gene transcription process. We suggest a model describing the process of sequential SWI/SNF complex formation during heat-shock induced transcription of the hsp 70 gene.

  5. Complex Events Initiated by Individual Spikes in the Human Cerebral Cortex

    PubMed Central

    Komlósi, Gergely; Füle, Miklós; Szabadics, János; Varga, Csaba; Barzó, Pál; Tamás, Gábor

    2008-01-01

    Synaptic interactions between neurons of the human cerebral cortex were not directly studied to date. We recorded the first dataset, to our knowledge, on the synaptic effect of identified human pyramidal cells on various types of postsynaptic neurons and reveal complex events triggered by individual action potentials in the human neocortical network. Brain slices were prepared from nonpathological samples of cortex that had to be removed for the surgical treatment of brain areas beneath association cortices of 58 patients aged 18 to 73 y. Simultaneous triple and quadruple whole-cell patch clamp recordings were performed testing mono- and polysynaptic potentials in target neurons following a single action potential fired by layer 2/3 pyramidal cells, and the temporal structure of events and underlying mechanisms were analyzed. In addition to monosynaptic postsynaptic potentials, individual action potentials in presynaptic pyramidal cells initiated long-lasting (37 ± 17 ms) sequences of events in the network lasting an order of magnitude longer than detected previously in other species. These event series were composed of specifically alternating glutamatergic and GABAergic postsynaptic potentials and required selective spike-to-spike coupling from pyramidal cells to GABAergic interneurons producing concomitant inhibitory as well as excitatory feed-forward action of GABA. Single action potentials of human neurons are sufficient to recruit Hebbian-like neuronal assemblies that are proposed to participate in cognitive processes. PMID:18767905

  6. Methane hydrate destabilization sensitivity to physical complexity and initial conditions in a numerical model

    NASA Astrophysics Data System (ADS)

    Darnell, K.; Flemings, P. B.; Bryant, S. L.

    2013-12-01

    We modify an existing dynamic, multiphase fluid flow model after Liu and Flemings (2007) to form methane hydrate and subsequently melt the hydrate in a marine, sedimentary environment. We then investigate the timing and evolution of hydrate melting when we include varying degrees of thermodynamic and chemical complexity. Our findings indicate that the incorporation of the latent heat of hydrate melting coupled with fresh water release retards the melting process. If the latent heat is neglected, the time required for the warming signal propagation to melt the hydrate completely is shorter by as much as a factor of two. Our basic model considers a one dimensional sedimentary column where the sediment is initially water saturated and supplied with a constant gas flux from below the hydrate stability zone, with the assumption that solid/gas/liquid phases are in equilibrium at the local pressure, temperature and salinity. We consider transport of water, methane, and salt over a 30 kyr interval to generate a modern hydrate deposit and corresponding salinity profile. Then, an instantaneous temperature increase is applied at the seafloor and held constant. This work suggests an alternative timing on the Gulf Stream shift that has been deduced from anomalous hydrate deposits by Phrampus and Hornbach (2012). Furthermore, we are able to show that current warming and relict warming from several hundreds years may be simultaneously convoluted in any current hydrate destabilization.

  7. Children With Medical Complexity: An Emerging Population for Clinical and Research Initiatives

    PubMed Central

    Kuo, Dennis Z.; Agrawal, Rishi; Berry, Jay G.; Bhagat, Santi K. M.; Simon, Tamara D.; Srivastava, Rajendu

    2011-01-01

    Children with medical complexity (CMC) have medical fragility and intensive care needs that are not easily met by existing health care models. CMC may have a congenital or acquired multisystem disease, a severe neurologic condition with marked functional impairment, and/or technology dependence for activities of daily living. Although these children are at risk of poor health and family outcomes, there are few well-characterized clinical initiatives and research efforts devoted to improving their care. In this article, we present a definitional framework of CMC that consists of substantial family-identified service needs, characteristic chronic and severe conditions, functional limitations, and high health care use. We explore the diversity of existing care models and apply the principles of the chronic care model to address the clinical needs of CMC. Finally, we suggest a research agenda that uses a uniform definition to accurately describe the population and to evaluate outcomes from the perspectives of the child, the family, and the broader health care system. PMID:21339266

  8. Post-transcription initiation function of the ubiquitous SAGA complex in tissue-specific gene activation

    PubMed Central

    Weake, Vikki M.; Dyer, Jamie O.; Seidel, Christopher; Box, Andrew; Swanson, Selene K.; Peak, Allison; Florens, Laurence; Washburn, Michael P.; Abmayr, Susan M.; Workman, Jerry L.

    2011-01-01

    The Spt–Ada–Gcn5–acetyltransferase (SAGA) complex was discovered from Saccharomyces cerevisiae and has been well characterized as an important transcriptional coactivator that interacts both with sequence-specific transcription factors and the TATA-binding protein TBP. SAGA contains a histone acetyltransferase and a ubiquitin protease. In metazoans, SAGA is essential for development, yet little is known about the function of SAGA in differentiating tissue. We analyzed the composition, interacting proteins, and genomic distribution of SAGA in muscle and neuronal tissue of late stage Drosophila melanogaster embryos. The subunit composition of SAGA was the same in each tissue; however, SAGA was associated with considerably more transcription factors in muscle compared with neurons. Consistent with this finding, SAGA was found to occupy more genes specifically in muscle than in neurons. Strikingly, SAGA occupancy was not limited to enhancers and promoters but primarily colocalized with RNA polymerase II within transcribed sequences. SAGA binding peaks at the site of RNA polymerase pausing at the 5′ end of transcribed sequences. In addition, many tissue-specific SAGA-bound genes required its ubiquitin protease activity for full expression. These data indicate that in metazoans SAGA plays a prominent post-transcription initiation role in tissue-specific gene expression. PMID:21764853

  9. Affinity labelling of Escherichia coli ribosomes with a benzylidene derivative of AUGU6 within initiation and pretranslocational complexes.

    PubMed

    Babkina, G T; Veniaminova, A G; Vladimirov, S N; Karpova, G G; Yamkovoy, V I; Berzin, V A; Gren, E J; Cielens, I E

    1986-07-01

    Affinity labelling of E. coli ribosomes with the 2',3'-O-[4-(N-2-chloroethyl)-N-methylamino]benzylidene derivative of AUGU6 was studied within the initiation complex (complex I) obtained by using fMet-tRNAMetf and initiation factors and within the pretranslocational complex (complex II) obtained by treatment of complex I with the ternary complex Phe-tRNAPhe.GTP.EF-Tu. Both proteins and rRNA of 30 S as well as 50 S subunits were found to be labelled. Sets of proteins labelled within complexes I and II differ considerably. Within complex II, proteins S13 and L10 were labelled preferentially. On the other hand, within complex I, multiple modification is observed (proteins S4, S12, S13, S14, S15, S18, S19, S20/L26 were found to be alkylated) despite the single fixation of a template in the ribosome by interaction of the AUG codon with fMet-tRNAMetf.

  10. Ubiquinone-binding site mutagenesis reveals the role of mitochondrial complex II in cell death initiation.

    PubMed

    Kluckova, K; Sticha, M; Cerny, J; Mracek, T; Dong, L; Drahota, Z; Gottlieb, E; Neuzil, J; Rohlena, J

    2015-01-01

    Respiratory complex II (CII, succinate dehydrogenase, SDH) inhibition can induce cell death, but the mechanistic details need clarification. To elucidate the role of reactive oxygen species (ROS) formation upon the ubiquinone-binding (Qp) site blockade, we substituted CII subunit C (SDHC) residues lining the Qp site by site-directed mutagenesis. Cell lines carrying these mutations were characterized on the bases of CII activity and exposed to Qp site inhibitors MitoVES, thenoyltrifluoroacetone (TTFA) and Atpenin A5. We found that I56F and S68A SDHC variants, which support succinate-mediated respiration and maintain low intracellular succinate, were less efficiently inhibited by MitoVES than the wild-type (WT) variant. Importantly, associated ROS generation and cell death induction was also impaired, and cell death in the WT cells was malonate and catalase sensitive. In contrast, the S68A variant was much more susceptible to TTFA inhibition than the I56F variant or the WT CII, which was again reflected by enhanced ROS formation and increased malonate- and catalase-sensitive cell death induction. The R72C variant that accumulates intracellular succinate due to compromised CII activity was resistant to MitoVES and TTFA treatment and did not increase ROS, even though TTFA efficiently generated ROS at low succinate in mitochondria isolated from R72C cells. Similarly, the high-affinity Qp site inhibitor Atpenin A5 rapidly increased intracellular succinate in WT cells but did not induce ROS or cell death, unlike MitoVES and TTFA that upregulated succinate only moderately. These results demonstrate that cell death initiation upon CII inhibition depends on ROS and that the extent of cell death correlates with the potency of inhibition at the Qp site unless intracellular succinate is high. In addition, this validates the Qp site of CII as a target for cell death induction with relevance to cancer therapy. PMID:25950479

  11. Ubiquinone-binding site mutagenesis reveals the role of mitochondrial complex II in cell death initiation

    PubMed Central

    Kluckova, K; Sticha, M; Cerny, J; Mracek, T; Dong, L; Drahota, Z; Gottlieb, E; Neuzil, J; Rohlena, J

    2015-01-01

    Respiratory complex II (CII, succinate dehydrogenase, SDH) inhibition can induce cell death, but the mechanistic details need clarification. To elucidate the role of reactive oxygen species (ROS) formation upon the ubiquinone-binding (Qp) site blockade, we substituted CII subunit C (SDHC) residues lining the Qp site by site-directed mutagenesis. Cell lines carrying these mutations were characterized on the bases of CII activity and exposed to Qp site inhibitors MitoVES, thenoyltrifluoroacetone (TTFA) and Atpenin A5. We found that I56F and S68A SDHC variants, which support succinate-mediated respiration and maintain low intracellular succinate, were less efficiently inhibited by MitoVES than the wild-type (WT) variant. Importantly, associated ROS generation and cell death induction was also impaired, and cell death in the WT cells was malonate and catalase sensitive. In contrast, the S68A variant was much more susceptible to TTFA inhibition than the I56F variant or the WT CII, which was again reflected by enhanced ROS formation and increased malonate- and catalase-sensitive cell death induction. The R72C variant that accumulates intracellular succinate due to compromised CII activity was resistant to MitoVES and TTFA treatment and did not increase ROS, even though TTFA efficiently generated ROS at low succinate in mitochondria isolated from R72C cells. Similarly, the high-affinity Qp site inhibitor Atpenin A5 rapidly increased intracellular succinate in WT cells but did not induce ROS or cell death, unlike MitoVES and TTFA that upregulated succinate only moderately. These results demonstrate that cell death initiation upon CII inhibition depends on ROS and that the extent of cell death correlates with the potency of inhibition at the Qp site unless intracellular succinate is high. In addition, this validates the Qp site of CII as a target for cell death induction with relevance to cancer therapy. PMID:25950479

  12. An impaired ubiquitin ligase complex favors initial growth of auxotrophic yeast strains in synthetic grape must.

    PubMed

    Mangado, Ana; Tronchoni, Jordi; Morales, Pilar; Novo, Maite; Quirós, Manuel; Gonzalez, Ramon

    2015-02-01

    We used experimental evolution in order to identify genes involved in the adaptation of Saccharomyces cerevisiae to the early stages of alcoholic fermentation. Evolution experiments were run for about 200 generations, in continuous culture conditions emulating the initial stages of wine fermentation. We performed whole-genome sequencing of four adapted strains from three independent evolution experiments. Mutations identified in these strains pointed to the Rsp5p-Bul1/2p ubiquitin ligase complex as the preferred evolutionary target under these experimental conditions. Rsp5p is a multifunctional enzyme able to ubiquitinate target proteins participating in different cellular processes, while Bul1p is an Rsp5p substrate adaptor specifically involved in the ubiquitin-dependent internalization of Gap1p and other plasma membrane permeases. While a loss-of-function mutation in BUL1 seems to be enough to confer a selective advantage under these assay conditions, this did not seem to be the case for RSP5 mutated strains, which required additional mutations, probably compensating for the detrimental effect of altered Rsp5p activity on essential cellular functions. The power of this experimental approach is illustrated by the identification of four independent mutants, each with a limited number of SNPs, affected within the same pathway. However, in order to obtain information relevant for a specific biotechnological process, caution must be taken in the choice of the background yeast genotype (as shown in this case for auxotrophies). In addition, the use of very stable continuous fermentation conditions might lead to the selection of a rather limited number of adaptive responses that would mask other possible targets for genetic improvement. PMID:25620600

  13. Crystal Structure of pi Initiator Protein-iteron Complex of Plasmid R6K: Implications for Initiation of Plasmid DNA Replication

    SciTech Connect

    Swan,M.; Bastia, D.; Davies, C.

    2006-01-01

    We have determined the crystal structure of a monomeric biologically active form of the {pi} initiator protein of plasmid R6K as a complex with a single copy of its cognate DNA-binding site (iteron) at 3.1-{angstrom} resolution. The initiator belongs to the family of winged helix type of proteins. The structure reveals that the protein contacts the iteron DNA at two primary recognition helices, namely the C-terminal {alpha}4' and the N-terminal {alpha}4 helices, that recognize the 5' half and the 3' half of the 22-bp iteron, respectively. The base-amino acid contacts are all located in {alpha}4', whereas the {alpha}4 helix and its vicinity mainly contact the phosphate groups of the iteron. Mutational analyses show that the contacts of both recognition helices with DNA are necessary for iteron binding and replication initiation. Considerations of a large number of site-directed mutations reveal that two distinct regions, namely {alpha}2 and {alpha}5 and its vicinity, are required for DNA looping and initiator dimerization, respectively. Further analysis of mutant forms of {pi} revealed the possible domain that interacts with the DnaB helicase. Thus, the structure-function analysis presented illuminates aspects of initiation mechanism of R6K and its control.

  14. Transcription initiation complexes and upstream activation with RNA polymerase II lacking the C-terminal domain of the largest subunit.

    PubMed Central

    Buratowski, S; Sharp, P A

    1990-01-01

    RNA polymerase II assembles with other factors on the adenovirus type 2 major late promoter to generate pairs of transcription initiation complexes resolvable by nondenaturing gel electrophoresis. The pairing of the complexes is caused by the presence or absence of the C-terminal domain of the largest subunit. This domain is not required for transcription stimulation by the major late transcription factor in vitro. Images PMID:2398901

  15. A marked stimulation of Fe2+-initiated lipid peroxidation in phospholipid liposomes by a lipophilic aluminum complex, aluminum acetylacetonate.

    PubMed

    Ohyashiki, T; Suzuki, S; Satoh, E; Uemori, Y

    1998-01-15

    In the present study, the efficacy of a lipophilic Al complex, aluminum acetylacetonate, as a stimulator of Fe2+-initiated lipid peroxidation in phospholipid liposomes was examined, and results were compared with those from the liposomes treated with AlCl3. The extent of lipid peroxidation was assessed by the formation of thiobarbituric acid-reactive substances (TBARS). The results indicated that the stimulatory effect of Al complex on Fe2+-initiated lipid peroxidation in phosphatidylcholine liposomes was more effective than that of AlCl3 under the same conditions. The concentration dependence of Al complex on TBARS production showed that the concentration of the complex required to induce half-maximal stimulation of TBARS production was 43 microM. In contrast, the stimulatory effect of AlCl3 was not observed until the AlCl3 concentration is increased above 300 microM. In addition, it was found that there is a linear relationship between the TBARS values and the residual amounts of Fe2+ at an earlier stage (within 2 min after the addition of Fe2+) of the lipid peroxidation in PC liposomes with different concentrations of Al complex, suggesting that Fe2+ oxidation process is closely related to the stimulatory effect of Al complex. The stimulatory effect of Al complex upon the lipid peroxidation completely disappeared by treatment of Al complex-treated liposomes with Triton X-100. The results of fluorescence anisotropy measurements using 12-(9-anthroyloxy)stearic acid-labeled liposomes suggested that treatment of the liposomes with Al complex caused a decrease in their lipid fluidity. Furthermore, it was found that there is a correlation between the extents of the fluorescence anisotropy and the Fe2+ oxidation parameters in the liposomes with different concentrations of Al complex. From these results, it is suggested that the Al effect on Fe2+-initiated lipid peroxidation in the phospholipid liposomes is markedly enhanced by incorporation of Al complex into the

  16. Developing Organizational Capacity for Implementing Complex Education Reform Initiatives: Insights from a Multiyear Study of a Teacher Incentive Fund Program

    ERIC Educational Resources Information Center

    Malen, Betty; Rice, Jennifer King; Matlach, Lauren K. B.; Bowsher, Amanda; Hoyer, Kathleen Mulvaney; Hyde, Laura H.

    2015-01-01

    Purpose: This article seeks to enhance our understanding of the ever-present challenge of developing organizational capacity to implement complex education reform initiatives. We analyze the strategies in one large metropolitan education system used to address the district-level and site-level capacity challenges that surfaced as they implemented…

  17. Highly heteroselective ring-opening polymerization of racemic lactide initiated by divalent ytterbium complexes bearing amino bis(phenolate) ligands.

    PubMed

    Yang, Sheng; Du, Zhu; Zhang, Yong; Shen, Qi

    2012-10-01

    Polymerization of racemic lactide initiated by divalent ytterbium complexes supported by either dimethylamino-amino bis(phenolate) or methoxy-amino bis(phenolate) ligands proceeds rapidly at room temperature in a living fashion to give heterotactic polylactide with the racemic enchainment of monomer units P(r) ranging from 0.97-0.99.

  18. Runoff initiation versus runoff yield: Understanding the complexity of the hydrological effect of biological soil crusts

    NASA Astrophysics Data System (ADS)

    Kidron, G. J.; Monger, H. C.; Büdel, B.; Vonshak, A.; Conrod, W.

    2012-04-01

    The differentiation between runoff initiation and runoff yield (amount) is not always clear. In many cases they often seem interchangeable. Some of the differences were pinpointed following research conducted at two sand fields in Israel (Nizzanim, NIM, at the southern coast and Nizzana, NIZ in the Negev) and three sites in the Chihuahuan Desert, New Mexico, USA (silty-loessial sediments at the Jornada Experimental Range, JER; quartzose sand in the Sevilleta Wildlife Refuge, SEV; gypseous sand at the White Sands National Monument, WS) during which intact plots were compared to scalped plots. While the parent material, the effective rain, and the exopolysacharide (EPS) content of the crust determined runoff initiation in the Chihuahuan Desert, the effective rain and the crust microrelief determined the amount (yield) of runoff in areas where runoff initiation took place. Low EPS-crusts did not facilitated runoff initiation, even at high-chlorophyll crusts such as in WS. Similar results were obtained for NIM. Data from NIZ also highlighted the fundamental role played by the EPS in the determination of the amounts of runoff. This however was not the case with the chlorophyll content per se, that did not determine runoff initiation or yield. The findings also indicate that under the conditions examined, microrelief could not have controlled runoff initiation. Nevertheless, it affected the runoff amounts, as found in the Chihuahuan Desert and the Negev. The presence of rills and gullies may be indicative of the potentiality of BSCs to initiate runoff.

  19. Dominant Rio1 kinase/ATPase catalytic mutant induces trapping of late pre-40S biogenesis factors in 80S-like ribosomes.

    PubMed

    Ferreira-Cerca, Sébastien; Kiburu, Irene; Thomson, Emma; LaRonde, Nicole; Hurt, Ed

    2014-07-01

    During eukaryotic ribosome biogenesis, members of the conserved atypical serine/threonine protein kinase family, the RIO kinases (Rio1, Rio2 and Rio3) function in small ribosomal subunit biogenesis. Structural analysis of Rio2 indicated a role as a conformation-sensing ATPase rather than a kinase to regulate its dynamic association with the pre-40S subunit. However, it remained elusive at which step and by which mechanism the other RIO kinase members act. Here, we have determined the crystal structure of the human Rio1-ATP-Mg(2+) complex carrying a phosphoaspartate in the active site indicative of ATPase activity. Structure-based mutations in yeast showed that Rio1's catalytic activity regulates its pre-40S association. Furthermore, we provide evidence that Rio1 associates with a very late pre-40S via its conserved C-terminal domain. Moreover, a rio1 dominant-negative mutant defective in ATP hydrolysis induced trapping of late biogenesis factors in pre-ribosomal particles, which turned out not to be pre-40S but 80S-like ribosomes. Thus, the RIO kinase fold generates a versatile ATPase enzyme, which in the case of Rio1 is activated following the Rio2 step to regulate one of the final 40S maturation events, at which time the 60S subunit is recruited for final quality control check.

  20. The Yeast Eukaryotic Translation Initiation Factor 2B Translation Initiation Complex Interacts with the Fatty Acid Synthesis Enzyme YBR159W and Endoplasmic Reticulum Membranes

    PubMed Central

    Browne, Christopher M.; Samir, Parimal; Fites, J. Scott; Villarreal, Seth A.

    2013-01-01

    Using affinity purifications coupled with mass spectrometry and yeast two-hybrid assays, we show the Saccharomyces cerevisiae translation initiation factor complex eukaryotic translation initiation factor 2B (eIF2B) and the very-long-chain fatty acid (VLCFA) synthesis keto-reductase enzyme YBR159W physically interact. The data show that the interaction is specifically between YBR159W and eIF2B and not between other members of the translation initiation or VLCFA pathways. A ybr159wΔ null strain has a slow-growth phenotype and a reduced translation rate but a normal GCN4 response to amino acid starvation. Although YBR159W localizes to the endoplasmic reticulum membrane, subcellular fractionation experiments show that a fraction of eIF2B cofractionates with lipid membranes in a YBR159W-independent manner. We show that a ybr159wΔ yeast strain and other strains with null mutations in the VLCFA pathway cause eIF2B to appear as numerous foci throughout the cytoplasm. PMID:23263984

  1. Molecular Architecture of the 40S⋅eIF1⋅eIF3 Translation Initiation Complex

    PubMed Central

    Erzberger, Jan P.; Stengel, Florian; Pellarin, Riccardo; Zhang, Suyang; Schaefer, Tanja; Aylett, Christopher H.S.; Cimermančič, Peter; Boehringer, Daniel; Sali, Andrej; Aebersold, Ruedi; Ban, Nenad

    2014-01-01

    Summary Eukaryotic translation initiation requires the recruitment of the large, multiprotein eIF3 complex to the 40S ribosomal subunit. We present X-ray structures of all major components of the minimal, six-subunit Saccharomyces cerevisiae eIF3 core. These structures, together with electron microscopy reconstructions, cross-linking coupled to mass spectrometry, and integrative structure modeling, allowed us to position and orient all eIF3 components on the 40S⋅eIF1 complex, revealing an extended, modular arrangement of eIF3 subunits. Yeast eIF3 engages 40S in a clamp-like manner, fully encircling 40S to position key initiation factors on opposite ends of the mRNA channel, providing a platform for the recruitment, assembly, and regulation of the translation initiation machinery. The structures of eIF3 components reported here also have implications for understanding the architecture of the mammalian 43S preinitiation complex and the complex of eIF3, 40S, and the hepatitis C internal ribosomal entry site RNA. PMID:25171412

  2. Attachment of ribosomal complexes and retrograde scanning during initiation on the Halastavi árva virus IRES

    PubMed Central

    Abaeva, Irina S.; Pestova, Tatyana V.; Hellen, Christopher U.T.

    2016-01-01

    Halastavi árva virus (HalV) has a positive-sense RNA genome, with an 827 nt-long 5′ UTR and an intergenic region separating two open reading frames. Whereas the encoded proteins are most homologous to Dicistrovirus polyproteins, its 5′ UTR is distinct. Here, we report that the HalV 5′ UTR comprises small stem-loop domains separated by long single-stranded areas and a large A-rich unstructured region surrounding the initiation codon AUG828, and possesses cross-kingdom internal ribosome entry site (IRES) activity. In contrast to most viral IRESs, it does not depend on structural integrity and specific interaction of a structured element with a translational component, and is instead determined by the unstructured region flanking AUG828. eIF2, eIF3, eIF1 and eIF1A promote efficient 48S initiation complex formation at AUG828, which is reduced ∼5-fold on omission of eIF1 and eIF1A. Initiation involves direct attachment of 43S preinitiation complexes within a short window at or immediately downstream of AUG828. 40S and eIF3 are sufficient for initial binding. After attachment, 43S complexes undergo retrograde scanning, strongly dependent on eIF1 and eIF1A. eIF4A/eIF4G stimulated initiation only at low temperatures or on mutants, in which areas surrounding AUG828 had been replaced by heterologous sequences. However, they strongly promoted initiation at AUG872, yielding a proline-rich oligopeptide. PMID:26783202

  3. Attachment of ribosomal complexes and retrograde scanning during initiation on the Halastavi árva virus IRES.

    PubMed

    Abaeva, Irina S; Pestova, Tatyana V; Hellen, Christopher U T

    2016-03-18

    Halastavi árva virus (HalV) has a positive-sense RNA genome, with an 827 nt-long 5' UTR and an intergenic region separating two open reading frames. Whereas the encoded proteins are most homologous to Dicistrovirus polyproteins, its 5' UTR is distinct. Here, we report that the HalV 5' UTR comprises small stem-loop domains separated by long single-stranded areas and a large A-rich unstructured region surrounding the initiation codon AUG828, and possesses cross-kingdom internal ribosome entry site (IRES) activity. In contrast to most viral IRESs, it does not depend on structural integrity and specific interaction of a structured element with a translational component, and is instead determined by the unstructured region flanking AUG828. eIF2, eIF3, eIF1 and eIF1A promote efficient 48S initiation complex formation at AUG828, which is reduced ∼5-fold on omission of eIF1 and eIF1A. Initiation involves direct attachment of 43S preinitiation complexes within a short window at or immediately downstream of AUG828. 40S and eIF3 are sufficient for initial binding. After attachment, 43S complexes undergo retrograde scanning, strongly dependent on eIF1 and eIF1A. eIF4A/eIF4G stimulated initiation only at low temperatures or on mutants, in which areas surrounding AUG828 had been replaced by heterologous sequences. However, they strongly promoted initiation at AUG872, yielding a proline-rich oligopeptide. PMID:26783202

  4. Differential evolution based on the node degree of its complex network: Initial study

    NASA Astrophysics Data System (ADS)

    Skanderova, Lenka; Zelinka, Ivan

    2016-06-01

    In this paper is reported our progress in the synthesis of two partially different areas of research: complex networks and evolutionary computation. Ideas and results reported and mentioned here are based on our previous results and experiments. The main core of our participation is an evolutionary algorithm performance improvement by means of complex network use. Complex network is related to the evolutionary dynamics and reflect it. We report here our latest results as well as propositions on further research that is in process in our group (http://navy.cs.vsb.cz/). Only the main ideas and results are reported here, for more details it is recommended to read related literature of our previous research and results.

  5. Through the '80s: thinking globally, acting locally. [Combined Canadian Futures Society and Third General Assembly of World Future Society

    SciTech Connect

    Feather, F.

    1980-01-01

    This volume was prepared in conjunction with the First Global Conference on the Future, held in Toronto, Canada, July 20-24, 1980. The conference combined the Third General Assembly of the World Future Society and the fifth annual conference of the Canadian Futures Society. The 59 papers presented here were selected from the very large number submitted to the conference committee; space limitations permitted only a small number of papers to be published in this volume. Included also are: the foreword, Mystery of the Future, by Edward R. Schreyer, Governor General of Canada; preface, A Time for Action, by Maurice F. Strong; introduction, Transition to Harmonic Globalism, by Frank Feather; conclusion, What We Must Do: An Agenda for Futurists; and postscript, The Challenge of the '80s, by Aurelio Peccei. The papers were presented under the following topics: The Trauma of Change (4); A Global Perspective (7); Inventorying Our Resources (7); The International Context (8); Economics: Getting Down to Business (9); Human Values: Personal, Social, Religious (6); Communications: Connecting Ourselves Together (4); Education: Learning to Meet Tomorrow (4); Health: New Approaches to Staying Fit (3); Futurism as a Way of Life (5); and Dreams into Action: Methods and Real-Life Experience (2).

  6. Disassembly of yeast 80S ribosomes into subunits is a concerted action of ribosome-assisted folding of denatured protein.

    PubMed

    Chakraborty, Biprashekhar; Bhakta, Sayan; Sengupta, Jayati

    2016-01-22

    It has been shown by several groups that ribosome can assist folding of denatured protein in vitro and the process is conserved across the species. Domain V of large ribosomal rRNA which occupies the intersubunit side of the large subunit was identified as the key player responsible for chaperoning the folding process. Thus, it is conceivable that denatured protein needs to access the intersubunit space of the ribosome in order to get folded. In this study, we have investigated the mechanism of release of the protein from the eukaryotic ribosome following reactivation. We have observed significant splitting of yeast 80S ribosome when incubated with the denatured BCAII protein. Energy-free disassembly mechanism functions in low Mg(+2) ion concentration for prokaryotic ribosomes. Eukaryotic ribosomes do not show significant splitting even at low Mg(+2) ion concentration. In this respect, denatured protein-induced disassembly of eukaryotic ribosome without the involvement of any external energy source is intriguing. For prokaryotic ribosomes, it was reported that the denatured protein induces ribosome splitting into subunits in order to access domain V-rRNA. In contrast, our results suggest an alternative mechanism for eukaryotic ribosomal rRNA-mediated protein folding and subsequent separation of the subunits by which release of the activated-protein occurs.

  7. Catalytic Isonitrile Insertions and Condensations Initiated by RNC–X Complexation

    PubMed Central

    Fleming, Fraser F.

    2014-01-01

    Isonitriles are delicately poised chemical entities capable of being coaxed to react as nucleophiles or electrophiles. Directing this tunable reactivity with metal and non-metal catalysts provides rapid access to a large array of complex nitrogenous structures ideally functionalized for medicinal applications. Isonitrile insertion into transition metal complexes has featured in numerous synthetic and mechanistic studies, leading to rapid deployment of isonitriles in numerous catalytic processes, including multicomponent reactions (MCR). Covering the literature from 1990–2014, the present review collates reaction types to highlight reactivity trends and allow catalyst comparison. PMID:25484847

  8. Waves of 3D marine structures slamming at different initial poses in complex wind-wave-flow environments

    NASA Astrophysics Data System (ADS)

    Zhu, Liang-sheng; Yu, Long-fei

    2016-10-01

    Aimed at the hydrodynamic response for marine structures slamming into water, based on the mechanism analysis to the slamming process, and by combining 3D N-S equation and k- ɛ turbulent kinetic equation with structure fully 6DOF motion equation, a mathematical model for the wind-fluid-solid interaction is established in 3D marine structure slamming wave at free poses and wind-wave-flow complex environments. Compared with the results of physical model test, the numerical results from the slamming wave well correspond with the experimental results. Through the mathematical model, the wave-making issue of 3D marine structure at initial pose falls into water in different complex wind, wave and flow environments is investigated. The research results show that various kinds of natural factors and structure initial poses have different influence on the slamming wave, and there is an obvious rule in this process.

  9. Plant Cap-binding Complexes Eukaryotic Initiation Factors eIF4F and eIFISO4F

    PubMed Central

    Mayberry, Laura K.; Allen, M. Leah; Nitka, Kelley R.; Campbell, Lara; Murphy, Patricia A.; Browning, Karen S.

    2011-01-01

    The initiation of translation in eukaryotes requires a suite of eIFs that include the cap-binding complex, eIF4F. eIF4F is comprised of the subunits eIF4G and eIF4E and often the helicase, eIF4A. The eIF4G subunit serves as an assembly point for other initiation factors, whereas eIF4E binds to the 7-methyl guanosine cap of mRNA. Plants have an isozyme form of eIF4F (eIFiso4F) with comparable subunits, eIFiso4E and eIFiso4G. Plant eIF4A is very loosely associated with the plant cap-binding complexes. The specificity of interaction of the individual subunits of the two complexes was previously unknown. To address this issue, mixed complexes (eIF4E-eIFiso4G or eIFiso4E-eIF4G) were expressed and purified from Escherichia coli for biochemical analysis. The activity of the mixed complexes in in vitro translation assays correlated with the large subunit of the respective correct complex. These results suggest that the eIF4G or eIFiso4G subunits influence translational efficiency more than the cap-binding subunits. The translation assays also showed varying responses of the mRNA templates to eIF4F or eIFiso4F, suggesting that some level of mRNA discrimination is possible. The dissociation constants for the correct complexes have KD values in the subnanomolar range, whereas the mixed complexes were found to have KD values in the ∼10 nm range. Displacement assays showed that the correct binding partner readily displaces the incorrect binding partner in a manner consistent with the difference in KD values. These results show molecular specificity for the formation of plant eIF4F and eIFiso4F complexes and suggest a role in mRNA discrimination during initiation of translation. PMID:21965660

  10. Dealing with Complexity: Theory of Change Evaluation and the Full Service Extended Schools Initiative

    ERIC Educational Resources Information Center

    Dyson, Alan; Todd, Liz

    2010-01-01

    The full service extended schools (FSES) initiative in England sought to build the capacity of schools to deploy multiple interventions across a range of child, family, and community contexts in order to improve the lives of children and families, and to enhance the sustainability of the areas where they live. As such, it was part of wider…

  11. TARGETING THE eIF4F TRANSLATION INITIATION COMPLEX: A CRITICAL NEXUS FOR CANCER DEVELOPMENT

    PubMed Central

    Pelletier, Jerry; Graff, Jeremy; Ruggero, Davide; Sonenberg, Nahum

    2014-01-01

    Elevated protein synthesis is an important feature of many cancer cells and often arises as a consequence of increased signaling flux channeled to eukaryotic initiation factor (eIF) 4F, the key regulator of the mRNA-ribosome recruitment phase of translation initiation. In many cellular and pre-clinical models of cancer, eIF4F deregulation results in changes in translational efficiency of specific mRNA classes. Importantly, many of these mRNAs code for proteins that potently regulate critical cellular processes such as cell growth and proliferation, enhanced cell survival, and cell migration that ultimately impinge on several hallmarks of cancer, including increased angiogenesis, deregulated growth control, enhanced cellular survival, epithelial-to-mesenchymal transition, invasion and metastasis. By being positioned as the molecular nexus downstream of key oncogenic signaling pathways (e.g. Ras, PI3K/AKT/TOR, and Myc), eIF4F serves as a direct link between important steps in cancer development and translation initiation. Identification of mRNAs particularly responsive to elevated eIF4F activity that typifies tumorigenesis underscores the critical role of eIF4F in cancer and raises the exciting possibility of developing new-in-class small molecules targeting translation initiation as anti-neoplastic agents. PMID:25593033

  12. Confinement regulates complex biochemical networks: initiation of blood clotting by "diffusion acting".

    PubMed

    Shen, Feng; Pompano, Rebecca R; Kastrup, Christian J; Ismagilov, Rustem F

    2009-10-21

    This study shows that environmental confinement strongly affects the activation of nonlinear reaction networks, such as blood coagulation (clotting), by small quantities of activators. Blood coagulation is sensitive to the local concentration of soluble activators, initiating only when the activators surpass a threshold concentration, and therefore is regulated by mass transport phenomena such as flow and diffusion. Here, diffusion was limited by decreasing the size of microfluidic chambers, and it was found that microparticles carrying either the classical stimulus, tissue factor, or a bacterial stimulus, Bacillus cereus, initiated coagulation of human platelet-poor plasma only when confined. A simple analytical argument and numerical model were used to describe the mechanism for this phenomenon: confinement causes diffusible activators to accumulate locally and surpass the threshold concentration. To interpret the results, a dimensionless confinement number, Cn, was used to describe whether a stimulus was confined, and a Damköhler number, Da(2), was used to describe whether a subthreshold stimulus could initiate coagulation. In the context of initiation of coagulation by bacteria, this mechanism can be thought of as "diffusion acting", which is distinct from "diffusion sensing". The ability of confinement and diffusion acting to change the outcome of coagulation suggests that confinement should also regulate other biological "on" and "off" processes that are controlled by thresholds.

  13. Physical Education Initial Teacher Educators' Expressions of Critical Pedagogy(ies): Coherency, Complexity or Confusion?

    ERIC Educational Resources Information Center

    Philpot, Rod

    2016-01-01

    While an emphasis on social justice has emerged as a theme in initial teacher education (ITE) over the past decade, there is much debate about how to engage ITE students in foregrounding issues of equity and social justice in their own teaching. One strategy, the introduction of critical pedagogy in ITE, has been promoted in teacher education…

  14. Translation initiation factor (iso) 4E interacts with BTF3, the beta subunit of the nascent polypeptide-associated complex.

    PubMed

    Freire, Miguel Angel

    2005-01-31

    A two-hybrid screen with the translation initiation factor, eIF(iso)4E from Arabidopsis, identified a clone encoding a lipoxygenase type 2 [Freire, M.A., et al., 2000. Plant lipoxygenase 2 is a translation initiation factor-4E-binding protein. Plant Molecular Biology 44, 129-140], and three cDNA clones encoding the homologue of the mammalian BTF3 factor, the beta subunit of the nascent polypeptide-associated complex (NAC). Here we report on the interaction between the translation initiation factor eIF(iso)4E and AtBTF3. AtBTF3 protein is able to interact with the wheat initiation factors eIF4E and eIF(iso)4E. AtBTF3 contains a sequence related to the prototypic motif found on most of the 4E-binding proteins, and competes with the translation initiation factor eIF(iso)4G for eIF4(iso)4E binding, in a two hybrid interference assay. These findings provide a molecular link between the translation initiation mechanism and the emergence of the nascent polypeptide chains.

  15. When Complexity Theory Meets Critical Realism: A Platform for Research on Initial Teacher Education

    ERIC Educational Resources Information Center

    Cochran-Smith, Marilyn; Ell, Fiona; Grudnoff, Lexie; Ludlow, Larry; Haigh, Mavis; Hill, Mary

    2014-01-01

    Many scholars have concluded that teacher education research needs to take a complex view, resist simplification, and account more fully for teacher education's contexts and processes as well as its impact on teacher candidates' and school students' learning (Cochran-Smith & Zeichner, 2005; Grossman & McDonald, 2008; Opfer & Pedder,…

  16. Metal-mediated reaction modeled on nature: the activation of isothiocyanates initiated by zinc thiolate complexes.

    PubMed

    Eger, Wilhelm A; Presselt, Martin; Jahn, Burkhard O; Schmitt, Michael; Popp, Jürgen; Anders, Ernst

    2011-04-18

    On the basis of detailed theoretical studies of the mode of action of carbonic anhydrase (CA) and models resembling only its reactive core, a complete computational pathway analysis of the reaction between several isothiocyanates and methyl mercaptan activated by a thiolate-bearing model complex [Zn(NH(3))(3)SMe](+) was performed at a high level of density functional theory (DFT). Furthermore, model reactions have been studied in the experiment using relatively stable zinc complexes and have been investigated by gas chromatography/mass spectrometry and Raman spectroscopy. The model complexes used in the experiment are based upon the well-known azamacrocyclic ligand family ([12]aneN(4), [14]aneN(4), i-[14]aneN(4), and [15]aneN(4)) and are commonly formulated as ([Zn([X]aneN(4))(SBn)]ClO(4). As predicted by our DFT calculations, all of these complexes are capable of insertion into the heterocumulene system. Raman spectroscopic investigations indicate that aryl-substituted isothiocyanates predominantly add to the C═N bond and that the size of the ring-shaped ligands of the zinc complex also has a very significant influence on the selectivity and on the reactivity as well. Unfortunately, the activated isothiocyanate is not able to add to the thiolate-corresponding mercaptan to invoke a CA analogous catalytic cycle. However, more reactive compounds such as methyl iodide can be incorporated. This work gives new insight into the mode of action and reaction path variants derived from the CA principles. Further, aspects of the reliability of DFT calculations concerning the prediction of the selectivity and reactivity are discussed. In addition, the presented synthetic pathways can offer a completely new access to a variety of dithiocarbamates. PMID:21405064

  17. Autophagy initiation by ULK complex assembly on ER tubulovesicular regions marked by ATG9 vesicles

    PubMed Central

    Karanasios, Eleftherios; Walker, Simon A.; Okkenhaug, Hanneke; Manifava, Maria; Hummel, Eric; Zimmermann, Hans; Ahmed, Qashif; Domart, Marie-Charlotte; Collinson, Lucy; Ktistakis, Nicholas T.

    2016-01-01

    Autophagosome formation requires sequential translocation of autophagy-specific proteins to membranes enriched in PI3P and connected to the ER. Preceding this, the earliest autophagy-specific structure forming de novo is a small punctum of the ULK1 complex. The provenance of this structure and its mode of formation are unknown. We show that the ULK1 structure emerges from regions, where ATG9 vesicles align with the ER and its formation requires ER exit and coatomer function. Super-resolution microscopy reveals that the ULK1 compartment consists of regularly assembled punctate elements that cluster in progressively larger spherical structures and associates uniquely with the early autophagy machinery. Correlative electron microscopy after live imaging shows tubulovesicular membranes present at the locus of this structure. We propose that the nucleation of autophagosomes occurs in regions, where the ULK1 complex coalesces with ER and the ATG9 compartment. PMID:27510922

  18. Autophagy initiation by ULK complex assembly on ER tubulovesicular regions marked by ATG9 vesicles.

    PubMed

    Karanasios, Eleftherios; Walker, Simon A; Okkenhaug, Hanneke; Manifava, Maria; Hummel, Eric; Zimmermann, Hans; Ahmed, Qashif; Domart, Marie-Charlotte; Collinson, Lucy; Ktistakis, Nicholas T

    2016-01-01

    Autophagosome formation requires sequential translocation of autophagy-specific proteins to membranes enriched in PI3P and connected to the ER. Preceding this, the earliest autophagy-specific structure forming de novo is a small punctum of the ULK1 complex. The provenance of this structure and its mode of formation are unknown. We show that the ULK1 structure emerges from regions, where ATG9 vesicles align with the ER and its formation requires ER exit and coatomer function. Super-resolution microscopy reveals that the ULK1 compartment consists of regularly assembled punctate elements that cluster in progressively larger spherical structures and associates uniquely with the early autophagy machinery. Correlative electron microscopy after live imaging shows tubulovesicular membranes present at the locus of this structure. We propose that the nucleation of autophagosomes occurs in regions, where the ULK1 complex coalesces with ER and the ATG9 compartment. PMID:27510922

  19. A critical role of downstream RNA polymerase-promoter interactions in the formation of initiation complex.

    PubMed

    Mekler, Vladimir; Minakhin, Leonid; Severinov, Konstantin

    2011-06-24

    Nucleation of promoter melting in bacteria is coupled with RNA polymerase (RNAP) binding to a conserved -10 promoter element located at the upstream edge of the transcription bubble. The mechanism of downstream propagation of the transcription bubble to include the transcription start site is unclear. Here we introduce new model downstream fork junction promoter fragments that specifically bind RNAP and mimic the downstream segment of promoter complexes. We demonstrate that RNAP binding to downstream fork junctions is coupled with DNA melting around the transcription start point. Consequently, certain downstream fork junction probes can serve as transcription templates. Using a protein beacon fluorescent method, we identify structural determinants of affinity and transcription activity of RNAP-downstream fork junction complexes. Measurements of RNAP interaction with double-stranded promoter fragments reveal that the strength of RNAP interactions with downstream DNA plays a critical role in promoter opening and that the length of the downstream duplex must exceed a critical length for efficient formation of transcription competent open promoter complex.

  20. Template recognition and formation of initiation complexes by the replicase of a segmented double-stranded RNA virus.

    PubMed

    Tortorici, M Alejandra; Broering, Teresa J; Nibert, Max L; Patton, John T

    2003-08-29

    Replication of the segmented double-stranded (ds) RNA genome of viruses belonging to the Reoviridae family requires the RNA-dependent RNA polymerase (RdRP) to use 10-12 different mRNAs as templates for (-) strand synthesis. Rotavirus serves as a model system for study of this process, since its RdRP (VP1) is catalytically active and can specifically recognize template mRNAs in vitro. Here, we have analyzed the requirements for template recognition by the rotavirus RdRP and compared those to the requirements for formation of (-) strand initiation complexes. The results show that multiple functionally independent recognition signals are present at the 3'-end of viral mRNAs, some positioned in nonconserved regions upstream of the highly conserved 3'-terminal consensus sequence. We also found that RdRP recognition signals are distinct from cis-acting signals that promote (-) strand synthesis, because deletions of portions of the 3'-consensus sequence that caused viral mRNAs to be poorly replicated in vitro did not necessarily prevent efficient recognition of the RNA by the RdRP. Although the RdRP alone can specifically bind to viral mRNAs, our analysis reveals that this interaction is not sufficient to generate initiation complexes, even in the presence of nucleotides and divalent cations. Rather, the formation of initiation complexes also requires the core lattice protein (VP2), a virion component that forms a T = 1 icosahedral shell that encapsidates the segmented dsRNA genome. The essential role that the core lattice protein has in (-) strand initiation provides a mechanism for the coordination of genome replication and virion assembly.

  1. Preoperative Portal Vein Embolization Tailored to Prepare the Liver for Complex Resections: Initial Experience

    SciTech Connect

    Baere, T. de Robinson, J. M.; Deschamps, F.; Rao, P.; Teriitheau, C.; Goere, D.; Elias, D.

    2010-10-15

    The purpose of this study was to evaluate the safety and efficacy of preoperative portal vein embolization (PVE) tailored to prepare the liver for complex and extended resections. During the past 5 years, 12 PVEs were performed in noncirrhotic patients with liver metastases from colon cancer (n = 10), choroidal melanoma (n = 1), and leiomyosarcoma (n = 1) to prepare complex anatomical liver resections in patients with small future remnant livers. These liver resections planned to preserve only segment IV in four patients, segments IV, V, and VIII in four patients, segments II, III, VI, and VII in three patients, and segments V and VI in one patient. PVE was performed under general anesthesia with a flow-guided injection of a mixture of cyanoacrylate and Lipiodol using a 5-Fr catheter. All portal branches feeding the liver segments to be resected were successfully embolized with cyanoacrylate except one, which was occluded with coils due to the risk of reflux with cyanoacrylate. After a mean of 32 days, CT volumetry revealed a mean hypertrophy of the unembolized liver of 47 {+-} 25% (range, 21-88%). Liver resections could be performed in 10 patients but were canceled in 2, due to the occurrence of a new hepatic tumor in one and an insufficiently increased volume in the other. Among the 10 patients who underwent the liver resection, 1 died of postoperative sepsis, 3 died 3 to 32 months after surgery, including 1 death unrelated to cancer, and 6 were alive after 6 to 36 months after surgery. In conclusion, in this preliminary report, PVE appears to be feasible and able to induce hypertrophy of the future remnant liver before a complex and extended hepatectomy. Further evaluation is needed in a larger cohort.

  2. Deformylation Reaction by a Nonheme Manganese(III)-Peroxo Complex via Initial Hydrogen-Atom Abstraction.

    PubMed

    Barman, Prasenjit; Upadhyay, Pranav; Faponle, Abayomi S; Kumar, Jitendra; Nag, Sayanta Sekhar; Kumar, Devesh; Sastri, Chivukula V; de Visser, Sam P

    2016-09-01

    Metal-peroxo intermediates are key species in the catalytic cycles of nonheme metalloenzymes, but their chemical properties and reactivity patterns are still poorly understood. The synthesis and characterization of a manganese(III)-peroxo complex with a pentadentate bispidine ligand system and its reactivity with aldehydes was studied. Manganese(III)-peroxo can react through hydrogen-atom abstraction reactions instead of the commonly proposed nucleophilic addition reaction. Evidence of the mechanism comes from experiments which identify a primary kinetic isotope effect of 5.4 for the deformylation reaction. Computational modeling supports the established mechanism and identifies the origin of the reactivity preference of hydrogen-atom abstraction over nucleophilic addition.

  3. RNA polymerase-promoter interactions determining different stability of the Escherichia coli and Thermus aquaticus transcription initiation complexes.

    PubMed

    Mekler, Vladimir; Minakhin, Leonid; Kuznedelov, Konstantin; Mukhamedyarov, Damir; Severinov, Konstantin

    2012-12-01

    Transcription initiation complexes formed by bacterial RNA polymerases (RNAPs) exhibit dramatic species-specific differences in stability, leading to different strategies of transcription regulation. The molecular basis for this diversity is unclear. Promoter complexes formed by RNAP from Thermus aquaticus (Taq) are considerably less stable than Escherichia coli RNAP promoter complexes, particularly at temperatures below 37°C. Here, we used a fluorometric RNAP molecular beacon assay to discern partial RNAP-promoter interactions. We quantitatively compared the strength of E. coli and Taq RNAPs partial interactions with the -10, -35 and UP promoter elements; the TG motif of the extended -10 element; the discriminator and the downstream duplex promoter segments. We found that compared with Taq RNAP, E. coli RNAP has much higher affinity only to the UP element and the downstream promoter duplex. This result indicates that the difference in stability between E. coli and Taq promoter complexes is mainly determined by the differential strength of core RNAP-DNA contacts. We suggest that the relative weakness of Taq RNAP interactions with DNA downstream of the transcription start point is the major reason of low stability and temperature sensitivity of promoter complexes formed by this enzyme.

  4. Sunlight-initiated chemistry of aqueous pyruvic acid: building complexity in the origin of life.

    PubMed

    Griffith, Elizabeth C; Shoemaker, Richard K; Vaida, Veronica

    2013-10-01

    Coupling chemical reactions to an energy source is a necessary step in the origin of life. Here, we utilize UV photons provided by a simulated sun to activate aqueous pyruvic acid and subsequently prompt chemical reactions mimicking some of the functions of modern metabolism. Pyruvic acid is interesting in a prebiotic context due to its prevalence in modern metabolism and its abiotic availability on early Earth. Here, pyruvic acid (CH3COCOOH, a C3 molecule) photochemically reacts to produce more complex molecules containing four or more carbon atoms. Acetoin (CH3CHOHCOCH3), a C4 molecule and a modern bacterial metabolite, is produced in this chemistry as well as lactic acid (CH3CHOHCOOH), a molecule which, when coupled with other abiotic chemical reaction pathways, can provide a regeneration pathway for pyruvic acid. This chemistry is discussed in the context of plausible environments on early Earth such as near the ocean surface and atmospheric aerosol particles. These environments allow for combination and exchange of reactants and products of other reaction environments (such as shallow hydrothermal vents). The result could be a contribution to the steady increase in chemical complexity requisite in the origin of life.

  5. Sunlight-initiated Chemistry of Aqueous Pyruvic Acid: Building Complexity in the Origin of Life

    NASA Astrophysics Data System (ADS)

    Griffith, Elizabeth C.; Shoemaker, Richard K.; Vaida, Veronica

    2013-10-01

    Coupling chemical reactions to an energy source is a necessary step in the origin of life. Here, we utilize UV photons provided by a simulated sun to activate aqueous pyruvic acid and subsequently prompt chemical reactions mimicking some of the functions of modern metabolism. Pyruvic acid is interesting in a prebiotic context due to its prevalence in modern metabolism and its abiotic availability on early Earth. Here, pyruvic acid (CH3COCOOH, a C3 molecule) photochemically reacts to produce more complex molecules containing four or more carbon atoms. Acetoin (CH3CHOHCOCH3), a C4 molecule and a modern bacterial metabolite, is produced in this chemistry as well as lactic acid (CH3CHOHCOOH), a molecule which, when coupled with other abiotic chemical reaction pathways, can provide a regeneration pathway for pyruvic acid. This chemistry is discussed in the context of plausible environments on early Earth such as near the ocean surface and atmospheric aerosol particles. These environments allow for combination and exchange of reactants and products of other reaction environments (such as shallow hydrothermal vents). The result could be a contribution to the steady increase in chemical complexity requisite in the origin of life.

  6. Isolation and initial characterization of the bipartite contractile vacuole complex from Dictyostelium discoideum.

    PubMed

    Nolta, K V; Steck, T L

    1994-01-21

    The contractile vacuole complex serves to excrete excess cytosolic water from protists. In the amoeba, Dictyostelium discoideum, the organelle had a bipartite morphology: a large main vacuole (bladder) marked by lumenal alkaline phosphatase was surrounded by numerous satellite vacuoles (spongiomes). Bladders and spongiomes have now been purified for the first time. The spongiome membranes had a high density of surface projections identified as catalytically-active vacuolar proton pumps (V-H(+)-ATPase). Spongiomes were resolved from the pump-poor bladders by immunogold buoyant density shift with antibodies to the V-H(+)-ATPase; they contained little protein other than this pump. It appears that, following homogenization, most of the spongiome dissociated from bladders and populated the proton pump-rich membrane fraction called acidosomes. Isolated bladders were enriched > 40-fold in alkaline phosphatase and phosphodiesterase, the activities of which were > 85% latent. Bladders depleted of spongiomes bore several distinctive polypeptides; they also had an excess of the basepieces of the proton pump over the catalytic heads. Bladder membranes were also lipid-rich and had a distinctive lipid composition. We conclude that the contractile vacuole system in Dictyostelium is a complex of discrete, separable bladder and spongiome membranes. The V-H(+)-ATPase in the spongiome may catalyze the primary energy transduction step for pumping water out of the cytoplasm.

