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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. Cryo-EM of ribosomal 80S complexes with termination factors reveal the translocated cricket paralysis virus IRES

    PubMed Central

    Muhs, Margarita; Hilal, Tarek; Mielke, Thorsten; Skabkin, Maxim A.; Sanbonmatsu, Karissa Y.; Pestova, Tatyana V.; Spahn, Christian M.T.

    2015-01-01

    Summary The Cricket paralysis virus (CrPV) uses an internal ribosomal entry site (IRES) to hijack the ribosome. In a remarkable RNA-based mechanism involving neither initiation factor nor initiator tRNA, the CrPV IRES jump starts translation in the elongation phase from the ribosomal A-site. Here we present cryo-EM maps of 80S•CrPV-STOP•eRF1•eRF3•GMPPNP and 80S•CrPV-STOP•eRF1 complexes revealing a previously unseen binding state of the IRES and directly rationalizing that an eEF2-dependent translocation of the IRES is required to allow the first A-site occupation. During this unusual translocation event the IRES undergoes a pronounced conformational change to a more stretched conformation. At the same time our structural analysis provides information about the binding modes of eRF1•eRF3•GMPPNP and eRF1 in a minimal system. It shows that neither eRF3 nor ABCE1 are required for the active conformation of eRF1 at the intersection between eukaryotic termination and recycling. PMID:25601755

  3. Cryo-EM of ribosomal 80S complexes with termination factors reveals the translocated cricket paralysis virus IRES.

    PubMed

    Muhs, Margarita; Hilal, Tarek; Mielke, Thorsten; Skabkin, Maxim A; Sanbonmatsu, Karissa Y; Pestova, Tatyana V; Spahn, Christian M T

    2015-02-01

    The cricket paralysis virus (CrPV) uses an internal ribosomal entry site (IRES) to hijack the ribosome. In a remarkable RNA-based mechanism involving neither initiation factor nor initiator tRNA, the CrPV IRES jumpstarts translation in the elongation phase from the ribosomal A site. Here, we present cryoelectron microscopy (cryo-EM) maps of 80S⋅CrPV-STOP ⋅ eRF1 ⋅ eRF3 ⋅ GMPPNP and 80S⋅CrPV-STOP ⋅ eRF1 complexes, revealing a previously unseen binding state of the IRES and directly rationalizing that an eEF2-dependent translocation of the IRES is required to allow the first A-site occupation. During this unusual translocation event, the IRES undergoes a pronounced conformational change to a more stretched conformation. At the same time, our structural analysis provides information about the binding modes of eRF1 ⋅ eRF3 ⋅ GMPPNP and eRF1 in a minimal system. It shows that neither eRF3 nor ABCE1 are required for the active conformation of eRF1 at the intersection between eukaryotic termination and recycling. PMID:25601755

  4. 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.

  5. Life in the '80s and Beyond.

    ERIC Educational Resources Information Center

    Morris, Joan, Ed.

    1982-01-01

    Contains nine articles discussing how lives of students will be affected by future changes. Discusses the work ethic and work values in a time of change, entering the 80s job market, women and employment. Describes students' changing sexual values, and the impact of computers and declining enrollment on education. (RC)

  6. Structures of the human and Drosophila 80S ribosome.

    PubMed

    Anger, Andreas M; Armache, Jean-Paul; Berninghausen, Otto; Habeck, Michael; Subklewe, Marion; Wilson, Daniel N; Beckmann, Roland

    2013-05-01

    Protein synthesis in all cells is carried out by macromolecular machines called ribosomes. Although the structures of prokaryotic, yeast and protist ribosomes have been determined, the more complex molecular architecture of metazoan 80S ribosomes has so far remained elusive. Here we present structures of Drosophila melanogaster and Homo sapiens 80S ribosomes in complex with the translation factor eEF2, E-site transfer RNA and Stm1-like proteins, based on high-resolution cryo-electron-microscopy density maps. These structures not only illustrate the co-evolution of metazoan-specific ribosomal RNA with ribosomal proteins but also reveal the presence of two additional structural layers in metazoan ribosomes, a well-ordered inner layer covered by a flexible RNA outer layer. The human and Drosophila ribosome structures will provide the basis for more detailed structural, biochemical and genetic experiments. PMID:23636399

  7. Features of 80S mammalian ribosome and its subunits

    PubMed Central

    Budkevich, Tatyana V.; El'skaya, Anna V.; Nierhaus, Knud H.

    2008-01-01

    It is generally believed that basic features of ribosomal functions are universally valid, but a systematic test still stands out for higher eukaryotic 80S ribosomes. Here we report: (i) differences in tRNA and mRNA binding capabilities of eukaryotic and bacterial ribosomes and their subunits. Eukaryotic 40S subunits bind mRNA exclusively in the presence of cognate tRNA, whereas bacterial 30S do bind mRNA already in the absence of tRNA. 80S ribosomes bind mRNA efficiently in the absence of tRNA. In contrast, bacterial 70S interact with mRNA more productively in the presence rather than in the absence of tRNA. (ii) States of initiation (Pi), pre-translocation (PRE) and post-translocation (POST) of the ribosome were checked and no significant functional differences to the prokaryotic counterpart were observed including the reciprocal linkage between A and E sites. (iii) Eukaryotic ribosomes bind tetracycline with an affinity 15 times lower than that of bacterial ribosomes (Kd 30 μM and 1–2 μM, respectively). The drug does not effect enzymatic A-site occupation of 80S ribosomes in contrast to non-enzymatic tRNA binding to the A-site. Both observations explain the relative resistance of eukaryotic ribosomes to this antibiotic. PMID:18632761

  8. Initiation complex structure and promoter proofreading.

    PubMed

    Liu, Xin; Bushnell, David A; Silva, Daniel-Adriano; Huang, Xuhui; Kornberg, Roger D

    2011-07-29

    The initiation of transcription by RNA polymerase II is a multistage process. X-ray crystal structures of transcription complexes containing short RNAs reveal three structural states: one with 2- and 3-nucleotide RNAs, in which only the 3'-end of the RNA is detectable; a second state with 4- and 5-nucleotide RNAs, with an RNA-DNA hybrid in a grossly distorted conformation; and a third state with RNAs of 6 nucleotides and longer, essentially the same as a stable elongating complex. The transition from the first to the second state correlates with a markedly reduced frequency of abortive initiation. The transition from the second to the third state correlates with partial "bubble collapse" and promoter escape. Polymerase structure is permissive for abortive initiation, thereby setting a lower limit on polymerase-promoter complex lifetime and allowing the dissociation of nonspecific complexes. Abortive initiation may be viewed as promoter proofreading, and the structural transitions as checkpoints for promoter control. PMID:21798951

  9. 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

  10. 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

  11. 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. PMID:27193681

  12. Visualization of the joining of ribosomal subunits reveals the presence of 80S ribosomes in the nucleus

    PubMed Central

    Al-Jubran, Khalid; Wen, Jikai; Abdullahi, Akilu; Roy Chaudhury, Subhendu; Li, Min; Ramanathan, Preethi; Matina, Annunziata; De, Sandip; Piechocki, Kim; Rugjee, Kushal Nivriti; Brogna, Saverio

    2013-01-01

    In eukaryotes the 40S and 60S ribosomal subunits are assembled in the nucleolus, but there appear to be mechanisms preventing mRNA binding, 80S formation, and initiation of translation in the nucleus. To visualize association between ribosomal subunits, we tagged pairs of Drosophila ribosomal proteins (RPs) located in different subunits with mutually complementing halves of fluorescent proteins. Pairs of tagged RPs expected to interact, or be adjacent in the 80S structure, showed strong fluorescence, while pairs that were not in close proximity did not. Moreover, the complementation signal is found in ribosomal fractions and it was enhanced by translation elongation inhibitors and reduced by initiation inhibitors. Our technique achieved 80S visualization both in cultured cells and in fly tissues in vivo. Notably, while the main 80S signal was in the cytoplasm, clear signals were also seen in the nucleolus and at other nuclear sites. Furthermore, we detected rapid puromycin incorporation in the nucleolus and at transcription sites, providing an independent indication of functional 80S in the nucleolus and 80S association with nascent transcripts. PMID:24129492

  13. 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.

  14. 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

  15. 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.

  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. Characterizing the initial encounter complex in cadherin adhesion

    PubMed Central

    Sivasankar, Sanjeevi; Zhang, Yunxiang; Nelson, W. James; Chu, Steven

    2009-01-01

    Summary Cadherins are Ca2+-dependent cell-cell adhesion proteins with an extracellular region of five domains (EC1 to EC5). Adhesion is mediated by “strand-swapping” of a conserved tryptophan residue in position 2 between EC1 domains of opposing cadherins, but the formation of this structure is not well understood. Using single molecule Fluorescence Resonance Energy Transfer (FRET) and single molecule force measurements with the Atomic Force Microscope (AFM), we demonstrate that cadherins initially interact via EC1 domains without swapping tryptophan-2 to form a weak Ca2+ dependent initial encounter complex that has 25% of the bond strength of a strand-swapped dimer. We suggest that cadherin dimerization proceeds via an induced fit mechanism where the monomers first form a tryptophan-2 independent initial encounter complex and then undergo subsequent conformational changes to form the final strand-swapped dimer. PMID:19646884

  18. 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…

  19. Position of the CrPV IRES on the 40S subunit and factor dependence of IRES/80S ribosome assembly.

    PubMed

    Pestova, Tatyana V; Lomakin, Ivan B; Hellen, Christopher U T

    2004-09-01

    The cricket paralysis virus intergenic region internal ribosomal entry site (CrPV IGR IRES) can assemble translation initiation complexes by binding to 40S subunits without Met-tRNA(Met)(i) and initiation factors (eIFs) and then by joining directly with 60S subunits, yielding elongation-competent 80S ribosomes. Here, we report that eIF1, eIF1A and eIF3 do not significantly influence IRES/40S subunit binding but strongly inhibit subunit joining and the first elongation cycle. The IRES can avoid their inhibitory effect by its ability to bind directly to 80S ribosomes. The IRES's ability to bind to 40S subunits simultaneously with eIF1 allowed us to use directed hydroxyl radical cleavage to map its position relative to the known position of eIF1. A connecting loop in the IRES's pseudoknot (PK) III domain, part of PK II and the entire domain containing PK I are solvent-exposed and occupy the E site and regions of the P site that are usually occupied by Met-tRNA(Met)(i). PMID:15332113

  20. Fatigue damage initiation in Waspaloy under complex cyclic loading

    SciTech Connect

    Abdul-Latif, A.; Ferney, V.; Saanouni, K.

    1999-07-01

    The low-cycle fatigue damage initiation i n Waspaloy under complex cyclic loading (out-of-phase) is studied from experimental and theoretical viewpoints. Special emphasis is put on the transgranular damage development and results are compared to those reproduced in the literature. A physico-phenomenological model based on slip theory is used to predict the damage initiation lives as well as the directional aspect of the damage distribution. In this model, the micro-damage is supposed to initiate and then evolve on the activated crystallographic slip systems. The theoretical results are compared to both the experimental ones concerning the same material (Waspaloy) as well as other experimental results extracted from the literature.

  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. The Multimission Modular Spacecraft for the 80's

    NASA Technical Reports Server (NTRS)

    Bartlett, R. O.; Cepollina, F. J.

    1975-01-01

    The challenge to NASA is to prepare for the missions of tomorrow with manpower and funding constraints of today. The Goddard Space Flight Center has met this challenge with the Multimission Modular Spacecraft (MMS). This spacecraft design has evolved over the past six years while studying various potential missions. The key to the concept of the MMS is modularity and flexibility to accept mission unique hardware with minimum impact on the basic spacecraft bus. Beyond this, it was imperative that this multiple mission bus be cost effective even though it would not be of an optimum design for many missions having minimum performance requirements. The MMS performance and cost will capture 34 of the 43 potential spacecraft missions which have been initially studied. Gamma Ray Explorer (GRE) will be the first mission to utilize the MMS.

  4. 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.

  5. 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. PMID:25908488

  6. 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

  7. 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…

  8. 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

  9. Advertising for the 80's. Marketing and Distributive Education. Advertising. Instructor's Guide.

    ERIC Educational Resources Information Center

    Ault, Craig; Elias, John

    This module contains a teacher's guide, student materials for a seminar on "advertising for the 80's" conducted for small business representatives, a 35mm slide presentation, and an audiocassette. The instructor guide contains an outline of the course, time plan, end-of-course critique, a script for the slide-tape presentation (with content on the…

  10. 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.…

  11. 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…

  12. 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

  13. 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

  14. STATIC AND KINETIC SITE-SPECIFIC PROTEIN-DNA PHOTOCROSSLINKING: ANALYSIS OF BACTERIAL TRANSCRIPTION INITIATION COMPLEXES

    PubMed Central

    Naryshkin, Nikolai; Druzhinin, Sergei; Revyakin, Andrei; Kim, Younggyu; Mekler, Vladimir; Ebright, Richard H.

    2009-01-01

    Static site-specific protein-DNA photocrosslinking permits identification of protein-DNA interactions within multiprotein-DNA complexes. Kinetic site-specific protein-DNA photocrosslinking--involving rapid-quench-flow mixing and pulsed-laser irradiation--permits elucidation of pathways and kinetics of formation of protein-DNA interactions within multiprotein-DNA complexes. We present detailed protocols for application of static and kinetic site-specific protein-DNA photocrosslinking to bacterial transcription initiation complexes. PMID:19378179

  15. The activity of the acidic phosphoproteins from the 80 S rat liver ribosome.

    PubMed

    MacConnell, W P; Kaplan, N O

    1982-05-25

    The selective removal of acidic phosphoproteins from the 80 S rat liver ribosome was accomplished by successive alcohol extractions at low salt concentration. The resulting core ribosomes lost over 90% of their translation activity and were unable to support the elongation factor 2 GTPase reaction. Both activities were partially restored when the dialyzed extracts were added back to the core ribosome. The binding of labeled adenosine diphosphoribosyl-elongation factor 2 to ribosomes was also affected by extraction and could be reconstituted, although not to the same extent as the GTPase activity associated with elongation factor 2 in the presence of the ribosome. The alcohol extracts of the 80 S ribosome contained mostly phosphoproteins P1 and P2 which could be dephosphorylated and rephosphorylated in solution by alkaline phosphatase and protein kinase, respectively. Dephosphorylation of the P1/P2 mixture in the extracts caused a decrease in the ability of these proteins to reactivate the polyphenylalanine synthesis activity of the core ribosome. However, treatment of the dephosphorylated proteins with the catalytic subunit of 3':5'-cAMP-dependent protein kinase in the presence of ATP reactivated the proteins when compared to the activity of the native extracts. Rabbit antisera raised against the alcohol-extracted proteins were capable of impairing both the polyphenylalanine synthesis reaction and the elongation factor 2-dependent GTPase reaction in the intact ribosomes. PMID:6121796

  16. Human Mitochondrial Transcription Initiation Complexes Have Similar Topology on the Light and Heavy Strand Promoters.

    PubMed

    Morozov, Yaroslav I; Temiakov, Dmitry

    2016-06-24

    Transcription is a highly regulated process in all domains of life. In human mitochondria, transcription of the circular genome involves only two promoters, called light strand promoter (LSP) and heavy strand promoter (HSP), located in the opposite DNA strands. Initiation of transcription occurs upon sequential assembly of an initiation complex that includes mitochondrial RNA polymerase (mtRNAP) and the initiation factors mitochondrial transcription factor A (TFAM) and TFB2M. It has been recently suggested that the transcription initiation factor TFAM binds to HSP and LSP in opposite directions, implying that the mechanisms of transcription initiation are drastically dissimilar at these promoters. In contrast, we found that binding of TFAM to HSP and the subsequent recruitment of mtRNAP results in a pre-initiation complex that is remarkably similar in topology and properties to that formed at the LSP promoter. Our data suggest that assembly of the pre-initiation complexes on LSP and HSP brings these transcription units in close proximity, providing an opportunity for regulatory proteins to simultaneously control transcription initiation in both mtDNA strands. PMID:27226527

  17. 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

  18. Inhibition of replicon initiation in human cells following stabilization of topoisomerase-DNA cleavable complexes.

    PubMed Central

    Kaufmann, W K; Boyer, J C; Estabrooks, L L; Wilson, S J

    1991-01-01

    Diploid human fibroblast strains were treated for 10 min with inhibitors of type I and type II DNA topoisomerases, and after removal of the inhibitors, the rate of initiation of DNA synthesis at replicon origins was determined. By alkaline elution chromatography, 4'-(9-acridinylamino)methanesulfon-m-anisidide (amsacrine), an inhibitor of DNA topoisomerase II, was shown to produce DNA strand breaks. These strand breaks are thought to reflect drug-induced stabilization of topoisomerase-DNA cleavable complexes. Removal of the drug led to a rapid resealing of the strand breaks by dissociation of the complexes. Velocity sedimentation analysis was used to quantify the effects of amsacrine treatment on DNA replication. It was demonstrated that transient exposure to low concentrations of amsacrine inhibited replicon initiation but did not substantially affect DNA chainelongation within operating replicons. Maximal inhibition of replicon initiation occurred 20 to 30 min after drug treatment, and the initiation rate recovered 30 to 90 min later. Ataxia telangiectasia cells displayed normal levels of amsacrine-induced DNA strand breaks during stabilization of cleavable complexes but failed to downregulate replicon initiation after exposure to the topoisomerase inhibitor. Thus, inhibition of replicon initiation in response to DNA damage appears to be an active process which requires a gene product which is defective or missing in ataxia telangiectasia cells. In normal human fibroblasts, the inhibition of DNA topoisomerase I by camptothecin produced reversible DNA strand breaks. Transient exposure to this drug also inhibited replicon initiation. These results suggest that the cellular response pathway which downregulates replicon initiation following genotoxic damage may respond to perturbations of chromatin structure which accompany stabilization of topoisomerase-DNA cleavable complexes. PMID:1646393

  19. Analysis of the initial values in split-complex backpropagation algorithm.

    PubMed

    Yang, Sheng-Sung; Siu, Sammy; Ho, Chia-Lu

    2008-09-01

    When a multilayer perceptron (MLP) is trained with the split-complex backpropagation (SCBP) algorithm, one observes a relatively strong dependence of the performance on the initial values. For the effective adjustments of the weights and biases in SCBP, we propose that the range of the initial values should be greater than that of the adjustment quantities. This criterion can reduce the misadjustment of the weights and biases. Based on the this criterion, the suitable range of the initial values can be estimated. The results show that the suitable range of the initial values depends on the property of the used communication channel and the structure of the MLP (the number of layers and the number of nodes in each layer). The results are studied using the equalizer scenarios. The simulation results show that the estimated range of the initial values gives significantly improved performance. PMID:18779088

  20. 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.

  1. 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

  2. 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…

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

    PubMed Central

    Smith, Bruce D.; Yarnell, Richard A.

    2009-01-01

    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. PMID:19366669

  4. 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. PMID:19366669

  5. Structural insights into the initiating complex of the lectin pathway of complement activation.

    PubMed

    Kjaer, Troels R; Le, Le T M; Pedersen, Jan Skov; Sander, Bjoern; Golas, Monika M; Jensenius, Jens Christian; Andersen, Gregers R; Thiel, Steffen

    2015-02-01

    The proteolytic cascade of the complement system is initiated when pattern-recognition molecules (PRMs) bind to ligands, resulting in the activation of associated proteases. In the lectin pathway of complement, the complex of mannan-binding lectin (MBL) and MBL-associated serine protease-1 (MASP-1) initiates the pathway by activating a second protease, MASP-2. Here we present a structural study of a PRM/MASP complex and derive the overall architecture of the 450 kDa MBL/MASP-1 complex using small-angle X-ray scattering and electron microscopy. The serine protease (SP) domains from the zymogen MASP-1 dimer protrude from the cone-like MBL tetramer and are separated by at least 20 nm. This suggests that intracomplex activation within a single MASP-1 dimer is unlikely and instead supports intercomplex activation, whereby the MASP SP domains are accessible to nearby PRM-bound MASPs. This activation mechanism differs fundamentally from the intracomplex initiation models previously proposed for both the lectin and the classical pathway. PMID:25579818

  6. Structure of promoter-bound TFIID and model of human pre-initiation complex assembly.

    PubMed

    Louder, Robert K; He, Yuan; López-Blanco, José Ramón; Fang, Jie; Chacón, Pablo; Nogales, Eva

    2016-03-31

    The general transcription factor IID (TFIID) plays a central role in the initiation of RNA polymerase II (Pol II)-dependent transcription by nucleating pre-initiation complex (PIC) assembly at the core promoter. TFIID comprises the TATA-binding protein (TBP) and 13 TBP-associated factors (TAF1-13), which specifically interact with a variety of core promoter DNA sequences. Here we present the structure of human TFIID in complex with TFIIA and core promoter DNA, determined by single-particle cryo-electron microscopy at sub-nanometre resolution. All core promoter elements are contacted by subunits of TFIID, with TAF1 and TAF2 mediating major interactions with the downstream promoter. TFIIA bridges the TBP-TATA complex with lobe B of TFIID. We also present the cryo-electron microscopy reconstruction of a fully assembled human TAF-less PIC. Superposition of common elements between the two structures provides novel insights into the general role of TFIID in promoter recognition, PIC assembly, and transcription initiation. PMID:27007846

  7. 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

  8. 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

  9. 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

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

    PubMed

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

    2016-06-01

    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

  11. The Cryo-EM Structure of a Complete 30S Translation Initiation Complex from Escherichia coli

    PubMed Central

    Julián, Patricia; Milon, Pohl; Agirrezabala, Xabier; Lasso, Gorka; Gil, David; Rodnina, Marina V.; Valle, Mikel

    2011-01-01

    Formation of the 30S initiation complex (30S IC) is an important checkpoint in regulation of gene expression. The selection of mRNA, correct start codon, and the initiator fMet-tRNAfMet requires the presence of three initiation factors (IF1, IF2, IF3) of which IF3 and IF1 control the fidelity of the process, while IF2 recruits fMet-tRNAfMet. Here we present a cryo-EM reconstruction of the complete 30S IC, containing mRNA, fMet-tRNAfMet, IF1, IF2, and IF3. In the 30S IC, IF2 contacts IF1, the 30S subunit shoulder, and the CCA end of fMet-tRNAfMet, which occupies a novel P/I position (P/I1). The N-terminal domain of IF3 contacts the tRNA, whereas the C-terminal domain is bound to the platform of the 30S subunit. Binding of initiation factors and fMet-tRNAfMet induces a rotation of the head relative to the body of the 30S subunit, which is likely to prevail through 50S subunit joining until GTP hydrolysis and dissociation of IF2 take place. The structure provides insights into the mechanism of mRNA selection during translation initiation. PMID:21750663

  12. The Cryo-EM structure of a complete 30S translation initiation complex from Escherichia coli.

    PubMed

    Julián, Patricia; Milon, Pohl; Agirrezabala, Xabier; Lasso, Gorka; Gil, David; Rodnina, Marina V; Valle, Mikel

    2011-07-01

    Formation of the 30S initiation complex (30S IC) is an important checkpoint in regulation of gene expression. The selection of mRNA, correct start codon, and the initiator fMet-tRNA(fMet) requires the presence of three initiation factors (IF1, IF2, IF3) of which IF3 and IF1 control the fidelity of the process, while IF2 recruits fMet-tRNA(fMet). Here we present a cryo-EM reconstruction of the complete 30S IC, containing mRNA, fMet-tRNA(fMet), IF1, IF2, and IF3. In the 30S IC, IF2 contacts IF1, the 30S subunit shoulder, and the CCA end of fMet-tRNA(fMet), which occupies a novel P/I position (P/I1). The N-terminal domain of IF3 contacts the tRNA, whereas the C-terminal domain is bound to the platform of the 30S subunit. Binding of initiation factors and fMet-tRNA(fMet) induces a rotation of the head relative to the body of the 30S subunit, which is likely to prevail through 50S subunit joining until GTP hydrolysis and dissociation of IF2 take place. The structure provides insights into the mechanism of mRNA selection during translation initiation. PMID:21750663

  13. Impact of boron complexation by Tris buffer on the initial dissolution rate of borosilicate glasses.

    PubMed

    Tournié, A; Majérus, O; Lefèvre, G; Rager, M-N; Walmé, S; Caurant, D; Barboux, Ph

    2013-06-15

    Tris(hydroxymethyl)aminomethane is a commonly used buffer for leaching studies on glasses. In this work, we demonstrate that it plays a role on the alteration kinetics of borosilicate glasses. Comparative dissolution experiments on a soda-lime silicate glass and a sodium borosilicate glass, in several solutions with or without Tris at neutral pH, are carried out in order to assess the specific effects of the ionic strength and of the Tris molecules on the initial dissolution kinetics. Tris has no effect on the dissolution of the soda-lime silicate glass, while it significantly enhances the dissolution of the borosilicate glass, by increasing the B, Na, and Si release rates. This specific effect on the borosilicate glass is attributed to the Tris-boron complexation and discussed. The bidentate complexation of boron by Tris(hydroxymethyl)aminomethane (Tris) with a 1:1 stoichiometry is directly demonstrated by infrared and NMR spectroscopies. Complexation constants are determined for the Tris-borate complex and its protonated form Tris-boric, from the (11)B and (1)H NMR spectra. This complexation should be taken into account when using the Tris/HCl buffer in alteration experiments of borosilicate glasses. PMID:23578519

  14. Redundant cooperative interactions for assembly of a human U6 transcription initiation complex.

    PubMed

    Ma, Beicong; Hernandez, Nouria

    2002-11-01

    The core human U6 promoter consists of a proximal sequence element (PSE) located upstream of a TATA box. The PSE is recognized by the snRNA-activating protein complex (SNAP(c)), which consists of five types of subunits, SNAP190, SNAP50, SNAP45, SNAP43, and SNAP19. The TATA box is recognized by TATA box binding protein (TBP). In addition, basal U6 transcription requires the SANT domain protein Bdp1 and the transcription factor IIB-related factor Brf2. SNAP(c) and mini-SNAP(c), which consists of just SNAP43, SNAP50, and the N-terminal third of SNAP190, bind cooperatively with TBP to the core U6 promoter. By generating complexes smaller than mini-SNAP(c), we have identified a 50-amino-acid region within SNAP190 that is (i) required for cooperative binding with TBP in the context of mini-SNAP(c) and (ii) sufficient for cooperative binding with TBP when fused to a heterologous DNA binding domain. We show that derivatives of mini-SNAP(c) lacking this region are active for transcription and that with such complexes, TBP can still be recruited to the U6 promoter through cooperative interactions with Brf2. Our results identify complexes smaller than mini-SNAP(c) that are transcriptionally active and show that there are at least two redundant mechanisms to stably recruit TBP to the U6 transcription initiation complex. PMID:12391172

  15. Redundant Cooperative Interactions for Assembly of a Human U6 Transcription Initiation Complex

    PubMed Central

    Ma, Beicong; Hernandez, Nouria

    2002-01-01

    The core human U6 promoter consists of a proximal sequence element (PSE) located upstream of a TATA box. The PSE is recognized by the snRNA-activating protein complex (SNAPc), which consists of five types of subunits, SNAP190, SNAP50, SNAP45, SNAP43, and SNAP19. The TATA box is recognized by TATA box binding protein (TBP). In addition, basal U6 transcription requires the SANT domain protein Bdp1 and the transcription factor IIB-related factor Brf2. SNAPc and mini-SNAPc, which consists of just SNAP43, SNAP50, and the N-terminal third of SNAP190, bind cooperatively with TBP to the core U6 promoter. By generating complexes smaller than mini-SNAPc, we have identified a 50-amino-acid region within SNAP190 that is (i) required for cooperative binding with TBP in the context of mini-SNAPc and (ii) sufficient for cooperative binding with TBP when fused to a heterologous DNA binding domain. We show that derivatives of mini-SNAPc lacking this region are active for transcription and that with such complexes, TBP can still be recruited to the U6 promoter through cooperative interactions with Brf2. Our results identify complexes smaller than mini-SNAPc that are transcriptionally active and show that there are at least two redundant mechanisms to stably recruit TBP to the U6 transcription initiation complex. PMID:12391172

  16. 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.

  17. 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.

