A Transcript-Specific eIF3 Complex Mediates Global Translational Control of Energy Metabolism

Directory of Open Access Journals (Sweden)

Meera Shah

2016-08-01

Full Text Available The multi-subunit eukaryotic translation initiation factor eIF3 is thought to assist in the recruitment of ribosomes to mRNA. The expression of eIF3 subunits is frequently disrupted in human cancers, but the specific roles of individual subunits in mRNA translation and cancer remain elusive. Using global transcriptomic, proteomic, and metabolomic profiling, we found a striking failure of Schizosaccharomyces pombe cells lacking eIF3e and eIF3d to synthesize components of the mitochondrial electron transport chain, leading to a defect in respiration, endogenous oxidative stress, and premature aging. Energy balance was maintained, however, by a switch to glycolysis with increased glucose uptake, upregulation of glycolytic enzymes, and strict dependence on a fermentable carbon source. This metabolic regulatory function appears to be conserved in human cells where eIF3e binds metabolic mRNAs and promotes their translation. Thus, via its eIF3d-eIF3e module, eIF3 orchestrates an mRNA-specific translational mechanism controlling energy metabolism that may be disrupted in cancer.

Human eIF3b and eIF3a serve as the nucleation core for the assembly of eIF3 into two interconnected modules: the yeast-like core and the octamer

Czech Academy of Sciences Publication Activity Database

Wagner, Susan; Herrmannová, Anna; Šikrová, Darina; Valášek, Leoš Shivaya

2016-01-01

Roč. 44, č. 22 (2016), s. 10772-10788 ISSN 0305-1048 R&D Projects: GA ČR(CZ) GA14-05394S EU Projects: Wellcome Trust(GB) 090812/B/09/A Institutional support: RVO:61388971 Keywords : Human eIF3b * nucleation core * yeast -like core Subject RIV: EE - Microbiology, Virology Impact factor: 10.162, year: 2016

What if we are alone?

Science.gov (United States)

Waltham, D.

2013-09-01

The huge number of planets in the observable Universe, and beyond, means that worlds with Earth-like levels of biodiversity are inevitable even if the probability of any give n planet being inhabited is tiny. The corollary of this is that the existence of one such world (the Earth)tells us almost nothing about how common such places are in the Universe. Hence, given the present state of astrobiological know ledge, it is possible that there are no other inhabited planets within the detection-range of any conceivable technology. This is not a popular view currently but the little evidence we have (e.g. the coincidence of stellar-evolution and intelligence-evolution time-scales on Earth [1,2]; indications that many of the Earth's properties may be fine-tuned for complex life [3,4]; the fact that life on Earth was, for most of its history, single-celled [5]) points towards complex life, at least, being rare in the Universe. The plausibility of this "gloomy" view will be tested further incoming decades as we explore Mars, Europa, Titan and other astrobiologically interesting worlds in the Solar System and as we, hopefully, develop ever more sophisticated remote-sensing methods for assessing the biological state of exoplanets. Much thought has been given to the political, social and psychological effects of a positive detection of alien life or even the receiving of a confirmed SETI signal. However, in my view, it is equally important and interesting to consider the impact of negative results. What if we are alone? What if the only other life we find is "primitive"?

A Transcript-Specific eIF3 Complex Mediates Global Translational Control of Energy Metabolism.

Science.gov (United States)

Shah, Meera; Su, Dan; Scheliga, Judith S; Pluskal, Tomáš; Boronat, Susanna; Motamedchaboki, Khatereh; Campos, Alexandre Rosa; Qi, Feng; Hidalgo, Elena; Yanagida, Mitsuhiro; Wolf, Dieter A

2016-08-16

The multi-subunit eukaryotic translation initiation factor eIF3 is thought to assist in the recruitment of ribosomes to mRNA. The expression of eIF3 subunits is frequently disrupted in human cancers, but the specific roles of individual subunits in mRNA translation and cancer remain elusive. Using global transcriptomic, proteomic, and metabolomic profiling, we found a striking failure of Schizosaccharomyces pombe cells lacking eIF3e and eIF3d to synthesize components of the mitochondrial electron transport chain, leading to a defect in respiration, endogenous oxidative stress, and premature aging. Energy balance was maintained, however, by a switch to glycolysis with increased glucose uptake, upregulation of glycolytic enzymes, and strict dependence on a fermentable carbon source. This metabolic regulatory function appears to be conserved in human cells where eIF3e binds metabolic mRNAs and promotes their translation. Thus, via its eIF3d-eIF3e module, eIF3 orchestrates an mRNA-specific translational mechanism controlling energy metabolism that may be disrupted in cancer. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Spacer capture and integration by a type I-F Cas1-Cas2-3 CRISPR adaptation complex.

Science.gov (United States)

Fagerlund, Robert D; Wilkinson, Max E; Klykov, Oleg; Barendregt, Arjan; Pearce, F Grant; Kieper, Sebastian N; Maxwell, Howard W R; Capolupo, Angela; Heck, Albert J R; Krause, Kurt L; Bostina, Mihnea; Scheltema, Richard A; Staals, Raymond H J; Fineran, Peter C

2017-06-27

CRISPR-Cas adaptive immune systems capture DNA fragments from invading bacteriophages and plasmids and integrate them as spacers into bacterial CRISPR arrays. In type I-E and II-A CRISPR-Cas systems, this adaptation process is driven by Cas1-Cas2 complexes. Type I-F systems, however, contain a unique fusion of Cas2, with the type I effector helicase and nuclease for invader destruction, Cas3. By using biochemical, structural, and biophysical methods, we present a structural model of the 400-kDa Cas1 4 -Cas2-3 2 complex from Pectobacterium atrosepticum with bound protospacer substrate DNA. Two Cas1 dimers assemble on a Cas2 domain dimeric core, which is flanked by two Cas3 domains forming a groove where the protospacer binds to Cas1-Cas2. We developed a sensitive in vitro assay and demonstrated that Cas1-Cas2-3 catalyzed spacer integration into CRISPR arrays. The integrase domain of Cas1 was necessary, whereas integration was independent of the helicase or nuclease activities of Cas3. Integration required at least partially duplex protospacers with free 3'-OH groups, and leader-proximal integration was stimulated by integration host factor. In a coupled capture and integration assay, Cas1-Cas2-3 processed and integrated protospacers independent of Cas3 activity. These results provide insight into the structure of protospacer-bound type I Cas1-Cas2-3 adaptation complexes and their integration mechanism.

Control of eIF4E cellular localization by eIF4E-binding proteins, 4E-BPs

OpenAIRE

Rong, Liwei; Livingstone, Mark; Sukarieh, Rami; Petroulakis, Emmanuel; Gingras, Anne-Claude; Crosby, Katherine; Smith, Bradley; Polakiewicz, Roberto D.; Pelletier, Jerry; Ferraiuolo, Maria A.; Sonenberg, Nahum

2008-01-01

Eukaryotic initiation factor (eIF) 4E, the mRNA 5′-cap-binding protein, mediates the association of eIF4F with the mRNA 5′-cap structure to stimulate cap-dependent translation initiation in the cytoplasm. The assembly of eIF4E into the eIF4F complex is negatively regulated through a family of repressor proteins, called the eIF4E-binding proteins (4E-BPs). eIF4E is also present in the nucleus, where it is thought to stimulate nuclear-cytoplasmic transport of certain mRNAs. eIF4E is transported...

Dissociation of eIF4E-binding protein 2 (4E-BP2 from eIF4E independent of Thr37/Thr46 phosphorylation in the ischemic stress response.

Directory of Open Access Journals (Sweden)

María I Ayuso

Full Text Available Eukaryotic initiation factor (eIF 4E-binding proteins (4E-BPs are translational repressors that bind specifically to eIF4E and are critical in the control of protein translation. 4E-BP2 is the predominant 4E-BP expressed in the brain, but their role is not well known. Here, we characterized four forms of 4E-BP2 detected by two-dimensional gel electrophoresis (2-DGE in brain. The form with highest electrophoretic mobility was the main form susceptible to phosphorylation at Thr37/Thr46 sites, phosphorylation that was detected in acidic spots. Cerebral ischemia and subsequent reperfusion induced dephosphorylation and phosphorylation of 4E-BP2 at Thr37/Thr46, respectively. The induced phosphorylation was in parallel with the release of 4E-BP2 from eIF4E, although two of the phosphorylated 4E-BP2 forms were bound to eIF4E. Upon long-term reperfusion, there was a decrease in the binding of 4E-BP2 to eIF4E in cerebral cortex, demonstrated by cap binding assays and 4E-BP2-immunoprecipitation experiments. The release of 4E-BP2 from eIF4E was without changes in 4E-BP2 phosphorylation or other post-translational modification recognized by 2-DGE. These findings demonstrated specific changes in 4E-BP2/eIF4E association dependent and independent of 4E-BP2 phosphorylation. The last result supports the notion that phosphorylation may not be the uniquely regulation for the binding of 4E-BP2 to eIF4E under ischemic stress.

What if physics is wrong?

Science.gov (United States)

Tu, Zhoudunming

2011-11-01

Physics, an experiment-based science, seems to be the most appropriate subject in how to explain the inner workings of the world. We respect physics because it is based on facts that are perceived by our observations. However, what if we are not seeing the entire truth we seek? What if our observations are founded on sandy foundations? As humans, we desire to know what the truth is. Rene Descartes, a mathematician, philosopher, and physicist asked this question: what is the absolute truth in our universe? I want to solve the same puzzle. Many people believe that physics will reveal the truth of our universe. But, what if physics is wrong?

What If? Paths Not Taken

Science.gov (United States)

Logsdon, John M.

2002-01-01

I want to ask all of you to join me for a few minutes in a mental experiment. There is a certain sense of determinism as we review a period of history, like the forty years of U.S. human spaceflight. There is an implicit assumption that there were no alternatives to the way things happened. If you step back even half a step, you know that's not true; that along the way, history could have been very different if different choices had been made, if different events had happened, So I have arbitrarily picked a few situations in those forty years and invite you to ask along with me: "What If things had been different?" This notion of counterfactual history has some legitimacy. I have used it as a class assignment for my students in space policy, asking them to write about what might have occurred if different choices had been made. Dwayne Day, a former student and now a colleague, has suggested a whole symposium on counterfactual space history, and that might be an interesting thing to do someday. As I looked into preparation for this talk, I discovered there is a body of literature on counterfactual history. And, not surprisingly in the Internet age, there are even Web sites devoted to the topic!