  7. Localization of eukaryote-specific ribosomal proteins in a 5.5-Å cryo-EM map of the 80S eukaryotic ribosome

    PubMed Central

    Armache, Jean-Paul; Jarasch, Alexander; Anger, Andreas M.; Villa, Elizabeth; Becker, Thomas; Bhushan, Shashi; Jossinet, Fabrice; Habeck, Michael; Dindar, Gülcin; Franckenberg, Sibylle; Marquez, Viter; Mielke, Thorsten; Thomm, Michael; Berninghausen, Otto; Beatrix, Birgitta; Söding, Johannes; Westhof, Eric; Wilson, Daniel N.; Beckmann, Roland

    2010-01-01

    Protein synthesis in all living organisms occurs on ribonucleoprotein particles, called ribosomes. Despite the universality of this process, eukaryotic ribosomes are significantly larger in size than their bacterial counterparts due in part to the presence of 80 r proteins rather than 54 in bacteria. Using cryoelectron microscopy reconstructions of a translating plant (Triticum aestivum) 80S ribosome at 5.5-Å resolution, together with a 6.1-Å map of a translating Saccharomyces cerevisiae 80S ribosome, we have localized and modeled 74/80 (92.5%) of the ribosomal proteins, encompassing 12 archaeal/eukaryote-specific small subunit proteins as well as the complete complement of the ribosomal proteins of the eukaryotic large subunit. Near-complete atomic models of the 80S ribosome provide insights into the structure, function, and evolution of the eukaryotic translational apparatus. PMID:20974910

  8. Cryo-EM structure and rRNA model of a translating eukaryotic 80S ribosome at 5.5-Å resolution

    PubMed Central

    Armache, Jean-Paul; Jarasch, Alexander; Anger, Andreas M.; Villa, Elizabeth; Becker, Thomas; Bhushan, Shashi; Jossinet, Fabrice; Habeck, Michael; Dindar, Gülcin; Franckenberg, Sibylle; Marquez, Viter; Mielke, Thorsten; Thomm, Michael; Berninghausen, Otto; Beatrix, Birgitta; Söding, Johannes; Westhof, Eric; Wilson, Daniel N.; Beckmann, Roland

    2010-01-01

    Protein biosynthesis, the translation of the genetic code into polypeptides, occurs on ribonucleoprotein particles called ribosomes. Although X-ray structures of bacterial ribosomes are available, high-resolution structures of eukaryotic 80S ribosomes are lacking. Using cryoelectron microscopy and single-particle reconstruction, we have determined the structure of a translating plant (Triticum aestivum) 80S ribosome at 5.5-Å resolution. This map, together with a 6.1-Å map of a Saccharomyces cerevisiae 80S ribosome, has enabled us to model ∼98% of the rRNA. Accurate assignment of the rRNA expansion segments (ES) and variable regions has revealed unique ES–ES and r-protein–ES interactions, providing insight into the structure and evolution of the eukaryotic ribosome. PMID:20980660

  9. EPCR-dependent PAR2 activation by the blood coagulation initiation complex regulates LPS-triggered interferon responses in mice.

    PubMed

    Liang, Hai Po H; Kerschen, Edward J; Hernandez, Irene; Basu, Sreemanti; Zogg, Mark; Botros, Fady; Jia, Shuang; Hessner, Martin J; Griffin, John H; Ruf, Wolfram; Weiler, Hartmut

    2015-04-30

    Infection and inflammation are invariably associated with activation of the blood coagulation mechanism, secondary to the inflammation-induced expression of the coagulation initiator tissue factor (TF) on innate immune cells. By investigating the role of cell-surface receptors for coagulation factors in mouse endotoxemia, we found that the protein C receptor (ProcR; EPCR) was required for the normal in vivo and in vitro induction of lipopolysaccharide (LPS)-regulated gene expression. In cultured bone marrow-derived myeloid cells and in monocytic RAW264.7 cells, the LPS-induced expression of functionally active TF, assembly of the ternary TF-VIIa-Xa initiation complex of blood coagulation, and the EPCR-dependent activation of protease-activated receptor 2 (PAR2) by the ternary TF-VIIa-Xa complex were required for the normal LPS induction of messenger RNAs encoding the TLR3/4 signaling adaptor protein Pellino-1 and the transcription factor interferon regulatory factor 8. In response to in vivo challenge with LPS, mice lacking EPCR or PAR2 failed to fully initiate an interferon-regulated gene expression program that included the Irf8 target genes Lif, Iigp1, Gbp2, Gbp3, and Gbp6. The inflammation-induced expression of TF and crosstalk with EPCR, PAR2, and TLR4 therefore appear necessary for the normal evolution of interferon-regulated host responses.

  10. Spatially resolved ultrafast magnetic dynamics initiated at a complex oxide heterointerface.

    PubMed

    Först, M; Caviglia, A D; Scherwitzl, R; Mankowsky, R; Zubko, P; Khanna, V; Bromberger, H; Wilkins, S B; Chuang, Y-D; Lee, W S; Schlotter, W F; Turner, J J; Dakovski, G L; Minitti, M P; Robinson, J; Clark, S R; Jaksch, D; Triscone, J-M; Hill, J P; Dhesi, S S; Cavalleri, A

    2015-09-01

    Static strain in complex oxide heterostructures has been extensively used to engineer electronic and magnetic properties at equilibrium. In the same spirit, deformations of the crystal lattice with light may be used to achieve functional control across heterointerfaces dynamically. Here, by exciting large-amplitude infrared-active vibrations in a LaAlO3 substrate we induce magnetic order melting in a NdNiO3 film across a heterointerface. Femtosecond resonant soft X-ray diffraction is used to determine the spatiotemporal evolution of the magnetic disordering. We observe a magnetic melt front that propagates from the substrate interface into the film, at a speed that suggests electronically driven motion. Light control and ultrafast phase front propagation at heterointerfaces may lead to new opportunities in optomagnetism, for example by driving domain wall motion to transport information across suitably designed devices. PMID:26147844

  11. Spatially resolved ultrafast magnetic dynamics initiated at a complex oxide heterointerface

    SciTech Connect

    Forst, M.; Wilkins, S. B.; Caviglia, A. D.; Scherwitz, R.; Mankowsky, R.; Zubko, P.; Khanna, V.; Bromberger, H.; Chuang, Y. -D.; Lee, W. S.; Schlotter, W. F.; Turner, J. J.; Dakovski, G. L.; Minitti, M. P.; Robinson, J.; Clark, S. R.; Jaksch, D.; Triscone, J. -M.; Hill, J. P.; Dhesi, S. S.; Cavalleri, A.

    2015-07-06

    Static strain in complex oxide heterostructures1,2 has been extensively used to engineer electronic and magnetic properties at equilibrium3. In the same spirit, deformations of the crystal lattice with light may be used to achieve functional control across heterointerfaces dynamically4. Here, by exciting large-amplitude infrared-active vibrations in a LaAlO3 substrate we induce magnetic order melting in a NdNiO3 film across a heterointerface. Femtosecond resonant soft X-ray diffraction is used to determine the spatiotemporal evolution of the magnetic disordering. We observe a magnetic melt front that propagates from the substrate interface into the film, at a speed that suggests electronically driven motion. Lastly, light control and ultrafast phase front propagation at heterointerfaces may lead to new opportunities in optomagnetism, for example by driving domain wall motion to transport information across suitably designed devices.

  12. Spatially resolved ultrafast magnetic dynamics initiated at a complex oxide heterointerface

    DOE PAGES

    Forst, M.; Wilkins, S. B.; Caviglia, A. D.; Scherwitz, R.; Mankowsky, R.; Zubko, P.; Khanna, V.; Bromberger, H.; Chuang, Y. -D.; Lee, W. S.; et al

    2015-07-06

    Static strain in complex oxide heterostructures1,2 has been extensively used to engineer electronic and magnetic properties at equilibrium3. In the same spirit, deformations of the crystal lattice with light may be used to achieve functional control across heterointerfaces dynamically4. Here, by exciting large-amplitude infrared-active vibrations in a LaAlO3 substrate we induce magnetic order melting in a NdNiO3 film across a heterointerface. Femtosecond resonant soft X-ray diffraction is used to determine the spatiotemporal evolution of the magnetic disordering. We observe a magnetic melt front that propagates from the substrate interface into the film, at a speed that suggests electronically driven motion.more » Lastly, light control and ultrafast phase front propagation at heterointerfaces may lead to new opportunities in optomagnetism, for example by driving domain wall motion to transport information across suitably designed devices.« less

  13. Spatially resolved ultrafast magnetic dynamics initiated at a complex oxide heterointerface

    NASA Astrophysics Data System (ADS)

    Caviglia, Andrea

    Static strain in complex oxide heterostructures has been extensively used to engineer electronic and magnetic properties at equilibrium. In the same spirit, deformations of the crystal lattice with light may be used to achieve functional control across heterointerfaces dynamically. Here, by exciting large-amplitude infrared-active vibrations in a LaAlO3 substrate we induce magnetic order melting in a NdNiO3 film across a heterointerface. Femtosecond resonant soft X-ray diffraction is used to determine the spatiotemporal evolution of the magnetic disordering. We observe a magnetic melt front that propagates from the substrate interface into the film, at a speed that suggests electronically driven motion. Light control and ultrafast phase front propagation at heterointerfaces may lead to new opportunities in optomagnetism.

  14. Spatially resolved ultrafast magnetic dynamics initiated at a complex oxide heterointerface

    NASA Astrophysics Data System (ADS)

    Först, M.; Caviglia, A. D.; Scherwitzl, R.; Mankowsky, R.; Zubko, P.; Khanna, V.; Bromberger, H.; Wilkins, S. B.; Chuang, Y.-D.; Lee, W. S.; Schlotter, W. F.; Turner, J. J.; Dakovski, G. L.; Minitti, M. P.; Robinson, J.; Clark, S. R.; Jaksch, D.; Triscone, J.-M.; Hill, J. P.; Dhesi, S. S.; Cavalleri, A.

    2015-09-01

    Static strain in complex oxide heterostructures has been extensively used to engineer electronic and magnetic properties at equilibrium. In the same spirit, deformations of the crystal lattice with light may be used to achieve functional control across heterointerfaces dynamically. Here, by exciting large-amplitude infrared-active vibrations in a LaAlO3 substrate we induce magnetic order melting in a NdNiO3 film across a heterointerface. Femtosecond resonant soft X-ray diffraction is used to determine the spatiotemporal evolution of the magnetic disordering. We observe a magnetic melt front that propagates from the substrate interface into the film, at a speed that suggests electronically driven motion. Light control and ultrafast phase front propagation at heterointerfaces may lead to new opportunities in optomagnetism, for example by driving domain wall motion to transport information across suitably designed devices.

  15. Herpesvirus Late Gene Expression: A Viral-Specific Pre-initiation Complex Is Key

    PubMed Central

    Gruffat, Henri; Marchione, Roberta; Manet, Evelyne

    2016-01-01

    During their productive cycle, herpesviruses exhibit a strictly regulated temporal cascade of gene expression that can be divided into three general stages: immediate-early (IE), early (E), and late (L). This expression program is the result of a complex interplay between viral and cellular factors at both the transcriptional and post-transcriptional levels, as well as structural differences within the promoter architecture for each of the three gene classes. Since the cellular enzyme RNA polymerase II (RNAP-II) is responsible for the transcription of herpesvirus genes, most viral promoters contain DNA motifs that are common with those of cellular genes, although promoter complexity decreases from immediate-early to late genes. Immediate-early and early promoters contain numerous cellular and viral cis-regulating sequences upstream of a TATA box, whereas late promoters differ significantly in that they lack cis-acting sequences upstream of the transcription start site (TSS). Moreover, in the case of the β- and γ-herpesviruses, a TATT box motif is frequently found in the position where the consensus TATA box of eukaryotic promoters usually localizes. The mechanisms of transcriptional regulation of the late viral gene promoters appear to be different between α-herpesviruses and the two other herpesvirus subfamilies (β and γ). In this review, we will compare the mechanisms of late gene transcriptional regulation between HSV-1, for which the viral IE transcription factors – especially ICP4 – play an essential role, and the two other subfamilies of herpesviruses, with a particular emphasis on EBV, which has recently been found to code for its own specific TATT-binding protein. PMID:27375590

  16. The checkpoint protein MAD2 and the mitotic regulator CDC20 form a ternary complex with the anaphase-promoting complex to control anaphase initiation

    PubMed Central

    Fang, Guowei; Yu, Hongtao; Kirschner, Marc W.

    1998-01-01

    The spindle assembly checkpoint mechanism delays anaphase initiation until all chromosomes are aligned at the metaphase plate. Activation of the anaphase-promoting complex (APC) by binding of CDC20 and CDH1 is required for exit from mitosis, and APC has been implicated as a target for the checkpoint intervention. We show that the human checkpoint protein hMAD2 prevents activation of APC by forming a hMAD2–CDC20–APC complex. When injected into Xenopus embryos, hMAD2 arrests cells at mitosis with an inactive APC. The recombinant hMAD2 protein exists in two-folded states: a tetramer and a monomer. Both the tetramer and the monomer bind to CDC20, but only the tetramer inhibits activation of APC and blocks cell cycle progression. Thus, hMAD2 binding is not sufficient for inhibition, and a change in hMAD2 structure may play a role in transducing the checkpoint signal. There are at least three different forms of mitotic APC that can be detected in vivo: an inactive hMAD2–CDC20–APC ternary complex present at metaphase, a CDC20–APC binary complex active in degrading specific substrates at anaphase, and a CDH1–APC complex active later in mitosis and in G1. We conclude that the checkpoint-mediated cell cycle arrest involves hMAD2 receiving an upstream signal to inhibit activation of APC. PMID:9637688

  17. Initial experience using a hyaluronate-iodine complex for wound healing.

    PubMed

    Brenes, Robert A; Ajemian, Michael S; Macaron, Shady H; Panait, Lucian; Dudrick, Stanley J

    2011-03-01

    Hyaluronate-iodine complex is a wound healing adjuvant approved for use in the European Union. The objective of this study is to validate hyaluronate-iodine as a potential wound healing agent. Patients were recruited from the hospital, the outpatient clinic, and the wound healing center. Hyaluronate-iodine soaked gauze was applied to wounds either daily or every other day depending on the amount of wound exudate. Wounds were measured weekly, and progression was documented with digital photography. All wounds were debrided as needed using standard surgical techniques. Fourteen patients (19 wounds) were entered into this prospective study, and 10 patients completed treatment. Fourteen wounds progressed to complete healing with a mean healing time of 18.1 ± 15.1 weeks. Treatment was interrupted in four patients. One patient discontinued treatment due to pain related to application of hyaluronate-iodine, another patient for transportation issues, and the other two patients were lost to follow-up due to relocation out of state and noncompliance with scheduled appointments. Hyaluronate-iodine was helpful in the healing of all types of wounds treated in this pilot study. The antiadhesive and antimicrobial properties of hyaluronate-iodine create a desirable environment conducive to wound healing without apparent detrimental effects.

  18. Complex IV Deficient Surf1−/− Mice Initiate Mitochondrial Stress Responses

    PubMed Central

    Pulliam, Daniel A.; Deepa, Sathyaseelan S.; Liu, Yuhong; Hill, Shauna; Lin, Ai-Ling; Bhattacharya, Arunabh; Shi, Yun; Sloane, Lauren; Viscomi, Carlo; Zeviani, Massimo; Van Remmen, Holly

    2014-01-01

    Summary Mutations in SURF1 cytochrome c oxidase (COX) assembly protein are associated with Leigh’s syndrome, a human mitochondrial disorder that manifests as severe mitochondrial phenotypes and early lethality. In contrast, mice lacking the Surf1 protein (Surf1−/−) are viable and were previously shown to have enhanced longevity and a greater than 50% reduction in COX activity. We measured mitochondrial function in heart and skeletal muscle, and despite the significant reduction in COX activity, we found little or no difference in reactive oxygen species (ROS) generation, membrane potential, ATP production or respiration in isolated mitochondria from Surf1−/− mice compared to wild-type. However, blood lactate levels are elevated and Surf1−/− mice have reduced running endurance, suggesting compromised mitochondrial energy metabolism in vivo. Decreased COX activity in Surf1−/− mice is associated with increased markers of mitochondrial biogenesis (PGC-1α and VDAC) in both heart and skeletal muscle. While mitochondrial biogenesis is a common response in the two tissues, skeletal muscle have an up-regulation of the mitochondrial unfolded protein response (UPRMT) and heart exhibits induction of the Nrf2 antioxidant response pathway. These data are the first to report induction of the UPRMT in a mammalian model of diminished COX activity. In addition our results suggest that impaired mitochondrial function can lead to induction of mitochondrial stress pathways to confer protective effects on cellular homeostasis. Loss of complex IV assembly factor Surf1 in mice results in compensatory responses including mitochondrial biogenesis, the nrf2 pathway and the mitochondrial unfolded protein response. This compensatory response may contribute to the lack of deleterious phenotypes under basal conditions. PMID:24911525

  19. Translation Initiation on mRNAs Bound by Nuclear Cap-binding Protein Complex CBP80/20 Requires Interaction between CBP80/20-dependent Translation Initiation Factor and Eukaryotic Translation Initiation Factor 3g*

    PubMed Central

    Choe, Junho; Oh, Nara; Park, Sungjin; Lee, Ye Kyung; Song, Ok-Kyu; Locker, Nicolas; Chi, Sung-Gil; Kim, Yoon Ki

    2012-01-01

    In the cytoplasm of mammalian cells, either cap-binding proteins 80 and 20 (CBP80/20) or eukaryotic translation initiation factor (eIF) 4E can direct the initiation of translation. Although the recruitment of ribosomes to mRNAs during eIF4E-dependent translation (ET) is well characterized, the molecular mechanism for CBP80/20-dependent translation (CT) remains obscure. Here, we show that CBP80/20-dependent translation initiation factor (CTIF), which has been shown to be preferentially involved in CT but not ET, specifically interacts with eIF3g, a component of the eIF3 complex involved in ribosome recruitment. By interacting with eIF3g, CTIF serves as an adaptor protein to bridge the CBP80/20 and the eIF3 complex, leading to efficient ribosome recruitment during CT. Accordingly, down-regulation of CTIF using a small interfering RNA causes a redistribution of CBP80 from polysome fractions to subpolysome fractions, without significant consequence to eIF4E distribution. In addition, down-regulation of eIF3g inhibits the efficiency of nonsense-mediated mRNA decay, which is tightly coupled to CT but not to ET. Moreover, the artificial tethering of CTIF to an intercistronic region of dicistronic mRNA results in translation of the downstream cistron in an eIF3-dependent manner. These findings support the idea that CT mechanistically differs from ET. PMID:22493286

  20. Initial laboratory studies into the chemical and radiological aging of organic materials in underground storage tanks at the Hanford Complex

    SciTech Connect

    Samuels, W.D.; Camaioni, D.M.; Babad, H.

    1994-03-01

    The underground storage tanks at the Hanford Complex contain wastes generated over many years from plutonium production and recovery processes, and mixed wastes from radiological degradation processes. The chemical changes of the organic materials used in the extraction processes have a direct bearing on several specific safety issues, including potential energy releases from these tanks. The major portion of organic materials that have been added to the tanks consists of tributyl phosphate, dibutyl phosphate, butyl alcohol, hexone (methyl isobutyl ketone), normal paraffin hydrocarbons (NPH), ethylenediaminetetraacetic acid (EDTA), hydroxyethylethylenediaminetriadetic acid (HEDTA), other complexants, and lesser quantities of ion exchange polymers and minor organic compounds. A study of how thermal and radiological processes that may have changed the composition of organic tanks constituents has been initiated after a review of the open literature revealed little information was available about the rates and products of these processes under basic pH conditions. This paper will detail the initial findings as they relate to gas generation, e.g. H{sub 2}, CO, NH{sub 3}, CH{sub 4}, and to changes in the composition of the organic and inorganic components brought about by ``Aging`` processes.

  1. The CCA-end of P-tRNA Contacts Both the Human RPL36AL and the A-site Bound Translation Termination Factor eRF1 at the Peptidyl Transferase Center of the Human 80S Ribosome.

    PubMed

    Hountondji, Codjo; Bulygin, Konstantin; Créchet, Jean-Bernard; Woisard, Anne; Tuffery, Pierre; Nakayama, Jun-Ichi; Frolova, Ludmila; Nierhaus, Knud H; Karpova, Galina; Baouz, Soria

    2014-01-01

    We have demonstrated previously that the E-site specific protein RPL36AL present in human ribosomes can be crosslinked with the CCA-end of a P-tRNA in situ. Here we report the following: (i) We modeled RPL36AL into the structure of the archaeal ortholog RPL44E extracted from the known X-ray structure of the 50S subunit of Haloarcula marismortui. Superimposing the obtained RPL36AL structure with that of P/E tRNA observed in eukaryotic 80S ribosomes suggested that RPL36AL might in addition to its CCA neighbourhood interact with the inner site of the tRNA elbow similar to an interaction pattern known from tRNA•synthetase pairs. (ii) Accordingly, we detected that the isolated recombinant protein RPL36AL can form a tight binary complex with deacylated tRNA, and even tRNA fragments truncated at their CCA end showed a high affinity in the nanomolar range supporting a strong interaction outside the CCA end. (iii) We constructed programmed 80S complexes containing the termination factor eRF1 (stop codon UAA at the A-site) and a 2',3'-dialdehyde tRNA (tRNAox) analog at the P-site. Surprisingly, we observed a crosslinked ternary complex containing the tRNA, eRF1 and RPL36AL crosslinked both to the aldehyde groups of tRNAox at the 2'- and 3'-positions of the ultimate A. We also demonstrated that, upon binding to the ribosomal A-site, eRF1 induces an alternative conformation of the ribosome and/or the tRNA, leading to a novel crosslink of tRNAox to another large-subunit ribosomal protein (namely L37) rather than to RPL36AL, both ribosomal proteins being labeled in a mutually exclusive fashion. Since the human 80S ribosome in complex with P-site bound tRNAox and A-site bound eRF1 corresponds to the post-termination state of the ribosome, the results represent the first biochemical evidence for the positioning of the CCA-arm of the P-tRNA in close proximity to both RPL36AL and eRF1 at the end of the translation process.

  2. Crosslink Mapping at Amino Acid-Base Resolution Reveals the Path of Scrunched DNA in Initial Transcribing Complexes.

    PubMed

    Winkelman, Jared T; Winkelman, Bradford T; Boyce, Julian; Maloney, Michael F; Chen, Albert Y; Ross, Wilma; Gourse, Richard L

    2015-09-01

    RNA polymerase binds tightly to DNA to recognize promoters with high specificity but then releases these contacts during the initial stage of transcription. We report a site-specific crosslinking approach to map the DNA path in bacterial transcription intermediates at amino acid and nucleotide resolution. After validating the approach by showing that the DNA path in open complexes (RPO) is the same as in high-resolution X-ray structures, we define the path following substrate addition in "scrunched" complexes (RPITC). The DNA bulges that form within the transcription bubble in RPITC are positioned differently on the two strands. Our data suggest that the non-template strand bulge is extruded into solvent in complexes containing a 5-mer RNA, whereas the template strand bulge remains within the template strand tunnel, exerting stress on interactions between the β flap, β' clamp, and σ3.2. We propose that this stress contributes to σ3.2 displacement from the RNA exit channel, facilitating promoter escape. PMID:26257284

  3. SBI-0640756 Attenuates the Growth of Clinically Unresponsive Melanomas by Disrupting the eIF4F Translation Initiation Complex.

    PubMed

    Feng, Yongmei; Pinkerton, Anthony B; Hulea, Laura; Zhang, Tongwu; Davies, Michael A; Grotegut, Stefan; Cheli, Yann; Yin, Hongwei; Lau, Eric; Kim, Hyungsoo; De, Surya K; Barile, Elisa; Pellecchia, Maurizio; Bosenberg, Marcus; Li, Jian-Liang; James, Brian; Hassig, Christian A; Brown, Kevin M; Topisirovic, Ivan; Ronai, Ze'ev A

    2015-12-15

    Disrupting the eukaryotic translation initiation factor 4F (eIF4F) complex offers an appealing strategy to potentiate the effectiveness of existing cancer therapies and to overcome resistance to drugs such as BRAF inhibitors (BRAFi). Here, we identified and characterized the small molecule SBI-0640756 (SBI-756), a first-in-class inhibitor that targets eIF4G1 and disrupts the eIF4F complex. SBI-756 impaired the eIF4F complex assembly independently of mTOR and attenuated growth of BRAF-resistant and BRAF-independent melanomas. SBI-756 also suppressed AKT and NF-κB signaling, but small-molecule derivatives were identified that only marginally affected these pathways while still inhibiting eIF4F complex formation and melanoma growth, illustrating the potential for further structural and functional manipulation of SBI-756 as a drug lead. In the gene expression signature patterns elicited by SBI-756, DNA damage, and cell-cycle regulatory factors were prominent, with mutations in melanoma cells affecting these pathways conferring drug resistance. SBI-756 inhibited the growth of NRAS, BRAF, and NF1-mutant melanomas in vitro and delayed the onset and reduced the incidence of Nras/Ink4a melanomas in vivo. Furthermore, combining SBI-756 and a BRAFi attenuated the formation of BRAFi-resistant human tumors. Taken together, our findings show how SBI-756 abrogates the growth of BRAF-independent and BRAFi-resistant melanomas, offering a preclinical rationale to evaluate its antitumor effects in other cancers. PMID:26603897

  4. Sexual Initiation and Complex Recent Polydrug Use Patterns Among Male Sex Workers in Vietnam: A Preliminary Epidemiological Trajectory.

    PubMed

    Yu, Gary; Goldsamt, Lloyd A; Clatts, Michael C; Giang, Lê Minh

    2016-05-01

    Little is known about the age of onset of sexual and drug risk and their association with complex patterns of recent drug use among male sex workers (MSW) in a developing country, such as Vietnam. The aim of this study was to determine whether latent class analysis (LCA) would aid in the detection of current individual and polydrug use combinations to predict how different trajectories of sexual and drug initiation contribute to different patterns of current illicit drug use. Data were collected from a cross-sectional survey administered to young MSWs between 2010 and 2011 in Vietnam (N = 710). LCA clustered participants into recent drug use groups, incorporating both the specific types and overall count of different drugs used. Men reported drug use within a 1 month period from an 11-item drug use list. LCA identified three distinct drug use classes: (1) alcohol use, (2) alcohol and tobacco use, and (3) high polydrug use. The current drug use classes are associated with sex worker status, housing stability, income level, educational attainment, marital status, sexual identity, and sexual preferences. High levels of drug use are strongly associated with being a recent sex worker, not having recent stable housing, higher than median income, more than a high school education, less likely to be currently in school and more likely to have non-homosexual preferences and heterosexual partners. An event history analysis approach (time-event displays) examined the timing of the age of onset of drug and sexual risks. Early ages of drug and sexual initiation are seen for all three classes. High current drug users show earlier onset of these risks, which are significantly delayed for moderate and low current drug users. LCA incorporating an overall count of different drugs detected three distinct current drug use classes. The data illustrates that the complexity of drug factors that must be accounted for, both in advancing our epidemiological understanding of the complexity

  5. Sexual Initiation and Complex Recent Polydrug Use Patterns Among Male Sex Workers in Vietnam: A Preliminary Epidemiological Trajectory.

    PubMed

    Yu, Gary; Goldsamt, Lloyd A; Clatts, Michael C; Giang, Lê Minh

    2016-05-01

    Little is known about the age of onset of sexual and drug risk and their association with complex patterns of recent drug use among male sex workers (MSW) in a developing country, such as Vietnam. The aim of this study was to determine whether latent class analysis (LCA) would aid in the detection of current individual and polydrug use combinations to predict how different trajectories of sexual and drug initiation contribute to different patterns of current illicit drug use. Data were collected from a cross-sectional survey administered to young MSWs between 2010 and 2011 in Vietnam (N = 710). LCA clustered participants into recent drug use groups, incorporating both the specific types and overall count of different drugs used. Men reported drug use within a 1 month period from an 11-item drug use list. LCA identified three distinct drug use classes: (1) alcohol use, (2) alcohol and tobacco use, and (3) high polydrug use. The current drug use classes are associated with sex worker status, housing stability, income level, educational attainment, marital status, sexual identity, and sexual preferences. High levels of drug use are strongly associated with being a recent sex worker, not having recent stable housing, higher than median income, more than a high school education, less likely to be currently in school and more likely to have non-homosexual preferences and heterosexual partners. An event history analysis approach (time-event displays) examined the timing of the age of onset of drug and sexual risks. Early ages of drug and sexual initiation are seen for all three classes. High current drug users show earlier onset of these risks, which are significantly delayed for moderate and low current drug users. LCA incorporating an overall count of different drugs detected three distinct current drug use classes. The data illustrates that the complexity of drug factors that must be accounted for, both in advancing our epidemiological understanding of the complexity

  6. The scanning mechanism of eukaryotic translation initiation.

    PubMed

    Hinnebusch, Alan G

    2014-01-01

    In eukaryotes, the translation initiation codon is generally identified by the scanning mechanism, wherein every triplet in the messenger RNA leader is inspected for complementarity to the anticodon of methionyl initiator transfer RNA (Met-tRNAi). Binding of Met-tRNAi to the small (40S) ribosomal subunit, in a ternary complex (TC) with eIF2-GTP, is stimulated by eukaryotic initiation factor 1 (eIF1), eIF1A, eIF3, and eIF5, and the resulting preinitiation complex (PIC) joins the 5' end of mRNA preactivated by eIF4F and poly(A)-binding protein. RNA helicases remove secondary structures that impede ribosome attachment and subsequent scanning. Hydrolysis of eIF2-bound GTP is stimulated by eIF5 in the scanning PIC, but completion of the reaction is impeded at non-AUG triplets. Although eIF1 and eIF1A promote scanning, eIF1 and possibly the C-terminal tail of eIF1A must be displaced from the P decoding site to permit base-pairing between Met-tRNAi and the AUG codon, as well as to allow subsequent phosphate release from eIF2-GDP. A second GTPase, eIF5B, catalyzes the joining of the 60S subunit to produce an 80S initiation complex that is competent for elongation.

  7. Electrophilic Pt(II) complexes: precision instruments for the initiation of transformations mediated by the cation-olefin reaction.

    PubMed

    Felix, Ryan J; Munro-Leighton, Colleen; Gagné, Michel R

    2014-08-19

    A discontinuity exists between the importance of the cation-olefin reaction as the principal C-C bond forming reaction in terpene biosynthesis and the synthetic tools for mimicking this reaction under catalyst control; that is, having the product identity, stereochemistry, and functionality under the control of a catalyst. The main reason for this deficiency is that the cation-olefin reaction starts with a reactive intermediate (a carbocation) that reacts exothermically with an alkene to reform the reactive intermediate; not to mention that reactive intermediates can also react in nonproductive fashions. In this Account, we detail our efforts to realize catalyst control over this most fundamental of reactions and thereby access steroid like compounds. Our story is organized around our progress in each component of the cascade reaction: the metal controlled electrophilic initiation, the propagation and termination of the cyclization (the cyclase phase), and the turnover deplatinating events. Electrophilic Pt(II) complexes efficiently initiate the cation-olefin reaction by first coordinating to the alkene with selection rules that favor less substituted alkenes over more substituted alkenes. In complex substrates with multiple alkenes, this preference ensures that the least substituted alkene is always the better ligand for the Pt(II) initiator, and consequently the site at which all electrophilic chemistry is initiated. This control element is invariant. With a suitably electron deficient ligand set, the catalyst then activates the coordinated alkene to intramolecular addition by a second alkene, which initiates the cation-olefin reaction cascade and generates an organometallic Pt(II)-alkyl. Deplatination by a range of mechanisms (β-H elimination, single electron oxidation, two-electron oxidation, etc.) provides an additional level of control that ultimately enables A-ring functionalizations that are orthogonal to the cyclase cascade. We particularly focus on

  8. A receptor-like cytoplasmic kinase, BIK1, associates with a flagellin receptor complex to initiate plant innate immunity

    PubMed Central

    Lu, Dongping; Wu, Shujing; Gao, Xiquan; Zhang, Yulan; Shan, Libo; He, Ping

    2010-01-01

    Plants and animals rely on innate immunity to prevent infections by detection of microbe-associated molecular patterns (MAMPs) through pattern-recognition receptors (PRRs). The plant PRR FLS2, a leucine-rich repeat-receptor kinase, recognizes bacterial flagellin and initiates immune signaling by association with another leucine-rich repeat-receptor-like kinase, BAK1. It remains unknown how the FLS2/BAK1 receptor complex activates intracellular signaling cascades. Here we identified the receptor-like cytoplasmic kinase BIK1 that is rapidly phosphorylated upon flagellin perception, depending on both FLS2 and BAK1. BIK1 associates with FLS2 and BAK1 in vivo and in vitro. BIK1 is phosphorylated by BAK1, and BIK1 also directly phosphorylates BAK1 and FLS2 in vitro. The flagellin phosphorylation site Thr237 of BIK1 is required for its phosphorylation on BAK1 and FLS2, suggesting that BIK1 is likely first phosphorylated upon flagellin perception and subsequently transphosphorylates FLS2/BAK1 to propagate flagellin signaling. Importantly, bik1 mutants are compromised in diverse flagellin-mediated responses and immunity to the nonpathogenic bacterial infection. Thus, BIK1 is an essential component in MAMP signal transduction, which links the MAMP receptor complex to downstream intracellular signaling. PMID:20018686

  9. Binding of two PriA-PriB complexes to the primosome assembly site initiates primosome formation.

    PubMed

    Szymanski, Michal R; Jezewska, Maria J; Bujalowski, Wlodzimierz

    2011-08-01

    A direct quantitative analysis of the initial steps in primosome assembly, involving PriA and PriB proteins and the minimal primosome assembly site (PAS) of phage ϕX174, has been performed using fluorescence intensity, fluorescence anisotropy titration, and fluorescence resonance energy transfer techniques. We show that two PriA molecules bind to the PAS at both strong and weak binding sites on the DNA, respectively, without detectable cooperative interactions. Binding of the PriB dimer to the PriA-PAS complex dramatically increases PriA's affinity for the strong site, but only slightly affects its affinity for the weak site. Associations with the strong and weak sites are driven by apparent entropy changes, with binding to the strong site accompanied by a large unfavorable enthalpy change. The PriA-PriB complex, formed independently of the DNA, is able to directly recognize the PAS without the preceding the binding of PriA to the PAS. Thus, the high-affinity state of PriA for PAS is generated through PriA-PriB interactions. The effect of PriB is specific for PriA-PAS association, but not for PriA-double-stranded DNA or PriA-single-stranded DNA interactions. Only complexes containing two PriA molecules can generate a profound change in the PAS structure in the presence of ATP. The obtained results provide a quantitative framework for the elucidation of further steps in primosome assembly and for quantitative analyses of other molecular machines of cellular metabolism.

  10. Events during eucaryotic rRNA transcription initiation and elongation: Conversion from the closed to the open promoter complex requires nucleotide substrates

    SciTech Connect

    Bateman, E.; Paule, M.R.

    1988-05-01

    Chemical footprinting and topological analysis were carried out on the Acanthamoeba castellanii rRNA transcription initiation factor (TIF) and RNA polymerase I complexes with DNA during transcription initiation and elongation. The results show that the binding of TIF and polymerase to the promoter does not alter the supercoiling of the DNA template and the template does not become sensitive to modification by diethylpyro-carbonate, which can identify melted DNA regions. Thus, in contrast to bacterial RNA polymerase, the eucaryotic RNA polymerase I-promoter complex is in a closed configuration preceding addition of nucleotides in vitro. Initiation and 3'-O-methyl CTP-limited translocation by RNA polymerase I results in separation of the polymerase-TIF footprints, leaving the TIF footprint unaltered. In contrast, initiation and translocation result in a significant change in the conformation of the polymerase-DNA complex, culminating in an unwound DNA region of at least 10 base pairs.

  11. Specialization versus conservation: How Pol I and Pol III use the conserved architecture of the pre-initiation complex for specialized transcription

    PubMed Central

    Hoffmann, Niklas A.; Sadian, Yashar; Tafur, Lucas; Kosinski, Jan; Müller, Christoph W.

    2016-01-01

    ABSTRACT Here, we discuss the overall architecture of the RNA polymerase I (Pol I) and III (Pol III) core enzymes and their associated general transcription factors in the context of models of the Pol I and Pol III pre-initiation complexes, thereby highlighting potential functional adaptations of the Pol I and Pol III enzymes to their respective transcription tasks. Several new insights demonstrate the great degree of specialization of each of the eukaryotic RNA polymerases that is only beginning to be revealed as the structural and functional characterization of all eukaryotic RNA polymerases and their pre-initiation complexes progresses. PMID:27327079

  12. Contribution of the 80s loop of HIV-1 protease to the multidrug-resistance mechanism: crystallographic study of MDR769 HIV-1 protease variants

    SciTech Connect

    Yedidi, Ravikiran S.; Proteasa, Georghe; Martinez, Jorge L.; Vickrey, John F.; Martin, Philip D.; Wawrzak, Zdzislaw; Liu, Zhigang; Kovari, Iulia A.; Kovari, Ladislau C.

    2011-09-06

    The flexible flaps and the 80s loops (Pro79-Ile84) of HIV-1 protease are crucial in inhibitor binding. Previously, it was reported that the crystal structure of multidrug-resistant 769 (MDR769) HIV-1 protease shows a wide-open conformation of the flaps owing to conformational rigidity acquired by the accumulation of mutations. In the current study, the effect of mutations on the conformation of the 80s loop of MDR769 HIV-1 protease variants is reported. Alternate conformations of Pro81 (proline switch) with a root-mean-square deviation of 3-4.8 {angstrom} in the C{alpha} atoms of the I10V mutant and a side chain with a 'flipped-out' conformation in the A82F mutant cause distortion in the S1/S1' binding pockets that affects inhibitor binding. The A82S and A82T mutants show local changes in the electrostatics of inhibitor binding owing to the mutation from nonpolar to polar residues. In summary, the crystallographic studies of four variants of MDR769 HIV-1 protease presented in this article provide new insights towards understanding the drug-resistance mechanism as well as a basis for design of future protease inhibitors with enhanced potency.

  13. Inhibition of translation initiation complex formation by GE81112 unravels a 16S rRNA structural switch involved in P-site decoding

    PubMed Central

    Fabbretti, Attilio; Schedlbauer, Andreas; Brandi, Letizia; Kaminishi, Tatsuya; Giuliodori, Anna Maria; Garofalo, Raffaella; Ochoa-Lizarralde, Borja; Takemoto, Chie; Yokoyama, Shigeyuki; Connell, Sean R.; Gualerzi, Claudio O.

    2016-01-01

    In prokaryotic systems, the initiation phase of protein synthesis is governed by the presence of initiation factors that guide the transition of the small ribosomal subunit (30S) from an unlocked preinitiation complex (30S preIC) to a locked initiation complex (30SIC) upon the formation of a correct codon–anticodon interaction in the peptidyl (P) site. Biochemical and structural characterization of GE81112, a translational inhibitor specific for the initiation phase, indicates that the main mechanism of action of this antibiotic is to prevent P-site decoding by stabilizing the anticodon stem loop of the initiator tRNA in a distorted conformation. This distortion stalls initiation in the unlocked 30S preIC state characterized by tighter IF3 binding and a reduced association rate for the 50S subunit. At the structural level we observe that in the presence of GE81112 the h44/h45/h24a interface, which is part of the IF3 binding site and forms ribosomal intersubunit bridges, preferentially adopts a disengaged conformation. Accordingly, the findings reveal that the dynamic equilibrium between the disengaged and engaged conformations of the h44/h45/h24a interface regulates the progression of protein synthesis, acting as a molecular switch that senses and couples the 30S P-site decoding step of translation initiation to the transition from an unlocked preIC to a locked 30SIC state. PMID:27071098

  14. Inhibition of translation initiation complex formation by GE81112 unravels a 16S rRNA structural switch involved in P-site decoding.

    PubMed

    Fabbretti, Attilio; Schedlbauer, Andreas; Brandi, Letizia; Kaminishi, Tatsuya; Giuliodori, Anna Maria; Garofalo, Raffaella; Ochoa-Lizarralde, Borja; Takemoto, Chie; Yokoyama, Shigeyuki; Connell, Sean R; Gualerzi, Claudio O; Fucini, Paola

    2016-04-19

    In prokaryotic systems, the initiation phase of protein synthesis is governed by the presence of initiation factors that guide the transition of the small ribosomal subunit (30S) from an unlocked preinitiation complex (30S preIC) to a locked initiation complex (30SIC) upon the formation of a correct codon-anticodon interaction in the peptidyl (P) site. Biochemical and structural characterization of GE81112, a translational inhibitor specific for the initiation phase, indicates that the main mechanism of action of this antibiotic is to prevent P-site decoding by stabilizing the anticodon stem loop of the initiator tRNA in a distorted conformation. This distortion stalls initiation in the unlocked 30S preIC state characterized by tighter IF3 binding and a reduced association rate for the 50S subunit. At the structural level we observe that in the presence of GE81112 the h44/h45/h24a interface, which is part of the IF3 binding site and forms ribosomal intersubunit bridges, preferentially adopts a disengaged conformation. Accordingly, the findings reveal that the dynamic equilibrium between the disengaged and engaged conformations of the h44/h45/h24a interface regulates the progression of protein synthesis, acting as a molecular switch that senses and couples the 30S P-site decoding step of translation initiation to the transition from an unlocked preIC to a locked 30SIC state. PMID:27071098

  15. Challenges for the 80's

    SciTech Connect

    Lesch, J.R.

    1980-09-01

    Finding and developing the necessary petroleum reserves in the 1980's will require drilling deeper wells in more hostile environments, drilling in increasing water depths, drilling in hostile Arctic areas and in waters where icebergs must be dealt with, and exploring deeper onshore horizons in more difficult topographical areas. These conditions impose severe demands on drilling and production equipment. The deeper wells will challenge drilling and production capabilities because of higher down-hole temperatures, greater capacity requirements on surface equipment, and more critical demands on the associated down-hole equipment. Drilling fluids, tools, and elastomers will need to withstand higher temperatures and greater stresses. Drilling in deeper waters will require the development and refinement of better and more economical drilling and production platforms. Increased drilling from platforms will necessitate improved drilling fluids to minimize torque, drill string, and casing wear in highly deviated holes. Another technological challenge is rig automation to minimize the physical work and injury factors associated with tripping and to reduce personnel requirements on the drilling rig.

  16. Prototypes for the 80s.

    ERIC Educational Resources Information Center

    Instructor, 1980

    1980-01-01

    Presented are brief descriptions of the winning entries in this magazine's contest for existing programs to serve as prototypes for wide-scale use in elementary schools of the 1980s. Top prizes went to computer literacy, energy education, and nutrition projects. Twenty runners-up are also described. Project addresses are included. (SJL)

  17. Does complex absorption behavior leading to conditioning and damage in KDP/DKDP reflect the electronic structure of initiators?

    SciTech Connect

    Feit, M D; DeMange, P P; Negres, R A; Rubenchik, A M; Demos, S G

    2007-10-24

    Currently, most of our thinking about the defects responsible for initiating laser damage considers them as featureless absorbers. However, an increasing body of evidence, particularly involving multi-wavelength irradiation, suggests electronic structure of damage initiators is important in determining both initiation and conditioning behaviors in KDP. The effective absorption coefficient of energy under multi-wavelength irradiation cannot be accounted for by a structureless absorber, but is consistent with an initiator with a multi-level structure. We outline the evidence and assess the ability of such a simple multi-level model to explain these and other experimentally observed behaviors.

  18. "Mommy, You Are the Princess and I Am the Queen": How Preschool Children's Initiation and Language Use during Pretend Play Relate to Complexity

    ERIC Educational Resources Information Center

    Melzer, Dawn K.; Palermo, Cori A.

    2016-01-01

    The present study investigated the relationship between complexity of pretend play, initiation of pretense activities, and mental state utterances used during play. Children 3 to 4 years of age were videotaped while engaging in pretend play with a parent. The videotapes were coded according to mental state utterances (i.e. desire, emotion,…

  19. Polyhomologation based on in situ generated boron-thexyl-silaboracyclic initiating sites: a novel strategy towards the synthesis of polyethylene-based complex architectures.

    PubMed

    Zhang, Zhen; Zhang, Hefeng; Gnanou, Yves; Hadjichristidis, Nikos

    2015-06-21

    A novel strategy, based on the in situ generated boron-thexyl-silaboracyclic initiating sites for the polyhomologation of dimethylsulfoxonium methylide, has been developed for the synthesis of complex polyethylene-based architectures. As examples, the synthesis of a 4-arm polyethylene star, three (polystyrene)(polyethylene)2 3-miktoarm stars and a PE-branched double graft copolymer is given.

  20. Polyhomologation based on in situ generated boron-thexyl-silaboracyclic initiating sites: a novel strategy towards the synthesis of polyethylene-based complex architectures.

    PubMed

    Zhang, Zhen; Zhang, Hefeng; Gnanou, Yves; Hadjichristidis, Nikos

    2015-06-21

    A novel strategy, based on the in situ generated boron-thexyl-silaboracyclic initiating sites for the polyhomologation of dimethylsulfoxonium methylide, has been developed for the synthesis of complex polyethylene-based architectures. As examples, the synthesis of a 4-arm polyethylene star, three (polystyrene)(polyethylene)2 3-miktoarm stars and a PE-branched double graft copolymer is given. PMID:25900042

  1. eIF1A/eIF5B interaction network and its functions in translation initiation complex assembly and remodeling

    PubMed Central

    Nag, Nabanita; Lin, Kai Ying; Edmonds, Katherine A.; Yu, Jielin; Nadkarni, Devika; Marintcheva, Boriana; Marintchev, Assen

    2016-01-01

    Eukaryotic translation initiation is a highly regulated process involving multiple steps, from 43S pre-initiation complex (PIC) assembly, to ribosomal subunit joining. Subunit joining is controlled by the G-protein eukaryotic translation initiation factor 5B (eIF5B). Another protein, eIF1A, is involved in virtually all steps, including subunit joining. The intrinsically disordered eIF1A C-terminal tail (eIF1A-CTT) binds to eIF5B Domain-4 (eIF5B-D4). The ribosomal complex undergoes conformational rearrangements at every step of translation initiation; however, the underlying molecular mechanisms are poorly understood. Here we report three novel interactions involving eIF5B and eIF1A: (i) a second binding interface between eIF5B and eIF1A; (ii) a dynamic intramolecular interaction in eIF1A between the folded domain and eIF1A-CTT; and (iii) an intramolecular interaction between eIF5B-D3 and -D4. The intramolecular interactions within eIF1A and eIF5B interfere with one or both eIF5B/eIF1A contact interfaces, but are disrupted on the ribosome at different stages of translation initiation. Therefore, our results indicate that the interactions between eIF1A and eIF5B are being continuously rearranged during translation initiation. We present a model how the dynamic eIF1A/eIF5B interaction network can promote remodeling of the translation initiation complexes, and the roles in the process played by intrinsically disordered protein segments. PMID:27325746

  2. Are we there yet? Initial targeting of the Male-Specific Lethal and Polycomb group chromatin complexes in Drosophila

    PubMed Central

    McElroy, Kyle A.; Kang, Hyuckjoon; Kuroda, Mitzi I.

    2014-01-01

    Chromatin-binding proteins must navigate the complex nuclear milieu to find their sites of action, and a constellation of protein factors and other properties are likely to influence targeting specificity. Despite considerable progress, the precise rules by which binding specificity is achieved have remained elusive. Here, we consider early targeting events for two groups of chromatin-binding complexes in Drosophila: the Male-Specific Lethal (MSL) and the Polycomb group (PcG) complexes. These two serve as models for understanding targeting, because they have been extensively studied and play vital roles in Drosophila, and their targets have been documented at high resolution. Furthermore, the proteins and biochemical properties of both complexes are largely conserved in multicellular organisms, including humans. While the MSL complex increases gene expression and PcG members repress genes, the two groups share many similarities such as the ability to modify their chromatin environment to create active or repressive domains, respectively. With legacies of in-depth genetic, biochemical and now genomic approaches, the MSL and PcG complexes will continue to provide tractable systems for understanding the recruitment of multiprotein chromatin complexes to their target loci. PMID:24671948

  3. The proteolysis adaptor, NblA, initiates protein pigment degradation by interacting with the cyanobacterial light-harvesting complexes.

    PubMed

    Sendersky, Eleonora; Kozer, Noga; Levi, Mali; Garini, Yuval; Shav-Tal, Yaron; Schwarz, Rakefet

    2014-07-01

    Degradation of the cyanobacterial protein pigment complexes, the phycobilisomes, is a central acclimation response that controls light energy capture. The small protein, NblA, is essential for proteolysis of these large complexes, which may reach a molecular mass of up to 4 MDa. Interactions of NblA in vitro supported the suggestion that NblA is a proteolysis adaptor that labels the pigment proteins for degradation. The mode of operation of NblA in situ, however, remained unresolved. Particularly, it was unclear whether NblA interacts with phycobilisome proteins while part of the large complex, or alternatively interaction with NblA, necessitates dissociation of pigment subunits from the assembly. Fluorescence intensity profiles demonstrated the preferential presence of NblA::GFP (green fluorescent protein) at the photosynthetic membranes, indicating co-localization with phycobilisomes. Furthermore, fluorescence lifetime imaging microscopy provided in situ evidence for interaction of NblA with phycobilisome protein pigments. Additionally, we demonstrated the role of NblA in vivo as a proteolysis tag based on the rapid degradation of the fusion protein NblA::GFP compared with free GFP. Taken together, these observations demonstrated in vivo the role of NblA as a proteolysis adaptor. Additionally, the interaction of NblA with phycobilisomes indicates that the dissociation of protein pigment subunits from the large complex is not a prerequisite for interaction with this adaptor and, furthermore, implicates NblA in the disassembly of the protein pigment complex. Thus, we suggest that, in the case of proteolysis of the phycobilisome, the adaptor serves a dual function: undermining the complex stability and designating the dissociated pigments for degradation.

  4. Ethylene polymerization initiated by tertiary diamine/n-butyllithium complexes: an interpretation from density functional theory study.

    PubMed

    Li, Huayi; Zhang, Liaoyun; Wang, Zhi-Xiang; Hu, Youliang

    2010-02-25

    The mechanism of ethylene insertions into eight tertiary diamine/n-butyllithium complexes has been studied at the BLYP/DNP level. In contrast to the cationic coordination polymerization in which a strong coordination complex between ethylene and the metal center is formed prior to ethylene insertion, there is only a weak van der Waals complex between ethylene and tertiary diamine/n-butyllithium complex. After crossing a four-membered-ring transition state, ethylene inserts into the Li-C bond. The insertion barriers for the eight reactions are in the range of 6.9-11.0 kcal/mol, comparable to those of ethylene cationic coordination polymerizations. However, the polymerization activities of ethylene anionic polymerizations are much lower than those of cationic coordination polymerizations. Comparing the energy profiles of these ethylene anionic polymerizations with those of cationic coordination polymerizations, it can be found that the transition states in the ethylene anionic polymerizations are higher in energy than the reactants, while the transition states in ethylene cationic coordination polymerizations are lower than the reactants. Therefore, ethylene anionic polymerizations need additional energy to climb the energy barriers, while the energies for overcoming the transition states in the cationic coordination polymerizations can be obtained from reactants that are higher in energy than the reactants. We reason the differences in their energy profiles could be one of the reasons for the lower activity of ethylene anionic polymerization than ethylene cationic coordination polymerization despite their comparable insertion barriers.

  5. The 70 S monosome accumulation and in vitro initiation complex formation by Escherichia coli ribosomes at 5 C. Ph.D. Thesis

    NASA Technical Reports Server (NTRS)

    Broeze, R. J.; Pope, D. H.

    1978-01-01

    The inhibition of translation which is observed after shifting Escherichia coli to low temperature was investigated. 70 S ribosomes were isolated from E. coli 8 hours after a shift to 5 C synthesized protein in the absence of added mRNA (i.e., endogenous protein synthesis by 70 S monosomes) at a rate which was three times greater than the rate of endogenous protein synthesis by 70 S ribosomes which were isolated at the time of the shift to 5 C. Calculations based on the rates of endogenous protein synthesis and polyphenylalanine synthesis indicate that 70 S monosomes comprise only 0.1% of the total E. coli 70 S ribosome population after 8 hours at 5 c. Experiments designed to test initiation complex formation on ApUpG or formaldehyde treated MS-2 viral RNA demonstrated that, although the rate of formation of 30 S initiation complexes was not inhibited, the rate of formation of active 70 S initiation complexes, able to react with puromycin, was inhibited to a great extent at 5 C. A model depicting the effects of low temperature on the E. coli translation system is proposed.

  6. Mechanism of Origin DNA Recognition and Assembly of an Initiator-Helicase Complex by SV40 Large Tumor Antigen

    PubMed Central

    Chang, Y. Paul; Xu, Meng; Machado, Ana Carolina Dantas; Yu, Xian Jessica; Rohs, Remo; Chen, Xiaojiang S.

    2013-01-01

    SUMMARY The DNA tumor virus Simian virus 40 (SV40) is a model system for studying eukaryotic replication. SV40 large tumor antigen (LTag) is the initiator/helicase that is essential for genome replication. LTag recognizes and assembles at the viral replication origin. We determined the structure of two multidomain LTag subunits bound to origin DNA. The structure reveals that the origin binding domains (OBDs) and Zn and AAA+ domains are involved in origin recognition and assembly. Notably, the OBDs recognize the origin in an unexpected manner. The histidine residues of the AAA+ domains insert into a narrow minor groove region with enhanced negative electrostatic potential. Computational analysis indicates that this region is intrinsically narrow, demonstrating the role of DNA shape readout in origin recognition. Our results provide important insights into the assembly of the LTag initiator/ helicase at the replication origin and suggest that histidine contacts with the minor groove serve as a mechanism of DNA shape readout. PMID:23545501

  7. Recruitment of Mcm10 to Sites of Replication Initiation Requires Direct Binding to the Minichromosome Maintenance (MCM) Complex*

    PubMed Central

    Douglas, Max E.