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

    PubMed Central

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

    2015-01-01

    Summary 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. PMID:26212456

  19. 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

  20. 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

  1. Collybistin and gephyrin are novel components of the eukaryotic translation initiation factor 3 complex

    PubMed Central

    2010-01-01

    Background Collybistin (CB), a neuron-specific guanine nucleotide exchange factor, has been implicated in targeting gephyrin-GABAA receptors clusters to inhibitory postsynaptic sites. However, little is known about additional CB partners and functions. Findings Here, we identified the p40 subunit of the eukaryotic translation initiation factor 3 (eIF3H) as a novel binding partner of CB, documenting the interaction in yeast, non-neuronal cell lines, and the brain. In addition, we demonstrated that gephyrin also interacts with eIF3H in non-neuronal cells and forms a complex with eIF3 in the brain. Conclusions Together, our results suggest, for the first time, that CB and gephyrin associate with the translation initiation machinery, and lend further support to the previous evidence that gephyrin may act as a regulator of synaptic protein synthesis. PMID:20858277

  2. Structure of an RNA polymerase II-TFIIB complex and the transcription initiation mechanism.

    PubMed

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

    2010-01-01

    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. PMID:19965383

  3. 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.

  4. 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.

  5. 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

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

    PubMed

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

    2016-04-12

    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 σ(S) factor, a de novo synthesized RNA oligonucleotide, and a complete transcription bubble (σ(S)-TIC) at about 3.9-Å resolution. The structures show the 3D topology of the σ(S) factor and how it recognizes the promoter DNA, including likely specific interactions with the template-strand residues of the -10 element. In addition, σ(S)-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 σ(S)-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

  7. 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

  8. Structural Changes Enable Start Codon Recognition by the Eukaryotic Translation Initiation Complex

    PubMed Central

    Hussain, Tanweer; Llácer, Jose L.; Fernández, Israel S.; Munoz, Antonio; Martin-Marcos, Pilar; Savva, Christos G.; Lorsch, Jon R.; Hinnebusch, Alan G.; Ramakrishnan, V.

    2014-01-01

    Summary During eukaryotic translation initiation, initiator tRNA does not insert fully into the P decoding site on the 40S ribosomal subunit. This conformation (POUT) is compatible with scanning mRNA for the AUG start codon. Base pairing with AUG is thought to promote isomerization to a more stable conformation (PIN) that arrests scanning and promotes dissociation of eIF1 from the 40S subunit. Here, we present a cryoEM reconstruction of a yeast preinitiation complex at 4.0 Å resolution with initiator tRNA in the PIN state, prior to eIF1 release. The structure reveals stabilization of the codon-anticodon duplex by the N-terminal tail of eIF1A, changes in the structure of eIF1 likely instrumental in its subsequent release, and changes in the conformation of eIF2. The mRNA traverses the entire mRNA cleft and makes connections to the regulatory domain of eIF2α, eIF1A, and ribosomal elements that allow recognition of context nucleotides surrounding the AUG codon. PMID:25417110

  9. 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.

  10. 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

  11. Initial Characterization of the FlgE Hook High Molecular Weight Complex of Borrelia burgdorferi

    PubMed Central

    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

  12. The little elongation complex functions at initiation and elongation phases of snRNA gene transcription.

    PubMed

    Hu, Deqing; Smith, Edwin R; Garruss, Alexander S; Mohaghegh, Nima; Varberg, Joseph M; Lin, Chengqi; Jackson, Jessica; Gao, Xin; Saraf, Anita; Florens, Laurence; Washburn, Michael P; Eissenberg, Joel C; Shilatifard, Ali

    2013-08-22

    The small nuclear RNA (snRNA) genes have been widely used as a model system for understanding transcriptional regulation due to the unique aspects of their promoter structure, selectivity for either RNA polymerase (Pol) II or III, and because of their unique mechanism of termination that is tightly linked with the promoter. Recently, we identified the little elongation complex (LEC) in Drosophila that is required for the expression of Pol II-transcribed snRNA genes. Here, using Drosophila and mammalian systems, we provide genetic and molecular evidence that LEC functions in at least two phases of snRNA transcription: an initiation step requiring the ICE1 subunit, and an elongation step requiring ELL. PMID:23932780

  13. The Little Elongation Complex functions at initiation and elongation phases of snRNA gene transcription

    PubMed Central

    Hu, Deqing; Smith, Edwin R.; Garruss, Alexander S.; Mohaghegh, Nima; Varberg, Joseph M.; Lin, Chengqi; Jackson, Jessica; Gao, Xin; Saraf, Anita; Florens, Laurence; Washburn, Michael P.; Eissenberg, Joel C.; Shilatifard, Ali

    2014-01-01

    SUMMARY The small nuclear RNA (snRNA) genes have been widely used as a model system for understanding transcriptional regulation due to the unique aspects of their promoter structure, selectivity for either RNA Polymerase (Pol) II or III, and because of their unique mechanism of termination that is tightly linked with the promoter. Recently, we identified the Little Elongation Complex (LEC) in Drosophila that is required for the expression of Pol II-transcribed snRNA genes. Here, using Drosophila and mammalian systems, we provide genetic and molecular evidence that LEC functions in at least two phases of snRNA transcription: an initiation step requiring the ICE1 subunit, and an elongation step requiring ELL. PMID:23932780

  14. Rapidly progressed acquired immunodeficiency syndrome dementia complex as an initial manifestation.

    PubMed

    Takeuchi, Makoto; Nobukuni, Keigo; Takata, Hiroshi; Kawata, Noriko; Hayashibara, Noriko; Ishizu, Hideki; Takahashi, Kiyoshi

    2005-07-01

    We report a patient with acquired immunodeficiency syndrome dementia complex (ADC) that presented human immunodeficiency virus infection as an initial manifestation. A 34-year-old man developed disturbance of consciousness and severe abulia over 3 months. The CD4 lymphocyte count was 7.9/microl, while human immunodeficiency virus RNA in blood amounted to 4.2 x 10(4) copies/ml. T2-weighted magnetic resonance imaging showed diffusely high signal intensity in the deep white matter of both cerebral hemispheres. On the 20th hospital day, the patient died of sepsis caused by methicillin-resistant Staphylococcus aureus. Autopsy findings in the brain included increased glial cells and multinucleated giant cells in cerebral white matter and subcortical gray matter. These features were compatible with ADC. PMID:16093602

  15. 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.

  16. Xenopus origin recognition complex (ORC) initiates DNA replication preferentially at sequences targeted by Schizosaccharomyces pombe ORC.

    PubMed

    Kong, Daochun; Coleman, Thomas R; DePamphilis, Melvin L

    2003-07-01

    Budding yeast (Saccharomyces cerevisiae) origin recognition complex (ORC) requires ATP to bind specific DNA sequences, whereas fission yeast (Schizosaccharomyces pombe) ORC binds to specific, asymmetric A:T-rich sites within replication origins, independently of ATP, and frog (Xenopus laevis) ORC seems to bind DNA non-specifically. Here we show that despite these differences, ORCs are functionally conserved. Firstly, SpOrc1, SpOrc4 and SpOrc5, like those from other eukaryotes, bound ATP and exhibited ATPase activity, suggesting that ATP is required for pre-replication complex (pre-RC) assembly rather than origin specificity. Secondly, SpOrc4, which is solely responsible for binding SpORC to DNA, inhibited up to 70% of XlORC-dependent DNA replication in Xenopus egg extract by preventing XlORC from binding to chromatin and assembling pre-RCs. Chromatin-bound SpOrc4 was located at AT-rich sequences. XlORC in egg extract bound preferentially to asymmetric A:T-sequences in either bare DNA or in sperm chromatin, and it recruited XlCdc6 and XlMcm proteins to these sequences. These results reveal that XlORC initiates DNA replication preferentially at the same or similar sites to those targeted in S.pombe. PMID:12840006

  17. [Organization and development of neurochemical research in the Dnepr area (the 60-80s)].

    PubMed

    Chernaia, V I; Nazarenko, V I

    1996-01-01

    The development of neurochemical investigations at the Institute of Biochemistry of the National Academy of Sciences of Ukraine initiated by Academician A. V. Palladin, has impelled specialists in some regions of the country to start research in this trend. The Department of Biophysics and Biochemistry of Dniepropetrovsk State University founded and headed by Professor O. D. Reva became one of such centres in the Dnieper area. The chief developments of scientific-research inventions were devoted to radiational neurochemistry, O. D. Reva should be accounted as a pioneer of the study of chemical composition and metabolism in functional and morphologically logically different sites of cats spinal cord lumbar enlargement. Thus, the significant statement, proposed by A. V. Palladin, was confirmed about the presence of biochemical differentiation in cerebrum besides the morphological and functional ones. While analysing the test data concerning the biochemical and biophysical indices of roentgen irradiation of cats in different terms and conditions an original scheme of radiation-biophysical and radiation-biochemical injury of spinal cord was proposed. Some tissue proteinases, as well as some neurospecific proteins in the norm and under the gamma-irradiation were selected and assayed. An immunoelectrophoretic technique for estimating glyolic fibrilar acid protein and cellular adhesion (N-CAM) in blood and surrounding fluid, as well as in human brain tumour was developed and a method of early prenatal diagnosis of embryo developmental disorders was proposed in order to prevent the birth of the underdeveloped infants. PMID:9229846

  18. Molecular mechanisms of translation initiation in eukaryotes

    PubMed Central

    Pestova, Tatyana V.; Kolupaeva, Victoria G.; Lomakin, Ivan B.; Pilipenko, Evgeny V.; Shatsky, Ivan N.; Agol, Vadim I.; Hellen, Christopher U. T.

    2001-01-01

    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 mRNA. The cap-binding complex eIF4F and the factors eIF4A and eIF4B are required for binding of 43S complexes (comprising a 40S subunit, eIF2/GTP/Met-tRNAi and eIF3) to the 5′ end of capped mRNA but are not sufficient to promote ribosomal scanning to the initiation codon. eIF1A enhances the ability of eIF1 to dissociate aberrantly assembled complexes from mRNA, and these factors synergistically mediate 48S complex assembly at the initiation codon. Joining of 48S complexes to 60S subunits to form 80S ribosomes requires eIF5B, which has an essential ribosome-dependent GTPase activity and hydrolysis of eIF2-bound GTP induced by eIF5. Initiation on a few mRNAs is cap-independent and occurs instead by internal ribosomal entry. Encephalomyocarditis virus (EMCV) and hepatitis C virus epitomize distinct mechanisms of internal ribosomal entry site (IRES)-mediated initiation. The eIF4A and eIF4G subunits of eIF4F bind immediately upstream of the EMCV initiation codon and promote binding of 43S complexes. EMCV initiation does not involve scanning and does not require eIF1, eIF1A, and the eIF4E subunit of eIF4F. Initiation on some EMCV-like IRESs requires additional noncanonical initiation factors, which alter IRES conformation and promote binding of eIF4A/4G. Initiation on the hepatitis C virus IRES is even simpler: 43S complexes containing only eIF2 and eIF3 bind directly to the initiation codon as a result of specific interaction of the IRES and the 40S subunit. PMID:11416183

  19. Complexities in rift initiation and development within the Iceland Plateau, North-Atlantic.

    NASA Astrophysics Data System (ADS)

    Brandsdóttir, Bryndís; Hooft, Emilie; Mjelde, Rolf; Murai, Yoshio

    2015-04-01

    Spreading north of Iceland has been complex since the break-up of the North Atlantic in late Paleocene-early Eocene. Magnetic anomalies within the Iceland Plateau, west of the Ægir Ridge and along the Greenland-Iceland-Faeroe Ridge are irregular, formed by plate boundary complexities at breakup, branched accretion zones, westward rifting relocations, and large overlapping rifts. The 700 km long KRISE7 seismic refraction/reflection and gravity profile, straddles 66.5°N, between the Kolbeinsey and Ægir Ridges, crossing the three physiographic provinces that characterize this region: the Iceland Shelf, Iceland Plateau and Norway Basin. On the basis of crustal thickness and velocity structure, combined with older seismic reflection profiles and drill cores, these provinces correspond to three individual spreading rifts that were active at different time periods. The deep, fan shaped Norway basin was formed during the initial opening of the Atlantic by spreading at the now extinct Ægir Ridge. The oldest crust in the western Norway Basin has thickness 8-10 km and this thins to 4-5 km at the Ægir Ridge reflecting the progressive abandonment of spreading at this rift axis. The eastern Iceland Plateau was the locus of an extinct spreading center, which was segmented and overlapped the Ægir Ridge by 300 km. Spreading on the Iceland Plateau rift occurred simultaneously with that on the Ægir Ridge prior to 26 Ma, when the Kolbeinsey Ridge was initiated by a westward rift jump. The Iceland Plateau rift formed by rifting along the continent-ocean transition at the former central E-Greenland margin, associated with the formation of the Jan Mayen Ridge. Lower crustal domes and corresponding gravity highs across the Iceland Plateau mark the location of the extinct rift axis. The crust at the Iceland Plateau rift is thicker (12-15 km) that that at the conjugate Ægir Ridge and formed under active upwelling conditions (normal lower crustal velocities), which we attribute to

  20. [Contraceptive development--the view from the U.S.A. in the mid 80s].

    PubMed

    Potts, M; Siemens, A; Burton, N

    1986-03-01

    Contraceptive research and development in the US has been slowed by declining investment at a time of rising costs and increasingly complex US Food and Drug Administration (FDA) regulation. Public and private investment in contraceptive research reached its maximum in the early 1970s. Since then, investment has stagnated while research and development costs have continued to rise. Development of a new product costs between 50-60 million dollars and corresponds to over 2/3 of its legal life of 17 years. In addition, the majority of pharmaceutical liability cases in the past few years have involved contraceptives. Although recent epidemiological studies have demonstrated that oral contraceptives (OCs) have some significant benefits, such as prevention of at least 2 types of cancer, OCs continue to be held responsible for secondary cardiovascular effects as well as for some effects whose true etiology has not been demonstrated. The growing use of contraceptive sterilization at the expense of most other methods and the opposition to making contraceptives easily available among those who believe that contraception encourages premarital sexual activity are other factors which have resulted in the near abandonment of contraceptive research and development by American pharmaceutical companies, who no longer consider family planning a viable market. In the US, most research and innovation in the field of contraception now comes from not-for-profit institutions such as Family Health International (FHI) the Population Council, and to a lesser extent the Program of Applied Research for Fertility Regulation and some universities. Such organizations receive some research funds from the Agency for International Development and the National Institutes of Health. The role of FHI in the development of the contraceptive sponge and of the Population Council in developemnt of the Copper T 380A IUD demonstrate the transfer of supremacy in contraceptive development from the

  1. Initial experience with transluminally placed endovascular grafts for the treatment of complex vascular lesions.

    PubMed Central

    Marin, M L; Veith, F J; Cynamon, J; Sanchez, L A; Lyon, R T; Levine, B A; Bakal, C W; Suggs, W D; Wengerter, K R; Rivers, S P

    1995-01-01

    OBJECTIVES: Complex arterial occlusive, traumatic, and aneurysmal lesions may be difficult or impossible to treat successfully by standard surgical techniques when severe medical or surgical comorbidities exist. The authors describe a single center's experience over a 2 1/2-year period with 96 endovascular graft procedures performed to treat 100 arterial lesions in 92 patients. PATIENTS AND METHODS: Thirty-three patients had 36 large aortic and/or peripheral artery aneurysms, 48 had 53 multilevel limb-threatening aortoiliac and/or femoropopliteal occlusive lesions, and 11 had traumatic arterial injuries (false aneurysms and arteriovenous fistulas). Endovascular grafts were placed through remote arteriotomies under local (16[17%]), epidural (42[43%]), or general (38[40%]) anesthesia. RESULTS: Technical and clinical successes were achieved in 91% of the patients with aneurysms, 91% with occlusive lesions, and 100% with traumatic arterial lesions. These patients and grafts have been followed from 1 to 30 months (mean, 13 months). The primary and secondary patency rates at 18 months for aortoiliac occlusions were 77% and 95%, respectively. The 18-month limb salvage rate was 98%. Immediately after aortic aneurysm exclusion, a total of 6 (33%) perigraft channels were detected; 3 of these closed within 8 weeks. Endovascular stented graft procedures were associated with a 10% major and a 14% minor complication rate. The overall 30-day mortality rate for this entire series was 6%. CONCLUSIONS: This initial experience with endovascular graft repair of complex arterial lesions justifies further use and careful evaluation of this technique for major arterial reconstruction. Images Figure 1. Figure 4. Figure 5. Figure 5. Figure 6. Figure 7. Figure 8. Figure 9. Figure 11. PMID:7574926

  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. PMID:21749161

  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. 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.

  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. DIRAS3 regulates the autophagosome initiation complex in dormant ovarian cancer cells

    PubMed Central

    Lu, Zhen; Baquero, Maria T; Yang, Hailing; Yang, Maojie; Reger, Albert S; Kim, Choel; Levine, Douglas A; Clarke, Charlotte H; Liao, Warren S-L; Bast Jr, Robert C

    2014-01-01

    DIRAS3 is an imprinted tumor suppressor gene that is downregulated in 60% of human ovarian cancers. Re-expression of DIRAS3 at physiological levels inhibits proliferation, decreases motility, induces autophagy, and regulates tumor dormancy. Functional inhibition of autophagy with choroquine in dormant xenografts that express DIRAS3 significantly delays tumor regrowth after DIRAS3 levels are reduced, suggesting that autophagy sustains dormant ovarian cancer cells. This study documents a newly discovered role for DIRAS3 in forming the autophagosome initiation complex (AIC) that contains BECN1, PIK3C3, PIK3R4, ATG14, and DIRAS3. Participation of BECN1 in the AIC is inhibited by binding of BECN1 homodimers to BCL2. DIRAS3 binds BECN1, disrupting BECN1 homodimers and displacing BCL2. Binding of DIRAS3 to BECN1 increases the association of BECN1 with PIK3C3 and ATG14, facilitating AIC activation. Amino acid starvation of cells induces DIRAS3 expression, reduces BECN1-BCL2 interaction and promotes autophagy, whereas DIRAS3 depletion blocks amino acid starvation-induced autophagy. In primary ovarian cancers, punctate expression of DIRAS3, BECN1, and the autophagic biomarker MAP1LC3 are highly correlated (P < 0.0001), underlining the clinical relevance of these mechanistic studies. Punctate expression of DIRAS3 and MAP1LC3 was detected in only 21–23% of primary ovarian cancers but in 81–84% of tumor nodules found on the peritoneal surface at second-look operations following primary chemotherapy. This reflects a 4-fold increase (P < 0.0001) in autophagy between primary disease and post-treatment recurrence. We suggest that DIRAS3 not only regulates the AIC, but induces autophagy in dormant, nutrient-deprived ovarian cancer cells that remain after conventional chemotherapy, facilitating their survival. PMID:24879154

  7. Initial Isotopic Heterogeneities in ZAGAMI: Evidence of a Complex Magmatic History

    NASA Technical Reports Server (NTRS)

    Nyquist, L. E.; Shih, C.-Y.; Reese, Y. D.

    2006-01-01

    Interpretations of Zagami s magmatic history range from complex [1,2] to relatively simple [3]. Discordant radiometric ages led to a suggestion that the ages had been reset [4]. In an attempt to identify the mechanism, Rb-Sr isochrons were individually determined for both fine-grained and coarse-grained Zagami [5]. Ages of approx.180 Ma were obtained from both lithologies, but the initial Sr-87/Sr-86 (ISr) of the fine-grained lithology was higher by 8.6+/-0.4 e-units. Recently, a much older age of approx.4 Ga has been advocated [6]. Here, we extend our earlier investigation [5]. Rb-Sr Data: In [5] we applied identical, simplified, procedures to both lithologies to test whether a grain-size dependent process such as thermally-driven subsolidus isotopic reequilibration had caused age-resetting. Minerals were separated only by density. In the present experiment, purer mineral separates were analysed with improved techniques. Combined Rb-Sr results give ages (T) = 166+/-12 Ma and 177+/-9 Ma and I(subSr) = 0.72174+/-9 and 0.72227+/-7 for the coarse-grained and fine-grained lithologies, respectively. ISr in the fine-grained sample is thus higher than in the coarse-grained sample by 7.3+/-1.6 e-units. The results for the coarse-grained lithology are in close agreement with T = 166+/-6 Ma, ISr = 0.72157+/-8 for an adjacent sample [7] and T = 178+/-4 Ma, ISr = 0.72151+/-5 [4, adjusted] for a separate sample. Thus, fine-grained Zagami appears on average to be less typical of the bulk than coarse-grained Zagami.

  8. 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

  9. 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.

  10. 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

  11. COMPARATIVE TUMOR-INITIATING ACTIVITY OF COMPLEX MIXTURES FROM ENVIRONMENTAL PARTICULATE EMISSIONS ON SENCAR MOUSE SKIN

    EPA Science Inventory

    The value of the SENCAR mouse for testing tumorigenic properties of complex mixtures on mouse skin was studied. Seven complex mixtures were obtained as dichloromethane extracts of collected particulate emissions from three diesel-fueled automobiles, a heavy-duty diesel engine, a ...

  12. 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.

  13. Ctk1 function is necessary for full translation initiation activity in Saccharomyces cerevisiae.

    PubMed

    Coordes, Britta; Brünger, Katharina M; Burger, Kaspar; Soufi, Boumediene; Horenk, Juliane; Eick, Dirk; Olsen, Jesper V; Sträßer, Katja

    2015-01-01

    Translation is a fundamental and highly regulated cellular process. Previously, we reported that the kinase and transcription elongation factor Ctk1 increases fidelity during translation elongation in Saccharomyces cerevisiae. Here, we show that loss of Ctk1 function also affects the initiation step of translation. Translation active extracts from Ctk1-depleted cells show impaired translation activity of capped mRNA, but not mRNA reporters containing the cricket paralysis virus (CrPV) internal ribosome entry site (IRES). Furthermore, the formation of 80S initiation complexes is decreased, which is probably due to reduced subunit joining. In addition, we determined the changes in the phosphorylation pattern of a ribosome enriched fraction after depletion of Ctk1. Thus, we provide a catalogue of phosphoproteomic changes dependent on Ctk1. Taken together, our data suggest a stimulatory function of Ctk1 in 80S formation during translation initiation. PMID:25416238

  14. Molecular architecture of the 40S⋅eIF1⋅eIF3 translation initiation complex.

    PubMed

    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

    2014-08-28

    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

  15. 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

  16. 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

  17. 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

  18. 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

  19. Synthesis and structures of bis-ligated zinc complexes supported by tridentate ketoimines that initiate L-lactide polymerization.

    PubMed

    Gerling, Kimberly A; Rezayee, Nomaan M; Rheingold, Arnold L; Green, David B; Fritsch, Joseph M

    2014-11-21

    Eight bis-ligated, homoleptic, zinc complexes were synthesized through the reaction of NNO Schiff base ketoimines bearing varying substituents with diethyl zinc in an inert atmosphere glovebox at room temperature and isolated in 62-95% yield. The complexes were characterized with (1)H, (13)C, and (19)F nuclear magnetic resonance spectroscopy, absorbance spectroscopy, high resolution mass spectrometry, elemental analysis, and single crystal X-ray crystallography. The complexes were shown to adopt distorted octahedral coordination geometry around zinc. The (1)H and (19)F NMR spectra of complexes 1-7 showed stable zinc coordination at 300 K while the effect of steric encumbrance and two trifluoromethyl groups in complex 8 was investigated with variable temperature NMR. The bis-ligated zinc complexes were effective initiators for the ring opening polymerization of L-lactide into poly-L-lactic acid (PLLA). With [L-lac]/[Zn complex] = 50, the bis-ligated zinc complexes yielded percentage conversion of 14-98% with polymerization times varying from 15-1440 min, where the longest reaction times were required when two trifluoromethyl groups were present. The addition of 4-fluorophenol co-catalyst resulted in up to a 5-fold increase in the percentage conversion in toluene solution and up to a 14-fold increase in bulk melt polymerization with reductions in the poly-dispersity index values for the isolated PLLA. Addition of 4-fluorophenol to complex 1 was studied with (1)H and (19)F NMR and appeared to yield an in situ generated zinc alkoxide complex. PMID:25256407

  20. 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).

  1. 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. PMID:26723252

  2. 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.

  3. 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

  4. 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

  5. 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…

  6. 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,…

  7. 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

  8. Crystal structures of two intermediates in the assembly of the papillomavirus replication initiation complex.

    PubMed

    Enemark, Eric J; Stenlund, Arne; Joshua-Tor, Leemor

    2002-03-15

    Initiation of DNA replication of the papillomavirus genome is a multi-step process involving the sequential loading of viral E1 protein subunits onto the origin of replication. Here we have captured structural snapshots of two sequential steps in the assembly process. Initially, an E1 dimer binds to adjacent major grooves on one face of the double helix; a second dimer then binds to another face of the helix. Each E1 monomer has two DNA-binding modules: a DNA-binding loop, which binds to one DNA strand and a DNA-binding helix, which binds to the opposite strand. The nature of DNA binding suggests a mechanism for the transition between double- and single-stranded DNA binding that is implicit in the progression to a functional helicase. PMID:11889054

  9. 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

  10. 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

  11. 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.

  12. 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.

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

    PubMed Central

    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

    2015-01-01

    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. PMID:25733582

  14. Molecular Mechanisms of Transcription Initiation-Structure, Function, and Evolution of TFE/TFIIE-Like Factors and Open Complex Formation.

    PubMed

    Blombach, Fabian; Smollett, Katherine L; Grohmann, Dina; Werner, Finn

    2016-06-19

    Transcription initiation requires that the promoter DNA is melted and the template strand is loaded into the active site of the RNA polymerase (RNAP), forming the open complex (OC). The archaeal initiation factor TFE and its eukaryotic counterpart TFIIE facilitate this process. Recent structural and biophysical studies have revealed the position of TFE/TFIIE within the pre-initiation complex (PIC) and illuminated its role in OC formation. TFE operates via allosteric and direct mechanisms. Firstly, it interacts with the RNAP and induces the opening of the flexible RNAP clamp domain, concomitant with DNA melting and template loading. Secondly, TFE binds physically to single-stranded DNA in the transcription bubble of the OC and increases its stability. The identification of the β-subunit of archaeal TFE enabled us to reconstruct the evolutionary history of TFE/TFIIE-like factors, which is characterised by winged helix (WH) domain expansion in eukaryotes and loss of metal centres including iron-sulfur clusters and Zinc ribbons. OC formation is an important target for the regulation of transcription in all domains of life. We propose that TFE and the bacterial general transcription factor CarD, although structurally and evolutionary unrelated, show interesting parallels in their mechanism to enhance OC formation. We argue that OC formation is used as a way to regulate transcription in all domains of life, and these regulatory mechanisms coevolved with the basal transcription machinery. PMID:27107643

  15. A topological model for transcription based on unwinding angle analysis of E. coli RNA polymerase binary, initiation and ternary complexes.

    PubMed

    Gamper, H B; Hearst, J E

    1982-05-01

    DNA unwinding induced by Escherichia coli RNA polymerase is measured for binary, initiation and ternary complexes formed from a unique promoter sequence on simian virus 40 DNA. At 37 degrees C the complexes all have an unwinding angle of 17 +/- 1 base pairs (580 degrees +/- 30 degrees). This unwinding is attributed to an enzyme-stabilized separation of the double helix at the promoter site, which is maintained throughout initiation and elongation. There is no heterogeneity in the unwinding angle of the ternary complex as it progresses down the helical template. The constant DNA unwinding during all phases of transcription leads us to propose the existence of unwindase and rewindase activities on the enzyme that allow it to travel down the helix like a nut on a DNA bolt. During elongation, the unwindase unwinds the DNA helix while the rewindase, lagging by 17 base pairs, displaces the RNA transcript and reseals the helix. Both activities induce a rotation in the DNA double helix relative to the polymerase. The RNA-DNA hybrid also rotates, maintaining both ends of that helix fixed relative to the catalytic and windase sites. Formation of an RNA-DNA hybrid which spans the distal end of the DNA unwound region is proposed as a possible mechanism for polymerase pausing and termination. This model requires that the polymerase direct the transcript past the noncoding DNA strand. Pausing occurs 16-20 nucleotides downstream from the centers of appropriately sized dyad symmetry elements. PMID:6286146

  16. Initial application of tomographic particle image velocimetry to complex (dusty) plasmas

    NASA Astrophysics Data System (ADS)

    Williams, J.

    2010-11-01

    Over the last decade, two-dimensional and stereoscopic particle image velocimetry (PIV) techniques have been applied in the study of wave, transport and thermal properties of complex (dusty) plasma. While a great deal of insight has been gained from these studies, these studies have also indicated that volumetric three-dimensional information is needed. To address this need, the Wittenberg University Plasma Laboratory (WUPL) has recently acquired and installed a tomographic PIV (tomo-PIV) diagnostic system for dusty plasma investigations. It employs a synchronized dual YAG laser, four camera system for measuring the particle transport in three dimensions over an extended volume. This poster will present information on this diagnostic technique and preliminary results.

  17. 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.

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

    DOE PAGESBeta

    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

  19. 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

  20. 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.