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

Science.gov (United States)

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

Overexpression of eIF-5A2 in mice causes accelerated organismal aging by increasing chromosome instability

Directory of Open Access Journals (Sweden)

Chen Leilei

2011-05-01

Full Text Available Abstract Background Amplification of 3q26 is one of the most frequent genetic alterations in many human malignancies. Recently, we isolated a novel oncogene eIF-5A2 within the 3q26 region. Functional study has demonstrated the oncogenic role of eIF-5A2 in the initiation and progression of human cancers. In the present study, we aim to investigate the physiological and pathological effect of eIF-5A2 in an eIF-5A2 transgenic mouse model. Methods An eIF-5A2 transgenic mouse model was generated using human eIF-5A2 cDNA. The eIF-5A2 transgenic mice were characterized by histological and immunohistochemistry analyses. The aging phenotypes were further characterized by wound healing, bone X-ray imaging and calcification analysis. Mouse embryo fibroblasts (MEF were isolated to further investigate molecular mechanism of eIF-5A2 in aging. Results Instead of resulting in spontaneous tumor formation, overexpression of eIF-5A2 accelerated the aging process in adult transgenic mice. This included decreased growth rate and body weight, shortened life span, kyphosis, osteoporosis, delay of wound healing and ossification. Investigation of the correlation between cellular senescence and aging showed that cellular senescence is not required for the aging phenotypes in eIF-5A2 mice. Interestingly, we found that activation of eIF-5A2 repressed p19 level and therefore destabilized p53 in transgenic mouse embryo fibroblast (MEF cells. This subsequently allowed for the accumulation of chromosomal instability, such as errors in cell dividing during metaphase and anaphase. Additionally, a significantly increase in number of aneuploidy cells (p Conclusion These observations suggest that eIF-5A2 mouse models could accelerate organismal aging by increasing chromosome instability.

Molecular network including eIF1AX, RPS7, and 14-3-3γ regulates protein translation and cell proliferation in bovine mammary epithelial cells.

Science.gov (United States)

Yu, Cuiping; Luo, Chaochao; Qu, Bo; Khudhair, Nagam; Gu, Xinyu; Zang, Yanli; Wang, Chunmei; Zhang, Na; Li, Qingzhang; Gao, Xuejun

2014-12-15

14-3-3γ, an isoform of the 14-3-3 protein family, was proved to be a positive regulator of mTOR pathway. Here, we analyzed the function of 14-3-3γ in protein synthesis using bovine mammary epithelial cells (BMECs). We found that 14-3-3γ interacted with eIF1AX and RPS7 by 14-3-3γ coimmunoprecipitation (CoIP) and matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight (MALDI-TOF/TOF) peptide mass fingerprinting analysis. These interactions of 14-3-3γ with eIF1AX and RPS7 were further confirmed by colocalization and fluorescence resonance energy transfer (FRET) analysis. We also found that methionine could promote protein synthesis and trigger the protein expression levels of 14-3-3γ, eIF1AX and RPS7. Analysis of overexpression and inhibition of 14-3-3γ confirmed that it positively affected the protein expression levels of eIF1AX, RPS7, Stat5 and mTOR pathway to promote protein synthesis and cell proliferation in BMECs. We further showed that overexpression of eIF1AX and RPS7 also triggered protein translation and cell proliferation. From these results, we conclude that molecular network including eIF1AX, RPS7, and 14-3-3γ regulates protein translation and cell proliferation in BMECs. Copyright © 2014 Elsevier Inc. All rights reserved.

Translational control of auditory imprinting and structural plasticity by eIF2α

Science.gov (United States)

Batista, Gervasio; Johnson, Jennifer Leigh; Dominguez, Elena; Costa-Mattioli, Mauro; Pena, Jose L

2016-01-01

The formation of imprinted memories during a critical period is crucial for vital behaviors, including filial attachment. Yet, little is known about the underlying molecular mechanisms. Using a combination of behavior, pharmacology, in vivo surface sensing of translation (SUnSET) and DiOlistic labeling we found that, translational control by the eukaryotic translation initiation factor 2 alpha (eIF2α) bidirectionally regulates auditory but not visual imprinting and related changes in structural plasticity in chickens. Increasing phosphorylation of eIF2α (p-eIF2α) reduces translation rates and spine plasticity, and selectively impairs auditory imprinting. By contrast, inhibition of an eIF2α kinase or blocking the translational program controlled by p-eIF2α enhances auditory imprinting. Importantly, these manipulations are able to reopen the critical period. Thus, we have identified a translational control mechanism that selectively underlies auditory imprinting. Restoring translational control of eIF2α holds the promise to rejuvenate adult brain plasticity and restore learning and memory in a variety of cognitive disorders. DOI: http://dx.doi.org/10.7554/eLife.17197.001 PMID:28009255

What If Quantum Theory Violates All Mathematics?

Science.gov (United States)

Rosinger, Elemér Elad

2017-09-01

It is shown by using a rather elementary argument in Mathematical Logic that if indeed, quantum theory does violate the famous Bell Inequalities, then quantum theory must inevitably also violate all valid mathematical statements, and in particular, such basic algebraic relations like 0 = 0, 1 = 1, 2 = 2, 3 = 3, … and so on … An interest in that result is due to the following three alternatives which it imposes upon both Physics and Mathematics: Quantum Theory is inconsistent. Quantum Theory together with Mathematics are inconsistent. Mathematics is inconsistent. In this regard one should recall that, up until now, it is not known whether Mathematics is indeed consistent.

Binding of the Inhibitor Protein IF1 to Bovine F1-ATPase

Science.gov (United States)

Bason, John V.; Runswick, Michael J.; Fearnley, Ian M.; Walker, John E.

2011-01-01

In the structure of bovine F1-ATPase inhibited with residues 1–60 of the bovine inhibitor protein IF1, the α-helical inhibitor interacts with five of the nine subunits of F1-ATPase. In order to understand the contributions of individual amino acid residues to this complex binding mode, N-terminal deletions and point mutations have been introduced, and the binding properties of each mutant inhibitor protein have been examined. The N-terminal region of IF1 destabilizes the interaction of the inhibitor with F1-ATPase and may assist in removing the inhibitor from its binding site when F1Fo-ATPase is making ATP. Binding energy is provided by hydrophobic interactions between residues in the long α-helix of IF1 and the C-terminal domains of the βDP-subunit and βTP-subunit and a salt bridge between residue E30 in the inhibitor and residue R408 in the C-terminal domain of the βDP-subunit. Several conserved charged amino acids in the long α-helix of IF1 are also required for establishing inhibitory activity, but in the final inhibited state, they are not in contact with F1-ATPase and occupy aqueous cavities in F1-ATPase. They probably participate in the pathway from the initial interaction of the inhibitor and the enzyme to the final inhibited complex observed in the structure, in which two molecules of ATP are hydrolysed and the rotor of the enzyme turns through two 120° steps. These findings contribute to the fundamental understanding of how the inhibitor functions and to the design of new inhibitors for the systematic analysis of the catalytic cycle of the enzyme. PMID:21192948

Microbiology as if Bird Watching

Indian Academy of Sciences (India)

Home; Journals; Resonance – Journal of Science Education; Volume 1; Issue 10. Microbiology as if Bird Watching. Milind G Watve. Classroom Volume 1 Issue 10 October 1996 pp 78-81. Fulltext. Click here to view fulltext PDF. Permanent link: https://www.ias.ac.in/article/fulltext/reso/001/10/0078-0081. Author Affiliations.

eIF2α Kinases Control Chalone Production in Dictyostelium discoideum ▿

Science.gov (United States)

Bowman, Robert L.; Xiong, Yanhua; Kirsten, Janet H.; Singleton, Charles K.

2011-01-01

Growing Dictyostelium cells secrete CfaD and AprA, two proteins that have been characterized as chalones. They exist within a high-molecular-weight complex that reversibly inhibits cell proliferation, but not growth, via cell surface receptors and a signaling pathway that includes G proteins. How the production of these two proteins is regulated is unknown. Dictyostelium cells possess three GCN2-type eukaryotic initiation factor 2 α subunit (eIF2α) kinases, proteins that phosphorylate the translational initiation factor eIF2α and possess a tRNA binding domain involved in their regulation. The Dictyostelium kinases have been shown to function during development in regulating several processes. We show here that expression of an unregulated, activated kinase domain greatly inhibits cell proliferation. The inhibitory effect on proliferation is not due to a general inhibition of translation. Instead, it is due to enhanced production of a secreted factor(s). Indeed, extracellular CfaD and AprA proteins, but not their mRNAs, are overproduced in cells expressing the activated kinase domain. The inhibition of proliferation is not seen when the activated kinase domain is expressed in cells lacking CfaD or AprA or in cells that contain a nonphosphorylatable eIF2α. We conclude that production of the chalones CfaD and AprA is translationally regulated by eIF2α phosphorylation. Both proteins are upregulated at the culmination of development, and this enhanced production is lacking in a strain that possesses a nonphosphorylatable eIF2α. PMID:21278229

5 CFR 1302.1 - Rules for determining if an individual is the subject of a record.

Science.gov (United States)

2010-01-01

... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Rules for determining if an individual is the subject of a record. 1302.1 Section 1302.1 Administrative Personnel OFFICE OF MANAGEMENT AND BUDGET ADMINISTRATIVE PROCEDURES PRIVACY ACT PROCEDURES § 1302.1 Rules for determining if an individual...

The Indispensable N-Terminal Half of elF3j/HCR1 Cooperates with its Structurally Conserved Binding Partner eIF3b/PRT1-RRM and with eIF1A in Stringent AUG Selection

Czech Academy of Sciences Publication Activity Database

ElAntak, L.; Wagner, Susan; Herrmannová, Anna; Karásková, Martina; Rutkai, Edit; Lukavsky, P. J.; Valášek, Leoš

2010-01-01

Roč. 396, č. 4 (2010), s. 1097-1116 ISSN 0022-2836 Institutional research plan: CEZ:AV0Z50200510 Keywords : translation initiation * AUG recognition * eIF3 Subject RIV: CE - Biochemistry Impact factor: 4.008, year: 2010

Caliciviruses differ in their functional requirements for eIF4F components

DEFF Research Database (Denmark)

Chaudhry, Y.; Nayak, A.; Bordeleau, M-E.

2006-01-01

proteins can interact directly with the initiation factors eIF4E and eIF3. Translation initiation on feline calicivirus (FCV) RNA requires eIF4E because it is inhibited by recombinant 4E-BP1. However, to date, there have been no functional studies carried out with respect to norovirus translation...... translation require the RNA helicase component of the eIF4F complex, namely eIF4A, because translation was sensitive (albeit to different degrees) to a dominant negative form and to a small molecule inhibitor of eIF4A (hippuristanol). These results suggest that calicivirus RNAs differ with respect...... to their requirements for the components of the eIF4F translation initiation complex....

TOR and S6K1 promote translation reinitiation of uORF-containing mRNAs via phosphorylation of eIF3h.