    2016-01-01

    Mcm10 is required for the initiation of eukaryotic DNA replication and contributes in some unknown way to the activation of the Cdc45-MCM-GINS (CMG) helicase. How Mcm10 is localized to sites of replication initiation is unclear, as current models indicate that direct binding to minichromosome maintenance (MCM) plays a role, but the details and functional importance of this interaction have not been determined. Here, we show that purified Mcm10 can bind both DNA-bound double hexamers and soluble single hexamers of MCM. The binding of Mcm10 to MCM requires the Mcm10 C terminus. Moreover, the binding site for Mcm10 on MCM includes the Mcm2 and Mcm6 subunits and overlaps that for the loading factor Cdt1. Whether Mcm10 recruitment to replication origins depends on CMG helicase assembly has been unclear. We show that Mcm10 recruitment occurs via two modes: low affinity recruitment in the absence of CMG assembly (“G1-like”) and high affinity recruitment when CMG assembly takes place (“S-phase-like”). Mcm10 that cannot bind directly to MCM is defective in both modes of recruitment and is unable to support DNA replication. These findings indicate that Mcm10 is localized to replication initiation sites by directly binding MCM through the Mcm10 C terminus. PMID:26719337

  8. The human translation initiation multi-factor complex promotes methionyl-tRNAi binding to the 40S ribosomal subunit

    PubMed Central

    Sokabe, Masaaki; Fraser, Christopher S.; Hershey, John W. B.

    2012-01-01

    The delivery of Met-tRNAi to the 40S ribosomal subunit is thought to occur by way of a ternary complex (TC) comprising eIF2, GTP and Met-tRNAi. We have generated from purified human proteins a stable multifactor complex (MFC) comprising eIF1, eIF2, eIF3 and eIF5, similar to the MFC reported in yeast and plants. A human MFC free of the ribosome also is detected in HeLa cells and rabbit reticulocytes, indicating that it exists in vivo. In vitro, the MFC-GTP binds Met-tRNAi and delivers the tRNA to the ribosome at the same rate as the TC. However, MFC-GDP shows a greatly reduced affinity to Met-tRNAi compared to that for eIF2-GDP, suggesting that MFC components may play a role in the release of eIF2-GDP from the ribosome following AUG recognition. Since an MFC–Met-tRNAi complex is detected in cell lysates, it may be responsible for Met-tRNAi–40S ribosome binding in vivo, possibly together with the TC. However, the MFC protein components also bind individually to 40S ribosomes, creating the possibility that Met-tRNAi might bind directly to such 40S-factor complexes. Thus, three distinct pathways for Met-tRNAi delivery to the 40S ribosomal subunit are identified, but which one predominates in vivo remains to be elucidated. PMID:21940399

  9. Human eukaryotic initiation factor 2 (eIF2)-GTP-Met-tRNAi ternary complex and eIF3 stabilize the 43 S preinitiation complex.

    PubMed

    Sokabe, Masaaki; Fraser, Christopher S

    2014-11-14

    The formation of a stable 43 S preinitiation complex (PIC) must occur to enable successful mRNA recruitment. However, the contributions of eIF1, eIF1A, eIF3, and the eIF2-GTP-Met-tRNAi ternary complex (TC) in stabilizing the 43 S PIC are poorly defined. We have reconstituted the human 43 S PIC and used fluorescence anisotropy to systematically measure the affinity of eIF1, eIF1A, and eIF3j in the presence of different combinations of 43 S PIC components. Our data reveal a complicated network of interactions that result in high affinity binding of all 43 S PIC components with the 40 S subunit. Human eIF1 and eIF1A bind cooperatively to the 40 S subunit, revealing an evolutionarily conserved interaction. Negative cooperativity is observed between the binding of eIF3j and the binding of eIF1, eIF1A, and TC with the 40 S subunit. To overcome this, eIF3 dramatically increases the affinity of eIF1 and eIF3j for the 40 S subunit. Recruitment of TC also increases the affinity of eIF1 for the 40 S subunit, but this interaction has an important indirect role in increasing the affinity of eIF1A for the 40 S subunit. Together, our data provide a more complete thermodynamic framework of the human 43 S PIC and reveal important interactions between its components to maintain its stability.

  10. Dioxygen-Initiated Oxidation of Heteroatomic Substrates Incorporated into Ancillary Pyridine Ligands of Carboxylate-Rich Diiron(II) Complexes

    PubMed Central

    Carson, Emily C.; Lippard, Stephen J.

    2008-01-01

    Progress toward the development of functional models of the carboxylate-bridged diiron active site in soluble methane monooxygenase is described in which potential substrates are introduced as substituents on bound pyridine ligands. Thiol, sulfide, sulfoxide, and phosphine moieties incorporated into a pyridine ligand were allowed to react with the preassembled diiron(II) complex [Fe2(μ-O2CArR)2(O2CArR)2(THF)2], where -O2CArR is a sterically hindered 2,6-di(p-tolyl)- or 2,6-di(p-fluorophenyl)benzoate (R = Tol or 4-FPh). The resulting diiron(II) complexes were characterized crystallographically. Triply- and doubly-bridged compounds [Fe2(μ-O2CArTol)3(O2CArTol)(2-MeSpy)] (4) and [Fe2(μ-O2CArTol)2(O2CArTol)2(2-MeS(O)py)2] (5) resulted when 2-methylthiopyridine (2-MeSpy) and 2-pyridylmethylsulfoxide (2-MeS(O)py), respectively, were employed. Another triply-bridged diiron(II) complex, [Fe2(μ-O2CAr4-FPh)3(O2CAr4-FPh)(2-Ph2Ppy)] (3), was obtained containing 2-diphenylphosphinopyridine (2-Ph2Ppy). Use of 2-mercaptopyridine (2-HSpy) afforded the mononuclear complex [Fe(O2CArTol)2(2-HSpy)2] (6a). Together with that of previously reported [Fe2(μ-O2CArTol)3(O2CArTol)(2-PhSpy)] (2) and [Fe2(μ-O2CArTol)3(O2CArTol)(2-Ph2Ppy)] (1), the dioxygen reactivity of these iron(II) complexes was investigated. A dioxygen-dependent intermediate (6b) formed upon exposure of 6a to O2, the electronic structure of which was probed by various spectroscopic methods. Exposure of 4 and 5 to dioxygen revealed both sulfide and sulfoxide oxidation. Oxidation of 3 in CH2Cl2 affords [Fe2(μ-OH)2(μ-O2CAr4-FPh)(O2CAr4-FPh)3(OH2)(2-Ph2P(O)py)] (8), which contains the biologically relevant {Fe2(μ-OH)2(μ-O2CR)}3+ core. This reaction is sensitive to the choice of carboxylate ligands, however, since the p-tolyl analog 1 yielded a hexanuclear species, 7, upon oxidation. PMID:16411722

  11. Eukaryotic translation initiation factor eIF5 promotes the accuracy of start codon recognition by regulating Pi release and conformational transitions of the preinitiation complex.

    PubMed

    Saini, Adesh K; Nanda, Jagpreet S; Martin-Marcos, Pilar; Dong, Jinsheng; Zhang, Fan; Bhardwaj, Monika; Lorsch, Jon R; Hinnebusch, Alan G

    2014-09-01

    eIF5 is the GTPase activating protein (GAP) for the eIF2 · GTP · Met-tRNAi (Met) ternary complex with a critical role in initiation codon selection. Previous work suggested that the eIF5 mutation G31R/SUI5 elevates initiation at UUG codons by increasing GAP function. Subsequent work implicated eIF5 in rearrangement of the preinitiation complex (PIC) from an open, scanning conformation to a closed state at AUG codons, from which Pi is released from eIF2 · GDP · Pi. To identify eIF5 functions crucial for accurate initiation, we investigated the consequences of G31R on GTP hydrolysis and Pi release, and the effects of intragenic G31R suppressors on these reactions, and on the partitioning of PICs between open and closed states. eIF5-G31R altered regulation of Pi release, accelerating it at UUG while decreasing it at AUG codons, consistent with its ability to stabilize the closed complex at UUG. Suppressor G62S mitigates both defects of G31R, accounting for its efficient suppression of UUG initiation in G31R,G62S cells; however suppressor M18V impairs GTP hydrolysis with little effect on PIC conformation. The strong defect in GTP hydrolysis conferred by M18V likely explains its broad suppression of Sui(-) mutations in numerous factors. We conclude that both of eIF5's functions, regulating Pi release and stabilizing the closed PIC conformation, contribute to stringent AUG selection in vivo.

  12. Enantiopure N,N,O-scorpionate zinc amide and chloride complexes as efficient initiators for the heteroselective ROP of cyclic esters.

    PubMed

    Honrado, Manuel; Otero, Antonio; Fernández-Baeza, Juan; Sánchez-Barba, Luis F; Garcés, Andrés; Lara-Sánchez, Agustín; Rodríguez, Ana M

    2014-12-01

    The reaction of bpzbeH, bpzteH (racemic mixture) or (R,R)-bpzmmH (enantiopure) with the amide complexes Zn{N(SiMe3)2}2 or Zn{N(SiHMe2)2}2 in 1 : 1 molar ratio in toluene afforded the mononuclear amide zinc complexes [Zn(NR2)(κ(3)-NNO)] (1-6) [κ(3)-NNO = bpzbe, R = SiMe3 1, SiHMe2 2; bpzte, R = SiMe3 3, SiHMe2 4; (R,R)-bpzmm, SiMe3 5, SiHMe2 6]. These complexes were employed in a protonolysis reaction with HCl-Et2O in 2 : 1 molar ratio to yield the dinuclear amide/chloride zinc complexes [Zn(κ(2)-NN-μ-O)2{ZnCl(NR2)}] (7-12) [κ(2)-NN-μ-O = bpzbe, R = SiMe3 7, SiHMe2 8; bpzte, R = SiMe3 9, SiHMe2 10; (R,R)-bpzmm, SiMe3 11, SiHMe2 12]. The mononuclear complexes 5 and 6 and dinuclear complexes 11 and 12 are the first enantiopure-scorpionate zinc amide complexes to be synthesized. The single-crystal X-ray structure analysis of derivatives 1 and 3 confirmed a monomeric 4-coordinative structure in which the heteroscorpionate ligands are in a κ(3) coordination mode, while 8 had a dimeric molecular disposition with two μ-bridging alkoxides of the heteroscorpionate ligands between the two six- and four-coordinate Zn(II) centers. Interestingly, the chiral amide-containing zinc complexes 1-5 and 11 can act as single-component initiators for the ring-opening polymerization of ε-caprolactone and lactides under mild conditions, affording, in a few hours, medium/low molecular weight polymers with low polydispersity indices. MALDI-ToF mass spectra confirmed that the initiation occurred through a nucleophilic attack by the amide on the lactide monomer, and inspection of the kinetic parameters showed that propagations present the usual pseudo-first order dependence on monomer and catalyst concentrations. In addition, microstructural analysis of poly(rac-lactide)s revealed that the myrtenal substituent on the alkoxide fragment has a significant influence on the degree of stereoselectivity, producing enriched-heterotactic PLAs with a P(s) value of up to 0.79 under mild

  13. The B subunit of the DNA polymerase alpha-primase complex in Saccharomyces cerevisiae executes an essential function at the initial stage of DNA replication.

    PubMed Central

    Foiani, M; Marini, F; Gamba, D; Lucchini, G; Plevani, P

    1994-01-01

    The four-subunit DNA polymerase alpha-primase complex is unique in its ability to synthesize DNA chains de novo, and some in vitro data suggest its involvement in initiation and elongation of chromosomal DNA replication, although direct in vivo evidence for a role in the initiation reaction is still lacking. The function of the B subunit of the complex is unknown, but the Saccharomyces cerevisiae POL12 gene, which encodes this protein, is essential for cell viability. We have produced different pol12 alleles by in vitro mutagenesis of the cloned gene. The in vivo analysis of our 18 pol12 alleles indicates that the conserved carboxy-terminal two-thirds of the protein contains regions that are essential for cell viability, while the more divergent NH2-terminal portion is partially dispensable. The characterization of the temperature-sensitive pol12-T9 mutant allele demonstrates that the B subunit is required for in vivo DNA synthesis and correct progression through S phase. Moreover, reciprocal shift experiments indicate that the POL12 gene product plays an essential role at the early stage of chromosomal DNA replication, before the hydroxyurea-sensitive step. A model for the role of the B subunit in initiation of DNA replication at an origin is presented. Images PMID:8289832

  14. RecQ4 promotes the conversion of the pre-initiation complex at a site-specific origin for DNA unwinding in Xenopus egg extracts.

    PubMed

    Sanuki, Yosuke; Kubota, Yumiko; Kanemaki, Masato T; Takahashi, Tatsuro S; Mimura, Satoru; Takisawa, Haruhiko

    2015-01-01

    Eukaryotic DNA replication is initiated through stepwise assembly of evolutionarily conserved replication proteins onto replication origins, but how the origin DNA is unwound during the assembly process remains elusive. Here, we established a site-specific origin on a plasmid DNA, using in vitro replication systems derived from Xenopus egg extracts. We found that the pre-replicative complex (pre-RC) was preferentially assembled in the vicinity of GAL4 DNA-binding sites of the plasmid, depending on the binding of Cdc6 fused with a GAL4 DNA-binding domain in Cdc6-depleted extracts. Subsequent addition of nucleoplasmic S-phase extracts to the GAL4-dependent pre-RC promoted initiation of DNA replication from the origin, and components of the pre-initiation complex (pre-IC) and the replisome were recruited to the origin concomitant with origin unwinding. In this replication system, RecQ4 is dispensable for both recruitment of Cdc45 onto the origin and stable binding of Cdc45 and GINS to the pre-RC assembled plasmid. However, both origin binding of DNA polymerase α and unwinding of DNA were diminished upon depletion of RecQ4 from the extracts. These results suggest that RecQ4 plays an important role in the conversion of pre-ICs into active replisomes requiring the unwinding of origin DNA in vertebrates.

  15. Clinical Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder (Bipolar CHOICE): A Pragmatic Trial of Complex Treatment for a Complex Disorder

    PubMed Central

    Nierenberg, Andrew A.; Sylvia, Louisa G.; Leon, Andrew C.; Reilly-Harrington, Noreen; Shesler, Leah W.; McElroy, Susan L.; Friedman, Edward S.; Thase, Michael E.; Shelton, Richard C.; Bowden, Charles; Tohen, Mauricio; Singh, Vivek; Deckersbach, Thilo; Ketter, Terence; Kocsis, James; McInnis, Melvin G.; Schoenfeld, David; Bobo, William V.; Calabrese, Joseph R.

    2015-01-01

    Background Classic and second generation antipsychotic mood stabilizers are recommended for treatment of bipolar disorder, yet there are no randomized comparative effectiveness studies that have examined the “real-world” advantages and disadvantages of these medications Purpose We describe the strategic decisions in the design of the Clinical and Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder (Bipolar CHOICE). This paper outlines the key issues and solutions the investigators faced in designing a clinical trial that would maximize generalizability and inform real-world clinical treatment of bipolar disorder. Methods Bipolar CHOICE was a 6-month, multi-site, prospective, randomized clinical trial of outpatients with bipolar disorder. This study compares the effectiveness of quetiapine versus lithium, each with adjunctive personalized treatments. The co-primary outcomes selected are the overall benefits and harms of the study medications (as measured by the Clinical Global Impression-Efficacy Index) and the Necessary Clinical Adjustments (a measure of the number of medication changes). Secondary outcomes are continuous measures of mood, the Framingham General Cardiovascular Risk Score and the Longitudinal Interval Follow up Evaluation Range of Impaired Functioning Tool. Results The final study design consisted of a single-blind, randomized comparative effectiveness trial of quetiapine versus lithium, plus adjunctive personalized treatment (APT), across ten sites. Other important study considerations included limited exclusion criteria to maximize generalizability, flexible dosing of APT medications to mimic real-world treatment, and an intent-to-treat analysis plan. 482 participants were randomized to the study and 364 completed. Limitations The potential limitations of the study include the heterogeneity of APT, selection of study medications, lack of a placebo-control group, and participants’ ability to pay for study medications

  16. Novel One-Tube-One-Step Real-Time Methodology for Rapid Transcriptomic Biomarker Detection: Signal Amplification by Ternary Initiation Complexes.

    PubMed

    Fujita, Hiroto; Kataoka, Yuka; Tobita, Seiji; Kuwahara, Masayasu; Sugimoto, Naoki

    2016-07-19

    We have developed a novel RNA detection method, termed signal amplification by ternary initiation complexes (SATIC), in which an analyte sample is simply mixed with the relevant reagents and allowed to stand for a short time under isothermal conditions (37 °C). The advantage of the technique is that there is no requirement for (i) heat annealing, (ii) thermal cycling during the reaction, (iii) a reverse transcription step, or (iv) enzymatic or mechanical fragmentation of the target RNA. SATIC involves the formation of a ternary initiation complex between the target RNA, a circular DNA template, and a DNA primer, followed by rolling circle amplification (RCA) to generate multiple copies of G-quadruplex (G4) on a long DNA strand like beads on a string. The G4s can be specifically fluorescence-stained with N(3)-hydroxyethyl thioflavin T (ThT-HE), which emits weakly with single- and double-stranded RNA/DNA but strongly with parallel G4s. An improved dual SATIC system, which involves the formation of two different ternary initiation complexes in the RCA process, exhibited a wide quantitative detection range of 1-5000 pM. Furthermore, this enabled visual observation-based RNA detection, which is more rapid and convenient than conventional isothermal methods, such as reverse transcription-loop-mediated isothermal amplification, signal mediated amplification of RNA technology, and RNA-primed rolling circle amplification. Thus, SATIC methodology may serve as an on-site and real-time measurement technique for transcriptomic biomarkers for various diseases.

  17. Novel One-Tube-One-Step Real-Time Methodology for Rapid Transcriptomic Biomarker Detection: Signal Amplification by Ternary Initiation Complexes.

    PubMed

    Fujita, Hiroto; Kataoka, Yuka; Tobita, Seiji; Kuwahara, Masayasu; Sugimoto, Naoki

    2016-07-19

    We have developed a novel RNA detection method, termed signal amplification by ternary initiation complexes (SATIC), in which an analyte sample is simply mixed with the relevant reagents and allowed to stand for a short time under isothermal conditions (37 °C). The advantage of the technique is that there is no requirement for (i) heat annealing, (ii) thermal cycling during the reaction, (iii) a reverse transcription step, or (iv) enzymatic or mechanical fragmentation of the target RNA. SATIC involves the formation of a ternary initiation complex between the target RNA, a circular DNA template, and a DNA primer, followed by rolling circle amplification (RCA) to generate multiple copies of G-quadruplex (G4) on a long DNA strand like beads on a string. The G4s can be specifically fluorescence-stained with N(3)-hydroxyethyl thioflavin T (ThT-HE), which emits weakly with single- and double-stranded RNA/DNA but strongly with parallel G4s. An improved dual SATIC system, which involves the formation of two different ternary initiation complexes in the RCA process, exhibited a wide quantitative detection range of 1-5000 pM. Furthermore, this enabled visual observation-based RNA detection, which is more rapid and convenient than conventional isothermal methods, such as reverse transcription-loop-mediated isothermal amplification, signal mediated amplification of RNA technology, and RNA-primed rolling circle amplification. Thus, SATIC methodology may serve as an on-site and real-time measurement technique for transcriptomic biomarkers for various diseases. PMID:27347743

  18. Highly Selective Molybdenum ONO Pincer Complex Initiates the Living Ring-Opening Metathesis Polymerization of Strained Alkynes with Exceptionally Low Polydispersity Indices

    PubMed Central

    2015-01-01

    The pseudo-octahedral molybdenum benzylidyne complex [TolC≡Mo(ONO)(OR)]·KOR (R = CCH3(CF3)2) 1, featuring a stabilizing ONO pincer ligand, initiates the controlled living polymerization of strained dibenzocyclooctynes at T > 60 °C to give high molecular weight polymers with exceptionally low polydispersities (PDI ∼ 1.02). Kinetic analyses reveal that the growing polymer chain attached to the propagating catalyst efficiently limits the rate of propagation with respect to the rate of initiation (kp/ki ∼ 10–3). The reversible coordination of KOCCH3(CF3)2 to the propagating catalyst prevents undesired chain-termination and -transfer processes. The ring-opening alkyne metathesis polymerization with 1 has all the characteristics of a living polymerization and enables, for the first time, the controlled synthesis of amphiphilic block copolymers via ROAMP. PMID:25535767

  19. Hyperdigraph-Theoretic Analysis of the EGFR Signaling Network: Initial Steps Leading to GTP:Ras Complex Formation

    SciTech Connect

    Oliveira, Joseph S.; Jones-Oliveira, Janet B.; Dixon, David A.; Bailey, Colin G.; Gull, Dean W.

    2004-10-15

    We construct an algebraic-combinatorial model of the SOS compartment of the EGFR biochemical network. A Petri net is used to construct an initial representation of the biochemical decision-making network, which in turn defines a hyperdigraph. We observe that the linear algebraic structure of each hyperdigraph admits a canonical set of algebraic-combinatorial invariants that correspond to the information flow conservation laws governing a molecular kinetic reaction network. The linear algebraic structure of the hyperdigraph and its sets of invariants can be generalized to define a discrete algebraic-geometric structure, which is referred to as an oriented matroid. Oriented matroids define a polyhedral optimization geometry that is used to determine optimal subpaths that span the nullspace of a set of kinetic chemical reaction equations. Sets of constrained submodular path optimizations on the hyperdigraph are objectively obtained as a spanning tree of minimum cycle paths. This complete set of subcircuits is used to identify the network pinch points and invariant flow subpaths. We demonstrate that this family of minimal circuits also characteristically identifies additional significant biochemical reaction pattern features. We use the SOS Compartment A of the EGFR biochemical pathway to develop and demonstrate the application of our algebraic-combinatorial mathematical modeling methodology.

  20. Rb-Sr and Sm-Nd isotopic study of the Glen Mountains layered complex: initiation of rifting within the southern Oklahoma aulacogen

    SciTech Connect

    Lambert, D.D.; Unruh, D.M.; Gilbert, M.C.

    1988-01-01

    Rb-Sr and Sm-Nd isotopic data for rocks and minerals of the Glen Mountains layered complex (GMLC), a midcontinent mafic layered intrusion in the Wichita Mountains of southwestern Oklahoma, constrain the time of initiation of rifting within the southern Oklahoma aulacogen and provide information on the chemistry of the early Paleozoic mantle. Four whole-rock samples define a Rb-Sr isochron corresponding to a maximum crystallization age of 577 +/- 165 Ma and an initial Sr isotopic composition of 0.70359 +/- 2. A three-point Sm-Nd mineral-whole-rock (internal) isochron for an anorthositic gabbro provides a crystallization age of 528 +/- 29 Ma. These data suggest that the GMLC was emplaced into the southern Oklahoma aulacogen during the initial phase of rifting along the southern margin of the North American craton in the early Paleozoic. This Sm-Nd internal isochron age is within analytical uncertainty of U-Pb zircon ages for granites and rhyolites from the Wichita Mountains; therefore, mafic and felsic magmatism may have been contemporaneous within the rift during the early stages of development. Hybrid rocks and composite dikes in the Wichita Mountains provide field evidence for contemporaneous mafic and felsic magmas. Initial Sr and Nd isotopic data suggest that magmas parental to the GMLC were derived from a depleted mantle source. However, Nd isotopic data for the GMLC plot distinctly below data for the depleted mantle source cited by DePaolo and thus suggest that the parental magmas of the GMLC were either contaminated by Proterozoic crust of the southern midcontinent or were derived from a heterogenous mantle source region that had variable initial Nd isotopic compositions.

  1. Yeast eukaryotic initiation factor 4B (eIF4B) enhances complex assembly between eIF4A and eIF4G in vivo.

    PubMed

    Park, Eun-Hee; Walker, Sarah E; Zhou, Fujun; Lee, Joseph M; Rajagopal, Vaishnavi; Lorsch, Jon R; Hinnebusch, Alan G

    2013-01-25

    Translation initiation factor eIF4F (eukaryotic initiation factor 4F), composed of eIF4E, eIF4G, and eIF4A, binds to the m(7)G cap structure of mRNA and stimulates recruitment of the 43S preinitiation complex and subsequent scanning to the initiation codon. The HEAT domain of eIF4G stabilizes the active conformation of eIF4A required for its RNA helicase activity. Mammalian eIF4B also stimulates eIF4A activity, but this function appears to be lacking in yeast, making it unclear how yeast eIF4B (yeIF4B/Tif3) stimulates translation. We identified Ts(-) mutations in the HEAT domains of yeast eIF4G1 and eIF4G2 that are suppressed by overexpressing either yeIF4B or eIF4A, whereas others are suppressed only by eIF4A overexpression. Importantly, suppression of HEAT domain substitutions by yeIF4B overexpression was correlated with the restoration of native eIF4A·eIF4G complexes in vivo, and the rescue of specific mutant eIF4A·eIF4G complexes by yeIF4B was reconstituted in vitro. Association of eIF4A with WT eIF4G in vivo also was enhanced by yeIF4B overexpression and was impaired in cells lacking yeIF4B. Furthermore, we detected native complexes containing eIF4G and yeIF4B but lacking eIF4A. These and other findings lead us to propose that yeIF4B acts in vivo to promote eIF4F assembly by enhancing a conformation of the HEAT domain of yeast eIF4G conducive for stable binding to eIF4A.

  2. Enhanced eIF1 binding to the 40S ribosome impedes conformational rearrangements of the preinitiation complex and elevates initiation accuracy.

    PubMed

    Martin-Marcos, Pilar; Nanda, Jagpreet S; Luna, Rafael E; Zhang, Fan; Saini, Adesh K; Cherkasova, Vera A; Wagner, Gerhard; Lorsch, Jon R; Hinnebusch, Alan G

    2014-02-01

    In the current model of translation initiation by the scanning mechanism, eIF1 promotes an open conformation of the 40S subunit competent for rapidly loading the eIF2·GTP·Met-tRNAi ternary complex (TC) in a metastable conformation (POUT) capable of sampling triplets entering the P site while blocking accommodation of Met-tRNAi in the PIN state and preventing completion of GTP hydrolysis (Pi release) by the TC. All of these functions should be reversed by eIF1 dissociation from the preinitiation complex (PIC) on AUG recognition. We tested this model by selecting eIF1 Ssu(-) mutations that suppress the elevated UUG initiation and reduced rate of TC loading in vivo conferred by an eIF1 (Sui(-)) substitution that eliminates a direct contact of eIF1 with the 40S subunit. Importantly, several Ssu(-) substitutions increase eIF1 affinity for 40S subunits in vitro, and the strongest-binding variant (D61G), predicted to eliminate ionic repulsion with 18S rRNA, both reduces the rate of eIF1 dissociation and destabilizes the PIN state of TC binding in reconstituted PICs harboring Sui(-) variants of eIF5 or eIF2. These findings establish that eIF1 dissociation from the 40S subunit is required for the PIN mode of TC binding and AUG recognition and that increasing eIF1 affinity for the 40S subunit increases initiation accuracy in vivo. Our results further demonstrate that the GTPase-activating protein eIF5 and β-subunit of eIF2 promote accuracy by controlling eIF1 dissociation and the stability of TC binding to the PIC, beyond their roles in regulating GTP hydrolysis by eIF2.

  3. Existential vulnerability can be evoked by severe difficulties with initial breastfeeding: a lifeworld hermeneutical single case study for research on complex breastfeeding phenomena.

    PubMed

    Palmér, Lina; Carlsson, Gunilla; Brunt, David; Nyström, Maria

    2014-11-01

    Many mothers initiate breastfeeding, but some of these experience difficulties. This study has two aims in order to contribute to the development of optimal care for these mothers: firstly to explain and understand the existential meanings of one mother's severe initial breastfeeding difficulties and how these meanings affected her continued breastfeeding and secondly, to reflect on a method for applying lifeworld hermeneutics to research on complex breastfeeding phenomena. This is an approach that acknowledges and focuses on the concrete and lived existence and what it means for humans. Within this approach, humans are understood as whole human beings interacting in the world. The study was conducted using lifeworld interviews with Anna, focusing on meanings of her difficult lived experience of initial breastfeeding. The existential interpretation suggests that such an experience can evoke existential vulnerability, a vulnerability that becomes evident in shameful feelings, such as dislike of breastfeeding, aversion to the milk-producing body and anger towards the child. Anna continued breastfeeding as a way to rid herself of the shame, hoping to be confirmed as a good mother. Such an experience may have negative consequences for the mother-child relationship and it can create fear for future breastfeeding. This study concludes that carers should be aware of individual existential dimensions for breastfeeding mothers. PMID:25522459

  4. Mutations in CDC45, Encoding an Essential Component of the Pre-initiation Complex, Cause Meier-Gorlin Syndrome and Craniosynostosis.

    PubMed

    Fenwick, Aimee L; Kliszczak, Maciej; Cooper, Fay; Murray, Jennie; Sanchez-Pulido, Luis; Twigg, Stephen R F; Goriely, Anne; McGowan, Simon J; Miller, Kerry A; Taylor, Indira B; Logan, Clare; Bozdogan, Sevcan; Danda, Sumita; Dixon, Joanne; Elsayed, Solaf M; Elsobky, Ezzat; Gardham, Alice; Hoffer, Mariette J V; Koopmans, Marije; McDonald-McGinn, Donna M; Santen, Gijs W E; Savarirayan, Ravi; de Silva, Deepthi; Vanakker, Olivier; Wall, Steven A; Wilson, Louise C; Yuregir, Ozge Ozalp; Zackai, Elaine H; Ponting, Chris P; Jackson, Andrew P; Wilkie, Andrew O M; Niedzwiedz, Wojciech; Bicknell, Louise S

    2016-07-01

    DNA replication precisely duplicates the genome to ensure stable inheritance of genetic information. Impaired licensing of origins of replication during the G1 phase of the cell cycle has been implicated in Meier-Gorlin syndrome (MGS), a disorder defined by the triad of short stature, microtia, and a/hypoplastic patellae. Biallelic partial loss-of-function mutations in multiple components of the pre-replication complex (preRC; ORC1, ORC4, ORC6, CDT1, or CDC6) as well as de novo stabilizing mutations in the licensing inhibitor, GMNN, cause MGS. Here we report the identification of mutations in CDC45 in 15 affected individuals from 12 families with MGS and/or craniosynostosis. CDC45 encodes a component of both the pre-initiation (preIC) and CMG helicase complexes, required for initiation of DNA replication origin firing and ongoing DNA synthesis during S-phase itself, respectively, and hence is functionally distinct from previously identified MGS-associated genes. The phenotypes of affected individuals range from syndromic coronal craniosynostosis to severe growth restriction, fulfilling diagnostic criteria for Meier-Gorlin syndrome. All mutations identified were biallelic and included synonymous mutations altering splicing of physiological CDC45 transcripts, as well as amino acid substitutions expected to result in partial loss of function. Functionally, mutations reduce levels of full-length transcripts and protein in subject cells, consistent with partial loss of CDC45 function and a predicted limited rate of DNA replication and cell proliferation. Our findings therefore implicate the preIC as an additional protein complex involved in the etiology of MGS and connect the core cellular machinery of genome replication with growth, chondrogenesis, and cranial suture homeostasis. PMID:27374770

  5. Isolation and functional characterization of a temperature-sensitive mutant of the yeast Saccharomyces cerevisiae in translation initiation factor eIF5: an eIF5-dependent cell-free translation system.

    PubMed

    Maiti, T; Das, S; Maitra, U

    2000-02-22

    Eukaryotic translation initiation factor 5 (eIF5) interacts with the 40S ribosomal initiation complex (40S.eIF3.AUG.Met-tRNA(f).eIF2.GTP) to promote the hydrolysis of bound GTP. In Saccharomyces cerevisiae, eIF5, a protein of 45346Da, is encoded by a single-copy essential gene, TIF5. In this paper, we have isolated a temperature-sensitive S. cerevisiae strain, TMY5-1, by replacing the wild-type chromosomal copy of TIF5 with one mutagenized in vitro. The mutant yeast cells rapidly cease protein synthesis when grown under non-permissive conditions, lose polyribosomes and accumulate free 80S ribosomes. Further characterization of mutant eIF5 showed that the mutant protein, expressed in Escherichia coli, is defective both in its interaction with eIF2 as well as in mediating the hydrolysis of GTP bound to the 40S initiation complex and consequently in the formation of the 80S initiation complex. Additionally, the availability of a yeast strain containing temperature-sensitive mutation in the eIF5 gene allowed us to construct a cell-free translation system that was dependent on exogenously added eIF5 for translation of mRNAs in vitro. PMID:10689193

  6. Interaction of PABPC1 with the translation initiation complex is critical to the NMD resistance of AUG-proximal nonsense mutations.

    PubMed

    Peixeiro, Isabel; Inácio, Ângela; Barbosa, Cristina; Silva, Ana Luísa; Liebhaber, Stephen A; Romão, Luísa

    2012-02-01

    Nonsense-mediated mRNA decay (NMD) is a surveillance pathway that recognizes and rapidly degrades mRNAs containing premature termination codons (PTC). The strength of the NMD response appears to reflect multiple determinants on a target mRNA. We have previously reported that mRNAs containing PTCs in close proximity to the translation initiation codon (AUG-proximal PTCs) can substantially evade NMD. Here, we explore the mechanistic basis for this NMD resistance. We demonstrate that translation termination at an AUG-proximal PTC lacks the ribosome stalling that is evident in an NMD-sensitive PTC. This difference is associated with demonstrated interactions of the cytoplasmic poly(A)-binding protein 1, PABPC1, with the cap-binding complex subunit, eIF4G and the 40S recruitment factor eIF3 as well as the ribosome release factor, eRF3. These interactions, in combination, underlie critical 3'-5' linkage of translation initiation with efficient termination at the AUG-proximal PTC and contribute to an NMD-resistant PTC definition at an early phase of translation elongation.

  7. Vaccinia Virus Protein Synthesis Has a Low Requirement for the Intact Translation Initiation Factor eIF4F, the Cap-Binding Complex, within Infected Cells

    PubMed Central

    Mulder, Jacqueline; Robertson, Morwenna E. M.; Seamons, Rachael A.; Belsham, Graham J.

    1998-01-01

    The role of the cap-binding complex, eIF4F, in the translation of vaccinia virus mRNAs has been analyzed within infected cells. Plasmid DNAs, which express dicistronic mRNAs containing a picornavirus internal ribosome entry site, produced within vaccinia virus-infected cells both β-glucuronidase and a cell surface-targeted single-chain antibody (sFv). Cells expressing sFv were selected from nonexpressing cells, enabling analysis of protein synthesis specifically within the transfected cells. Coexpression of poliovirus 2A or foot-and-mouth disease virus Lb proteases, which cleaved translation initiation factor eIF4G, greatly inhibited cap-dependent protein (β-glucuronidase) synthesis. Under these conditions, internal ribosome entry site-directed expression of sFv continued and cell selection was maintained. Furthermore, vaccinia virus protein synthesis persisted in the selected cells containing cleaved eIF4G. Thus, late vaccinia virus protein synthesis has a low requirement for the intact cap-binding complex eIF4F. This may be attributed to the short unstructured 5′ noncoding regions of the vaccinia virus mRNAs, possibly aided by the presence of poly(A) at both 5′ and 3′ termini. PMID:9765426

  8. Structure of the AvrBs3–DNA complex provides new insights into the initial thymine-recognition mechanism

    SciTech Connect

    Stella, Stefano; Molina, Rafael; Yefimenko, Igor; Prieto, Jesús; Silva, George; Bertonati, Claudia; Juillerat, Alexandre; Duchateau, Phillippe; Montoya, Guillermo

    2013-09-01

    The crystal structure of the AvrBs3–DNA complex is reported. Transcription activator-like effectors contain a DNA-binding domain organized in tandem repeats. The repeats include two adjacent residues known as the repeat variable di-residue, which recognize a single base pair, establishing a direct code between the dipeptides and the target DNA. This feature suggests this scaffold as an excellent candidate to generate new protein–DNA specificities for biotechnological applications. Here, the crystal structure of AvrBs3 (residues 152–895, molecular mass 82 kDa) in complex with its target DNA sequence is presented, revealing a new mode of interaction with the initial thymine of the target sequence, together with an analysis of both the binding specificity and the thermodynamic properties of AvrBs3. This study quantifies the affinity and the specificity between AvrBs3 and its target DNA. Moreover, in vitro and in vivo analyses reveal that AvrBs3 does not show a strict nucleotide-binding preference for the nucleotide at the zero position of the DNA, widening the number of possible sequences that could be targeted by this scaffold.

  9. Architecture of the caveolar coat complex

    PubMed Central

    Nichols, Benjamin James; Sandin, Sara

    2016-01-01

    ABSTRACT Caveolae are specialized membrane domains that are crucial for the correct function of endothelial cells, adipocytes and muscle cells. Caveolins and cavins are both required for caveolae formation, and assemble into a large (80S) caveolar coat complex (80S-CCC). The architecture of the 80S-CCC, however, has not been analyzed. Here, we study the 80S-CCC isolated from mammalian cells using negative stain electron microscopy and 3D cryo-electron tomography. We show that the 80S-CCC is a hollow sphere with a diameter of 50–80 nm, and so has the same size and shape as individual caveolar bulbs. This provides strong evidence that the distinctive membrane shape of caveolae is generated by the shape of the 80S-CCC itself. The particle appears to be made up of two layers, an inner coat composed of polygonal units of caveolins that form a polyhedral cage, and an outer filamentous coat composed of cavins. The data suggest that the peripheral cavin coat is aligned along the edges of the inner polyhedral cage, thereby providing a mechanism for the generation of a morphologically stable caveolar coat. PMID:27369768

  10. PABP1 and eIF4GI associate with influenza virus NS1 protein in viral mRNA translation initiation complexes.

    PubMed

    Burgui, Idoia; Aragón, Tomás; Ortín, Juan; Nieto, Amelia

    2003-12-01

    It has previously been shown that influenza virus NS1 protein enhances the translation of viral but not cellular mRNAs. This enhancement occurs by increasing the rate of translation initiation and requires the 5'UTR sequence, common to all viral mRNAs. In agreement with these findings, we show here that viral mRNAs, but not cellular mRNAs, are associated with NS1 during virus infection. We have previously reported that NS1 interacts with the translation initiation factor eIF4GI, next to its poly(A)-binding protein 1 (PABP1)-interacting domain and that NS1 and eIF4GI are associated in influenza virus-infected cells. Here we show that NS1, although capable of binding poly(A), does not compete with PABP1 for association with eIF4GI and, furthermore, that NS1 and PABP1 interact both in vivo and in vitro in an RNA-independent manner. The interaction maps between residues 365 and 535 in PABP1 and between residues 1 and 81 in NS1. These mapping studies, together with those previously reported for NS1-eIF4GI and PABP1-eIF4GI interactions, imply that the binding of all three proteins would be compatible. Collectively, these and previously published data suggest that NS1 interactions with eIF4GI and PABP1, as well as with viral mRNAs, could promote the specific recruitment of 43S complexes to the viral mRNAs.

  11. Toluene and Ethylbenzene Aliphatic C-H Bond Oxidations Initiated by a Dicopper(II)-μ-1,2-Peroxo Complex

    PubMed Central

    Lucas, Heather R.; Li, Lei; Sarjeant, Amy A. Narducci; Vance, Michael A.; Solomon, Edward I.; Karlin, Kenneth D.

    2009-01-01

    With an anisole containing polypyridylamine potential tetradentate ligand OL, a μ-1,2-peroxo-dicopper(II) complex [{OLCuII}2(O22-)]2+ forms from the reaction of the mononuclear compound [CuI(OL)(MeCN)]B(C6F5)4(OLCuI) with O2 in non-coordinating solvents at -80 °C. Thermal decay of this peroxo complex in the presence of toluene or ethylbenzene leads to rarely seen C-H activation chemistry; benzaldehyde and acetophenone/1-phenylethanol mixtures, respectively, are formed. Experiments with 18O2 confirm that the oxygen source in the products is molecular O2 and deuterium labeling experiments indicate kH/kD = 7.5 ± 1 for the toluene oxygenation. The O2-reaction of [CuI(BzL)(CH3CN)]+ (BzLCuI) leads to a dicopper(III)-bis-μ-oxo species [{BzLCuIII}2(μ-O2-)2]2+ at -80 °C and from such solutions, very similar toluene oxygenation chemistry occurs. Ligand BzL is a tridentate chelate, possessing the same moiety found in OL, but without the anisole O-atom donor. In these contexts, the nature of the oxidant species in or derived from [{OLCuII}2(O22-)]2+ is discussed and likely mechanisms of reaction initiated by toluene H-atom abstraction chemistry are detailed. To confirm the structural formulations of the dioxygen-adducts, UV-vis and resonance Raman spectroscopic studies have been carried out and these results are reported and compared to previously described systems including [{CuII(PYL)}2(O2)]2+ (PYL =TMPA = tris(2-methylpyridyl)amine). Using (L)CuI, CO-binding properties (i.e., νC-O values) along with electrochemical property comparisons, the relative donor abilities of OL, BzL and PYL are assessed. PMID:19216527

  12. The U.S. Department of Education's Rural Education Initiative.

    ERIC Educational Resources Information Center

    Marshall, Robert

    1986-01-01

    Describes 1982 creation of United States Department of Education's Intra-Agency Committee on Rural Education. Summarizes 10 rural policy initiatives proposed in "Rural Education and Rural Family Education Policy for the 80s." Lists major accomplishments/strategies including conferences, annual reports, and information network. Outlines Fiscal Year…

  13. AMP as a low-energy charge signal autonomously initiates assembly of AXIN-AMPK-LKB1 complex for AMPK activation.

    PubMed

    Zhang, Ya-Lin; Guo, Huiling; Zhang, Chen-Song; Lin, Shu-Yong; Yin, Zhenyu; Peng, Yongying; Luo, Hui; Shi, Yuzhe; Lian, Guili; Zhang, Cixiong; Li, Mengqi; Ye, Zhiyun; Ye, Jing; Han, Jiahuai; Li, Peng; Wu, Jia-Wei; Lin, Sheng-Cai

    2013-10-01

    The AMP-activated protein kinase (AMPK) is a master regulator of metabolic homeostasis by sensing cellular energy status. AMPK is mainly activated via phosphorylation by LKB1 when cellular AMP/ADP levels are increased. However, how AMP/ADP brings about AMPK phosphorylation remains unclear. Here, we show that it is AMP, but not ADP, that drives AXIN to directly tether LKB1 to phosphorylate AMPK. The complex formation of AXIN-AMPK-LKB1 is greatly enhanced in glucose-starved or AICAR-treated cells and in cell-free systems supplemented with exogenous AMP. Depletion of AXIN abrogated starvation-induced AMPK-LKB1 colocalization. Importantly, adenovirus-based knockdown of AXIN in the mouse liver impaired AMPK activation and caused exacerbated fatty liver after starvation, underscoring an essential role of AXIN in AMPK activation. These findings demonstrate an initiating role of AMP and demonstrate that AXIN directly transmits AMP binding of AMPK to its activation by LKB1, uncovering the mechanistic route for AMP to elicit AMPK activation by LKB1.

  14. The Atg1 Kinase Complex Is Involved in the Regulation of Protein Recruitment to Initiate Sequestering Vesicle Formation for Nonspecific Autophagy in Saccharomyces cerevisiae

    PubMed Central

    Cheong, Heesun; Nair, Usha; Geng, Jiefei

    2008-01-01

    Autophagy is the major degradative process for recycling cytoplasmic constituents and eliminating unnecessary organelles in eukaryotic cells. Most autophagy-related (Atg) proteins are recruited to the phagophore assembly site (PAS), a proposed site for vesicle formation during either nonspecific or specific types of autophagy. Therefore, appropriate recruitment of Atg proteins to this site is critical for their function in autophagy. Atg11 facilitates PAS recruitment for the cytoplasm-to-vacuole targeting pathway, which is a specific, autophagy-like process that occurs under vegetative conditions. In contrast, it is not known how Atg proteins are recruited to the PAS, nor which components are involved in PAS formation under nonspecific autophagy-inducing, starvation conditions. Here, we studied PAS assembly during nonspecific autophagy, using an atg11Δ mutant background to eliminate the PAS formation that occurs during vegetative growth. We found that protein complexes containing the Atg1 kinase have two roles for PAS formation during nonspecific autophagy. The Atg1 C terminus mediates an interaction with Atg13 and Atg17, facilitating a structural role of Atg1 that is needed to efficiently organize an initial step of PAS assembly, whereas Atg1 kinase activity affects the dynamics of protein movement at the PAS involved in Atg protein cycling. PMID:18077553

  15. The interaction between eukaryotic initiation factor 1A and eIF5 retains eIF1 within scanning preinitiation complexes.

    PubMed

    Luna, Rafael E; Arthanari, Haribabu; Hiraishi, Hiroyuki; Akabayov, Barak; Tang, Leiming; Cox, Christian; Markus, Michelle A; Luna, Lunet E; Ikeda, Yuka; Watanabe, Ryosuke; Bedoya, Edward; Yu, Cathy; Alikhan, Shums; Wagner, Gerhard; Asano, Katsura

    2013-12-31

    Scanning of the mRNA transcript by the preinitiation complex (PIC) requires a panel of eukaryotic initiation factors, which includes eIF1 and eIF1A, the main transducers of stringent AUG selection. eIF1A plays an important role in start codon recognition; however, its molecular contacts with eIF5 are unknown. Using nuclear magnetic resonance, we unveil eIF1A's binding surface on the carboxyl-terminal domain of eIF5 (eIF5-CTD). We validated this interaction by observing that eIF1A does not bind to an eIF5-CTD mutant, altering the revealed eIF1A interaction site. We also found that the interaction between eIF1A and eIF5-CTD is conserved between humans and yeast. Using glutathione S-transferase pull-down assays of purified proteins, we showed that the N-terminal tail (NTT) of eIF1A mediates the interaction with eIF5-CTD and eIF1. Genetic evidence indicates that overexpressing eIF1 or eIF5 suppresses the slow growth phenotype of eIF1A-NTT mutants. These results suggest that the eIF1A-eIF5-CTD interaction during scanning PICs contributes to the maintenance of eIF1 within the open PIC.

  16. A novel initiation mechanism of death in Streptococcus pneumoniae induced by the human milk protein-lipid complex HAMLET and activated during physiological death.

    PubMed

    Clementi, Emily A; Marks, Laura R; Duffey, Michael E; Hakansson, Anders P

    2012-08-01

    To cause colonization or infection, most bacteria grow in biofilms where differentiation and death of subpopulations is critical for optimal survival of the whole population. However, little is known about initiation of bacterial death under physiological conditions. Membrane depolarization has been suggested, but never shown to be involved, due to the difficulty of performing such studies in bacteria and the paucity of information that exists regarding ion transport mechanisms in prokaryotes. In this study, we performed the first extensive investigation of ion transport and membrane depolarization in a bacterial system. We found that HAMLET, a human milk protein-lipid complex, kills Streptococcus pneumoniae (the pneumococcus) in a manner that shares features with activation of physiological death from starvation. Addition of HAMLET to pneumococci dissipated membrane polarity, but depolarization per se was not enough to trigger death. Rather, both HAMLET- and starvation-induced death of pneumococci specifically required a sodium-dependent calcium influx, as shown using calcium and sodium transport inhibitors. This mechanism was verified under low sodium conditions, and in the presence of ionomycin or monensin, which enhanced pneumococcal sensitivity to HAMLET- and starvation-induced death. Pneumococcal death was also inhibited by kinase inhibitors, and indicated the involvement of Ser/Thr kinases in these processes. The importance of this activation mechanism was made evident, as dysregulation and manipulation of physiological death was detrimental to biofilm formation, a hallmark of bacterial colonization. Overall, our findings provide novel information on the role of ion transport during bacterial death, with the potential to uncover future antimicrobial targets.

  17. Ash2L enables P53–dependent apoptosis by favoring stable transcription pre–initiation complex formation on its pro-apoptotic target promoters

    PubMed Central

    Mungamuri, Sathish Kumar; Wang, Shaomeng; Manfredi, James J.; Gu, Wei; Aaronson, Stuart A.

    2014-01-01

    Chromatin conformation plays a major role in all cellular decisions. We showed previously that P53 pro-apoptotic target promoters are enriched with H3K9me3 mark and induction of P53 abrogates this repressive chromatin conformation by down-regulating SUV39H1, the writer of this mark present on these promoters. In the present study, we demonstrate that in response to P53 stabilization, its pro-apoptotic target promoters become enriched with the H3K4me3 epigenetic mark as well as its readers, Wdr5, RbBP5 and Ash2L, which were not observed in response to SUV39H1 down-regulation alone. Overexpression of Ash2L enhanced P53–dependent apoptosis in response to chemotherapy, associated with increased P53 pro–apoptotic gene promoter occupancy and target gene expression. In contrast, pre–silencing of Ash2L abrogated P53's ability to induce the expression of these transcriptional targets, without affecting P53 or RNAP II recruitment. However, Ash2L pre–silencing, under the same conditions, resulted in reduced RNAP II ser5–CTD phosphorylation on these same pro-apoptotic target promoters, which correlated with reduced promoter occupancy of TFIIB as well as TFIIF (RAP74). Based on these findings, we propose that Ash2L acts in concert with P53 promoter occupancy to activate RNAP II by aiding formation of a stable transcription pre–initiation complex required for its activation. PMID:25023704

  18. A Novel Initiation Mechanism of Death in Streptococcus pneumoniae Induced by the Human Milk Protein-Lipid Complex HAMLET and Activated during Physiological Death*

    PubMed Central

    Clementi, Emily A.; Marks, Laura R.; Duffey, Michael E.; Hakansson, Anders P.

    2012-01-01

    To cause colonization or infection, most bacteria grow in biofilms where differentiation and death of subpopulations is critical for optimal survival of the whole population. However, little is known about initiation of bacterial death under physiological conditions. Membrane depolarization has been suggested, but never shown to be involved, due to the difficulty of performing such studies in bacteria and the paucity of information that exists regarding ion transport mechanisms in prokaryotes. In this study, we performed the first extensive investigation of ion transport and membrane depolarization in a bacterial system. We found that HAMLET, a human milk protein-lipid complex, kills Streptococcus pneumoniae (the pneumococcus) in a manner that shares features with activation of physiological death from starvation. Addition of HAMLET to pneumococci dissipated membrane polarity, but depolarization per se was not enough to trigger death. Rather, both HAMLET- and starvation-induced death of pneumococci specifically required a sodium-dependent calcium influx, as shown using calcium and sodium transport inhibitors. This mechanism was verified under low sodium conditions, and in the presence of ionomycin or monensin, which enhanced pneumococcal sensitivity to HAMLET- and starvation-induced death. Pneumococcal death was also inhibited by kinase inhibitors, and indicated the involvement of Ser/Thr kinases in these processes. The importance of this activation mechanism was made evident, as dysregulation and manipulation of physiological death was detrimental to biofilm formation, a hallmark of bacterial colonization. Overall, our findings provide novel information on the role of ion transport during bacterial death, with the potential to uncover future antimicrobial targets. PMID:22700972

  19. Isolation and mapping of the human eukaryotic translation initiation factor 5 to chromosome 14

    SciTech Connect

    Romano, D.M.; Wasco, W.; Murell, J.

    1994-09-01

    Eukaryotic translation initiation factor 5 (eIF-5) is essential for the initiation of protein synthesis. eIF-5 catalyzes the hydrolysis of GTP on the 40S ribosomal initiation complex. Subsequent to GTP hydrolysis and the release of eIF-2-GDP, the 60S ribosomal subunit is joined to the 40S subunit to form an 80S initiation complex which can engage in peptide transfer. In an effort to isolate the major early-onset familial Alzheimer`s disease (FAD) gene on chromosome 14, we have isolated expressed sequences from this autosome in the form of exons `trapped` from chromosome 14-specific cosmids (library provided by L. Deaven, Los Alamos, NM). One cosmid yielded multiple exons displaying strong DNA and amino acid homology (>90%) with the rat eIF-5 gene. These exons were used to isolate full-length cDNAs from a human brain library. The eIF-5 message is approximately 3.6 kB in size and is ubiquitously expressed. The predicted amino acid sequence reveals multiple phosphorylation sites which may be involved in regulation of activity of eIF-5 and regions with homology to the GTPase superfamily, consistent with eIF-5`s role in GTP hydrolysis. Further studies are underway to determine whether the eIF-5 gene resides within the FAD minimal candidate region on chromosome 14q24.3.

  20. Protection of rat liver 80 S ribosomes against ricin A chain inactivation by proteins extracted from rat liver and wheat germ ribosomal subunits with ammonium chloride/magnesium chloride.

    PubMed

    Chang, M S; Houston, L L

    1981-09-28

    Proteins extracted from wheat germ 60 S ribosomal subunits and rat liver 60 S and 40 S ribosomal subunits with 3 M NH4Cl/75 mM MgCl2 were able to prevent the ricin A chain-mediated inactivation of untreated 80 S rat liver ribosomes. The protection of polyphenylalanine synthetic capability of 80 S ribosomes was saturable and reached 100% protection in the presence of about 20 micrograms of extracted protein using a uniform set of assay conditions. No protection was observed using proteins extracted from wheat germ 40 S subunits or the core fraction of rat liver 60 S subunits or protein extracted from Escherichia coli ribosomes or ribosomal subunits. The conclusion that the protective effect of extracted 60 S subunit proteins was specific, was further strengthened by showing that unrelated proteins such as alpha-lactalbumin, bovine serum albumin and lysozyme, and polypeptides such as polylysine and poly(aspartic acid), also showed no protection. If 80 S ribosomes were first treated with ricin A chain and then incubated with proteins extracted from rat liver 60 S subunits, no protection was observed. Proteins extracted with NH4Cl/MgCl2 from 60 S rat liver subunits were applied to carboxymethylcellulose column equilibrated with 6 M urea. Stepwise elution with increasing concentrations of LiCl resulted in seven fractions. One fraction (D) contained most of the protective factor; one fraction (E) contained a lesser amount of the protective factor. Two-dimensional polyacrylamide gel electrophoresis of fraction D showed the presence of ten proteins. These data are consistent with the idea that the enzymatic target of ricin A chain is protein is nature and that fraction D contains one or more proteins that appear to act as a inhibitor against ricin A chain.