  1. [Ultrastructural and immunocytochemical analysis of the synaptonemal complex at the initiation of synapsis].

    PubMed

    Flores-Rivera, E; Villegas-Castrejon, H; Vazquez-Nin, G H

    1996-04-01

    The synaptonemal complexes (SCs) are nuclear structures specific for meiosis. They have a central role in homolog chromosomes coupling; they are essential in crossing over events and chromosomic segregation during the first meiotic division. When its joining ends in pakiteno stage, each synaptonemal extends along the bivalent joining the ends to nuclear wrapping. The SCs are characterized by the presence of two lateral elements and a central region. The lateral elements are parallel and equidistant. The chromatine of homolog chromosomes fixes in a series of loops to these elements. The central region is between the lateral elements. It is formed by the latero-medial fibers and the medial element. The first ones are perpendicularly oriented to the longitudinal axis of CS and connect lateral elements with the medial element. The recombination modules have an active role in recombination processes and quiasma formation, they are associated, at intervals, with the central region among the homolog chromosomes. The localization and function of nucleic acids in formation and coupling of synaptonemal complex is little known, so methodologic alternatives are looked for to resolve this type of problems. In this work, ADN distribution in chicken ovocytes in cigotene, using techniques for electronic microscopy of immuno-oro, were studied. Besides, cytochemical techniques, were used as preferential contrast for ADN or preferential for ribonucleoproteins (RNPs). The combination of preferential tincture for RNPs and immunolocalization of ADN show that chromatin accumulates jointly with ribonucleoproteins in nor coupled lateral elements and the presence of numerous RNPs fibers distributed around lateral elements. Recombination nodules were found among lateral elements during the coupling, these nodules are PTA positives, which means ADN presence, and so, ADN presence among lateral elements. THe presence of a bridge of marked fibers with coloidal gold (ADN) uniting not coupled

  2. A Day-Hospital Approach to Treatment of Pediatric Complex Regional Pain Syndrome: Initial Functional Outcomes

    PubMed Central

    Logan, Deirdre E.; Carpino, Elizabeth A.; Chiang, Gloria; Condon, Marianne; Firn, Emily; Gaughan, Veronica J.; Hogan, Melinda, P.T.; Leslie, David S.; Olson, Katie, P.T.; Sager, Susan; Sethna, Navil; Simons, Laura E.; Zurakowski, David; Berde, Charles B.

    2013-01-01

    Objectives To examine clinical outcomes of an interdisciplinary day hospital treatment program (comprised of physical, occupational, and cognitive-behavioral therapies with medical and nursing services) for pediatric complex regional pain syndrome (CRPS). Methods The study is a longitudinal case series of consecutive patients treated in a day hospital pediatric pain rehabilitation program. Participants were 56 children and adolescents ages 8–18 years (median = 14 years) with CRPS spectrum conditions who failed to progress sufficiently with a previous outpatient and/or inpatient treatments. Patients participated in daily physical therapy, occupational therapy and psychological treatment and received nursing and medical care as necessary. The model places equal emphasis on physical and cognitive-behavioral approaches to pain management. Median duration of stay was 3 weeks. Outcome measures included assessments of physical, occupational, and psychological functioning at program admission, discharge, and at post-treatment follow-up at a median of 10 months post-discharge. Scores at discharge and follow-up were compared with measures on admission by Wilcoxon tests, paired t tests, or ANOVA as appropriate, with corrections for multiple comparisons. Results Outcomes demonstrate clinically and statistically significant improvements from admission to discharge in pain intensity (p<0.001), functional disability (p<0.001), subjective report of limb function (p<0.001), timed running (p<0.001) occupational performance (p<0.001), medication use (p<0.01), use of assistive devices (p<0.001), and emotional functioning (anxiety, p<0.001; depression, p<0.01). Functional gains were maintained or further improved at follow-up. Discussion A day-hospital interdisciplinary rehabilitation approach appears effective in reducing disability and improving physical and emotional functioning and occupational performance among children and adolescents with complex regional pain syndromes that

  3. 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

  4. Two styles of faulting associated with metamorphic core complexes: Importance of initial crustal configuration and mid-crustal flow

    NASA Astrophysics Data System (ADS)

    Wu, G.; Lavier, L. L.; Choi, E.

    2012-12-01

    Two styles of faulting, sequential- and domino-style, have been identified in metamorphic core complexes (MCCs) and discussed by various workers, however, a consensus has not been reached on the exact mechanisms and relationships between the two styles of faulting. We used a three layered model of the crust, i.e., upper, middle and lower crust and used numerical method to study the formation of different types of MCCs. We found that the initial crustal structure and crustal strength of each layer, viscosity contrast between upper and middle crust particularly, are of great importance. An initially symmetric crustal structure, i.e., uniform thickness of each layer throughout the crust, generally favors sequential normal faulting, and leads to MCCs beneath sequentially initiated and then deactivated normal faults. However, an initially asymmetric crustal structure, i.e., variable thickness of each layer of the crust, favors sequential-style migratory low angle master faults to the first order, and domino-style high angle normal faults above their associated low angle master faults to the second order. High angle normal faults in each sequence are active simultaneously with their correlated master low angle normal fault. This correlation implies that the sequential normal faulting is more important in areas where the crust has a relatively uniform thickness, while sequential- and domino-style faulting are both important in provinces where the initial crustal structure is of variable thickness with changing topography and Moho relief, such as central Basin and Range in the Cenozoic for instance. Mid-crustal flow has been proved important in the formation of orogeny. Instead of locally isostatic balance in the crust with initially symmetric crustal structure, we found a long wavelength isostatic balance between the upper and middle crust in the crust with initially asymmetric structure, which is strong evidence that mid-crustal flow plays an important role in extension

  5. 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

  6. 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.

  7. Observing Initial Steps in Gold-Catalyzed Alkyne Transformations by Utilizing Bodipy-Tagged Phosphine-Gold Complexes.

    PubMed

    Vasiuta, Roman; Plenio, Herbert

    2016-04-25

    The Pd-catalyzed reactions of 3-chloro-bodipy with R2 PH (R=Ph, Cy) provide nonfluorescent bodipy-phosphines 3-PR2 -bodipy 3 a (R=Ph) and 3 b (R=Cy; quantum yield Φ<0.001). Metal complexes such as [AgCl(3 b)] and [AuCl(3 b)] were prepared and shown to display much higher fluorescence (Φ=0.073 and 0.096). In the gold complexes, the level of fluorescence was found to be qualitatively correlated with the electron density at gold. Consequently, the fluorescence brightness of [AuCl(3 b)] increases when the chloro ligand is replaced by a weakly coordinating anion, whereas upon formation of the electron-rich complex [Au(SR)(3 b)] the fluorescence is almost quenched. Related reactions of [AuCl(3 b)] with [Ag]ONf)] (Nf= nonaflate) and phenyl acetylenes enable the tracking of initial steps in gold-catalyzed reactions by using fluorescence spectroscopy. Treatment of [AuCl(3 b)] with [Ag(ONf)] gave the respective [Au(ONf)(3 b)] only when employing more than 2.5 equivalents of silver salt. The reaction of the "cationic" gold complex with phenyl acetylenes leads to the formation of the respective dinuclear cationic [{(3 b)Au}2 (CCPh)](+) and an increase in the level of fluorescence. The rate of the reaction of [Au(ONf)(3 b)] with PhCCH depends on the amount of silver salt in the reaction mixture; a large excess of silver salt accelerates this transformation. In situ fluorescence spectroscopy thus provides valuable information on the association of gold complexes with acetylenes. PMID:27011061

  8. The role of the poly(A) binding protein in the assembly of the Cap-binding complex during translation initiation in plants.

    PubMed

    Gallie, Daniel R

    2014-09-01

    Translation initiation in eukaryotes requires the involvement of multiple initiation factors (eIFs) that facilitate the binding of the 40 S ribosomal subunit to an mRNA and assemble the 80 S ribosome at the correct initiation codon. eIF4F, composed of eIF4E, eIF4A, and eIF4G, binds to the 5'-cap structure of an mRNA and prepares an mRNA for recruitment of a 40 S subunit. eIF4B promotes the ATP-dependent RNA helicase activity of eIF4A and eIF4F needed to unwind secondary structure present in a 5'-leader that would otherwise impede scanning of the 40 S subunit during initiation. The poly(A) binding protein (PABP), which binds the poly(A) tail, interacts with eIF4G and eIF4B to promote circularization of an mRNA and stimulates translation by promoting 40 S subunit recruitment. Thus, these factors serve essential functions in the early steps of protein synthesis. Their assembly and function requires multiple interactions that are competitive in nature and determine the nature of interactions between the termini of an mRNA. In this review, the domain organization and partner protein interactions are presented for the factors in plants which share similarities with those in animals and yeast but differ in several important respects. The functional consequences of their interactions on factor activity are also discussed. PMID:26779409

  9. The ULK1 complex mediates MTORC1 signaling to the autophagy initiation machinery via binding and phosphorylating ATG14.

    PubMed

    Park, Ji-Man; Jung, Chang Hwa; Seo, Minchul; Otto, Neil Michael; Grunwald, Douglas; Kim, Kwan Hyun; Moriarity, Branden; Kim, Young-Mi; Starker, Colby; Nho, Richard Seonghun; Voytas, Daniel; Kim, Do-Hyung

    2016-03-01

    ULK1 (unc-51 like autophagy activating kinase 1), the key mediator of MTORC1 signaling to autophagy, regulates early stages of autophagosome formation in response to starvation or MTORC1 inhibition. How ULK1 regulates the autophagy induction process remains elusive. Here, we identify that ATG13, a binding partner of ULK1, mediates interaction of ULK1 with the ATG14-containing PIK3C3/VPS34 complex, the key machinery for initiation of autophagosome formation. The interaction enables ULK1 to phosphorylate ATG14 in a manner dependent upon autophagy inducing conditions, such as nutrient starvation or MTORC1 inhibition. The ATG14 phosphorylation mimics nutrient deprivation through stimulating the kinase activity of the class III phosphatidylinositol 3-kinase (PtdIns3K) complex and facilitates phagophore and autophagosome formation. By monitoring the ATG14 phosphorylation, we determined that the ULK1 activity requires BECN1/Beclin 1 but not the phosphatidylethanolamine (PE)-conjugation machinery and the PIK3C3 kinase activity. Monitoring the phosphorylation also allowed us to identify that ATG9A is required to suppress the ULK1 activity under nutrient-enriched conditions. Furthermore, we determined that ATG14 phosphorylation depends on ULK1 and dietary conditions in vivo. These results define a key molecular event for the starvation-induced activation of the ATG14-containing PtdIns3K complex by ULK1, and demonstrate hierarchical relations between the ULK1 activation and other autophagy proteins involved in phagophore formation. PMID:27046250

  10. 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

  11. Topology and regulation of the human eIF4A/4G/4H helicase complex in translation initiation

    PubMed Central

    Marintchev, Assen; Edmonds, Katherine A.; Marintcheva, Boriana; Hendrickson, Elthea; Oberer, Monika; Suzuki, Chikako; Herdy, Barbara; Sonenberg, Nahum; Wagner, Gerhard

    2009-01-01

    Summary The RNA helicase eIF4A plays a key role in unwinding of mRNA and scanning during translation initiation. Free eIF4A is a poor helicase and requires the accessory proteins eIF4G and eIF4H. However, the structure of the helicase complex and the mechanisms of stimulation of eIF4A activity have remained elusive. Here we report the topology of the eIF4A/4G/4H helicase complex, which is built from multiple experimentally observed domain-domain contacts. Remarkably, some of the interactions are continuously rearranged during the ATP binding/hydrolysis cycle of the helicase. We show that the accessory proteins modulate the affinity of eIF4A for ATP by interacting simultaneously with both helicase domains and promoting either the closed, ATP-bound conformation or the open, nucleotide-free conformation. The topology of the complex and the spatial arrangement of the RNA-binding surfaces offer insights into their roles in stimulation of helicase activity and the mechanisms of mRNA unwinding and scanning. PMID:19203580

  12. 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

  13. Electrophilic Pt(II) Complexes: Precision Instruments for the Initiation of Transformations Mediated by the Cation–Olefin Reaction

    PubMed Central

    2015-01-01

    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

  14. HCV IRES manipulates the ribosome to promote the switch from translation initiation to elongation

    PubMed Central

    Filbin, Megan E.; Vollmar, Breanna S.; Shi, Dan; Gonen, Tamir; Kieft, Jeffrey S.

    2012-01-01

    The hepatitis C virus (HCV) internal ribosome entry site (IRES) drives non-canonical initiation of protein synthesis necessary for viral replication. HCV IRES functional studies have focused on 80S ribosome formation, but have not explored roles after the 80S ribosome is poised at the start codon. Here, we report that mutations of an IRES domain that docks in the 40S subunit’s decoding groove and cause only a local perturbation in IRES structure result in conformational changes in the IRES-rabbit 40S subunit complex. Functionally, we find the mutation decreases IRES activity by inhibiting the first ribosome translocation event, and modeling suggests that this effect is through an interaction with a single ribosomal protein. The HCV IRES’ ability to manipulate the ribosome provides insight into how the ribosome’s structure and function can be altered by bound RNAs, including those derived from cellular invaders. PMID:23262488

  15. HCV IRES manipulates the ribosome to promote the switch from translation initiation to elongation.

    PubMed

    Filbin, Megan E; Vollmar, Breanna S; Shi, Dan; Gonen, Tamir; Kieft, Jeffrey S

    2013-02-01

    The internal ribosome entry site (IRES) of the hepatitis C virus (HCV) drives noncanonical initiation of protein synthesis necessary for viral replication. Functional studies of the HCV IRES have focused on 80S ribosome formation but have not explored its role after the 80S ribosome is poised at the start codon. Here, we report that mutations of an IRES domain that docks in the 40S subunit's decoding groove cause only a local perturbation in IRES structure and result in conformational changes in the IRES-rabbit 40S subunit complex. Functionally, the mutations decrease IRES activity by inhibiting the first ribosomal translocation event, and modeling results suggest that this effect occurs through an interaction with a single ribosomal protein. The ability of the HCV IRES to manipulate the ribosome provides insight into how the ribosome's structure and function can be altered by bound RNAs, including those derived from cellular invaders. PMID:23262488

  16. 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.

  17. Interaction of 2-aminopyrimidine with σ- and π-acceptors involving chemical reactions via initial charge transfer complexation

    NASA Astrophysics Data System (ADS)

    Rabie, U. M.; Abou-El-Wafa, M. H.; Mohamed, R. A.

    2007-12-01

    Interaction of 2-aminopyrimidine (AP) with iodine as a typical σ-type acceptor and with a typical π-type acceptor, 2,3,5,6-tetrachloro-1,4-benzoquinone, p-chloranil (CHL) have been studied spectrophotometrically. Electronic absorption spectra of the system AP-I 2 in several organic solvents of different polarities have performed clear charge transfer (CT) band(s). Formation constants ( KCT) and molar absorption coefficients ( ɛCT) and thermodynamic properties, Δ H, Δ S, and Δ G, of this system in various organic solvents were determined and discussed. Interaction of AP with the π-acceptor has shown unique behaviors. Chemical reaction has occurred via prior or initial formation of the outer-sphere CT complex followed by formation of the corresponding anion radicals, CHL rad - , as intermediates. UV-vis, 1H NMR, Mass, and FT-IR spectra in addition to the elemental analysis were used to confirm the proposed occurrence of the chemical reaction and to investigate the synthesized solid products.

  18. 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

  19. 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.

  20. 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)

  1. 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.

  2. 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.

  3. 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

  4. "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,…

  5. Regioselective Lithium-Iodine Exchange-Initiated Cleavage of 2-Iodomethyl-1,3-dioxanes: A Complex-Induced Proximity Effect.

    PubMed

    Bailey, William F; Fair, Justin D

    2016-05-01

    Lithium-iodine exchange-initiated fragmentation of a series of 4-substituted 2-iodomethyl-1,3-dioxanes proceeds rapidly and regioselectively to afford enol ether alcohols by preferential cleavage of the less congested C(2)-O(1) bond. The results demonstrate that a complex-induced proximity effect (CIPE) is likely responsible for the selectivity of the cleavage. PMID:27074433

  6. Tenosynovitis caused by a novel nontuberculous Mycobacterium species initially misidentified as a member of the Mycobacterium tuberculosis complex.

    PubMed

    Simner, Patricia J; Hyle, Emily P; Buckwalter, Seanne P; Branda, John A; Brown-Elliott, Barbara A; Franklin, Jameelah; Toney, Nadege C; de Man, Tom J B; Wallace, Richard J; Vasireddy, Ravikiran; Gandhi, Rajesh T; Wengenack, Nancy L

    2014-12-01

    We present a case of tenosynovitis caused by a novel, slowly growing, nonchromogenic, nontuberculous mycobacterium (NTM). Originally misidentified as Mycobacterium tuberculosis complex, the NTM cross-reacts with the M. tuberculosis complex nucleic acid hybridization probe, a M. tuberculosis gamma interferon release assay, and is closely related to M. tuberculosis by 16S rRNA gene sequencing. PMID:25253791

  7. 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

  8. Severe acute respiratory syndrome coronavirus protein nsp1 is a novel eukaryotic translation inhibitor that represses multiple steps of translation initiation.

    PubMed

    Lokugamage, Kumari G; Narayanan, Krishna; Huang, Cheng; Makino, Shinji

    2012-12-01

    Severe acute respiratory syndrome (SARS) coronavirus nonstructural protein 1 (nsp1) binds to the 40S ribosomal subunit and inhibits translation, and it also induces a template-dependent endonucleolytic cleavage of host mRNAs. nsp1 inhibits the translation of cap-dependent and internal ribosome entry site (IRES)-driven mRNAs, including SARS coronavirus mRNAs, hepatitis C virus (HCV), and cricket paralysis virus (CrPV) IRES-driven mRNAs that are resistant to nsp1-induced RNA cleavage. We used an nsp1 mutant, nsp1-CD, lacking the RNA cleavage function, to delineate the mechanism of nsp1-mediated translation inhibition and identify the translation step(s) targeted by nsp1. nsp1 and nsp1-CD had identical inhibitory effects on mRNA templates that are resistant to nsp1-induced RNA cleavage, implying the validity of using nsp1-CD to dissect the translation inhibition function of nsp1. We provide evidence for a novel mode of action of nsp1. nsp1 inhibited the translation initiation step by targeting at least two separate stages: 48S initiation complex formation and the steps involved in the formation of the 80S initiation complex from the 48S complex. nsp1 had a differential, mRNA template-dependent, inhibitory effect on 48S and 80S initiation complex formation. nsp1 inhibited different steps of translation initiation on CrPV and HCV IRES, both of which initiate translation via an IRES-40S binary complex intermediate; nsp1 inhibited binary complex formation on CrPV IRES and 48S complex formation on HCV IRES. Collectively, the data revealed that nsp1 inhibited translation by exerting its effect on multiple stages of translation initiation, depending on the mechanism of initiation operating on the mRNA template. PMID:23035226

  9. [Internal initiation of translation in eukaryotes. Chemical probing of the encephalomyocarditis virus RNA IRES-element in the 48S preinitiation complex].

    PubMed

    Boroviagin, A V; Ezrokhi, M V; Shatskiĭ, I N

    1995-01-01

    Using in vitro T7 polymerase system, the transcript containing the IRES-element (nts 315-833), and the initial part of the coding sequence of encephalomyocarditis virus (EMCV) RNA (nts 834-1155) was prepared. Its complex with the 40S ribosomal subunit (48S preinitiation complex) was then isolated by sucrose gradient sedimentation from ascites carcinoma Krebs2 cell extracts after preincubation with the transcript. The complex was treated with dimethylsulphate (DMS), a common reagent for chemical probing of A and C residues in single-stranded RNA regions. The modified nucleotides were identified by primer extension inhibition analysis in reverse transcription reaction. The pattern of modification of the 48S complex was compared with that for the corresponding free mRNP. Multiple protection of A residues against DMS modification was found in the domains of the IRES-element proximal to the initiation AUG codon (nt 834-836). The mechanism of internal translational initiation of EMCV RNA and other picornaviral RNAs is discussed. PMID:8552069

  10. Protein synthesis in brine shrimp embryos and rabbit reticulocytes. The effect of Mg2+ on binary (eukaryotic initiation factor 2 X GDP) and ternary (eukaryotic initiation factor 2 X GTP X met-tRNAf) complex formation.

    PubMed

    Mehta, H B; Woodley, C L; Wahba, A J

    1983-03-25

    We have prepared eukaryotic initiation factor 2 (eIF-2) from rabbit reticulocytes and Artemia embryos and studied the effect of Mg2+ on binary (eIF-2 X GDP) and ternary (eIF-2 X GTP X Met-tRNAf) complex formation. Under conditions where Mg2+ inhibits Met-tRNAf binding to reticulocyte eIF-2, ternary complex formation with Artemia eIF-2 is not inhibited. Similarly, the formation of eIF-2 X GDP with Artemia eIF-2 is stimulated by Mg2+, whereas the corresponding reticulocyte binary complex is strongly inhibited. In the presence of 1 mM Mg2+, the isolated Artemia eIF-2 X GDP complex is stable in the absence of any added nucleotide, but readily exchanges bound GDP for free GTP. However, the reticulocyte eIF-2 X GDP complex is significantly more stable in the presence of GTP, and nucleotide exchange is dependent upon the addition of a factor isolated from either the postribosomal supernatant or the high salt wash of rabbit reticulocyte ribosomes. This factor also stimulates Met-tRNAf binding to both Artemia and reticulocyte eIF-2. PMID:6550599

  11. TBC1D5 and the AP2 complex regulate ATG9 trafficking and initiation of autophagy

    PubMed Central

    Popovic, Doris; Dikic, Ivan

    2014-01-01

    The RabGAP protein TBC1D5 controls cellular endomembrane trafficking processes and binds the retromer subunit VPS29 and the ubiquitin-like protein ATG8 (LC3). Here, we describe that TBC1D5 also associates with ATG9 and the active ULK1 complex during autophagy. Moreover, ATG9 and TBC1D5 interact with clathrin and the AP2 complex. Depletion of TBC1D5 leads to missorting of ATG9 to late endosomes upon activation of autophagy, whereas inhibition of clathrin-mediated endocytosis or AP2 depletion alters ATG9 trafficking and its association with TBC1D5. Taken together, our data show that TBC1D5 and the AP2 complex are important novel regulators of the rerouting of ATG9-containing vesicular carriers toward sites of autophagosome formation. PMID:24603492

  12. Plant cap-binding complexes eukaryotic initiation factors eIF4F and eIFISO4F: molecular specificity of subunit binding.

    PubMed

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

    2011-12-01

    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 K(D) values in the subnanomolar range, whereas the mixed complexes were found to have K(D) 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 K(D) 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

  13. 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.

  14. Ethylenediamine-palladium(II) complexes with pyridine and its derivatives: synthesis, molecular structure and initial antitumor studies.

    PubMed

    Zhao, G; Lin, H; Yu, P; Sun, H; Zhu, S; Su, X; Chen, Y

    1999-03-01

    The synthesis of four mononuclear palladium complexes of general formula [Pd(en)Cl(L)]NO3 (en = ethylenediamine; L = pyridine (I), 4-methylpyridine (II), 4-hydroxypyridine (III) or 4-aminopyridine (IV) has been achieved. The structure of these compounds was studied by elemental analysis, IR, far-IR and 1H NMR; complex I was analyzed by X-ray diffraction. The crystal of [Pd(en)(pyridine)Cl]NO3 is monoclinic, space group P21/c (a = 7.990(2), b = 16.058(3), c = 9.846(2) A, beta = 103.81(3) degrees, Z = 4, R = 0.067, Rw = 0.066). The Pd(II) atom exhibits an approximately square planar coordination with bond lengths in the range 2.017-2.042 A for Pd-N and 2.320 A for Pd-Cl. In order to determine the donor strength of the aromatic pyridine ligands, the stability constants of binary complex ML2+ (M = [Pd(en) (H2O)2]2+; L = pyridine, 4-Me-pyridine, 4-OH-pyridine and 4-NH2-pyridine) were determined by potentiometric pH titration in aqueous solution (T = 25 degrees C, I = 0.1 mol l-1 NaNO3). The results show that the stability constants of the binary complexes systematically increase with increasing pKa of the pyridines. The above four palladium complexes, [Pt(en)(pyridine)Cl]NO3 and cis-diamminedichloroplatinum (II) (cis-DDP) were assayed for cytotoxicity in vitro against the human leukemia cell line HL-60, and compounds I, II, III and cis-DDP show significant cytotoxic activity against HL-60. PMID:10331244

  15. 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

  16. Structural analysis of an eIF3 subcomplex reveals conserved interactions required for a stable and proper translation pre-initiation complex assembly

    PubMed Central

    Herrmannová, Anna; Daujotytė, Dalia; Yang, Ji-Chun; Cuchalová, Lucie; Gorrec, Fabrice; Wagner, Susan; Dányi, István; Lukavsky, Peter J.; Shivaya Valášek, Leoš

    2012-01-01

    Translation initiation factor eIF3 acts as the key orchestrator of the canonical initiation pathway in eukaryotes, yet its structure is greatly unexplored. We report the 2.2 Å resolution crystal structure of the complex between the yeast seven-bladed β-propeller eIF3i/TIF34 and a C-terminal α-helix of eIF3b/PRT1, which reveals universally conserved interactions. Mutating these interactions displays severe growth defects and eliminates association of eIF3i/TIF34 and strikingly also eIF3g/TIF35 with eIF3 and 40S subunits in vivo. Unexpectedly, 40S-association of the remaining eIF3 subcomplex and eIF5 is likewise destabilized resulting in formation of aberrant pre-initiation complexes (PICs) containing eIF2 and eIF1, which critically compromises scanning arrest on mRNA at its AUG start codon suggesting that the contacts between mRNA and ribosomal decoding site are impaired. Remarkably, overexpression of eIF3g/TIF35 suppresses the leaky scanning and growth defects most probably by preventing these aberrant PICs to form. Leaky scanning is also partially suppressed by eIF1, one of the key regulators of AUG recognition, and its mutant sui1G107R but the mechanism differs. We conclude that the C-terminus of eIF3b/PRT1 orchestrates co-operative recruitment of eIF3i/TIF34 and eIF3g/TIF35 to the 40S subunit for a stable and proper assembly of 48S pre-initiation complexes necessary for stringent AUG recognition on mRNAs. PMID:22090426

  17. Evidence for a role of initiation factor 3 in recycling of ribosomal complexes stalled on mRNAs in Escherichia coli

    PubMed Central

    Singh, N. S.; Das, G.; Seshadri, A.; Sangeetha, R.; Varshney, U.

    2005-01-01

    Specific interactions between ribosome recycling factor (RRF) and elongation factor-G (EFG) mediate disassembly of post-termination ribosomal complexes for new rounds of initiation. The interactions between RRF and EFG are also important in peptidyl-tRNA release from stalled pre-termination complexes. Unlike the post-termination complexes (harboring deacylated tRNA), the pre-termination complexes (harboring peptidyl-tRNA) are not recycled by RRF and EFG in vitro, suggesting participation of additional factor(s) in the process. Using a combination of biochemical and genetic approaches, we show that, (i) Inclusion of IF3 with RRF and EFG results in recycling of the pre-termination complexes; (ii) IF3 overexpression in Escherichia coli LJ14 rescues its temperature sensitive phenotype for RRF; (iii) Transduction of infC135 (which encodes a functionally compromised IF3) in E.coli LJ14 generates a ‘synthetic severe’ phenotype; (iv) The infC135 and frr1 (containing an insertion in the RRF gene promoter) alleles synergistically rescue a temperature sensitive mutation in peptidyl-tRNA hydrolase in E.coli; and (v) IF3 facilitates ribosome recycling by Thermus thermophilus RRF and E.coli EFG in vivo and in vitro. These lines of evidence clearly demonstrate the physiological importance of IF3 in the overall mechanism of ribosome recycling in E.coli. PMID:16199751

  18. 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

  19. Characterization of the Initial Intermediate Formed during Photoinduced Oxygenation of the Ruthenium(II) Bis(bipyridyl)flavonolate Complex.