Science.gov (United States)

Schepetilnikov, Mikhail; Dimitrova, Maria; Mancera-Martínez, Eder; Geldreich, Angèle; Keller, Mario; Ryabova, Lyubov A

2013-04-17

Mammalian target-of-rapamycin (mTOR) triggers S6 kinase (S6K) activation to phosphorylate targets linked to translation in response to energy, nutrients, and hormones. Pathways of TOR activation in plants remain unknown. Here, we uncover the role of the phytohormone auxin in TOR signalling activation and reinitiation after upstream open reading frame (uORF) translation, which in plants is dependent on translation initiation factor eIF3h. We show that auxin triggers TOR activation followed by S6K1 phosphorylation at T449 and efficient loading of uORF-mRNAs onto polysomes in a manner sensitive to the TOR inhibitor Torin-1. Torin-1 mediates recruitment of inactive S6K1 to polysomes, while auxin triggers S6K1 dissociation and recruitment of activated TOR instead. A putative target of TOR/S6K1-eIF3h-is phosphorylated and detected in polysomes in response to auxin. In TOR-deficient plants, polysomes were prebound by inactive S6K1, and loading of uORF-mRNAs and eIF3h was impaired. Transient expression of eIF3h-S178D in plant protoplasts specifically upregulates uORF-mRNA translation. We propose that TOR functions in polysomes to maintain the active S6K1 (and thus eIF3h) phosphorylation status that is critical for translation reinitiation.

Crystal structure of a minimal eIF4E–Cup complex reveals a general mechanism of eIF4E regulation in translational repression

Science.gov (United States)

Kinkelin, Kerstin; Veith, Katharina; Grünwald, Marlene; Bono, Fulvia

2012-01-01

Cup is an eIF4E-binding protein (4E-BP) that plays a central role in translational regulation of localized mRNAs during early Drosophila development. In particular, Cup is required for repressing translation of the maternally contributed oskar, nanos, and gurken mRNAs, all of which are essential for embryonic body axis determination. Here, we present the 2.8 Å resolution crystal structure of a minimal eIF4E–Cup assembly, consisting of the interacting regions of the two proteins. In the structure, two separate segments of Cup contact two orthogonal faces of eIF4E. The eIF4E-binding consensus motif of Cup (YXXXXLΦ) binds the convex side of eIF4E similarly to the consensus of other eIF4E-binding proteins, such as 4E-BPs and eIF4G. The second, noncanonical, eIF4E-binding site of Cup binds laterally and perpendicularly to the eIF4E β-sheet. Mutations of Cup at this binding site were shown to reduce binding to eIF4E and to promote the destabilization of the associated mRNA. Comparison with the binding mode of eIF4G to eIF4E suggests that Cup and eIF4G binding would be mutually exclusive at both binding sites. This shows how a common molecular surface of eIF4E might recognize different proteins acting at different times in the same pathway. The structure provides insight into the mechanism by which Cup disrupts eIF4E–eIF4G interaction and has broader implications for understanding the role of 4E-BPs in translational regulation. PMID:22832024

Structure of the nucleotide exchange factor eIF2B reveals mechanism of memory-enhancing molecule.

Science.gov (United States)

Tsai, Jordan C; Miller-Vedam, Lakshmi E; Anand, Aditya A; Jaishankar, Priyadarshini; Nguyen, Henry C; Renslo, Adam R; Frost, Adam; Walter, Peter

2018-03-30

Regulation by the integrated stress response (ISR) converges on the phosphorylation of translation initiation factor eIF2 in response to a variety of stresses. Phosphorylation converts eIF2 from a substrate to a competitive inhibitor of its dedicated guanine nucleotide exchange factor, eIF2B, thereby inhibiting translation. ISRIB, a drug-like eIF2B activator, reverses the effects of eIF2 phosphorylation, and in rodents it enhances cognition and corrects cognitive deficits after brain injury. To determine its mechanism of action, we solved an atomic-resolution structure of ISRIB bound in a deep cleft within decameric human eIF2B by cryo-electron microscopy. Formation of fully active, decameric eIF2B holoenzyme depended on the assembly of two identical tetrameric subcomplexes, and ISRIB promoted this step by cross-bridging a central symmetry interface. Thus, regulation of eIF2B assembly emerges as a rheostat for eIF2B activity that tunes translation during the ISR and that can be further modulated by ISRIB. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

If You Think Your Child Is Stuttering...

Science.gov (United States)

... Employers Tweet If You Think Your Child Is Stuttering... Parents of Preschoolers Parents of School-Age Children ... Edward G. Conture, Vanderbilt University. Is Your Child Stuttering? If your child has difficulty speaking and tends ...

Degradation of 4-fluorophenol by Arthrobacter sp strain IF1

NARCIS (Netherlands)

Ferreira, Maria Isabel M.; Marchesi, Julian R.; Janssen, Dick B.

A Gram-positive bacterial strain capable of aerobic biodegradation of 4-fluorophenol (4-FP) as the sole source of carbon and energy was isolated by selective enrichment from soil samples collected near an industrial site. The organism, designated strain IF1, was identified as a member of the genus

22 CFR 72.9 - Responsibility if legal representative is present.

Science.gov (United States)

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Responsibility if legal representative is... Nationals § 72.9 Responsibility if legal representative is present. (a) A consular officer should not act as provisional conservator if the consular officer knows that a legal representative is present in the foreign...

Geographical gradient of the eIF4E alleles conferring resistance to potyviruses in pea (Pisum) germplasm.

Science.gov (United States)

Konečná, Eva; Šafářová, Dana; Navrátil, Milan; Hanáček, Pavel; Coyne, Clarice; Flavell, Andrew; Vishnyakova, Margarita; Ambrose, Mike; Redden, Robert; Smýkal, Petr

2014-01-01

The eukaryotic translation initiation factor 4E was shown to be involved in resistance against several potyviruses in plants, including pea. We combined our knowledge of pea germplasm diversity with that of the eIF4E gene to identify novel genetic diversity. Germplasm of 2803 pea accessions was screened for eIF4E intron 3 length polymorphism, resulting in the detection of four eIF4E(A-B-C-S) variants, whose distribution was geographically structured. The eIF4E(A) variant conferring resistance to the P1 PSbMV pathotype was found in 53 accessions (1.9%), of which 15 were landraces from India, Afghanistan, Nepal, and 7 were from Ethiopia. A newly discovered variant, eIF4E(B), was present in 328 accessions (11.7%) from Ethiopia (29%), Afghanistan (23%), India (20%), Israel (25%) and China (39%). The eIF4E(C) variant was detected in 91 accessions (3.2% of total) from India (20%), Afghanistan (33%), the Iberian Peninsula (22%) and the Balkans (9.3%). The eIF4E(S) variant for susceptibility predominated as the wild type. Sequencing of 73 samples, identified 34 alleles at the whole gene, 26 at cDNA and 19 protein variants, respectively. Fifteen alleles were virologically tested and 9 alleles (eIF4E(A-1-2-3-4-5-6-7), eIF4E(B-1), eIF4E(C-2)) conferred resistance to the P1 PSbMV pathotype. This work identified novel eIF4E alleles within geographically structured pea germplasm and indicated their independent evolution from the susceptible eIF4E(S1) allele. Despite high variation present in wild Pisum accessions, none of them possessed resistance alleles, supporting a hypothesis of distinct mode of evolution of resistance in wild as opposed to crop species. The Highlands of Central Asia, the northern regions of the Indian subcontinent, Eastern Africa and China were identified as important centers of pea diversity that correspond with the diversity of the pathogen. The series of alleles identified in this study provides the basis to study the co-evolution of potyviruses and the

Caenorhabditis elegans ATPase inhibitor factor 1 (IF1 MAI-2 preserves the mitochondrial membrane potential (Δψm and is important to induce germ cell apoptosis.

Directory of Open Access Journals (Sweden)

L P Fernández-Cárdenas

Full Text Available When the electrochemical proton gradient is disrupted in the mitochondria, IF1 (Inhibitor Factor-1 inhibits the reverse hydrolytic activity of the F1Fo-ATP synthase, thereby allowing cells to conserve ATP at the expense of losing the mitochondrial membrane potential (Δψm. The function of IF1 has been studied mainly in different cell lines, but these studies have generated contrasting results, which have not been helpful to understand the real role of this protein in a whole organism. In this work, we studied IF1 function in Caenorhabditis elegans to understand IF1´s role in vivo. C. elegans has two inhibitor proteins of the F1Fo-ATPase, MAI-1 and MAI-2. To determine their protein localization in C. elegans, we generated translational reporters and found that MAI-2 is expressed ubiquitously in the mitochondria; conversely, MAI-1 was found in the cytoplasm and nuclei of certain tissues. By CRISPR/Cas9 genome editing, we generated mai-2 mutant alleles. Here, we showed that mai-2 mutant animals have normal progeny, embryonic development and lifespan. Contrasting with the results previously obtained in cell lines, we found no evident defects in the mitochondrial network, dimer/monomer ATP synthase ratio, ATP concentration or respiration. Our results suggest that some of the roles previously attributed to IF1 in cell lines could not reflect the function of this protein in a whole organism and could be attributed to specific cell lines or methods used to silence, knockout or overexpress this protein. However, we did observe that animals lacking IF1 had an enhanced Δψm and lower physiological germ cell apoptosis. Importantly, we found that mai-2 mutant animals must be under stress to observe the role of IF1. Accordingly, we observed that mai-2 mutant animals were more sensitive to heat shock, oxidative stress and electron transport chain blockade. Furthermore, we observed that IF1 is important to induce germ cell apoptosis under certain types of

Eukaryotic translation initiation factor 2B-beta (eIF2Bβ), a new class of plant virus resistance gene.

Science.gov (United States)

Shopan, Jannat; Mou, Haipeng; Zhang, Lili; Zhang, Changtong; Ma, Weiwei; Walsh, John A; Hu, Zhongyuan; Yang, Jinghua; Zhang, Mingfang

2017-06-01

Recessive resistances to plant viruses in the Potyvirus genus have been found to be based on mutations in the plant eukaryotic translation initiation factors, eIF4E and eIF4G or their isoforms. Here we report that natural, monogenic recessive resistance to the Potyvirus Turnip mosaic virus (TuMV) has been found in a number of mustard (Brassica juncea) accessions. Bulked segregant analysis and sequencing of resistant and susceptible plant lines indicated the resistance is controlled by a single recessive gene, recessive TuMV resistance 03 (retr03), an allele of the eukaryotic translation initiation factor 2B-beta (eIF2Bβ). Silencing of eIF2Bβ in a TuMV-susceptible mustard plant line and expression of eIF2Bβ from a TuMV-susceptible line in a TuMV-resistant mustard plant line confirmed the new resistance mechanism. A functional copy of a specific allele of eIF2Bβ is required for efficient TuMV infection. eIF2Bβ represents a new class of virus resistance gene conferring resistance to any pathogen. eIF2B acts as a guanine nucleotide exchange factor (GEF) for its GTP-binding protein partner eIF2 via interaction with eIF2·GTP at an early step in translation initiation. Further genotyping indicated that a single non-synonymous substitution (A120G) in the N-terminal region of eIF2Bβ was responsible for the TuMV resistance. A reproducible marker has been developed, facilitating marker-assisted selection for TuMV resistance in B. juncea. Our findings provide a new target for seeking natural resistance to potyviruses and new opportunities for the control of potyviruses using genome editing techniques targeted on eIF2Bβ. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

What If No One Wants to be Friends with Me Anymore

DEFF Research Database (Denmark)

Noesgaard, Pernille Ida; Kristensen, Ole Steen

2015-01-01

moral dilemmas are described: 1) the dilemma between accepting being bullied and yet feeling hurt, 2) the dilemma between staying isolated and the fear of escalating the bullying, if adults interfere, and 3) the dilemma between ending the bullying and losing friendships. The conclusion is that bullying...