  1. Synthesis of the first radiolabeled 188Re N-heterocyclic carbene complex and initial studies on its potential use in radiopharmaceutical applications

    PubMed Central

    Wagner, Thomas; Zeglis, Brian M.; Groveman, Sam; Hille, Claudia; Pöthig, Alexander; Francesconi, Lynn C.; Herrmann, Wolfgang A.; Kühn, Fritz E.; Reiner, Thomas

    2015-01-01

    A novel approach towards the synthesis of radiolabeled organometallic rhenium complexes is presented. We successfully synthesized and analyzed the first 188Re-labeled N-heterocyclic biscarbene complex, trans-dioxobis(1,1′-methylene-bis(3,3′-diisopropylimidazolium-2-ylidene))188rhenium(V) hexafluorophosphate (188Re-4) via transmetalation using an air-stable and moisture-stable silver(I) biscarbene complex. In order to assess the viability of this complex as a potential lead structure for in vivo applications, the stability of the 188Re-NHC complex was tested in physiologically relevant media. Ultimately, our studies illustrate that the complex we synthesized dissociates rapidly and is therefore unsuitable for use in radiopharmaceuticals. However, it is clear that the transmetalation approach we have developed is a rapid, robust, and mild method for the synthesis of new 188Re-labeled carbene complexes. PMID:24889257

  2. Three-dimensional dose-rate distribution of X-ray beams of linac neptun 10p and gamma-rays from Co-60 gammatron 80S for rectangular fields.

    PubMed

    Lobodziec, W; Lambrinow, N; Stala, T; Kośniewski, W

    1981-05-01

    A method of calculation of the three-dimensional dose-rate distribution for X-rays of Linac Neptun 10p and gamma-rays of Gamma-tron 80S is presented. The experimental results show that the profiles function defined as the relative dose-rate across the radiation beam is useful for this purpose, and it is sufficient to determine the profile function only at one depth and for one field size. The results of measurements are presented on the graphs. PMID:7245280

  3. Origin of ophiolite complexes related to intra-oceanic subduction initiation: implications of IODP Expedition 352 (Izu-Bonin fore arc)

    NASA Astrophysics Data System (ADS)

    Robertson, Alastair; Avery, Aaron; Carvallo, Claire; Christeson, Gail; Ferré, Eric; Kurz, Walter; Kutterolf, Steffen; Morgan, Sally; Pearce, Julian; Reagan, Mark; Sager, William; Shervais, John; Whattam, Scott; International Ocean Discovery Program Expedition 352 (Izu-Bonin-Mariana Fore Arc), the Scientific Party of

    2015-04-01

    modern arc formed c. 200 km westwards of the trench. The new drilling evidence proves that both fore arc-type basalt and boninite formed in a fore arc setting soon after subduction initiation (c.52 Ma). Comparisons with ophiolites reveal many similarities, especially the presence of fore arc-type basalts and low calcium boninites. The relative positions of the fore arc basalts, boninites and arc basalts in the Izu Bonin and Mariana forearc (based on previous studies) can be compared with the positions of comparable units in a range of ophiolite complexes in orogenic belts including the Troodos, Oman, Greek (e.g. Vourinos), Albanian (Mirdita), Coast Range (California) and Bay of Islands (Newfoundland) ophiolites. The comparisons support the interpretation that all of the ophiolites formed during intra-oceanic subduction initiation. There are also some specific differences between the individual ophiolites suggesting that ophiolites should be interpreted individually in their regional tectonic settings.

  4. Having a multi facetted approach to complex organic molecules formation: the European COST initiative ‘Our Astochemical History’ and the formaldehyde/methanol formation example

    NASA Astrophysics Data System (ADS)

    Wiesenfeld, Laurent; Ceccarelli, Cecilia; Lefloch, Bertrand

    2015-08-01

    Formaldehyde (H2CO) and methanol (CH3OH) are among the few molecules that have been detected in the solid phase, in the icy mantles that cover interstellar grains. They have been also widely observed in the gas phase of many cold gases, with high somewhat comparable abundances. The synthetic routes leading from ubiquitous CO to these hydrogenated CO molecules have been widely discussed in the literature. Also, deuterated (and per-deuterated) isotopomers of both H2CO and CH3OH have been detected, with very high enrichment in D over the 10-5 cosmic abundance of D with respect to H.In this presentation, we wish to review the first steps of the hysdrogenation processes and describe how they have been recently treated, in the laboratory, the modelling and in theoretical chemical physics.We take and discuss this example as the perfect illustration of the necessity of having a multifaceted approach to the problems we face:1. How to hydrogenated CO towards H2CO: gas phase/solid phase chemistry. (Peters29013; Rimola2014)2. How to detect H2CO / HDCO in the gas phase, in a quantitative manner: LTE vs. non-LTE excitation. (Wiesenfeld2014)3. What is the role of laboratory experiments, how relevant are they, and more important, how challenging are they? (Hama2013)4. Is deuterium enrichment a good tracer for the history ? (Taquet2013)Some of the questions have received an answer in recent years, and we shall briefly describe those, with special emphasis to a joint chemistry-astrophysics approach.We describe the European COST network ‘Our Astrochemical History’ (http://prague2015astrohistory.vscht.cz/) , whichbrings together specialists of many areas of chemistry together with astronomy, in order to address this kind of problem. Succeeding former European initiatives that shaped the field of Astrochemistry, it focussses on the molecular evolution towards higher complexity and aim sat delivering new schemes for physical chemistry at large, like chemistry of transient species

  5. Effect of intravenous administration of D-lysergic acid diethylamide on initiation of protein synthesis in a cell-free system derived from brain.

    PubMed

    Cosgrove, J W; Brown, I R

    1984-05-01

    An initiating cell-free protein synthesis system derived from brain was utilized to demonstrate that the intravenous injection of D-lysergic acid diethylamide (LSD) to rabbits resulted in a lesion at the initiation stage of brain protein synthesis. Three inhibitors of initiation, edeine, poly(I), and aurintricarboxylic acid were used to demonstrate a reduction in initiation-dependent amino acid incorporation in the brain cell-free system. One hour after LSD injection, there was also a measurable decrease in the formation of 40S and 80S initiation complexes in vitro, using either [35S]methionine or [35S]Met-tRNAf. Analysis of the methionine pool size after LSD administration indicated there was no change in methionine levels. Analysis of the formation of initiation complexes in the brain cell-free protein synthesis system prepared 6 h after LSD administration indicated that there was a return to control levels at this time. The effects of LSD on steps in the initiation process are thus reversible.

  6. Job Sharing for the 80's.

    ERIC Educational Resources Information Center

    Notowitz, Carol

    1982-01-01

    Discusses the advantages and disadvantages of job-sharing as an alternative to part-time employment in libraries and describes a job-sharing experiment at the Parson Branch of the Public Library of Columbus and Franklin County. Six references are included. (CHC)

  7. Education in the 80's: Health Education.

    ERIC Educational Resources Information Center

    Russell, Robert D., Ed.; And Others

    Current and future status of issues in health education are discussed in thirteen articles by health educators. The topics of the essays are: (1) holistic health; (2) a holistic approach to stress reduction; (3) stress management education; (4) heart disease education; (5) consumer health education; (6) acceptance of traditional, nonscientific…

  8. Planning for the 80s and Beyond.

    ERIC Educational Resources Information Center

    De Anza Coll., Cupertino, CA.

    Designed as a guide for policy formation, program development, and resource allocation, this report identifies and evaluates future trends and their implications for California's De Anza College (DAC). Section 1 contains introductory information on the purposes, processes, and components of institutional planning at DAC. Section 2 assesses the…

  9. Transpersonalizing Education in the '80s.

    ERIC Educational Resources Information Center

    Vizbara-Kessler, Barbara

    1981-01-01

    The author explains how transpersonal psychology can be applied to education. She lists the emotional and academic benefits to students of relaxation and meditation, guided fantasy, dreams, parapsychology, biofeedback, and centering. (SJL)

  10. Education in the 80's: Speech Communication.

    ERIC Educational Resources Information Center

    Friedrich, Gustav W., Ed.

    Taken together, the 20 chapters in this book provide many suggestions, predictions, alternatives, innovations, and improvements in the speech communication curriculum that can be either undertaken or accomplished during the 1980s. The first five chapters speculate positively about the future of speech communication instruction in five of its most…

  11. Synfuels: nukes of the 80's

    SciTech Connect

    Feeney, A.

    1980-05-01

    Toxic pollutants released to the air and water, as well as the impacts of massive strip mining, will characterize the era of synfuel development as a time of environmental costs which could be life-threatening. Tough water regulations in the western states may result in a few states bearing all the related social and economic impacts. Government incentives for utilities to develop synfuels have already resulted in major development projects in Illinois, Tennessee, Kentucky, and Alabama. Synfuel research by the Electric Power Research Institute has been costly, rivaling nuclear power as a main focus of interest and burying the scattered opposition. How the utilities will overcome the lack of a reliable synfuels market should be of interest to critics as well as the environmental implication. (DCK)

  12. Management Tools for the 80's.

    ERIC Educational Resources Information Center

    Seivert, Dick; Thomas, Frank B.

    Two functions necessary for managing a computer center (organizing and controlling) are discussed with a focus on a nomenclature that was found to be useful for identifying parts of a system and was compatible with the definitions of most operational systems. For example, it is necessary to identify files, reports, and programs used in daily…

  13. Is Anything Clear for the 80's?

    ERIC Educational Resources Information Center

    Puffer, Richard J.

    Community college planners must be futurists, projecting institutional and program enrollments and funding from tuition and state sources. Yet it is increasingly difficult to make accurate projections even for one year, when factors do not operate as they have in the past. Nevertheless, new trends in people, programs, finances, and facilities can…

  14. Human Resource Strategies for the '80s.

    ERIC Educational Resources Information Center

    Odiorne, George S.

    1985-01-01

    Areas of concern for human resource managers include a move toward management by anticipation, relating people to organizations, motivational effects of physical plant design and layout, more use of work teams, better strategies for managing managers and professionals, treating employees as assets, new systems of managing managers and…

  15. Fuel cycles for the 80's

    SciTech Connect

    Not Available

    1980-01-01

    Papers presented at the American Nuclear Society's topical meeting on the fuel cycle are summarized. Present progress and goals in the areas of fuel fabrication, fuel reprocessing, spent fuel storage, accountability, and safeguards are reported. Present governmental policies which affect the fuel cycle are also discussed. Individual presentations are processed for inclusion in the Energy Data Base.(DMC)

  16. A Peek Into the 80's.

    ERIC Educational Resources Information Center

    Sagness, Richard L.

    An overview of issues that will have an impact on educational practice in the 1980s is presented. Issues in the following areas are outlined: (1) control of education by states rather than by the federal government; (2) educational issues that should be the concern of the federal government; (3) education for the handicapped; (4) the future role…

  17. Initial Events in Bacterial Transcription Initiation

    PubMed Central

    Ruff, Emily F.; Record, M. Thomas; Artsimovitch, Irina

    2015-01-01

    Transcription initiation is a highly regulated step of gene expression. Here, we discuss the series of large conformational changes set in motion by initial specific binding of bacterial RNA polymerase (RNAP) to promoter DNA and their relevance for regulation. Bending and wrapping of the upstream duplex facilitates bending of the downstream duplex into the active site cleft, nucleating opening of 13 bp in the cleft. The rate-determining opening step, driven by binding free energy, forms an unstable open complex, probably with the template strand in the active site. At some promoters, this initial open complex is greatly stabilized by rearrangements of the discriminator region between the −10 element and +1 base of the nontemplate strand and of mobile in-cleft and downstream elements of RNAP. The rate of open complex formation is regulated by effects on the rapidly-reversible steps preceding DNA opening, while open complex lifetime is regulated by effects on the stabilization of the initial open complex. Intrinsic DNA opening-closing appears less regulated. This noncovalent mechanism and its regulation exhibit many analogies to mechanisms of enzyme catalysis. PMID:26023916

  18. Large phreatomagmatic vent complex at Coombs Hills, Antarctica: Wet, explosive initiation of flood basalt volcanism in the Ferrar-Karoo LIP

    NASA Astrophysics Data System (ADS)

    McClintock, Murray; White, James D. L.

    2006-01-01

    The Mawson Formation and correlatives in the Transantarctic Mountains and South Africa record an early eruption episode related to the onset of Ferrar-Karoo flood basalt volcanism. Mawson Formation rocks at Coombs Hills comprise mainly (≥80% vol) structureless tuff breccia and coarse lapilli tuff cut by irregular dikes and sills, within a large vent complex (>30 km2). Quenched juvenile fragments of generally low but variable vesicularity, accretionary lapilli and country rock clasts within vent-fill, and pyroclastic density current deposits point to explosive interaction of basalt with groundwater in porous country rock and wet vent filling debris. Metre-scale dikes and pods of coherent basalt in places merge imperceptibly into peperite and then into surrounding breccia. Steeply dipping to sub-vertical depositional contacts juxtapose volcaniclastic rocks of contrasting componentry and grainsize. These sub-vertical tuff breccia zones are inferred to have formed when jets of debris + steam + water passed through unconsolidated vent-filling deposits. These jets of debris may have sometimes breached the surface to form subaerial tephra jets which fed subaerial pyroclastic density currents and fall deposits. Others, however, probably died out within vent fill before reaching the surface, allowing mixing and recycling of clasts which never reached the atmosphere. Most of the ejecta that did escape the debris-filled vents was rapidly recycled as vents broadened via lateral quarrying of country rock and bedded pyroclastic vent-rim deposits, which collapsed along the margins into individual vents. The unstratified, poorly sorted deposits comprising most of the complex are capped by tuff, lapilli tuff and tuff breccia beds inferred to have been deposited on the floor of the vent complex by pyroclastic density currents. Development of the extensive Coombs Hills vent-complex involved interaction of large volumes of magma and water. We infer that recycling of water, as well

  19. Leucine-induced activation of translational initiation is partly regulated by the branched-chain {alpha}-keto acid dehydrogenase complex in C2C12 cells

    SciTech Connect

    Nakai, Naoya . E-mail: nakai@hss.osaka-u.ac.jp; Shimomura, Yoshiharu; Tamura, Tomohiro; Tamura, Noriko; Hamada, Koichiro; Kawano, Fuminori; Ohira, Yoshinobu

    2006-05-19

    Branched-chain amino acid leucine has been shown to activate the translational regulators through the mammalian target of rapamycin. However, the leucine's effects are self-limiting because leucine promotes its own disposal by an oxidative pathway. The irreversible and rate-limiting step in the leucine oxidation pathway is catalyzed by the branched-chain {alpha}-keto acid dehydrogenase (BCKDH) complex. The complex contains E1 ({alpha}2{beta}2), E2, and E3 subunits, and its activity is abolished by phosphorylation of the E1{alpha} subunit by BCKDH kinase. The relationship between the activity of BCKDH complex and leucine-mediated activation of the protein translation was investigated using the technique of RNA interference. The activity of BCKDH complex in C2C12 cell was modulated by transfection of small interfering RNA (siRNA) for BCKDH E2 subunit or BCKDH kinase. Transfection of siRNAs decreased the mRNA expression and protein amount of corresponding gene. Suppression of either E2 subunit or kinase produced opposite effects on the cell proliferation and the activation of translational regulators by leucine. Suppression of BCKDH kinase for 48 h resulted in decreasing cell proliferation. In contrast, E2 suppression led to increased amount of total cellular protein. The phosphorylation of p70 S6 kinase by leucine was increased in E2-siRNA transfected C2C12 cells, whereas the leucine's effect was diminished in kinase-siRNA transfected cells. These results suggest that the activation of the translational regulators by leucine was partly regulated by the activity of BCKDH complex.

  20. Superiority of pictorial versus verbal presentation and initial exposure in the P300-based, complex trial protocol for concealed memory detection.

    PubMed

    Rosenfeld, J Peter; Ward, Anne; Thai, Michelle; Labkovsky, Elena

    2015-06-01

    Two mock guilty groups had either pictorial or verbal initial exposure to crime items (probes) on which they were told they would later be tested. Then each subject was tested in two sessions on two successive days with both verbal and pictorial presentation, one test modality per session/day. The three dependent variables analyzed were three different estimates of the same basic measurement: the difference between P300s evoked by key (probe) and irrelevant stimuli. All three indexes were significantly increased more by both initial pictorial exposure, as well as by pictorial presentation modality, than by verbal exposure and presentation. We saw no main effect of exposure-presentation modality congruence, as congruence interacted with exposure: The largest probe-irrelevant differences were evoked by congruent pictorial exposure and presentation modality, and the smallest by congruent verbal exposure and presentation modality. PMID:25772317

  1. Smart grid initialization reduces the computational complexity of multi-objective image registration based on a dual-dynamic transformation model to account for large anatomical differences

    NASA Astrophysics Data System (ADS)

    Bosman, Peter A. N.; Alderliesten, Tanja

    2016-03-01

    We recently demonstrated the strong potential of using dual-dynamic transformation models when tackling deformable image registration problems involving large anatomical differences. Dual-dynamic transformation models employ two moving grids instead of the common single moving grid for the target image (and single fixed grid for the source image). We previously employed powerful optimization algorithms to make use of the additional flexibility offered by a dual-dynamic transformation model with good results, directly obtaining insight into the trade-off between important registration objectives as a result of taking a multi-objective approach to optimization. However, optimization has so far been initialized using two regular grids, which still leaves a great potential of dual-dynamic transformation models untapped: a-priori grid alignment with image structures/areas that are expected to deform more. This allows (far) less grid points to be used, compared to using a sufficiently refined regular grid, leading to (far) more efficient optimization, or, equivalently, more accurate results using the same number of grid points. We study the implications of exploiting this potential by experimenting with two new smart grid initialization procedures: one manual expert-based and one automated image-feature-based. We consider a CT test case with large differences in bladder volume with and without a multi-resolution scheme and find a substantial benefit of using smart grid initialization.

  2. Trypanosoma brucei translation initiation factor homolog EIF4E6 forms a tripartite cytosolic complex with EIF4G5 and a capping enzyme homolog.

    PubMed

    Freire, Eden R; Malvezzi, Amaranta M; Vashisht, Ajay A; Zuberek, Joanna; Saada, Edwin A; Langousis, Gerasimos; Nascimento, Janaína D F; Moura, Danielle; Darzynkiewicz, Edward; Hill, Kent; de Melo Neto, Osvaldo P; Wohlschlegel, James A; Sturm, Nancy R; Campbell, David A

    2014-07-01

    Trypanosomes lack the transcriptional control characteristic of the majority of eukaryotes that is mediated by gene-specific promoters in a one-gene-one-promoter arrangement. Rather, their genomes are transcribed in large polycistrons with no obvious functional linkage. Posttranscriptional regulation of gene expression must thus play a larger role in these organisms. The eIF4E homolog TbEIF4E6 binds mRNA cap analogs in vitro and is part of a complex in vivo that may fulfill such a role. Knockdown of TbEIF4E6 tagged with protein A-tobacco etch virus protease cleavage site-protein C to approximately 15% of the normal expression level resulted in viable cells that displayed a set of phenotypes linked to detachment of the flagellum from the length of the cell body, if not outright flagellum loss. While these cells appeared and behaved as normal under stationary liquid culture conditions, standard centrifugation resulted in a marked increase in flagellar detachment. Furthermore, the ability of TbEIF4E6-depleted cells to engage in social motility was reduced. The TbEIF4E6 protein forms a cytosolic complex containing a triad of proteins, including the eIF4G homolog TbEIF4G5 and a hypothetical protein of 70.3 kDa, referred to as TbG5-IP. The TbG5-IP analysis revealed two domains with predicted secondary structures conserved in mRNA capping enzymes: nucleoside triphosphate hydrolase and guanylyltransferase. These complex members have the potential for RNA interaction, either via the 5' cap structure for TbEIF4E6 and TbG5-IP or through RNA-binding domains in TbEIF4G5. The associated proteins provide a signpost for future studies to determine how this complex affects capped RNA molecules. PMID:24839125

  3. Trypanosoma brucei translation initiation factor homolog EIF4E6 forms a tripartite cytosolic complex with EIF4G5 and a capping enzyme homolog.

    PubMed

    Freire, Eden R; Malvezzi, Amaranta M; Vashisht, Ajay A; Zuberek, Joanna; Saada, Edwin A; Langousis, Gerasimos; Nascimento, Janaína D F; Moura, Danielle; Darzynkiewicz, Edward; Hill, Kent; de Melo Neto, Osvaldo P; Wohlschlegel, James A; Sturm, Nancy R; Campbell, David A

    2014-07-01

    Trypanosomes lack the transcriptional control characteristic of the majority of eukaryotes that is mediated by gene-specific promoters in a one-gene-one-promoter arrangement. Rather, their genomes are transcribed in large polycistrons with no obvious functional linkage. Posttranscriptional regulation of gene expression must thus play a larger role in these organisms. The eIF4E homolog TbEIF4E6 binds mRNA cap analogs in vitro and is part of a complex in vivo that may fulfill such a role. Knockdown of TbEIF4E6 tagged with protein A-tobacco etch virus protease cleavage site-protein C to approximately 15% of the normal expression level resulted in viable cells that displayed a set of phenotypes linked to detachment of the flagellum from the length of the cell body, if not outright flagellum loss. While these cells appeared and behaved as normal under stationary liquid culture conditions, standard centrifugation resulted in a marked increase in flagellar detachment. Furthermore, the ability of TbEIF4E6-depleted cells to engage in social motility was reduced. The TbEIF4E6 protein forms a cytosolic complex containing a triad of proteins, including the eIF4G homolog TbEIF4G5 and a hypothetical protein of 70.3 kDa, referred to as TbG5-IP. The TbG5-IP analysis revealed two domains with predicted secondary structures conserved in mRNA capping enzymes: nucleoside triphosphate hydrolase and guanylyltransferase. These complex members have the potential for RNA interaction, either via the 5' cap structure for TbEIF4E6 and TbG5-IP or through RNA-binding domains in TbEIF4G5. The associated proteins provide a signpost for future studies to determine how this complex affects capped RNA molecules.

  4. Trypanosoma brucei Translation Initiation Factor Homolog EIF4E6 Forms a Tripartite Cytosolic Complex with EIF4G5 and a Capping Enzyme Homolog

    PubMed Central

    Freire, Eden R.; Malvezzi, Amaranta M.; Vashisht, Ajay A.; Zuberek, Joanna; Saada, Edwin A.; Langousis, Gerasimos; Nascimento, Janaína D. F.; Moura, Danielle; Darzynkiewicz, Edward; Hill, Kent; de Melo Neto, Osvaldo P.; Wohlschlegel, James A.; Sturm, Nancy R.

    2014-01-01

    Trypanosomes lack the transcriptional control characteristic of the majority of eukaryotes that is mediated by gene-specific promoters in a one-gene–one-promoter arrangement. Rather, their genomes are transcribed in large polycistrons with no obvious functional linkage. Posttranscriptional regulation of gene expression must thus play a larger role in these organisms. The eIF4E homolog TbEIF4E6 binds mRNA cap analogs in vitro and is part of a complex in vivo that may fulfill such a role. Knockdown of TbEIF4E6 tagged with protein A-tobacco etch virus protease cleavage site-protein C to approximately 15% of the normal expression level resulted in viable cells that displayed a set of phenotypes linked to detachment of the flagellum from the length of the cell body, if not outright flagellum loss. While these cells appeared and behaved as normal under stationary liquid culture conditions, standard centrifugation resulted in a marked increase in flagellar detachment. Furthermore, the ability of TbEIF4E6-depleted cells to engage in social motility was reduced. The TbEIF4E6 protein forms a cytosolic complex containing a triad of proteins, including the eIF4G homolog TbEIF4G5 and a hypothetical protein of 70.3 kDa, referred to as TbG5-IP. The TbG5-IP analysis revealed two domains with predicted secondary structures conserved in mRNA capping enzymes: nucleoside triphosphate hydrolase and guanylyltransferase. These complex members have the potential for RNA interaction, either via the 5′ cap structure for TbEIF4E6 and TbG5-IP or through RNA-binding domains in TbEIF4G5. The associated proteins provide a signpost for future studies to determine how this complex affects capped RNA molecules. PMID:24839125

  5. Initiation of Electron Transport Chain Activity in the Embryonic Heart Coincides with the Activation of Mitochondrial Complex 1 and the Formation of Supercomplexes

    PubMed Central

    Beutner, Gisela; Eliseev, Roman A.; Porter, George A.

    2014-01-01

    Mitochondria provide energy in form of ATP in eukaryotic cells. However, it is not known when, during embryonic cardiac development, mitochondria become able to fulfill this function. To assess this, we measured mitochondrial oxygen consumption and the activity of the complexes (Cx) 1 and 2 of the electron transport chain (ETC) and used immunoprecipitation to follow the generation of mitochondrial supercomplexes. We show that in the heart of mouse embryos at embryonic day (E) 9.5, mitochondrial ETC activity and oxidative phosphorylation (OXPHOS) are not coupled, even though the complexes are present. We show that Cx-1 of the ETC is able to accept electrons from the Krebs cycle, but enzyme assays that specifically measure electron flow to ubiquinone or Cx-3 show no activity at this early embryonic stage. At E11.5, mitochondria appear functionally more mature; ETC activity and OXPHOS are coupled and respond to ETC inhibitors. In addition, the assembly of highly efficient respiratory supercomplexes containing Cx-1, -3, and -4, ubiquinone, and cytochrome c begins at E11.5, the exact time when Cx-1 becomes functional activated. At E13.5, ETC activity and OXPHOS of embryonic heart mitochondria are indistinguishable from adult mitochondria. In summary, our data suggest that between E9.5 and E11.5 dramatic changes occur in the mitochondria of the embryonic heart, which result in an increase in OXPHOS due to the activation of complex 1 and the formation of supercomplexes. PMID:25427064

  6. Mitotic phosphorylation of eukaryotic initiation factor 4G1 (eIF4G1) at Ser1232 by Cdk1:cyclin B inhibits eIF4A helicase complex binding with RNA.

    PubMed

    Dobrikov, Mikhail I; Shveygert, Mayya; Brown, Michael C; Gromeier, Matthias

    2014-02-01

    During mitosis, global translation is suppressed, while synthesis of proteins with vital mitotic roles must go on. Prior evidence suggests that the mitotic translation shift involves control of initiation. Yet, no signals specifically targeting translation initiation factors during mitosis have been identified. We used phosphoproteomics to investigate the central translation initiation scaffold and "ribosome adaptor," eukaryotic initiation factor 4G1 (eIF4G1) in interphase or nocodazole-arrested mitotic cells. This approach and kinase inhibition assays, in vitro phosphorylation with recombinant kinase, and kinase depletion-reconstitution experiments revealed that Ser1232 in eIF4G1 is phosphorylated by cyclin-dependent kinase 1 (Cdk1):cyclin B during mitosis. Ser1232 is located in an unstructured region of the C-terminal portion of eIF4G1 that coordinates assembly of the eIF4G/-4A/-4B helicase complex and binding of the mitogen-activated protein kinase (MAPK) signal-integrating kinase, Mnk. Intense phosphorylation of Ser1232 in mitosis strongly enhanced the interactions of eIF4A with HEAT domain 2 of eIF4G and decreased association of eIF4G/-4A with RNA. Our findings implicate phosphorylation of eIF4G1(Ser1232) by Cdk1:cyclin B and its inhibitory effects on eIF4A helicase activity in the mitotic translation initiation shift.

  7. Distinctive activation and functionalization of hydrocarbon C-H bonds initiated by Cp*W(NO)(η(3)-allyl)(CH2CMe3) complexes.

    PubMed

    Baillie, Rhett A; Legzdins, Peter

    2014-02-18

    Converting hydrocarbon feedstocks into value-added chemicals continues to offer challenges to contemporary preparative chemists. A particularly important remaining challenge is the selective activation and functionalization of the C(sp(3))-H linkages of alkanes, which are relatively abundant but chemically inert. This Account outlines the discovery and development of C-H bond functionalization mediated by a family of tungsten organometallic nitrosyl complexes. Specifically, it describes how gentle thermolyses of any of four 18-electron Cp*W(NO)(η(3)-allyl)(CH2CMe3) complexes (Cp* = η(5)-C5Me5; η(3)-allyl = η(3)-H2CCHCHMe, η(3)-H2CCHCHSiMe3, η(3)-H2CCHCHPh, or η(3)-H2CCHCMe2) results in the loss of neopentane and the transient formation of a 16-electron intermediate species, Cp*W(NO)(η(2)-allene) and/or Cp*W(NO)(η(2)-diene). We have never detected any of these species spectroscopically, but we infer their existence based on trapping experiments with trimethylphosphine (PMe3) and labeling experiments using deuterated hydrocarbon substrates. This Account first summarizes the syntheses and properties of the four chiral Cp*W(NO)(η(3)-allyl)(CH2CMe3) complexes. It then outlines the various types of C-H activations we have effected with each of the 16-electron (η(2)-allene) or (η(2)-diene) intermediate nitrosyl complexes, and presents the results of mechanistic investigations of some of these processes. It next describes the characteristic chemical properties of the Cp*W(NO)(η(3)-allyl)(η(1)-hydrocarbyl) compounds formed by the single activations of C(sp(3))-H bonds, with particular emphasis on those reactions that result in the selective functionalization of the original hydrocarbon substrate. We are continuing development of methods to release the acyl ligands from the metal centers while keeping the Cp*W(NO)(η(3)-allyl) fragments intact, with the ultimate aim of achieving these distinctive conversions of alkanes into functionalized organics in a

  8. WAVE2-Abi2 complex controls growth cone activity and regulates the multipolar-bipolar transition as well as the initiation of glia-guided migration.

    PubMed

    Xie, Min-Jue; Yagi, Hideshi; Kuroda, Kazuki; Wang, Chen-Chi; Komada, Munekazu; Zhao, Hong; Sakakibara, Akira; Miyata, Takaki; Nagata, Koh-Ichi; Oka, Yuichiro; Iguchi, Tokuichi; Sato, Makoto

    2013-06-01

    Glia-guided migration (glia-guided locomotion) during radial migration is a characteristic yet unique mode of migration. In this process, the directionality of migration is predetermined by glial processes and not by growth cones. Prior to the initiation of glia-guided migration, migrating neurons transform from multipolar to bipolar, but the molecular mechanisms underlying this multipolar-bipolar transition and the commencement of glia-guided migration are not fully understood. Here, we demonstrate that the multipolar-bipolar transition is not solely a cell autonomous event; instead, the interaction of growth cones with glial processes plays an essential role. Time-lapse imaging with lattice assays reveals the importance of vigorously active growth cones in searching for appropriate glial scaffolds, completing the transition, and initiating glia-guided migration. These growth cone activities are regulated by Abl kinase and Cdk5 via WAVE2-Abi2 through the phosphorylation of tyrosine 150 and serine 137 of WAVE2. Neurons that do not display such growth cone activities are mispositioned in a more superficial location in the neocortex, suggesting the significance of growth cones for the final location of the neurons. This process occurs in spite of the "inside-out" principle in which later-born neurons are situated more superficially. PMID:22617848

  9. The shoot regeneration capacity of excised Arabidopsis cotyledons is established during the initial hours after injury and is modulated by a complex genetic network of light signalling.

    PubMed

    Nameth, Blair; Dinka, Steven J; Chatfield, Steven P; Morris, Adam; English, Jenny; Lewis, Dorrett; Oro, Rosalinda; Raizada, Manish N

    2013-01-01

    Excised plant tissues (explants) can regenerate new shoot apical meristems in vitro, but regeneration rates can be inexplicably variable. Light affects rates of shoot regeneration, but the underlying mechanisms are poorly understood. Here, excised Arabidopsis cotyledons were dark-light shifted to define the timing of explant light sensitivity. Mutants and pharmacological agents were employed to uncover underlying physiological and genetic mechanisms. Unexpectedly, explants were most light sensitive during the initial hours post-excision with respect to shoot regeneration. Only ∼100 µmol m(-2 ) s(-1) of fluorescent light was sufficient to induce reactive oxygen species (ROS) accumulation in new explants. By 48 h post-excision, induction of ROS, or quenching of ROS by xanthophylls, increased or decreased shoot regeneration, respectively. Phytochrome A-mediated signalling suppressed light inhibition of regeneration. Early exposure to blue/UV-A wavelengths inhibited regeneration, involving photoreceptor CRY1. Downstream transcription factor HY5 mediated explant photoprotection, perhaps by promoting anthocyanin accumulation, a pigment also induced by cytokinin. Surprisingly, early light inhibition of shoot regeneration was dependent on polar auxin transport. Early exposure to ethylene stimulated dark-treated explants to regenerate, but inhibited light-treated explants. We propose that variability in long-term shoot regeneration may arise within the initial hours post-excision, from inadvertent, variable exposure of explants to light, modulated by hormones.

  10. WAVE2-Abi2 complex controls growth cone activity and regulates the multipolar-bipolar transition as well as the initiation of glia-guided migration.

    PubMed

    Xie, Min-Jue; Yagi, Hideshi; Kuroda, Kazuki; Wang, Chen-Chi; Komada, Munekazu; Zhao, Hong; Sakakibara, Akira; Miyata, Takaki; Nagata, Koh-Ichi; Oka, Yuichiro; Iguchi, Tokuichi; Sato, Makoto

    2013-06-01

    Glia-guided migration (glia-guided locomotion) during radial migration is a characteristic yet unique mode of migration. In this process, the directionality of migration is predetermined by glial processes and not by growth cones. Prior to the initiation of glia-guided migration, migrating neurons transform from multipolar to bipolar, but the molecular mechanisms underlying this multipolar-bipolar transition and the commencement of glia-guided migration are not fully understood. Here, we demonstrate that the multipolar-bipolar transition is not solely a cell autonomous event; instead, the interaction of growth cones with glial processes plays an essential role. Time-lapse imaging with lattice assays reveals the importance of vigorously active growth cones in searching for appropriate glial scaffolds, completing the transition, and initiating glia-guided migration. These growth cone activities are regulated by Abl kinase and Cdk5 via WAVE2-Abi2 through the phosphorylation of tyrosine 150 and serine 137 of WAVE2. Neurons that do not display such growth cone activities are mispositioned in a more superficial location in the neocortex, suggesting the significance of growth cones for the final location of the neurons. This process occurs in spite of the "inside-out" principle in which later-born neurons are situated more superficially.

  11. Atg29 phosphorylation regulates coordination of the Atg17-Atg31-Atg29 complex with the Atg11 scaffold during autophagy initiation

    PubMed Central

    Mao, Kai; Chew, Leon H.; Inoue-Aono, Yuko; Cheong, Heesun; Nair, Usha; Popelka, Hana; Yip, Calvin K.; Klionsky, Daniel J.

    2013-01-01

    Macroautophagy (hereafter autophagy) functions in the nonselective clearance of cytoplasm. This process participates in many aspects of cell physiology, and is conserved in all eukaryotes. Autophagy begins with the organization of the phagophore assembly site (PAS), where most of the AuTophaGy-related (Atg) proteins are at least transiently localized. Autophagy occurs at a basal level and can be induced by various types of stress; the process must be tightly regulated because insufficient or excessive autophagy can be deleterious. A complex composed of Atg17-Atg31-Atg29 is vital for PAS organization and autophagy induction, implying a significant role in autophagy regulation. In this study, we demonstrate that Atg29 is a phosphorylated protein and that this modification is critical to its function; alanine substitution at the phosphorylation sites blocks its interaction with the scaffold protein Atg11 and its ability to facilitate assembly of the PAS. Atg29 has the characteristics of an intrinsically disordered protein, suggesting that it undergoes dynamic conformational changes on interaction with a binding partner(s). Finally, single-particle electron microscopy analysis of the Atg17-Atg31-Atg29 complex reveals an elongated structure with Atg29 located at the opposing ends. PMID:23858448

  12. TRF2 is recruited to the pre-initiation complex as a testis-specific subunit of TFIIA/ALF to promote haploid cell gene expression.

    PubMed

    Martianov, Igor; Velt, Amandine; Davidson, Guillaume; Choukrallah, Mohamed-Amin; Davidson, Irwin

    2016-01-01

    Mammalian genomes encode two genes related to the TATA-box binding protein (TBP), TBP-related factors 2 and 3 (TRF2 and TRF3). Male Trf2(-/-) mice are sterile and characterized by arrested spermatogenesis at the transition from late haploid spermatids to early elongating spermatids. Despite this characterization, the molecular function of murine Trf2 remains poorly characterized and no direct evidence exists to show that it acts as a bona fide chromatin-bound transcription factor. We show here that Trf2 forms a stable complex with TFIIA or the testis expressed paralogue ALF chaperoned in the cytoplasm by heat shock proteins. We demonstrate for the first time that Trf2 is recruited to active haploid cell promoters together with Tbp, Taf7l and RNA polymerase II. RNA-seq analysis identifies a set of genes activated in haploid spermatids during the first wave of spermatogenesis whose expression is down-regulated by Trf2 inactivation. We therefore propose that Trf2 is recruited to the preinitiation complex as a testis-specific subunit of TFIIA/ALF that cooperates with Tbp and Taf7l to promote haploid cell gene expression. PMID:27576952

  13. TRF2 is recruited to the pre-initiation complex as a testis-specific subunit of TFIIA/ALF to promote haploid cell gene expression

    PubMed Central

    Martianov, Igor; Velt, Amandine; Davidson, Guillaume; Choukrallah, Mohamed-Amin; Davidson, Irwin

    2016-01-01

    Mammalian genomes encode two genes related to the TATA-box binding protein (TBP), TBP-related factors 2 and 3 (TRF2 and TRF3). Male Trf2−/− mice are sterile and characterized by arrested spermatogenesis at the transition from late haploid spermatids to early elongating spermatids. Despite this characterization, the molecular function of murine Trf2 remains poorly characterized and no direct evidence exists to show that it acts as a bona fide chromatin-bound transcription factor. We show here that Trf2 forms a stable complex with TFIIA or the testis expressed paralogue ALF chaperoned in the cytoplasm by heat shock proteins. We demonstrate for the first time that Trf2 is recruited to active haploid cell promoters together with Tbp, Taf7l and RNA polymerase II. RNA-seq analysis identifies a set of genes activated in haploid spermatids during the first wave of spermatogenesis whose expression is down-regulated by Trf2 inactivation. We therefore propose that Trf2 is recruited to the preinitiation complex as a testis-specific subunit of TFIIA/ALF that cooperates with Tbp and Taf7l to promote haploid cell gene expression. PMID:27576952

  14. The initial effects of orthopedic forces: a study of alterations in the craniofacial complex of a macerated human skull owing to high-pull headgear traction.

    PubMed

    Kragt, G; Duterloo, H S

    1982-01-01

    The initial reaction of components of the craniofacial skeleton of a macerated human skull was studied after high-pull headgear traction. The applied forces were increased step by step from 0.5 N to 3.25 N per side (1N = 100 grams). Laser holography was used for measuring displacements in three dimensions in seventeen indicator points on the skull. These points were located near sutures or on the outer surface of individual bones. The skull was observed from the right frontal and from the left lateral side. Results indicate that displacements range from 0 micrometer to 17.0 micrometers, depending on force magnitude and on the location of the observed point. Individual components of the craniofacial skeleton were mostly displaced in a horizontal backward direction when the skull was viewed from the frontal aspect. Various compression and shearing patterns were observed in the craniofacial sutures, apparently depending on their spatial locations and intersutural surface morphology.

  15. Controlling Mercury Release from Source Zones to Surface Water: Initial Results of Pilot Tests at the Y-12 National Security Complex

    SciTech Connect

    Southworth, George R; Brooks, Scott C; Peterson, Mark J; Bogle, Mary Anna; Miller, Carrie L; Liang, Liyuan; Elliott, Mike

    2009-01-01

    This report presents initial results obtained during year 2008 and satisfies a deliverable listed in the work breakdown structure (WBS) element OR081301. Broad objectives of the multi-year project are: (1) evaluation of remediation technologies for waterborne mercury, (2) development of treatment methods for soil mercury, and (3) source identification, characterization and analyses to improve mass balance on mercury estimates. This report presents the results of pilot tests, conducted in summer and fall 2008, which focused on remediation of waterborne mercury. The goal of this task is to develop strategies and treatment technologies that reduce the concentration and loading of waterborne mercury discharges to the UEFPC, thus minimizing mercury uptake by fish. The two specific studies are: (1) reducing flow augmentation in UEFPC to lessen mercury mobilization from contaminated stream sediments, and (2) treatment of contaminated source waters with a chemical reductant to convert dissolved mercury to a volatile form that can be removed by air stripping or natural evasion. Diversion of 50% of the flow currently added to UEFPC by the flow management system appeared to reduce mercury inputs from a localized, highly contaminated streambed by 0.6-1.5 grams per day (g/d). A reduction of 0.6 g/d represents {approx} 7-10% decrease in mercury input to UEFPC. Mercury concentrations within UEFPC did not rise proportionately with the loss of dilution, in part because of the reduction in input from the streambed source and in part because of reduced flow from the Y-12 NSC storm drain system. A longer-term test that includes seasonal variability will be the next step to validate these initial field observations of the flow diversion experiment. Preliminary laboratory experiments show that a large fraction ({approx} 90%) of the mercury can be chemically reduced to Hg(0) by addition of low concentrations of tin, Sn(II). Conversion of mercury to volatile Hg(0) in UEFPC was also

  16. Deletion of the eIFiso4G subunit of the Arabidopsis eIFiso4F translation initiation complex impairs health and viability.

    PubMed

    Lellis, Andrew D; Allen, M Leah; Aertker, Alice W; Tran, Jonathan K; Hillis, David M; Harbin, Courtney R; Caldwell, Christian; Gallie, Daniel R; Browning, Karen S

    2010-10-01

    Arabidopsis thaliana knockout lines for the plant-specific eukaryotic translation initiation factors eIFiso4G1 (i4g1) and eIFiso4G2 (i4g2) genes have been obtained. To address the potential for functional redundancy of these genes, homozygous double mutant lines were generated by crossing individual knockout lines. Both single and double mutant plants were analyzed for changes in gross morphology, development, and responses to selected environmental stressors. Single gene knockouts appear to have minimal effect on morphology, germination rate, growth rate, flowering time, or fertility. However, double mutant i4g1/i4g2 knockout plants show reduced germination rates, slow growth rates, moderate chlorosis, impaired fertility and reduced long term seed viability. Double mutant plants also exhibit altered responses to dehydration, salinity, and heat stress. The i4g2 and i4g1/i4g2 double mutant has reduced amounts of chlorophyll a and b suggesting a role in the expression of chloroplast proteins. General protein synthesis did not appear to be affected as the levels of gross protein expression did not appear to change in the mutants. The lack of a phenotype for either of the single mutants suggests there is considerable functional overlap. However, the strong phenotypes observed for the double mutant indicates that the individual gene products may have specialized roles in the expression of proteins involved in plant growth and development.

  17. Nitrosothiol formation and protection against Fenton chemistry by nitric oxide-induced dinitrosyliron complex formation from anoxia-initiated cellular chelatable iron increase.

    PubMed

    Li, Qian; Li, Chuanyu; Mahtani, Harry K; Du, Jian; Patel, Aashka R; Lancaster, Jack R

    2014-07-18

    Dinitrosyliron complexes (DNIC) have been found in a variety of pathological settings associated with (•)NO. However, the iron source of cellular DNIC is unknown. Previous studies on this question using prolonged (•)NO exposure could be misleading due to the movement of intracellular iron among different sources. We here report that brief (•)NO exposure results in only barely detectable DNIC, but levels increase dramatically after 1-2 h of anoxia. This increase is similar quantitatively and temporally with increases in the chelatable iron, and brief (•)NO treatment prevents detection of this anoxia-induced increased chelatable iron by deferoxamine. DNIC formation is so rapid that it is limited by the availability of (•)NO and chelatable iron. We utilize this ability to selectively manipulate cellular chelatable iron levels and provide evidence for two cellular functions of endogenous DNIC formation, protection against anoxia-induced reactive oxygen chemistry from the Fenton reaction and formation by transnitrosation of protein nitrosothiols (RSNO). The levels of RSNO under these high chelatable iron levels are comparable with DNIC levels and suggest that under these conditions, both DNIC and RSNO are the most abundant cellular adducts of (•)NO.

  18. The functional BPV-1 E2 trans-activating protein can act as a repressor by preventing formation of the initiation complex.

    PubMed

    Dostatni, N; Lambert, P F; Sousa, R; Ham, J; Howley, P M; Yaniv, M

    1991-09-01

    The products encoded by the E2 open reading frame of the papillomaviruses are DNA-binding transcription factors involved in the positive or negative regulation of multiple viral promoters. To further understand the mechanisms by which the same transcription factor may act differentially, the full-length BPV-1 E2 protein was expressed and purified from yeast and assayed in vitro for its capacity to modulate transcription. E2 stimulated transcription of the HSV thymidine kinase (TK) promoter when E2-binding sites were positioned in an enhancer configuration approximately 100 bp upstream of the promoter start site. In contrast, the same full-length E2 protein repressed transcription of the HPV-18 E6/E7 P105 promoter. This repression was mediated through binding to the E2 DNA-binding site immediately upstream of the P105 promoter TATA box and could be abrogated by preincubation of the HPV-18 P105 promoter template with the nuclear extract allowing the formation of the preinitiation complex. In vitro DNA-binding experiments with purified E2 and TFIID showed that binding of E2 to its DNA target placed at different positions with respect to the TATA box differentially affects binding of TFIID to its cognate site. In these respects, E2 is similar to the bacteriophage lambda repressor, which can act either as a repressor or an activator of transcription depending on the position of its binding sites relative to the promoter sequences. PMID:1653173

  19. A fast-initiating ionically tagged ruthenium complex: a robust supported pre-catalyst for batch-process and continuous-flow olefin metathesis.

    PubMed

    Borré, Etienne; Rouen, Mathieu; Laurent, Isabelle; Magrez, Magaly; Caijo, Fréderic; Crévisy, Christophe; Solodenko, Wladimir; Toupet, Loic; Frankfurter, René; Vogt, Carla; Kirschning, Andreas; Mauduit, Marc

    2012-12-14

    In this study, a new pyridinium-tagged Ru complex was designed and anchored onto sulfonated silica, thereby forming a robust and highly active supported olefin-metathesis pre-catalyst for applications under batch and continuous-flow conditions. The involvement of an oxazine-benzylidene ligand allowed the reactivity of the formed Ru pre-catalyst to be efficiently controlled through both steric and electronic activation. The oxazine scaffold facilitated the introduction of the pyridinium tag, thereby affording the corresponding cationic pre-catalyst in good yield. Excellent activities in ring-closing (RCM), cross (CM), and enyne metathesis were observed with only 0.5 mol % loading of the pre-catalyst. When this powerful pre-catalyst was immobilized onto a silica-based cationic-exchange resin, a versatile catalytically active material for batch reactions was generated that also served as fixed-bed material for flow reactors. This system could be reused at 1 mol % loading to afford metathesis products in high purity with very low ruthenium contamination under batch conditions (below 5 ppm). Scavenging procedures for both batch and flow processes were conducted, which led to a lowering of the ruthenium content to as little as one tenth of the original values.

  20. The Cambrian initiation of intra-oceanic subduction in the southern Paleo-Asian Ocean: Further evidence from the Barleik subduction-related metamorphic complex in the West Junggar region, NW China

    NASA Astrophysics Data System (ADS)

    Liu, Bo; Han, Bao-Fu; Xu, Zhao; Ren, Rong; Zhang, Jin-Rui; Zhou, Jing; Su, Li; Li, Qiu-Li

    2016-06-01

    In this study, we present new evidence from the Barleik subduction-related metamorphic complex in the southern West Junggar region, northwestern China, for the Cambrian initiation of intra-oceanic subduction in the southern Paleo-Asian Ocean. The Barleik metamorphic complex is mainly composed of blueschist and amphibolite blocks within an ophiolitic mélange and their protoliths are calc-alkaline andesite and alkali and tholeiitic basalts. The calc-alkaline andesite has a zircon U-Pb age of 502 ± 2 Ma, obtained from magmatic cores of zircon grains, and shares geochemical features similar to the 515-485 Ma intra-oceanic arc magmatic rocks in the West Junggar region. By contrast, the alkali and tholeiitic basalts have trace element features similar to ocean island and enriched mid-ocean ridge basalts, respectively. Rutile and sodic-calcic amphibole from the amphibolite have a U-Pb age of 502 ± 25 Ma and a 40Ar/39Ar age of ∼504 Ma, respectively, which are in good agreement within errors with a 40Ar/39Ar age of 492 ± 4 Ma for phengite from the blueschist. These metamorphic ages of ∼500 Ma are interpreted to represent the timing of Pacific-type subduction-related metamorphism and are also compatible with ages of the oldest supra-subduction zone ophiolites (531-512 Ma) and intra-oceanic arc plutons (515-485 Ma) in the southern West Junggar region. Being one of the oldest subduction-related metamorphic complexes (509-490 Ma) in the southern Central Asian Orogenic Belt, the Barleik metamorphic complex, together with the oldest arc plutons, definitely indicate the initial intra-oceanic subduction in the southern Paleo-Asian Ocean at least in the Early Cambrian.

  1. Research Initiatives

    Cancer.gov

    This page provides detailed information about currently funded RFA initiatives both led by DCCPS, and those led by other NIH Institutes and Centers (I/Cs) that include DCCPS as a partner. Each initiative includes a table of funded grants and a map that shows the location of funded institutions.

  2. Eukaryotic initiation factor 5B: a new player for the anti-hepatitis C virus effect of ribavirin?

    PubMed

    Galmozzi, E; Aghemo, A; Colombo, M

    2012-10-01

    The addition of the broad-spectrum antiviral agent ribavirin (RBV), a synthetic guanosine analog, to interferon-alpha (IFNα) monotherapy has been a major breakthrough in the treatment of patients with hepatitis C virus (HCV), as it greatly improved treatment response rates. Although several mechanisms of action have been proposed for RBV's antiviral activity, each with some experimental evidence, the precise mechanism by which it acts synergistically with IFNα has remained elusive. A cornerstone of the antiviral IFNα response is phosphorylation of the α subunit of eukaryotic initiation factor (eIF)2. This limits the availability of eIF2⋅GTP⋅Met-tRNA(i)(Met) ternary complexes, reduces formation of the 43S preinitiation complexes, ultimately blocking viral (and most cellular) mRNA translation. However recent studies indicated that translation driven by the HCV internal ribosome entry site (IRES) is insensitive to eIF2α phosphorylation. Particularly, in addition to the general eIF2-dependent pathway of translation, the HCV IRES makes use of a bacterial-like, eIF2-independent pathway requiring as initiation factors only eIF5B (an analog of bacterial IF2) and eIF3. Together, these observations support a model in which cellular stresses that induce eIF2α phosphorylation (e.g. treatment with IFNα) cause HCV IRES-directed translation to switch from an eIF2-dependent mode to an eIF5B-dependent mode, defining a tactic used by HCV to evade the INFα response. Eukaryotic eIF5B is a ribosome-dependent GTPase that is responsible for 80S complex formation in translation initiation but shows much lower affinities for GTP than to other GTPases, thus suggesting that it may mis-incorporate the RBV triphosphate (RTP) in place of GTP even at the RBV concentrations achieved in clinical use. Consequently, we theorize that RTP bound to eIF5B lowering its affinity for ribosome, blocks the 80S complex formation on HCV IRES inhibiting the eIF5B-dependent translation used by HCV to

  3. Wildfire Impacts on Water Quality, Macroinvertebrates and Trout: An Initial Survey After the West Fork Complex Fire in the Upper Rio Grande

    NASA Astrophysics Data System (ADS)

    Rust, A.; Knipper, K. R.; Randall, J.; Hogue, T. S.

    2014-12-01

    Forest fires affect water quality in the disrupted watershed, which can devastate the aquatic ecosystem including sensitive trout (Salmonidae) and macroinvertebrate species. The West Fork Fire Complex consumed 88,724 acres of forest in the state of Colorado during the summer of 2013. The majority (88%) of the burn area was comprised of Engelmann spruce (Picea engelmanii) trees killed previously by Spruce Beetle (Ips spp.). Damage to the soils was of moderate to high severity in the majority of the area (60%). The recent fire surrounded the Rio Grande, affecting water quality and habitat critical to insects and fish. The water quality of the Rio Grande (above and below the burn) and some of the effected tributaries is currently being monitored for both quality and quantity. Parameters important to the survival of aquatic life, such as flow, temperature, dissolved oxygen, pH, conductivity, total dissolved solids, total suspended solids, turbidity, nutrients, and suspended and dissolved metals are being monitored along the Rio Grande and in tributaries. Macroinvertebrate and fish populations are sampled in the same locations. First year observations showed the ecosystem to be relatively resilient, with stable water quality and survival of insects and fish. However, an intense monsoon season this summer is driving extensive sediments into tributaries from steep, severely burned hillslopes. These monsoon events have caused acute and dramatic fish kills, where hundreds of trout were reported killed in one tributary in a single day event. Turbidity was observed as high as 488 NTU in the impacted stream with fish kill, whereas the turbidity was 25 NTU in a neighboring tributary outside of the burn area. Salmonids can be negatively impacted by relatively low turbidity, with prior studies noting that the turbidity threshold for rainbow trout is 70 NTU. Continued monitoring of water quality, macroinvertebrate populations, and fish populations is being undertaken to determine

  4. Structure of the eukaryotic translation initiation factor eIF4E in complex with 4EGI-1 reveals an allosteric mechanism for dissociating eIF4G.