    PubMed

    Han, Xiaozhen; Klausmeyer, Kevin K; Farmer, Patrick J

    2016-08-01

    A ruthenium(II) flavonolate complex, [Ru(II)(bpy)2fla][BF4], was synthesized to model the reactivity of the flavonol dioxygenases. The treatment of dry CH3CN solutions of [Ru(II)(bpy)2fla][BF4] with dioxygen under light leads to the oxidative O-heterocyclic ring opening of the coordinated substrate flavonolate, resulting in the formation of [Ru(II)(bpy)2(carboxylate)][BF4] (carboxylate = O-benzoylsalicylate or benzoate) species, as determined by electrospray ionization mass spectrometry. Moderation of the excitation and temperature allowed isolation and characterization of an intermediate, [Ru(II)(bpy)2bpg][BF4] (bpg = 2-benzoyloxyphenylglyoxylate), generated by the 1,2-addition of dioxygen to the central flavonolate ring. PMID:27437831

  20. Self-organization of alcohol-related attitudes and beliefs in a campus housing complex: an initial investigation.

    PubMed

    Bourgeois, M J; Bowen, A

    2001-11-01

    The self-organization of college students' alcohol-related attitudes and their beliefs about other students' attitudes were assessed within a campus housing complex. Pluralistic ignorance was widespread, in that, compared with their own self-ratings, students rated their friends and the "typical" student as being more in favor of alcohol and more lax in the number of drinks per hour that were acceptable and the number of drinks that were acceptable before driving. They also perceived typical students as more risky than their friends. Dynamic social impact theory was also supported, as students' dormitory building and floor of residence reliably predicted both their personal drinking attitudes and their beliefs about the drinking attitudes of other students. PMID:11714185

  1. Evaluating key parameters for the initiation of a Neoproterozoic Snowball Earth with a single Earth System Model of intermediate complexity

    NASA Astrophysics Data System (ADS)

    Spiegl, T. C.; Paeth, H.; Frimmel, H. E.

    2015-04-01

    Even after more than two decades of intense research the main drivers for a potential Neoproterozoic Snowball Earth continue to be discussed controversially. In this study we present results from 37 sensitivity experiments that were performed with the Planet Simulator (PlaSim), an Earth System Model of intermediate complexity. In contrast to previous studies, in which only a limited number of potential climate-controlling parameters were assessed with different climate models, we tested our presumed key parameters within one single model. This approach makes it easier to compare the influence of the various parameters on extreme climate change as postulated for the Neoproterozoic Era. Furthermore we compare the results obtained to most recent high complexity state-of-the-art approaches. This comparison helps to estimate, which internal model interactions and physics are crucial for a Snowball Earth simulation and hence should be included into a model that is capable of realistically simulating a Neoproterozoic climate. To this effect we carried out simulations that involved reduced solar irradiation, land-sea distributions, atmospheric CO2 concentrations, relief of the land surface and length of day. In addition, we focus on different land surface albedo values, which were most likely exceptionally low and similar to the Martian albedo, and obliquity changes between 23.5° and 80°. Our findings suggest that changes in land surface albedo are a strong climate driver that can compensate a much lower Neoproterozoic total solar irradiance if it is combined with shifts in obliquity or atmospheric CO2 levels. We also obtained a critical threshold for increased obliquities beyond which a Snowball Earth situation turns into an extreme greenhouse climate with almost absent cryosphere, and furthermore, obliquity values that lead to a tropical ice age with sea ice spreading from the equator to high latitudes.

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

    NASA Astrophysics Data System (ADS)

    Lambert, David D.; Unruh, D. M.; Gilbert, M. Charles

    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. These whole-rock analyses do not define a Sm-Nd isochron; rather, they display a significant range in initial Nd isotopic composition (ɛNd = 3.63-5.35). 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 heterogeneous mantle source region that had variable initial Nd isotopic compositions.

  3. 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

  4. Assembly of Helicobacter pylori initiation complex is determined by sequence-specific and topology-sensitive DnaA-oriC interactions.

    PubMed

    Donczew, Rafał; Mielke, Thorsten; Jaworski, Paweł; Zakrzewska-Czerwińska, Jolanta; Zawilak-Pawlik, Anna

    2014-07-29

    In bacteria, chromosome replication is initiated by binding of the DnaA initiator protein to DnaA boxes located in the origin of chromosomal replication (oriC). This leads to DNA helix opening within the DNA-unwinding element. Helicobacter pylori oriC, the first bipartite origin identified in Gram-negative bacteria, contains two subregions, oriC1 and oriC2, flanking the dnaA gene. The DNA-unwinding element region is localized in the oriC2 subregion downstream of dnaA. Surprisingly, oriC2-DnaA interactions were shown to depend on DNA topology, which is unusual in bacteria but is similar to initiator-origin interactions observed in higher organisms. In this work, we identified three DnaA boxes in the oriC2 subregion, two of which were bound only as supercoiled DNA. We found that all three DnaA boxes play important roles in orisome assembly and subsequent DNA unwinding, but different functions can be assigned to individual boxes. This suggests that the H. pylori oriC may be functionally divided, similar to what was described recently for Escherichia coli oriC. On the basis of these results, we propose a model of initiation complex formation in H. pylori. PMID:24862285

  5. Hyperdigraph-theoretic analysis of the EGFR signaling network: initial steps leading to GTP:Ras complex formation.

    PubMed

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

    2004-01-01

    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. PMID:15700404

  6. 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.

  7. Inflammation induced NFATc1-STAT3 Transcription Complex Promotes Pancreatic Cancer initiation by KrasG12D

    PubMed Central

    Baumgart, Sandra; Chen, Nai-ming; Siveke, Jens T.; König, Alexander; Zhang, Jin-San; Singh, Shiv K.; Wolf, Elmar; Bartkuhn, Marek; Esposito, Irene; Heßmann, Elisabeth; Reinecke, Johanna; Nikorowitsch, Julius; Brunner, Marius; Singh, Garima; Fernandez-Zapico, Martin E.; Smyrk, Thomas; Bamlet, William R.; Eilers, Martin; Neesse, Albrecht; Gress, Thomas M.; Billadeau, Daniel D.; Tuveson, David; Urrutia, Raul; Ellenrieder, Volker

    2014-01-01

    Summary Cancer-associated inflammation is a molecular key feature in pancreatic ductal adenocarcinoma. Oncogenic KRAS in conjunction with persistent inflammation is known to accelerate carcinogenesis, although the underlying mechanisms remain poorly understood. Here we outline a novel pathway whereby the transcription factors NFATc1 and STAT3 cooperate in pancreatic epithelial cells to promote KrasG12D-driven carcinogenesis. NFATc1 activation is induced by inflammation and itself accelerates inflammation-induced carcinogenesis in KrasG12D mice, whereas genetic or pharmacological ablation of NFATc1 attenuates this effect. Mechanistically, NFATc1 complexes with STAT3 for enhancer-promoter communications at jointly regulated genes involved in oncogenesis, e.g. Cyclin, EGFR and WNT family members. The NFATc1-STAT3 cooperativity is operative in pancreatitis-mediated carcinogenesis as well as in established human pancreatic cancer. Together, these studies unravel new mechanisms of inflammatory driven pancreatic carcinogenesis and suggest beneficial effects of chemopreventive strategies using drugs which are currently available for targeting these factors in clinical trials. PMID:24694735

  8. Identification and initial characterization of a rat monoclonal antibody reactive with the murine interleukin 2 receptor-ligand complex.

    PubMed Central

    Malek, T R; Robb, R J; Shevach, E M

    1983-01-01

    Xenogeneic monoclonal antibodies were prepared to the murine interleukin 2 (IL-2)-dependent HT2 cell line. One rat IgM monoclonal antibody (7D4) was identified that inhibited proliferation of the HT2 cells and of IL-2-dependent CTLL cells in the presence of crude rat IL-2 as well as of purified human IL-2. The level of inhibition was dependent on both antibody and IL-2 concentration. Cell distribution studies using a fluorescence-activated cell sorter showed that the antigen identified by 7D4 is expressed at a high density on HT2 cells and on concanavalin A (Con A)-induced T-cell blasts and at a substantially lower density on lipopolysaccharide-induced B-cell blasts; 7D4 binding was not detected on greater than 95% of nonactivated thymocytes, T cells, or B cells. Competition binding studies indicated that 7D4 fails to inhibit the binding of 3H-labeled human IL-2 to CTLL cells. However, 7D4 specifically immunoprecipitated 3H-labeled human IL-2 from detergent extracts of HT2 cells or Con A-induced T-cell blasts that had been pulsed with [3H]IL-2; in contrast, 7D4 did not react with free [3H]IL-2. Initial biochemical analysis of immunoprecipitates with 7D4 of detergent extracts from surface-iodinated Con A-activated spleen cells showed a major band having apparent molecular weight of 48,000-62,000. Collectively, these results suggest that 7D4 detects an epitope on the IL-2 receptor distal to the ligand binding site or another molecule that physically associates with the receptor. Images PMID:6412230

  9. Eduction, extension, and exhumation of ultrahigh-pressure rocks in metamorphic core complexes due to subduction initiation

    NASA Astrophysics Data System (ADS)

    Petersen, Kenni Dinesen; Buck, W. Roger

    2015-09-01

    The controversy over the exhumation of ultrahigh-pressure (UHP) rocks centers on whether it involves rising of pieces of crust detached from subducted continental lithosphere or an entire subducted plate that undergoes "eduction," i.e., reverse subduction. We present a new thermomechanical model of continental subduction showing that these apparently contrasting mechanisms can occur together: crust subducted deep enough is heated and weakened, causing limited diapiric rise, while crust subducted to shallower depths retains strength and is exhumed only by eduction. The model also shows for the first time how eduction followed by seafloor spreading can occur in a zone of regional convergence. This occurs spontaneously when subduction of buoyant crust causes a subduction zone to "lock up" in one place causing a new subduction zone to form in another. The model is consistent with many features of the youngest region of UHP rock exhumation on earth: the D'Entrecasteaux Islands. UHP exhumation and the amount of regional extension, as well as the seismic structure around the islands, can be explained by eduction. Ductile flow fabrics, seen on the islands, would result from exhumation of the most deeply subducted crust heated enough to undergo partial melting. Reversal of motion on the north-dipping continental subduction zone, required by this model, was likely triggered by initiation of the New Britain Trench, as suggested previously. Our model implies that the crust of Goodenough Basin, south of the islands, was exhumed by eduction in the last 5 Ma and this hypothesis can be tested by drilling.

  10. Tissue factor initiates glomerular fibrin deposition and promotes major histocompatibility complex class II expression in crescentic glomerulonephritis.

    PubMed Central

    Erlich, J. H.; Holdsworth, S. R.; Tipping, P. G.

    1997-01-01

    Increased glomerular tissue factor (TF) expression is associated with glomerular fibrin deposition and renal failure in human and experimental crescentic glomerulonephritis (GN). However, the in vivo functional contribution of TF to the development of glomerular fibrin deposition, crescent formation, and renal failure in GN has not been established. The contribution of TF to fibrin deposition and renal injury was studied in a rabbit model of crescentic GN in which glomerular macrophage infiltration, augmented TF expression, and fibrin deposition are prominent. Administration of anti-TF antibody inhibited glomerular TF activity in nephritic glomeruli by 96%, without affecting macrophage accumulation or systemic indices of coagulation. Anti-TF antibody significantly reduced glomerular fibrin deposition (fibrin scores, 0.43 +/- 0.10 (treated) and 1.40 +/- 0.19 (control); P < 0.0005), crescent formation (0.33 +/- 0.05 (treated) and 1.0 +/- 0.06 (control); P < 0.0005), and development of renal failure (serum creatinine, 168 +/- 22 mumol/l (treated) and 267 +/- 35 mumol/l (control); P < 0.04). This was associated with significant reduction in proteinuria (1189 +/- 277 mg/24 hours (treated) and 2060 +/- 336 mg/24 hours (control); P < 0.03) and expression of MHC class II antigen in glomeruli (1.25 +/- 0.41 (treated) and 2.83 +/- 0.53 (control); P < 0.03) and in tubules and interstitial areas. These data demonstrate that TF is the major in vivo initiator of fibrin deposition in crescentic GN. The reduction in proteinuria and glomerular major histocompatibility class II antigen expression by TF inhibition suggests that TF may also activate other mediators that contribute to glomerular injury. Images Figure 1 PMID:9060825

  11. 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.

  12. 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

  13. Mammalian ataxin-2 modulates translation control at the pre-initiation complex via PI3K/mTOR and is induced by starvation.

    PubMed

    Lastres-Becker, Isabel; Nonis, David; Eich, Florian; Klinkenberg, Michael; Gorospe, Myriam; Kötter, Peter; Klein, Fabrice A C; Kedersha, Nancy; Auburger, Georg

    2016-09-01

    Ataxin-2 is a cytoplasmic protein, product of the ATXN2 gene, whose deficiency leads to obesity, while its gain-of-function leads to neural atrophy. Ataxin-2 affects RNA homeostasis, but its effects are unclear. Here, immunofluorescence analysis suggested that ataxin-2 associates with 48S pre-initiation components at stress granules in neurons and mouse embryonic fibroblasts, but is not essential for stress granule formation. Coimmunoprecipitation analysis showed associations of ataxin-2 with initiation factors, which were concentrated at monosome fractions of polysome gradients like ataxin-2, unlike its known interactor PABP. Mouse embryonic fibroblasts lacking ataxin-2 showed increased phosphorylation of translation modulators 4E-BP1 and ribosomal protein S6 through the PI3K-mTOR pathways. Indeed, human neuroblastoma cells after trophic deprivation showed a strong induction of ATXN2 transcript via mTOR inhibition. Our results support the notion that ataxin-2 is a nutritional stress-inducible modulator of mRNA translation at the pre-initiation complex. PMID:27240544

  14. 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

  15. Members of the NODE (Nanog and Oct4-associated deacetylase) complex and SOX-2 promote the initiation of a natural cellular reprogramming event in vivo

    PubMed Central

    Kagias, Konstantinos; Ahier, Arnaud; Fischer, Nadine; Jarriault, Sophie

    2012-01-01

    Differentiated cells can be forced to change identity, either to directly adopt another differentiated identity or to revert to a pluripotent state. Direct reprogramming events can also occur naturally. We recently characterized such an event in Caenorhabditis elegans, in which a rectal cell switches to a neuronal cell. Here we have used this single-cell paradigm to investigate the molecular requirements of direct cell-type conversion, with a focus on the early steps. Our genetic analyses revealed the requirement of sem-4/Sall, egl-27/Mta, and ceh-6/Oct, members of the NODE complex recently identified in embryonic stem (ES) cells, and of the OCT4 partner sox-2, for the initiation of this natural direct reprogramming event. These four factors have been shown to individually impact on ES cell pluripotency; however, whether they act together to control cellular potential during development remained an open question. We further found that, in addition to acting at the same time, these factors physically associate, suggesting that they could act together as a NODE-like complex during this in vivo process. Finally, we have elucidated the functional domains in EGL-27/MTA that mediate its reprogramming activity in this system and have found that modulation of the posterior HOX protein EGL-5 is a downstream event to allow the initiation of Y identity change. Our data reveal unique in vivo functions in a natural direct reprogramming event for these genes that impact on ES cells pluripotency and suggest that conserved nuclear events could be shared between different cell plasticity phenomena across phyla. PMID:22493276

  16. Members of the NODE (Nanog and Oct4-associated deacetylase) complex and SOX-2 promote the initiation of a natural cellular reprogramming event in vivo.

    PubMed

    Kagias, Konstantinos; Ahier, Arnaud; Fischer, Nadine; Jarriault, Sophie

    2012-04-24

    Differentiated cells can be forced to change identity, either to directly adopt another differentiated identity or to revert to a pluripotent state. Direct reprogramming events can also occur naturally. We recently characterized such an event in Caenorhabditis elegans, in which a rectal cell switches to a neuronal cell. Here we have used this single-cell paradigm to investigate the molecular requirements of direct cell-type conversion, with a focus on the early steps. Our genetic analyses revealed the requirement of sem-4/Sall, egl-27/Mta, and ceh-6/Oct, members of the NODE complex recently identified in embryonic stem (ES) cells, and of the OCT4 partner sox-2, for the initiation of this natural direct reprogramming event. These four factors have been shown to individually impact on ES cell pluripotency; however, whether they act together to control cellular potential during development remained an open question. We further found that, in addition to acting at the same time, these factors physically associate, suggesting that they could act together as a NODE-like complex during this in vivo process. Finally, we have elucidated the functional domains in EGL-27/MTA that mediate its reprogramming activity in this system and have found that modulation of the posterior HOX protein EGL-5 is a downstream event to allow the initiation of Y identity change. Our data reveal unique in vivo functions in a natural direct reprogramming event for these genes that impact on ES cells pluripotency and suggest that conserved nuclear events could be shared between different cell plasticity phenomena across phyla. PMID:22493276

  17. Structure of Complement C6 Suggests a Mechanism for Initiation and Unidirectional, Sequential Assembly of Membrane Attack Complex (MAC)*♦

    PubMed Central

    Aleshin, Alexander E.; Schraufstatter, Ingrid U.; Stec, Boguslaw; Bankston, Laurie A.; Liddington, Robert C.; DiScipio, Richard G.

    2012-01-01

    The complement membrane attack complex (MAC) is formed by the sequential assembly of C5b with four homologous proteins as follows: one copy each of C6, C7, and C8 and 12–14 copies of C9. Together these form a lytic pore in bacterial membranes. C6 through C9 comprise a MAC-perforin domain flanked by 4–9 “auxiliary” domains. Here, we report the crystal structure of C6, the first and longest of the pore proteins to be recruited by C5b. Comparisons with the structures of the C8αβγ heterodimer and perforin show that the central domain of C6 adopts a “closed” (perforin-like) state that is distinct from the “open” conformations in C8. We further show that C6, C8α, and C8β contain three homologous subdomains (“upper,” “lower,” and “regulatory”) related by rotations about two hinge points. In C6, the regulatory segment includes four auxiliary domains that stabilize the closed conformation, inhibiting release of membrane-inserting elements. In C8β, rotation of the regulatory segment is linked to an opening of the central β-sheet of its clockwise partner, C8α. Based on these observations, we propose a model for initiation and unidirectional propagation of the MAC in which the auxiliary domains play key roles: in the assembly of the C5b-8 initiation complex; in driving and regulating the opening of the β-sheet of the MAC-performin domain of each new recruit as it adds to the growing pore; and in stabilizing the final pore. Our model of the assembled pore resembles those of the cholesterol-dependent cytolysins but is distinct from that recently proposed for perforin. PMID:22267737

  18. A complex MLL rearrangement identified five years after initial MDS diagnosis results in out-of-frame fusions without progression to acute leukemia.

    PubMed

    Meyer, Claus; Kowarz, Eric; Yip, Sze-Fai; Wan, Thomas Shek-Kong; Chan, Tai-Kwong; Dingermann, Theo; Chan, Li-Chong; Marschalek, Rolf

    2011-10-01

    Chromosomal rearrangements of the MLL gene are uncommon in myelodysplastic syndromes (MDSs), and few studies of their molecular structures and oncogenic mechanisms exist. Here, we present a case of de novo MDS with a normal karyotype at initial diagnosis and a mild clinical course. Five years after the initial diagnosis, investigators identified a complex rearrangement of the MLL gene without progression to acute leukemia. The 5' part of the MLL gene is fused out of frame with the LOC100131626 gene, and the 3' part of the MLL gene out of frame with the TCF12 gene. Rapid amplification of complementary DNA 3' ends yielded two main fusion transcripts, which is in concordance with the two described isoforms of the LOC100131626 gene. For both isoform-fusion transcripts, the open reading frame terminates shortly after the breakpoint that is predicted to form two de facto truncated MLL proteins and disrupts the open reading frame of the LOC100131626, TCF12, and UBE4A genes. Neither dimerization nor a transcriptional activation domain, each of which is causally linked to MLL protein-mediated transformation, is present. This and other unusual MLL rearrangements probably represent a subclass of MLL gene abnormalities that have intrinsically no ability or only a weak ability to transform hematopoeitic cells and are identified only in the context of other hematopoetic malignancies. PMID:22137486

  19. Hmo1 directs pre-initiation complex assembly to an appropriate site on its target gene promoters by masking a nucleosome-free region.

    PubMed

    Kasahara, Koji; Ohyama, Yoshifumi; Kokubo, Tetsuro

    2011-05-01

    Saccharomyces cerevisiae Hmo1 binds to the promoters of ∼ 70% of ribosomal protein genes (RPGs) at high occupancy, but is observed at lower occupancy on the remaining RPG promoters. In Δhmo1 cells, the transcription start site (TSS) of the Hmo1-enriched RPS5 promoter shifted upstream, while the TSS of the Hmo1-limited RPL10 promoter did not shift. Analyses of chimeric RPS5/RPL10 promoters revealed a region between the RPS5 upstream activating sequence (UAS) and core promoter, termed the intervening region (IVR), responsible for strong Hmo1 binding and an upstream TSS shift in Δhmo1 cells. Chromatin immunoprecipitation analyses showed that the RPS5-IVR resides within a nucleosome-free region and that pre-initiation complex (PIC) assembly occurs at a site between the IVR and a nucleosome overlapping the TSS (+1 nucleosome). The PIC assembly site was shifted upstream in Δhmo1 cells on this promoter, indicating that Hmo1 normally masks the RPS5-IVR to prevent PIC assembly at inappropriate site(s). This novel mechanism ensures accurate transcriptional initiation by delineating the 5'- and 3'-boundaries of the PIC assembly zone. PMID:21288884

  20. 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.

  1. 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

  2. Architecture of the caveolar coat complex.

    PubMed

    Ludwig, Alexander; Nichols, Benjamin James; Sandin, Sara

    2016-08-15

    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

  3. Translation initiation factors are not required for Dicistroviridae IRES function in vivo

    PubMed Central

    Deniz, Nilsa; Lenarcic, Erik M.; Landry, Dori M.; Thompson, Sunnie R.

    2009-01-01

    The cricket paralysis virus (CrPV) intergenic region (IGR) internal ribosome entry site (IRES) uses an unusual mechanism of initiating translation, whereby the IRES occupies the P-site of the ribosome and the initiating tRNA enters the A-site. In vitro experiments have demonstrated that the CrPV IGR IRES is able to bind purified ribosomes and form 80S complexes capable of synthesizing small peptides in the absence of any translation initiation factors. These results suggest that initiation by this IRES is factor-independent. To determine whether the IGR IRES functions in the absence of initiation factors in vivo, we assayed IGR IRES activity in various yeast strains harboring mutations in canonical translation initiation factors. We used a dicistronic reporter assay in yeast to determine whether the CrPV IGR IRES is able to promote translation sufficient to support growth in the presence of various deletions or mutations in translation initiation factors. Using this assay, we have previously shown that the CrPV IGR IRES functions efficiently in yeast when ternary complexes (eIF2•GTP•initiator tRNAmet) are reduced. Here, we demonstrate that the CrPV IGR IRES activity does not require the eukaryotic initiation factors eIF4G1 or eIF5B, and it is enhanced when eIF2B, the eIF3b subunit of eIF3, or eIF4E are impaired. Taken together, these data support a model in which the CrPV IGR IRES is capable of initiating protein synthesis in the absence of any initiation factors in vivo, and suggests that the CrPV IGR IRES initiates translation by directly recruiting the ribosomal subunits in vivo. PMID:19299549

  4. Structural studies of the carbon monoxide complex of [NiFe]hydrogenase from Desulfovibrio vulgaris Miyazaki F: suggestion for the initial activation site for dihydrogen.

    PubMed

    Ogata, Hideaki; Mizoguchi, Yasutaka; Mizuno, Nobuhiro; Miki, Kunio; Adachi, Shin-ichi; Yasuoka, Noritake; Yagi, Tatsuhiko; Yamauchi, Osamu; Hirota, Shun; Higuchi, Yoshiki

    2002-10-01

    The carbon monoxide complex of [NiFe]hydrogenase from Desulfovibrio vulgaris Miyazaki F has been characterized by X-ray crystallography and absorption and resonance Raman spectroscopy. Nine crystal structures of the [NiFe]hydrogenase in the CO-bound and CO-liberated forms were determined at 1.2-1.4 A resolution. The exogenously added CO was assigned to be bound to the Ni atom at the Ni-Fe active site. The CO was not replaced with H(2) in the dark at 100 K, but was liberated by illumination with a strong white light. The Ni-C distances and Ni-C-O angles were about 1.77 A and 160 degrees, respectively, except for one case (1.72 A and 135 degrees ), in which an additional electron density peak between the CO and Sgamma(Cys546) was recognized. Distinct changes were observed in the electron density distribution of the Ni and Sgamma(Cys546) atoms between the CO-bound and CO-liberated structures for all the crystals tested. The novel structural features found near the Ni and Sgamma(Cys546) atoms suggest that these two atoms at the Ni-Fe active site play a role during the initial H(2)-binding process. Anaerobic addition of CO to dithionite-reduced [NiFe]hydrogenase led to a new absorption band at about 470 nm ( approximately 3000 M(-1)cm(-1)). Resonance Raman spectra (excitation at 476.5 nm) of the CO complex revealed CO-isotope-sensitive bands at 375/393 and 430 cm(-1) (368 and 413 cm(-1) for (13)C(18)O). The frequencies and relative intensities of the CO-related Raman bands indicated that the exogenous CO is bound to the Ni atom with a bent Ni-C-O structure in solution, in agreement with the refined structure determined by X-ray crystallography. PMID:12296727

  5. 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

  6. Primary cilia membrane assembly is initiated by Rab11 and transport protein particle II (TRAPPII) complex-dependent trafficking of Rabin8 to the centrosome

    PubMed Central

    Westlake, Christopher J.; Baye, Lisa M.; Nachury, Maxence V.; Wright, Kevin J.; Ervin, Karen E.; Phu, Lilian; Chalouni, Cecile; Beck, John S.; Kirkpatrick, Donald S.; Slusarski, Diane C.; Sheffield, Val C.; Scheller, Richard H.; Jackson, Peter K.

    2011-01-01

    Sensory and signaling pathways are exquisitely organized in primary cilia. Bardet-Biedl syndrome (BBS) patients have compromised cilia and signaling. BBS proteins form the BBSome, which binds Rabin8, a guanine nucleotide exchange factor (GEF) activating the Rab8 GTPase, required for ciliary assembly. We now describe serum-regulated upstream vesicular transport events leading to centrosomal Rab8 activation and ciliary membrane formation. Using live microscopy imaging, we show that upon serum withdrawal Rab8 is observed to assemble the ciliary membrane in ∼100 min. Rab8-dependent ciliary assembly is initiated by the relocalization of Rabin8 to Rab11-positive vesicles that are transported to the centrosome. After ciliogenesis, Rab8 ciliary transport is strongly reduced, and this reduction appears to be associated with decreased Rabin8 centrosomal accumulation. Rab11-GTP associates with the Rabin8 COOH-terminal region and is required for Rabin8 preciliary membrane trafficking to the centrosome and for ciliogenesis. Using zebrafish as a model organism, we show that Rabin8 and Rab11 are associated with the BBS pathway. Finally, using tandem affinity purification and mass spectrometry, we determined that the transport protein particle (TRAPP) II complex associates with the Rabin8 NH2-terminal domain and show that TRAPP II subunits colocalize with centrosomal Rabin8 and are required for Rabin8 preciliary targeting and ciliogenesis. PMID:21273506

  7. Plantar-flexion of the ankle joint complex in terminal stance is initiated by subtalar plantar-flexion: A bi-planar fluoroscopy study.

    PubMed

    Koo, Seungbum; Lee, Kyoung Min; Cha, Young Joo

    2015-10-01

    Gross motion of the ankle joint complex (AJC) is a summation of the ankle and subtalar joints. Although AJC kinematics have been widely used to evaluate the function of the AJC, the coordinated movements of the ankle and subtalar joints are not well understood. The purpose of this study was to accurately quantify the individual kinematics of the ankle and subtalar joints in the intact foot during ground walking by using a bi-planar fluoroscopic system. Bi-planar fluoroscopic images of the foot and ankle during walking and standing were acquired from 10 healthy subjects. The three-dimensional movements of the tibia, talus, and calcaneus were calculated with a three-dimensional/two-dimensional registration method. The skeletal kinematics were quantified from 9% to 86% of the full stance phase because of the limited camera speed of the X-ray system. At the beginning of terminal stance, plantar-flexion of the AJC was initiated in the subtalar joint on average at 75% ranging from 62% to 76% of the stance phase, and plantar-flexion of the ankle joint did not start until 86% of the stance phase. The earlier change to plantar-flexion in the AJC than the ankle joint due to the early plantar-flexion in the subtalar joint was observed in 8 of the 10 subjects. This phenomenon could be explained by the absence of direct muscle insertion on the talus. Preceding subtalar plantar-flexion could contribute to efficient and stable ankle plantar-flexion by locking the midtarsal joint, but this explanation needs further investigation. PMID:26238571

  8. Host translational control of a polydnavirus, Cotesia plutellae bracovirus, by sequestering host eIF4A to prevent formation of a translation initiation complex.