The role of the ATPase inhibitor factor 1 (IF1) in cancer cells adaptation to hypoxia and anoxia.

Science.gov (United States)

Sgarbi, G; Barbato, S; Costanzini, A; Solaini, G; Baracca, A

2018-02-01

The physiological role of the mitochondrial ATP synthase complex is to generate ATP through oxidative phosphorylation. Indeed, the enzyme can reverse its activity and hydrolyze ATP under ischemic conditions, as shown in isolated mitochondria and in mammalian heart and liver. However, what occurs when cancer cells experience hypoxia or anoxia has not been well explored. In the present study, we investigated the bioenergetics of cancer cells under hypoxic/anoxic conditions with particular emphasis on ATP synthase, and the conditions driving it to work in reverse. In this context, we further examined the role exerted by its endogenous inhibitor factor, IF 1 , that it is overexpressed in cancer cells. Metabolic and bioenergetic analysis of cancer cells exposed to severe hypoxia (down to 0.1% O 2 ) unexpectedly showed that Δψ m is preserved independently of the presence of IF 1 and that ATP synthase still phosphorylates ADP though at a much lower rate than in normoxia. However, when we induced an anoxia-mimicking condition by collapsing Δμ Η + with the FCCP uncoupler, the IF 1 -silenced clones only reversed the ATP synthase activity hydrolyzing ATP in order to reconstitute the electrochemical proton gradient. Notably, in cancer cells IF 1 overexpression fully prevents ATP synthase hydrolytic activity activation under uncoupling conditions. Therefore, our results suggest that IF 1 overexpression promotes cancer cells survival under temporary anoxic conditions by preserving cellular ATP despite mitochondria dysfunction. Copyright © 2017 Elsevier B.V. All rights reserved.

48 CFR 49.603-3 - Cost-reimbursement contracts-complete termination, if settlement includes cost.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Cost-reimbursement... Termination Forms and Formats 49.603-3 Cost-reimbursement contracts—complete termination, if settlement includes cost. [Insert the following in Block 14 of SF 30 for settlement of cost-reimbursement contracts...

If only it could speak

DEFF Research Database (Denmark)

Jensen, Ole B.

of the ‘place' notion advocated here. If we give voice to the hard infrastructures, they would tell stories about how infrastructures and mobility systems are both material and cultural artifacts that we need to understand very different from the utilitarian and instrumental perception guiding much urban...

The eIF4E-binding proteins are modifiers of cytoplasmic eIF4E relocalization during the heat shock response.

Science.gov (United States)

Sukarieh, R; Sonenberg, N; Pelletier, J

2009-05-01

Stress granules (SGs) arise as a consequence of cellular stress, contain stalled translation preinitiation complexes, and are associated with cell survival during environmental insults. SGs are dynamic entities with proteins relocating into and out of them during stress. Among the repertoire of proteins present in SGs is eukaryotic initiation factor 4E (eIF4E), a translation factor required for cap-dependent translation and that regulates a rate-limiting step for protein synthesis. Herein, we demonstrate that localization of eIF4E to SGs is dependent on the presence of a family of repressor proteins, eIF4E-binding proteins (4E-BPs). Our results demonstrate that 4E-BPs regulate the SG localization of eIF4E.

Trypanosoma brucei TbIF1 inhibits the essential F1-ATPase in the infectious form of the parasite.

Directory of Open Access Journals (Sweden)

Brian Panicucci

2017-04-01

Full Text Available The mitochondrial (mt FoF1-ATP synthase of the digenetic parasite, Trypanosoma brucei, generates ATP during the insect procyclic form (PF, but becomes a perpetual consumer of ATP in the mammalian bloodstream form (BF, which lacks a canonical respiratory chain. This unconventional dependence on FoF1-ATPase is required to maintain the essential mt membrane potential (Δψm. Normally, ATP hydrolysis by this rotary molecular motor is restricted to when eukaryotic cells experience sporadic hypoxic conditions, during which this compulsory function quickly depletes the cellular ATP pool. To protect against this cellular treason, the highly conserved inhibitory factor 1 (IF1 binds the enzyme in a manner that solely inhibits the hydrolytic activity. Intriguingly, we were able to identify the IF1 homolog in T. brucei (TbIF1, but determined that its expression in the mitochondrion is tightly regulated throughout the life cycle as it is only detected in PF cells. TbIF1 appears to primarily function as an emergency brake in PF cells, where it prevented the restoration of the Δψm by FoF1-ATPase when respiration was chemically inhibited. In vitro, TbIF1 overexpression specifically inhibits the hydrolytic activity but not the synthetic capability of the FoF1-ATP synthase in PF mitochondria. Furthermore, low μM amounts of recombinant TbIF1 achieve the same inhibition of total mt ATPase activity as the FoF1-ATPase specific inhibitors, azide and oligomycin. Therefore, even minimal ectopic expression of TbIF1 in BF cells proved lethal as the indispensable Δψm collapsed due to inhibited FoF1-ATPase. In summary, we provide evidence that T. brucei harbors a natural and potent unidirectional inhibitor of the vital FoF1-ATPase activity that can be exploited for future structure-based drug design.

Inorganic fullerene-like IF-WS_2/PVB nanocomposites of improved thermo-mechanical and tribological properties

International Nuclear Information System (INIS)

Simić, Danica; Stojanović, Dušica B.; Kojović, Aleksandar; Dimić, Mirjana; Totovski, Ljubica; Uskoković, Petar S.; Aleksić, Radoslav

2016-01-01

The subject of this research is to explore the possibility of preparation of nanocomposite material of improved thermo-mechanical and tribological properties, using inorganic fullerene-like tungsten disulfide nanostructures (IF-WS_2) as reinforcement in poly(vinyl butyral) (PVB). This paper also reports investigation of the effects of using different solvents in preparation of PVB/IF-WS_2 nanocomposite on the thermo-mechanical behavior of the resulting material. PVB was dissolved in ethanol, isopropanol, n-butanol and ethyl acetate. IF-WS_2 nanoparticles were added to these PVB solutions and dispersed by different deagglomeration techniques. Samples were dried and thin films were obtained. Their microstructure and the quality of IF-WS_2 dispersion and deagglomeration in PVB matrix was analyzed by scanning electron microscope (SEM). The reinforcing effect of IF-WS_2 is examined by determining hardness, reduced modulus of elasticity and coefficient of friction, by nanoindentation and nanoscratch test, in terms of the different solvents applied in preparation of the samples, mode of stirring and different contents of IF-WS_2. The glass transition temperature (T_g) was determined for the prepared samples using differential scanning calorimetry (DSC) and dynamic mechanical thermal analysis (DMA). Storage modulus and mechanical loss factor were observed in a defined temperature range using DMA. - Highlights: • Poly(vinyl butyral)/tungsten disulfide nanocomposites were examined. • Different solvents and deagglomeration methods affect the properties of composites. • Nanoindentation and scratch test, PSD, SEM, DSC and DMTA were analyzed. • Thermo-mechanical and antifriction properties of composite material are improved.

miR-434-3p and DNA hypomethylation co-regulate eIF5A1 to increase AChRs and to improve plasticity in SCT rat skeletal muscle.

Science.gov (United States)

Shang, Fei-Fei; Xia, Qing-Jie; Liu, Wei; Xia, Lei; Qian, Bao-Jiang; You, Ling; He, Mu; Yang, Jin-Liang; Wang, Ting-Hua

2016-03-11

Acetylcholine receptors (AChRs) serve as connections between motor neurons and skeletal muscle and are essential for recovery from spinal cord transection (SCT). Recently, microRNAs have emerged as important potential biotherapeutics for several diseases; however, whether miRNAs operate in the modulation of AChRs remains unknown. We found increased AChRs numbers and function scores in rats with SCT; these increases were reduced following the injection of a eukaryotic translation initiation factor 5A1 (eIF5A1) shRNA lentivirus into the hindlimb muscle. Then, high-throughput screening for microRNAs targeting eIF5A1 was performed, and miR-434-3p was found to be robustly depleted in SCT rat skeletal muscle. Furthermore, a highly conserved miR-434-3p binding site was identified within the mRNA encoding eIF5A1 through bioinformatics analysis and dual-luciferase assay. Overexpression or knockdown of miR-434-3p in vivo demonstrated it was a negative post-transcriptional regulator of eIF5A1 expression and influenced AChRs expression. The microarray-enriched Gene Ontology (GO) terms regulated by miR-434-3p were muscle development terms. Using a lentivirus, one functional gene (map2k6) was confirmed to have a similar function to that of miR-434-3p in GO terms. Finally, HRM and MeDIP-PCR analyses revealed that DNA demethylation also up-regulated eIF5A1 after SCT. Consequently, miR-434-3p/eIF5A1 in muscle is a promising potential biotherapy for SCI repair.

Identification of Plasmodium falciparum Translation Initiation eIF2β Subunit: Direct Interaction with Protein Phosphatase Type 1

Czech Academy of Sciences Publication Activity Database

Tellier, G.; Lenne, A.; Cailliau-Maggio, K.; Cabezas-Cruz, A.; Valdés, James J.; Martoriati, A.; Aliouat, El M.; Gosset, P.; Delaire, B.; Fréville, A.; Pierrot, C.; Khalife, J.

2016-01-01

Roč. 7, MAY 26 (2016), č. článku 777. ISSN 1664-302X Institutional support: RVO:60077344 Keywords : Plasmodium falciparum * Protein Phosphatase type1 * eIF2b * protein-protein interaction * translation complex Subject RIV: EE - Microbiology, Virology Impact factor: 4.076, year: 2016

Translation initiation factors eIF3 and HCR1 control translation termination and stop codon read-through in yeast cells

Czech Academy of Sciences Publication Activity Database

Beznosková, P.; Cuchalová, Lucie; Wagner, S.; Shoemaker, Ch. J.; Gunišová, S.; von der Haar, T.; Valášek, L. S.