    PubMed

    Papadopoulos, Evangelos; Jenni, Simon; Kabha, Eihab; Takrouri, Khuloud J; Yi, Tingfang; Salvi, Nicola; Luna, Rafael E; Gavathiotis, Evripidis; Mahalingam, Poornachandran; Arthanari, Haribabu; Rodriguez-Mias, Ricard; Yefidoff-Freedman, Revital; Aktas, Bertal H; Chorev, Michael; Halperin, Jose A; Wagner, Gerhard

    2014-08-01

    The interaction of the eukaryotic translation initiation factor eIF4E with the initiation factor eIF4G recruits the 40S ribosomal particle to the 5' end of mRNAs, facilitates scanning to the AUG start codon, and is crucial for eukaryotic translation of nearly all genes. Efficient recruitment of the 40S particle is particularly important for translation of mRNAs encoding oncoproteins and growth-promoting factors, which often harbor complex 5' UTRs and require efficient initiation. Thus, inhibiting the eIF4E/eIF4G interaction has emerged as a previously unpursued route for developing anticancer agents. Indeed, we discovered small-molecule inhibitors of this eIF4E/eIF4G interaction (4EGIs) that inhibit translation initiation both in vitro and in vivo and were used successfully in numerous cancer-biology and neurobiology studies. However, their detailed molecular mechanism of action has remained elusive. Here, we show that the eIF4E/eIF4G inhibitor 4EGI-1 acts allosterically by binding to a site on eIF4E distant from the eIF4G binding epitope. Data from NMR mapping and high-resolution crystal structures are congruent with this mechanism, where 4EGI-1 attaches to a hydrophobic pocket of eIF4E between β-sheet2 (L60-T68) and α-helix1 (E69-N77), causing localized conformational changes mainly in the H78-L85 region. It acts by unfolding a short 310-helix (S82-L85) while extending α-helix1 by one turn (H78-S82). This unusual helix rearrangement has not been seen in any previous eIF4E structure and reveals elements of an allosteric inhibition mechanism leading to the dislocation of eIF4G from eIF4E.

  5. Climatic and human impacts on the ligneous cover in the Sahel from analysis of aerial photographs before and after the drought periods of the 70's and 80's

    NASA Astrophysics Data System (ADS)

    San Emeterio, J. L.; Mering, C.

    2012-04-01

    The purpose of the work is to retrieve the major changes in the spatial organization of the ligneous cover in the Sahel due to the climate variability during the last fifty years from the comparison between ancient aerial photos and recent high resolution panchromatic remotely sensed images. Vegetation may be considered as one of the essential resources for the rural societies of the Sahel. Degradation of vegetation cover which has followed the decrease in rainfall from the early 1970s to the mid 1990 have often been considered as a premonitory sign of non reversing desertification. In Sahelian regions, vegetation cover becomes more and more discontinuous with the increasing of dryness and demographic growth. This phenomenon, called 'patchiness' is a good indicator for climate stress. According to some topoedaphic and societal conditions, patchiness leads to various kinds of facies of the ligneous cover from dotted spatial organizations to banded ones, well known as tiger bush. As shrub is overexploited by rural populations for pastoral and domestic use, contraction of the vegetation has negative consequences on human activity in the whole Sahelian zone. In the context of the rainfall increase all over the west African Sahel since the second part of the 1990s, a widespread increase in vegetation productivity has been detected at regional scale. Although, some local observations of recent land clearance seem to be contradictory with such recent greening of the Sahel. As a matter of fact, human actions such as intensive farming and urbanization as a response to recent demographic increase in West Africa have also strong impacts on the degradation of ligneous cover. In order to shed light on the respective parts of climate, environment and human practices in the sahelian vegetation dynamics at local scale in various sahelian sites , a comparison between aerial photographs taken before the severe droughts in West Africa of the 70 and 80's and after the increase of

  6. [Study of the mRNA-binding region of ribosomes at different steps of translation. II. Affinity modification of Escherichia coli ribosomes by benzylidene derivative of AUGU6 in the 70S initiation complex].

    PubMed

    Babkina, G T; Karpova, G G; Matasova, N B; Berzin', V M; Gren, E Ia

    1985-01-01

    2',3'-O-(4-[N-(2-chloroethyl)-N-methylamino]) benzylidene derivative of AUGU6 was used for identification of the proteins in the region of the mRNA-binding centre of E. coli ribosomes. This derivative alkylated ribosomes (preferentially 30S ribosomal) with high efficiency within the 70S initiation complex. In both 30S and 50S ribosomal subunits proteins and rRNA were modified. Specificity of the alkylation of ribosomal proteins and rRNA with the reagent was proved by the inhibitory action of AUGU6. Using the method of two-dimensional electrophoresis in polyacrylamide gel the proteins S4, S12, S13, S14, S15, S18, S19 and S20/L26 which are labelled by the analog of mRNA were identified.

  7. Re-analysis of human immunodeficiency virus type 1 isolates from Cyprus and Greece, initially designated 'subtype I', reveals a unique complex A/G/H/K/? mosaic pattern.

    PubMed

    Paraskevis, D; Magiorkinis, M; Vandamme, A M; Kostrikis, L G; Hatzakis, A

    2001-03-01

    Human immunodeficiency virus type 1 (HIV-1) has been classified into three main groups and 11 distinct subtypes. Moreover, several circulating recombinant forms (CRFs) of HIV-1 have been recently documented to have spread widely causing extensive HIV-1 epidemics. A subtype, initially designated I (CRF04_cpx), was documented in Cyprus and Greece and was found to comprise regions of sequence derived from subtypes A and G as well as regions of unclassified sequence. Re-analysis of the three full-length CRF04_cpx sequences that were available revealed a mosaic genomic organization of unique complexity comprising regions of sequence from at least five distinct subtypes, A, G, H, K and unclassified regions. These strains account for approximately 2% of the total HIV-1-infected population in Greece, thus providing evidence of the great capability of HIV-1 to recombine and produce highly divergent strains which can be spread successfully through different infection routes.

  8. Initiation and propagation of complex 3D networks of cracks in heterogeneous quasi-brittle materials: Direct comparison between in situ testing-microCT experiments and phase field simulations

    NASA Astrophysics Data System (ADS)

    Nguyen, T. T.; Yvonnet, J.; Bornert, M.; Chateau, C.

    2016-10-01

    We provide the first direct comparisons, to our knowledge, of complex 3D micro cracking initiation and propagation in heterogeneous quasi-brittle materials modelled by the phase field numerical method and observed in X-ray microtomography images recorded during in situ mechanical testing. Some material parameters of the damage model, including the process zone (internal) length, are identified by an inverse approach combining experimental data and 3D simulations. A new technique is developed to study the micro cracking at a finer scale by prescribing the local displacements measured by digital volume correlation over the boundary of a small sub-volume inside the sample during the numerical simulations. The comparisons, performed on several samples of lightweight plaster and concrete, show a remarkable quantitative agreement between the 3D crack morphology obtained by the model and by the experiments, without any a priori knowledge about the location of the initiation of the cracks in the numerical model. The results indicate that the crack paths can be predicted in a fully deterministic way in spite of the highly random geometry of the microstructure and the brittle nature of its constituents.

  9. SCB initiator

    DOEpatents

    Bickes, Jr., Robert W.; Renlund, Anita M.; Stanton, Philip L.

    1994-01-01

    A detonator for high explosives initiated by mechanical impact includes a cylindrical barrel, a layer of flyer material mechanically covering the barrel at one end, and a semiconductor bridge ignitor including a pair of electrically conductive pads connected by a semiconductor bridge. The bridge is in operational contact with the layer, whereby ignition of said bridge forces a portion of the layer through the barrel to detonate the explosive. Input means are provided for igniting the semiconductor bridge ignitor.

  10. SCB initiator

    DOEpatents

    Bickes Jr., Robert W.; Renlund, Anita M.; Stanton, Philip L.

    1994-11-01

    A detonator for high explosives initiated by mechanical impact includes a cylindrical barrel, a layer of flyer material mechanically covering the barrel at one end, and a semiconductor bridge ignitor including a pair of electrically conductive pads connected by a semiconductor bridge. The bridge is in operational contact with the layer, whereby ignition of said bridge forces a portion of the layer through the barrel to detonate the explosive. Input means are provided for igniting the semiconductor bridge ignitor.

  11. Environmental initiatives

    SciTech Connect

    James, R.C. Jr.

    1991-11-01

    J I Case, a leading worldwide maker of agricultural and construction equipment based in Racine, Wisconsin, is taking an aggressive and responsible approach to environmental issues. From integrated solid waste handling plans and Freon recovery initiatives, to special employee training programs and voluntary participation in the EPA's Industrial Toxics Program, Case is addressing environmental issues at its facilities and in its products. One of the key environmental initiatives at Case is the company's voluntary participation in the US EPA's Industrial Toxics Program, also known as the 33/50 Program. This program is an EPA pollution prevention initiative started in 1990 that is designed to reduce industrial toxics generation quickly through voluntary actions by industry. The program derives its name from the EPA's national reduction goals for 17 high priority toxic pollutants - 33 percent reduction by 1992 and 50 percent by 1995. As a result, the Pryor Foundry has slashed its emissions of industrial toxic pollutants by 98 percent, from over 350,000 pounds (159 metric tons) in 1988 to around 5,000 pounds (2.27 metric tons) in 1991, with a projected reduction to only 750 pounds (340 kilograms) by 1995.

  12. Interaction between 25S rRNA A loop and eukaryotic translation initiation factor 5B promotes subunit joining and ensures stringent AUG selection.

    PubMed

    Hiraishi, Hiroyuki; Shin, Byung-Sik; Udagawa, Tsuyoshi; Nemoto, Naoki; Chowdhury, Wasimul; Graham, Jymie; Cox, Christian; Reid, Megan; Brown, Susan J; Asano, Katsura

    2013-09-01

    In yeast, 25S rRNA makes up the major mass and shape of the 60S ribosomal subunit. During the last step of translation initiation, eukaryotic initiation factor 5B (eIF5B) promotes the 60S subunit joining with the 40S initiation complex (IC). Malfunctional 60S subunits produced by misfolding or mutation may disrupt the 40S IC stalling on the start codon, thereby altering the stringency of initiation. Using several point mutations isolated by random mutagenesis, here we studied the role of 25S rRNA in start codon selection. Three mutations changing bases near the ribosome surface had strong effects, allowing the initiating ribosomes to skip both AUG and non-AUG codons: C2879U and U2408C, altering the A loop and P loop, respectively, of the peptidyl transferase center, and G1735A, mapping near a Eukarya-specific bridge to the 40S subunit. Overexpression of eIF5B specifically suppressed the phenotype caused by C2879U, suggesting functional interaction between eIF5B and the A loop. In vitro reconstitution assays showed that C2879U decreased eIF5B-catalyzed 60S subunit joining with a 40S IC. Thus, eIF5B interaction with the peptidyl transferase center A loop increases the accuracy of initiation by stabilizing the overall conformation of the 80S initiation complex. This study provides an insight into the effect of ribosomal mutations on translation profiles in eukaryotes.

  13. Structure of the eukaryotic translation initiation factor eIF4E in complex with 4EGI-1 reveals an allosteric mechanism for dissociating eIF4G

    PubMed Central

    Papadopoulos, Evangelos; Jenni, Simon; Kabha, Eihab; Takrouri, Khuloud J.; Yi, Tingfang; Salvi, Nicola; Luna, Rafael E.; Gavathiotis, Evripidis; Mahalingam, Poornachandran; Arthanari, Haribabu; Rodriguez-Mias, Ricard; Yefidoff-Freedman, Revital; Aktas, Bertal H.; Chorev, Michael; Halperin, Jose A.; Wagner, Gerhard

    2014-01-01

    The interaction of the eukaryotic translation initiation factor eIF4E with the initiation factor eIF4G recruits the 40S ribosomal particle to the 5′ end of mRNAs, facilitates scanning to the AUG start codon, and is crucial for eukaryotic translation of nearly all genes. Efficient recruitment of the 40S particle is particularly important for translation of mRNAs encoding oncoproteins and growth-promoting factors, which often harbor complex 5′ UTRs and require efficient initiation. Thus, inhibiting the eIF4E/eIF4G interaction has emerged as a previously unpursued route for developing anticancer agents. Indeed, we discovered small-molecule inhibitors of this eIF4E/eIF4G interaction (4EGIs) that inhibit translation initiation both in vitro and in vivo and were used successfully in numerous cancer–biology and neurobiology studies. However, their detailed molecular mechanism of action has remained elusive. Here, we show that the eIF4E/eIF4G inhibitor 4EGI-1 acts allosterically by binding to a site on eIF4E distant from the eIF4G binding epitope. Data from NMR mapping and high-resolution crystal structures are congruent with this mechanism, where 4EGI-1 attaches to a hydrophobic pocket of eIF4E between β-sheet2 (L60-T68) and α-helix1 (E69-N77), causing localized conformational changes mainly in the H78-L85 region. It acts by unfolding a short 310-helix (S82-L85) while extending α-helix1 by one turn (H78-S82). This unusual helix rearrangement has not been seen in any previous eIF4E structure and reveals elements of an allosteric inhibition mechanism leading to the dislocation of eIF4G from eIF4E. PMID:25049413

  14. Sequential eukaryotic translation initiation factor 5 (eIF5) binding to the charged disordered segments of eIF4G and eIF2β stabilizes the 48S preinitiation complex and promotes its shift to the initiation mode.

    PubMed

    Singh, Chingakham Ranjit; Watanabe, Ryosuke; Chowdhury, Wasimul; Hiraishi, Hiroyuki; Murai, Marcelo J; Yamamoto, Yasufumi; Miles, David; Ikeda, Yuka; Asano, Masayo; Asano, Katsura

    2012-10-01

    During translation initiation in Saccharomyces cerevisiae, an Arg- and Ser-rich segment (RS1 domain) of eukaryotic translation initiation factor 4G (eIF4G) and the Lys-rich segment (K-boxes) of eIF2β bind three common partners, eIF5, eIF1, and mRNA. Here, we report that both of these segments are involved in mRNA recruitment and AUG recognition by distinct mechanisms. First, the eIF4G-RS1 interaction with the eIF5 C-terminal domain (eIF5-CTD) directly links eIF4G to the preinitiation complex (PIC) and enhances mRNA binding. Second, eIF2β-K-boxes increase mRNA binding to the 40S subunit in vitro in a manner reversed by the eIF5-CTD. Third, mutations altering eIF4G-RS1, eIF2β-K-boxes, and eIF5-CTD restore the accuracy of start codon selection impaired by an eIF2β mutation in vivo, suggesting that the mutual interactions of the eIF segments within the PIC prime the ribosome for initiation in response to start codon selection. We propose that the rearrangement of interactions involving the eIF5-CTD promotes mRNA recruitment through mRNA binding by eIF4G and eIF2β and assists the start codon-induced release of eIF1, the major antagonist of establishing tRNA(i)(Met):mRNA binding to the P site.

  15. Coordinated movements of eukaryotic translation initiation factors eIF1, eIF1A, and eIF5 trigger phosphate release from eIF2 in response to start codon recognition by the ribosomal preinitiation complex.

    PubMed

    Nanda, Jagpreet S; Saini, Adesh K; Muñoz, Antonio M; Hinnebusch, Alan G; Lorsch, Jon R

    2013-02-22

    Accurate recognition of the start codon in an mRNA by the eukaryotic translation preinitiation complex (PIC) is essential for proper gene expression. The process is mediated by eukaryotic translation initiation factors (eIFs) in conjunction with the 40 S ribosomal subunit and (initiator) tRNA(i). Here, we provide evidence that the C-terminal tail (CTT) of eIF1A, which we previously implicated in start codon recognition, moves closer to the N-terminal domain of eIF5 when the PIC encounters an AUG codon. Importantly, this movement is coupled to dissociation of eIF1 from the PIC, a critical event in start codon recognition, and is dependent on the scanning enhancer elements in the eIF1A CTT. The data further indicate that eIF1 dissociation must be accompanied by the movement of the eIF1A CTT toward eIF5 in order to trigger release of phosphate from eIF2, which converts the latter to its GDP-bound state. Our results also suggest that release of eIF1 from the PIC and movement of the CTT of eIF1A are triggered by the same event, most likely accommodation of tRNA(i) in the P site of the 40 S subunit driven by base pairing between the start codon in the mRNA and the anticodon in tRNA(i). Finally, we show that the C-terminal domain of eIF5 is responsible for the factor's activity in antagonizing eIF1 binding to the PIC. Together, our data provide a more complete picture of the chain of molecular events that is triggered when the scanning PIC encounters an AUG start codon in the mRNA.

  16. Two Arabidopsis loci encode novel eukaryotic initiation factor 4E isoforms that are functionally distinct from the conserved plant eukaryotic initiation factor 4E.

    PubMed

    Patrick, Ryan M; Mayberry, Laura K; Choy, Grace; Woodard, Lauren E; Liu, Joceline S; White, Allyson; Mullen, Rebecca A; Tanavin, Toug M; Latz, Christopher A; Browning, Karen S

    2014-04-01

    Canonical translation initiation in eukaryotes begins with the Eukaryotic Initiation Factor 4F (eIF4F) complex, made up of eIF4E, which recognizes the 7-methylguanosine cap of messenger RNA, and eIF4G, which serves as a scaffold to recruit other translation initiation factors that ultimately assemble the 80S ribosome. Many eukaryotes have secondary EIF4E genes with divergent properties. The model plant Arabidopsis (Arabidopsis thaliana) encodes two such genes in tandem loci on chromosome 1, EIF4E1B (At1g29550) and EIF4E1C (At1g29590). This work identifies EIF4E1B/EIF4E1C-type genes as a Brassicaceae-specific diverged form of EIF4E. There is little evidence for EIF4E1C gene expression; however, the EIF4E1B gene appears to be expressed at low levels in most tissues, though microarray and RNA Sequencing data support enrichment in reproductive tissue. Purified recombinant eIF4E1b and eIF4E1c proteins retain cap-binding ability and form functional complexes in vitro with eIF4G. The eIF4E1b/eIF4E1c-type proteins support translation in yeast (Saccharomyces cerevisiae) but promote translation initiation in vitro at a lower rate compared with eIF4E. Findings from surface plasmon resonance studies indicate that eIF4E1b and eIF4E1c are unlikely to bind eIF4G in vivo when in competition with eIF4E. This study concludes that eIF4E1b/eIF4E1c-type proteins, although bona fide cap-binding proteins, have divergent properties and, based on apparent limited tissue distribution in Arabidopsis, should be considered functionally distinct from the canonical plant eIF4E involved in translation initiation.

  17. Two Arabidopsis Loci Encode Novel Eukaryotic Initiation Factor 4E Isoforms That Are Functionally Distinct from the Conserved Plant Eukaryotic Initiation Factor 4E1[W][OPEN

    PubMed Central

    Patrick, Ryan M.; Mayberry, Laura K.; Choy, Grace; Woodard, Lauren E.; Liu, Joceline S.; White, Allyson; Mullen, Rebecca A.; Tanavin, Toug M.; Latz, Christopher A.; Browning, Karen S.

    2014-01-01

    Canonical translation initiation in eukaryotes begins with the Eukaryotic Initiation Factor 4F (eIF4F) complex, made up of eIF4E, which recognizes the 7-methylguanosine cap of messenger RNA, and eIF4G, which serves as a scaffold to recruit other translation initiation factors that ultimately assemble the 80S ribosome. Many eukaryotes have secondary EIF4E genes with divergent properties. The model plant Arabidopsis (Arabidopsis thaliana) encodes two such genes in tandem loci on chromosome 1, EIF4E1B (At1g29550) and EIF4E1C (At1g29590). This work identifies EIF4E1B/EIF4E1C-type genes as a Brassicaceae-specific diverged form of EIF4E. There is little evidence for EIF4E1C gene expression; however, the EIF4E1B gene appears to be expressed at low levels in most tissues, though microarray and RNA Sequencing data support enrichment in reproductive tissue. Purified recombinant eIF4E1b and eIF4E1c proteins retain cap-binding ability and form functional complexes in vitro with eIF4G. The eIF4E1b/eIF4E1c-type proteins support translation in yeast (Saccharomyces cerevisiae) but promote translation initiation in vitro at a lower rate compared with eIF4E. Findings from surface plasmon resonance studies indicate that eIF4E1b and eIF4E1c are unlikely to bind eIF4G in vivo when in competition with eIF4E. This study concludes that eIF4E1b/eIF4E1c-type proteins, although bona fide cap-binding proteins, have divergent properties and, based on apparent limited tissue distribution in Arabidopsis, should be considered functionally distinct from the canonical plant eIF4E involved in translation initiation. PMID:24501003

  18. Openness initiative

    SciTech Connect

    Duncan, S.S.

    1995-12-31

    Although antinuclear campaigns seem to be effective, public communication and education efforts on low-level radioactive waste have mixed results. Attempts at public information programs on low-level radioactive waste still focus on influencing public opinion. A question then is: {open_quotes}Is it preferable to have a program focus on public education that will empower individuals to make informed decisions rather than trying to influence them in their decisions?{close_quotes} To address this question, a case study with both quantitative and qualitative data will be used. The Ohio Low-Level Radioactive Waste Education Program has a goal to provide people with information they want/need to make their own decisions. The program initiated its efforts by conducting a statewide survey to determine information needed by people and where they turned for that information. This presentation reports data from the survey and then explores the program development process in which programs were designed and presented using the information. Pre and post data from the programs reveal attitude and knowledge shifts.

  19. Studies of electrical conductivity and complex initial permeability of multiferroic xBa0.95Sr0.05TiO3-(1-x)BiFe0.90Gd0.10O3 ceramics

    NASA Astrophysics Data System (ADS)

    Miah, Mohammad J.; Khan, M. N. I.; Hossain, A. K. M. Akther

    2016-07-01

    Multiferroic xBa0.95Sr0.05TiO3-(1-x)BiFe0.90Gd0.10O3 [xBST-(1-x)BFGO] (x = 0.00, 0.10 and 0.20) ceramics were prepared by the standard solid-state reaction technique. Crystal structure of the ceramics was determined by X-ray diffraction pattern. All the compositions exhibited rhombohedral crystal structure. The tolerance factor `t' varied from 0.847 to 0.864. The AC conductivity spectrum followed the Jonscher's power law. The Nyquist plots indicated that only grains have the contribution to the resistance in this material and the values of grain resistance (Rg) increased with BST content. The real part of complex initial permeability decreased with the increase in frequency and increased with increasing BST content. Magnetoelectric coefficient was determined for all compositions. The maximum value of magnetoelectric coefficient was found to be 1.467 mV.cm-1.Oe-1 for x = 0.20.

  20. A novel interaction of Cap-binding protein complexes eukaryotic initiation factor (eIF) 4F and eIF(iso)4F with a region in the 3'-untranslated region of satellite tobacco necrosis virus.

    PubMed

    Gazo, Brandy M; Murphy, Patricia; Gatchel, Jennifer R; Browning, Karen S

    2004-04-01

    Satellite tobacco necrosis virus (STNV) RNA is naturally uncapped at its 5' end and lacks polyadenylation at its 3' end. Despite lacking these two hallmarks of eukaryotic mRNAs, STNV-1 RNA is translated very efficiently. A approximately 130-nucleotide translational enhancer (TED), located 3' to the termination codon, is necessary for efficient cap-independent translation of STNV-1 RNA. The STNV-1 TED RNA fragment binds to the eukaryotic cap-binding complexes, initiation factor (eIF) 4F and eIF(iso)4F, as measured by nitrocellulose binding and fluorescence titration. STNV-1 TED is a potent inhibitor of in vitro translation when added in trans. This inhibition is reversed by the addition of eIF4F or eIF(iso)4F, and the subunits of eIF4F and eIF(iso)4F cross-link to STNV-1 TED, providing additional evidence that these factors interact directly with STNV-1 TED. Deletion mutagenesis of the STNV-1 TED indicates that a minimal region of approximately 100 nucleotides is necessary to promote cap-independent translation primarily through interaction with the cap binding subunits (eIF4E or eIF(iso)4E) of eIF4F or eIF(iso)4F.

  1. Atom transfer radical addition (ATRA) catalyzed by copper complexes with tris[2-(dimethylamino)ethyl]amine (Me6TREN) ligand in the presence of free-radical diazo initiator AIBN.

    PubMed

    Eckenhoff, William T; Pintauer, Tomislav

    2011-05-14

    In this article, we focus on the evaluation of tris[2-(dimethylamino)ethyl]amine (Me(6)TREN) ligand in copper catalyzed ATRA in the presence of free-radical diazo initiator AIBN (2,2'-azobis(2-methylpropionitrile)). The addition of carbon tetrachloride to 1-hexene, 1-octene and cis-cyclooctene proceeded efficiently to yield 89, 85 and 85% of monoadduct, respectively, using the catalyst to alkene ratio of 1 : 2500. For alkenes that readily undergo free radical polymerization, such as methyl acrylate, catalyst loadings as high as 0.4 mol-% were required. Furthermore, modest yields of the monoadduct were obtained with less active alkyl halides (chloroform and bromoform) using 250 : 1 and 500 : 1 ratios of alkene to copper(II). Interestingly, the addition of carbon tetrachloride to cis-cyclooctene produced only 1-chloro-4-(trichloromethyl)-cyclooctene, while carbon tetrabromide yielded 1,2 and 1,4-regioisomers in 75 : 25 ratio. The activity of [Cu(II)(Me(6)TREN)X][X] (X = Br(-) and Cl(-)) complexes in ATRA in the presence of AIBN was additionally probed by adding excess free ligand, source of halide anions and triphenylphosphine. The results indicated that disproportionation is a likely cause for lower activity of Me(6)TREN as compared to TPMA (tris(2-pyridylmethyl)amine).

  2. EUROANDRILL Initiative

    NASA Astrophysics Data System (ADS)

    Florindo, Fabio; Steering Committee, Euroandrill

    2010-05-01

    EuroANDRILL is a new initiative to create a European network with the goal to increase future involvement of European countries in the ANDRILL [ANtarctic geological DRILLing] Programme. Antarctica has been heavily glaciated for approximately 34 million years, but its ice sheets have fluctuated considerably and are one of the major driving forces for changes in climate throughout the Cenozoic Era. The spatial scale and temporal pattern of these fluctuations is subject to considerable debate. Understanding the response of large ice masses to climatic forcing is of vital importance because ice volume variations drive global sea level changes and also alter the capacity of ice sheets and sea-ice to act as major heat sinks/insulators. It is particularly important to assess the stability of the cryosphere in the face of rising CO2 levels, as modelling of the climate shift from a warm, vegetated Antarctica to a cold, ice-covered state 34 million years ago suggests a powerful greenhouse gas influence. As Antarctica is the major driver of Earth's climate and sea level, much effort has been expended in deriving models of its behaviour. Some of these models have been successfully validated against modern conditions. EuroANDRILL will provide a coherent, integrated platform for European leadership and involvement in the international ANDRILL programme. The coordination and networking provided by EuroANDRILL will seek to expand participation by European nations, institutions, and individual scientists in the study of the geologic history of the polar regions and their paleoclimatic significance. During the IPY, ANDRILL has been a highly visible and successful programme. This programme seeks to expand on this legacy beyond the IPY and make these contributions sustainable in the European Research Area through networking of research projects and future planning efforts, which establish Europe as a key player in future polar sediment and rock drilling. EuroANDRILL is set up under

  3. Microdrill Initiative - Initial Market Evaluation

    SciTech Connect

    Spears & Associates, Inc

    2003-07-01

    The U.S. Department of Energy (DOE) is launching a major research and development initiative to create a small, fast, inexpensive and environmentally friendly rig for drilling 5000 feet boreholes to investigate potential oil and gas reservoirs. DOE wishes to get input from petroleum industry operators, service companies and equipment suppliers on the operation and application of this coiled-tubing-based drilling unit. To that end, DOE has asked Spears & Associates, Inc. (SAI) to prepare a special state-of-the-market report and assist during a DOE-sponsored project-scoping workshop in Albuquerque near the end of April 2003. The scope of the project is four-fold: (1) Evaluate the history, status and future of demand for very small bore-hole drilling; (2) Measure the market for coiled tubing drilling and describe the state-of-the-art; (3) Identify companies and individuals who should have an interest in micro drilling and invite them to the DOE workshop; and (4) Participate in 3 concurrent workshop sessions, record and evaluate participant comments and report workshop conclusions.

  4. Potential role of the posterior cruciate ligament synovio-entheseal complex in joint effusion in early osteoarthritis: a magnetic resonance imaging and histological evaluation of cadaveric tissue and data from the Osteoarthritis Initiative

    PubMed Central

    Binks, D.A.; Bergin, D.; Freemont, A.J.; Hodgson, R.J.; Yonenaga, T.; McGonagle, D.; Radjenovic, A.

    2014-01-01

    Summary Objective This study explored posterior cruciate ligament (PCL) synovio-entheseal complex (SEC) microanatomy to determine whether it may participate in the early osteoarthritis (OA) disease process. Methods SEC microanatomy and OA features were evaluated in 14 non-arthritic cadaveric knees (mean age = 69.9) using magnetic resonance imaging (MRI) and histology. MRI images of 49 subjects selected from the progression cohort of the Osteoarthritis Initiative (OAI) were evaluated by a musculoskeletal radiologist using an original semi-quantitative method for features associated with OA at the PCL tibial enthesis. Statistical analysis was performed using chi-square and Wilcoxon signed-rank tests to evaluate associations between SEC configuration and OA features. Results The PCL formed a SEC-like structure encompassing bone- and ligament-lining intra-articular cartilages to which the posterior root of the medial meniscus contributed. Degenerative features at the PCL-SEC included: neovascularisation (44%), enthesis chondrocyte clustering (44%), collagen matrix fissuring at the enthesis (56%) and in the PCL itself (67%), tidemark duplication (44%), bone remodelling (44%) and microscopic inflammatory changes (33%). In the OAI cohort, SEC-related pathology included bone marrow lesions (BMLs) (69%) and osteophytosis (94%) at locations that corresponded to SEC-related cartilages. Posterior joint recess effusion (49%) was linked to MRI abnormalities at PCL-SEC cartilages (χ2 = 7.27, P = 0.007). Conclusions The PCL has a prominent SEC configuration that is associated with microscopic OA changes in aged clinically non-diseased joints. MRI determined knee OA commonly exhibited pathological features at this site which was associated with adjacent joint effusion. Thus, the PCL-SEC could play a hitherto unappreciated role in the early OA disease process. PMID:25008208

  5. Combat Wound Initiative program.

    PubMed

    Stojadinovic, Alexander; Elster, Eric; Potter, Benjamin K; Davis, Thomas A; Tadaki, Doug K; Brown, Trevor S; Ahlers, Stephen; Attinger, Christopher E; Andersen, Romney C; Burris, David; Centeno, Jose; Champion, Hunter; Crumbley, David R; Denobile, John; Duga, Michael; Dunne, James R; Eberhardt, John; Ennis, William J; Forsberg, Jonathan A; Hawksworth, Jason; Helling, Thomas S; Lazarus, Gerald S; Milner, Stephen M; Mullick, Florabel G; Owner, Christopher R; Pasquina, Paul F; Patel, Chirag R; Peoples, George E; Nissan, Aviram; Ring, Michael; Sandberg, Glenn D; Schaden, Wolfgang; Schultz, Gregory S; Scofield, Tom; Shawen, Scott B; Sheppard, Forest R; Stannard, James P; Weina, Peter J; Zenilman, Jonathan M

    2010-07-01

    The Combat Wound Initiative (CWI) program is a collaborative, multidisciplinary, and interservice public-private partnership that provides personalized, state-of-the-art, and complex wound care via targeted clinical and translational research. The CWI uses a bench-to-bedside approach to translational research, including the rapid development of a human extracorporeal shock wave therapy (ESWT) study in complex wounds after establishing the potential efficacy, biologic mechanisms, and safety of this treatment modality in a murine model. Additional clinical trials include the prospective use of clinical data, serum and wound biomarkers, and wound gene expression profiles to predict wound healing/failure and additional clinical patient outcomes following combat-related trauma. These clinical research data are analyzed using machine-based learning algorithms to develop predictive treatment models to guide clinical decision-making. Future CWI directions include additional clinical trials and study centers and the refinement and deployment of our genetically driven, personalized medicine initiative to provide patient-specific care across multiple medical disciplines, with an emphasis on combat casualty care. PMID:23634474

  6. Exploring accessibility of structural elements of the mammalian 40S ribosomal mRNA entry channel at various steps of translation initiation.

    PubMed

    Sharifulin, Dmitri E; Bartuli, Yulia S; Meschaninova, Maria I; Ven'yaminova, Aliya G; Graifer, Dmitri M; Karpova, Galina G

    2016-10-01

    In this work, we studied how the accessibility of structural elements of the mammalian 40S ribosomal mRNA entry channel, ribosomal protein (rp) uS3 and helix (h) 16 of the 18S rRNA, changes upon the translation initiation. In particular, we examined the accessibility of rp uS3 for binding of unstructured RNAs and of riboses in h16 towards attack with benzoyl cyanide (BzCN) in complexes assembled in rabbit reticulocyte lysate utilizing synthetic oligoribonucleotides as well as full-length and truncated up to the initiation AUG codon hepatitis C virus IRES as model mRNAs. With both mRNA types, the rp uS3 peptide recognizing single-stranded RNAs was shown to become shielded only in those 48S preinitiation complexes (PICs) that contained eIF3j bound to 40S subunit in the area between the decoding site and the mRNA entry channel. Chemical probing with BzCN revealed that h16 in the 48S PICs containing eIF3j or scanning factor DHX29 is strongly shielded; the effect was observed with all the mRNAs used, and h16 remained protected as well in 80S post-initiation complexes lacking these factors. Altogether, the obtained results allowed us to suggest that eIF3j bound at the 48S PICs makes the rp uS3 inaccessible for binding of RNAs and this factor subunit is responsible for the decrease of h16 conformational flexibility; the latter is manifested as reduced accessibility of h16 to BzCN. Thus, our findings provide new insights into how eIF3j is implicated in ensuring the proper conformation of the mRNA entry channel, thereby facilitating mRNA loading. PMID:27346718

  7. Optimod – An automated approach for constructing and optimizing initial models for single-particle electron microscopy

    PubMed Central

    Lyumkis, Dmitry; Vinterbo, Staal; Potter, Clinton S.; Carragher, Bridget

    2013-01-01

    Single-particle cryo-electron microscopy is now well established as a technique for the structural characterization of large macromolecules and macromolecular complexes. The raw data is very noisy and consists of two-dimensional projections, from which the 3D biological object must be reconstructed. The 3D object depends upon knowledge of proper angular orientations assigned to the 2D projection images. Numerous algorithms have been developed for determining relative angular orientations between 2D images, but the transition from 2D to 3D remains challenging and can result in erroneous and conflicting results. Here we describe a general, automated procedure, called OptiMod, for reconstructing and optimizing 3D models using common-lines methodologies. OptiMod approximates orientation angles and reconstructs independent maps from 2D class averages. It then iterates the procedure, while considering each map as a raw solution that needs to be compared with other possible outcomes. We incorporate procedures for 3D alignment, clustering, and refinement to optimize each map, as well as standard scoring metrics to facilitate the selection of the optimal model. We also show that small angle tilt-pair data can be included as one of the scoring metrics to improve the selection of the optimal initial model, and also to provide a validation check. The overall approach is demonstrated using two experimental cryo-EM data sets – the 80S ribosome that represents a relatively straightforward case for ab initio reconstruction, and the Tf–TfR complex that represents a challenging case in that it has previously been shown to provide multiple equally plausible solutions to the initial model problem. PMID:24161732

  8. Dynamics of ribosome scanning and recycling revealed by translation complex profiling.

    PubMed

    Archer, Stuart K; Shirokikh, Nikolay E; Beilharz, Traude H; Preiss, Thomas

    2016-07-28

    Regulation of messenger RNA translation is central to eukaryotic gene expression control. Regulatory inputs are specified by them RNA untranslated regions (UTRs) and often target translation initiation. Initiation involves binding of the 40S ribosomal small subunit (SSU) and associated eukaryotic initiation factors (eIFs)near the mRNA 5′ cap; the SSU then scans in the 3′ direction until it detects the start codon and is joined by the 60S ribosomal large subunit (LSU) to form the 80S ribosome. Scanning and other dynamic aspects of the initiation model have remained as conjectures because methods to trap early intermediates were lacking. Here we uncover the dynamics of the complete translation cycle in live yeast cells using translation complex profile sequencing (TCP-seq), a method developed from the ribosome profiling approach. We document scanning by observing SSU footprints along 5′ UTRs. Scanning SSU have 5′-extended footprints (up to~75 nucleotides), indicative of additional interactions with mRNA emerging from the exit channel, promoting forward movement. We visualized changes in initiation complex conformation as SSU footprints coalesced into three major sizes at start codons (19, 29 and 37 nucleotides). These share the same 5′ start site but differ at the 3′ end, reflecting successive changes at the entry channel from an open to a closed state following start codon recognition. We also observe SSU 'lingering' at stop codons after LSU departure. Our results underpin mechanistic models of translation initiation and termination, built on decades of biochemical and structural investigation, with direct genome-wide in vivo evidence. Our approach captures ribosomal complexes at all phases of translation and will aid in studying translation dynamics in diverse cellular contexts. Dysregulation of translation is common in disease and, for example, SSU scanning is a target of anti-cancer drug development. TCP-seq will prove useful in discerning differences

  9. Eukaryotic translation initiation is controlled by cooperativity effects within ternary complexes of 4E-BP1, eIF4E, and the mRNA 5' cap.

    PubMed

    Modrak-Wojcik, Anna; Gorka, Michal; Niedzwiecka, Katarzyna; Zdanowski, Konrad; Zuberek, Joanna; Niedzwiecka, Anna; Stolarski, Ryszard

    2013-12-11

    Initiation is the rate-limiting step during mRNA 5' cap-dependent translation, and thus a target of a strict control in the eukaryotic cell. It is shown here by analytical ultracentrifugation and fluorescence spectroscopy that the affinity of the human translation inhibitor, eIF4E-binding protein (4E-BP1), to the translation initiation factor 4E is significantly higher when eIF4E is bound to the cap. The 4E-BP1 binding stabilizes the active eIF4E conformation and, on the other hand, can facilitate dissociation of eIF4E from the cap. These findings reveal the particular allosteric effects forming a thermodynamic cycle for the cooperative regulation of the translation initiation inhibition.

  10. Math Anxiety and the Student of the '80's.

    ERIC Educational Resources Information Center

    Smith, Jean Burr

    As colleges take on increasing numbers of nontraditional students who have had only minimal exposure to mathematics, instructors must alleviate patterns of math anxiety and math avoidance which impede academic success, and, in a technological society, limit career opportunities. Among the obvious causes of math anxiety are: instructors' insistence…

  11. Testing in the '80s: An Agenda for Action.

    ERIC Educational Resources Information Center

    Rentz, Charlotte C.

    Today, in this country, there is widespread public support for educational testing, evidenced by the large amount of state minimum competency testing legislation, and recent public opinion surveys. Despite a basically favorable view of standardized testing, parents are concerned about the effects of test anxiety and poor test-taking skills on…

  12. Resource Sharing: A Necessity for the '80s.

    ERIC Educational Resources Information Center

    Lavo, Barbara, Comp.

    Papers presented at a 1981 seminar on library resource sharing covered topics related to Australasian databases, Australian and New Zealand document delivery systems, and shared acquisition and cataloging for special libraries. The papers included: (1) "AUSINET: Australasia's Information Network?" by Ian McCallum; (2) "Australia/New Zealand Shared…

  13. Solar '80s: A Teacher's Handbook for Solar Energy Education.

    ERIC Educational Resources Information Center

    LaHart, David E.

    This guide is intended to assist the teacher in exploring energy issues and the technology of solar energy conversion and associated technologies. Sections of the guide include: (1) Rationale; (2) Technology Overview; (3) Sun Day Suggestions for School; (4) Backyard Solar Water Heater; (5) Solar Tea; (6) Biogas; (7) Solar Cells; (8) Economics; (9)…

  14. Unesco's General Information Programme for the 80s.

    ERIC Educational Resources Information Center

    United Nations Educational, Scientific and Cultural Organization, Paris (France). General Information Programme.

    Developing countries are becoming increasingly aware of the fact that specialized information is essential to their economic and social development, and that it is an indispensable factor in the rational use of natural resources, the development of human resources, scientific and technological advancement, and progress in agriculture, industry,…

  15. Teaching Canada for the '80s. Curriculum Series, 35.

    ERIC Educational Resources Information Center

    Hodgetts, A. B.; Gallagher, Paul

    A rationale for Canadian studies and outlines of appropriate content for various grade levels are presented. The book is designed to help teachers, curriculum planners, and teacher educators in preparing effective Canadian studies programs. Chapter I offers a discussion of the need for pan-Canadian understanding. Canadian studies can help young…

  16. Managing Campus Security Programs in the 80's.

    ERIC Educational Resources Information Center

    Kimble, Joseph Paul

    After presenting an imaginative depiction of the fiscal and administrative changes that may overwhelm community colleges during the 1980's, this paper looks at several factors that should be considered in planning and managing campus security departments. The paper offers suggestions related to: (1) the development of master parking plans which…

  17. Budgeting--A Management Approach for the '80s.

    ERIC Educational Resources Information Center

    Hodel, Ross A.

    1980-01-01

    Zero-base budgeting is a management tool that provides a system that is responsive to change, incorporates sound principles of management, satisfies the need to effectively shift resources, and does not overload the budget staff. (Author/MLF)

  18. Tribology in the 80's. Volume 2: Sessions 5 - 8

    NASA Technical Reports Server (NTRS)

    1984-01-01

    Tender standing and technical advancement of various disciplines and subdisciplines on tribology were discussed. Topics discussed included importance and definition of materials in tribology; directions of research in adhesion and friction; research in wear and wear resistant materials; liquid lubricants and additives; solid lubricants; and tribological materials for mechanical components of the future.

  19. Planning for the 80's: Workforce Educational Development Project Report.

    ERIC Educational Resources Information Center

    Cuyahoga Community Coll., Cleveland, OH.

    The findings and recommendations found in this report are the result of a cooperative planning process undertaken by Cuyahoga Community College (CCC) to determine the best way of meeting the training and educational needs of the employed adults in its service district. Background information is presented first, describing the composition and…

  20. Home Based Care: Direction for the 80s.

    ERIC Educational Resources Information Center

    Bryce, Marvin E.

    Home based family centered (HBFC) service programs have been developed as alternatives to out-of-home placement. These programs have reported relatively high service success rates at costs signficantly lower than foster home and institutional care while, at the same time, avoiding the social and psychological risks of out-of-home placement.…

  1. Benefits from space applications in the 80's.

    NASA Technical Reports Server (NTRS)

    Von Braun, W.

    1971-01-01

    A summary of our nation's space capability as we enter the decade of the 1980's is given. The environment in which man lives; the demands he places on this environment; and the natural and man-made problems that beset him are examined. The application of our space capability to help man solve some of his problems, and the attendant benefits that would be derived, are postulated. Particular emphasis is given to man's more pressing problems: the resources of the earth, the weather, and communications needs. The benefits are viewed as accruing to all peoples of the world, which could be ultimately attained through cooperative efforts on an international basis.

  2. Energy in New England: Transition to the 80's

    NASA Astrophysics Data System (ADS)

    Katz, R.; Pawlick, L.; Spencer, B.

    1981-06-01

    Activities in New England which result in more efficient consumption of energy are discussed. Change in aggregate energy demand since the oil embargo, energy use and the regional economy, incentives for conservation, and decline in electricity growth are also discussed. The conributions made by wood products, hydroelectric power, solid waste, solar, wind, alcohol fuels, peat, and tidal power are disclosed. Changes in consumption of individual conventional energy products (petroleum, natural gas, nuclear power, coal, purchased electricity) and activity currently underway in the conventional fuel area are summarized.

  3. Hispanics in the 80's: Retrenchment of Self-Renewal?

    ERIC Educational Resources Information Center

    Florez, John

    1981-01-01

    Examines the characteristics of the Hispanic movement and the changes in its orientation as a result of economic, social, and political influences since 1960. Emphasizes self-renewal rather than survival and retrenchment as a strategy for solving current social problems. (JCD)

  4. Teaching the New History: Thoughts for the 80s.

    ERIC Educational Resources Information Center

    Carroll, Peter

    1985-01-01

    History has previously been learned as a long parade; making it wider, not just a single file of great men, is certainly an improvement. But whole areas of life reflect patterns of change that are apart from the major concerns of political leaders. Humanizing history makes it memorable and gives children a sense of connection. (MT)

  5. Overview of speech technology of the 80's

    SciTech Connect

    Crook, S.B.

    1981-01-01

    The author describes the technology innovations necessary to accommodate the market need which is the driving force toward greater perceived computer intelligence. The author discusses aspects of both speech synthesis and speech recognition.

  6. Public Elementary and Secondary Education in the '80s.

    ERIC Educational Resources Information Center

    Broudy, H. S.

    Privatism, vouchers, too many pressure groups, and a deemphasis of citizenship present the worst stumbling blocks to education. A five-point curriculum model includes: (1) the symbolics of information--the skills of language and computation; (2) the key concepts of a selected set of the physical sciences and mathematics; (3) developmental studies…

  7. Technologies of the '80s: Their Impact on Distribution Occupations.

    ERIC Educational Resources Information Center

    Jaffe, J. A., Ed.; And Others

    This report is one of seven that identify major new and emerging technological advances expected to influence major vocational education program areas and to describe the programmatic implications in terms of skill-knowledge requirements, occupations most directly affected, and the anticipated diffusion rate. Chapter 1 considers technology as…

  8. Technologies of the '80s: Their Impact on Office Occupations.

    ERIC Educational Resources Information Center

    Jaffe, J. A., Ed.; And Others

    This report is one of seven that identify major new and emerging technological advances expected to influence major vocational education program areas and to describe the programmatic implications in terms of skill-knowledge requirements, occupations most directly affected, and the anticipated diffusion rate. Chapter 1 considers technology as…

  9. Technologies of the '80s: Their Impact on Health Occupations.

    ERIC Educational Resources Information Center

    Jaffe, J. A., Ed.; And Others

    This report is one of seven that identify major new and emerging technological advances expected to influence major vocational education program areas and to describe the programmatic implications in terms of skill-knowledge requirements, occupations most directly affected, and the anticipated diffusion rate. Chapter 1 considers technology as…

  10. A New School Board for the 80's?

    ERIC Educational Resources Information Center

    Jakes, Harold E.

    1980-01-01

    The government of Ontario (Canada) announced, in December 1979, its position on three major issues of school governance currently in dispute in the Ottawa and Carleton school systems. The first announcement (overriding recommendations made in 1974 by the Mayo Commission and again in March 1979 in the government's "Education Green Paper") was that…

  11. IEA predicts late '80s oil crisis, urges conservation

    SciTech Connect

    Betts, M.

    1982-10-18

    The International Energy Agency (IEA) is urging industrial conservation to offset a major oil crisis in the late 1980s. IEA foresees that growing demand and shrinking production will cause price increases and market disruptions. Their concern is that industrialists are misreading the market signals of the current oil glut and stable prices. IEA urges oil-importing countries to conserve energy and to substitute more non-oil energy. Among its recommendations are heat-recovery technology, decontrol of energy prices, and government efficiency standards. (DCK)

  12. An American Profile: Trends and Issues in the 80s.

    ERIC Educational Resources Information Center

    Long, Sandra M.

    1982-01-01

    Migrations to the Sun Belt, exodus from urban areas, the aging of the baby-boom generation, and single-parent families are significantly altering the needs and priorities of America's schools. (Author/JM)

  13. Puerto Ricans in the Mid '80s: An American Challenge.

    ERIC Educational Resources Information Center

    National Puerto Rican Coalition, Inc., Alexandria, VA.

    Taken together, the contents of this document provide a picture of the Puerto Rican community, both on the mainland and on the island, in the mid-1980s. First, a brief overview of the Puerto Rican community is provided. Next, a demographic profile compares Puerto Ricans on the mainland with those on the island and both with the general U.S.…

  14. Adolescent Pregnancy Prevention: Strategies for the '80's.

    ERIC Educational Resources Information Center

    Ortiz, Elizabeth T.; Bassoff, Betty Z.

    Most efforts at combating teenage pregnancy have focused on cognitive/educational levels felt by concerned adults to be of greatest importance. However, recent research has demonstrated the connection between lack of career goals, low self-esteem, perception of narrow options, and risk-taking behavior as factors leading to pregnancy. A 3-year…

  15. Job Options for Women in the 80's. Pamphlet 18.

    ERIC Educational Resources Information Center

    Women's Bureau (DOL), Washington, DC.

    This booklet is intended to provide guidance to women who are making decisions about their lives and work and to help them take advantage of the opportunities that are now open to them. Part I gives an overview of the status of women in the work force and some of the factors that affect women's employment. Alternative work patterns are a special…

  16. Television in the 80's: New Technologies, New Challenges.

    ERIC Educational Resources Information Center

    Alvarez, Sally

    Electronic media have undergone substantial growth and change in the past two decades, and the structure of the programming industry has also changed, with the competition for programming becoming more intense. At the same time, government has moved toward deregulation in this area, with the result being increasing concentration,…

  17. Perspectives on Child Maltreatment in the Mid '80s.

    ERIC Educational Resources Information Center

    National Center on Child Abuse and Neglect (DHHS/OHDS), Washington, DC.

    This book presents 19 papers on child abuse and neglect. A brief introduction by Health and Human Services Secretary, Margaret Heckler is followed by 13 major issue papers: "Combatting Child Abuse and Neglect" by the assistant secretary for Human Development Services, Dorcas R. Hardy; "What Have We Learned about Child Maltreatment" by James…

  18. Technologies of the '80s: Their Impact on Technical Occupations.

    ERIC Educational Resources Information Center

    Jaffe, J. A., Ed.; And Others

    This report is one of seven that identify major new and emerging technological advances expected to influence major vocational education program areas and to describe the programmatic implications in terms of skill-knowledge requirements, occupations most directly affected, and the anticipated diffusion rate. Chapter 1 considers technology as…

  19. Leadership in the '80s: Essays on Higher Education.

    ERIC Educational Resources Information Center

    Argyris, Chris; Cyert, Richard M.

    Two essays and two commentaries on leadership in higher education in the 1980s are presented. In "Education Administrators and Professionals," Chris Argyris considers the decline of public confidence in institutions and professionals by elaborating the concepts of single-loop (detecting and correcting error without altering underlying values or…

  20. Two Year Computer System Technology Curricula for the '80's.

    ERIC Educational Resources Information Center

    Palko, Donald N.; Hata, David M.

    1982-01-01

    The computer industry is viewed on a collision course with a human resources crisis. Changes expected during the next decade are outlined, with expectations noted that merging of hardware and software skills will be met in a technician's skill set. Essential curricula components of a computer system technology program are detailed. (MP)

  1. Two Energy Futures: A National Choice for the 80s.

    ERIC Educational Resources Information Center

    American Petroleum Inst., Washington, DC.

    Examined in this American Petroleum Institute (API) publication on energy technology and energy policy, is the future potential of oil, natural gas, coal, nuclear energy, synthetic fuels, and renewable energy resources. Among the related issues emphasized are environmental protection, access to federal lands, government policies, and the national…

  2. Urban Education in the 80s: The Never Ending Challenge.

    ERIC Educational Resources Information Center

    National Association of Secondary School Principals, Reston, VA.

    Contemporary problems in urban education are explored in this collection of papers. The leading article discusses the implications of urban decay and demographic change for school finance and educational accountability. The second paper stresses the need for a basic skills curriculum, well-trained teachers, and the inclusion of parents in…

  3. Energy in the '80s: decade of decision

    SciTech Connect

    Not Available

    1980-06-01

    This proceeding includes the six papers presented at the Public Awareness Symposium plus the WATTEC/Engineers' Week banquet address on nuclear power by Dr. Harold M. Agnew of General Atomic Co.; these presentations on the final day, February 22, concluded the 1980 WATTEC conference. A separate abstract was prepared for each paper and for the banquet address.

  4. Two Energy Futures: A National Choice for the 80s.

    ERIC Educational Resources Information Center

    American Petroleum Inst., Washington, DC.

    In 1980, the American Petroleum Institute published the first edition of "Two Energy Futures." It described the U.S. energy experience of the 1970s and prospects for the 1980s, concluding that the nation could drastically reduce its dependence on uncertain sources of imported oil if the right choices were made by individuals and the government.…

  5. Partners for the 80's: Business and Education.

    ERIC Educational Resources Information Center

    Purcell, Elizabeth A., Ed.; And Others

    Following a brief introduction that defines types of business/education partnerships and outlines their financial and educational benefits for schools, students, and businesses, 24 profiles of existing and effective cooperative programs are presented. Profiles are given a page and a half to two pages of coverage and provide the following…

  6. Functional dissection of eukaryotic initiation factor 4F: the 4A subunit and the central domain of the 4G subunit are sufficient to mediate internal entry of 43S preinitiation complexes.