    PubMed

    Surakasi, V P; Nalini, M; Kim, Yonggyun

    2011-10-01

    Host translational control is a viral strategy to exploit host cellular resources. Parasitization by some endoparasitoids containing polydnaviruses inhibits the synthesis of specific host proteins at post-transcriptional level. Two host translation inhibitory factors (HTIFs) have been proposed in Cotesia plutellae bracovirus (CpBV). Parasitization by C. plutellae inhibited storage protein 1 (SP1) synthesis of Plutella xylostella at post-transcriptional level. One HTIF, CpBV15β, inhibited the translation of SP1 mRNA in an in vitro translation assay using rabbit reticulocyte lysate, but did not inhibit its own mRNA. To further analyse the discrimination of target and nontarget mRNAs of the inhibitory effect of HTIF, 5' untranslated regions (UTRs) of SP1 and CpBV15β mRNA were reciprocally exchanged. In the presence of HTIFs, the chimeric CpBV15β mRNA that contained SP1 5' UTR was not translated, whereas the chimeric SP1 mRNA that contained CpBV15β 5' UTR was translated. There was a difference in the 5' UTR secondary structures between target (SP1) and nontarget (CpBV15α and CpBV15β) mRNAs in terms of thermal stability. Different mutant 5' UTRs of SP1 mRNA were prepared by point mutations to modify their secondary structures. The constructs containing 5' UTRs of high thermal stability in their secondary structures were inhibited by HTIF, but those of low thermal stability were not. Immunoprecipitation with CpBV15β antibody coprecipitated eIF4A, which would be required for unwinding the secondary structure of the 5' UTR. These results indicate that the viral HTIF discriminates between host mRNAs according to their dependency on eIF4A to form a functional initiation complex for translation. PMID:21699595

  9. 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.

  10. Rps5-Rps16 communication is essential for efficient translation initiation in yeast S. cerevisiae

    PubMed Central

    Ghosh, Arnab; Jindal, Supriya; Bentley, Amber A.; Hinnebusch, Alan G.; Komar, Anton A.

    2014-01-01

    Conserved ribosomal proteins frequently harbor additional segments in eukaryotes not found in bacteria, which could facilitate eukaryotic-specific reactions in the initiation phase of protein synthesis. Here we provide evidence showing that truncation of the N-terminal domain (NTD) of yeast Rps5 (absent in bacterial ortholog S7) impairs translation initiation, cell growth and induction of GCN4 mRNA translation in a manner suggesting incomplete assembly of 48S preinitiation complexes (PICs) at upstream AUG codons in GCN4 mRNA. Rps5 mutations evoke accumulation of factors on native 40S subunits normally released on conversion of 48S PICs to 80S initiation complexes (ICs) and this abnormality and related phenotypes are mitigated by the SUI5 variant of eIF5. Remarkably, similar effects are observed by substitution of Lys45 in the Rps5-NTD, involved in contact with Rps16, and by eliminating the last two residues of the C-terminal tail (CTT) of Rps16, believed to contact initiator tRNA base-paired to AUG in the P site. We propose that Rps5-NTD-Rps16-NTD interaction modulates Rps16-CTT association with Met-tRNAiMet to promote a functional 48S PIC. PMID:24948608

  11. 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

  12. 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.

  13. 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

  14. 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…

  15. 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…

  16. Audiovisual Technology for the '80's.

    ERIC Educational Resources Information Center

    Wyman, Raymond

    1979-01-01

    Originally part of a symposium on educational media for the deaf, the paper describes the seven formats or media needed in the eighties: (1) sound recording and reproduction, (2) still image recording and reproduction, (3) sound plus still images, (4) silent moving passages, (5) moving passages with sound, (6) sound plus still plus moving images,…

  17. STD Education: Challenge for the 80s.

    ERIC Educational Resources Information Center

    Kroger, Fred; Wiesner, Paul J.

    1981-01-01

    Sexually transmitted diseases (STD) are the most pervasive, destructive, and costly communicable disease problems facing America's youth. The need for and appropriateness of school-based STD education, some elements of high-quality STD education, and strategies for dealing constructively with controversy are discussed. (JN)

  18. Teaching the Adult of the "80"s.

    ERIC Educational Resources Information Center

    Kreitlow, Burton W.

    Intended for reading specialists and adult education teachers, this paper assesses the current state of adult basic skills, the general education degree, and English as a second language teaching. The first part of the paper consists of a series of tables representing demographics of participants in adult education programs. The second part…

  19. 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…

  20. Human Resource Perspectives for the '80s.

    ERIC Educational Resources Information Center

    Jordan, Vernon E.

    1979-01-01

    Blacks still suffer from the effects of past discrimination combined with continuing discrimination based on negative stereotypes and irrational prejudices. That disadvantage must be overcome through vigorous affirmative action programs. (Author/IRT)

  1. Technological Innovation in the 80's.

    ERIC Educational Resources Information Center

    Coles, James S., Ed.

    This six-chapter book presents background papers used by participants at a meeting designed to examine the prospects for and roadblocks to scientific and technological innovations as the 21st century is approached. They include: (1) "Research Universities and Industrial Innovation in America" (Steven Muller); (2) "The Role of Government in…

  2. Numeric Databases in the 80s.

    ERIC Educational Resources Information Center

    Fried, John B.; Kovacs, Gabor J.

    1982-01-01

    Defining a numeric database as a computer-readable collection of data predominantly numeric in nature, this article reviews techniques and technologies having a positive influence on the growth of numeric databases, such as videotex, mini- and microcomputers, artificial intelligence, improved software, telecommunications, and office automation.…

  3. Consuming in the 80's and Beyond.

    ERIC Educational Resources Information Center

    Texas Tech Univ., Lubbock. Home Economics Curriculum Center.

    This guide is designed to give advanced or upper-level consumer and homemaking education students a chance to take a futuristic look at the roles they will have as consumers in the next years. Divided into 12 units, the first three cover the consumer, the family, and consumer responsibilities. The next eight units are on the goods and services…

  4. 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…

  5. Education in the 80's: English.

    ERIC Educational Resources Information Center

    Shuman, R. Baird, Ed.

    The essays in this collection are designed to provide an overview of the most pressing issues and ideas with which English teachers contend today and will contend in the near future. The contributors, 22 English teachers and educators, have attempted to view change in a sufficiently broad perspective to enable them to make responsible predictions…

  6. Drama of the 80s (Booksearch).

    ERIC Educational Resources Information Center

    English Journal, 1990

    1990-01-01

    Recommends eight plays from the 1980s which will challenge the thinking of students with issues such as evolving independence of young people, growing up in the context of racism and discrimination, insights into the world of the deaf, and the suffering of humanity during the French Revolution. (MG)

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

    ERIC Educational Resources Information Center

    Christian, Nancy K., Ed.

    This collection of 13 articles by vocational educators discusses issues that confront vocational education in the 1980s. It is designed for the practicing vocational teacher and for persons who are enrolled in preservice vocational education courses. Two major themes running through the papers are: (1) the need to keep existing vocational…

  8. Science policy for the '80s

    NASA Astrophysics Data System (ADS)

    Bell, Peter M.

    Science policy (if it ever was a policy) usually was to support ill-defined or ‘basic’ research in science; the ‘policy’ was embodied in the hope that supported research would someday pay off in the form of improved technology. One of the fathers of this policy during the post-WW-II period was Simon Ramo, a founding member of the National Academy of Engineering, chief scientist of United States ICBM defense operation, founder of the TRW Corporation, and now a member of President Reagan's science and technology task force. Simon Ramo represents an influential group dedicated to a ‘systems analysis’ approach to forecasting technological progress, and as such the ‘systems’ approach emerges as a central theme for science policy in the 1980s.The new shift in national policy introduced by the Reagan administration includes revisions in science policy that have recently been termed as ‘searching examination’ (Chemical & Engineering News, Feb. 23, 1981, p. 22), ‘Unkind cuts’ (New Scientist, Feb. 12, 1981), and ‘The Spectrum from Truth to Power’ (Science, Technology, and National Policy, edited by T. Kuehn and A. Porter, Cornell University Press, Ithaca, N.Y., 1981). The idea now is to speed the conversion of scientific discovery into technology in an orderly way. As never before, there are growing debates over the roles of science in society, its lines of support, its applications. More than ever, social scientists, economists, and philosophical types are trying their hand at influencing science policy in very different ways than scientists themselves, as Vannevar Bush did 30 years ago.

  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. 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…

  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. 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)

  13. Photochemical Hydrogen Generation Initiated by Oxidative Quenching of the Excited Ru(bpy)3 (2+) * by a Bio-Inspired [2Fe2S] Complex.

    PubMed

    Na, Yong; Wei, Peicheng; Zhou, Li

    2016-07-18

    A diiron dithiolate complex 1 containing 1,8-naphthalic anhydride bridge was prepared, which possessed the lowest reduction potential for the synthetic diiron complexes modeled on the active site of [FeFe] hydrogenase reported so far. For the first time, oxidative quenching of the excited Ru(bpy)3 (2+) * through electron transfer to a bio-inspired [2Fe2S] complex was corroborated. Hydrogen evolution, driven by visible light, was successfully observed for a three-component system, consisting of Ru(bpy)3 (2+) , complex 1, and EDTA as electron donor in aqueous/organic media. These results provide a basis and also opportunity to develop a photo water splitting system employing Fe-based catalysts without sacrificial electron donors. PMID:26879325

  14. Synthesis and structures of tridentate ketoiminate zinc complexes bearing trifluoromethyl substituents that act as L-lactide ring opening polymerization initiators.

    PubMed

    Rezayee, Nomaan M; Gerling, Kimberly A; Rheingold, Arnold L; Fritsch, Joseph M

    2013-04-21

    A series of NNO ketoimines bearing trifluoromethyl substituents were synthesized from the Schiff base condensation of 1,3-diketones (1,1,1-trifluoro-5,5-dimethyl-2,4-hexanedione, 4,4,4-trifluoro-1-phenyl-1,3-butanedione, and 1,1,1-trifluoro-2,4-pentanedione, 1,1,1,5,5,5-hexafluoroacetylacetone) and 8-aminoquinoline or 8-amino-2-methylquinoline and isolated in 40-70% yield. The ketoimines were combined with zinc bis-(trimethylsilyl)amide to prepare a zinc amide complex in 41% yield or were combined with zinc bis-(trimethylsilyl)amide and 2,6-di-tert-butylphenol to prepare zinc phenoxide complexes in 81-94% yield. The ketoimines and zinc complexes were characterized with (1)H, (13)C, and (19)F NMR, absorbance spectroscopy, mass spectrometry, elemental analysis and X-ray crystallography. The mononuclear solid state structures of the zinc amide and phenoxide complexes showed tridentate coordination of the zinc center by the ketoiminate and monodentate coordination by the amide or phenoxide. The zinc complexes were assessed for their ability to catalyze the ring opening polymerization (ROP) of L-lactide into poly-lactic acid (PLA) with some complexes reaching 100% conversion in 3 h. As the monomer to catalyst ratio increased, the molecular weight of the isolated polymeric material increased in a nearly linear fashion while retaining a narrow molecular weight distribution. Homonuclear decoupled (1)H NMR spectra of the isolated polymeric material showed the retention of stereochemistry in the isotactic poly-L-lactic acid. Kinetic studies, where the substituents on the ketoiminate and quinolyl moiety were varied, showed that lower electron density on the Zn metal center yielded lower ROP catalytic activity than their electron rich counterparts. The complexes are proposed to use the coordination-insertion mechanism for living polymerization of L-lactide. PMID:23435405

  15. Kinetics of initiating polypeptide elongation in an IRES-dependent system

    PubMed Central

    Zhang, Haibo; Ng, Martin Y; Chen, Yuanwei; Cooperman, Barry S

    2016-01-01

    The intergenic IRES of Cricket Paralysis Virus (CrPV-IRES) forms a tight complex with 80S ribosomes capable of initiating the cell-free synthesis of complete proteins in the absence of initiation factors. Such synthesis raises the question of what effect the necessary IRES dissociation from the tRNA binding sites, and ultimately from all of the ribosome, has on the rates of initial peptide elongation steps as nascent peptide is formed. Here we report the first results measuring rates of reaction for the initial cycles of IRES-dependent elongation. Our results demonstrate that 1) the first two cycles of elongation proceed much more slowly than subsequent cycles, 2) these reduced rates arise from slow pseudo-translocation and translocation steps, and 3) the retarding effect of ribosome-bound IRES on protein synthesis is largely overcome following translocation of tripeptidyl-tRNA. Our results also provide a straightforward approach to detailed mechanistic characterization of many aspects of eukaryotic polypeptide elongation. DOI: http://dx.doi.org/10.7554/eLife.13429.001 PMID:27253065

  16. Kinetics of initiating polypeptide elongation in an IRES-dependent system.

    PubMed

    Zhang, Haibo; Ng, Martin Y; Chen, Yuanwei; Cooperman, Barry S

    2016-01-01

    The intergenic IRES of Cricket Paralysis Virus (CrPV-IRES) forms a tight complex with 80S ribosomes capable of initiating the cell-free synthesis of complete proteins in the absence of initiation factors. Such synthesis raises the question of what effect the necessary IRES dissociation from the tRNA binding sites, and ultimately from all of the ribosome, has on the rates of initial peptide elongation steps as nascent peptide is formed. Here we report the first results measuring rates of reaction for the initial cycles of IRES-dependent elongation. Our results demonstrate that 1) the first two cycles of elongation proceed much more slowly than subsequent cycles, 2) these reduced rates arise from slow pseudo-translocation and translocation steps, and 3) the retarding effect of ribosome-bound IRES on protein synthesis is largely overcome following translocation of tripeptidyl-tRNA. Our results also provide a straightforward approach to detailed mechanistic characterization of many aspects of eukaryotic polypeptide elongation. PMID:27253065

  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. Increased generation of intracellular reactive oxygen species initiates selective cytotoxicity against the MCF-7 cell line resultant from redox active combination therapy using copper-thiosemicarbazone complexes.

    PubMed

    Akladios, Fady N; Andrew, Scott D; Parkinson, Christopher J

    2016-06-01

    The combination of cytotoxic copper-thiosemicarbazone complexes with phenoxazines results in an up to 50-fold enhancement in the cytotoxic potential of the thiosemicarbazone against the MCF-7 human breast adenocarcinoma cell line over the effect attributable to drug additivity-allowing minimization of the more toxic copper-thiosemicarbazone component of the therapy. The combination of a benzophenoxazine with all classes of copper complex examined in this study proved more effective than combinations of the copper complexes with related isoelectronic azines. The combination approach results in rapid elevation of intracellular reactive oxygen levels followed by apoptotic cell death. Normal fibroblasts representative of non-cancerous cells (MRC-5) did not display a similar elevation of reactive oxygen levels when exposed to similar drug levels. The minimization of the copper-thiosemicarbazone component of the therapy results in an enhanced safety profile against normal fibroblasts. PMID:26951232

  19. 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

  20. Initial Stages of V(D)J Recombination: the Organization of RAG1/2 and RSS DNA in the Post-cleavage Complex

    PubMed Central

    Grundy, Gabrielle J.; Ramón-Maiques, Santiago; Dimitriadis, Emilios K.; Kotova, Svetlana; Biertümpfel, Christian; Heymann, J. Bernard; Steven, Alasdair C.; Gellert, Martin; Yang, Wei

    2009-01-01

    SUMMARY To obtain structural information on the early stages of V(D)J recombination, we isolated a complex of the core RAG1 and RAG2 proteins with DNA containing a pair of cleaved recombination signal sequences (RSS). Stoichiometric and molecular mass analysis established that this signal end complex (SEC) contains two protomers each of RAG1 and RAG2. Visualization of the SEC by negative staining electron microscopy revealed an anchor-shaped particle with approximate two-fold symmetry. Consistent with a parallel arrangement of DNA and protein subunits, the N-termini of RAG1 and RAG2 are positioned at opposing ends of the complex, and the DNA chains beyond the RSS nonamer emerge from the same face of the complex, near to the RAG1 N-termini. These first images of the V(D)J recombinase in its post-cleavage state provide a framework for modeling RAG domains and their interactions with DNA. PMID:19647518

  1. 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.

  2. Initial use of dioximate ligands in 3d/4f cluster chemistry: synthesis, structure, and magnetic studies of an unusual [Gd(III)2Mn(IV)O]8+ complex.

    PubMed

    Lampropoulos, Christos; Stamatatos, Theocharis C; Abboud, Khalil A; Christou, George

    2009-01-19

    An unusual [Mn(IV)Gd(III)(2)(mu(3)-O(2-))](8+) triangular complex has been prepared from the initial use of 2,6-diacetylpyridine dioxime (dapdoH(2)) in 3d/4f cluster chemistry. The complex has an S = (13)/(2) ground state, with exchange parameters J = +0.49 cm(-1) and J' = -0.12 cm(-1) [H = -2J(S(i) x S(j)) convention] for the Gd(III)...Mn(IV) and Gd(III)...Gd(III) interactions, respectively. The origin of this ground state has been rationalized by consideration of the spin frustration occurring within the complex as a function of the relative magnitude of the competing interactions. PMID:19072591

  3. 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

  4. 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.

  5. 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

  6. Systematic Study Related to the Role of Initial Impurities and Irradiation Rates in the Formation and Evolution of Complex Defects in Silicon for Detectors in HEP Experiments

    NASA Astrophysics Data System (ADS)

    Lazanu, S.; Lazanu, I.

    The influence of oxygen and carbon impurities on the concentrations of defects in silicon for detector uses, in complex fields of radiation, characteristic to high energy physics experiments, is investigated in the frame of the quantitative phenomenological model developed previously by the authors and extended in the present paper. Continuous irradiation conditions are considered, simulating realistically the environments for these experiments. The generation rate of primary defects is calculated starting from the projectile-silicon interaction and from the recoil energy redistribution in the lattice. The mechanisms of formation of complex defects are explicitly analysed. Vacancy-interstitial annihilation, interstitial and vacancy migration to sinks, divacancy, vacancy- and interstitial-impurity complex formation and decomposition are considered. Oxygen and carbon impurities present in silicon could monitor the concentration of all stable defects, due to their interaction with vacancies and interstitials. Their role in the mechanisms of formation and decomposition of the following stable defects: V2, VO, V2O, Ci, CiOi, CiCs and VP, is studied. The model predictions cover a generation rate of primary defects between 102 pairs/cm3/s and 1011 pairs/cm3/s, and could be a useful clue in obtaining harder materials for detectors for space missions, at the new generation of accelerators, as, e.g. LHC, Super-LHC and Eloisatron, or for industrial applications.

  7. 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. PMID:24248602

  8. Spectroscopic and theoretical studies on the nucleophilic substitution of 2,3-dichloronaphthoquinone with para-substituted anilines in solid state via initial charge transfer complexation

    NASA Astrophysics Data System (ADS)

    Satheshkumar, Angupillai; Elango, Kuppanagounder P.

    2012-12-01

    Various spectroscopy techniques (UV-Vis, DRS, FT-IR, 1H NMR, LC-MS) and theoretical computations have been employed to investigate the mechanism of the nucleophilic substitution reaction of 2,3-dichloronaphthoquinone (DCNQ) with para-substituted anilines in solid state under base- and solvent-free conditions against traditional synthetic routes. The initial formations of electron donor acceptor (EDA) adduct between DCNQ and aniline was found to be the driving force for the substitution reaction to occur in solid phase.

  9. Magnesium chelatase from Rhodobacter sphaeroides: initial characterization of the enzyme using purified subunits and evidence for a BchI-BchD complex.

    PubMed Central

    Gibson, L C; Jensen, P E; Hunter, C N

    1999-01-01

    The enzyme magnesium-protoporphyrin IX chelatase (Mg chelatase) catalyses the insertion of Mg into protoporphyrin IX, the first committed step in (bacterio)chlorophyll biosynthesis. In the photosynthetic bacterium Rhodobacter sphaeroides, this reaction is catalysed by the products of the bchI, bchD and bchH genes. These genes have been expressed in Escherichia coli so that the BchI, BchD and BchH proteins are produced with N-terminal His6 affinity tags, which has led to the production of large amounts of highly purified, highly active Mg chelatase subunits from a single chromatography step. Furthermore, BchD has been purifed free of contamination with the chaperone GroEL, which had proven to be a problem in the past. BchD, present largely as an insoluble protein in E. coli, was purified in 6 M urea and refolded by addition of BchI, MgCl2 and ATP, yielding highly active protein. BchI/BchD mixtures prepared in this way were used in conjunction with BchH to determine the kinetic parameters of R. sphaeroides Mg chelatase for its natural substrates. We have been able to demonstrate for the first time that BchI and BchD form a complex, and that Mg2+ and ATP are required to establish and maintain this complex. Gel filtration data suggest that BchI and BchD form a complex of molecular mass 200 kDa in the presence of Mg2+ and ATP. Our data suggest that, in vivo, BchD is only folded correctly and maintained in its correct conformation in the presence of BchI, Mg2+ and ATP. PMID:9882621

  10. Evidence for variation in the optimal translation initiation complex: plant eIF4B, eIF4F, and eIF(iso)4F differentially promote translation of mRNAs.

    PubMed

    Mayberry, Laura K; Allen, M Leah; Dennis, Michael D; Browning, Karen S

    2009-08-01

    Eukaryotic initiation factor (eIF) 4B is known to interact with multiple initiation factors, mRNA, rRNA, and poly(A) binding protein (PABP). To gain a better understanding of the function of eIF4B, the two isoforms from Arabidopsis (Arabidopsis thaliana) were expressed and analyzed using biophysical and biochemical methods. Plant eIF4B was found by ultracentrifugation and light scattering analysis to most likely be a monomer with an extended structure. An extended structure would facilitate the multiple interactions of eIF4B with mRNA as well as other initiation factors (eIF4A, eIF4G, PABP, and eIF3). Eight mRNAs, barley (Hordeum vulgare) alpha-amylase mRNA, rabbit beta-hemoglobin mRNA, Arabidopsis heat shock protein 21 (HSP21) mRNA, oat (Avena sativa) globulin, wheat (Triticum aestivum) germin, maize (Zea mays) alcohol dehydrogenase, satellite tobacco necrosis virus RNA, and alfalfa mosaic virus (AMV) 4, were used in wheat germ in vitro translation assays to measure their dependence on eIF4B and eIF4F isoforms. The two Arabidopsis eIF4B isoforms, as well as native and recombinant wheat eIF4B, showed similar responses in the translation assay. AMV RNA 4 and Arabidopsis HSP21 showed only a slight dependence on the presence of eIF4B isoforms, whereas rabbit beta-hemoglobin mRNA and wheat germin mRNA showed modest dependence. Barley alpha-amylase, oat globulin, and satellite tobacco necrosis virus RNA displayed the strongest dependence on eIF4B. These results suggest that eIF4B has some effects on mRNA discrimination during initiation of translation. Barley alpha-amylase, oat globulin, and rabbit beta-hemoglobin mRNA showed the highest activity with eIF4F, whereas Arabidopsis HSP21 and AMV RNA 4 used both eIF4F and eIF(iso)4F equally well. These results suggest that differential or optimal translation of mRNAs may require initiation complexes composed of specific isoforms of initiation factor gene products. Thus, individual mRNAs or classes of mRNAs may respond to the

  11. 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

  12. A Bub1–Mad1 interaction targets the Mad1–Mad2 complex to unattached kinetochores to initiate the spindle checkpoint

    PubMed Central

    Moyle, Mark W.; Kim, Taekyung; Hattersley, Neil; Espeut, Julien; Cheerambathur, Dhanya K.; Oegema, Karen

    2014-01-01

    Recruitment of Mad1–Mad2 complexes to unattached kinetochores is a central event in spindle checkpoint signaling. Despite its importance, the mechanism that recruits Mad1–Mad2 to kinetochores is unclear. In this paper, we show that MAD-1 interacts with BUB-1 in Caenorhabditis elegans. Mutagenesis identified specific residues in a segment of the MAD-1 coiled coil that mediate the BUB-1 interaction. In addition to unattached kinetochores, MAD-1 localized between separating meiotic chromosomes and to the nuclear periphery. Mutations in the MAD-1 coiled coil that selectively disrupt interaction with BUB-1 eliminated MAD-1 localization to unattached kinetochores and between meiotic chromosomes, both of which require BUB-1, and abrogated checkpoint signaling. The identified MAD-1 coiled-coil segment interacted with a C-terminal region of BUB-1 that contains its kinase domain, and mutations in this region prevented MAD-1 kinetochore targeting independently of kinase activity. These results delineate an interaction between BUB-1 and MAD-1 that targets MAD-1–MAD-2 complexes to kinetochores and is essential for spindle checkpoint signaling. PMID:24567362

  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. MiR-215 Is Induced Post-transcriptionally via HIF-Drosha Complex and Mediates Glioma-Initiating Cell Adaptation to Hypoxia by Targeting KDM1B.

    PubMed

    Hu, Jing; Sun, Tao; Wang, Hui; Chen, Zhengxin; Wang, Shuai; Yuan, Lifeng; Liu, Tingyu; Li, Hai-Ri; Wang, Pingping; Feng, Yukuan; Wang, Qinhong; McLendon, Roger E; Friedman, Allan H; Keir, Stephen T; Bigner, Darell D; Rathmell, Jeff; Fu, Xiang-Dong; Li, Qi-Jing; Wang, Huibo; Wang, Xiao-Fan

    2016-01-11

    The hypoxic tumor microenvironment serves as a niche for maintaining the glioma-initiating cells (GICs) that are critical for glioblastoma (GBM) occurrence and recurrence. Here, we report that hypoxia-induced miR-215 is vital for reprograming GICs to fit the hypoxic microenvironment via suppressing the expression of an epigenetic regulator KDM1B and modulating activities of multiple pathways. Interestingly, biogenesis of miR-215 and several miRNAs is accelerated post-transcriptionally by hypoxia-inducible factors (HIFs) through HIF-Drosha interaction. Moreover, miR-215 expression correlates inversely with KDM1B while correlating positively with HIF1α and GBM progression in patients. These findings reveal a direct role of HIF in regulating miRNA biogenesis and consequently activating the miR-215-KDM1B-mediated signaling required for GIC adaptation to hypoxia. PMID:26766590

  15. Depletion of eIF2·GTP·Met-tRNAi translation initiation complex up-regulates BRCA1 expression in vitro and in vivo.

    PubMed

    Aktas, Bertal H; Bordelois, Paula; Peker, Selen; Merajver, Sophia; Halperin, Jose A

    2015-03-30

    Most sporadic breast and ovarian cancers express low levels of the breast cancer susceptibility gene, BRCA1. The BRCA1 gene produces two transcripts, mRNAa and mRNAb. mRNAb, present in breast cancer but not in normal mammary epithelial cells, contains three upstream open reading frames (uORFs) in its 5'UTR and is translationally repressed. Comparable tandem uORFs are characteristically seen in mRNAs whose translational efficiency paradoxically increases when the overall translation rate is decreased due to phosphorylation of eukaryotic translation initiation factor 2 α (eIF2α). Here we show fish oil derived eicosopanthenoic acid (EPA) that induces eIF2α phosphorylation translationally up-regulates the expression of BRCA1 in human breast cancer cells. We demonstrate further that a diet rich in EPA strongly induces expression of BRCA1 in human breast cancer xenografts. PMID:25762631

  16. 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

  17. 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.

  18. Suppression of alveolar macrophage membrane receptor-mediated phagocytosis by model and actual particle-adsorbate complexes. Initial contact with the alveolar macrophage membrane.