2013-01-01

Roč. 9, č. 11 (2013), e1003962_1-e1003962_17 ISSN 1553-7404 Institutional support: RVO:61389013 Keywords : translation initiation * translation termination * eIF3 Subject RIV: CD - Macromolecular Chemistry Impact factor: 8.167, year: 2013

Cadmium induces cytotoxicity in human bronchial epithelial cells through upregulation of eIF5A1 and NF-kappaB

Energy Technology Data Exchange (ETDEWEB)

Chen, De-Ju; Xu, Yan-Ming; Du, Ji-Ying [Laboratory of Cancer Biology and Epigenetics, Shantou University Medical College, Shantou, Guangdong 515041 (China); Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong 515041 (China); Huang, Dong-Yang [Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong 515041 (China); Lau, Andy T.Y., E-mail: andytylau@stu.edu.cn [Laboratory of Cancer Biology and Epigenetics, Shantou University Medical College, Shantou, Guangdong 515041 (China); Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong 515041 (China)

2014-02-28

Highlights: • Normal human bronchial epithelial cells (BEAS-2B) were dosed with cadmium (Cd). • A low level (2 μM) of Cd treatment for 36 h elicited negligible cytotoxicity. • High levels (20 or 30 μM) of Cd treatment for 36 h induced cell death. • High levels of Cd can upregulate the protein levels of eIF5A1 and NF-κB p65. • We suggest that eIF5A1 level is possibly modulated by NF-κB. - Abstract: Cadmium (Cd) and Cd compounds are widely-distributed in the environment and well-known carcinogens. Here, we report that in CdCl{sub 2}-exposed human bronchial epithelial cells (BEAS-2B), the level of p53 is dramatically decreased in a time- and dose-dependent manner, suggesting that the observed Cd-induced cytotoxicity is not likely due to the pro-apoptotic function of p53. Therefore, this prompted us to further study the responsive pro-apoptotic factors by proteomic approaches. Interestingly, we identified that high levels (20 or 30 μM) of Cd can significantly upregulate the protein levels of eukaryotic translation initiation factor 5A1 (eIF5A1) and redox-sensitive transcription factor NF-κB p65. Moreover, there is an enhanced NF-κB nuclear translocation as well as chromatin-binding in Cd-treated BEAS-2B cells. We also show that small interfering RNA-specific knockdown of eIF5A1 in Cd-exposed cells attenuated the Cd cytotoxicity, indicating the potential role of eIF5A1 in Cd cytotoxicity. As eIF5A1 is reported to be related with cell apoptosis but little is known about its transcriptional control, we hypothesize that NF-κB might likely modulate eIF5A1 gene expression. Notably, by bioinformatic analysis, several potential NF-κB binding sites on the upstream promoter region of eIF5A1 gene can be found. Subsequent chromatin immunoprecipitation assay revealed that indeed there is enhanced NF-κB binding on eIF5A1 promoter region of Cd-treated BEAS-2B cells. Taken together, our findings suggest for the first time a regulatory mechanism for the pro

Phosphorylation of eIF2α is required for mRNA translation inhibition and survival during moderate hypoxia

International Nuclear Information System (INIS)

Koritzinsky, Marianne; Rouschop, Kasper M.A.; Beucken, Twan van den; Magagnin, Michael G.; Savelkouls, Kim; Lambin, Philippe; Wouters, Bradly G.

2007-01-01

Abstracts: Background and purpose: Human tumors are characterized by temporal fluctuations in oxygen tension. The biological pathways that respond to the dynamic tumor microenvironment represent potential molecular targets for cancer therapy. Anoxic conditions result in eIF2α dependent inhibition of overall mRNA translation, differential gene expression, hypoxia tolerance and tumor growth. The signaling pathway which governs eIF2α phosphorylation has therefore emerged as a potential molecular target. In this study, we investigated the role of eIF2α in regulating mRNA translation and hypoxia tolerance during moderate hypoxia. Since other molecular pathways that regulate protein synthesis are frequently mutated in cancer, we also assessed mRNA translation in a panel of cell lines from different origins. Materials and methods: Immortalized human fibroblast, transformed mouse embryo fibroblasts (MEFs) and cells from six cancer cell lines were exposed to 0.2% or 0.0% oxygen. We assayed global mRNA translation efficiency by polysome analysis, as well as proliferation and clonogenic survival. The role of eIF2α was assessed in MEFs harboring a homozygous inactivating mutation (S51A) as well as in U373-MG cells overexpressing GADD34 (C-term) under a tetracycline-dependent promoter. The involvement of eIF4E regulation was investigated in HeLa cells stably expressing a short hairpin RNA (shRNA) targeting 4E-BP1. Results: All cells investigated inhibited mRNA translation severely in response to anoxia and modestly in response to hypoxia. Two independent genetic cell models demonstrated that inhibition of mRNA translation in response to moderate hypoxia was dependent on eIF2α phosphorylation. Disruption of eIF2α phosphorylation caused sensitivity to hypoxia and anoxia. Conclusions: Disruption of eIF2α phosphorylation is a potential target for hypoxia-directed molecular cancer therapy

30 CFR 285.224 - What happens if MMS accepts my bid?

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 2 2010-07-01 2010-07-01 false What happens if MMS accepts my bid? 285.224... Renewable Energy Leases Competitive Lease Award Process § 285.224 What happens if MMS accepts my bid? If we... withdraw an OCS area in which we have held a lease sale before you and MMS execute the lease in that area...

Eukaryotic translation initiation factor 5A (eIF5A) is essential for HIF-1α activation in hypoxia

Energy Technology Data Exchange (ETDEWEB)

Tariq, Mohammad [Chemical Genetics Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Graduate School of Science and Engineering, Saitama University, 645 Shimo-Okubo, Sakura-ku, Saitama 338-8570 (Japan); Ito, Akihiro, E-mail: akihiro-i@riken.jp [Chemical Genetics Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Chemical Genomics Research Group, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Japan Agency for Medical Research and Development, AMED-CREST, 1-7-1 Otemachi, Chiyoda-ku, Tokyo, 100-0004 (Japan); Ishfaq, Muhammad; Bradshaw, Elliot [Chemical Genetics Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Graduate School of Science and Engineering, Saitama University, 645 Shimo-Okubo, Sakura-ku, Saitama 338-8570 (Japan); Yoshida, Minoru [Chemical Genetics Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Chemical Genomics Research Group, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Graduate School of Science and Engineering, Saitama University, 645 Shimo-Okubo, Sakura-ku, Saitama 338-8570 (Japan); Japan Agency for Medical Research and Development, AMED-CREST, 1-7-1 Otemachi, Chiyoda-ku, Tokyo, 100-0004 (Japan)

2016-02-05

The eukaryotic initiation factor 5A (eIF5A) is an essential protein involved in translation elongation and cell proliferation. eIF5A undergoes several post-translational modifications including hypusination and acetylation. Hypusination is indispensable for the function of eIF5A. On the other hand, the precise function of acetylation remains unknown, but it may render the protein inactive since hypusination blocks acetylation. Here, we report that acetylation of eIF5A increases under hypoxia. During extended hypoxic periods an increase in the level of eIF5A acetylation correlated with a decrease in HIF-1α, suggesting involvement of eIF5A activity in HIF-1α expression under hypoxia. Indeed, suppression of eIF5A by siRNA oligo-mediated knockdown or treatment with GC7, a deoxyhypusine synthase inhibitor, led to significant reduction of HIF-1α activity. Furthermore, knockdown of eIF5A or GC7 treatment reduced tumor spheroid formation with a concomitant decrease in HIF-1α expression. Our results suggest that functional, hypusinated eIF5A is necessary for HIF-1α expression during hypoxia and that eIF5A is an attractive target for cancer therapy. - Highlights: • Hypoxia induces acetylation of eIF5A. • Active eIF5A is necessary for HIF-1α activation in hypoxia. • Active eIF5A is important for tumor spheroid growth.

Eukaryotic translation initiation factor 5A (eIF5A) is essential for HIF-1α activation in hypoxia

International Nuclear Information System (INIS)

Tariq, Mohammad; Ito, Akihiro; Ishfaq, Muhammad; Bradshaw, Elliot; Yoshida, Minoru

2016-01-01

The eukaryotic initiation factor 5A (eIF5A) is an essential protein involved in translation elongation and cell proliferation. eIF5A undergoes several post-translational modifications including hypusination and acetylation. Hypusination is indispensable for the function of eIF5A. On the other hand, the precise function of acetylation remains unknown, but it may render the protein inactive since hypusination blocks acetylation. Here, we report that acetylation of eIF5A increases under hypoxia. During extended hypoxic periods an increase in the level of eIF5A acetylation correlated with a decrease in HIF-1α, suggesting involvement of eIF5A activity in HIF-1α expression under hypoxia. Indeed, suppression of eIF5A by siRNA oligo-mediated knockdown or treatment with GC7, a deoxyhypusine synthase inhibitor, led to significant reduction of HIF-1α activity. Furthermore, knockdown of eIF5A or GC7 treatment reduced tumor spheroid formation with a concomitant decrease in HIF-1α expression. Our results suggest that functional, hypusinated eIF5A is necessary for HIF-1α expression during hypoxia and that eIF5A is an attractive target for cancer therapy. - Highlights: • Hypoxia induces acetylation of eIF5A. • Active eIF5A is necessary for HIF-1α activation in hypoxia. • Active eIF5A is important for tumor spheroid growth.

When Can We Say "If"?

Science.gov (United States)

Evans, Jonathan St. B. T.; Neilens, Helen; Handley, Simon J.; Over, David E.

2008-01-01

In this study, we focus on the conditions which permit people to assert a conditional statement of the form "if p then q" with conversational relevance. In a broadly decision-theoretic approach, also drawing on hypothetical thinking theory [Evans, J. St. B. T. (2007). "Hypothetical thinking: Dual processes in reasoning and judgement". Hove, UK:…

Small Ribosomal Protein RPS0 Stimulates Translation Initiation by Mediating 40S-Binding of eIF3 via Its Direct Contact with the eIF3a/TIF32 Subunit

Czech Academy of Sciences Publication Activity Database

Kouba, Tomáš; Dányi, István; Gunišová, Stanislava; Munzarová, Vanda; Vlčková, Vladislava; Cuchalová, Lucie; Neueder, A.; Milkereit, P.; Valášek, Leoš Shivaya

2012-01-01

Roč. 7, č. 7 (2012), e40464 E-ISSN 1932-6203 R&D Projects: GA ČR(CZ) GAP305/11/0172 Institutional research plan: CEZ:AV0Z50200510 Keywords : eIF3a/TIF32 * mRNAs * protein Subject RIV: EE - Microbiology, Virology Impact factor: 3.730, year: 2012

13 CFR 114.109 - What if my claim is denied?

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2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false What if my claim is denied? 114.109 Section 114.109 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION ADMINISTRATIVE CLAIMS... representative in writing by certified or registered mail if it denies your claim. You have a right to file suit...

The deoxyhypusine synthase mutant dys1-1 reveals the association of eIF5A and Asc1 with cell wall integrity.