    PubMed Central

    Pestova, T V; Shatsky, I N; Hellen, C U

    1996-01-01

    Eukaryotic translation is initiated following binding of ribosomes either to the capped 5' end of an mRNA or to an internal ribosomal entry site (IRES) within its 5' nontranslated region. These processes are both mediated by eukaryotic initiation factor 4F (eIF4F), which consists of eIF4A (helicase), eIF4E (cap-binding protein), and eIF4G subunits. Here we present a functional analysis of eIF4F which defines the subunits and subunit domains necessary for its function in initiation mediated by the prototypical IRES element of encephalomyocarditis virus. In an initiation reaction reconstituted in vitro from purified translation components and lacking eIF4A and -4F, IRES-mediated initiation did not require the cap-binding protein eIF4E but was absolutely dependent on eIF4A and the central third of eIF4G. This central domain of eIF4G bound strongly and specifically to a structural element within the encephalomyocarditis virus IRES upstream of the initiation codon in an ATP-independent manner and with the same specificity as eIF4F. The carboxy-terminal third of eIF4G did not bind to the IRES. The central domain of eIF4G was itself UV cross-linked to the IRES and strongly stimulated UV cross-linking of eIF4A to the IRES in conjunction with either eIF4B or with the carboxy-terminal third of eIF4G. PMID:8943342

  7. RNA Polymerase Pausing during Initial Transcription.

    PubMed

    Duchi, Diego; Bauer, David L V; Fernandez, Laurent; Evans, Geraint; Robb, Nicole; Hwang, Ling Chin; Gryte, Kristofer; Tomescu, Alexandra; Zawadzki, Pawel; Morichaud, Zakia; Brodolin, Konstantin; Kapanidis, Achillefs N

    2016-09-15

    In bacteria, RNA polymerase (RNAP) initiates transcription by synthesizing short transcripts that are either released or extended to allow RNAP to escape from the promoter. The mechanism of initial transcription is unclear due to the presence of transient intermediates and molecular heterogeneity. Here, we studied initial transcription on a lac promoter using single-molecule fluorescence observations of DNA scrunching on immobilized transcription complexes. Our work revealed a long pause ("initiation pause," ∼20 s) after synthesis of a 6-mer RNA; such pauses can serve as regulatory checkpoints. Region sigma 3.2, which contains a loop blocking the RNA exit channel, was a major pausing determinant. We also obtained evidence for RNA backtracking during abortive initial transcription and for additional pausing prior to escape. We summarized our work in a model for initial transcription, in which pausing is controlled by a complex set of determinants that modulate the transition from a 6- to a 7-nt RNA. PMID:27618490

  8. RNA Polymerase Pausing during Initial Transcription.

    PubMed

    Duchi, Diego; Bauer, David L V; Fernandez, Laurent; Evans, Geraint; Robb, Nicole; Hwang, Ling Chin; Gryte, Kristofer; Tomescu, Alexandra; Zawadzki, Pawel; Morichaud, Zakia; Brodolin, Konstantin; Kapanidis, Achillefs N

    2016-09-15

    In bacteria, RNA polymerase (RNAP) initiates transcription by synthesizing short transcripts that are either released or extended to allow RNAP to escape from the promoter. The mechanism of initial transcription is unclear due to the presence of transient intermediates and molecular heterogeneity. Here, we studied initial transcription on a lac promoter using single-molecule fluorescence observations of DNA scrunching on immobilized transcription complexes. Our work revealed a long pause ("initiation pause," ∼20 s) after synthesis of a 6-mer RNA; such pauses can serve as regulatory checkpoints. Region sigma 3.2, which contains a loop blocking the RNA exit channel, was a major pausing determinant. We also obtained evidence for RNA backtracking during abortive initial transcription and for additional pausing prior to escape. We summarized our work in a model for initial transcription, in which pausing is controlled by a complex set of determinants that modulate the transition from a 6- to a 7-nt RNA.

  9. Initialized Fractional Calculus

    NASA Technical Reports Server (NTRS)

    Lorenzo, Carl F.; Hartley, Tom T.

    2000-01-01

    This paper demonstrates the need for a nonconstant initialization for the fractional calculus and establishes a basic definition set for the initialized fractional differintegral. This definition set allows the formalization of an initialized fractional calculus. Two basis calculi are considered; the Riemann-Liouville and the Grunwald fractional calculi. Two forms of initialization, terminal and side are developed.

  10. Scientific Component Technology Initiative

    SciTech Connect

    Kohn, S; Bosl, B; Dahlgren, T; Kumfert, G; Smith, S

    2003-02-07

    The laboratory has invested a significant amount of resources towards the development of high-performance scientific simulation software, including numerical libraries, visualization, steering, software frameworks, and physics packages. Unfortunately, because this software was not designed for interoperability and re-use, it is often difficult to share these sophisticated software packages among applications due to differences in implementation language, programming style, or calling interfaces. This LDRD Strategic Initiative investigated and developed software component technology for high-performance parallel scientific computing to address problems of complexity, re-use, and interoperability for laboratory software. Component technology is an extension of scripting and object-oriented software development techniques that specifically focuses on the needs of software interoperability. Component approaches based on CORBA, COM, and Java technologies are widely used in industry; however, they do not support massively parallel applications in science and engineering. Our research focused on the unique requirements of scientific computing on ASCI-class machines, such as fast in-process connections among components, language interoperability for scientific languages, and data distribution support for massively parallel SPMD components.

  11. Strategic Initiatives and Goals.

    ERIC Educational Resources Information Center

    Howard Community Coll., Columbia, MD.

    This document outlines Howard Community College's (HCC) six strategic initiatives and goals. Each of the strategic initiatives is presented, along with a context for the statement and a list of goals to be achieved in support of the overall initiative. First, HCC will be a learning community that provides possibilities for learning that address…

  12. APEC Smart Grid Initiative

    SciTech Connect

    Bloyd, Cary N.

    2012-03-01

    This brief paper describes the activities of the Asia Pacific Economic Cooperation (APEC) Smart Grid Initiative (ASGI) which is being led by the U.S. and developed by the APEC Energy Working Group. In the paper, I describe the origin of the initiative and briefly mention the four major elements of the initiative along with existing APEC projects which support it.

  13. Initiation of vascular development.

    PubMed

    Ohashi-Ito, Kyoko; Fukuda, Hiroo

    2014-06-01

    The initiation of vascular development occurs during embryogenesis and the development of lateral organs, such as lateral roots and leaves. Understanding the mechanism underlying the initiation of vascular development has been an important goal of plant biologists. Auxin flow is a crucial factor involved in the initiation of vascular development. In addition, recent studies have identified key factors that regulate the establishment of vascular initial cells in embryos and roots. In this review, we summarize the recent findings in this field and discuss the initiation of vascular development.

  14. Robonaut Mobile Autonomy: Initial Experiments

    NASA Technical Reports Server (NTRS)

    Diftler, M. A.; Ambrose, R. O.; Goza, S. M.; Tyree, K. S.; Huber, E. L.

    2006-01-01

    A mobile version of the NASA/DARPA Robonaut humanoid recently completed initial autonomy trials working directly with humans in cluttered environments. This compact robot combines the upper body of the Robonaut system with a Segway Robotic Mobility Platform yielding a dexterous, maneuverable humanoid ideal for interacting with human co-workers in a range of environments. This system uses stereovision to locate human teammates and tools and a navigation system that uses laser range and vision data to follow humans while avoiding obstacles. Tactile sensors provide information to grasping algorithms for efficient tool exchanges. The autonomous architecture utilizes these pre-programmed skills to form complex behaviors. The initial behavior demonstrates a robust capability to assist a human by acquiring a tool from a remotely located individual and then following the human in a cluttered environment with the tool for future use.

  15. DICE: Disk Initial Conditions Environment

    NASA Astrophysics Data System (ADS)

    Perret, Valentin

    2016-07-01

    DICE models initial conditions of idealized galaxies to study their secular evolution or their more complex interactions such as mergers or compact groups using N-Body/hydro codes. The code can set up a large number of components modeling distinct parts of the galaxy, and creates 3D distributions of particles using a N-try MCMC algorithm which does not require a prior knowledge of the distribution function. The gravitational potential is then computed on a multi-level Cartesian mesh by solving the Poisson equation in the Fourier space. Finally, the dynamical equilibrium of each component is computed by integrating the Jeans equations for each particles. Several galaxies can be generated in a row and be placed on Keplerian orbits to model interactions. DICE writes the initial conditions in the Gadget1 or Gadget2 (ascl:0003.001) format and is fully compatible with Ramses (ascl:1011.007).

  16. Progress in Initiator Modeling

    SciTech Connect

    Hrousis, C A; Christensen, J S

    2009-05-04

    There is great interest in applying magnetohydrodynamic (MHD) simulation techniques to the designs of electrical high explosive (HE) initiators, for the purpose of better understanding a design's sensitivities, optimizing its performance, and/or predicting its useful lifetime. Two MHD-capable LLNL codes, CALE and ALE3D, are being used to simulate the process of ohmic heating, vaporization, and plasma formation in the bridge of an initiator, be it an exploding bridgewire (EBW), exploding bridgefoil (EBF) or slapper type initiator. The initiation of the HE is simulated using Tarver Ignition & Growth reactive flow models. 1-D, 2-D and 3-D models have been constructed and studied. The models provide some intuitive explanation of the initiation process and are useful for evaluating the potential impact of identified aging mechanisms (such as the growth of intermetallic compounds or powder sintering). The end product of this work is a simulation capability for evaluating margin in proposed, modified or aged initiation system designs.

  17. Initiation precursors and initiators in laser-induced copolymerization of styrene and maleic anhydride in acetone

    NASA Technical Reports Server (NTRS)

    Miner, Gilda A.; Meador, Willard E.; Chang, C. Ken

    1990-01-01

    The initiation step of photopolymerized styrene/maleic anhydride copolymer was investigated at 365 nm. UV absorption measurements provide decisive evidence that the styrene/maleic anhydride charge transfer complex is the sole absorbing species; however, key laser experiments suggest intermediate reactions lead to a monoradical initiating species. A mechanism for the photoinitiation step of the copolymer is proposed.

  18. Who initiates emergency commitments?

    PubMed

    Christy, Annette; Handelsman, Jessica B; Hanson, Ardis; Ochshorn, Ezra

    2010-04-01

    Florida's Mental Health Act was amended in 2005 and 2006 to include licensed mental health counselors and licensed marriage and family therapists, respectively, to the list of professionals authorized to initiate emergency commitments. The present study evaluates the volume of involuntary emergency commitments by type of initiator for a 5 year period. The results indicate that allowing licensed mental health counselors and licensed marriage and family therapist to initiate emergency commitments has not been related to increased numbers of emergency commitments or a higher proportion of emergency commitments being initiated by mental health professionals. Potential policy and fiscal implications, as well as future directions for research, are discussed. PMID:19597746

  19. Complexity Survey.

    ERIC Educational Resources Information Center

    Gordon, Sandra L.; Anderson, Beth C.

    To determine whether consensus existed among teachers about the complexity of common classroom materials, a survey was administered to 66 pre-service and in-service kindergarten and prekindergarten teachers. Participants were asked to rate 14 common classroom materials as simple, complex, or super-complex. Simple materials have one obvious part,…

  20. Illinois: Prevention Initiative

    ERIC Educational Resources Information Center

    Center for Law and Social Policy, Inc. (CLASP), 2012

    2012-01-01

    The Illinois Prevention Initiative provides grants to home-based and center-based programs to expand access to the Early Head Start (EHS) model as well as other birth to 3 models. The goal is to serve additional children birth to age 3 and help grantees increase program quality. The initiative to expand access to EHS and other models was…

  1. Prioritizing Scientific Initiatives.

    ERIC Educational Resources Information Center

    Bahcall, John N.

    1991-01-01

    Discussed is the way in which a limited number of astronomy research initiatives were chosen and prioritized based on a consensus of members from the Astronomy and Astrophysics Survey Committee. A list of recommended equipment initiatives and estimated costs is provided. (KR)

  2. Sustainable Forest Bioenergy Initiative

    SciTech Connect

    Breger, Dwayne; Rizzo, Rob

    2011-09-20

    associated with biomass usage, an understanding of forest management trends including harvesting and fuel processing methods, and the carbon profile of utilizing forest based woody biomass for the emerging biomass markets. Each of the tasks and subtasks have provided an increased level of understanding to support new directives, policies and adaptation of existing regulations within Massachusetts. The project has provided the essential information to allow state policymakers and regulators to address emerging markets, while ensuring forest sustainability and understanding the complex science on CO2 accounting and impacts as a result of biomass harvesting for power generation. The public at large and electricity ratepayers in Massachusetts will all benefit from the information garnered through this project. This is a result of the state’s interest to provide financial incentives to only biomass projects that demonstrate an acceptable carbon profile, an efficient use of the constrained supply of fuel, and the harvest of biomass to ensure forest sustainability. The goals of the Massachusetts Sustainable Forest Bioenergy Initiative as proposed in 2006 were identified as: increase the diversity of the Massachusetts energy mix through biomass; promote economic development in the rural economy through forest industry job creation; help fulfill the state’s energy and climate commitments under the Renewable Energy Portfolio Standard and Climate Protection Plan; assist the development of a biomass fuel supply infrastructure to support energy project demands; provide education and outreach to the public on the benefits and impacts of bioenergy; improve the theory and practice of sustainable forestry in the Commonwealth. Completed project activities summarized below will demonstrate the effectiveness of the project in meeting the above goals. In addition, as discussed above, Massachusetts DOER needed to make some modifications to its work plan and objectives during the term of this

  3. Collaborative Initiative in Biomedical Imaging to Study Complex Diseases

    SciTech Connect

    Lin, Weili; Fiddy, Michael A.

    2012-03-31

    The work reported addressed these topics: Fluorescence imaging; Optical coherence tomography; X-ray interferometer/phase imaging system; Quantitative imaging from scattered fields, Terahertz imaging and spectroscopy; and Multiphoton and Raman microscopy.

  4. ICT Reform Initiatives in Singapore Schools: A Complexity Theory Perspective

    ERIC Educational Resources Information Center

    Toh, Yancy; So, Hyo-Jeong

    2011-01-01

    The past two decades have witnessed an exponential growth in the use of technology in our daily life. Notwithstanding its phenomenal influence, the use of technology in education remains sporadic and disjointed. The promise that technology will bring deep-seated changes in the way that educators teach and students learn remains, disappointedly,…

  5. ELECTRICAL SAFETY IMPROVEMENT PROJECT A COMPLEX WIDE TEAMING INITIATIVE

    SciTech Connect

    GRAY BJ

    2007-11-26

    This paper describes the results of a year-long project, sponsored by the Energy Facility Contractors Group (EFCOG) and designed to improve overall electrical safety performance throughout Department of Energy (DOE)-owned sites and laboratories. As evidenced by focused metrics, the Project was successful primarily due to the joint commitment of contractor and DOE electrical safety experts, as well as significant support from DOE and contractor senior management. The effort was managed by an assigned project manager, using classical project-management principles that included execution of key deliverables and regular status reports to the Project sponsor. At the conclusion of the Project, the DOE not only realized measurable improvement in the safety of their workers, but also had access to valuable resources that will enable them to do the following: evaluate and improve electrical safety programs; analyze and trend electrical safety events; increase electrical safety awareness for both electrical and non-electrical workers; and participate in ongoing processes dedicated to continued improvement.

  6. DiffPy-CMI-Python libraries for Complex Modeling Initiative

    SciTech Connect

    Billinge, Simon; Juhas, Pavol; Farrow, Christopher; McKerns, Michael

    2014-02-01

    Software to manipulate and describe crystal and molecular structures and set up structural refinements from multiple experimental inputs. Calculation and simulation of structure derived physical quantities. Library for creating customized refinements of atomic structures from available experimental and theoretical inputs.

  7. COMPLEX FLARE DYNAMICS INITIATED BY A FILAMENT–FILAMENT INTERACTION

    SciTech Connect

    Zhu, Chunming; McAteer, R. T. James; Liu, Rui; Alexander, David; Sun, Xudong

    2015-11-01

    We report on an eruption involving a relatively rare filament–filament interaction on 2013 June 21, observed by SDO and STEREO-B. The two filaments were separated in height with a “double-decker” configuration. The eruption of the lower filament began simultaneously with a descent of the upper filament, resulting in a convergence and direct interaction of the two filaments. The interaction was accompanied by the heating of surrounding plasma and an apparent crossing of a loop-like structure through the upper filament. The subsequent coalescence of the filaments drove a bright front ahead of the erupting structures. The whole process was associated with a C3.0 flare followed immediately by an M2.9 flare. Shrinking loops and descending dark voids were observed during the M2.9 flare at different locations above a C-shaped flare arcade as part of the energy release, giving us unique insight into the flare dynamics.

  8. Autonomous aircraft initiative study

    NASA Technical Reports Server (NTRS)

    Hewett, Marle D.

    1991-01-01

    The results of a consulting effort to aid NASA Ames-Dryden in defining a new initiative in aircraft automation are described. The initiative described is a multi-year, multi-center technology development and flight demonstration program. The initiative features the further development of technologies in aircraft automation already being pursued at multiple NASA centers and Department of Defense (DoD) research and Development (R and D) facilities. The proposed initiative involves the development of technologies in intelligent systems, guidance, control, software development, airborne computing, navigation, communications, sensors, unmanned vehicles, and air traffic control. It involves the integration and implementation of these technologies to the extent necessary to conduct selected and incremental flight demonstrations.

  9. The RAS Initiative

    Cancer.gov

    NCI established the RAS Initiative to explore innovative approaches for attacking the proteins encoded by mutant forms of RAS genes and to ultimately create effective, new therapies for RAS-related cancers.

  10. RAS Initiative - Community Outreach

    Cancer.gov

    Through community and technical collaborations, workshops and symposia, and the distribution of reference reagents, the RAS Initiative seeks to increase the sharing of knowledge and resources essential to defeating cancers caused by mutant RAS genes.

  11. Advanced Concepts Research Initiative

    EPA Science Inventory

    This initiative is investigating various approaches to controlling and treating wet-weather flow (WWF) discharges in the urban watershed. WWF, including combined sewer overflow (CSO), sanitary sewer overflow (SSO) and stormwater discharges are leading causes of receiving water q...

  12. RAS Initiative - Events

    Cancer.gov

    The NCI RAS Initiative has organized multiple events with outside experts to discuss how the latest scientific and technological breakthroughs can be applied to discover vulnerabilities in RAS-driven cancers.

  13. Piezoelectrically Initiated Pyrotechnic Igniter

    NASA Technical Reports Server (NTRS)

    Quince, Asia; Dutton, Maureen; Hicks, Robert; Burnham, Karen

    2013-01-01

    This innovation consists of a pyrotechnic initiator and piezoelectric initiation system. The device will be capable of being initiated mechanically; resisting initiation by EMF, RF, and EMI (electromagnetic field, radio frequency, and electromagnetic interference, respectively); and initiating in water environments and space environments. Current devices of this nature are initiated by the mechanical action of a firing pin against a primer. Primers historically are prone to failure. These failures are commonly known as misfires or hang-fires. In many cases, the primer shows the dent where the firing pin struck the primer, but the primer failed to fire. In devices such as "T" handles, which are commonly used to initiate the blowout of canopies, loss of function of the device may result in loss of crew. In devices such as flares or smoke generators, failure can result in failure to spot a downed pilot. The piezoelectrically initiated ignition system consists of a pyrotechnic device that plugs into a mechanical system (activator), which on activation, generates a high-voltage spark. The activator, when released, will strike a stack of electrically linked piezo crystals, generating a high-voltage, low-amperage current that is then conducted to the pyro-initiator. Within the initiator, an electrode releases a spark that passes through a pyrotechnic first-fire mixture, causing it to combust. The combustion of the first-fire initiates a primary pyrotechnic or explosive powder. If used in a "T" handle, the primary would ramp the speed of burn up to the speed of sound, generating a shock wave that would cause a high explosive to go "high order." In a flare or smoke generator, the secondary would produce the heat necessary to ignite the pyrotechnic mixture. The piezo activator subsystem is redundant in that a second stack of crystals would be struck at the same time with the same activation force, doubling the probability of a first strike spark generation. If the first

  14. TAF7: traffic controller in transcription initiation.

    PubMed

    Gegonne, Anne; Devaiah, Ballachanda N; Singer, Dinah S

    2013-01-01

    TAF7, a component of the TFIID complex, controls the first steps of transcription. It interacts with and regulates the enzymatic activities of transcription factors that regulate RNA polymerase II progression. Its diverse functions in transcription initiation are consistent with its essential role in cell proliferation.

  15. Tunnelling from non-localised initial states

    NASA Technical Reports Server (NTRS)

    Bowcock, Peter; Gregory, Ruth

    1991-01-01

    An approach for calculating tunneling amplitudes from a nonlocalized initial state is presented. Generalizing the matching conditions and equations of motion to allow for complex momentum permits a description of tunneling in the presence of so-called classical motion. Possible applications of the method are presented.

  16. Complex derivatives

    NASA Astrophysics Data System (ADS)

    Battiston, Stefano; Caldarelli, Guido; Georg, Co-Pierre; May, Robert; Stiglitz, Joseph

    2013-03-01

    The intrinsic complexity of the financial derivatives market has emerged as both an incentive to engage in it, and a key source of its inherent instability. Regulators now faced with the challenge of taming this beast may find inspiration in the budding science of complex systems.

  17. Designing Complexity

    ERIC Educational Resources Information Center

    Glanville, Ranulph

    2007-01-01

    This article considers the nature of complexity and design, as well as relationships between the two, and suggests that design may have much potential as an approach to improving human performance in situations seen as complex. It is developed against two backgrounds. The first is a world view that derives from second order cybernetics and radical…

  18. Research on diabatic initialization

    NASA Technical Reports Server (NTRS)

    Kashara, Akira

    1993-01-01

    The objective of this research is to contribute to the improvement of the analyses of irrotational wind and moisture fields in the tropics through advancement in the technique of initialization, incorporating diabatic effects and use of satellite-derived, radiometric imagery data that are not used currently by operational centers. Significant accomplishments during the period of May 1991 - April 1992 in research involving the following are presented: impact of tropical initialization upon the spin-up of precipitation forecasts; and a unified approach to diabatic initialization for improvement in the analysis of divergence and water vapor fields in the tropics. Focus of current research and plans for next year are discussed with respect to the topics of controlling the precipitation over shoot during the early part of a numerical forecast and the use of satellite imagery data for improvement of the tropical analysis.

  19. On the initiation of subduction

    NASA Technical Reports Server (NTRS)

    Mueller, Steve; Phillips, Roger J.

    1991-01-01

    Estimates of shear resistance associated with lithospheric thrusting and convergence represent lower bounds on the force necessary to promote trench formation. Three environments proposed as preferential sites of incipient subduction are investigated: passive continental margins, transform faults/fracture zones, and extinct ridges. None of these are predicted to convert into subduction zones simply by the accumulation of local gravitational stresses. Subduction cannot initiate through the foundering of dense oceanic lithosphere immediately adjacent to passive continental margins. The attempted subduction of buoyant material at a mature trench can result in large compressional forces in both subducting and overriding plates. This is the only tectonic force sufficient to trigger the nucleation of a new subduction zone. The ubiquitous distribution of transform faults and fracture zones, combined with the common proximity of these features to mature subduction complexes, suggests that they may represent the most likely sites of trench formation if they are even marginally weaker than normal oceanic lithosphere.

  20. On the initiation of subduction

    SciTech Connect

    Mueller, S.; Phillips, R.J. )

    1991-01-10

    Estimates of shear resistance associated with lithospheric thrusting and convergence represent lower bounds on the force necessary to promote trench formation. Three environments proposed as preferential sites of incipient subduction are investigated: passive continental margins, transform faults/fracture zones, and extinct ridges. None of these are predicted to convert into subduction zones simply by the accumulation of local gravitational stresses. Subduction cannot initiate through the foundering of dense oceanic lithosphere immediately adjacent to passive continental margins. The attempted subduction of buoyant material at a mature trench can result in large compressional forces in both subducting and overriding plates. This is the only tectonic force sufficient to trigger the nucleation of a new subduction zone. The ubiquitous distribution of transform faults and fracture zones, combined with the common proximity of these features to mature subduction complexes, suggests that they may represent the most likely sites of trench formation if they are even marginally weaker than normal oceanic lithosphere.

  1. Civil space technology initiative

    NASA Technical Reports Server (NTRS)

    1990-01-01

    The Civil Space Technology Initiative (CSTI) is a major, focused, space technology program of the Office of Aeronautics, Exploration and Technology (OAET) of NASA. The program was initiated to advance technology beyond basic research in order to expand and enhance system and vehicle capabilities for near-term missions. CSTI takes critical technologies to the point at which a user can confidently incorporate the new or expanded capabilities into relatively near-term, high-priority NASA missions. In particular, the CSTI program emphasizes technologies necessary for reliable and efficient access to and operation in Earth orbit as well as for support of scientific missions from Earth orbit.

  2. Clean Coal Power Initiative

    SciTech Connect

    Doug Bartlett; Rob James; John McDermott; Neel Parikh; Sanjay Patnaik; Camilla Podowski

    2006-03-31

    This report is the fifth quarterly Technical Progress Report submitted by NeuCo, Incorporated, under Award Identification Number, DE-FC26-04NT41768. This award is part of the Clean Coal Power Initiative (''CCPI''), the ten-year, $2B initiative to demonstrate new clean coal technologies in the field. This report is one of the required reports listed in Attachment B Federal Assistance Reporting Checklist, part of the Cooperative Agreement. The report covers the award period January 1, 2006 - March 31, 2006 and NeuCo's efforts within design, development, and deployment of on-line optimization systems during that period.

  3. Life’s Order, Complexity, Organization, and Its Thermodynamic–Holistic Imperatives

    PubMed Central

    Egel, Richard

    2012-01-01

    In memoriam Jeffrey S. Wicken (1942–2002)—the evolutionarily minded biochemist, who in the 1970/80s strived for a synthesis of biological and physical theories to fathom the tentative origins of life. Several integrative concepts are worth remembering from Wicken’s legacy. (i) Connecting life’s origins and complex organization to a preexisting physical world demands a thermodynamically sound transition. (ii) Energetic ‘charging’ of the prebiosphere must precede the emergence of biological organization. (iii) Environmental energy gradients are exploited progressively, approaching maximum interactive structure and minimum dissipation. (iv) Dynamic self-assembly of prebiotic organic matter is driven by hydrophobic tension between water and amphiphilic building blocks, such as aggregating peptides from non-polar amino acids and base stacking in nucleic acids. (v) The dynamics of autocatalytic self-organization are facilitated by a multiplicity of weak interactions, such as hydrogen bonding, within and between macromolecular assemblies. (vi) The coevolution of (initially uncoded) proteins and nucleic acids in energy-coupled and metabolically active so-called ‘microspheres’ is more realistic as a kinetic transition model of primal biogenesis than ‘hypercycle replication’ theories for nucleic acid replicators on their own. All these considerations blend well with the current understanding that sunlight UV-induced photo-electronic excitation of colloidal metal sulfide particles appears most suitable as a prebiotic driver of organic synthesis reactions, in tight cooperation with organic, phase-separated, catalytic ‘microspheres’. On the ‘continuist vs. miraculist’ schism described by Iris Fry for origins-of-life considerations (Table 1), Wicken was a fervent early protagonist of holistic ‘continuist’ views and agenda. PMID:25371269

  4. Mixed-Initiative Clustering

    ERIC Educational Resources Information Center

    Huang, Yifen

    2010-01-01

    Mixed-initiative clustering is a task where a user and a machine work collaboratively to analyze a large set of documents. We hypothesize that a user and a machine can both learn better clustering models through enriched communication and interactive learning from each other. The first contribution or this thesis is providing a framework of…

  5. Best Practices & Outstanding Initiatives

    ERIC Educational Resources Information Center

    Training, 2011

    2011-01-01

    In this article, "Training" editors recognize innovative and successful learning and development programs and practices. They share best practices from Automatic Data Processing, Inc., Farmers Insurance Group, FedEx Express, InterContinental Hotels Group, and Oakwood Temporary Housing. They also present the outstanding initiatives of EMD Serono,…

  6. The SEED Initiative

    ERIC Educational Resources Information Center

    Teich, Carolyn R.

    2011-01-01

    Committed to fulfilling the promise of the green economy, the American Association of Community Colleges (AACC) launched the Sustainability Education and Economic Development (SEED) initiative (www.theseedcenter.org) in October 2010. The project advances sustainability and clean energy workforce development practices at community colleges by…

  7. Envisioning Effective Laptop Initiatives

    ERIC Educational Resources Information Center

    Clausen, Jon M.; Britten, Jody; Ring, Gail

    2008-01-01

    A recent survey of 74 building-level school administrators in Indiana challenged many of the assumptions regarding 1:1 laptop initiatives and how 1:1 access would affect teaching and learning. It also revealed disturbing realities regarding instructional practices of teachers, as well as efforts to improve school technology integration. The intent…

  8. Funds Fuel Graduation Initiatives

    ERIC Educational Resources Information Center

    Gewertz, Catherine

    2010-01-01

    In the first wave of funding under a revitalized high school graduation initiative, the U.S. Department of Education is betting nearly $50 million that it can help states and school districts find better ways to hang onto students who might drop out and bring back those who have disappeared without diplomas. Twenty-nine states and districts won…

  9. Focusing educational initiatives

    NASA Technical Reports Server (NTRS)

    Parks, George K.

    1990-01-01

    The United States will soon be facing a critical shortage of aerospace scientists and engineers. To address this problem, Space Grant Colleges can assist in focusing interest in existing educational initiatives and in creating new educational opportunities, particularly for women and underrepresented minorities.

  10. Clean Energy Manufacturing Initiative

    SciTech Connect

    2013-04-01

    The initiative will strategically focus and rally EERE’s clean energy technology offices and Advanced Manufacturing Office around the urgent competitive opportunity for the United States to be the leader in the clean energy manufacturing industries and jobs of today and tomorrow.

  11. Monolithic exploding foil initiator

    DOEpatents

    Welle, Eric J; Vianco, Paul T; Headley, Paul S; Jarrell, Jason A; Garrity, J. Emmett; Shelton, Keegan P; Marley, Stephen K

    2012-10-23

    A monolithic exploding foil initiator (EFI) or slapper detonator and the method for making the monolithic EFI wherein the exploding bridge and the dielectric from which the flyer will be generated are integrated directly onto the header. In some embodiments, the barrel is directly integrated directly onto the header.

  12. Transformative Change Initiative

    ERIC Educational Resources Information Center

    Bragg, D. D.; Kirby, C.; Witt, M. A.; Richie, D.; Mix, S.; Feldbaum, M.; Liu, S.; Mason, M.

    2014-01-01

    The Transformative Change Initiative (TCI) is dedicated to assisting community colleges to scale up innovation in the form of guided pathways, programs of study, and evidence-based strategies to improve student outcomes and program, organization, and system performance. The impetus for TCI is the Trade Adjustment Assistance Community College and…

  13. Global healthy backpack initiatives.

    PubMed

    Jayaratne, Kapila; Jacobs, Karen; Fernando, Dulitha

    2012-01-01

    Schoolbag use by children is a global common concern.. Children carry school books and other amenities in their school bags. Global evidence indicates that daily load carried by school children may have negative health implications. Backpack as a school bag model, is the healthiest way of load carriage for school children. Several initiatives have been launched world over to minimize unhealthy consequences resulting from schoolbags. Based on a situation analysis, Sri Lanka implemented a national healthy schoolbag campaign by joint efforts of Ministries of Health and Education. Actions were contemplated on; strategies for bag weight reduction, introduction of an ergonomically modeled schoolbag and bag behaviour change. New strategies were introduced with awareness campaigns to policy makers, bag manufacturers, parents, teachers and children. Four million schoolchildren benefitted. In 2000, the backpack strategy of "Pack it Light, Wear it Right" was started as a public health initiative in the United States by the American Occupational Therapy Association (AOTA). Over the last eleven years, thousands of occupational therapy practitioners and students participated in educational programs and outreach activities. In 2004, modeled after the success AOTA initiative, the Icelandic Occupational Therapy Association launched a national backpack awareness initiative. This article shares examples of practices that could be implemented in any context to the promote health of children.

  14. Initiating Change in Schools.

    ERIC Educational Resources Information Center

    Bowers, Bruce C.

    1990-01-01

    Schools are expected not only to conserve society's values and standards, but to be dynamic organizations with built-in mechanisms for incorporating rapid, far-reaching change. Although change is unlikely unless at least one highly motivated individual assumes the role of initial change agent, lasting change requires more than the efforts of a…

  15. Taking Initiative on Writing

    ERIC Educational Resources Information Center

    Gere, Anne Ruggles

    2010-01-01

    A strong schoolwide writing program supports learning across disciplines and provides a focus for collaboration and professional development for all teachers. The elements for schoolwide writing initiatives include: (1) Setting schoolwide goals for student achievement in writing; (2) Developing and implementing action steps that address both…

  16. Harmonization Initiatives in Europe

    PubMed Central

    2016-01-01

    Introduction Modern medicine is more and more based on protocols and guidelines; clinical laboratory data play very often a relevant role in these documents and for this reason the need for their harmonization is increasing. To achieve harmonized results the harmonization process must not be limited to only the analytical part, but has to include the pre- and the post-analytical phases. Results To fulfill this need the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) has started several initiatives. A Working Group on harmonization of the total testing process (WG-H) has been created with the aims of: 1) surveying and summarizing national European and pan European harmonization initiatives; 2) promoting and coordinating the dissemination of especially promising harmonization initiatives among the EFLM member societies; and 3) taking initiatives to harmonize nomenclature, units and reference intervals at a European level. The activity of the WG started this year with a questionnaire targeted at surveying the status of various harmonization activities, especially those in the pre- and post-analytical phase categories, among the European laboratory medicine societies. Conclusions Based on the results of the questionnaire, some activities promoting the dissemination of best practice in blood sampling, sample storage and transportation, in collaboration with WG on the pre-analytical phase, will be promoted, and initiatives to spread to all the European countries the use of SI units in reporting, will be undertaken. Moreover, EFLM has created a Task and Finish Group on standardization of the color coding for blood collection tube closures that is actively working to accomplish this difficult task through collaboration with manufacturers. PMID:27683503

  17. Next generation initiation techniques

    NASA Technical Reports Server (NTRS)

    Warner, Tom; Derber, John; Zupanski, Milija; Cohn, Steve; Verlinde, Hans

    1993-01-01

    Four-dimensional data assimilation strategies can generally be classified as either current or next generation, depending upon whether they are used operationally or not. Current-generation data-assimilation techniques are those that are presently used routinely in operational-forecasting or research applications. They can be classified into the following categories: intermittent assimilation, Newtonian relaxation, and physical initialization. It should be noted that these techniques are the subject of continued research, and their improvement will parallel the development of next generation techniques described by the other speakers. Next generation assimilation techniques are those that are under development but are not yet used operationally. Most of these procedures are derived from control theory or variational methods and primarily represent continuous assimilation approaches, in which the data and model dynamics are 'fitted' to each other in an optimal way. Another 'next generation' category is the initialization of convective-scale models. Intermittent assimilation systems use an objective analysis to combine all observations within a time window that is centered on the analysis time. Continuous first-generation assimilation systems are usually based on the Newtonian-relaxation or 'nudging' techniques. Physical initialization procedures generally involve the use of standard or nonstandard data to force some physical process in the model during an assimilation period. Under the topic of next-generation assimilation techniques, variational approaches are currently being actively developed. Variational approaches seek to minimize a cost or penalty function which measures a model's fit to observations, background fields and other imposed constraints. Alternatively, the Kalman filter technique, which is also under investigation as a data assimilation procedure for numerical weather prediction, can yield acceptable initial conditions for mesoscale models. The

  18. A discussion of numerical subduction initiation

    NASA Astrophysics Data System (ADS)

    Buiter, Susanne; Ellis, Susan

    2016-04-01

    In nature, subduction can initiate in various ways: Shortening can localise at oceanic transform faults, extinct spreading centres, or inherited passive margin faults; or, alternatively, subduction can be triggered from existing subduction systems by along-strike trench propagation, polarity reversals, or trench jumps. Numerical studies that specifically address subduction initiation have highlighted the roles of sediment loading, rheological strength contrasts, strain softening, and continental topographic gradients, among others. Usually, however, numerical models that aim to investigate subduction dynamics prefer to bypass the subduction initiation phase and its complexities, and focus instead on the stages during which the slab is descending into the mantle. However, even in these models, subduction still needs to begin. It is disturbingly easy to define initial model geometries that do not result in subduction. The specific combination of initial model geometries and values for rheological parameters that successfully initiates subduction has even been referred to as 'the sweet spot' in model space. One cause of subduction initiation failure is when the subducting and overriding plates lock, resulting in either indentation or severe dragging downwards of the overriding plate. This may point to a difficulty in maintaining a weak subduction interface during model evolution. A second factor that may cause difficulties is that initial model geometry and stresses need to balance, as otherwise the first model stages may show spurious deformation associated with reaching equilibrium. A third requirement that may cause problems is that the surface needs to have sufficient displacement freedom to allow the overriding plate to overthrust the subducting plate. That also implies an exclusion of sharp corners in the subduction interface near the surface. It is the interplay of subduction interface geometry, interface strength and subducting plate rheology that determines

  19. Carney Complex

    MedlinePlus

    ... Screening guidelines may change over time as new technologies are developed and more is learned about Carney complex. It is important to talk with your doctor about appropriate screening tests. Learn more about what to expect when having ...

  20. The Biophysics Microgravity Initiative

    NASA Technical Reports Server (NTRS)

    Gorti, S.

    2016-01-01

    Biophysical microgravity research on the International Space Station using biological materials has been ongoing for several decades. The well-documented substantive effects of long duration microgravity include the facilitation of the assembly of biological macromolecules into large structures, e.g., formation of large protein crystals under micro-gravity. NASA is invested not only in understanding the possible physical mechanisms of crystal growth, but also promoting two flight investigations to determine the influence of µ-gravity on protein crystal quality. In addition to crystal growth, flight investigations to determine the effects of shear on nucleation and subsequent formation of complex structures (e.g., crystals, fibrils, etc.) are also supported. It is now considered that long duration microgravity research aboard the ISS could also make possible the formation of large complex biological and biomimetic materials. Investigations of various materials undergoing complex structure formation in microgravity will not only strengthen NASA science programs, but may also provide invaluable insight towards the construction of large complex tissues, organs, or biomimetic materials on Earth.

  1. Electrogenic Tuning of the Axon Initial Segment

    PubMed Central

    Clark, Brian D.; Goldberg, Ethan M.; Rudy, Bernardo

    2010-01-01

    Action potentials (APs) provide the primary means of rapid information transfer in the nervous system. Where exactly these signals are initiated in neurons has been a basic question in neurobiology and the subject of extensive study. Converging lines of evidence indicate that APs are initiated in a discrete and highly specialized portion of the axon—the axon initial segment (AIS). The authors review key aspects of the organization and function of the AIS and focus on recent work that has provided important insights into its electrical signaling properties. In addition to its main role in AP initiation, the new findings suggest that the AIS is also a site of complex AP modulation by specific types of ion channels localized to this axonal domain. PMID:20007821

  2. Gravity wave initiated convection

    NASA Technical Reports Server (NTRS)

    Hung, R. J.

    1990-01-01

    The vertical velocity of convection initiated by gravity waves was investigated. In one particular case, the convective motion-initiated and supported by the gravity wave-induced activity (excluding contributions made by other mechanisms) reached its maximum value about one hour before the production of the funnel clouds. In another case, both rawinsonde and geosynchronous satellite imagery were used to study the life cycles of severe convective storms. Cloud modelling with input sounding data and rapid-scan imagery from GOES were used to investigate storm cloud formation, development and dissipation in terms of growth and collapse of cloud tops, as well as, the life cycles of the penetration of overshooting turrets above the tropopause. The results based on these two approaches are presented and discussed.

  3. The space exploration initiative

    NASA Technical Reports Server (NTRS)

    Priest, Pete

    1991-01-01

    A number of view graph charts are presented which outline the presentation. Outlined are reasons for going to Mars, why it is necessary to go to the Moon first, and the presidential decision on the space exploration initiative. Other representative charts are entitled: Lunar transportation system requirement drivers; Mars transportation system requirement drivers; National space policy goals; Exploration hardware needed; Mars mission profile; Science on the Moon and Mars; and Two independent reviews.

  4. International perspectives and initiatives.

    PubMed

    Murphy, Jeannette

    2007-03-01

    This article introduces a new column which will explore the way different regions and nation states are dealing with the challenges of managing health information. The intention is to draw together trends which are relevant to both health science librarians and health informatics professionals. This inaugural piece maps out the territory. It provides a rationale for the column, along with evidence of current initiatives to articulate a global perspective on the application of communication and information technologies to health information. PMID:17331146

  5. Complex networks: Patterns of complexity

    NASA Astrophysics Data System (ADS)

    Pastor-Satorras, Romualdo; Vespignani, Alessandro

    2010-07-01

    The Turing mechanism provides a paradigm for the spontaneous generation of patterns in reaction-diffusion systems. A framework that describes Turing-pattern formation in the context of complex networks should provide a new basis for studying the phenomenon.

  6. Precision flyer initiator

    SciTech Connect

    Frank, A

    1999-04-19

    A propulsion point design is presented for lifting geological samples from Mars. Vehicle complexity is kept low by choosing a monopropellant single stage. Little new development is needed, as miniature pump fed hydrazine has been demonstrated. Loading the propellant just prior to operation avoids structural, thermal, and safety constraints otherwise imposed by earlier mission phases. hardware mass and engineering effort are thereby diminished. The Mars liftoff mass is 7/8 hydrazine, <5% propulsion hardware, and >3% each for the payload and guidance.

  7. Complex chimerism

    PubMed Central

    Ma, Kimberly K.; Petroff, Margaret G.; Coscia, Lisa A.; Armenti, Vincent T.; Adams Waldorf, Kristina M.

    2013-01-01

    Thousands of women with organ transplantation have undergone successful pregnancies, however little is known about how the profound immunologic changes associated with pregnancy might influence tolerance or rejection of the allograft. Pregnant women with a solid organ transplant are complex chimeras with multiple foreign cell populations from the donor organ, fetus, and mother of the pregnant woman. We consider the impact of complex chimerism and pregnancy-associated immunologic changes on tolerance of the allograft both during pregnancy and the postpartum period. Mechanisms of allograft tolerance are likely dynamic during pregnancy and affected by the influx of fetal microchimeric cells, HLA relationships (between the fetus, pregnant woman and/or donor), peripheral T cell tolerance to fetal cells, and fetal minor histocompatibility antigens. Further research is necessary to understand the complex immunology during pregnancy and the postpartum period of women with a solid organ transplant. PMID:23974274

  8. Canonical eukaryotic initiation factors determine initiation of translation by internal ribosomal entry.

    PubMed Central

    Pestova, T V; Hellen, C U; Shatsky, I N

    1996-01-01

    Translation of picornavirus RNA is initiated after ribosomal binding to an internal ribosomal entry site (IRES) within the 5' untranslated region. We have reconstituted IRES-mediated initiation on encephalomyocarditis virus RNA from purified components and used primer extension analysis to confirm the fidelity of 48S preinitiation complex formation. Eukaryotic initiation factor 2 (eIF2), eIF3, and eIF4F were required for initiation; eIF4B and to a lesser extent the pyrimidine tract-binding protein stimulated this process. We show that eIF4F binds to the IRES in a novel cap-independent manner and suggest that cap- and IRES-dependent initiation mechanisms utilize different modes of interaction with this factor to promote ribosomal attachment to mRNA. PMID:8943341

  9. 70S-scanning initiation is a novel and frequent initiation mode of ribosomal translation in bacteria

    PubMed Central

    Yamamoto, Hiroshi; Wittek, Daniela; Gupta, Romi; Qin, Bo; Ueda, Takuya; Krause, Roland; Yamamoto, Kaori; Albrecht, Renate; Pech, Markus; Nierhaus, Knud H.

    2016-01-01

    According to the standard model of bacterial translation initiation, the small ribosomal 30S subunit binds to the initiation site of an mRNA with the help of three initiation factors (IF1–IF3). Here, we describe a novel type of initiation termed “70S-scanning initiation,” where the 70S ribosome does not necessarily dissociate after translation of a cistron, but rather scans to the initiation site of the downstream cistron. We detailed the mechanism of 70S-scanning initiation by designing unique monocistronic and polycistronic mRNAs harboring translation reporters, and by reconstituting systems to characterize each distinct mode of initiation. Results show that 70S scanning is triggered by fMet-tRNA and does not require energy; the Shine–Dalgarno sequence is an essential recognition element of the initiation site. IF1 and IF3 requirements for the various initiation modes were assessed by the formation of productive initiation complexes leading to synthesis of active proteins. IF3 is essential and IF1 is highly stimulating for the 70S-scanning mode. The task of IF1 appears to be the prevention of untimely interference by ternary aminoacyl (aa)-tRNA•elongation factor thermo unstable (EF-Tu)•GTP complexes. Evidence indicates that at least 50% of bacterial initiation events use the 70S-scanning mode, underscoring the relative importance of this translation initiation mechanism. PMID:26888283

  10. Initial blood storage experiment

    NASA Technical Reports Server (NTRS)

    Surgenor, Douglas MACN.

    1988-01-01

    The design of the Initial Blood Storage Experiment (IBSE) was based upon a carefully controlled comparison between identical sets of human blood cell suspensions - red cells, white cell, and platelets - one set of which was transported aboard the Columbia on a 6 day 11 hour mission, and the other held on the ground. Both sets were carried inside stainless steel dewars within specially fabricated flight hardware. Individual bags of cell suspensions were randomly assigned with respect to ground vs orbit status, dewar chamber, and specific location within the dewar. To foster optimal preservation, each cell type was held under specific optimal conditions of pH, ionic strength, solute concentration, gas tension, and temperature. An added variable in this initial experiment was provided by the use of three different polymer/plasticizer formulations for the sealed bags which held the blood cells. At termination of the experiment, aliquots of the suspensions, identified only by code, were distributed to be assayed. Assays were selected to constitute a broad survey of cellular properties and thereby maximize the chances of detection of gravitational effects. A total of 74 different outcome measurements were reported for statistical analysis. When the measurements were completed, the results were entered into the IBSE data base, at which time the data were matched with the original blood bag numbers to determine their status with respect to polymer/plasticizer type, orbit status (orbit or ground), and storage position within the experimental hardware. The data were studied by analysis of variance. Initially, type of bag and orbital status were main factors; later more detailed analyses were made on specific issues such as position in the hardware and specific plastic. If the analysis of variance indicated a statistical significance at the 5 percent level the corresponding p-value was reported.

  11. Through bulkhead initiator studies

    SciTech Connect

    Begeal, D.R.

    1997-03-01

    This report describes recent work done to demonstrate feasibility of a fail-safe Through Bulkhead Initiator with minimum dimensions and suitable for use in cyclical thermal environments. Much of the ground work for a fail-safe TBI was previously done by A.C. Schwartz. This study is an expansion of Schwartz`s work to evaluate devices with bulkheads of 304 stainless steel and Inconel 718; explosive donors of PETN, BNCP, and a 0.005 inch thick steel flying plate donor traveling at 2.6 mm/{micro}s; and explosive acceptors of PETN and BNCP. Bulkhead thickness were evaluated in the range of 0.040 to 0.180 inch. The explosive acceptors initiated a small HMX pellet to drive a 0.005 inch thick steel flying plate, and VISAR histories of the HMX-driven flying plates were the measure of acceptable performance. A companion set of samples used a PMMA acceptor to measure the particle velocities at the bulkhead/PMMA interface with VISAR. These data were used to compute the input pressure to the acceptor explosives in an attempt to measure initiation threshold. Unfortunately, the range of bulkhead thicknesses tested did not give any failures, thus the threshold was not determined. It was found that either explosive or the flying plate would perform as a TBI in the bulkhead thickness range tested. The optimum TBI is about 0.060 inches thick, and steel bulkheads seem to be more structurally sound than those made of Inconel. That is, cross section views of the Inconel bulkheads showed it to be more prone to stress cracking than was the 304 stainless steel. Both PETN and BNCP showed good performance when tested at {minus}65 F following thermal cycling of {minus}65 F to +165 F. Analysis of the TBI function times showed that BNCP acceptor explosives were undergoing the classical deflagration to detonation process. The PETN acceptors were undergoing prompt detonation.

  12. Human Research Initiative (HRI)

    NASA Technical Reports Server (NTRS)

    Motil, Brian

    2003-01-01

    A code U initiative starting in the FY04 budget includes specific funding for 'Phase Change' and 'Multiphase Flow Research' on the ISS. NASA GRC developed a concept for two facilities based on funding/schedule constraints: 1) Two Phase Flow Facility (TphiFFy) which assumes integrating into FIR; 2) Contact Line Dynamics Experiment Facility (CLiDE) which assumes integration into MSG. Each facility will accommodate multiple experiments conducted by NRA selected PIs with an overall goal of enabling specific NASA strategic objectives. There may also be a significant ground-based component.

  13. Feedback stabilization initiative

    SciTech Connect

    1997-06-01

    Much progress has been made in attaining high confinement regimes in magnetic confinement devices. These operating modes tend to be transient, however, due to the onset of MHD instabilities, and their stabilization is critical for improved performance at steady state. This report describes the Feedback Stabilization Initiative (FSI), a broad-based, multi-institutional effort to develop and implement methods for raising the achievable plasma betas through active MHD feedback stabilization. A key element in this proposed effort is the Feedback Stabilization Experiment (FSX), a medium-sized, national facility that would be specifically dedicated to demonstrating beta improvement in reactor relevant plasmas by using a variety of MHD feedback stabilization schemes.

  14. UNLV Nuclear Hydrogen Initiative

    SciTech Connect

    Hechanova, Anthony E.; Johnson, Allen; O'Toole, Brendan; Trabia, Mohamed; Peterson, Per

    2012-10-25

    Evaluation of the Crack growth rate (CGR) of Alloy 617 and Alloy 276 under constant K at ambient temperature has been completed. Creep deformation of Alloy 230 at different temperature range and load level has been completed and heat to heat variation has been noticed. Creep deformation study of Alloy 276 has been completed under an applied initial stress level of 10% of yield stress at 950ºC. The grain size evaluation of the tested creep specimens of Alloy 276 has been completed.

  15. Advanced Monitoring systems initiative

    SciTech Connect

    R.J. Venedam; E.O. Hohman; C.F. Lohrstorfer; S.J. Weeks; J.B. Jones; W.J. Haas

    2004-09-30

    The Advanced Monitoring Systems Initiative (AMSI) actively searches for promising technologies and aggressively moves them from the research bench into DOE/NNSA end-user applications. There is a large unfulfilled need for an active element that reaches out to identify and recruit emerging sensor technologies into the test and evaluation function. Sensor research is ubiquitous, with the seeds of many novel concepts originating in the university systems, but at present these novel concepts do not move quickly and efficiently into real test environments. AMSI is a widely recognized, self-sustaining ''business'' accelerating the selection, development, testing, evaluation, and deployment of advanced monitoring systems and components.

  16. Hanford tanks initiative plan

    SciTech Connect

    McKinney, K.E.

    1997-07-01

    Abstract: The Hanford Tanks Initiative (HTI) is a five-year project resulting from the technical and financial partnership of the U.S. Department of Energy`s Office of Waste Management (EM-30) and Office of Science and Technology Development (EM-50). The HTI project accelerates activities to gain key technical, cost performance, and regulatory information on two high-level waste tanks. The HTI will provide a basis for design and regulatory decisions affecting the remainder of the Tank Waste Remediation System`s tank waste retrieval Program.

  17. Stirling to Flight Initiative

    NASA Technical Reports Server (NTRS)

    Hibbard, Kenneth E.; Mason, Lee S.; Ndu, Obi; Smith, Clayton; Withrow, James P.

    2016-01-01

    Flight (S2F) initiative with the objective of developing a 100-500 We Stirling generator system. Additionally, a different approach is being devised for this initiative to avoid pitfalls of the past, and apply lessons learned from the recent ASRG experience. Two key aspects of this initiative are a Stirling System Technology Maturation Effort, and a Surrogate Mission Team (SMT) intended to provide clear mission pull and requirements context. The S2F project seeks to lead directly into a DOE flight system development of a new SRG. This paper will detail the proposed S2F initiative, and provide specifics on the key efforts designed to pave a forward path for bringing Stirling technology to flight.

  18. Initiation of slug flow

    SciTech Connect

    Hanratty, T.J.; Woods, B.D.

    1995-12-31

    The initiation of slug flow in a horizontal pipe can be predicted either by considering the stability of a slug or by considering the stability of a stratified flow. Measurements of the shedding rate of slugs are used to define necessary conditions for the existence of a slug. Recent results show that slugs develop from an unstable stratified flow through the evolution of small wavelength waves into large wavelength waves that have the possibility of growing to form a slug. The mechanism appears to be quite different for fluids with viscosities close to water than for fluids with large viscosities (20 centipoise).

  19. Researching Complexity.

    ERIC Educational Resources Information Center

    Sumara, Dennis J.

    2000-01-01

    Discusses what Complexity Theory (presented as a rubric that collects theoretical understandings from a number of domains such as ecology, biology, neurology, and education) suggests about mind, selfhood, intelligence, and practices of reading, and the import of these reconceptualizations to reader-response researchers. Concludes that developing…

  20. Complex interactions

    NASA Astrophysics Data System (ADS)

    de Régules, Sergio

    2016-04-01

    Complexity science - which describes phenomena such as collective and emergent behaviour - is the focus of a new centre where researchers are examining everything from the spread of influenza to what a healthy heartbeat looks like. Sergio de Régules reports.