    PubMed Central

    Jakab, G J; Risby, T H; Sehnert, S S; Hmieleski, R R; Farrington, J E

    1990-01-01

    Alveolar macrophages were treated with carbon blacks and adsorbates in order to evaluate the biologic effect of adsorbate, adsorbent and adsorbate-adsorbent complexes. Their capacity to phagocytize a subsequent challenge via the Fc-membrane receptor was quantified. Phagocytosis was suppressed in a dose-related manner with increasing concentrations of both carbon blacks and adsorbates. Carbon black N339 covered with 0.5 monolayers of the adsorbates suppressed phagocytosis more than N339 without the adsorbates. Increasing the adsorbate acrolein coverage from 0.5 to greater than 2.0 monolayers suppressed phagocytosis in a dose-related manner. Finally, samples of diesel particulate matter collected from an engine operated on a pure hydrocarbon fuel with various oxidizers, air (PSU #1) and an oxidizer free of nitrogen (N-free) were tested. Treatment of the macrophages with PSU #1 had a negligible effect on phagocytosis whereas the N-free sample suppressed phagocytosis in a dose-related manner. The data show that alveolar macrophage Fc-receptor-mediated phagocytosis is affected by: carbon black and adsorbate identity and concentration, coverage of the carbon black with adsorbates, and the oxidizer used in the generation of particles emitted by a diesel engine. Images FIGURE 6. PMID:2401270

  19. The dimer state of GyrB is an active form: implications for the initial complex assembly and processive strand passage

    PubMed Central

    Wu, Jinjun; Zhang, Zhiping; Mitchenall, Lesley A.; Maxwell, Anthony; Deng, Jiaoyu; Zhang, Hongtai; Zhou, Ying; Chen, Yuan-yuan; Wang, Da-Cheng; Zhang, Xian-En; Bi, Lijun

    2011-01-01

    In a previous study, we presented the dimer structure of DNA gyrase B′ domain (GyrB C-terminal domain) from Mycobacterium tuberculosis and proposed a ‘sluice-like’ model for T-segment transport. However, the role of the dimer structure is still not well understood. Cross-linking and analytical ultracentrifugation experiments showed that the dimer structure exists both in the B′ protein and in the full-length GyrB in solution. The cross-linked dimer of GyrB bound GyrA very weakly, but bound dsDNA with a much higher affinity than that of the monomer state. Using cross-linking and far-western analyses, the dimer state of GyrB was found to be involved in the ternary GyrA–GyrB–DNA complex. The results of mutational studies reveal that the dimer structure represents a state before DNA cleavage. Additionally, these results suggest that the dimer might also be present between the cleavage and reunion steps during processive transport. PMID:21745817

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

    PubMed Central

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

    2010-01-01

    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. Electronic supplementary material The online version of this article (doi:10.1007/s11103-010-9670-z) contains supplementary material, which is available to authorized users. PMID:20694742

  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. 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

  3. 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

  4. Study of Cyclin Proteolysis in Anaphase-Promoting Complex (APC) Mutant Cells Reveals the Requirement for APC Function in the Final Steps of the Fission Yeast Septation Initiation Network

    PubMed Central

    Chang, Louise; Morrell, Jennifer L.; Feoktistova, Anna; Gould, Kathleen L.

    2001-01-01

    Cytokinesis in eukaryotic cells requires the inactivation of mitotic cyclin-dependent kinase complexes. An apparent exception to this relationship is found in Schizosaccharomyces pombe mutants with mutations of the anaphase-promoting complex (APC). These conditional lethal mutants arrest with unsegregated chromosomes because they cannot degrade the securin, Cut2p. Although failing at nuclear division, these mutants septate and divide. Since septation requires Cdc2p inactivation in wild-type S. pombe, it has been suggested that Cdc2p inactivation occurs in these mutants by a mechanism independent of cyclin degradation. In contrast to this prediction, we show that Cdc2p kinase activity fluctuates in APC cut mutants due to Cdc13/cyclin B destruction. In APC-null mutants, however, septation and cutting do not occur and Cdc13p is stable. We conclude that APC cut mutants are hypomorphic with respect to Cdc13p degradation. Indeed, overproduction of nondestructible Cdc13p prevents septation in APC cut mutants and the normal reorganization of septation initiation network components during anaphase. PMID:11533255

  5. Fusel Alcohols Regulate Translation Initiation by Inhibiting eIF2B to Reduce Ternary Complex in a Mechanism That May Involve Altering the Integrity and Dynamics of the eIF2B Body

    PubMed Central

    Taylor, Eleanor J.; Campbell, Susan G.; Griffiths, Christian D.; Reid, Peter J.; Slaven, John W.; Harrison, Richard J.; Sims, Paul F.G.; Pavitt, Graham D.; Delneri, Daniela

    2010-01-01

    Recycling of eIF2-GDP to the GTP-bound form constitutes a core essential, regulated step in eukaryotic translation. This reaction is mediated by eIF2B, a heteropentameric factor with important links to human disease. eIF2 in the GTP-bound form binds to methionyl initiator tRNA to form a ternary complex, and the levels of this ternary complex can be a critical determinant of the rate of protein synthesis. Here we show that eIF2B serves as the target for translation inhibition by various fusel alcohols in yeast. Fusel alcohols are endpoint metabolites from amino acid catabolism, which signal nitrogen scarcity. We show that the inhibition of eIF2B leads to reduced ternary complex levels and that different eIF2B subunit mutants alter fusel alcohol sensitivity. A DNA tiling array strategy was developed that overcame difficulties in the identification of these mutants where the phenotypic distinctions were too subtle for classical complementation cloning. Fusel alcohols also lead to eIF2α dephosphorylation in a Sit4p-dependent manner. In yeast, eIF2B occupies a large cytoplasmic body where guanine nucleotide exchange on eIF2 can occur and be regulated. Fusel alcohols impact on both the movement and dynamics of this 2B body. Overall, these results confirm that the guanine nucleotide exchange factor, eIF2B, is targeted by fusel alcohols. Moreover, they highlight a potential connection between the movement or integrity of the 2B body and eIF2B regulation. PMID:20444979

  6. 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.

  7. 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.

  8. Development of a complex amino acid supplement, Fatigue Reviva™, for oral ingestion: initial evaluations of product concept and impact on symptoms of sub-health in a group of males

    PubMed Central

    2013-01-01

    Background A new dietary supplement, Fatigue Reviva™, has been recently developed to address issues related to amino acid depletion following illness or in conditions of sub-health where altered amino acid homeostasis has been associated with fatigue. Complex formulations of amino acids present significant challenges due to solubility and taste constraints. This initial study sets out to provide an initial appraisal of product palatability and to gather pilot evidence for efficacy. Methods Males reporting symptoms of sub-health were recruited on the basis of being free from any significant medical or psychological condition. Each participant took an amino acid based dietary supplement (Fatigue Reviva™) daily for 30 days. Comparisons were then made between pre- and post-supplement general health symptoms and urinary amino acid profiles. Results Seventeen men took part in the study. Following amino acid supplementation the total Chalder fatigue score improved significantly (mean ± SEM, 12.5 ± 0.9 versus 10.0 ± 1.0, P<0.03). When asked whether they thought that the supplement had improved their health, 65% of participants responded positively. A subgroup of participants reported gastrointestinal symptoms which were attributed to the supplement and which were believed to result from the component fructooligosaccharide. Analysis of urinary amino acids revealed significant alterations in the relative abundances of a number of amino acids after supplementation including an increase in valine, isoleucine and glutamic acid and reduced levels of glutamine and ornithine. Discriminant function analysis of the urinary amino acid data revealed significant differences between the pre- and post-supplement urine excretion profiles. Conclusions The results indicated that Fatigue Reviva™ was palatable and that 65% of the study group reported that they felt the product had improved their health. The product could provide an effective tool for the management of unexplained

  9. 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.

  10. 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.

  11. Metformin inhibits mammalian target of rapamycin-dependent translation initiation in breast cancer cells.

    PubMed

    Dowling, Ryan J O; Zakikhani, Mahvash; Fantus, I George; Pollak, Michael; Sonenberg, Nahum

    2007-11-15

    Metformin is used for the treatment of type 2 diabetes because of its ability to lower blood glucose. The effects of metformin are explained by the activation of AMP-activated protein kinase (AMPK), which regulates cellular energy metabolism. Recently, we showed that metformin inhibits the growth of breast cancer cells through the activation of AMPK. Here, we show that metformin inhibits translation initiation. In MCF-7 breast cancer cells, metformin treatment led to a 30% decrease in global protein synthesis. Metformin caused a dose-dependent specific decrease in cap-dependent translation, with a maximal inhibition of 40%. Polysome profile analysis showed an inhibition of translation initiation as metformin treatment of MCF-7 cells led to a shift of mRNAs from heavy to light polysomes and a concomitant increase in the amount of 80S ribosomes. The decrease in translation caused by metformin was associated with mammalian target of rapamycin (mTOR) inhibition, and a decrease in the phosphorylation of S6 kinase, ribosomal protein S6, and eIF4E-binding protein 1. The effects of metformin on translation were mediated by AMPK, as treatment of cells with the AMPK inhibitor compound C prevented the inhibition of translation. Furthermore, translation in MDA-MB-231 cells, which lack the AMPK kinase LKB1, and in tuberous sclerosis complex 2 null (TSC2(-/-)) mouse embryonic fibroblasts was unaffected by metformin, indicating that LKB1 and TSC2 are involved in the mechanism of action of metformin. These results show that metformin-mediated AMPK activation leads to inhibition of mTOR and a reduction in translation initiation, thus providing a possible mechanism of action of metformin in the inhibition of cancer cell growth. PMID:18006825

  12. 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

  13. Critical role of 5-HT1A, 5-HT3, and 5-HT7 receptor subtypes in the initiation, generation, and propagation of the murine colonic migrating motor complex.

    PubMed

    Dickson, Eamonn J; Heredia, Dante J; Smith, Terence K

    2010-07-01

    The colonic migrating motor complex (CMMC) is necessary for fecal pellet propulsion in the murine colon. We have previously shown that 5-hydroxytryptamine (5-HT) released from enterochromaffin cells activates 5-HT(3) receptors on the mucosal processes of myenteric Dogiel type II neurons to initiate the events underlying the CMMC. Our aims were to further investigate the roles of 5-HT(1A), 5-HT(3), and 5-HT(7) receptor subtypes in generating and propagating the CMMC using intracellular microelectrodes or tension recordings from the circular muscle (CM) in preparations with and without the mucosa. Spontaneous CMMCs were recorded from the CM in isolated murine colons but not in preparations without the mucosa. In mucosaless preparations, ondansetron (3 microM; 5-HT(3) antagonist) plus hexamethonium (100 microM) completely blocked spontaneous inhibitory junction potentials, depolarized the CM. Ondansetron blocked the preceding hyperpolarization associated with a CMMC. Spontaneous CMMCs and CMMCs evoked by spritzing 5-HT (10 and 100 microM) or nerve stimulation in preparations without the mucosa were blocked by SB 258719 or SB 269970 (1-5 microM; 5-HT(7) antagonists). Both NAN-190 and (S)-WAY100135 (1-5 microM; 5-HT(1A) antagonists) blocked spontaneous CMMCs and neurally evoked CMMCs in preparations without the mucosa. Both NAN-190 and (S)-WAY100135 caused an atropine-sensitive depolarization of the CM. The precursor of 5-HT, 5-hydroxytryptophan (5-HTP) (10 microM), and 5-carboxamidotryptamine (5-CT) (5 microM; 5-HT(1/5/7) agonist) increased the frequency of spontaneous CMMCs. 5-HTP and 5-CT also induced CMMCs in preparations with and without the mucosa, which were blocked by SB 258719. 5-HT(1A), 5-HT(3), and 5-HT(7) receptors, most likely on Dogiel Type II/AH neurons, are important in initiating, generating, and propagating the CMMC. Tonic inhibition of the CM appears to be driven by ongoing activity in descending serotonergic interneurons; by activating 5-HT(7

  14. 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.

  15. 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

  16. 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

  17. 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

  18. 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…

  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. 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,…

  1. Facing the Pressures of the '80's: A Cooperative Venture.

    ERIC Educational Resources Information Center

    Rushing, Joe B.

    The role of community services and continuing education in the community college must be carefully analyzed by educational leaders in the changing milieu of the 1980's. Never has close affiliation with the parent institution been more critical to the welfare of continuing education, which gains strength from being mainstreamed in terms of…

  2. 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.…

  3. 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…

  4. 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…

  5. 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)

  6. Photovoltaic solar energy conversion in the '80s

    NASA Astrophysics Data System (ADS)

    Chevalier, I.

    1981-04-01

    The potential for photovoltaic solar energy conversion in the generation of electricity to meet the needs of industrial and developing nations in the 1980s is discussed. The current technology of photovoltaic cells and modules, which are for the most part based on single crystal silicon and can deliver peak powers of 2 to 40 W at 6 to 12 V, is reviewed and prospects for cost reduction in the short- and medium-term by the development of new materials and production methods and increased cell efficiency and in the long term by the development of thin film cells, alternative compounds and mass production are indicated. Possible applications of photovoltaic-derived electricity are pointed out, including educational television receivers, rural telephones, refrigerators, water pumping and hospitals in developing nations and telecommunications, cathodic protection, signaling, telemetry and low-power pumping applications in industrial nations. Predictions of a photovoltaic peak Watt installed costing less than 10 francs by 1990 and a market above 100 MW in 1985 are pointed out.

  7. 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.

  8. 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…

  9. 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…

  10. Special Education: A Challenge for the 80's.

    ERIC Educational Resources Information Center

    Chapey, Geraldine

    The special education referral-placement phenomenon has reached crisis proportions in New York City. Problems affecting effectiveness of approaches include: inadequate state and federal funding; fragmented decision making; lack of uniform terminology and standardized criteria for special education; lack of training, support services, and resources…

  11. Policies for Tomorrow: Illinois Community Colleges in the 80's.

    ERIC Educational Resources Information Center

    Illinois Community Coll. Trustees Association, Springfield.

    This six-part report is the result of a 1980-81 study by the Illinois Community College Trustees Association of the fundamental questions that underlie the common educational enterprise of the community college system. It seeks to provide community college trustees and state policy-makers with guidelines for governing and planning higher education…

  12. 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…

  13. Public Education. Task Forces on the 80s.

    ERIC Educational Resources Information Center

    Gartner, Alan

    This report addresses current concerns in public education defined as being important to American Jews. Issues discussed include strategies for improving educational quality; the effects of funding disparities, tax credits and vouchers on public education; and the importance of integration and bilingual education in the public schools. Also…

  14. 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)…

  15. 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.

  16. Productivity Pay: A Goal for the '80's.

    ERIC Educational Resources Information Center

    Stewart, John A.

    The enactment of a compensation model that rewards educators' efficiency and creativity is a goal for the current decade. Both inflationary trends and the accountability movement act as motivators for the introduction of a merit pay scale. Current compensation models guarantee income regardless of effort. Through this failure to reward…

  17. Mild hydrocracking in heavy oils in the 80's

    SciTech Connect

    Sonnemans, J.W.M.; D'Amico, V.J.; Desai, P.H.; Dixon, P.H.; Plantenga, F.L.

    1984-03-01

    Many refiners have determined that mild hydrocracking (MHC) is an attractive alternative for converting heavy fuel oils to lighter mid-distillates which are increasingly in demand. Important advantages of MHC are the selective formation of high quality diesel blendstock and the ability to apply this technology in existing vacuum gas oil (VGO) desulfurizers. This paper discusses the criteria for optimizing both catalyst choice and utilization to maximize the economic benefits of MHC. The MHC performance of conventional hydrotreating catalysts and a new generation of MHC catalysts developed by AKZO Chemie's Ketjen Catalyst Group is compared. By applying these new catalysts, conversion levels of 45%, representing an absolute increase of up to 12% over conventional catalysts, may be realized. The improved MHC catalysts have excellent stability. Application studies demonstrate that more than one catalyst type may be needed to optimize conversion for a specific application. Reactor configuration (e.g. single versus multiple bed), feedstock and processing conditions determine the choice of the optimal catalyst(s). Process studies and economic evaluations by Lummus-Crest Inc. indicate that the mild hydrocracking process is an effective way to upgrade heavy oils. For a 20,000 BPSD unit, additional revenue as high as 15 million dollars per year may be realized when going from the HDS to MHC mode of operation. Payout times for revamp investments, when necessary to optimize either conversion and/or the refiner's product slate, are estimated to be about one year.

  18. 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…

  19. Training in the '80's: An Economic Perspective.

    ERIC Educational Resources Information Center

    Klein, Carl

    During the last decade, the manufacture of commodities has become increasingly simple, and as a result, has increasingly been exported from the United States to low-wage regions of the world. On the other hand, the U.S. economy has become increasingly service oriented, with service-sector jobs growing rapidly while manufacturing jobs decline. In…

  20. 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…

  1. 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.…

  2. 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.

  3. 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)

  4. 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…

  5. Kentucky Families in the '80s: A Survey Summary Report.

    ERIC Educational Resources Information Center

    Bokemeier, Janet L.; Maurer, Richard C.

    1983-01-01

    In the spring of 1981, two questionnaires (one for the adult male and one for the adult female) were mailed to households (randomly selected from voter registration lists) in nonmetropolitan counties throughout Kentucky to examine their satisfaction with their communities and personal situations, family interaction, and marital quality. A total of…

  6. The Plus 50 Initiative Evaluation: Initiative Impact

    ERIC Educational Resources Information Center

    American Association of Community Colleges (NJ1), 2012

    2012-01-01

    The American Association of Community Colleges (AACC), with funding from The Atlantic Philanthropies, created the Plus 50 Initiative (2008-2012). This initiative was designed to build the capacity of community colleges nationwide to develop programming that engages the plus 50 learner. This report contains: (1) An overview of the Plus 50…

  7. Initial rate kinetic studies show an unexpected influence of para-substituents on the catalytic behaviour of manganese complexes of TMTACN in the epoxidation of styrenes with H2O2.

    PubMed

    Ilyashenko, Gennadiy; De Faveri, Giorgio; Masoudi, Shirin; Al-Safadi, Rawan; Watkinson, Michael

    2013-03-28

    Investigations into the efficacy of a range of enantiomerically pure BINOL additives in the epoxidation of styrene substrates with a number of manganese catalysts prepared from the ligand 1,4,7-trimethyl-1,4,7-triazacyclononane, TMTACN, using hydrogen peroxide as the oxidant have revealed that there are fundamental differences in reactivity between apparently similar systems. Whilst no asymmetric induction was obtained in the styrene oxide products formed, the data obtained from initial rate kinetic studies appear to be consistent with a number of different catalytically active species operating, the nature of which are profoundly affected by the starting materials used. PMID:23358659

  8. A Kinase Activity Associated with Simian Virus 40 Large T Antigen Phosphorylates Upstream Binding Factor (UBF) and Promotes Formation of a Stable Initiation Complex between UBF and SL1

    PubMed Central

    Zhai, Weiguo; Comai, Lucio

    1999-01-01

    Simian virus 40 large T antigen is a multifunctional protein which has been shown to modulate the expression of genes transcribed by RNA polymerase I (Pol I), II, and III. In all three transcription systems, a key step in the activation process is the recruitment of large T antigen to the promoter by direct protein-protein interaction with the TATA binding protein (TBP)-TAF complexes, namely, SL1, TFIID, and TFIIIB. However, our previous studies on large T antigen stimulation of Pol I transcription also revealed that the binding to the TBP-TAFI complex SL1 is not sufficient to activate transcription. To further define the molecular mechanism involved in large T antigen-mediated Pol I activation, we examined whether the high-mobility group box-containing upstream binding factor (UBF) plays any role in this process. Here, using cell labeling experiments, we showed that large T antigen expression induces an increase in UBF phosphorylation. Further biochemical analysis demonstrated that UBF is phosphorylated by a kinase activity that is strongly associated with large T antigen, and that the carboxy-terminal activation domain of UBF is required for the phosphorylation to occur. Using in vitro reconstituted transcription assays, we demonstrated that the inability of alkaline phosphatase treated UBF to efficiently activate transcription can be rescued by large T antigen. Moreover, we showed that large T antigen-induced UBF phosphorylation promotes the formation of a stable UBF-SL1 complex. Together, these results provide strong evidence for an important role for the large T antigen-associated kinase in mediating the stimulation of RNA Pol I transcription. PMID:10082545

  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. Translation Initiation Factors eIF3 and HCR1 Control Translation Termination and Stop Codon Read-Through in Yeast Cells

    PubMed Central

    Wagner, Susan; Shoemaker, Christopher J.; Gunišová, Stanislava; von der Haar, Tobias; Valášek, Leoš Shivaya

    2013-01-01

    Translation is divided into initiation, elongation, termination and ribosome recycling. Earlier work implicated several eukaryotic initiation factors (eIFs) in ribosomal recycling in vitro. Here, we uncover roles for HCR1 and eIF3 in translation termination in vivo. A substantial proportion of eIF3, HCR1 and eukaryotic release factor 3 (eRF3) but not eIF5 (a well-defined “initiation-specific” binding partner of eIF3) specifically co-sediments with 80S couples isolated from RNase-treated heavy polysomes in an eRF1-dependent manner, indicating the presence of eIF3 and HCR1 on terminating ribosomes. eIF3 and HCR1 also occur in ribosome- and RNA-free complexes with both eRFs and the recycling factor ABCE1/RLI1. Several eIF3 mutations reduce rates of stop codon read-through and genetically interact with mutant eRFs. In contrast, a slow growing deletion of hcr1 increases read-through and accumulates eRF3 in heavy polysomes in a manner suppressible by overexpressed ABCE1/RLI1. Based on these and other findings we propose that upon stop codon recognition, HCR1 promotes eRF3·GDP ejection from the post-termination complexes to allow binding of its interacting partner ABCE1/RLI1. Furthermore, the fact that high dosage of ABCE1/RLI1 fully suppresses the slow growth phenotype of hcr1Δ as well as its termination but not initiation defects implies that the termination function of HCR1 is more critical for optimal proliferation than its function in translation initiation. Based on these and other observations we suggest that the assignment of HCR1 as a bona fide eIF3 subunit should be reconsidered. Together our work characterizes novel roles of eIF3 and HCR1 in stop codon recognition, defining a communication bridge between the initiation and termination/recycling phases of translation. PMID:24278036

  12. Two-step regulation of Ad4BP/SF-1 gene transcription during fetal adrenal development: initiation by a Hox-Pbx1-Prep1 complex and maintenance via autoregulation by Ad4BP/SF-1.

    PubMed

    Zubair, Mohamad; Ishihara, Satoru; Oka, Sanae; Okumura, Katsuzumi; Morohashi, Ken-ichirou

    2006-06-01

    The orphan nuclear receptor Ad4BP/SF-1 (adrenal 4 binding protein/steroidogenic factor 1) is essential for the proper development and function of reproductive and steroidogenic tissues. Although the expression of Ad4BP/SF-1 is specific for those tissues, the mechanisms underlying this tissue-specific expression remain unknown. In this study, we used transgenic mouse assays to examine the regulation of the tissue-specific expression of Ad4BP/SF-1. An investigation of the entire Ad4BP/SF-1 gene locus revealed a fetal adrenal enhancer (FAdE) in intron 4 containing highly conserved binding sites for Pbx-Prep, Pbx-Hox, and Ad4BP/SF-1. Transgenic assays revealed that the Ad4 sites, together with Ad4BP/SF-1, develop an autoregulatory loop and thereby maintain transcription, while the Pbx/Prep and Pbx/Hox sites initiate transcription prior to the establishment of the autoregulatory loop. Indeed, a limited number of Hox family members were found to be expressed in the adrenal primordia. Whether a true fetal-type adrenal cortex is present in mice remained controversial, and this argument was complicated by the postnatal development of the so-called X zone. Using transgenic mice with lacZ driven by the FAdE, we clearly identified a fetal adrenal cortex in mice, and the X zone is the fetal adrenal cells accumulated at the juxtamedullary region after birth. PMID:16705164

  13. 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.

  14. 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

  15. [Complexity: an introduction].

    PubMed

    Gómez, Carlos Alberto Palacio; Jaramillo, Francisco Luis Ochoa

    2011-01-01

    Complexity appears in the twentieth century as a way to understand many phenomena that are perceived as chaotic and complex from classical thought, which still persist in our way of explaining the world. Its purpose is to study the complex and adaptive systems that are sensitive to initial conditions. Some of the characteristics of complex thought are systemic perspective, autopoiesis, self-organization, emergent properties, unpredictability of the systems, analogic thought, and the complementarity of the phenomena, among others. Living systems respond to a complex logic, and in that sense, our vision of human populations and patients, and how we try to solve problems and human diseases, should be open to the possibilities that arise from this form of understand the world. PMID:21503430

  16. 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.

  17. 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).

  18. 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.

  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. 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.

  1. Communication complexity and information complexity

    NASA Astrophysics Data System (ADS)

    Pankratov, Denis

    Information complexity enables the use of information-theoretic tools in communication complexity theory. Prior to the results presented in this thesis, information complexity was mainly used for proving lower bounds and direct-sum theorems in the setting of communication complexity. We present three results that demonstrate new connections between information complexity and communication complexity. In the first contribution we thoroughly study the information complexity of the smallest nontrivial two-party function: the AND function. While computing the communication complexity of AND is trivial, computing its exact information complexity presents a major technical challenge. In overcoming this challenge, we reveal that information complexity gives rise to rich geometrical structures. Our analysis of information complexity relies on new analytic techniques and new characterizations of communication protocols. We also uncover a connection of information complexity to the theory of elliptic partial differential equations. Once we compute the exact information complexity of AND, we can compute exact communication complexity of several related functions on n-bit inputs with some additional technical work. Previous combinatorial and algebraic techniques could only prove bounds of the form theta( n). Interestingly, this level of precision is typical in the area of information theory, so our result demonstrates that this meta-property of precise bounds carries over to information complexity and in certain cases even to communication complexity. Our result does not only strengthen the lower bound on communication complexity of disjointness by making it more exact, but it also shows that information complexity provides the exact upper bound on communication complexity. In fact, this result is more general and applies to a whole class of communication problems. In the second contribution, we use self-reduction methods to prove strong lower bounds on the information

  2. The Ndc80 kinetochore complex forms oligomeric arrays along microtubules

    PubMed Central

    Alushin, Gregory M.; Ramey, Vincent H.; Pasqualato, Sebastiano; Ball, David A.; Grigorieff, Nikolaus; Musacchio, Andrea; Nogales, Eva

    2010-01-01

    The Ndc80 complex is a key site of regulated kinetochore-microtubule attachment, but the molecular mechanism underlying its function remains unknown. Here we present a subnanometer resolution cryo-electron microscopy reconstruction of the human Ndc80 complex bound to microtubules, sufficient for precise docking of crystal structures of the component proteins. We find that Ndc80 binds the microtubule with a tubulin monomer repeat, recognizing α- and β-tubulin at both intra- and inter-dimer interfaces in a manner that is sensitive to tubulin conformation. Furthermore, Ndc80 complexes self-associate along protofilaments via interactions mediated by the amino-terminal tail of the Ndc80 protein, the site of phospho-regulation by the Aurora B kinase. Ndc80's mode of interaction with the microtubule and its oligomerization suggest a mechanism by which Aurora B could regulate the stability of load-bearing Ndc80-microtubule attachments. PMID:20944740

  3. 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)

  4. 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…

  5. An Urban Initiative.

    ERIC Educational Resources Information Center

    New Jersey State Dept. of Education, Trenton.

    New Jersey's urban initiative has two components. The first is a broad-based program that addresses critical issues common to most urban districts Statewide. The second is a comprehensive program (Operation School Renewal) that concentrates the State's resources in three urban districts. The concentrated initiative, Operation School Renewal, will…

  6. Community Marriage Initiatives

    ERIC Educational Resources Information Center

    Doherty, William J.; Anderson, Jared R.

    2004-01-01

    This article reviews the development of community marriage initiatives and their relationship with family professionals, with particular emphasis on sociohistorical context. We describe five leading community marriage initiatives, discuss the state of the evaluation research, and propose new directions for this promising area of work.

  7. 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.

  8. 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,…

  9. DiffPy-CMI-Python libraries for Complex Modeling Initiative

    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.

  10. 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.

  11. 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.

  12. 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…

  13. 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.

  14. 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...

  15. 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.

  16. 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

  17. Youth Initiatives and the Black College.

    ERIC Educational Resources Information Center

    Williams, Lea E.

    1979-01-01

    Youth initiatives at four predominantly Black colleges are examined. Generally, Black institutions, it was found, lack available personnel to read and decipher complex CETA regulations; tend to remain clear of local political maneuvering; and are rarely sought out by local CETA delivery systems. (CT)

  18. 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.

  19. Research on diabatic initialization

    NASA Technical Reports Server (NTRS)

    Kasahara, Akira

    1990-01-01

    The objective of this research project is to contribute to improvement in the synoptic analyses in the tropics for numerical weather prediction and climate research. In addition to a prediction model, four dimensional data assimilation systems have two principal components. One is objective analysis and the other is initialization. Various methods of objective analysis are designed primarily to analyze the mass and rotational wind fields. Methods of initialization are developed to obtain the irrotational wind and its associated vertical velocity field which are balanced with the mass field and free from meteorological noise. There are essentially three approaches to the problem of initialization: quasi-geostrophic theory, bounded derivative method and nonlinear normal mode method. In the midlatitudes, these approaches generally produce satisfactory results even without diabatic effects for large-scale motions. In the tropics, the situation is quite different from that in the midlatitudes. Because of a small magnitude of the Coriolis parameter and a weak horizontal temperature gradient in the tropics, any method of initialization must incorporate diabatic effects. In fact, it can be said that understanding the problem of diabatic initialization is the key to improving the analysis and weather forecasting in the tropics.

  20. 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

  1. 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 ...

  2. 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.