Directory of Open Access Journals (Sweden)

Fabio Carrilho Galvão

Full Text Available The putative eukaryotic translation initiation factor 5A (eIF5A is a highly conserved protein among archaea and eukaryotes that has recently been implicated in the elongation step of translation. eIF5A undergoes an essential and conserved posttranslational modification at a specific lysine to generate the residue hypusine. The enzymes deoxyhypusine synthase (Dys1 and deoxyhypusine hydroxylase (Lia1 catalyze this two-step modification process. Although several Saccharomyces cerevisiae eIF5A mutants have importantly contributed to the study of eIF5A function, no conditional mutant of Dys1 has been described so far. In this study, we generated and characterized the dys1-1 mutant, which showed a strong depletion of mutated Dys1 protein, resulting in more than 2-fold decrease in hypusine levels relative to the wild type. The dys1-1 mutant demonstrated a defect in total protein synthesis, a defect in polysome profile indicative of a translation elongation defect and a reduced association of eIF5A with polysomes. The growth phenotype of dys1-1 mutant is severe, growing only in the presence of 1 M sorbitol, an osmotic stabilizer. Although this phenotype is characteristic of Pkc1 cell wall integrity mutants, the sorbitol requirement from dys1-1 is not associated with cell lysis. We observed that the dys1-1 genetically interacts with the sole yeast protein kinase C (Pkc1 and Asc1, a component of the 40S ribosomal subunit. The dys1-1 mutant was synthetically lethal in combination with asc1Δ and overexpression of TIF51A (eIF5A or DYS1 is toxic for an asc1Δ strain. Moreover, eIF5A is more associated with translating ribosomes in the absence of Asc1 in the cell. Finally, analysis of the sensitivity to cell wall-perturbing compounds revealed a more similar behavior of the dys1-1 and asc1Δ mutants in comparison with the pkc1Δ mutant. These data suggest a correlated role for eIF5A and Asc1 in coordinating the translational control of a subset of m

Identification of the Drosophila eIF4A gene as a target of the DREF transcription factor

International Nuclear Information System (INIS)

Ida, Hiroyuki; Yoshida, Hideki; Nakamura, Kumi; Yamaguchi, Masamitsu

2007-01-01

The DNA replication-related element-binding factor (DREF) regulates cell proliferation-related gene expression in Drosophila. We have carried out a genetic screening, taking advantage of the rough eye phenotype of transgenic flies that express full-length DREF in the eye imaginal discs and identified the eukaryotic initiation factor 4A (eIF4A) gene as a dominant suppressor of the DREF-induced rough eye phenotype. The eIF4A gene was here found to carry three DRE sequences, DRE1 (- 40 to - 47), DRE2 (- 48 to - 55), and DRE3 (- 267 to - 274) in its promoter region, these all being important for the eIF4A gene promoter activity in cultured Drosophila Kc cells and in living flies. Knockdown of DREF in Drosophila S2 cells decreased the eIF4A mRNA level and the eIF4A gene promoter activity. Furthermore, specific binding of DREF to genomic regions containing DRE sequences was demonstrated by chromatin immunoprecipitation assays using anti-DREF antibodies. Band mobility shift assays using Kc cell nuclear extracts revealed that DREF could bind to DRE1 and DRE3 sequences in the eIF4A gene promoter in vitro, but not to the DRE2 sequence. The results suggest that the eIF4A gene is under the control of the DREF pathway and DREF is therefore involved in the regulation of protein synthesis

The structure of F1-ATPase from Saccharomyces cerevisiae inhibited by its regulatory protein IF1

Science.gov (United States)

Robinson, Graham C.; Bason, John V.; Montgomery, Martin G.; Fearnley, Ian M.; Mueller, David M.; Leslie, Andrew G. W.; Walker, John E.

2013-01-01

The structure of F1-ATPase from Saccharomyces cerevisiae inhibited by the yeast IF1 has been determined at 2.5 Å resolution. The inhibitory region of IF1 from residues 1 to 36 is entrapped between the C-terminal domains of the αDP- and βDP-subunits in one of the three catalytic interfaces of the enzyme. Although the structure of the inhibited complex is similar to that of the bovine-inhibited complex, there are significant differences between the structures of the inhibitors and their detailed interactions with F1-ATPase. However, the most significant difference is in the nucleotide occupancy of the catalytic βE-subunits. The nucleotide binding site in βE-subunit in the yeast complex contains an ADP molecule without an accompanying magnesium ion, whereas it is unoccupied in the bovine complex. Thus, the structure provides further evidence of sequential product release, with the phosphate and the magnesium ion released before the ADP molecule. PMID:23407639

AMPK activation regulates apoptosis, adipogenesis, and lipolysis by eIF2α in adipocytes

International Nuclear Information System (INIS)

Dagon, Yossi; Avraham, Yosefa; Berry, Elliot M.

2006-01-01

AMP-activated protein kinase (AMPK) is a metabolic master switch regulating glucose and lipid metabolism. Recently, AMPK has been implicated in the control of adipose tissue content. Yet, the nature of this action is controversial. We examined the effect on F442a adipocytes of the AMPK activator-AICAR. Activation of AMPK induced dose-dependent apoptotic cell death, inhibition of lipolysis, and downregulatation key adipogenic genes, such as peroxisome proliferator-activated receptor (PPARγ) and CCAAT/enhancer-binding protein alpha (C/EBPα). We have identified the α-subunit of the eukaryotic initiation factor-2 (eIF2α) as a target gene which is phosphorylated following AICAR treatment. Such phosphorylation is one of the best-characterized mechanisms for downregulating protein synthesis. 2-Aminopurine (2-AP), an inhibitor of eIF2α kinases, could overcome the apoptotic effect of AICAR, abolishing the reduction of PPARγ and C/EBPα and the lipolytic properties of AMPK. Thus, AMPK may diminish adiposity via reduction of fat cell number through eIF2α-dependent translation shutdown

A Yeast Purification System for Human Translation Initiation Factors eIF2 and eIF2B epsilon and Their Use in the Diagnosis of CACH/VWM Disease

NARCIS (Netherlands)

de Almeida, R.A.; Fogli, A.; Gaillard, M.; Scheper, G.C.; Boesflug-Tanguy, O.; Pavitt, G.D.

2013-01-01

Recessive inherited mutations in any of five subunits of the general protein synthesis factor eIF2B are responsible for a white mater neurodegenerative disease with a large clinical spectrum. The classical form is called Childhood Ataxia with CNS hypomyelination (CACH) or Vanishing White Matter

Leishmania eukaryotic initiation factor (LeIF inhibits parasite growth in murine macrophages.

Directory of Open Access Journals (Sweden)

Olga Koutsoni

Full Text Available The leishmaniases constitute neglected global public health problems that require adequate control measures, prophylactic clinical vaccines and effective and non-toxic drug treatments. In this study, we explored the potential of Leishmania infantum eukaryotic initiation factor (LieIF, an exosomal protein, as a novel anti-infective therapeutic molecule. More specifically, we assessed the efficacy of recombinant LieIF, in combination with recombinant IFN-γ, in eliminating intracellular L. donovani parasites in an in vitro macrophage model. J774A.1 macrophages were initially treated with LieIF/IFN-γ prior to in vitro infection with L. donovani stationary phase promastigotes (pre-infection treatment, and resistance to infection was observed 72 h after infection. J774A.1 macrophages were also treated with LieIF/IFN-γ after L. donovani infection (post-infection treatment, and resistance to infection was also observed at both time points tested (19 h and 72 h after infection. To elucidate the LieIF/IFN-γ-induced mechanism(s that mediate the reduction of intracellular parasite growth, we examined the generation of potent microbicidal molecules, such as nitric oxide (NO and reactive oxygen species (ROS, within infected macrophages. Furthermore, macrophages pre-treated with LieIF/IFN-γ showed a clear up-regulation in macrophage inflammatory protein 1α (MIP-1α as well as tumor necrosis factor alpha (TNF-α expression. However, significant different protein levels were not detected. In addition, macrophages pre-treated with LieIF/IFN-γ combined with anti-TNF-α monoclonal antibody produced significantly lower amounts of ROS. These data suggest that during the pre-treatment state, LieIF induces intramacrophage parasite growth inhibition through the production of TNF-α, which induces microbicidal activity by stimulating NO and ROS production. The mechanisms of NO and ROS production when macrophages are treated with LieIF after infection are probably

Inorganic fullerene-like IF-WS{sub 2}/PVB nanocomposites of improved thermo-mechanical and tribological properties

Energy Technology Data Exchange (ETDEWEB)

Simić, Danica [Military Technical Institute, Ratka Resanovića 1, 11132 Belgrade (Serbia); Stojanović, Dušica B., E-mail: duca@tmf.bg.ac.rs [University of Belgrade, Faculty of Technology and Metallurgy, 11120 Belgrade (Serbia); Kojović, Aleksandar [University of Belgrade, Faculty of Technology and Metallurgy, 11120 Belgrade (Serbia); Dimić, Mirjana; Totovski, Ljubica [Military Technical Institute, Ratka Resanovića 1, 11132 Belgrade (Serbia); Uskoković, Petar S.; Aleksić, Radoslav [University of Belgrade, Faculty of Technology and Metallurgy, 11120 Belgrade (Serbia)

2016-12-01

The subject of this research is to explore the possibility of preparation of nanocomposite material of improved thermo-mechanical and tribological properties, using inorganic fullerene-like tungsten disulfide nanostructures (IF-WS{sub 2}) as reinforcement in poly(vinyl butyral) (PVB). This paper also reports investigation of the effects of using different solvents in preparation of PVB/IF-WS{sub 2} nanocomposite on the thermo-mechanical behavior of the resulting material. PVB was dissolved in ethanol, isopropanol, n-butanol and ethyl acetate. IF-WS{sub 2} nanoparticles were added to these PVB solutions and dispersed by different deagglomeration techniques. Samples were dried and thin films were obtained. Their microstructure and the quality of IF-WS{sub 2} dispersion and deagglomeration in PVB matrix was analyzed by scanning electron microscope (SEM). The reinforcing effect of IF-WS{sub 2} is examined by determining hardness, reduced modulus of elasticity and coefficient of friction, by nanoindentation and nanoscratch test, in terms of the different solvents applied in preparation of the samples, mode of stirring and different contents of IF-WS{sub 2}. The glass transition temperature (T{sub g}) was determined for the prepared samples using differential scanning calorimetry (DSC) and dynamic mechanical thermal analysis (DMA). Storage modulus and mechanical loss factor were observed in a defined temperature range using DMA. - Highlights: • Poly(vinyl butyral)/tungsten disulfide nanocomposites were examined. • Different solvents and deagglomeration methods affect the properties of composites. • Nanoindentation and scratch test, PSD, SEM, DSC and DMTA were analyzed. • Thermo-mechanical and antifriction properties of composite material are improved.

"What If" Analyses in Investment Decision Making

Directory of Open Access Journals (Sweden)

Katarína Belanová

2012-09-01

Full Text Available In general, each project`s value is estimated using a discounted cash flow (DCF valuation, and the opportunity with the highest value, as measured by the resultant net present value (NPV will be selected. The problem with such NPV estimates is that they depend on projected future cash flows. If there are errors in those projections, then estimated net present values can be misleading (a forecasting risk. Basic approach to evaluating cash flow and NPV estimates involves asking “what – if” questions. Accordingly, the paper discusses some organized ways of going about a what – if analysis. Its goal in doing so is to assess the degree of forecasting risk and to identify those elements that are the most critical to the success or failure of an investment. However, as we show in examples, as well as in the practical study, though what – if analysis really allows us to obtain the certain idea of degree of forecasting risk, it does not tell us what to do about the possible errors.