  1. Amorphic complexity

    NASA Astrophysics Data System (ADS)

    Fuhrmann, G.; Gröger, M.; Jäger, T.

    2016-02-01

    We introduce amorphic complexity as a new topological invariant that measures the complexity of dynamical systems in the regime of zero entropy. Its main purpose is to detect the very onset of disorder in the asymptotic behaviour. For instance, it gives positive value to Denjoy examples on the circle and Sturmian subshifts, while being zero for all isometries and Morse-Smale systems. After discussing basic properties and examples, we show that amorphic complexity and the underlying asymptotic separation numbers can be used to distinguish almost automorphic minimal systems from equicontinuous ones. For symbolic systems, amorphic complexity equals the box dimension of the associated Besicovitch space. In this context, we concentrate on regular Toeplitz flows and give a detailed description of the relation to the scaling behaviour of the densities of the p-skeletons. Finally, we take a look at strange non-chaotic attractors appearing in so-called pinched skew product systems. Continuous-time systems, more general group actions and the application to cut and project quasicrystals will be treated in subsequent work.

  2. Star wars: A question of initiative

    SciTech Connect

    Ennals, R.

    1987-01-01

    This book discusses U.K. and European participation in the Strategic Defense Initiative. The author, a cofounder of The Strategic Research Initiative, participated in research and research management concerned with developing tools for analyzing the complexity of nuclear diplomacy and how international politics are affected by the new technology. It covers research and varying national strategies for applying advanced information technology, intelligent machinery, logic programming in both education and training, and artificial intelligence issues. It introduces the field of computational politics, examining the political importance of computer systems and computational concepts that can help analyze complex political phenomena. It also gives special attention to the American SDI, ''Star Wars,'' which has necessitated the development and deployment of new techniques of political analysis. A section on constructive alternatives to SDI is also included.

  3. Cell complexes through time

    NASA Astrophysics Data System (ADS)

    Klette, Reinhard

    2000-10-01

    The history of cell complexes is closely related to the birth and development of topology in general. Johann Benedict Listing (1802 - 1882) introduced the term 'topology' into mathematics in a paper published in 1847, and he also defined cell complexes for the first time in a paper published in 1862. Carl Friedrich Gauss (1777 - 1855) is often cited as the one who initiated these ideas, but he did not publish either on topology or on cell complexes. The pioneering work of Leonhard Euler (1707 - 1783) on graphs is also often cited as the birth of topology, and Euler's work was cited by Listing in 1862 as a stimulus for his research on cell complexes. There are different branches in topology which have little in common: point set topology, algebraic topology, differential topology etc. Confusion may arise if just 'topology' is specified, without clarifying the used concept. Topological subjects in mathematics are often related to continuous models, and therefore quite irrelevant to computer based solutions in image analysis. Compared to this, only a minority of topology publications in mathematics addresses discrete spaces which are appropriate for computer-based image analysis. In these cases, often the notion of a cell complex plays a crucial role. This paper briefly reports on a few of these publications. This paper is not intended to cover the very lively progress in cell complex studies within the context of image analysis during the last two decades. Basically it stops its historic review at the time when this subject in image analysis research gained speed in 1980 - 1990. As a general point of view, the paper indicates that image analysis contributes to a fusion of topological concepts, the geometric and the abstract cell structure approach and point set topology, which may lead towards new problems for the study of topologies defined on geometric or abstract cell complexes.

  4. Precision flyer initiator

    DOEpatents

    Frank, Alan M.; Lee, Ronald S.

    1998-01-01

    A precision flyer initiator forms a substantially spherical detonation wave in a high explosive (HE) pellet. An explosive driver, such as a detonating cord, a wire bridge circuit or a small explosive, is detonated. A flyer material is sandwiched between the explosive driver and an end of a barrel that contains an inner channel. A projectile or "flyer" is sheared from the flyer material by the force of the explosive driver and projected through the inner channel. The flyer than strikes the HE pellet, which is supported above a second end of the barrel by a spacer ring. A gap or shock decoupling material delays the shock wave in the barrel from predetonating the HE pellet before the flyer. A spherical detonation wave is formed in the HE pellet. Thus, a shock wave traveling through the barrel fails to reach the HE pellet before the flyer strikes the HE pellet. The precision flyer initiator can be used in mining devices, well-drilling devices and anti-tank devices.

  5. Precision flyer initiator

    DOEpatents

    Frank, A.M.; Lee, R.S.

    1998-05-26

    A precision flyer initiator forms a substantially spherical detonation wave in a high explosive (HE) pellet. An explosive driver, such as a detonating cord, a wire bridge circuit or a small explosive, is detonated. A flyer material is sandwiched between the explosive driver and an end of a barrel that contains an inner channel. A projectile or ``flyer`` is sheared from the flyer material by the force of the explosive driver and projected through the inner channel. The flyer than strikes the HE pellet, which is supported above a second end of the barrel by a spacer ring. A gap or shock decoupling material delays the shock wave in the barrel from predetonating the HE pellet before the flyer. A spherical detonation wave is formed in the HE pellet. Thus, a shock wave traveling through the barrel fails to reach the HE pellet before the flyer strikes the HE pellet. The precision flyer initiator can be used in mining devices, well-drilling devices and anti-tank devices. 10 figs.

  6. Global cancer research initiative.

    PubMed

    Love, Richard R

    2010-05-03

    Cancer is an increasing problem for low- and middle-income countries undergoing an epidemiologic transition from dominantly acute communicable disease to more frequent chronic disease with increased public health successes in the former domain. Progress against cancer in high-income countries has been modest and has come at enormous expense. There are several well-conceived global policy and planning initiatives which, with adequate political will, can favorably impact the growing global cancer challenges. Most financial resources for cancer, however, are spent on diagnosis and management of patients with disease in circumstances where specific knowledge about effective approaches is significantly limited, and the majority of interventions, other than surgery, are not cost-effective in resource-limited countries by global standards. In summary, how to intervene effectively on a global scale for the majority of citizens who develop cancer is poorly defined. In contrast to technology-transfer approaches, markedly increased clinical research activities are more likely to benefit cancer sufferers. In these contexts, a global cancer research initiative is proposed, and mechanisms for realizing such an effort are suggested.

  7. Brazilian Nanotechnology Initiative

    NASA Astrophysics Data System (ADS)

    Fazzio, Adalberto

    2015-03-01

    In Brazil there is intense research activity in nanotechnology, most of these developed in universities and research institutes. The Brazilian Nanotechnology Initiative (BNI) aims to integrate government actions to promote the competitiveness of the Brazilian industry. This initiative is founded on support for research and development in the laboratories of the National Laboratories for Nanotechnology (SisNANO), starting from an improvement in infrastructure and opening of laboratories for users of academia and business, promoting interaction and transfer knowledge between academia and business. Country currently has 26 thematic networks of nanotechnology, 16 -Virtual-National Institutes of Technology, seven National- Laboratories and 18 Associate Laboratories, which comprise the SisNANO. Seeking to expand and share governance with other government actors, the Interministries Committee for Nanotechnology was set up, composed of 10 ministries, and has the task of coordinating the entire program of the Federal Government Nanotechnology.Cooperation activities are an important part of BNI. Currently Brazil has cooperation programs with U.S., China, Canada and European Union among others. Recently, Brazil decided to join the European NanoReg program where 60 research groups are joining efforts to provide protocols and standards that can help regulatory agencies and governments.

  8. Humane Neonatal Care Initiative.

    PubMed

    Levin, A

    1999-04-01

    The author has worked for many years in experimental departments in the former Soviet health system. Now, with integration into the western health system, many questions are being asked about high-technology neonatal medicine and whether it is sufficiently humane. The Baby Friendly Hospital Initiative (BFHI) movement is well known all over the world, but unfortunately it is only used for healthy children in maternity hospitals. A paradoxical situation has been created: the routines of maternity wards comply with the BFHI, whereas a neonatal intensive care unit in the same hospital may not meet the requirements of the BFHI. BFHI mainly cover breastfeeding in maternity hospitals. Humane Neonatal Care Initiatives include minimum aggressive therapy, minimum contact between sick newborns and medical staff, and maximum contact with mothers; the number of tests and examinations should be reduced to a minimum. Eleven steps towards the improvement of psychosocial and medical care in units for sick newborns are presented. This article is intended to provoke serious discussion. PMID:10342526

  9. Initiatives for proliferation prevention

    SciTech Connect

    1997-04-01

    Preventing the proliferation of weapons of mass destruction is a central part of US national security policy. A principal instrument of the Department of Energy`s (DOE`s) program for securing weapons of mass destruction technology and expertise and removing incentives for scientists, engineers and technicians in the newly independent states (NIS) of the former Soviet Union to go to rogue countries or assist terrorist groups is the Initiatives for Proliferation Prevention (IPP). IPP was initiated pursuant to the 1994 Foreign Operations Appropriations Act. IPP is a nonproliferation program with a commercialization strategy. IPP seeks to enhance US national security and to achieve nonproliferation objectives by engaging scientists, engineers and technicians from former NIS weapons institutes; redirecting their activities in cooperatively-developed, commercially viable non-weapons related projects. These projects lead to commercial and economic benefits for both the NIS and the US IPP projects are funded in Russian, Ukraine, Kazakhstan and Belarus. This booklet offers an overview of the IPP program as well as a sampling of some of the projects which are currently underway.

  10. Kazakhstan Space Weather Initiative

    NASA Astrophysics Data System (ADS)

    Kryakunova, Olga

    2012-07-01

    Kazakhstan experimental complex is a center of experimental study of space weather. This complex is situated near Almaty, Kazakhstan and includes experimental setup for registration of cosmic ray intensity (neutron monitor) at altitude of 3340 m above sea level, geomagnetic observatory and setup for registration of solar flux density with frequency of 1 and 3 GHz with 1 second time resolution. Results of space environment monitoring in real time are accessible via Internet. This experimental information is used for space weather investigations and different cosmic ray effects. Almaty mountain cosmic ray station is one of the most suitable and sensitive stations for investigation and forecasting of the dangerous situations for satellites; for this reason Almaty cosmic ray station is included in the world-wide neutron monitor network for the real-time monitoring of the space weather conditions and European Database NMDB (www.nmdb.eu). All data are represented on the web-site of the Institute of Ionosphere (www.ionos.kz) in real time. Since July, 2006 the space environment prediction laboratory represents the forecast of geomagnetic activity every day on the same site (www.ionos.kz/?q=en/node/21).

  11. Combined 40Ar/39Ar and Fission-Track study of the Freetown Layered Igneous Complex, Freetown, Sierra Leone, West Africa: Implications for the Initial Break-up of Pangea to form the Central Atlantic Ocean and Insight into the Post-rift Evolution of the Sie

    NASA Astrophysics Data System (ADS)

    Barrie, Ibrahim; Wijbrans, Jan; Andriessen, Paul; Beunk, Frank; Strasser-King, Victor; Fode, Daniel

    2010-05-01

    good plateaus that range from 196.3 ± 3 Ma to 232.1 ± 9 Ma with the best-fit isochron plots showing a range from 193.3± 10 Ma to 234.1 ± 11 Ma. Because these dates represent cooling ages, we interpret them as representing a minimum intrusion-age of the Complex implying that its true emplacement age might be somewhat older than 230 Ma. Given that most established CAMP ages revolve around 200 Ma or younger, we hypothesise that FLIC represents a hitherto unknown pre-CAMP magmatic event that might have thermally triggered the initial break-up of Pangaea to form the Central Atlantic. This view is consistent with field-observations that the Complex is cross-cut by predominantly coast-parallel mafic dykes attributed to the CAMP dyke-swarm. To ascertain the hypothesis, we are currently carrying out U-Pb zircon dating to establish, precisely, the true emplacement age of the Complex. The Fission-track ages vary from 91.7 ± 7 Ma to 114.6 ± 9 Ma. This age range shows that after emplacement and crystallisation, the FLIC underwent an extremely slow cooling for a long period of time. This in turn implies that after the break-up of Pangea to form, in part, the Sierra Leone margin, a late and slow uplift (Erosion/denudation) that took place during the Cretaceous was a very important geological process that characterised the post-rift evolution of the margin. References: Barrie, I.J., P.A.M. Andriessen, F.F. Beunk, J.R. Wijbrans, V.E.H. Strasser-King, D.V.A.Fode. (2006). Tectonothermal Evolution of the Sierra Leone Passive Continental Margin, West Africa: Constraints from Thermochronology. Geochemica et Cosmochemica Acta 70 (18): A36- A36 Suppl. S Aug-Sep 2006. Marzoli, A., P.R. Renne, E.M. Piccirillo, M. Ernesto, G. Bellieni, A De Min. (1999). Extensive 200-Million-Year-Old Continental Flood Basalts of the Central Atlantic Magmatic Province. Science284: 616-618. McHone, J.G. (2000). Non-plume magmatism and rifting during the opening of the central Atlantic Ocean. Tectonophysics

  12. Instrumented Pipeline Initiative

    SciTech Connect

    Thomas Piro; Michael Ream

    2010-07-31

    This report summarizes technical progress achieved during the cooperative agreement between Concurrent Technologies Corporation (CTC) and U.S. Department of Energy to address the need for a for low-cost monitoring and inspection sensor system as identified in the Department of Energy (DOE) National Gas Infrastructure Research & Development (R&D) Delivery Reliability Program Roadmap.. The Instrumented Pipeline Initiative (IPI) achieved the objective by researching technologies for the monitoring of pipeline delivery integrity, through a ubiquitous network of sensors and controllers to detect and diagnose incipient defects, leaks, and failures. This report is organized by tasks as detailed in the Statement of Project Objectives (SOPO). The sections all state the objective and approach before detailing results of work.

  13. The Knowledge Stealing Initiative?

    NASA Technical Reports Server (NTRS)

    Goshorn, Larry

    2005-01-01

    I have the honor of being on the Academy of Program and Project Leadership (APPL) Knowledge Sharing Feedback and Assessment Team (FAA), and as such, I am privileged to receive the feedback written by many of you as attendees of the Project Management (PM) Master s Forums. It is the intent of the FAA Team and APPL leadership to use this feedback as a tool for continuous program improvement. As a retired (sort of) PM in the payload contracting industry, I'm a big supporter of NASA s Knowledge Sharing Initiative (KSI), especially the Master's Forums. I really enjoy participating in them. Unfortunately I had to miss the 8th forum in Pasadena this past Spring, but I did get the feedback package for the Assessment Team work. So here I was, reviewing twelve pages of comments, reflections, learning notes and critiques from attendees of the 8th forum.

  14. The Gossamer Initiative

    NASA Technical Reports Server (NTRS)

    Chmielewski, Artur B.; Moore, Chris; Howard, Rick

    2000-01-01

    The Gossamer Spacecraft Initiative is a new NASA program to begin long-range development of enabling technologies for very large, ultra-lightweight structures and apertures. Large apertures include optical, infrared and submillimeter telescopes, "photon buckets" for optical communications and "non-coherent" imaging, solar concentrators, and radio frequency antennas. Developments in the very large ultra-light structures will be forces on one of their most challenging applications-solar sails. The sail structures will include both 3-axis stabilizing and spinning. Gossamer spacecraft technology will eventually allow NASA to undertake bold new missions of discovery, such as searching for the signs of life on planets orbiting nearby stars and sailing through space on beams of light of places beyond our solar system.

  15. Congress initiates science study

    NASA Astrophysics Data System (ADS)

    Showstack, Randy

    The U.S. House of Representatives announced in October a year-long study to review the nation's science and technology policy and the government's role in funding scientific research. The Science Policy Study, led by Rep. Vernon Ehlers (R-MI), is the first comprehensive review by Congress since 1985—a time when the Cold War still was being fought and the Internet was largely unknown.At a workshop to discuss the initiative, House Science Committee Chair James Sensenbrenner, Jr., told about 30 scientists and policy experts that the challenge is “to develop a new, sensible, coherent long-range science and technology policy, including a review of our nation's science and math education programs.”

  16. Breckinridge Project, initial effort

    SciTech Connect

    None, None

    1982-09-01

    Report III, Volume 1 contains those specifications numbered A through J, as follows: General Specifications (A); Specifications for Pressure Vessels (C); Specifications for Tanks (D); Specifications for Exchangers (E); Specifications for Fired Heaters (F); Specifications for Pumps and Drivers (G); and Specifications for Instrumentation (J). The standard specifications of Bechtel Petroleum Incorporated have been amended as necessary to reflect the specific requirements of the Breckinridge Project, and the more stringent specifications of Ashland Synthetic Fuels, Inc. These standard specifications are available to the Initial Effort (Phase Zero) work performed by all contractors and subcontractors. Report III, Volume 1 also contains the unique specifications prepared for Plants 8, 15, and 27. These specifications will be substantially reviewed during Phase I of the project, and modified as necessary for use during the engineering, procurement, and construction of this project.

  17. MONTANA PALLADIUM RESEARCH INITIATIVE

    SciTech Connect

    Peters, John; McCloskey, Jay; Douglas, Trevor; Young, Mark; Snyder, Stuart; Gurney, Brian

    2012-05-09

    Project Objective: The overarching objective of the Montana Palladium Research Initiative is to perform scientific research on the properties and uses of palladium in the context of the U.S. Department of Energy's Hydrogen, Fuel Cells and Infrastructure Technologies Program. The purpose of the research will be to explore possible palladium as an alternative to platinum in hydrogen-economy applications. To achieve this objective, the Initiatives activities will focus on several cutting-edge research approaches across a range of disciplines, including metallurgy, biomimetics, instrumentation development, and systems analysis. Background: Platinum-group elements (PGEs) play significant roles in processing hydrogen, an element that shows high potential to address this need in the U.S. and the world for inexpensive, reliable, clean energy. Platinum, however, is a very expensive component of current and planned systems, so less-expensive alternatives that have similar physical properties are being sought. To this end, several tasks have been defined under the rubric of the Montana Palladium Research Iniative. This broad swath of activities will allow progress on several fronts. The membrane-related activities of Task 1 employs state-of-the-art and leading-edge technologies to develop new, ceramic-substrate metallic membranes for the production of high-purity hydrogen, and develop techniques for the production of thin, defect-free platinum group element catalytic membranes for energy production and pollution control. The biomimetic work in Task 2 explores the use of substrate-attached hydrogen-producing enzymes and the encapsulation of palladium in virion-based protein coats to determine their utility for distributed hydrogen production. Task 3 work involves developing laser-induced breakdown spectroscopy (LIBS) as a real-time, in situ diagnostic technique to characterize PGEs nanoparticles for process monitoring and control. The systems engineering work in task 4 will

  18. The Enzyme Function Initiative.

    PubMed

    Gerlt, John A; Allen, Karen N; Almo, Steven C; Armstrong, Richard N; Babbitt, Patricia C; Cronan, John E; Dunaway-Mariano, Debra; Imker, Heidi J; Jacobson, Matthew P; Minor, Wladek; Poulter, C Dale; Raushel, Frank M; Sali, Andrej; Shoichet, Brian K; Sweedler, Jonathan V

    2011-11-22

    The Enzyme Function Initiative (EFI) was recently established to address the challenge of assigning reliable functions to enzymes discovered in bacterial genome projects; in this Current Topic, we review the structure and operations of the EFI. The EFI includes the Superfamily/Genome, Protein, Structure, Computation, and Data/Dissemination Cores that provide the infrastructure for reliably predicting the in vitro functions of unknown enzymes. The initial targets for functional assignment are selected from five functionally diverse superfamilies (amidohydrolase, enolase, glutathione transferase, haloalkanoic acid dehalogenase, and isoprenoid synthase), with five superfamily specific Bridging Projects experimentally testing the predicted in vitro enzymatic activities. The EFI also includes the Microbiology Core that evaluates the in vivo context of in vitro enzymatic functions and confirms the functional predictions of the EFI. The deliverables of the EFI to the scientific community include (1) development of a large-scale, multidisciplinary sequence/structure-based strategy for functional assignment of unknown enzymes discovered in genome projects (target selection, protein production, structure determination, computation, experimental enzymology, microbiology, and structure-based annotation), (2) dissemination of the strategy to the community via publications, collaborations, workshops, and symposia, (3) computational and bioinformatic tools for using the strategy, (4) provision of experimental protocols and/or reagents for enzyme production and characterization, and (5) dissemination of data via the EFI's Website, http://enzymefunction.org. The realization of multidisciplinary strategies for functional assignment will begin to define the full metabolic diversity that exists in nature and will impact basic biochemical and evolutionary understanding, as well as a wide range of applications of central importance to industrial, medicinal, and pharmaceutical efforts.

  19. Managing Complexity

    SciTech Connect

    Chassin, David P.; Posse, Christian; Malard, Joel M.

    2004-08-01

    Physical analogs have shown considerable promise for understanding the behavior of complex adaptive systems, including macroeconomics, biological systems, social networks, and electric power markets. Many of today’s most challenging technical and policy questions can be reduced to a distributed economic control problem. Indeed, economically-based control of large-scale systems is founded on the conjecture that the price-based regulation (e.g., auctions, markets) results in an optimal allocation of resources and emergent optimal system control. This paper explores the state of the art in the use physical analogs for understanding the behavior of some econophysical systems and to deriving stable and robust control strategies for them. In particular we review and discussion applications of some analytic methods based on the thermodynamic metaphor according to which the interplay between system entropy and conservation laws gives rise to intuitive and governing global properties of complex systems that cannot be otherwise understood.

  20. Control of Initialized Fractional-Order Systems

    NASA Technical Reports Server (NTRS)

    Hartly, Tom T.; Lorenzo, Carl F.

    2002-01-01

    Due to the importance of historical effects in fractional-order systems, this paper presents a general fractional-order control theory that includes the time-varying initialization response. Previous studies have not properly accounted for these historical effects. The initialization response, along with the forced response, for fractional-order systems is determined. Stability properties of fractional-order systems are presented in the complex Airplane, which is a transformation of the s-plane. Time responses are discussed with respect to pole positions in the complex Airplane and frequency response behavior is included. A fractional-order vector space representation, which is a generalization of the state space concept, is presented including the initialization response. Control methods for vector representations of initialized fractional-order systems are shown. Nyquist, root-locus, and other input-output control methods are adapted to the control of fractional-order systems. Finally, the fractional-order differintegral is generalized to continuous order-distributions that have the possibility of including a continuum of fractional orders in a system element.

  1. Local Signs of MJO Convection Initiation

    NASA Astrophysics Data System (ADS)

    Bowers, M.; Tung, W. W.

    2014-12-01

    The Madden-Julian Oscillation (MJO) is an eastward-propagating, planetary-scale envelope of organized convective activity in the tropical atmosphere. Of particular research interest is the dynamic and thermodynamic configurations typically associated with initiation of MJO convection. In light of recent results indicating a build up of lower-tropospheric moisture due to advection over the Western Indian Ocean preceding initiation of MJO convection, here we propose an approach for detecting the typical local change of atmospheric states prior to initiation of the MJO. Permutation entropy (PE), a measure of randomness capable of detecting dynamical changes in a temporal process, is used to characterize the complex time evolution of kinematic and thermodynamic fields in the lower troposphere of selected tropical locations. PE computed within a ~10-day window is compared with phase indices of MJO convective activity to identify the typical dynamical configuration of states and changes which occur throughout the MJO life cycle. In preliminary results, the lower-tropospheric moisture field over the Western Indian Ocean is found to be well organized prior to initiation, transitioning to a disorganized state as MJO convection becomes fully developed. The lower-tropospheric perturbation kinetic energy, on the other hand, is found to exhibit systematic disorganization prior to MJO initiation followed by increased organization during the development of MJO circulation. These results indicate that low-level wind and moisture signals in this region could indeed offer some precursory sign of MJO genesis. It is noted that the complexity measure provided by permutation entropy is independent of signal amplitudes, so that it could be possible to detect these systematic dynamical changes operationally even during a quiescent regime prior to MJO initiation.

  2. Complex Event Recognition Architecture

    NASA Technical Reports Server (NTRS)

    Fitzgerald, William A.; Firby, R. James

    2009-01-01

    Complex Event Recognition Architecture (CERA) is the name of a computational architecture, and software that implements the architecture, for recognizing complex event patterns that may be spread across multiple streams of input data. One of the main components of CERA is an intuitive event pattern language that simplifies what would otherwise be the complex, difficult tasks of creating logical descriptions of combinations of temporal events and defining rules for combining information from different sources over time. In this language, recognition patterns are defined in simple, declarative statements that combine point events from given input streams with those from other streams, using conjunction, disjunction, and negation. Patterns can be built on one another recursively to describe very rich, temporally extended combinations of events. Thereafter, a run-time matching algorithm in CERA efficiently matches these patterns against input data and signals when patterns are recognized. CERA can be used to monitor complex systems and to signal operators or initiate corrective actions when anomalous conditions are recognized. CERA can be run as a stand-alone monitoring system, or it can be integrated into a larger system to automatically trigger responses to changing environments or problematic situations.

  3. Complexity in Dynamical Systems

    NASA Astrophysics Data System (ADS)

    Moore, Cristopher David

    The study of chaos has shown us that deterministic systems can have a kind of unpredictability, based on a limited knowledge of their initial conditions; after a finite time, the motion appears essentially random. This observation has inspired a general interest in the subject of unpredictability, and more generally, complexity; how can we characterize how "complex" a dynamical system is?. In this thesis, we attempt to answer this question with a paradigm of complexity that comes from computer science, we extract sets of symbol sequences, or languages, from a dynamical system using standard methods of symbolic dynamics; we then ask what kinds of grammars or automata are needed a generate these languages. This places them in the Chomsky heirarchy, which in turn tells us something about how subtle and complex the dynamical system's behavior is. This gives us insight into the question of unpredictability, since these automata can also be thought of as computers attempting to predict the system. In the culmination of the thesis, we find a class of smooth, two-dimensional maps which are equivalent to the highest class in the Chomsky heirarchy, the turning machine; they are capable of universal computation. Therefore, these systems possess a kind of unpredictability qualitatively different from the usual "chaos": even if the initial conditions are known exactly, questions about the system's long-term dynamics are undecidable. No algorithm exists to answer them. Although this kind of unpredictability has been discussed in the context of distributed, many-degree-of -freedom systems (for instance, cellular automata) we believe this is the first example of such phenomena in a smooth, finite-degree-of-freedom system.

  4. Cordycepin as a sensitizer to tumour necrosis factor (TNF)-α-induced apoptosis through eukaryotic translation initiation factor 2α (eIF2α)- and mammalian target of rapamycin complex 1 (mTORC1)-mediated inhibition of nuclear factor (NF)-κB

    PubMed Central

    Kadomatsu, M; Nakajima, S; Kato, H; Gu, L; Chi, Y; Yao, J; Kitamura, M

    2012-01-01

    Cordycepin (3′-deoxyadenosine) is one of the major bioactive substances produced by Cordyceps militaris, a traditional medicinal mushroom. Cordycepin possesses several biological activities, including both pro-apoptotic and anti-apoptotic properties. In the present report, we investigated an effect of cordycepin on the survival of cells exposed to tumour necrosis factor (TNF)-α. We found that subtoxic doses of cordycepin increased susceptibility of cells to TNF-α-induced apoptosis. It was associated with suppression of nuclear factor-κB (NF-κB), a major prosurvival component involved in TNF-α signalling. The adenosine transporter and A3 adenosine receptor, but not A1 and A2 adenosine receptors, mediated both anti-NF-κB and pro-apoptotic effects. We found that cordycepin had the potential to phosphorylate eukaryotic translation initiation factor 2α (eIF2α) and that activation of eIF2α mimicked the suppressive effect of cordycepin on the NF-κB pathway. Furthermore, activation of eIF2α sensitized cells to TNF-α-induced apoptosis. To identify molecular events downstream of eIF2α, the role of mammalian target of rapamycin complex 1 (mTORC1) was examined. Selective activation of 3eIF2α, as well as treatment with cordycepin, caused phosphorylation of mTORC1. Rapamycin, an inhibitor of mTORC1, significantly reversed the suppressive effects of eIF2α on NF-κB. These results suggest that cordycepin sensitizes cells to TNF-α-induced apoptosis, at least in part, via induction of the eIF2α–mTORC1 pathway and consequent suppression of NF-κB. PMID:22519596

  5. Research initiatives in Mauritius.

    PubMed

    Persand, Sharveen

    2005-01-15

    Mauritius forms part of the Mascarene Islands of the Indian Ocean and is situated ca. 700 km to the east of Madagascar at latitude 20 degrees S and longitude 57.5 degrees E. Mauritius has jurisdiction over a proclaimed Exclusive Economic Zone that stretches over 1,900,000 km2. This extensive area holds an immense potential for exploration and presents a wide range of scientific and industrial challenges and opportunities. At present, ocean-related activities are undertaken by various governmental and para-statal institutions as well as non-governmental organizations. Mauritius recognizes the need to coordinate all efforts in order to eliminate wasteful duplication and focus on potential for development, and this has seen the establishment of different forums and committees. This paper gives a brief overview of the different institutions involved in marine science and oceanography in Mauritius and lists the major projects that are being undertaken as well as some of the projects or new research initiatives that are in the pipeline.

  6. Research initiatives in Mauritius.

    PubMed

    Persand, Sharveen

    2005-01-15

    Mauritius forms part of the Mascarene Islands of the Indian Ocean and is situated ca. 700 km to the east of Madagascar at latitude 20 degrees S and longitude 57.5 degrees E. Mauritius has jurisdiction over a proclaimed Exclusive Economic Zone that stretches over 1,900,000 km2. This extensive area holds an immense potential for exploration and presents a wide range of scientific and industrial challenges and opportunities. At present, ocean-related activities are undertaken by various governmental and para-statal institutions as well as non-governmental organizations. Mauritius recognizes the need to coordinate all efforts in order to eliminate wasteful duplication and focus on potential for development, and this has seen the establishment of different forums and committees. This paper gives a brief overview of the different institutions involved in marine science and oceanography in Mauritius and lists the major projects that are being undertaken as well as some of the projects or new research initiatives that are in the pipeline. PMID:15598638

  7. Urban Environment Initiative

    NASA Technical Reports Server (NTRS)

    1998-01-01

    The Urban Environment Initiative (UEI), has been established as part of a Cooperative Agreement with the National Aeronautics and Space Administration (NASA). The UEI is part of NASA's overall High Performance Computing and Communications (HPCC) and the Information Infrastructure Technology Applications (IITA) programs. The goal of the UEI is to provide public access to Earth Science information and promote its use with a focus on the environment of urban areas. This goal will be accomplished through collaborative efforts of the UEI team with both community-based and local/regional governmental organizations. The UEI team is comprised of four organizations representing private industry, NASA, and universities: Prime Technologies Service Corporation, NASA's Minority University Space Interdisciplinary Network (MU-SPIN) California State University, at Los Angeles, and Central State University (Wilberforce, OH). "Urban Environment" refers to the web of environmental, economic, and social factors that combine to create the urban world in which we live. Examples of these factors are population distribution, neighborhood demographic profiles, economic resources, business activities, location and concentration of environmental hazards and various pollutants, proximity and level of urban services, which form the basis of the urban environment and ultimately affect our lives and experiences. The use of Geographic Information Systems (GIS) and remote sensing allows data to be visualized in the forms of maps and spatial images. The use of these tools allow analysis of information about urban environments. Also included are descriptions of the four query types which will assist in understanding the maps.

  8. TFTR initial operations

    SciTech Connect

    Young, K.M.; Bell, M.; Blanchard, W.R.; Bretz, N.; Cecchi, J.; Coonrod, J.; Davis, S.; Dylla, H.F.; Efthimion, P.C.; Fonck, R.

    1983-11-01

    The Tokamak Fusion Test Reactor (TFTR) has operated since December 1982 with ohmically heated plasmas. Routine operation with feedback control of plasma current, position, and density has been obtained for plasmas with I/sub p/ approx. = 800 kA, a = 68 cm, R = 250 cm, and B/sub t/ = 27 kG. A maximum plasma current of 1 MA was achieved with q approx. = 2.5. Energy confinement times of approx. 150 msec were measured for hydrogen and deuterium plasmas with anti n/sub e/ approx. = 2 x 10/sup 13/ cm/sup -3/, T/sub e/ (0) approx. = 1.5 keV, T/sub i/ (0) approx. = 1.5 keV, and Z/sub eff/ approx. = 3. The preliminary results suggest a size-cubed scaling from PLT and are consistent with Alcator C scaling where tau approx. nR/sup 2/a. Initial measurements of plasma disruption characteristics indicate current decay rates of approx. 800 kA in 8 ms which is within the TFTR design requirement of 3 MA in 3 ms.

  9. [Carney complex].

    PubMed

    Kacerovská, D; Michal, M; Síma, R; Grossmann, P; Kazakov, D V

    2011-10-01

    Carney complex is a clinically and genetically heterogeneous disease, with at least two genetic loci including the PRKAR1A gene located on chromosome 17 and the CNC2 locus mapped to chromosome 2. Clinically this syndrome is characterized by multiple myxomas occurring in different anatomic sites, mucocutaneous pigmentary lesions, and a variety of non-endocrine and endocrine tumors, often causing endocrine abnormalities, involving various organs. Knowledge of morphological findings in CNC patients with their typical locations is necessary to raise suspicion of this syndrome by pathologists. Confirmation of the diagnosis allows regular clinical check-ups and early treatment of these patients. PMID:22145222

  10. Complex Systems

    PubMed Central

    Goldberger, Ary L.

    2006-01-01

    Physiologic systems in health and disease display an extraordinary range of temporal behaviors and structural patterns that defy understanding based on linear constructs, reductionist strategies, and classical homeostasis. Application of concepts and computational tools derived from the contemporary study of complex systems, including nonlinear dynamics, fractals and “chaos theory,” is having an increasing impact on biology and medicine. This presentation provides a brief overview of an emerging area of biomedical research, including recent applications to cardiopulmonary medicine and chronic obstructive lung disease. PMID:16921107

  11. Combined 40Ar/39Ar and Fission-Track study of the Freetown Layered Igneous Complex, Freetown, Sierra Leone, West Africa: Implications for the Initial Break-up of Pangea to form the Central Atlantic Ocean and Insight into the Post-rift Evolution of the Sie

    NASA Astrophysics Data System (ADS)

    Barrie, Ibrahim; Wijbrans, Jan; Andriessen, Paul; Beunk, Frank; Strasser-King, Victor; Fode, Daniel

    2010-05-01

    good plateaus that range from 196.3 ± 3 Ma to 232.1 ± 9 Ma with the best-fit isochron plots showing a range from 193.3± 10 Ma to 234.1 ± 11 Ma. Because these dates represent cooling ages, we interpret them as representing a minimum intrusion-age of the Complex implying that its true emplacement age might be somewhat older than 230 Ma. Given that most established CAMP ages revolve around 200 Ma or younger, we hypothesise that FLIC represents a hitherto unknown pre-CAMP magmatic event that might have thermally triggered the initial break-up of Pangaea to form the Central Atlantic. This view is consistent with field-observations that the Complex is cross-cut by predominantly coast-parallel mafic dykes attributed to the CAMP dyke-swarm. To ascertain the hypothesis, we are currently carrying out U-Pb zircon dating to establish, precisely, the true emplacement age of the Complex. The Fission-track ages vary from 91.7 ± 7 Ma to 114.6 ± 9 Ma. This age range shows that after emplacement and crystallisation, the FLIC underwent an extremely slow cooling for a long period of time. This in turn implies that after the break-up of Pangea to form, in part, the Sierra Leone margin, a late and slow uplift (Erosion/denudation) that took place during the Cretaceous was a very important geological process that characterised the post-rift evolution of the margin. References: Barrie, I.J., P.A.M. Andriessen, F.F. Beunk, J.R. Wijbrans, V.E.H. Strasser-King, D.V.A.Fode. (2006). Tectonothermal Evolution of the Sierra Leone Passive Continental Margin, West Africa: Constraints from Thermochronology. Geochemica et Cosmochemica Acta 70 (18): A36- A36 Suppl. S Aug-Sep 2006. Marzoli, A., P.R. Renne, E.M. Piccirillo, M. Ernesto, G. Bellieni, A De Min. (1999). Extensive 200-Million-Year-Old Continental Flood Basalts of the Central Atlantic Magmatic Province. Science284: 616-618. McHone, J.G. (2000). Non-plume magmatism and rifting during the opening of the central Atlantic Ocean. Tectonophysics

  12. An Archean Biosphere Initiative

    NASA Technical Reports Server (NTRS)

    Anbar, A. D.; Boyd, E. S.; Buick, R.; Claire, M.; DesMarais, D.; Domagal-Goldman, D.; Eigenbrode, J.; Erwin, D.; Freeman, K.; Hazen, R.; Johnson, C.; Lyons, T.; Meadows, V.; Ohmoto, H.; Ono, S.; Peters, J. W.; Shapiro, B.; Summons, R.; Walter, M.

    2011-01-01

    The search for life on extrasolar planets will necessarily focus on the imprints of biolgy on the composition of planetary atmospheres. The most notable biological imprint on the modern terrestrial atmosphere is the presence of 21 % O2, However, during most of the past 4 billion years, life and the surface environments on Earth were profoundly different than they are today. It is therefore a major goal of the astrobiology community to ascertain how the O2 content of the atmosphere has varied with time. and to understand the causes of these variations. The NAI and NASA Exobiology program have played critical roles in developing our current understanding of the ancient Earth's atmosphere, supporting diverse observational, analytical, and computational research in geoscience, life science, and related fields. In the present incarnation of the NAI, ongoing work is investigating (i) variations in atmospheric O2 in the Archean to the Cambrian, (ii) characterization of the redox state of the oceans shortly before, during and after the Great Oxidation Event (GOE), and (iii) unraveling the complex connections between environmental oxygenation, global climate, and the evolution of life.

  13. Carney complex.

    PubMed

    Espiard, Stéphanie; Bertherat, Jérôme

    2013-01-01

    Carney complex is a rare, dominantly inherited multiple endocrine neoplasia syndrome, affecting endocrine glands as the adrenal cortex (causing Cushing's syndrome), the pituitary and the thyroid. It is associated with many other nonendocrine tumors, including cardiac myxomas, testicular tumors, melanotic schwannoma, breast myxomatosis, and abnormal pigmentation (lentiginosis) or myxomas of the skin. The gene located on the CNC1 locus was identified 12 years ago as the regulatory subunit 1A (R1A) of the protein kinase A (PRKAR1A) located at 17q22-24. Inactivating heterozygous germline mutations of PRKAR1A are observed in about two thirds of Carney complex patients with some genotype-phenotype correlation useful for follow-up and prognosis. More rarely, mutations of phosphodiesterase genes have been reported in patients presenting mainly with Cushing's syndrome. In vitro and in vivo studies help to understand how R1A inactivation leads to tumorigenesis. PRKAR1A appears to be a relatively weak tumorigenic signal which can cooperate with other signaling pathways and tumor suppressors. PMID:23652670

  14. Initial Radionuclide Inventories

    SciTech Connect

    Miller, H

    2005-07-12

    The purpose of this analysis is to provide an initial radionuclide inventory (in grams per waste package) and associated uncertainty distributions for use in the Total System Performance Assessment for the License Application (TSPA-LA) in support of the license application for the repository at Yucca Mountain, Nevada. This document is intended for use in postclosure analysis only. Bounding waste stream information and data were collected that capture probable limits. For commercially generated waste, this analysis considers alternative waste stream projections to bound the characteristics of wastes likely to be encountered using arrival scenarios that potentially impact the commercial spent nuclear fuel (CSNF) waste stream. For TSPA-LA, this radionuclide inventory analysis considers U.S. Department of Energy (DOE) high-level radioactive waste (DHLW) glass and two types of spent nuclear fuel (SNF): CSNF and DOE-owned (DSNF). These wastes are placed in two groups of waste packages: the CSNF waste package and the codisposal waste package (CDSP), which are designated to contain DHLW glass and DSNF, or DHLW glass only. The radionuclide inventory for naval SNF is provided separately in the classified ''Naval Nuclear Propulsion Program Technical Support Document'' for the License Application. As noted previously, the radionuclide inventory data presented here is intended only for TSPA-LA postclosure calculations. It is not applicable to preclosure safety calculations. Safe storage, transportation, and ultimate disposal of these wastes require safety analyses to support the design and licensing of repository equipment and facilities. These analyses will require radionuclide inventories to represent the radioactive source term that must be accommodated during handling, storage and disposition of these wastes. This analysis uses the best available information to identify the radionuclide inventory that is expected at the last year of last emplacement, currently identified as

  15. Initial Radionuclide Inventories

    SciTech Connect

    H. Miller

    2004-09-19

    The purpose of this analysis is to provide an initial radionuclide inventory (in grams per waste package) and associated uncertainty distributions for use in the Total System Performance Assessment for the License Application (TSPA-LA) in support of the license application for the repository at Yucca Mountain, Nevada. This document is intended for use in postclosure analysis only. Bounding waste stream information and data were collected that capture probable limits. For commercially generated waste, this analysis considers alternative waste stream projections to bound the characteristics of wastes likely to be encountered using arrival scenarios that potentially impact the commercial spent nuclear fuel (CSNF) waste stream. For TSPA-LA, this radionuclide inventory analysis considers U.S. Department of Energy (DOE) high-level radioactive waste (DHLW) glass and two types of spent nuclear fuel (SNF): CSNF and DOE-owned (DSNF). These wastes are placed in two groups of waste packages: the CSNF waste package and the codisposal waste package (CDSP), which are designated to contain DHLW glass and DSNF, or DHLW glass only. The radionuclide inventory for naval SNF is provided separately in the classified ''Naval Nuclear Propulsion Program Technical Support Document'' for the License Application. As noted previously, the radionuclide inventory data presented here is intended only for TSPA-LA postclosure calculations. It is not applicable to preclosure safety calculations. Safe storage, transportation, and ultimate disposal of these wastes require safety analyses to support the design and licensing of repository equipment and facilities. These analyses will require radionuclide inventories to represent the radioactive source term that must be accommodated during handling, storage and disposition of these wastes. This analysis uses the best available information to identify the radionuclide inventory that is expected at the last year of last emplacement, currently identified as

  16. Initial Cladding Condition

    SciTech Connect

    E. Siegmann

    2000-08-22

    The purpose of this analysis is to describe the condition of commercial Zircaloy clad fuel as it is received at the Yucca Mountain Project (YMP) site. Most commercial nuclear fuel is encased in Zircaloy cladding. This analysis is developed to describe cladding degradation from the expected failure modes. This includes reactor operation impacts including incipient failures, potential degradation after reactor operation during spent fuel storage in pool and dry storage and impacts due to transportation. Degradation modes include cladding creep, and delayed hydride cracking during dry storage and transportation. Mechanical stresses from fuel handling and transportation vibrations are also included. This Analysis and Model Report (AMR) does not address any potential damage to assemblies that might occur at the YMP surface facilities. Ranges and uncertainties have been defined. This analysis will be the initial boundary condition for the analysis of cladding degradation inside the repository. In accordance with AP-2.13Q, ''Technical Product Development Planning'', a work plan (CRWMS M&O 2000c) was developed, issued, and utilized in the preparation of this document. There are constraints, caveats and limitations to this analysis. This cladding degradation analysis is based on commercial Pressurized Water Reactor (PWR) fuel with Zircaloy cladding but is applicable to Boiling Water Reactor (BWR) fuel. Reactor operating experience for both PWRs and BWRs is used to establish fuel reliability from reactor operation. It is limited to fuel exposed to normal operation and anticipated operational occurrences (i.e. events which are anticipated to occur within a reactor lifetime), and not to fuel that has been exposed to severe accidents. Fuel burnup projections have been limited to the current commercial reactor licensing environment with restrictions on fuel enrichment, oxide coating thickness and rod plenum pressures. The information provided in this analysis will be used in

  17. Breckinridge Project, initial effort

    SciTech Connect

    1982-01-01

    This report presents an overview of the Breckinridge Project and summarizes the results achieved during the development phase of the project performed under a Cooperative Agreement with the United States Department of Energy. The Breckinridge Project provides for the design, construction and operation of a 50,000 barrel per day coal liquefaction facility in Breckinridge County, Kentucky. The development of the basic technology used in the Breckinridge Project dates back to the late 1950's and the invention by Hydrocarbon Research, Inc., (HRI) of the ebullated-bed reactor and the H-OIL process. The H-COAL process is based on the H-OIL technology. This coal liquefaction process produces clean low-sulfur petroleum substitutes suitable for most types of hydrocarbon-based fuel and chemical uses regardless of the sulfur content of the coal. A large H-COAL Pilot Plant in operation at Catlettsburg, Kentucky, is converting 220 tons of coal per day into 600 barrels of distillate products by catalytic hydrogenation. The estimated capital cost of the commercial facility is $3.17 billion, and the associated out-of-pocket operating cost is $18 per barrel, both in January 1981 dollars. Financial analysis shows the project to be an attractive investment under certain leveraged conditions which are possible through the assistance of the Synthetic Fuels Corporation. Ashland Synthetic Fuels, Inc. is currently working with the Synthetic Fuels Corporation and potential partners to develop financing for the commercial venture. Critical permits are being obtained and an Environmental Impact Statement is being prepared pursuant to initiating site preparation in early 1983. Commercial operations are expected to start up in early 1988.

  18. Incidentalomas: initial management.

    PubMed

    Hitzeman, Nathan; Cotton, Erin

    2014-12-01

    Incidentalomas are increasingly common findings on radiologic studies, causing worry for physicians and patients. Physicians should consider the risk of discovering incidentalomas when contemplating imaging. Patients may assume that incidentalomas are cancer, and may not be aware of the radiation risks associated with repeat imaging. Once incidentalomas are detected, appropriate management is dependent on an informed patient's wishes and the clinical situation. Guidelines are provided for the initial management of eight incidentalomas (pituitary, thyroid, pulmonary, hepatic, pancreatic, adrenal, renal, and ovarian). Patients presenting with pituitary incidentalomas should undergo pituitary-specific magnetic resonance imaging if the lesion is 1 cm or larger, or if it abuts the optic chiasm. Thyroid incidentalomas are ubiquitous, but nodules larger than 1 to 2 cm are of greater concern. Worrisome pulmonary incidentalomas are those larger than 8 mm or those with irregular borders, eccentric calcifications, or low density. However, current guidelines recommend that even pulmonary incidentalomas as small as 4 mm be followed. Solid hepatic incidentalomas 5 mm or larger should be monitored closely, and multiphasic scanning is helpful. Pancreatic cystic neoplasms have malignant potential, and surgery is recommended for pancreatic cysts larger than 3 cm with suspicious features. Adrenal lesions larger than 4 cm are usually biopsied. The Bosniak classification is a well-accepted means of triaging renal incidentalomas. Lesions at category IIF or greater require serial monitoring or surgery. Benign or probably benign ovarian cysts 3 cm or smaller in premenopausal women or 1 cm or smaller in postmenopausal women do not require follow-up. Ovarian cysts with thickened walls or septa, or solid components with blood flow, should be managed closely.

  19. Glennan Microsystems Initiative

    NASA Technical Reports Server (NTRS)

    Brillson, Leonard J.

    2002-01-01

    During the 2001-2002 award period, we performed research on Pt/Ti/bare 6H-SiC and bare 4H-SiC interfaces in order to identify their electronic properties as a function of surface preparation. The overall aim of this work is to optimize the electronic properties of metal contacts to SiC as well as the active SiC material itself as a function of surface preparation and subsequent processing. Initially, this work has involved identifying bare surface, subsurface, and metal induced gap states at the metal-SiC contact and correlating energies and densities of deep levels with Schottky barrier heights. We used low energy electron-excited nanoluminescence (LEEN) spectroscopy, X-ray photoemission spectroscopy (XPS), and Secondary Ion Mass Spectrometry (SIMS) in order to correlate electronic states and energy bands with chemical composition, bonding, and crystal structure. A major development has been the discovery of polytype transformations that occur in 4H-SiC under standard microelectronic process conditions used to fabricate SiC devices. Our results are consistent with the stacking fault generation, defect formation, and consequent degradation of SiC recently reported for state-of-the-art ABB commercial diodes under localized electrical stress. Our results highlight the importance of -optimizing process conditions and material properties - anneal times, temperatures and doping to control such structural changes within epitaxial SiC layers. Thus far, we have established threshold times and temperatures beyond which 4H-SiC exhibits 3C-SiC transformation bands for a subset of dopant concentrations and process conditions. On the basis of this temperature time behavior, we have been able to establish an activation energy of approximately 2.5 eV for polytype transformation and dislocation motion. Work continues to establish the fundamental mechanisms underlying the polytype changes and its dependence on material parameters.

  20. Cable Diagnostic Focused Initiative

    SciTech Connect

    Hartlein, R.A.; Hampton, R.N.

    2010-12-30

    This report summarizes an extensive effort made to understand how to effectively use the various diagnostic technologies to establish the condition of medium voltage underground cable circuits. These circuits make up an extensive portion of the electric delivery infrastructure in the United States. Much of this infrastructure is old and experiencing unacceptable failure rates. By deploying efficient diagnostic testing programs, electric utilities can replace or repair circuits that are about to fail, providing an optimal approach to improving electric system reliability. This is an intrinsically complex topic. Underground cable systems are not homogeneous. Cable circuits often contain multiple branches with different cable designs and a range of insulation materials. In addition, each insulation material ages differently as a function of time, temperature and operating environment. To complicate matters further, there are a wide variety of diagnostic technologies available for assessing the condition of cable circuits with a diversity of claims about the effectiveness of each approach. As a result, the benefits of deploying cable diagnostic testing programs have been difficult to establish, leading many utilities to avoid the their use altogether. This project was designed to help address these issues. The information provided is the result of a collaborative effort between Georgia Tech NEETRAC staff, Georgia Tech academic faculty, electric utility industry participants, as well as cable system diagnostic testing service providers and test equipment providers. Report topics include: •How cable systems age and fail, •The various technologies available for detecting potential failure sites, •The advantages and disadvantages of different diagnostic technologies, •Different approaches for utilities to employ cable system diagnostics. The primary deliverables of this project are this report, a Cable Diagnostic Handbook (a subset of this report) and an online

  1. Cosmic Complexity

    NASA Technical Reports Server (NTRS)

    Mather, John C.

    2012-01-01

    What explains the extraordinary complexity of the observed universe, on all scales from quarks to the accelerating universe? My favorite explanation (which I certainty did not invent) ls that the fundamental laws of physics produce natural instability, energy flows, and chaos. Some call the result the Life Force, some note that the Earth is a living system itself (Gaia, a "tough bitch" according to Margulis), and some conclude that the observed complexity requires a supernatural explanation (of which we have many). But my dad was a statistician (of dairy cows) and he told me about cells and genes and evolution and chance when I was very small. So a scientist must look for me explanation of how nature's laws and statistics brought us into conscious existence. And how is that seemll"!gly Improbable events are actually happening a!1 the time? Well, the physicists have countless examples of natural instability, in which energy is released to power change from simplicity to complexity. One of the most common to see is that cooling water vapor below the freezing point produces snowflakes, no two alike, and all complex and beautiful. We see it often so we are not amazed. But physlc!sts have observed so many kinds of these changes from one structure to another (we call them phase transitions) that the Nobel Prize in 1992 could be awarded for understanding the mathematics of their common features. Now for a few examples of how the laws of nature produce the instabilities that lead to our own existence. First, the Big Bang (what an insufficient name!) apparently came from an instability, in which the "false vacuum" eventually decayed into the ordinary vacuum we have today, plus the most fundamental particles we know, the quarks and leptons. So the universe as a whole started with an instability. Then, a great expansion and cooling happened, and the loose quarks, finding themselves unstable too, bound themselves together into today's less elementary particles like protons and

  2. Cosmic Complexity

    NASA Technical Reports Server (NTRS)

    Mather, John C.

    2012-01-01

    What explains the extraordinary complexity of the observed universe, on all scales from quarks to the accelerating universe? My favorite explanation (which I certainty did not invent) ls that the fundamental laws of physics produce natural instability, energy flows, and chaos. Some call the result the Life Force, some note that the Earth is a living system itself (Gaia, a "tough bitch" according to Margulis), and some conclude that the observed complexity requires a supernatural explanation (of which we have many). But my dad was a statistician (of dairy cows) and he told me about cells and genes and evolution and chance when I was very small. So a scientist must look for me explanation of how nature's laws and statistics brought us into conscious existence. And how is that seemll"!gly Improbable events are actually happening a!1 the time? Well, the physicists have countless examples of natural instability, in which energy is released to power change from simplicity to complexity. One of the most common to see is that cooling water vapor below the freezing point produces snowflakes, no two alike, and all complex and beautiful. We see it often so we are not amazed. But physlc!sts have observed so many kinds of these changes from one structure to another (we call them phase transitions) that the Nobel Prize in 1992 could be awarded for understanding the mathematics of their common features. Now for a few examples of how the laws of nature produce the instabilities that lead to our own existence. First, the Big Bang (what an insufficient name!) apparently came from an instability, in which the "false vacuum" eventually decayed into the ordinary vacuum we have today, plus the most fundamental particles we know, the quarks and leptons. So the universe as a whole started with an instability. Then, a great expansion and cooling happened, and the loose quarks, finding themselves unstable too, bound themselves together into today's less elementary particles like protons and

  3. National Take-Back Initiative

    MedlinePlus

    ... Physicians Drug Disposal Information Drug and Chemical Information E-commerce Initiatives Federal Agencies & Related Links Federal Register Notices ... Physicians Drug Disposal Information Drug and Chemical Information E-commerce Initiatives Federal Agencies & Related Links Federal Register Notices ...