  3. STI Program Multimedia Initiative

    NASA Technical Reports Server (NTRS)

    Cotter, Gladys A.; Kaye, Karen

    1993-01-01

    This paper relates the experience of the NASA Scientific and Technical Information Program in introducing multimedia within the STI Program framework. A discussion of multimedia technology is included to provide context for the STI Program effort. The STI Program's Multimedia Initiative is discussed in detail. Parallels and differences between multimedia and traditional information systems project development are highlighted. Challenges faced by the program in initiating its multimedia project are summarized along with lessons learned. The paper concludes with a synopsis of the benefits the program hopes to provide its users through the introduction of multimedia illustrated by examples of successful multimedia projects.

  4. 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

  5. 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.

  6. 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,…

  7. 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.

  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. The Core Skills Initiative.

    ERIC Educational Resources Information Center

    Further Education Unit, London (England).

    A British initiative that aims to identify, develop, and assess core skills in post-16 courses and qualifications is summarized in this bulletin. The first section discusses expectations regarding what core skills can achieve. The following section focuses on other purposes to which core skills could contribute, such as broadening the post-16…

  10. DIOXIN EXPOSURE INITIATIVE PUBLICATIONS

    EPA Science Inventory

    Following is a listing of published articles that have come out of EPA's Dioxin Exposure Initiative

    SOURCES:

      <...

    1. 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…

    2. 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…

    3. Department-Initiated Change

      ERIC Educational Resources Information Center

      Watson, Anne; De Geest, Els

      2014-01-01

      This paper reports the activity of three secondary school mathematics departments in England in self-initiated states of change that led to overall improvements in students' achievements when compared to previous cohorts. This took place without intervention and without their participation in external projects. They provide examples of…

    4. Sourcebook of Restructuring Initiatives.

      ERIC Educational Resources Information Center

      Stefkovich, Jacqueline A., Ed.

      This three-part sourcebook identifies school restructuring initiatives with a national scope and presents comprehensive information about them. Part 1 identifies and describes national restructuring programs (e.g., Coalition of Essential Schools, Learning Tomorrow, Success for All). Each program description provides an overview of the program as…

    5. 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.

    6. 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…

    7. 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.

    8. 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

    9. 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.

    10. 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.

  1. 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.

  2. Chinese biobanking initiatives.

    PubMed

    Gan, Rongxing; Wang, Huiyuan; Song, Yutong; Fan, Jinli; Xiong, Yan

    2015-02-01

    Due to the requirement for comprehensive clinical research efforts in China, the importance of biobanking in modern clinical research is outlined in this overview. Hospitals, universities, and research institutes have been well organized as fundamental resources for Chinese biobanking initiatives and the resulting bio-sample collections. Here, a brief history and time line of development of biobanking in China will be introduced, as well as strategic designs for future biobanking development. PMID:25686040

  3. Laser Initiated Actuator study

    SciTech Connect

    Watson, B.

    1991-06-27

    The program task was to design and study a laser initiated actuator. The design of the actuator is described, it being comprised of the fiber and body subassemblies. The energy source for all experiments was a Spectra Diode 2200-H2 laser diode. The diode is directly coupled to a 100 micron core, 0.3 numerical aperture fiber optic terminated with an SMA connector. The successful testing results are described and recommendations are made.

  4. Initiation Train Experiments

    NASA Astrophysics Data System (ADS)

    Francois, Elizabeth; Johnson, Carl; Liechty, Gary; Whitley, Von

    2015-06-01

    In an effort to evaluate and qualify a new detonator diagnostic, booster selection and main charge configuration, a variety of small-scale tests have been conducted. This paper will describe the needs, testing approach and model validation. Because of the limited size available some novel approaches were made to understand the observed phenomenon. Function time and time of arrival at various locations in the initiation train are desirable data points. Knowing when each segment initiates the next segment and the time to run up to detonation is critical. Results of our experiments were modeled for timing accuracy, wave shape and pressure. Agreement between the experiments and models will be discussed. The testing that will be discussed is time of arrival wires, PDV, and fiber optic arrays. The time of arrival wire measures the detonator cup breakout time. When correlated to bridge burst, an absolute time is collected. This data point also gives time zero for the booster initiation. Many models actually start at the booster, rather than the detonator, so the inclusion of this data point will improve modeling efforts.

  5. 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…

  6. Complex Clouds

    Atmospheric Science Data Center

    2013-04-16

    ...     View Larger Image The complex structure and beauty of polar clouds are highlighted by these images acquired ... Multi-angle Imaging SpectroRadiometer observes the daylit Earth continuously from pole to pole, and every 9 days views the entire globe ...

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. Initial Ada components evaluation

    NASA Technical Reports Server (NTRS)

    Moebes, Travis

    1989-01-01

    The SAIC has the responsibility for independent test and validation of the SSE. They have been using a mathematical functions library package implemented in Ada to test the SSE IV and V process. The library package consists of elementary mathematical functions and is both machine and accuracy independent. The SSE Ada components evaluation includes code complexity metrics based on Halstead's software science metrics and McCabe's measure of cyclomatic complexity. Halstead's metrics are based on the number of operators and operands on a logical unit of code and are compiled from the number of distinct operators, distinct operands, and total number of occurrences of operators and operands. These metrics give an indication of the physical size of a program in terms of operators and operands and are used diagnostically to point to potential problems. McCabe's Cyclomatic Complexity Metrics (CCM) are compiled from flow charts transformed to equivalent directed graphs. The CCM is a measure of the total number of linearly independent paths through the code's control structure. These metrics were computed for the Ada mathematical functions library using Software Automated Verification and Validation (SAVVAS), the SSE IV and V tool. A table with selected results was shown, indicating that most of these routines are of good quality. Thresholds for the Halstead measures indicate poor quality if the length metric exceeds 260 or difficulty is greater than 190. The McCabe CCM indicated a high quality of software products.

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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).

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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).

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. The Advanced Energy Initiative

    NASA Astrophysics Data System (ADS)

    Milliken, JoAnn; Joseck, Fred; Wang, Michael; Yuzugullu, Elvin

    The President's Advanced Energy Initiative (AEI), launched in 2006, addresses the challenges of energy supply and demand facing our Nation by supporting research and development of advanced technologies for transportation and stationary power generation. The AEI portfolio includes clean coal, nuclear and renewable energy technologies (solar and wind) for stationary power generation and advanced battery technologies, cellulosic ethanol as a fuel and hydrogen fuel cells for transportation. These research and development programs are underpinned by comprehensive life-cycle analysis efforts using models such as Hydrogen Analysis (H2A) and Greenhouse Gases, Regulated Emissions and Energy Use in Transportation (GREET) to enable a better understanding of the characteristics and trade-offs associated with advanced energy options and to help decision makers choose viable pathways for clean, reliable and affordable energy.

  16. 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.

  17. [Advanced Composites Technology Initiatives

    NASA Technical Reports Server (NTRS)

    Julian, Mark R.

    2002-01-01

    This final report closes out the W02 NASA Grant #NCC5-646. The FY02 grant for advanced technology initiatives through the Advanced Composites Technology Institute in Bridgeport, WV, at the Robert C. Byrd Institute (RCBI) Bridgeport Manufacturing Technology Center, is complete; all funding has been expended. RCBI continued to expand access to technology; develop and implement a workforce-training curriculum; improve material development; and provide prototyping and demonstrations of new and advanced composites technologies for West Virginia composites firms. The FY 02 efforts supported workforce development, technical training and the HST development effort of a super-lightweight composite carrier prototype and expanded the existing technical capabilities of the growing aerospace industry across West Virginia to provide additional support for NASA missions. Additionally, the Composites Technology and Training Center was awarded IS0 9001 - 2000 certification and Cleanroom Class 1000 certification during this report period.

  18. 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

  19. 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

  20. [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

  1. THE MECHANISM OF EUKARYOTIC TRANSLATION INITIATION AND PRINCIPLES OF ITS REGULATION

    PubMed Central

    Jackson, Richard J.; Hellen, Christopher U.T.; Pestova, Tatyana V.

    2015-01-01

    PREFACE Protein synthesis is principally regulated at the initiation stage (rather than during elongation or termination), allowing rapid, reversible and spatial control over gene expression. Progress over recent years in determining the structures and activities of initiation factors, and in mapping their interactions within ribosomal initiation complexes, has significantly advanced our understanding of the complex translation initiation process. These developments have provided a solid foundation for studies of regulation of initiation by mechanisms that include modulation of the activity of initiation factors (which affects almost all scanning-dependent initiation), or via sequence-specific RNA-binding proteins and microRNAs (which thus impact individual mRNAs). PMID:20094052

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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.

  7. A dynamic RNA loop in an IRES affects multiple steps of elongation factor-mediated translation initiation.

    PubMed

    Ruehle, Marisa D; Zhang, Haibo; Sheridan, Ryan M; Mitra, Somdeb; Chen, Yuanwei; Gonzalez, Ruben L; Cooperman, Barry S; Kieft, Jeffrey S

    2015-01-01

    Internal ribosome entry sites (IRESs) are powerful model systems to understand how the translation machinery can be manipulated by structured RNAs and for exploring inherent features of ribosome function. The intergenic region (IGR) IRESs from the Dicistroviridae family of viruses are structured RNAs that bind directly to the ribosome and initiate translation by co-opting the translation elongation cycle. These IRESs require an RNA pseudoknot that mimics a codon-anticodon interaction and contains a conformationally dynamic loop. We explored the role of this loop and found that both the length and sequence are essential for translation in different types of IGR IRESs and from diverse viruses. We found that loop 3 affects two discrete elongation factor-dependent steps in the IRES initiation mechanism. Our results show how the IRES directs multiple steps after 80S ribosome placement and highlights the often underappreciated significance of discrete conformationally dynamic elements within the context of structured RNAs. PMID:26523395

  8. Space Climate Initiative

    NASA Astrophysics Data System (ADS)

    Gibson, S. E.; Dikpati, M.; Miesch, M. S.

    2013-12-01

    Solar variability drives our space environment and upper atmosphere, both on short-term "space-weather" time scales and longer "space-climate" time scales. The goal of the proposed initiative is to understand how extremes of solar variability affect space and terrestrial climate by modeling the system from the Sun's interior to the Earth's atmosphere. We have developed a fully 3D Babcock-Leighton solar dynamo model that incorporates the new "BASH" code and "spot-maker" flux emergence technique. This enables us to run dynamo-driven, physically self-consistent experiments that vary flux emergence to examine extreme scenarios of long-term solar variability. For example, motivated by the recent extended solar minimum and possible long-term changes in sunspots, we can address the question "What happens to the solar dynamo and the surface magnetic flux distribution if flux emergence occurs only on scales too small to form sunspots?" From another extreme, we might ask, "What sort of time-evolving flux emergence is likely to foster superstorms such as the 1859 "Carrington flare"? The photospheric magnetic fields arising from such dynamo experiments then provide a boundary condition that may be used for solar irradiance and heliospheric magnetic field models. These models in turn enable studies probing the effects of solar variability extremes on terrestrial climate, geospace environment, and galactic cosmic rays throughout the heliosphere.

  9. 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.

  10. 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.

  11. ALOS-2 initial results

    NASA Astrophysics Data System (ADS)

    Kankaku, Yukihiro; Suzuki, Shinichi; Shimada, Masanobu

    2015-10-01

    The Advanced Land Observing Satellite-2 (ALOS-2) was launched from Tanegashima Space Center by H-IIA rocket successfully on 24th May 2014. ALOS-2 carries the Phased Array type L-band Synthetic Aperture Radar-2 (PALSAR-2) as the state-of-the-art L-band SAR system which succeeds to PALSAR onboard ALOS. PALSAR-2 uses almost whole bandwidth allocated for L-band active sensor of Earth Exploration Satellites Service specified by the Radio Regulation in order to realize the high resolution observation, and also, it transmits more than 6 kW power for lower Noise Equivalent Sigma Zero using 180 TRMs driven by Gallium Nitride (GaN) amplifier which is the first use in space. Furthermore, because ALOS-2 carries the SAR system only, PALSAR-2 antenna can be mounted under the satellite body. It enables to observe right-/left-looking observation by satellite maneuvering. And the high accuracy orbit control to maintain the satellite within 500 m radius tube against the reference orbit enables high coherence for the InSAR processing. Using these new technologies, ALOS-2 has been operating to fulfill the mission requirements such as disaster monitoring and so on. This document introduces the initial result of ALOS-2 from the first year operation.

  12. Moon-Mars Initiative

    NASA Astrophysics Data System (ADS)

    2005-06-01

    On 27 May, the AGU Council unanimously adopted a position statement on NASA's strategic plan released in February 2005:: "A New Age of Exploration: NASA's Direction for 2005 and Beyond". This strategy incorporates U.S. President Bush's vision for manned space flight to Moon and Mars as described in "A Renewed Spirit of Discovery: The President's Vision for U.S. Space Exploration" announced in January 2004. The statement was drafted by a panel chaired by Eric Barron of Penn State University. AGU calls for the U.S. Administration, Congress, and NASA to continue their commitment to innovative Earth and space science programs. This commitment has placed the U.S. in an international leadership position. It enables environmental stewardship, promotes economic vitality, engages the next generation of scientists and engineers, protects life and property, and fosters exploration. It is, however, threatened by new financial demands placed on NASA by the return to human space flight using the space shuttle, finishing the space station, and launching the Moon-Mars initiative.

  13. 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.

  14. Gauging without initial symmetry

    NASA Astrophysics Data System (ADS)

    Kotov, Alexei; Strobl, Thomas

    2016-01-01

    The gauge principle is at the heart of a good part of fundamental physics: Starting with a group G of so-called rigid symmetries of a functional defined over space-time Σ, the original functional is extended appropriately by additional Lie(G) -valued 1-form gauge fields so as to lift the symmetry to Maps(Σ , G) . Physically relevant quantities are then to be obtained as the quotient of the solutions to the Euler-Lagrange equations by these gauge symmetries. In this article we show that one can construct a gauge theory for a standard sigma model in arbitrary space-time dimensions where the target metric is not invariant with respect to any rigid symmetry group, but satisfies a much weaker condition: It is sufficient to find a collection of vector fields va on the target M satisfying the extended Killing equationv a(i ; j) = 0 for some connection acting on the index a. For regular foliations this is equivalent to requiring the conormal bundle to the leaves with its induced metric to be invariant under leaf-preserving diffeomorphisms of M, which in turn generalizes Riemannian submersions to which the notion reduces for smooth leaf spaces M / ∼. The resulting gauge theory has the usual quotient effect with respect to the original ungauged theory: in this way, much more general orbits can be factored out than usually considered. In some cases these are orbits that do not correspond to an initial symmetry, but still can be generated by a finite-dimensional Lie group G. Then the presented gauging procedure leads to an ordinary gauge theory with Lie algebra valued 1-form gauge fields, but showing an unconventional transformation law. In general, however, one finds that the notion of an ordinary structural Lie group is too restrictive and should be replaced by the much more general notion of a structural Lie groupoid.

  15. 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

  16. 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.

  17. 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

  18. 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

  19. 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

  20. 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 ...

  1. 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

  2. Architecture of human translation initiation factor 3

    PubMed Central

    Querol-Audi, Jordi; Sun, Chaomin; Vogan, Jacob M.; Smith, Duane; Gu, Yu; Cate, Jamie; Nogales, Eva

    2013-01-01

    SUMMARY Eukaryotic translation initiation factor 3 (eIF3) plays a central role in protein synthesis by organizing the formation of the 43S preinitiation complex. Using genetic tag visualization by electron microscopy, we reveal the molecular organization of ten human eIF3 subunits, including an octameric core. The structure of eIF3 bears a close resemblance to that of the proteasome lid, with a conserved spatial organization of eight core subunits containing PCI and MPN domains that coordinate functional interactions in both complexes. We further show that eIF3 subunits a and c interact with initiation factors eIF1 and eIF1A, which control the stringency of start codon selection. Finally, we find that subunit j, which modulates messenger RNA interactions with the small ribosomal subunit, makes multiple independent interactions with the eIF3 octameric core. These results highlight the conserved architecture of eIF3 and how it scaffolds key factors that control translation initiation in higher eukaryotes, including humans. PMID:23623729

  3. Catholic Health Initiatives at 10.

    PubMed

    Ross, Joyce M

    2007-01-01

    The summer of 2006 marked the 10th anniversary of the formation of Denver-based Catholic Health Initiatives (CHI). Formed in 1996 as the result of the merger of three Catholic health care systems, and soon joined by a fourth, the system integrated a diverse collection of health care facilities previously sponsored by 12 different religious congregations. It was the first Catholic health system to give laity a sponsorship role in its facilities. CHI's facilities are sponsored by a public juridic person (PJP), the Catholic Health Care Federation (CHCF). The same people who sit on the system's board also constitute CHCF. They are thus responsible for both governance and sponsorship. CHI was the first Catholic health care system to give laypersons a sponsorship role in its facilities. Establishing the PJP was a long and complex task. Eventually, the church determined that CHI's PJP should be pontifical, accountable to the Congregation for Institutes of Consecrated Life and Societies of Apostolic Life in Rome. CHCF in 1991 became the first PJP in health care in the United States. CHI's staff, led by its first president and chief executive officer, Patricia Cahill, quickly took steps to help the new system begin to coalesce, establishing a single, systemwide pension plan, debt policy, and so forth. Also challenging was the creation of a systemwide new culture. An essential step in the development of CHI's culture was the involvement of employees in the identification of its core values: reverence, integrity, compassion, and excellence, The creation of CHI's Mission and Ministry Fund also helped give the system an identity. This fund provides grants to programs that take an innovative approach to building healthy communities, a goal expressed in CHI's mission and vision statements. The people who created CHI and nurtured it during its first decade give it high marks for faithful adherence to its mission. Even so, they acknowledge that there is always more work to be done

  4. [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

  5. Axon initial segment dysfunction in epilepsy

    PubMed Central

    Wimmer, Verena C; Reid, Christopher A; So, Eva Y-W; Berkovic, Samuel F; Petrou, Steven

    2010-01-01

    The axon initial segment (AIS) contains the site of action potential initiation and plays a major role in neuronal excitability. AIS function relies on high concentrations of different ion channels and complex regulatory mechanisms that orchestrate molecular microarchitecture. We review recent evidence that a large number of ion channels associated with epilepsy are enriched at the AIS, making it a ‘hotspot’ for epileptogenesis. Furthermore, we present novel data on the clustering of GABRγ2 receptors in the AIS of cortical and hippocampal neurons in a knock in mouse model of a human genetic epilepsy. This article highlights the molecular coincidence of epilepsy mutations at the AIS and reviews pathogenic mechanisms converging at the AIS. PMID:20375142

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. Complex and liquid hydrides for energy storage

    NASA Astrophysics Data System (ADS)

    Callini, Elsa; Atakli, Zuleyha Özlem Kocabas; Hauback, Bjørn C.; Orimo, Shin-ichi; Jensen, Craig; Dornheim, Martin; Grant, David; Cho, Young Whan; Chen, Ping; Hjörvarsson, Bjørgvin; de Jongh, Petra; Weidenthaler, Claudia; Baricco, Marcello; Paskevicius, Mark; Jensen, Torben R.; Bowden, Mark E.; Autrey, Thomas S.; Züttel, Andreas

    2016-04-01

    The research on complex hydrides for hydrogen storage was initiated by the discovery of Ti as a hydrogen sorption catalyst in NaAlH4 by Boris Bogdanovic in 1996. A large number of new complex hydride materials in various forms and combinations have been synthesized and characterized, and the knowledge regarding the properties of complex hydrides and the synthesis methods has grown enormously since then. A significant portion of the research groups active in the field of complex hydrides is collaborators in the International Energy Agreement Task 32. This paper reports about the important issues in the field of complex hydride research, i.e. the synthesis of borohydrides, the thermodynamics of complex hydrides, the effects of size and confinement, the hydrogen sorption mechanism and the complex hydride composites as well as the properties of liquid complex hydrides. This paper is the result of the collaboration of several groups and is an excellent summary of the recent achievements.

  11. Complex regional pain syndrome

    PubMed Central

    Carr, Emily S.; De La Cerda, Ashley

    2016-01-01

    Complex regional pain syndrome (CRPS) is a neurologic disorder that often results in debilitating chronic pain, but the diagnosis may elude providers as it is one of exclusion. A history of trauma may be elucidated. We report a case of CRPS and review the clinical findings, appropriate workup, and treatment options for the patient. The patient we describe went through an extensive workup before receiving the correct diagnosis. Delay in diagnosis leads to prolonged suffering for the patient and, at times, unnecessary invasive debridement procedures. Raising awareness of this entity may help physicians make the correct diagnosis early, as well as initiate a collaborative effort between neurology, anesthesiology, and dermatology to provide the patient the most favorable outcome. PMID:27365892

  12. 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)

  13. [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

  14. Transient kinetics, fluorescence, and FRET in studies of initiation of translation in bacteria.

    PubMed

    Milon, Pohl; Konevega, Andrey L; Peske, Frank; Fabbretti, Attilio; Gualerzi, Claudio O; Rodnina, Marina V

    2007-01-01

    Initiation of mRNA translation in prokaryotes requires the small ribosomal subunit (30S), initiator fMet-tRNA(fMet), three initiation factors, IF1, IF2, and IF3, and the large ribosomal subunit (50S). During initiation, the 30S subunit, in a complex with IF3, binds mRNA, IF1, IF2.GTP, and fMet-tRNA(fMet) to form a 30S initiation complex which then recruits the 50S subunit to yield a 70S initiation complex, while the initiation factors are released. Here we describe a transient kinetic approach to study the timing of elemental steps of 30S initiation complex formation, 50S subunit joining, and the dissociation of the initiation factors from the 70S initiation complex. Labeling of ribosomal subunits, fMet-tRNA(fMet), mRNA, and initiation factors with fluorescent reporter groups allows for the direct observation of the formation or dissociation of complexes by monitoring changes in the fluorescence of single dyes or fluorescence resonance energy transfer (FRET) between two fluorophores. Subunit joining was monitored by light scattering or by FRET between dyes attached to the ribosomal subunits. The kinetics of chemical steps, that is, GTP hydrolysis by IF2 and peptide bond formation following the binding of aminoacyl-tRNA to the 70S initiation complex, were measured by the quench-flow technique. The methods described here are based on results obtained with initiation components from Escherichia coli but can be adopted for mechanistic studies of initiation in other prokaryotic or eukaryotic systems. PMID:17913632

  15. 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. PMID:21326901

  16. 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.

  17. 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…

  18. 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…

  19. 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…

  20. Alternative mechanisms of initiating translation of mammalian mRNAs.

    PubMed

    Jackson, R J

    2005-12-01

    Of all the steps in mRNA translation, initiation is the one that differs most radically between prokaryotes and eukaryotes. Not only is there no equivalent of the prokaryotic Shine-Dalgarno rRNA-mRNA interaction, but also what requires only three initiation factor proteins (aggregate size approximately 125 kDa) in eubacteria needs at least 28 different polypeptides (aggregate >1600 kDa) in mammalian cells, which is actually larger than the size of the 40 S ribosomal subunit. Translation of the overwhelming majority of mammalian mRNAs occurs by a scanning mechanism, in which the 40 S ribosomal subunit, primed for initiation by the binding of several initiation factors including the eIF2 (eukaryotic initiation factor 2)-GTP-MettRNA(i) complex, is loaded on the mRNA immediately downstream of the 5'-cap, and then scans the RNA in the 5'-->3' direction. On recognition of (usually) the first AUG triplet via base-pairing with the Met-tRNA(i) anticodon, scanning ceases, triggering GTP hydrolysis and release of eIF2-GDP. Finally, ribosomal subunit joining and the release of the other initiation factors completes the initiation process. This sketchy outline conceals the fact that the exact mechanism of scanning and the precise roles of the initiation factors remain enigmatic. However, the factor requirements for initiation site selection on some viral IRESs (internal ribosome entry sites/segments) are simpler, and investigations into these IRES-dependent mechanisms (particularly picornavirus, hepatitis C virus and insect dicistrovirus IRESs) have significantly enhanced our understanding of the standard scanning mechanism. This article surveys the various alternative mechanisms of initiation site selection on mammalian (and other eukaryotic) cellular and viral mRNAs, starting from the simplest (in terms of initiation factor requirements) and working towards the most complex, which paradoxically happens to be the reverse order of their discovery. PMID:16246087

  1. 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

  2. Heat fluctuations and initial ensembles.

    PubMed

    Kim, Kwangmoo; Kwon, Chulan; Park, Hyunggyu

    2014-09-01

    Time-integrated quantities such as work and heat increase incessantly in time during nonequilibrium processes near steady states. In the long-time limit, the average values of work and heat become asymptotically equivalent to each other, since they only differ by a finite energy change in average. However, the fluctuation theorem (FT) for the heat is found not to hold with the equilibrium initial ensemble, while the FT for the work holds. This reveals an intriguing effect of everlasting initial memory stored in rare events. We revisit the problem of a Brownian particle in a harmonic potential dragged with a constant velocity, which is in contact with a thermal reservoir. The heat and work fluctuations are investigated with initial Boltzmann ensembles at temperatures generally different from the reservoir temperature. We find that, in the infinite-time limit, the FT for the work is fully recovered for arbitrary initial temperatures, while the heat fluctuations significantly deviate from the FT characteristics except for the infinite initial-temperature limit (a uniform initial ensemble). Furthermore, we succeed in calculating finite-time corrections to the heat and work distributions analytically, using the modified saddle point integral method recently developed by us. Interestingly, we find noncommutativity between the infinite-time limit and the infinite-initial-temperature limit for the probability distribution function (PDF) of the heat. PMID:25314405

  3. 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.

  4. 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.

  5. Initiation of parturition in humans.

    PubMed Central

    Drover, J. W.; Casper, R. F.

    1983-01-01

    The mechanism by which parturition is initiated in humans is largely unknown. The placenta and fetal membranes appear to play the major role in the initiation of labour, and the fetus may influence the timing of labour. Clinical observations and experiments with animals have revealed that placental neuropeptides may be able to control steroid metabolism and trigger the onset of labour, while the fetus may be able to interact with such events to initiate parturition at an appropriate time. However, further study is needed to determine the role of placental releasing factors and glycoprotein hormones and their ability to control placental steroid metabolism. PMID:6401583

  6. 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.

  7. 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,…

  8. Towards initiation of explosives utilizing ultrafast laser quantum control

    NASA Astrophysics Data System (ADS)

    Greenfield, Margo; McGrane, Shawn; Scharff, Jason; Moore, David

    2011-06-01

    Time dependent shaped electric fields can be utilized to control energetic materials by driving their reaction to initiation. This direct quantum controlled initiation (QCI) employs ultrafast shaped ultraviolet light to optimally control the explosives initiation reaction. QCI will enhance the understanding of energetic material reactions by yielding insight into the characteristics, such as reaction dynamics, necessary for initiation. Initial investigation into solutions of hexanitroazobenzene (HNAB), trinitroanaline (TNA), 1,1-diamino-2,2-dinitroethene (FOX-7), and diaminoazozyfurazan (DAAF) have been performed. Novel transient absorption spectra have been obtained for each material and note worthy regions have been further investigated for simple control response. The explosives not controlled through a single parameter have been further investigated with complex control. Further experimentation will be performed to explore the effect of QCI on thin films as the optimally shaped ultrafast laser pulses guide the energy flow along the desired paths.

  9. Initiation and re-initiation of DNA unwinding by the Escherichia coli Rep helicase

    NASA Astrophysics Data System (ADS)

    Ha, Taekjip; Rasnik, Ivan; Cheng, Wei; Babcock, Hazen P.; Gauss, George H.; Lohman, Timothy M.; Chu, Steven

    2002-10-01

    Helicases are motor proteins that couple conformational changes induced by ATP binding and hydrolysis with unwinding of duplex nucleic acid, and are involved in several human diseases. Some function as hexameric rings, but the functional form of non-hexameric helicases has been debated. Here we use a combination of a surface immobilization scheme and single-molecule fluorescence assays-which do not interfere with biological activity-to probe DNA unwinding by the Escherichia coli Rep helicase. Our studies indicate that a Rep monomer uses ATP hydrolysis to move toward the junction between single-stranded and double-stranded DNA but then displays conformational fluctuations that do not lead to DNA unwinding. DNA unwinding initiates only if a functional helicase is formed via additional protein binding. Partial dissociation of the functional complex during unwinding results in interruptions (`stalls') that lead either to duplex rewinding upon complete dissociation of the complex, or to re-initiation of unwinding upon re-formation of the functional helicase. These results suggest that the low unwinding processivity observed in vitro for Rep is due to the relative instability of the functional complex. We expect that these techniques will be useful for dynamic studies of other helicases and protein-DNA interactions.