Translational control by eIF2α phosphorylation regulates vulnerability to the synaptic and behavioral effects of cocaine

Science.gov (United States)

Huang, Wei; Placzek, Andon N; Viana Di Prisco, Gonzalo; Khatiwada, Sanjeev; Sidrauski, Carmela; Krnjević, Krešimir; Walter, Peter; Dani, John A; Costa-Mattioli, Mauro

2016-01-01

Adolescents are especially prone to drug addiction, but the underlying biological basis of their increased vulnerability remains unknown. We reveal that translational control by phosphorylation of the translation initiation factor eIF2α (p-eIF2α) accounts for adolescent hypersensitivity to cocaine. In adolescent (but not adult) mice, a low dose of cocaine reduced p-eIF2α in the ventral tegmental area (VTA), potentiated synaptic inputs to VTA dopaminergic neurons, and induced drug-reinforced behavior. Like adolescents, adult mice with reduced p-eIF2α-mediated translational control were more susceptible to cocaine-induced synaptic potentiation and behavior. Conversely, like adults, adolescent mice with increased p-eIF2α became more resistant to cocaine's effects. Accordingly, metabotropic glutamate receptor-mediated long-term depression (mGluR-LTD)—whose disruption is postulated to increase vulnerability to drug addiction—was impaired in both adolescent mice and adult mice with reduced p-eIF2α mediated translation. Thus, during addiction, cocaine hijacks translational control by p-eIF2α, initiating synaptic potentiation and addiction-related behaviors. These insights may hold promise for new treatments for addiction. DOI: http://dx.doi.org/10.7554/eLife.12052.001 PMID:26928234

20 CFR 416.998 - If you become disabled by another impairment(s).

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false If you become disabled by another impairment... Disability Or Blindness § 416.998 If you become disabled by another impairment(s). If a new severe impairment(s) begins in or before the month in which your last impairment(s) ends, we will find that your...

20 CFR 404.1598 - If you become disabled by another impairment(s).

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2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false If you become disabled by another impairment... Disability § 404.1598 If you become disabled by another impairment(s). If a new severe impairment(s) begins in or before the month in which your last impairment(s) ends, we will find that your disability is...

The RNA recognition motif of eukaryotic translation initiation factor 3g (eIF3g) is required for resumption of scanning of posttermination ribosomes for reinitiation on GCN4 and together with eIF3i stimulates linear scanning.

Science.gov (United States)

Cuchalová, Lucie; Kouba, Tomás; Herrmannová, Anna; Dányi, István; Chiu, Wen-Ling; Valásek, Leos

2010-10-01

Recent reports have begun unraveling the details of various roles of individual eukaryotic translation initiation factor 3 (eIF3) subunits in translation initiation. Here we describe functional characterization of two essential Saccharomyces cerevisiae eIF3 subunits, g/Tif35 and i/Tif34, previously suggested to be dispensable for formation of the 48S preinitiation complexes (PICs) in vitro. A triple-Ala substitution of conserved residues in the RRM of g/Tif35 (g/tif35-KLF) or a single-point mutation in the WD40 repeat 6 of i/Tif34 (i/tif34-Q258R) produces severe growth defects and decreases the rate of translation initiation in vivo without affecting the integrity of eIF3 and formation of the 43S PICs in vivo. Both mutations also diminish induction of GCN4 expression, which occurs upon starvation via reinitiation. Whereas g/tif35-KLF impedes resumption of scanning for downstream reinitiation by 40S ribosomes terminating at upstream open reading frame 1 (uORF1) in the GCN4 mRNA leader, i/tif34-Q258R prevents full GCN4 derepression by impairing the rate of scanning of posttermination 40S ribosomes moving downstream from uORF1. In addition, g/tif35-KLF reduces processivity of scanning through stable secondary structures, and g/Tif35 specifically interacts with Rps3 and Rps20 located near the ribosomal mRNA entry channel. Together these results implicate g/Tif35 and i/Tif34 in stimulation of linear scanning and, specifically in the case of g/Tif35, also in proper regulation of the GCN4 reinitiation mechanism.

Alcohol Use: If You Drink, Keep It Moderate

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... drink include: Beer: 12 fluid ounces (355 milliliters) Wine: 5 fluid ounces (148 milliliters) Distilled spirits (80 proof): 1.5 fluid ounces (44 milliliters) Moderate alcohol use may be of most benefit if you have existing risk factors for heart ...

If Your Child Has a Heart Defect (For Parents)

Science.gov (United States)

... Videos for Educators Search English Español If Your Child Has a Heart Defect KidsHealth / For Parents / If ... has any of these symptoms. Caring for Your Child Parenting kids with heart defects includes learning about ...

29 CFR 778.323 - Effect if salary is for variable workweek.

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2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Effect if salary is for variable workweek. 778.323 Section... Special Problems Reduction in Workweek Schedule with No Change in Pay § 778.323 Effect if salary is for... employees hired on a salary basis, the regular rate depends in part on the agreement of the parties as to...

Phytoplankton IF-FISH: Species-specific labeling of cellular proteins by immunofluorescence (IF) with simultaneous species identification by fluorescence immunohybridization (FISH).

Science.gov (United States)

Meek, Megan E; Van Dolah, Frances M

2016-05-01

Phytoplankton rarely occur as unialgal populations. Therefore, to study species-specific protein expression, indicative of physiological status in natural populations, methods are needed that will both assay for a protein of interest and identify the species expressing it. Here we describe a protocol for IF-FISH, a dual labeling procedure using immunofluorescence (IF) labeling of a protein of interest followed by fluorescence in situ hybridization (FISH) to identify the species expressing that protein. The protocol was developed to monitor expression of the cell cycle marker proliferating cell nuclear antigen (PCNA) in the red tide dinoflagellate, Karenia brevis, using a large subunit (LSU) rRNA probe to identify K. brevis in a mixed population of morphologically similar Karenia species. We present this protocol as proof of concept that IF-FISH can be successfully applied to phytoplankton cells. This method is widely applicable for the analysis of single-cell protein expression of any protein of interest within phytoplankton communities. Copyright © 2016 Elsevier B.V. All rights reserved.

50 CFR 86.74 - What if I need more money?

Science.gov (United States)

2010-10-01

... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 false What if I need more money? 86.74 Section...) PROGRAM How States Manage Grants § 86.74 What if I need more money? Funds for grants are available only on a competitive basis. Therefore, if you need more money, you must compete in the next grant cycle. ...

If war is "just," so is abortion.

Science.gov (United States)

Kissling, F

1991-01-01

Currently Catholic bishops are applying an inconsistent ethical paradigm to the issues of war and abortion. Based on the seamless garment theory war, abortion and capital punishment are all immoral acts because they are of the same garment. They are all "killing acts" and as such they are immoral. However there is within the Catholic paradigm the idea of a just war. The just war theory states that the destruction of human life in war is justified if it is for a greater good. However abortion has no exceptions, there is no just abortion in the rules of the Catholic Church. The author takes the just war doctrine as presented by the Catholic Church and shows how it could easily apply to abortion. Both war and abortion involve the taking of a human life, but in the case of war the taking of a life is justified if it is done to protect your own life. The same exception in abortion would be to allow abortion when the mother's life is in danger. yet no such exception exists. The just war theory further states that was is necessary to protect national integrity, particularly if the violation erodes the quality of life for its citizens. The same exception for abortion would include allowing abortions for women who already have more children then they can care for or if having the child would erode the quality of life for the woman. Other aspects of the just war theory include the competence and goals of the national leaders. Women must also be allowed to be competent moral agents. Proponents of the seamless garment theory will bring up the fact that in a just war only combatants die yet the fetus is innocent. But no war has ever been fought without the loss of innocent civilians.

Analysis of the interacting partners eIF4F and 3'-CITE required for Melon necrotic spot virus cap-independent translation.

Science.gov (United States)

Miras, Manuel; Truniger, Verónica; Querol-Audi, Jordi; Aranda, Miguel A

2017-06-01

We have shown previously that the translation of Melon necrotic spot virus (MNSV, family Tombusviridae, genus Carmovirus) RNAs is controlled by a 3'-cap-independent translation enhancer (CITE), which is genetically and functionally dependent on the eukaryotic translation initiation factor (eIF) 4E. Here, we describe structural and functional analyses of the MNSV-Mα5 3'-CITE and its translation initiation factor partner. We first mapped the minimal 3'-CITE (Ma5TE) to a 45-nucleotide sequence, which consists of a stem-loop structure with two internal loops, similar to other I-shaped 3'-CITEs. UV crosslinking, followed by gel retardation assays, indicated that Ma5TE interacts in vitro with the complex formed by eIF4E + eIF4G 980-1159 (eIF4F p20 ), but not with each subunit alone or with eIF4E + eIF4G 1003-1092 , suggesting binding either through interaction with eIF4E following a conformational change induced by its binding to eIF4G 980-1159 , or through a double interaction with eIF4E and eIF4G 980-1159 . Critical residues for this interaction reside in an internal bulge of Ma5TE, so that their mutation abolished binding to eIF4E + eIF4G 1003-1092 and cap-independent translation. We also developed an in vivo system to test the effect of mutations in eIF4E in Ma5TE-driven cap-independent translation, showing that conserved amino acids in a positively charged RNA-binding motif around amino acid position 228, implicated in eIF4E-eIF4G binding or belonging to the cap-recognition pocket, are essential for cap-independent translation controlled by Ma5TE, and thus for the multiplication of MNSV. © 2016 BSPP AND JOHN WILEY & SONS LTD.

Rheb Inhibits Protein Synthesis by Activating the PERK-eIF2α Signaling Cascade

Directory of Open Access Journals (Sweden)

Richa Tyagi

2015-02-01

Full Text Available Rheb, a ubiquitous small GTPase, is well known to bind and activate mTOR, which augments protein synthesis. Inhibition of protein synthesis is also physiologically regulated. Thus, with cell stress, the unfolded protein response system leads to phosphorylation of the initiation factor eIF2α and arrest of protein synthesis. We now demonstrate a major role for Rheb in inhibiting protein synthesis by enhancing the phosphorylation of eIF2α by protein kinase-like ER kinase (PERK. Interplay between the stimulatory and inhibitory roles of Rheb may enable cells to modulate protein synthesis in response to varying environmental stresses.

40 CFR Table 1 to Subpart Jjjj of... - Operating Limits if Using Add-On Control Devices and Capture System

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2010-07-01

... Limits if Using Add-On Control Devices and Capture System If you are required to comply with operating... 40 Protection of Environment 12 2010-07-01 2010-07-01 true Operating Limits if Using Add-On Control Devices and Capture System 1 Table 1 to Subpart JJJJ of Part 63 Protection of Environment...

30 CFR 227.301 - What are a State's responsibilities if it performs audits?

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2010-07-01

... 30 Mineral Resources 2 2010-07-01 2010-07-01 false What are a State's responsibilities if it... Functions § 227.301 What are a State's responsibilities if it performs audits? If you perform audits you must: (a) Comply with the MMS Audit Procedures Manual and the Government Auditing Standards issued by...