  4. Attack vulnerability of complex networks

    NASA Astrophysics Data System (ADS)

    Holme, Petter; Kim, Beom Jun; Yoon, Chang No; Han, Seung Kee

    2002-05-01

    We study the response of complex networks subject to attacks on vertices and edges. Several existing complex network models as well as real-world networks of scientific collaborations and Internet traffic are numerically investigated, and the network performance is quantitatively measured by the average inverse geodesic length and the size of the largest connected subgraph. For each case of attacks on vertices and edges, four different attacking strategies are used: removals by the descending order of the degree and the betweenness centrality, calculated for either the initial network or the current network during the removal procedure. It is found that the removals by the recalculated degrees and betweenness centralities are often more harmful than the attack strategies based on the initial network, suggesting that the network structure changes as important vertices or edges are removed. Furthermore, the correlation between the betweenness centrality and the degree in complex networks is studied.

  5. The national geomagnetic initiative

    NASA Technical Reports Server (NTRS)

    1993-01-01

    The Earth's magnetic field, through its variability over a spectrum of spatial and temporal scales, contains fundamental information on the solid Earth and geospace environment (the latter comprising the atmosphere, ionosphere, and magnetosphere). Integrated studies of the geomagnetic field have the potential to address a wide range of important processes in the deep mantle and core, asthenosphere, lithosphere, oceans, and the solar-terrestrial environment. These studies have direct applications to important societal problems, including resource assessment and exploration, natural hazard mitigation, safe navigation, and the maintenance and survivability of communications and power systems on the ground and in space. Studies of the Earth's magnetic field are supported by a variety of federal and state agencies as well as by private industry. Both basic and applied research is presently supported by several federal agencies, including the National Science Foundation (NSF), U.S. Geological Survey (USGS), U.S. Department of Energy (DOE), National Oceanic and Atmospheric Administration (NOAA), National Aeronautics and Space Administration (NASA), and U.S. Department of Defense (DOD) (through the Navy, Air Force, and Defense Mapping Agency). Although each agency has a unique, well-defined mission in geomagnetic studies, many areas of interest overlap. For example, NASA, the Navy, and USGS collaborate closely in the development of main field reference models. NASA, NSF, and the Air Force collaborate in space physics. These interagency linkages need to be strengthened. Over the past decade, new opportunities for fundamental advances in geomagnetic research have emerged as a result of three factors: well-posed, first-order scientific questions; increased interrelation of research activities dealing with geomagnetic phenomena; and recent developments in technology. These new opportunities can be exploited through a national geomagnetic initiative to define objectives and

  6. Florida Hydrogen Initiative

    SciTech Connect

    Block, David L

    2013-06-30

    The Florida Hydrogen Initiative (FHI) was a research, development and demonstration hydrogen and fuel cell program. The FHI program objectives were to develop Florida?s hydrogen and fuel cell infrastructure and to assist DOE in its hydrogen and fuel cell activities The FHI program funded 12 RD&D projects as follows: Hydrogen Refueling Infrastructure and Rental Car Strategies -- L. Lines, Rollins College This project analyzes strategies for Florida's early stage adaptation of hydrogen-powered public transportation. In particular, the report investigates urban and statewide network of refueling stations and the feasibility of establishing a hydrogen rental-car fleet based in Orlando. Methanol Fuel Cell Vehicle Charging Station at Florida Atlantic University ? M. Fuchs, EnerFuel, Inc. The project objectives were to design, and demonstrate a 10 kWnet proton exchange membrane fuel cell stationary power plant operating on methanol, to achieve an electrical energy efficiency of 32% and to demonstrate transient response time of less than 3 milliseconds. Assessment of Public Understanding of the Hydrogen Economy Through Science Center Exhibits, J. Newman, Orlando Science Center The project objective was to design and build an interactive Science Center exhibit called: ?H2Now: the Great Hydrogen Xchange?. On-site Reformation of Diesel Fuel for Hydrogen Fueling Station Applications ? A. Raissi, Florida Solar Energy Center This project developed an on-demand forecourt hydrogen production technology by catalytically converting high-sulfur hydrocarbon fuels to an essentially sulfur-free gas. The removal of sulfur from reformate is critical since most catalysts used for the steam reformation have limited sulfur tolerance. Chemochromic Hydrogen Leak Detectors for Safety Monitoring ? N. Mohajeri and N. Muradov, Florida Solar Energy Center This project developed and demonstrated a cost-effective and highly selective chemochromic (visual) hydrogen leak detector for safety monitoring

  7. Damage detection in initially nonlinear systems

    SciTech Connect

    Bornn, Luke; Farrar, Charles; Park, Gyuhae

    2009-01-01

    The primary goal of Structural Health Monitoring (SHM) is to detect structural anomalies before they reach a critical level. Because of the potential life-safety and economic benefits, SHM has been widely studied over the past decade. In recent years there has been an effort to provide solid mathematical and physical underpinnings for these methods; however, most focus on systems that behave linearly in their undamaged state - a condition that often does not hold in complex 'real world' systems and systems for which monitoring begins mid-lifecycle. In this work, we highlight the inadequacy of linear-based methodology in handling initially nonlinear systems. We then show how the recently developed autoregressive support vector machine (AR-SVM) approach to time series modeling can be used for detecting damage in a system that exhibits initially nonlinear response. This process is applied to data acquired from a structure with induced nonlinearity tested in a laboratory environment.

  8. Initial development of 5D COGENT

    NASA Astrophysics Data System (ADS)

    Cohen, R. H.; Lee, W.; Dorf, M.; Dorr, M.

    2015-11-01

    COGENT is a continuum gyrokinetic edge code being developed by the by the Edge Simulation Laboratory (ESL) collaboration. Work to date has been primarily focussed on a 4D (axisymmetric) version that models transport properties of edge plasmas. We have begun development of an initial 5D version to study edge turbulence, with initial focus on kinetic effects on blob dynamics and drift-wave instability in a shearless magnetic field. We are employing compiler directives and preprocessor macros to create a single source code that can be compiled in 4D or 5D, which helps to ensure consistency of physics representation between the two versions. A key aspect of COGENT is the employment of mapped multi-block grid capability to handle the complexity of diverter geometry. It is planned to eventually exploit this capability to handle magnetic shear, through a series of successively skewed unsheared grid blocks. The initial version has an unsheared grid and will be used to explore the degree to which a radial domain must be block decomposed. We report on the status of code development and initial tests. Work performed for USDOE, at LLNL under contract DE-AC52-07NA27344.

  9. EPA`s clean air power initiative

    SciTech Connect

    Critchfield, L.R.

    1997-12-31

    The Clean Air Power Initiative (CAPI) is a multi-stakeholder project intended to improve air pollution control efforts involving the power generating industry. This paper documents the progress made in the first year of the initiative, which included a number of meetings with interested stakeholders and development and analysis of alternative approaches for more efficient and effective pollution control. The project`s goal is to develop an integrated regulatory strategy or three major pollutants emitted from electric power generators; namely, sulfur dioxide, nitrogen oxides, and, potentially, mercury. Major reductions in these pollutants are expected to be needed to reduce the detrimental health effects of ground-level ozone, fine particles, and hazardous air pollutants and reduce the environmental effects of acidification, eutrophication, ecosystem, crop, and materials damage, and regional haze. The Clean Air Power Initiative has considered, where feasible, new approaches to pollution control that recognize the long-range transport of many air pollutants and the economic benefits of emissions trading. The project was initiated by EPA`s Assistant Administrator for Air and Radiation in 1995. As individual companies develop and implement strategies to participate in more competitive power markets, they could benefit from greater certainty in being able to plan for and reduce costs of future environmental regulations. The EPA is interested in reinventing its regulatory approach to reduce the number, administrative complexity, and cost of its requirements while improving the likelihood of achieving environmental results.

  10. [Carney complex].

    PubMed

    Losada Grande, Eladio José; Al Kassam Martínez, Daniel; González Boillos, Margarita

    2011-01-01

    Carney complex (CNC) is an autosomal dominantly inherited syndrome characterized by spotty skin pigmentation, cardiac and cutaneous myxoma, and endocrine overactivity. Skin pigmentation includes lentigines and blue nevi. Myxomas may occur in breast, skin and heart. Cardiac myxomas may be multiple and occur in any cardiac chamber, and are more prone to recurrence. The most common endocrine gland manifestation is an ACTH-independent Cushing's syndrome due to primary pigmented nodular adrenocortical disease (PPNAD). PPNAD may occur isolated, with no other signs of CNC. Pituitary and thyroid glands and gonads are also involved. The PRKAR1A gene, located in 17 q22-24, encodes type 1A regulatory subunit of protein kinase A. Inactivating germline mutations of this gene are found in 70% of patients with CNC. PRKAR1A is a key component of the c-AMP signaling pathway that has been implicated in endocrine tumorigenesis. Many different mutations have been reported in the PRKAR1A gene. In almost all cases the sequence change was predicted to lead to a premature stop codon and the resultant mutant mRNA was subject to nonsense-mediated mRNA decay. There is no clear genotype-phenotype correlation in patients with CNC. Genetic analysis should be performed in all CNC index cases. All affected patients should be monitored for clinical signs of CNC at least once a year. Genetic diagnosis allows for more effective preparation of more appropriate and effective therapeutic strategies and genetic counseling for patients and gene carriers, and to avoid unnecessary tests to relatives not carrying the gene. PMID:21536508

  11. Initiation into Adolescent Marijuana Use.

    ERIC Educational Resources Information Center

    Brook, Judith S.; And Others

    1980-01-01

    This longitudinal study examined the relationship of three domains (personality/attitudinal orientations, peer relationships, and family socialization factors) with initiation into adolescent marihuana use. (Author/DB)

  12. Complex Regional Pain Syndrome.

    PubMed

    Ersoy, Hale; Pomeranz, Stephen J

    2016-01-01

    Complex regional pain syndrome (CRPS) is a neurological disorder producing peripheral neurogenic inflammatory process in hands and feet distal to injury, which may lead to severe disability. Symptoms are often out of proportion to the initiating event and not limited to a single peripheral nerve. There is no gold standard in diagnosis of this entity, and a multidisciplinary approach is necessary for proper diagnosis. Magnetic resonance imaging (MRI) is one of the most useful diagnostic modalities in early stages of CRPS (when clinical diagnosis is most difficult), the most desirable time to diagnose this disorder to expedite treatment and improve function. This article discusses MRI findings of CRPS, particularly in the early phase, and differential considerations. PMID:27518298

  13. Human Translation Initiation Factor eIF4G1 Possesses a Low-Affinity ATP Binding Site Facing the ATP-Binding Cleft of eIF4A in the eIF4G/eIF4A Complex

    PubMed Central

    2015-01-01

    Eukaryotic translation initiation factor 4G (eIF4G) plays a crucial role in translation initiation, serving as a scaffolding protein binding several other initiation factors, other proteins, and RNA. Binding of eIF4G to the ATP-dependent RNA helicase eukaryotic translation initiation factor 4A (eIF4A) enhances the activity of eIF4A in solution and in crowded environments. Previously, this activity enhancement was solely attributed to eIF4G, conferring a closed, active conformation upon eIF4A. Here we show that eIF4G contains a low-affinity binding site at the entrance to the ATP-binding cleft on eIF4A, suggesting that regulation of the local ATP concentration may be an additional reason for the enhancement in activity. PMID:25255371

  14. Nebraska: Early Head Start Initiative

    ERIC Educational Resources Information Center

    Center for Law and Social Policy, Inc. (CLASP), 2012

    2012-01-01

    Since 1999, Nebraska's Early Head Start Infant/Toddler Quality Initiative has supported Early Head Start (EHS) and community child care partnerships to improve the quality and professionalism of infant and toddler care. EHS programs apply to receive funding to establish partnerships with center-based or home-based child care.The initiative has…

  15. Two black hole initial data

    SciTech Connect

    Leski, Szymon

    2005-06-15

    The Misner initial data are a standard example of time-symmetric initial data with two apparent horizons. Compact formulae describing such data are presented in the cases of equal or nonequal masses (i.e. isometric or nonisometric horizons). The interaction energy in the 'Schwarzschild + test-particle' limit of the Misner data is analyzed.

  16. Education as Initiation into Practices

    ERIC Educational Resources Information Center

    Smeyers, Paul; Burbules, Nicholas C.

    2006-01-01

    In this essay, Paul Smeyers and Nicholas Burbules reexamine the concept of "practice" and propose a new way of conceiving it that does justice to the idea that education is in some sense an initiation into practices without endorsing either the conservative and reproductive conception of what initiation entails or the radically social…

  17. Washington State's Student Achievement Initiative

    ERIC Educational Resources Information Center

    Pettitt, Maureen; Prince, David

    2010-01-01

    This article describes Washington State's Student Achievement Initiative, an accountability system implemented in 2005-06 that measures students' gains in college readiness, college credits earned, and degree or certificate completion. The goal of the initiative is to increase educational attainment by focusing on the critical momentum points…

  18. Career Technical Education Pathways Initiative

    ERIC Educational Resources Information Center

    California Community Colleges, Chancellor's Office, 2013

    2013-01-01

    California's education system--the largest in the United States--is an essential resource for ensuring strong economic growth in the state. The Career Technical Education Pathways Initiative (referred to as the Initiative in this report), which became law in 2005, brings together community colleges, K-12 school districts, employers, organized…

  19. Molecular basis of transcription initiation in Archaea.

    PubMed

    De Carlo, Sacha; Lin, Shih-Chieh; Taatjes, Dylan J; Hoenger, Andreas

    2010-01-01

    Compared with eukaryotes, the archaeal transcription initiation machinery-commonly known as the Pre-Initiation Complex-is relatively simple. The archaeal PIC consists of the TFIIB ortholog TFB, TBP, and an 11-subunit RNA polymerase (RNAP). The relatively small size of the entire archaeal PIC makes it amenable to structural analysis. Using purified RNAP, TFB, and TBP from the thermophile Pyrococcus furiosus, we assembled the biochemically active PIC at 65ºC. The intact archaeal PIC was isolated by implementing a cross-linking technique followed by size-exclusion chromatography, and the structure of this 440 kDa assembly was determined using electron microscopy and single-particle reconstruction techniques. Combining difference maps with crystal structure docking of various sub-domains, TBP and TFB were localized within the macromolecular PIC. TBP/TFB assemble near the large RpoB subunit and the RpoD/L "foot" domain behind the RNAP central cleft. This location mimics that of yeast TBP and TFIIB in complex with yeast RNAP II. Collectively, these results define the structural organization of the archaeal transcription machinery and suggest a conserved core PIC architecture.

  20. Cost estimate of initial SSC experimental equipment

    SciTech Connect

    1986-06-01

    The cost of the initial detector complement at recently constructed colliding beam facilities (or at those under construction) has been a significant fraction of the cost of the accelerator complex. Because of the complexity of large modern-day detectors, the time-scale for their design and construction is comparable to the time-scale needed for accelerator design and construction. For these reasons it is appropriate to estimate the cost of the anticipated detector complement in parallel with the cost estimates of the collider itself. The fundamental difficulty with this procedure is that, whereas a firm conceptual design of the collider does exist, comparable information is unavailable for the detectors. Traditionally, these have been built by the high energy physics user community according to their perception of the key scientific problems that need to be addressed. The role of the accelerator laboratory in that process has involved technical and managerial coordination and the allocation of running time and local facilities among the proposed experiments. It seems proper that the basic spirit of experimentation reflecting the scientific judgment of the community should be preserved at the SSC. Furthermore, the formal process of initiation of detector proposals can only start once the SSC has been approved as a construction project and a formal laboratory administration put in place. Thus an ad hoc mechanism had to be created to estimate the range of potential detector needs, potential detector costs, and associated computing equipment.

  1. [Complex decongestive therapy].

    PubMed

    Heinig, B; Wollina, U

    2015-11-01

    The amount of physical pressure plays an important role in complex decongestive therapy (CDT). As a function of pressure, microcirculation takes place between blood vessels and tissue. As part of the total lymphatic system, lymphatic vessels transport the lymphatic load from the interstitial space to the blood stream. The lymphatic vessel system, characterized by specific anatomical conditions like initial lymphatic vessels, precollectors, collectors, and lymphatic strains, is the therapeutic target of complex decongestive therapy. Components of CDT include manual lymphatic drainage, compression therapy, decongestive kinesitherapy, and good skin care, which increase the transport capacity of the lymphatic vessel system. Currently, CDT is acknowledged as the main conservative treatment of lymphedema of primary and secondary genesis, lipolymphedema, and phlebolymphedema. In clinical practice, we are increasingly confronted with edema of multifactorial genesis requiring a critical discussion and stocktaking of comprehensive clinical findings in terms of the indication for CDT. Therapeutic success depends on a joint application of all CDT components and patient compliance. To an increasing extent, medical research tries to combine successfully CDT with adjunct treatment options. PMID:26315101

  2. Interferometric Observations of Lightning Initiation

    NASA Astrophysics Data System (ADS)

    Rison, W.; Krehbiel, P. R.; Stock, M.; Edens, H. E.; Shao, X. M.; Thomas, R. J.; Stanley, M. A.

    2014-12-01

    Observations of the initial parts of lightning flashes close to Langmuir Laboratory in central New Mexico appear to show the lightning initiation process. The observations were made on August 5, 2013, from a number of flashes within 5 km of the New Mexico Tech broadband VHF interferometer (INTF). In addition to the INTF, the flashes were observed by the Langmuir Laboratory Lightning Mapping Array (LMA), and by close fast and slow antennas. For those flashes where the powers of the initial sources detected by the LMA were stronger than about 5 dBW (4 watts), the INTF observations showed that the initial LMA source was associated with a previously unidentified form of fast positive breakdown. No activity was detected prior to the positive breakdown, either by the sensitive INTF or fast electric measurements. The VHF radiation and electric field changes develop simultaneously, and the INTF shows a positive breakdown which propagates about one hundred meters. This and other features of the observations indicate that the breakdown occurs in virgin air and is produced by dielectric streamer processes in localized regions of strong electric fields. We observed both normal intracloud and cloud-to-ground discharges to be initiated by such breakdown. After the fast positive breakdown died out, the INTF showed continuous negative breakdown at the start of the positive channel, which subsequently developed into a negative leader propagating in the opposite direction of the initial positive breakdown. The results are fundamentally consistent with those obtained from modelling studies by Liu et al. (Phys. Rev. Lett.109, 025002, 2012), in which positive sprite streamers were shown to be initiated by purely dielectric breakdown, without the need of an initiating event such as a cosmic ray or energetic electron avalanches. We speculate that all lightning flashes are initiated by the fast positive events.

  3. Stochastic dynamics of cancer initiation

    NASA Astrophysics Data System (ADS)

    Foo, Jasmine; Leder, Kevin; Michor, Franziska

    2011-02-01

    Most human cancer types result from the accumulation of multiple genetic and epigenetic alterations in a single cell. Once the first change (or changes) have arisen, tumorigenesis is initiated and the subsequent emergence of additional alterations drives progression to more aggressive and ultimately invasive phenotypes. Elucidation of the dynamics of cancer initiation is of importance for an understanding of tumor evolution and cancer incidence data. In this paper, we develop a novel mathematical framework to study the processes of cancer initiation. Cells at risk of accumulating oncogenic mutations are organized into small compartments of cells and proliferate according to a stochastic process. During each cell division, an (epi)genetic alteration may arise which leads to a random fitness change, drawn from a probability distribution. Cancer is initiated when a cell gains a fitness sufficiently high to escape from the homeostatic mechanisms of the cell compartment. To investigate cancer initiation during a human lifetime, a 'race' between this fitness process and the aging process of the patient is considered; the latter is modeled as a second stochastic Markov process in an aging dimension. This model allows us to investigate the dynamics of cancer initiation and its dependence on the mutational fitness distribution. Our framework also provides a methodology to assess the effects of different life expectancy distributions on lifetime cancer incidence. We apply this methodology to colorectal tumorigenesis while considering life expectancy data of the US population to inform the dynamics of the aging process. We study how the probability of cancer initiation prior to death, the time until cancer initiation, and the mutational profile of the cancer-initiating cell depends on the shape of the mutational fitness distribution and life expectancy of the population.

  4. Human-Modified Permafrost Complexes in Urbanized Areas of the Russian North

    NASA Astrophysics Data System (ADS)

    Grebenets, V. I.; Streletskiy, D. A.

    2013-12-01

    Economic development in permafrost regions is accompanied by modification of natural geocryological conditions. Drastic landscape transformations in urbanized areas on permafrost are characterized by changes of heat and moisture exchange in permafrost - atmosphere system, and by engineering and technogenic influence upon the frozen ground, leading to alteration of its physical, thermal and mechanical properties. In northern cities this leads to overall increase of ground temperature relative to undisturbed areas and intensification of hazardous cryogenic processes in areas under engineering development, which together leads to reduction in stability of geotechnical environment. For example, deformations of structures in Norilsk district, Northern Siberia, in the last 15 years, became much more abundant than those revealed throughout the previous 50 years. About 250 large buildings in the local towns were deformed considerably due to deterioration of geocryological conditions, about 100 structures were functioning in emergency state, and almost 50 nine- and five-storey houses, built in the 1960-80s, have been recently disassembled. Increase in accident risk for various facilities (water and oil pipelines, industrial enterprises, etc.) enhances the technogenic pressure on permafrost, leading to the new milestone of changes in permafrost characteristics, i.e. to creation of 'another reality' of geocryological conditions. Social and natural factors dictate clustered spatial pattern of industrial development in permafrost regions. Cryogenic processes within the urban areas on permafrost are seldom similar with those under the natural conditions as intensity, duration and extent of the processes changes under technogenic impacts. Moreover, new cryogenic processes and phenomena may occur, which have not been typical for a given region. This makes mapping and characterization of these processes difficult task. Peculiar natural-technogenic geocryological complexes (NTGC

  5. Thin-film optical initiator

    DOEpatents

    Erickson, Kenneth L.

    2001-01-01

    A thin-film optical initiator having an inert, transparent substrate, a reactive thin film, which can be either an explosive or a pyrotechnic, and a reflective thin film. The resultant thin-film optical initiator system also comprises a fiber-optic cable connected to a low-energy laser source, an output charge, and an initiator housing. The reactive thin film, which may contain very thin embedded layers or be a co-deposit of a light-absorbing material such as carbon, absorbs the incident laser light, is volumetrically heated, and explodes against the output charge, imparting about 5 to 20 times more energy than in the incident laser pulse.

  6. Federal government expands compliance initiatives.

    PubMed

    Dugan, J K

    1997-09-01

    In 1995, the Federal government initiated Operation Restore Trust to increase enforcement of fraud and abuse regulations in Medicare and Medicaid programs. With the success of the original initiative, the government is expanding the project to additional states and program areas. The initial scrutiny of home health agencies, nursing homes, hospice care, and durable medical equipment is being expanded to managed care plans and acute care hospitals with an eye toward DRG creep. To manage this increased enforcement activity, healthcare organizations should institute comprehensive corporate compliance programs. Such programs should provide a framework that delineates responsibilities and provides a systematic means to resolve issues in a timely manner. PMID:10170318

  7. Federal government expands compliance initiatives.

    PubMed

    Dugan, J K

    1997-09-01

    In 1995, the Federal government initiated Operation Restore Trust to increase enforcement of fraud and abuse regulations in Medicare and Medicaid programs. With the success of the original initiative, the government is expanding the project to additional states and program areas. The initial scrutiny of home health agencies, nursing homes, hospice care, and durable medical equipment is being expanded to managed care plans and acute care hospitals with an eye toward DRG creep. To manage this increased enforcement activity, healthcare organizations should institute comprehensive corporate compliance programs. Such programs should provide a framework that delineates responsibilities and provides a systematic means to resolve issues in a timely manner.

  8. GALIC: Galaxy initial conditions construction

    NASA Astrophysics Data System (ADS)

    Yurin, Denis; Springel, Volker

    2014-08-01

    GalIC (GALaxy Initial Conditions) is an implementation of an iterative method to construct steady state composite halo-disk-bulge galaxy models with prescribed density distribution and velocity anisotropy that can be used as initial conditions for N-body simulations. The code is parallelized for distributed memory based on MPI. While running, GalIC produces "snapshot files" that can be used as initial conditions files. GalIC supports the three file formats ('type1' format, the slightly improved 'type2' format, and an HDF5 format) of the GADGET (ascl:0003.001) code for its output snapshot files.

  9. The myth of peer influence in adolescent smoking initiation.

    PubMed

    Arnett, Jeffrey Jensen

    2007-08-01

    The widespread belief that peer influence is the primary cause of adolescent smoking initiation is examined and called into question. Correlational and longitudinal studies purporting to demonstrate peer influence are analyzed, and their limitations described. Qualitative interview studies of adolescent smoking initiation are presented as depicting the more complex role of the peer context. Finally, a new model of the role of peers in smoking initiation is offered, with an emphasis on how adolescents' characteristics lead to the selection of their friends, who then provide a peer context that may or may not support smoking.

  10. Step initiation in Parkinson's disease: influence of initial stance conditions.

    PubMed

    Rocchi, Laura; Chiari, Lorenzo; Mancini, Martina; Carlson-Kuhta, Patricia; Gross, Anne; Horak, Fay B

    2006-10-01

    In this study, we investigated how the size of preparatory postural adjustments prior to step initiation, and step length and velocity depend on initial stance width in patients with Parkinson's disease (PD) both in the ON and OFF levodopa states and in healthy elderly subjects. Twenty-one subjects with idiopathic PD and 24 age-matched healthy control subjects took two steps starting with feet on a two-plate force-platform, from either narrow or wide stance width. We measured how the magnitude of anticipatory postural adjustments (APA) and step characteristics scaled with stance width. Results showed that preparation for step initiation from wide stance was associated with a larger lateral and backward center of pressure (CoP) displacement than from narrow stance. Velocity and length of the first step were also sensitive to initial stance conditions, probably in relation with the differences in the corresponding APA. On the contrary, the duration of APA was not significantly affected by initial stance width, but it was longer in PD compared to healthy subjects, and speeded up by levodopa. Although subjects with PD did scale up the size of their APA with stance width, they had much more difficulty initiating a step from a wide stance than from a narrow stance, as shown by the greater differences from control subjects in the magnitude of the APA. Our results support the hypothesis that PD subjects maintain a narrow stance as a compensation for their inability to sufficiently increase the size of their lateral APA to allow fast step initiation in wide stance.

  11. Genomics Nursing Faculty Champion Initiative

    PubMed Central

    Jenkins, Jean; Calzone, Kathleen A.

    2016-01-01

    Nurse faculty are challenged to keep up with the emerging and fast-paced field of genomics and the mandate to prepare the nursing workforce to be able to translate genomic research advances into routine clinical care. Using Faculty Champions and other options, the initiative stimulated curriculum development and promoted genomics curriculum integration. The authors summarize this yearlong initiative for undergraduate and graduate nursing faculty. PMID:24300251

  12. Initiation of lymphocyte DNA synthesis.

    PubMed

    Coffman, F D; Fresa, K L; Cohen, S

    1991-01-01

    The initiation of DNA replication in T lymphocytes appears to be regulated by two distinct activities: one associated with proliferation which mediates initiation, and another associated with quiescence which blocks initiation. Activated lymphocytes and proliferating lymphoid cell lines produce an activity, termed ADR, which can initiate DNA replication in isolated, quiescent nuclei. ADR is heat-labile, has protease activity or interacts closely with a protease, and is distinct from the DNA polymerases. ADR activity is absent in quiescent lymphocytes and appears in mitogen-stimulated lymphocytes after IL-2 binding. The generation of active ADR appears to be mediated by phosphorylation of a precursor which is present in resting cells. Nuclei from mitogen-unresponsive lymphocytes fail to initiate DNA replication in response to ADR, of potential importance in the age-related decline of immunity. Quiescent lymphocytes lack ADR and synthesize an ADR-inhibitory activity. The ADR inhibitor is a heat-stable protein which suppresses the initiation of DNA synthesis, but is ineffective at suppressing elongation once DNA strand replication has begun. Nuclei from several neoplastic cell lines fail to respond to the ADR inhibitor, which may play a role in the continuous proliferation of these cells. At least one of these neoplastic cell lines produces both ADR and an inhibitory factor. These findings suggest that the regulation of proliferation is dependent on the balance between activating and inhibitory pathways. PMID:2005180

  13. Shock Initiation of Energetic Materials at Different Initial Temperatures

    SciTech Connect

    Urtiew, P A; Tarver, C M

    2005-01-14

    Shock initiation is one of the most important properties of energetic materials, which must transition to detonation exactly as intended when intentionally shocked and not detonate when accidentally shocked. The development of manganin pressure gauges that are placed inside the explosive charge and record the buildup of pressure upon shock impact has greatly increased the knowledge of these reactive flows. This experimental data, together with similar data from electromagnetic particle velocity gauges, has allowed us to formulate the Ignition and Growth model of shock initiation and detonation in hydrodynamic computer codes for predictions of shock initiation scenarios that cannot be tested experimentally. An important problem in shock initiation of solid explosives is the change in sensitivity that occurs upon heating (or cooling). Experimental manganin pressure gauge records and the corresponding Ignition and Growth model calculations are presented for two solid explosives, LX-17 (92.5 % triaminotrinitrobenzene (TATB) with 7.5 % Kel-F binder) and LX-04 (85 % octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazine (HMX) with 15 % Viton binder) at several initial temperatures.

  14. On State Complexes and Special Cube Complexes

    ERIC Educational Resources Information Center

    Peterson, Valerie J.

    2009-01-01

    This thesis presents the first steps toward a classification of non-positively curved cube complexes called state complexes. A "state complex" is a configuration space for a "reconfigurable system," i.e., an abstract system in which local movements occur in some discrete manner. Reconfigurable systems can be used to describe, for example,…

  15. A National Network of Neurotechnology Centers for the BRAIN Initiative.

    PubMed

    Alivisatos, A Paul; Chun, Miyoung; Church, George M; Greenspan, Ralph J; Roukes, Michael L; Yuste, Rafael

    2015-11-01

    We propose the creation of a national network of neurotechnology centers to enhance and accelerate the BRAIN Initiative and optimally leverage the effort and creativity of individual laboratories involved in it. As "brain observatories," these centers could provide the critical interdisciplinary environment both for realizing ambitious and complex technologies and for providing individual investigators with access to them. PMID:26481036

  16. The Text Encoding Initiative: Flexible and Extensible Document Encoding.

    ERIC Educational Resources Information Center

    Barnard, David T.; Ide, Nancy M.

    1997-01-01

    The Text Encoding Initiative (TEI), an international collaboration aimed at producing a common encoding scheme for complex texts, examines the requirement for generality versus the requirement to handle specialized text types. Discusses how documents and users tax the limits of fixed schemes requiring flexible extensible encoding to support…

  17. Protein complexes that control renal epithelial polarity

    PubMed Central

    Pieczynski, Jay

    2011-01-01

    Establishment of epithelial apicobasal polarity is crucial for proper kidney development and function. In recent years, there have been important advances in our understanding of the factors that mediate the initiation of apicobasal polarization. Key among these are the polarity complexes that are evolutionarily conserved from simple organisms to humans. Three of these complexes are discussed in this review: the Crumbs complex, the Par complex, and the Scribble complex. The apical Crumbs complex consists of three proteins, Crumbs, PALS1, and PATJ, whereas the apical Par complex consists of Par-3, Par-6, and atypical protein kinase C. The lateral Scribble complex consists of Scribble, discs large, and lethal giant larvae. These complexes modulate kinase and small G protein activity such that the apical and basolateral complexes signal antagonistically, leading to the segregation of the apical and basolateral membranes. The polarity complexes also serve as scaffolds to direct and retain proteins at the apical membrane, the basolateral membrane, or the intervening tight junction. There is plasticity in apicobasal polarity, and this is best seen in the processes of epithelial-to-mesenchymal transition and the converse mesenchymal-to-epithelial transition. These transitions are important in kidney disease as well as kidney development, and modulation of the polarity complexes are critical for these transitions. PMID:21228104

  18. Quantum Measurement and Initial Conditions

    NASA Astrophysics Data System (ADS)

    Stoica, Ovidiu Cristinel

    2016-03-01

    Quantum measurement finds the observed system in a collapsed state, rather than in the state predicted by the Schrödinger equation. Yet there is a relatively spread opinion that the wavefunction collapse can be explained by unitary evolution (for instance in the decoherence approach, if we take into account the environment). In this article it is proven a mathematical result which severely restricts the initial conditions for which measurements have definite outcomes, if pure unitary evolution is assumed. This no-go theorem remains true even if we take the environment into account. The result does not forbid a unitary description of the measurement process, it only shows that such a description is possible only for very restricted initial conditions. The existence of such restrictions of the initial conditions can be understood in the four-dimensional block universe perspective, as a requirement of global self-consistency of the solutions of the Schrödinger equation.

  19. Initial State Radiation: A success story

    NASA Astrophysics Data System (ADS)

    Kluge, W.

    2008-09-01

    The investigation of events with Initial State Radiation(ISR) and subsequent Radiative Return has become an impressively successful and guiding tool in low and intermediate energy hadron physics with electron positron colliders: it allows to measure hadronic cross sections and the ratio R from threshold up to the maximum energy of the colliders running at fixed energy, to clarify reaction mechanisms and reveal substructures (intermediate states and their decay mechanisms) and to search for new highly excited mesonic states with J=1. While being discussed since the sixties-seventies ISR became a powerful tool for experimentalists only with the development of EVA-PHOKHARA, a Monte Carlo generator developed over almost 10 years, while increasing its complexity, which is user friendly, flexible and easy to implement into the software of existing detectors.

  20. Initial operation of the Tevatron collider

    SciTech Connect

    Johnson, R.

    1987-03-01

    The Tevatron is now the highest energy proton synchrotron and the only accelerator made with superconducting magnets. Operating since 1983 as a fixed-target machine at energies up to 800 GeV, it has now been modified to operate as a 900 GeV antiproton-proton collider. This paper describes the initial operation of the machine in this mode. The new features of the Fermilab complex, including the antiproton source and the Main Ring injector with its two overpasses and new rf requirements, are discussed. Beam characteristics in the Tevatron (including lifetimes, emittances, luminosity, beam-beam tune shifts, backgrounds, and low beta complications), the coordination of the steps in the accelerator chain, and the commissioning history are also discussed. Finally, some plans for the improvement of the collider are presented.

  1. Initial conditions and quantum cosmology

    NASA Technical Reports Server (NTRS)

    Hartle, James B.

    1987-01-01

    A theory of initial conditions is necessary for a complete explanation of the presently observed large scale structural features of the universe, and a quantum theory of cosmology is probably needed for its formulation. The kinematics of quantum cosmology are reviewed, and some candidates for a law of initial conditions are discussed. The proposal that the quantum state of a closed universe is the natural analog of the ground state for closed cosmologies and is specified by a Euclidean sum over histories is sketched. When implemented in simple models, this proposal is consistent with the most important large-scale observations.

  2. The radiowave propagation environment - Science and technology objectives for the 80's

    NASA Astrophysics Data System (ADS)

    Goodman, J. M.; Aarons, J.

    The ionosphere has a strong influence on the personality of radiowaves which propagate beneath, within, or through it; and this influence derives from the spatial and temporal nonuniformity in the refractivity of the magneto-ionic medium. Basic research objectives in environmental monitoring are examined, taking into account ionospheric research, magnetospheric research, interplanetary field and solar wind research, solar radiation and magnetic field research, and propagation studies. Operational systems which basic research will support are related to communications systems, navigation systems, and surveillance. Environmental effects/system deficiencies by frequency band are discussed, giving attention to the ELF frequency band (30-300 Hz), the VLF band (3-30 kHz), the MF/HF band (300 kHz - 30 MHz), and the UHF/SHF (300 MHz - 30 GHz). It is concluded that there is already a need to study the ionosphere and its coupling to the magnetosphere above and the troposphere below in order to more fully develop the insight required to specify the radiowave propagation effects introduced by the various media.

  3. New York in Review, Theme: "Issues in Science Education for the '80s."

    ERIC Educational Resources Information Center

    Science Teacher, 1981

    1981-01-01

    Presents edited excerpts of some of the major convention speeches presented at the National Science Teacher's Association National Convention in New York City, including those of Rosalyn Yalow, Peter Fenner, Verne N. Rockcastle, F. James Rutherford, John Brooks Slaughter, and Majorie H. Gardner. (CS)

  4. Radiation immune RAM semiconductor technology for the 80's. [Random Access Memory

    NASA Technical Reports Server (NTRS)

    Hanna, W. A.; Panagos, P.

    1983-01-01

    This paper presents current and short term future characteristics of RAM semiconductor technologies which were obtained by literature survey and discussions with cognizant Government and industry personnel. In particular, total ionizing dose tolerance and high energy particle susceptibility of the technologies are addressed. Technologies judged compatible with spacecraft applications are ranked to determine the best current and future technology for fast access (less than 60 ns), radiation tolerant RAM.

  5. American Foreign Policy for the '80s: A Voter's Guide to the Facts and Issues.

    ERIC Educational Resources Information Center

    Irwin, Wallace, Jr., Ed.; And Others

    The purpose of this guide is to provide voters, officeholders, and candidates with background information on major foreign policy issues so that they can follow the 1980 presidential debates and reach their own informed conclusions. Thirteen major foreign policy topics are covered. The material is written in telegraphic style to get the essential…

  6. Jobs in Unexpected Places--A Pattern for the 80s.

    ERIC Educational Resources Information Center

    Samuels, Jack B.

    1983-01-01

    Opportunities now await the leisure service professional in several employment areas not traditionally occupied by people with training or experience in the recreation or leisure service profession. Areas include theme parks, auditorium and arena management, themed restaurants, shopping centers, and resort management. (CJ)

  7. Technologies of the '80s: Their Impact on Vocational Agriculture Occupations.

    ERIC Educational Resources Information Center

    Jaffe, J. A., Ed.; And Others

    This report is one of seven that identify major new and emerging technological advances expected to influence major vocational education program areas and to describe the programmatic implications in terms of skill-knowledge requirements, occupations most directly affected, and the anticipated diffusion rate. Chapter 1 considers technology as…

  8. New Voices: Student Political Activism in the '80s and '90s.

    ERIC Educational Resources Information Center

    Vellela, Tony

    An examination of the state of student activism in American higher education is based on a study of the focus and direction of campus activism and on interviews and surveys of undergraduate and graduate students who consider themselves activists. The first two chapters are devoted to an assessment of the overall situation and of the strategies…

  9. The Budget Challenge of the 80's--Where Will the Money Come From.

    ERIC Educational Resources Information Center

    O'Day, George

    1979-01-01

    To handle the major school budgetary and operating challenges posed by the energy, transportation, food service, maintenance, equipment, and material problems, administrators must look to improved management, improved operations, and optimization of existing resources. (Author/MLF)

  10. Public Confidence in Public Education: A Growing Concern in the 80's.

    ERIC Educational Resources Information Center

    Achilles, C. M.; Lintz, M. N.

    This literature review and analysis of the problem of building community confidence focuses on the work of the Phi Delta Kappa (PDK) Commission on Developing Public Confidence in Schools. Approaches to confidence building are categorized as: communications, concentrating on expanding communications one-way between school and the home; public…

  11. Toe of Ganges Chasma Landslide ( 8.0 S, 44.4W)

    NASA Technical Reports Server (NTRS)

    2001-01-01

    This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows shear striations, dark dunes banked up against the toe of the slide and over-riding light-toned ripples and boulders on surface of slide. These features can be used to determine quantitative aspects of surface processes.

    Malin Space Science Systems and the California Institute of Technology built the MOC using spare hardware from the Mars Observer mission. MSSS operates the camera from its facilities in San Diego, CA. The Jet Propulsion Laboratory's Mars Surveyor Operations Project operates the Mars Global Surveyor spacecraft with its industrial partner, Lockheed Martin Astronautics, from facilities in Pasadena, CA and Denver, CO.

  12. The Mnemonic '80s: Keywords in the Classroom. Theoretical Paper No. 86.

    ERIC Educational Resources Information Center

    Levin, Joel R.

    Research concerning the applied educational potential of Richard Atkinson's mnemonic "keyword method" is reported in this paper. Included are possibilities for stretching the limits of the keyword method by combining it with other mnemonic and prose-learning strategies. The first half of the paper provides an overview of mnemonics--the systems'…

  13. I. D. S. [Interdisciplinary Studies in General Education]: A Program for the 80's.

    ERIC Educational Resources Information Center

    Valencia Community Coll., Orlando, FL.

    Interdisciplinary Studies in General Education (IDS) is Valencia Community College's alternative to the fragmented approach to general education reflected in many schools' unrelated requirements of survey courses and laboratories. A two-year course of study, IDS brings together literature, mathematics, social science, natural science, philosophy,…

  14. Directions for the '80s: Educational Master Plan. San Francisco Community College District.

    ERIC Educational Resources Information Center

    Duncan-Hall, Tyra L., Ed.

    Designed to assist staff in the San Francisco Community College District (SFCCD) in synthesizing the trends, events and issues that are likely to influence educational programs and services, this master plan assesses the district's internal and external environments and describes the SFCCD's two-phase planning process. Chapter 1 discusses the…

  15. Giant fields of the `80s associated with an ``A`` subduction in S. America

    SciTech Connect

    Duval, B.C.; Cramez, C.; Valdes, G.E.

    1995-07-17

    This article results from 12 years of close scientific and technical collaboration between Total and Pdvsa. When the Venezuelan petroleum industry was nationalized in 1976, the remaining hydrocarbon potential of south America was thought to be very limited, mainly because most visible traps had already been drilled. The discovery of four giant oil fields in the northern part of South America in the last 10 years has proved how wrong that judgment was. The reserves of these fields are either confidential or not fully determined. However, existing public information indicates that they are all well over the 1 billion bbl of oil equivalent mark. The aim of this article is to illustrate how it can help to look at things in a very regional way: (1) to understand the petroleum systems; (2) to establish similarities and differences between the systems, and (3) to explain why the giant fields are there.

  16. Improving Student Discipline in the 80s: The Revival of Deterrance.

    ERIC Educational Resources Information Center

    Wynne, Edward A.

    1980-01-01

    The approach taken by Thomas Jefferson concerning problems of student discipline in colleges is viewed in historical perspective and comparisons are made to the contemporary view of adolescent disorder. Recommendations are made for the coming decade. (JN)

  17. The Budget Deficit--The "Crisis" of the 80's. Series on Public Issues No. 13.

    ERIC Educational Resources Information Center

    Greenhut, Melvin L.; Smithson, Charles W.

    In this booklet, one of a series intended to apply economic principles to major social and political issues of the day, an analogy is drawn between the dire predictions once made about the energy crisis and those now being made about a budget crisis. Concerns about the deficit have centered on inflation, interest rates, and growth of the economy.…

  18. Beta titanium alloys in the 80's; Proceedings of the Symposium, Atlanta, GA, March 8, 1983

    SciTech Connect

    Boyer, R.R.; Rosenberg, H.W.

    1984-01-01

    Among the topics discussed are the use of beta-Ti in the SR-71 aircraft, the microstructure and properties of beta-Ti alloys, the effects of hydrogen, heat treatment, and omega-phase formation on beta-Ti, the primary processing of beta- and near-beta-Ti alloys, the processing window for grain size control in metastable beta-Ti, grain growth in beta III-Ti, the processing and properties of Ti-17 alloy for aircraft and turbine applications, the isothermal forging of beta- and near-beta-Ti alloys, the torsional properties of beta-Ti in automotive suspension springs, and the martensitic Transage Ti alloys. Also covered are Ti-Nb superconductors, and property compilations for such commercial and developmental beta-Ti alloys as beta-III, Ti-15-3, Ti-17, Transage 134, and cast and wrought Transage 175.

  19. Preparation for the Battle against Censorship of Film and Video in the 80s.

    ERIC Educational Resources Information Center

    Cohen, David

    1986-01-01

    Documentation of the spread of censorship is extensive, and although challenges to films and videocassettes have not figured prominently in the literature, in the future there may be more emphasis on these media than on print material. On the state level, increasing censorship of films and videocassettes has occurred in North Carolina, California,…

  20. Transformations in Higher Education: Looking Ahead at Management Issues in the '80s.

    ERIC Educational Resources Information Center

    Peat, Marwick, Mitchell and Co., New York, NY.

    Future changes that may affect higher education and management approaches that should be used by governing boards and administrators are discussed. Population trends that will affect academic and support programs are noted, and it is suggested that a declining demand from traditional students may cause institutions to specialize in selected…

  1. Advanced Dental Education: Recommendations for the 80's. Issues in Dental Health Policy.

    ERIC Educational Resources Information Center

    American Association of Dental Schools, Washington, DC.

    Six statements of working principles and 11 major recommendations falling within those areas, as established by the Task Force on Advanced Dental Education, are presented. Supporting recommendations are also provided. The six principles include: (1) no change is recommended in the present goal of predoctoral education, to prepare students for…

  2. A Kaleidoscope: Children Viewing the World through Books of the Late '80's.

    ERIC Educational Resources Information Center

    Corboy, Margaret; And Others

    This paper presents nine sets of books which focus on specific contemporary international issues, and which have been used successfully with upper elementary grade students. The paper shows how the books (including picture books), which include subjects such as the preservation of the environment, world peace, endangered animals, and the coming of…

  3. Communicating in the '80s. New Options for the Nonprofit Community.

    ERIC Educational Resources Information Center

    Green, Alan

    This booklet includes descriptions of new communications technologies and case studies of how they can be used in planning for appropriate and effective use of technology to enhance service to the public. Single-page overviews of satellites, broadcasting, videotex, cable television, microcomputers, teleconferencing, personal video, and telephones…

  4. Mental Health and the Adolescent in the 80s: A Perspective.

    ERIC Educational Resources Information Center

    Lee, Beverley A.

    1980-01-01

    Preoccupation with food and weight, low levels of physical activity and fitness, and moving patterns are only a few indicators of adolescent difficulties. Educational alternatives to meet adolescent needs include integrated studies, multi-disciplinary approaches to critical issues, cooperative education and work study programs, and community and…

  5. Managing Higher Education in the 80s: Trying to Do More with Less. Touche Ross Roundtable.

    ERIC Educational Resources Information Center

    Touche Ross & Co., New York, NY.

    Issues concerning the management of colleges and universities are considered in a roundtable discussion. It is suggested that higher education may be at a decisive juncture with respect to demographics, finances, institutional structure, and the political context. Attention is directed to the decline in the number of 18- to 22-year-olds and the…

  6. An ABC Model for College Health Services in the '80s.

    ERIC Educational Resources Information Center

    Zirkle, Kenneth E.; Papalia, Anthony S.

    1980-01-01

    Presents a model for the concurrent staffing of a hospital ambulatory care/emergency department and a student health service. The model was created by interfacing the services and needs of two institutions and incorporates accountability, budget restraints, and creativity. (Author/RC)

  7. Parenting in the '80s. . . Student Guide. Brookhaven College Child Development Program.

    ERIC Educational Resources Information Center

    Linn, Hilda; And Others

    This guide was developed to accompany a series of 16 seminars on parenting offered by the Brookhaven College Child Development Program to help meet the concerns and needs of working parents in a time of changing lifestyles and family patterns. In addition to providing an overview of each seminar topic, the guide contains informational essays…

  8. At the Edges of Perception: Humanistic Education in the 80's and Beyond.

    ERIC Educational Resources Information Center

    McCarty, F. Hanoch

    The agenda for humanistic education in the 1980s needs to go beyond psychological concerns to address the political, social, ecological, and spiritual side of the human experience. The goals of humanistic education focus on the development of intelligence, self-understanding, interpersonal relationships, and a concept of physical health. Equally…

  9. Non-Credit Education's Response to the Challenges of the 80's.

    ERIC Educational Resources Information Center

    Bazik, Martha S.

    Five of the major issues confronting postsecondary education today are the decline in the quality of education, the increase in competition from other education service providers for a share of the postsecondary market, the increase in the demand on education as a result of rapid changes in technology, the decline in educational revenues, and the…

  10. Technologies of the '80s: Their Impact on Home Economics Occupations.

    ERIC Educational Resources Information Center

    Jaffe, J. A., Ed.; And Others

    This report is one of seven that identify major new and emerging technological advances expected to influence major vocational education program areas and describe the programmatic implications in terms of skill-knowledge requirements, occupations most directly affected, and the anticipated diffusion rate. Chapter 1 considers technology as…

  11. Technologies of the '80s: Their Impact on Trade and Industrial Occupations.

    ERIC Educational Resources Information Center

    Jaffe, J. A., Ed.; And Others

    This report is one of seven that identify major new and emerging technological advances expected to influence major vocational education program areas and to describe the programmatic implications in terms of skill-knowledge requirements, occupations most directly affected, and the anticipated diffusion rate. Chapter 1 considers technology as…

  12. Violence, Stress and Punitiveness: Educational and Social Policy Implications for the 80's.

    ERIC Educational Resources Information Center

    Hyman, Irwin A.

    1981-01-01

    Paper presented at the 66th Convention of the International Association of Pupil Personnel Workers, October 23, 1980, Baltimore, Maryland, expresses concern about the future of education and the growing problem of school violence. Suggests corporal punishment amounts to child abuse and does little to help students learn problem-solving techniques.…

  13. Niosomes from 80s to present: the state of the art.

    PubMed

    Marianecci, Carlotta; Di Marzio, Luisa; Rinaldi, Federica; Celia, Christian; Paolino, Donatella; Alhaique, Franco; Esposito, Sara; Carafa, Maria

    2014-03-01

    Efficient and safe drug delivery has always been a challenge in medicine. The use of nanotechnology, such as the development of nanocarriers for drug delivery, has received great attention owing to the potential that nanocarriers can theoretically act as "magic bullets" and selectively target affected organs and cells while sparing normal tissues. During the last decades the formulation of surfactant vesicles, as a tool to improve drug delivery, brought an ever increasing interest among the scientists working in the area of drug delivery systems. Niosomes are self assembled vesicular nanocarriers obtained by hydration of synthetic surfactants and appropriate amounts of cholesterol or other amphiphilic molecules. Just like liposomes, niosomes can be unilamellar or multilamellar, are suitable as carriers of both hydrophilic and lipophilic drugs and are able to deliver drugs to the target site. Furthermore, niosomal vesicles, that are usually non-toxic, require less production costs and are stable over a longer period of time in different conditions, so overcoming some drawbacks of liposomes. The niosome properties are specifically dictated by size, shape, and surface chemistry which are able to modify the drug's intrinsic pharmacokinetics and eventual drug targeting to the areas of pathology. This up-to-date review deals with composition, preparation, characterization/evaluation, advantages, disadvantages and application of niosomes. PMID:24369107

  14. Engine condition monitoring: CF6 family 60's through the 80's

    NASA Technical Reports Server (NTRS)

    Kent, H. J.; Dienger, G.

    1981-01-01

    The on condition program is described in terms of its effectiveness as a maintenance tool both at the line station as well as at home base by the early detection of engine faults, erroneous instrumentation signals and by verification of engine health. The system encompasses all known methods from manual procedures to the fully automated airborne integrated data system.

  15. Search for an identity: the energy manager in the '80s

    SciTech Connect

    Butler, R.

    1985-05-27

    The energy manager for most of industry is a new phenomenon of the 1970s, although some existed in the energy-intensive industries before that. A casual observer of today's evidence would see the energy crisis as overblown and the energy manager as a creature who could never survive without an illusory crisis to sustain his position. A survey of users finds that many are dropping the position because of the current surplus and declining prices of oil. The editor traces the impact of economic recession, the deindustrialization of America, and the restriction of energy managers to a role of energy conservers. He explores the need to expand the role to include fuel and power contract negotiation and intervention in rate-setting procedures and energy transport contracts. Other areas needing the attention of an energy manager are cogeneration, pollution control equipment, water issues, and quality assurance.

  16. Resource Management for the 80's. (Gloom and Doom in Academia or How to Live Underwater).

    ERIC Educational Resources Information Center

    Stilwell, William E., III

    Trends in human resource management and the preparation/employment of psychologists are considered, along with the types of available data on training and employment. Because of Russia's Sputnik, the 1950s in the United States were characterized by an infusion of federal funds to college science and human service programs. During the 1970s, the…

  17. SLA Responds to U.S. Government Information Issues in the '80s.

    ERIC Educational Resources Information Center

    Morton, Sandy I.

    1988-01-01

    Summarizes Special Libraries Association activities on (1) Office of Management and Budget (OMB) Circular A-76 on contracting out of library services; (2) OMB Circular A-130 on management of federal information; (3) privatization and the National Technical Information Service (NTIS); (4) Federal Communications Commission (FCC) access charges; (5)…

  18. Aspects and Implications of Parent-Infant Bonding: Pathway to the '80's. A Study Review.

    ERIC Educational Resources Information Center

    Brice, Carol H.

    Parent/infant bonding is discussed in this study review. Bonding is defined prior to a discussion of research that places the concept in historical perspective. The discussion of research since 1950 focuses on Bowlby, Klaus and Kennell, Helfer, Mahler and Rheingold, and Brazelton. Attention is given to the capacities of the newborn, child abuse,…

  19. A Quest for Quality: Consumer and Homemaking Education in the 80s.

    ERIC Educational Resources Information Center

    Illinois Teacher of Home Economics, 1985

    1985-01-01

    Discusses the contributions that consumer and homemaking education make towards improving students' basic skills. These skills include verbal (discussing consumer issues, family relations, child development); reading (product labels, magazine articles, newspapers); writing (reports, notes, term papers); mathematics (budgets, recipe ingredients,…

  20. Impact for the 80's: Proceedings of a Conference on Selected Technology for Business and Industry

    NASA Technical Reports Server (NTRS)

    1980-01-01

    Various aspects of advanced energy technology are discussed. Specific emphasis is given to: aircraft propulsion; wind power commercialization; materials and structures, lubrication and bearings; Stirling and gas turbine engines; and electric and hybrid vehicles.