  10. Subduction initiation at relic arcs

    NASA Astrophysics Data System (ADS)

    Leng, Wei; Gurnis, Michael

    2015-09-01

    Although plate tectonics is well established, how a new subduction zone initiates remains controversial. Based on plate reconstruction and recent ocean drilling within the Izu-Bonin-Mariana, we advance a new geodynamic model of subduction initiation (SI). We argue that the close juxtaposition of the nascent plate boundary with relic oceanic arcs is a key factor localizing initiation of this new subduction zone. The combination of thermal and compositional density contrasts between the overriding relic arc, and the adjacent old Pacific oceanic plate promoted spontaneous SI. We suggest that thermal rejuvenation of the overriding plate just before 50 Ma caused a reduction in overriding plate strength and an increase in the age contrast (hence buoyancy) between the two plates, leading to SI. The computational models map out a framework in which rejuvenated relic arcs are a favorable tectonic environment for promoting subduction initiation, while transform faults and passive margins are not.

  11. The Transverse Radial Diverging Initiation Behavior of PBX 9502

    NASA Astrophysics Data System (ADS)

    Salyer, Terry; Aslam, Tariq

    2015-06-01

    A series of experiments examining the transverse radial initiation behavior of PBX 9502 has been fielded in a geometric configuration of PBX 9502 acceptor annulus and PBX 9501 donor core. The experiments were specifically designed to examine diverging initiation from the core. For sufficient diameter, the cylindrical donor core initiates the acceptor annulus with behavior akin to typical corner turning with the expected dead zone features. Even though PBX 9501 is significantly more energetic than PBX 9502, the critical initiation diameter is greater than the critical failure diameter of PBX 9502. The behavior of this initiation threshold is studied along with the dynamics of the shock initiating layer between the two dissimilar explosives. Streak camera imaging is used to examine the wave dynamics at the periphery of the PBX 9502 acceptor annulus, and to take measurements of the initiating layer at the material interface for comparison to the analogous behavior in the layered slab geometry. Additionally, proton radiographic imaging is used to examine the complex internal initiation dynamics, and high fidelity reactive flow modeling is used to accurately predict the transverse radial initiation behavior in the geometry of the test.

  12. 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

  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. Evaluation of a State Initiative to Improve Child Care Quality

    ERIC Educational Resources Information Center

    Roach, Mary A.; Riley, David A.; Adams, Diane; Edie, David

    2005-01-01

    Wisconsin's Early Childhood Excellence Initiative was a $15 million public policy effort designed in 2000 to increase child care quality for low-income children. An evaluation revealed significant improvement in classroom quality, the quality of caregiver interaction, and caregivers' beliefs about children following a complex multi-faceted…

  15. Antecedents of Adolescent Initiation of Sex, Contraceptive Use, and Pregnancy.

    ERIC Educational Resources Information Center

    Kirby, Douglas

    2002-01-01

    Reviews the literature to identify the most important antecedents associated with adolescent initiation of sex, contraception use, and pregnancy. Results indicate that over 100 antecedents create a complex, detailed picture of the correlates of adolescent sexual behaviors. They describe characteristics of adolescents themselves, their partners,…

  16. 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

  17. 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…

  18. Complexity matching in neural networks

    NASA Astrophysics Data System (ADS)

    Usefie Mafahim, Javad; Lambert, David; Zare, Marzieh; Grigolini, Paolo

    2015-01-01

    In the wide literature on the brain and neural network dynamics the notion of criticality is being adopted by an increasing number of researchers, with no general agreement on its theoretical definition, but with consensus that criticality makes the brain very sensitive to external stimuli. We adopt the complexity matching principle that the maximal efficiency of communication between two complex networks is realized when both of them are at criticality. We use this principle to establish the value of the neuronal interaction strength at which criticality occurs, yielding a perfect agreement with the adoption of temporal complexity as criticality indicator. The emergence of a scale-free distribution of avalanche size is proved to occur in a supercritical regime. We use an integrate-and-fire model where the randomness of each neuron is only due to the random choice of a new initial condition after firing. The new model shares with that proposed by Izikevich the property of generating excessive periodicity, and with it the annihilation of temporal complexity at supercritical values of the interaction strength. We find that the concentration of inhibitory links can be used as a control parameter and that for a sufficiently large concentration of inhibitory links criticality is recovered again. Finally, we show that the response of a neural network at criticality to a harmonic stimulus is very weak, in accordance with the complexity matching principle.

  19. Action Potentials Initiate in the Axon Initial Segment and Propagate Through Axon Collaterals Reliably in Cerebellar Purkinje Neurons

    PubMed Central

    Foust, Amanda; Popovic, Marko; Zecevic, Dejan; McCormick, David A.

    2010-01-01

    Purkinje neurons are the output cells of the cerebellar cortex and generate spikes in two distinct modes, known as simple and complex spikes. Revealing the point of origin of these action potentials, and how they conduct into local axon collaterals, is important for understanding local and distal neuronal processing and communication. By utilizing a recent improvement in voltage sensitive dye imaging technique that provided exceptional spatial and temporal resolution, we were able to resolve the region of spike initiation as well as follow spike propagation into axon collaterals for each action potential initiated on single trials. All fast action potentials, for both simple and complex spikes, whether occurring spontaneously or in response to a somatic current pulse or synaptic input, initiated in the axon initial segment. At discharge frequencies of less than approximately 250 Hz, spikes propagated faithfully through the axon and axon collaterals, in a saltatory manner. Propagation failures were only observed for very high frequencies or for the spikelets associated with complex spikes. These results demonstrate that the axon initial segment is a critical decision point in Purkinje cell processing and that the properties of axon branch points are adjusted to maintain faithful transmission. PMID:20484631

  20. Citizen Involvement in the Public Schools. Trends for the 80's.

    ERIC Educational Resources Information Center

    Simon, Toby R.

    This is a resource booklet designed to facilitate the involvement of all citizens, not just parents, in the public schools. Citizen involvement in education is examined from an historical perspective, and legal mandates for citizen involvement in the state of New Jersey are outlined. Presented in the pamphlet are guidelines for the formation of…

  1. 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…

  2. The Challenge of the '80's and Beyond: Career Planning and the Adult Blue Collar Worker.

    ERIC Educational Resources Information Center

    Jaffe, Martin Elliot

    Career counseling is a particularly critical need for blue collar men, displaced workers from the declining industries of manufacturing. This article uses developmental theory based on the model of adult development of Daniel Levinson (1978), "Seasons of a Man's Life," to discuss the difficulty of blue collar men in attaining developmental…

  3. 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…

  4. 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…

  5. IGE and Basic Skills in the 80's: A Case for Effective Schooling.

    ERIC Educational Resources Information Center

    Beck, John J.; Bechtol, William M.

    The educational system known as Individually Guided Education (IGE) will become increasingly important as schools enter a period of retrenchment in the 1980's. Four factors necessary for basic skills achievement can be achieved through the use of IGE: (1) strong leadership by the school principal; (2) time spent in direct instruction by the…

  6. 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.

  7. Continuing Education for Private Piano Teachers: A Breakthrough for the '80s.

    ERIC Educational Resources Information Center

    Hugdahl, Edward O.

    For nine years, the Educational Telephone Network (ETN) operated by the University of Wisconsin Extension has been used to meet the continuing education needs of private piano teachers in the state by the UWEX Music Department. The interactive aural communications system has over 100 listening locations throughout Wisconsin, with at least one in…

  8. 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…

  9. 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.

  10. 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)

  11. Perspectives on College Health in the 80's: A President's View.

    ERIC Educational Resources Information Center

    Enarson, Harold L.

    1981-01-01

    College health services today have the responsibility for bringing a wide range of health education and medical, dental, and mental health services to a changing population of college students. The history of student health is described, and recommendations are made for the efficient handling of acute problems by college health services. (JN)

  12. 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.

  13. 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,…

  14. 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…

  15. 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…

  16. Planning for the 80's: Post Secondary Education and the Maine Economy.

    ERIC Educational Resources Information Center

    1982

    The Maine postsecondary education situation, the state's economy, and their interrelationships are considered. The analysis is based on interviews with leaders of Maine private enterprises, postsecondary institutions, professional and trade union organizations, and state government. An operational model for higher education and economic…

  17. Dilemmas of and Challenges for Black University Marching Bands in the 80's: A Personal View.

    ERIC Educational Resources Information Center

    Bowie, Lenard C.

    1984-01-01

    Discusses development of creative performance routines by Black university marching bands in the 1950s and 1960s and the negative impact of desegregation on these bands. Deplores new emphasis on entertainment rather than musical education and creativity and calls for reexamination of Black university band programs. (CJM)

  18. Community College Leadership for the '80s. AACJC Leadership Bookshelf Series, Number 1.

    ERIC Educational Resources Information Center

    Roueche, John E., Ed.; Baker, George A., III, Ed.

    These essays were prepared by leaders with recognized success in community college and university management, who were asked to share their experiences, the techniques they have found useful, and their personal views about community college leadership. After an introduction by Dale Parnell to the importance of leadership in institutional success,…

  19. 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…

  20. Automation Challenges of the 80's: What to Do until Your Integrated Library System Arrives.

    ERIC Educational Resources Information Center

    Allan, Ferne C.; Shields, Joyce M.

    1986-01-01

    A medium-sized aerospace library has developed interim solutions to automation needs by using software and equipment that were available in-house in preparation for an expected integrated library system. Automated processes include authors' file of items authored by employees, journal routing (including routing slips), statistics, journal…

  1. Managing and Financing Urban Community Colleges in the '80s: The Case for Strategic Management.

    ERIC Educational Resources Information Center

    Ellison, Nolen M.

    New approaches to planning and management will be required in the 1980s if community colleges are to deal with the challenges posed by declining enrollments and funds and changing public attitudes toward financing higher education. In the past two decades, management development and college planning have emphasized the creation and expansion of…

  2. 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,…

  3. 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…

  4. 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,…

  5. New directions in lubrication, materials, wear, and surface interactions - Tribology in the 80's

    NASA Technical Reports Server (NTRS)

    Loomis, W. R. (Editor)

    1985-01-01

    New directions in tribology are described. A range of topics is addressed, extending from fundamental research on tribological materials of all kinds and their surface effects, to final technological applications in mechanical components such as bearings, gears, and seals. The general topics addressed include: importance and definition of materials in tribology; future directions of research in adhesion and friction, wear and wear-resistant materials, and liquid lubricants and additives; status and new directions in elastohydrodynamic lubrication and solid lubricants; and tribological materials for mechanical components of the future.

  6. Status and Direction of Tribology as a Science in the 80's. Understanding and Prediction

    NASA Technical Reports Server (NTRS)

    Tabor, D.

    1984-01-01

    The most challenging research problems in tribology for the next decade or beyond are classified horizontally into two categories: (1) understanding of basic mechanisms and (2) prediction of practical performance. Vertical classifications are in terms of particular themes or fields of interest. Areas where more fundamental work is required are: adhesion and friction of clean and contaminated surfaces; lubrication; new materials; surface characterization at the engineering level (topography) and at the atomic levels (various spectroscopies); and wear.

  7. 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…

  8. 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)

  9. 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)

  10. 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…

  11. Developing Teacher Efficacy: A Triple Challenge to Professional Development in the 80's.

    ERIC Educational Resources Information Center

    Amodeo, Luiza; And Others

    1981-01-01

    The challenge to teacher development in the 1980s focuses on three areas: (1) multicultural education; (2) diagnosis and prescription based on learning styles, as well as on achievement level; and (3) awareness of the differences in function of the right and left hemispheres of the brain. (JN)

  12. Apprenticeship in the 80's. A Training Program for the Bureau of Apprenticeship and Training.

    ERIC Educational Resources Information Center

    SRA Technologies, Inc., Arlington, VA.

    This training package is designed for use by staff of the U.S. Bureau of Apprenticeship and Training who are participating in a course dealing with apprenticeship in the future. Addressed in the individual units of the course are the following topics: employment trends of the future (computers, robotics, communications, growth and declining…

  13. The Literary Form of the 80s: Using Quotations to Teach English.

    ERIC Educational Resources Information Center

    Miller, Dan L.

    1987-01-01

    Enumerates reasons for using quotations as a staple in the English classroom, such as: to lend authority to words, to summarize a concept, to motivate or inspire, or to enhance vocabulary growth. (NKA)

  14. 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…

  15. Conversion of the 80's - slurry pumping - a vital economic decision

    SciTech Connect

    Kalchthaler, R.F. Jr.

    1985-12-09

    An increasing portion of the total cost of mining and processing coal is associated with the disposal of coal refuse. In addition, current regulatory requirements and rising labor and energy (fuel) costs continue to increase the cost of refuse disposal. Of particular importance is the decision to install or continue to operate fine refuse dewatering systems or to convert to slurry pumping. With today's market conditions and regulatory atmosphere major capital investments and increasing operational costs associated with the transportation and placement of combined coal refuse demand a careful evaluation of the economics of converting to slurry pumping. The results of an industry survey which correlates with SRW Associates Inc.'s experience in the conversion process indicates a significant cost savings when converting to slurry pumping. 2 references, 15 figures.

  16. 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.

  17. [Eating disorders in adolescents in East and West Berlin in the 80's].

    PubMed

    Neumärker, K J; Steinhausen, H C; Dudeck, U; Neumärker, U; Seidel, R; Reitzle, M

    1994-02-01

    Data collected in the 1980's, before the reunification of Germany, and comparing 39 patients in former East Berlin and 60 patients in former West Berlin are presented in this second report on the Berlin longitudinal study of eating disorders in adolescence. The clinical profiles of patients of former East Berlin were found to differ from those of their West Berlin counterparts in the following assessed measures: younger age at disease onset and at admission for inpatient treatment; greater number of siblings; fewer accounts of the clinical symptoms lanugo, bradycardia, hypothermia, constipation; lower rate of premorbid psychopathological features; lower number of psychopathological findings; less frequent sibling rivalry; lower rate of psychopathological attributes among the siblings; lower incidence of maternal mental and physical illness; higher parental educational status; fewer number of complaints, and better sense of well-being. PMID:8165205

  18. Participatory Management in Organizations of Higher Education: Leadership Mandate for the 80's.

    ERIC Educational Resources Information Center

    Kowalski, Casimir J.; Bryson, J. Richard

    1982-01-01

    The participatory management philosophy is alive and well at numerous institutions of higher education. Results, both objective and subjective, are in evidence at many colleges and universities and lend validity to the perception that participatory management can, and does, work if properly nurtured by top administrators in a collegial…

  19. 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…

  20. 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.…

  1. 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)

  2. Professional Dress for the 80's. Marketing and Distributive Education Program, Professional Dress Unit. Instructor's Guide.

    ERIC Educational Resources Information Center

    Holmes, Wally; And Others

    This guide for an adult marketing education course provides instructors with the necessary materials to present a seminar about "image management to project professionalism." General teaching suggestions are provided as well as a course outline and a time chart that provides guidelines for the minimum and maximum time to be spent on each section.…

  3. The ACT transport: Panacea for the 80's or designer's illusion (panel discussion)

    NASA Technical Reports Server (NTRS)

    1976-01-01

    A panel discussion was held which attempted to make an objective and pragmatic assessment of the standing of active control technology. The discussion focused on the standing of active control technology relative to civil air transport applications, the value as opposed to the cost of the projected benefits, the need for research, development, and demonstration, the role of government and industry in developing the technology, the major obstacles to its implementation, and the probable timing of the full utilization of active control technology in commercial transportation. An edited transcription of the prepared statements of the panel members and the subsequent open discussion between the panel and the audience is presented.

  4. Visibility study of S -T+ Landau-Zener-Stückelberg oscillations without applied initialization

    NASA Astrophysics Data System (ADS)

    Granger, G.; Aers, G. C.; Studenikin, S. A.; Kam, A.; Zawadzki, P.; Wasilewski, Z. R.; Sachrajda, A. S.

    2015-03-01

    Probabilities deduced from quantum information studies are usually based on averaging many identical experiments separated by an initialization step. Such initialization steps become experimentally more challenging to implement as the complexity of quantum circuits increases. To better understand the consequences of imperfect initialization on the deduced probabilities, we study the effect of not initializing the system between measurements. For this we utilize Landau-Zener-Stückelberg oscillations in a double quantum dot circuit. Experimental results are successfully compared to theoretical simulations.

  5. 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.

  6. The mechanism of translation initiation on Type 1 picornavirus IRESs

    PubMed Central

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

    2014-01-01

    Picornavirus Type 1 IRESs comprise five principal domains (dII–dVI). Whereas dV binds eIF4G, a conserved AUG in dVI was suggested to stimulate attachment of 43S ribosomal preinitiation complexes, which then scan to the initiation codon. Initiation on Type 1 IRESs also requires IRES trans-acting factors (ITAFs), and several candidates have been proposed. Here, we report the in vitro reconstitution of initiation on three Type 1 IRESs: poliovirus (PV), enterovirus 71 (EV71), and bovine enterovirus (BEV). All of them require eIF2, eIF3, eIF4A, eIF4G, eIF4B, eIF1A, and a single ITAF, poly(C) binding protein 2 (PCBP2). In each instance, initiation starts with binding of eIF4G/eIF4A. Subsequent recruitment of 43S complexes strictly requires direct interaction of their eIF3 constituent with eIF4G. The following events can differ between IRESs, depending on the stability of dVI. If it is unstructured (BEV), all ribosomes scan through dVI to the initiation codon, requiring eIF1 to bypass its AUG. If it is structured (PV, EV71), most initiation events occur without inspection of dVI, implying that its AUG does not determine ribosomal attachment. PMID:24357634

  7. Temporal variability of the initial threshold for motion - initial bed conditions and morphological trajectory

    NASA Astrophysics Data System (ADS)

    Marquis, G. A.; Roy, A. G.

    2012-12-01

    Sediment transport as bedload has been studied for decades and as new data were collected both in the laboratory and in the field, it became more and more obvious that the phenomenon was utterly complex and consequently difficult to predict. Furthermore, in gravel-bed rivers , bedload transport and the consequent morphological changes are still not well understood as the factors involved have proven to be numerous and their interactions complex. A key variable in bedload transport predictions is the initial threshold for particle motion, often expressed as a critical flow shear stress or discharge. Typically, the initial threshold for motion is estimated using the channel bed slope and a representative grain size diameter. This implies that bedload motion will begin at a constant critical flow strength in a reach, which does not apply to gravel-bed rivers with a broad grain-size distribution due to the possible variations in grain arrangements. This raises issues about the implications of varying conditions for the onset of motion on the magnitude of the bedload fluxes and the morphological changes. Using a unique field data set, we will show how the threshold of incipient motion reflects the initial bed conditions and the morphological trajectory through a complex web of interactions and feedbacks. Bedload fluxes and morphological changes were monitored for 21 bedload events over three years at Béard Creek, a small gravel-bed river located in southern Quebec (Canada). Bankfull width, depth and discharge of the stream are 5 m, 1 m and 2.5 cumecs respectively. Median b axis of the bed surface material is 40 mm. Two 20 meters reaches were equipped with Birkbeck type bedload samplers with load cells recording real-time bedload rates. Morphological changes were tracked using repeated topographical surveys upstream of the bedload samplers. To circumvent the issue of the identification of bed areas that were mobilised without any elevation change, we completed the data

  8. 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.

  9. Translation initiation in colorectal cancer.

    PubMed

    Parsyan, Armen; Hernández, Greco; Meterissian, Sarkis

    2012-06-01

    Colorectal cancers (CRC) are one of the most common causes of morbidity and mortality in high-income countries. Targeted screening programs have resulted in early treatment and a substantial decrease in mortality. However, treatment strategies for CRC still require improvement. Understanding the etiology and pathogenesis of CRC would provide tools for improving treatment of patients with this disease. It is only recently that deregulation of the protein synthesis apparatus has begun to gain attention as a major player in cancer development and progression. Among the numerous steps of protein synthesis, deregulation of the process of translation initiation appears to play a key role in cancer growth and proliferation. This manuscript discusses a fascinating and rapidly growing field exploring translation initiation as a fundamental component in CRC development and progression and summarizing CRC treatment perspectives based on agents targeting translation initiation. PMID:22418835

  10. 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.

  11. [Initiation and monitoring of contraception].

    PubMed

    Sannisto, Tuire; Kuortti, Marjo; Kuukankorpi, Aki; Niitty, Siina

    2012-01-01

    The majority of those requiring contraception may safely use any available contraceptive method. Each method has, however, its particular contraindications, which should be screened by applying careful anamnesis and focused status, when contraception is being initiated. Gynecologic examination is not a prerequisite for the initiation of hormonal contraception, but measurement and monitoring of blood pressure is important. Testing for sexually transmitted diseases is readily worthwhile. Follow-up visits provide a chance for comprehensive support for a woman or a young person concerning sexual health. PMID:22822602

  12. Information Complexity and Biology

    NASA Astrophysics Data System (ADS)

    Bagnoli, Franco; Bignone, Franco A.; Cecconi, Fabio; Politi, Antonio

    Kolmogorov contributed directly to Biology in essentially three problems: the analysis of population dynamics (Lotka-Volterra equations), the reaction-diffusion formulation of gene spreading (FKPP equation), and some discussions about Mendel's laws. However, the widely recognized importance of his contribution arises from his work on algorithmic complexity. In fact, the limited direct intervention in Biology reflects the generally slow growth of interest of mathematicians towards biological issues. From the early work of Vito Volterra on species competition, to the slow growth of dynamical systems theory, contributions to the study of matter and the physiology of the nervous system, the first 50-60 years have witnessed important contributions, but as scattered pieces apparently uncorrelated, and in branches often far away from Biology. Up to the 40' it is hard to see the initial loose build up of a convergence, for those theories that will become mainstream research by the end of the century, and connected by the study of biological systems per-se.

  13. OPM: The Open Porous Media Initiative

    NASA Astrophysics Data System (ADS)

    Flemisch, B.; Flornes, K. M.; Lie, K.; Rasmussen, A.

    2011-12-01

    The principal objective of the Open Porous Media (OPM) initiative is to develop a simulation suite that is capable of modeling industrially and scientifically relevant flow and transport processes in porous media and bridge the gap between the different application areas of porous media modeling, including reservoir mechanics, CO2 sequestration, biological systems, and product development of engineered media. The OPM initiative will provide a long-lasting, efficient, and well-maintained open-source software for flow and transport in porous media built on modern software principles. The suite is released under the GNU General Public License (GPL). Our motivation is to provide a means to unite industry and public research on simulation of flow and transport in porous media. For academic users, we seek to provide a software infrastructure that facilitates testing of new ideas on models with industry-standard complexity, while at the same time giving the researcher control over discretization and solvers. Similarly, we aim to accelerate the technology transfer from academic institutions to professional companies by making new research results available as free software of professional standard. The OPM initiative is currently supported by six research groups in Norway and Germany and funded by existing grants from public research agencies as well as from Statoil Petroleum and Total E&P Norge. However, a full-scale development of the OPM initiative requires substantially more funding and involvement of more research groups and potential end users. In this talk, we will provide an overview of the current activities in the OPM initiative. Special emphasis will be given to the demonstration of the synergies achieved by combining the strengths of individual open-source software components. In particular, a new fully implicit solver developed within the DUNE-based simulator DuMux could be enhanced by the ability to read industry-standard Eclipse input files and to run on

  14. A quantitative description of Ndc80 complex linkage to human kinetochores

    PubMed Central

    Suzuki, Aussie; Badger, Benjamin L.; Salmon, Edward D.

    2015-01-01

    The Ndc80 complex, which mediates end-on attachment of spindle microtubules, is linked to centromeric chromatin in human cells by two inner kinetochore proteins, CENP-T and CENP-C. Here to quantify their relative contributions to Ndc80 recruitment, we combine measurements of kinetochore protein copy number with selective protein depletion assays. This approach reveals about 244 Ndc80 complexes per human kinetochore (∼14 per kinetochore microtubule), 215 CENP-C, 72 CENP-T and only 151 Ndc80s as part of the KMN protein network (1:1:1 Knl1, Mis12 and Ndc80 complexes). Each CENP-T molecule recruits ∼2 Ndc80 complexes; one as part of a KMN network. In contrast, ∼40% of CENP-C recruits only a KMN network. Replacing the CENP-C domain that binds KMN with the CENP-T domain that recruits both an Ndc80 complex and KMN network yielded functional kinetochores. These results provide a quantitative picture of the linkages between centromeric chromatin and the microtubule-binding Ndc80 complex at the human kinetochore. PMID:26345214

  15. The AGU Data Management Maturity Model Initiative

    NASA Astrophysics Data System (ADS)

    Bates, J. J.

    2015-12-01

    In September 2014, the AGU Board of Directors approved two initiatives to help the Earth and space sciences community address the growing challenges accompanying the increasing size and complexity of data. These initiatives are: 1) Data Science Credentialing: development of a continuing education and professional certification program to help scientists in their careers and to meet growing responsibilities and requirements around data science; and 2) Data Management Maturity (DMM) Model: development and implementation of a data management maturity model to assess process maturity against best practices, and to identify opportunities in organizational data management processes. Each of these has been organized within AGU as an Editorial Board and both Boards have held kick off meetings. The DMM model Editorial Board will recommend strategies for adapting and deploying a DMM model to the Earth and space sciences create guidance documents to assist in its implementation, and provide input on a pilot appraisal process. This presentation will provide an overview of progress to date in the DMM model Editorial Board and plans for work to be done over the upcoming year.

  16. Savannah River Remediation Cost Savings Initiative - 12339

    SciTech Connect

    Davis, Neil R.

    2012-07-01

    Savannah River enjoyed two years of increased funding as a result of the American Reinvestment and Recovery Act and Department of Energy (DOE) directed scope additions. Moving into FY2012, a much lower funding level is anticipated. In the past, the first response to a reduced funding scenario was to defer scope and slow down the program. This time, Savannah River decided that a better process was needed to try to maximize value to the government. This approach was named the Cost Savings Initiative (CSI). The CSI process is similar to a zero-based budget concept. Every element of work scope was screened to eliminate everything that was not directly related to safety and regulatory compliance. Then the schedules for the regulatory-driven scope were deferred such that the regulatory milestones were achieved just in time with no acceleration. This resulted in a strategy that met regulatory requirements in FY2012-13 with some remaining funding but not in FY2014-15. The remaining funding was then invested in cost savings initiatives in FY2012-13 to reduce the future cost of doing business in the FY2014-15 timeframe and beyond. This resulted in a Strategy that: - Meets all regulatory commitments; - Meets some regulatory commitments early; and - Preserves most of the life cycle savings that were built in to the baseline plan The CSI process used at Savannah River may be considered for application elsewhere in the DOE Complex. (authors)

  17. Laser Initiated Ordnance (LIO) activities in NASA

    NASA Technical Reports Server (NTRS)

    Schulze, Norman R.

    1994-01-01

    Laser initiated ordnance appears to offer the advantages of greater reliability, enhanced safety, lighter, less costly products, and improvements in spacecraft system designs which can lead to higher operational efficiency. But the lack of flight demonstrations has prevented the application of this new technology into new programs. Hence, a three-phase technology program was initiated by NASA to provide flight proof of their technical and programmatic feasibility: flight demonstration aboard an unmanned commercial vehicle (Pegasus), use as a Space Shuttle payload, and the most demanding of applications, namely, solid rocket motor vehicle ignition and flight termination. The programs investigate, via flight demonstrations the use of fully solid state laser diode systems to reduce potential hazards imposed by stray electrical signals. Inadvertent ignition has proven to cause serious problems. While the current electromechanical have been made safe, the result has been complex systems. Now is the time to take advantage of this new technology to further enhance safety and reliability of spacecraft systems. Two of the three phases are underway; an announcement of opportunity for the third, a sounding rocket flight demonstration, was made at the workshop.

  18. Internet 2 Health Sciences Initiative.

    ERIC Educational Resources Information Center

    Simco, Greg

    2003-01-01

    The Internet 2 (I2) health sciences initiative (I2HSI) involves the formulation of applications and supporting technologies, and guidelines for their use in the health sciences. Key elements of I2HSI include use of visualization, collaboration, medical informatics, telemedicine, and educational tools that support the health sciences. Specific…

  19. Big Data Initiatives for Agroecosystems

    Technology Transfer Automated Retrieval System (TEKTRAN)

    NAL has developed a workspace for research groups associated with the i5k initiative, which aims to sequence the genomes of all insesct species known to be important to worldwide agriculture, food safety, medicine, and energy production; all those used as models in biology; the most abundant in worl...

  20. Initiative Activities: A Good Risk.

    ERIC Educational Resources Information Center

    Boyer, Allan C.

    1980-01-01

    Initiative activities are fabricated problems that require the mental and physical cooperation of a group of 8 to 15 people. A typical activity is the electric fence, in which students are instructed to get everyone over a chest-high barrier without touching it or reaching through it. (Author/IRT)