45 CFR 261.56 - What happens if a parent cannot obtain needed child care?

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2010-10-01

... care arrangements are unavailable. (2) Refusal to work when an acceptable form of child care is... child care? 261.56 Section 261.56 Public Welfare Regulations Relating to Public Welfare OFFICE OF FAMILY....56 What happens if a parent cannot obtain needed child care? (a)(1) If the individual is a single...

Characterization of the functional role of nucleotides within the URE2 IRES element and the requirements for eIF2A-mediated repression.

Science.gov (United States)

Reineke, Lucas C; Merrick, William C

2009-12-01

Cap-independent initiation of translation is thought to promote protein synthesis on some mRNAs during times when cap-dependent initiation is down-regulated. However, the mechanism of cap-independent initiation is poorly understood. We have previously reported the secondary structure within the yeast minimal URE2 IRES element. In this study, we sought to investigate the mechanism of internal initiation in yeast by assessing the functional role of nucleotides within the minimal URE2 IRES element, and delineating the cis-sequences that modulate levels of internal initiation using a monocistronic reporter vector. Furthermore, we compared the eIF2A sensitivity of the URE2 IRES element with some of the invasive growth IRES elements using DeltaeIF2A yeast. We found that the stability of the stem-loop structure within the minimal URE2 IRES element is not a critical determinant of optimal IRES activity, and the downstream sequences that modulate URE2 IRES-mediated translation can be defined to discrete regions within the URE2 coding region. Repression of internal initiation on the URE2 minimal IRES element by eIF2A is not dependent on the stability of the secondary structure within the URE2 IRES element. Our data also indicate that eIF2A-mediated repression is not specific to the URE2 IRES element, as both the GIC1 and PAB1 IRES elements are repressed by eIF2A. These data provide valuable insights into the mRNA requirements for internal initiation in yeast, and insights into the mechanism of eIF2A-mediated suppression.

Defect in the GTPase activating protein (GAP) function of eIF5 causes repression of GCN4 translation.

Science.gov (United States)

Antony A, Charles; Alone, Pankaj V

2017-05-13

In eukaryotes, the eIF5 protein plays an important role in translation start site selection by providing the GAP (GTPase activating protein) function. However, in yeast translation initiation fidelity defective eIF5 G31R mutant causes preferential utilization of UUG as initiation codon and is termed as Suppressor of initiation codon (Sui - ) phenotype due to its hyper GTPase activity. The eIF5 G31R mutant dominantly represses GCN4 expression and confers sensitivity to 3-Amino-1,2,4-Trizole (3AT) induced starvation. The down-regulation of the GCN4 expression (Gcn - phenotype) in the eIF5 G31R mutant was not because of leaky scanning defects; rather was due to the utilization of upUUG initiation codons at the 5' regulatory region present between uORF1 and the main GCN4 ORF. Copyright © 2017 Elsevier Inc. All rights reserved.

40 CFR Table 2 to Subpart Oooo of... - Operating Limits if Using Add-On Control Devices and Capture System

Science.gov (United States)

2010-07-01

... OOOO of Part 63—Operating Limits if Using Add-On Control Devices and Capture System If you are required... 40 Protection of Environment 12 2010-07-01 2010-07-01 true Operating Limits if Using Add-On Control Devices and Capture System 2 Table 2 to Subpart OOOO of Part 63 Protection of Environment...

Role of p70S6K1-mediated phosphorylation of eIF4B and PDCD4 proteins in the regulation of protein synthesis.

Science.gov (United States)

Dennis, Michael D; Jefferson, Leonard S; Kimball, Scot R

2012-12-14

Modulation of mRNA binding to the 40 S ribosomal subunit during translation initiation controls not only global rates of protein synthesis but also regulates the pattern of protein expression by allowing for selective inclusion, or exclusion, of mRNAs encoding particular proteins from polysomes. The mRNA binding step is modulated by signaling through a protein kinase known as the mechanistic target of rapamycin complex 1 (mTORC1). mTORC1 directly phosphorylates the translational repressors eIF4E binding proteins (4E-BP) 1 and 2, releasing them from the mRNA cap binding protein eIF4E, thereby promoting assembly of the eIF4E·eIF4G complex. mTORC1 also phosphorylates the 70-kDa ribosomal protein S6 kinase 1 (p70S6K1), which subsequently phosphorylates eIF4B, and programmed cell death 4 (PDCD4), which sequesters eIF4A from the eIF4E·eIF4G complex, resulting in repressed translation of mRNAs with highly structured 5'-untranslated regions. In the present study, we compared the role of the 4E-BPs in the regulation of global rates of protein synthesis to that of eIF4B and PDCD4. We found that maintenance of eIF4E interaction with eIF4G was not by itself sufficient to sustain global rates of protein synthesis in the absence of mTORC1 signaling to p70S6K1; phosphorylation of both eIF4B and PDCD4 was additionally required. We also found that the interaction of eIF4E with eIF4G was maintained in the liver of fasted rats as well as in serum-deprived mouse embryo fibroblasts lacking both 4E-BP1 and 4E-BP2, suggesting that the interaction of eIF4G with eIF4E is controlled primarily through the 4E-BPs.

Surface enrichment with chrome and nitriding of IF steel under an abnormal glow discharge; Enriquecimento superficial com cromo e nitretacao do aco IF em descarga eletrica em regime anormal

Energy Technology Data Exchange (ETDEWEB)

Meira, S.R.; Borges, P.C., E-mail: sabrina.r.meira@gmail.com [Universidade Tecnologica Federal do Parana (UTFPR), Curitiba, PR (Brazil). Grupo de Materiais; Bernardelli, E.A. [Instituto Federal do Parana (IFPR), Paranagua, PR (Brazil). Laboratorio de Materiais

2014-07-01

The objective of this work is to evaluate the influence of surface enrichment of IF steel with chrome, and nitriding, the formation of the nitrided layer. Thus, IF steel samples were subjected to surface enrichment process, using 409 stainless steel as a target for sputtering, followed by plasma nitriding, both under a dc abnormal glow discharge. The enrichment treatment was operated at 1200 ° C for 3h. The nitriding treatment was operated at 510 ° C for 2 h. The influence of the treatments on the layers formed was studied through optical microscopy (OM), scan electron microscopy (SEM), X-ray diffraction (XRD) and Vickers microindentation. The results show that the enrichment is effective to enrich the IF surface, furthermore, improves the characteristics of nitriding, comparing nitriding samples to nitriding and enriched, was observed needles of nitrides, as well as a higher hardness, which is associated with the nitrides of chrome, on the nitriding and enriched samples. (author)

Thermal analyses of the IF-300 shipping cask

International Nuclear Information System (INIS)

Meier, J.K.

1978-07-01

In order to supply temperature data for structural testing and analysis of shipping casks, a series of thermal analyses using the TRUMP thermal analyzer program were performed on the GE IF-300 spent fuel shipping cask. Major conclusions of the analyses are: (1) Under normal cooling conditions and a cask heat load of 262,000 BTU/h, the seal area of the cask will be roughly 100 0 C (180 0 F) above the ambient surroundings. (2) Under these same conditions the uranium shield at the midpoint of the cask will be between 69 0 C (125 0 F) and 92 0 C (166 0 F) above the ambient surroundings. (3) Significant thermal gradients are not likely to develop between the head studs and the surrounding metal. (4) A representative time constant for the cask as a whole is on the order of one day

41 CFR 102-33.130 - If we hire CAS, what are our management responsibilities?

Science.gov (United States)

2010-07-01

... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false If we hire CAS, what are our management responsibilities? 102-33.130 Section 102-33.130 Public Contracts and Property... § 102-33.130 If we hire CAS, what are our management responsibilities? If you hire CAS, you are...

Catch Me If You Can

DEFF Research Database (Denmark)

Rehm, Matthias; André, Elisabeth

2005-01-01

? Masking ones real emotions with a smile is a naturally occuring example of such a discrepancy. But such masks are often deficient and thus subtle clues of lying and deceiving manifest themselves in facial expressions. The questions is how users will react to these clues if they are conveyed by an agent....... Will they render an application unattractive or on the contrary more human-like? In this paper, we examine such facial clues to deception and present the results of two empirical studies: i.) lies in monologues by a talking head presenting movies, ii.) lies in an interactive game of dice....

Molecular Regulation of the Mitochondrial F1Fo-ATPsynthase: Physiological and Pathological Significance of the Inhibitory Factor 1 (IF 1

Directory of Open Access Journals (Sweden)

Danilo Faccenda

2012-01-01

Full Text Available In mammals, the mitochondrial F1Fo-ATPsynthase sets out the energy homeostasis by producing the bulk of cellular ATP. As for every enzyme, the laws of thermodynamics command it; however, it is privileged to have a dedicated molecular regulator that controls its rotation. This is the so-called ATPase Inhibitory Factor 1 (IF1 that blocks its reversal to avoid the consumption of cellular ATP when the enzyme acts as an ATP hydrolase. Recent evidence has also demonstrated that IF1 may control the alignment of the enzyme along the mitochondrial inner membrane, thus increasing the interest for the molecule. We conceived this review to outline the fundamental knowledge of the F1Fo-ATPsynthase and link it to the molecular mechanisms by which IF1 regulates its way of function, with the ultimate goal to highlight this as an important and possibly unique means to control this indispensable enzyme in both physiological and pathological settings.

The Distribution of eIF4E-Family Members across Insecta

Directory of Open Access Journals (Sweden)

Gritta Tettweiler

2012-01-01

Full Text Available Insects are part of the earliest faunas that invaded terrestrial environments and are the first organisms that evolved controlled flight. Nowadays, insects are the most diverse animal group on the planet and comprise the majority of extant animal species described. Moreover, they have a huge impact in the biosphere as well as in all aspects of human life and economy; therefore understanding all aspects of insect biology is of great importance. In insects, as in all cells, translation is a fundamental process for gene expression. However, translation in insects has been mostly studied only in the model organism Drosophila melanogaster. We used all publicly available genomic sequences to investigate in insects the distribution of the genes encoding the cap-binding protein eIF4E, a protein that plays a crucial role in eukaryotic translation. We found that there is a diversity of multiple ortholog genes encoding eIF4E isoforms within the genus Drosophila. In striking contrast, insects outside this genus contain only a single eIF4E gene, related to D. melanogaster eIF4E-1. We also found that all insect species here analyzed contain only one Class II gene, termed 4E-HP. We discuss the possible evolutionary causes originating the multiplicity of eIF4E genes within the genus Drosophila.

Structural modelling and phylogenetic analyses of PgeIF4A2 (Eukaryotic translation initiation factor) from Pennisetum glaucum reveal signature motifs with a role in stress tolerance and development.

Science.gov (United States)

Agarwal, Aakrati; Mudgil, Yashwanti; Pandey, Saurabh; Fartyal, Dhirendra; Reddy, Malireddy K

2016-01-01

Eukaryotic translation initiation factor 4A (eIF4A) is an indispensable component of the translation machinery and also play a role in developmental processes and stress alleviation in plants and animals. Different eIF4A isoforms are present in the cytosol of the cell, namely, eIF4A1, eIF4A2, and eIF4A3 and their expression is tightly regulated in cap-dependent translation. We revealed the structural model of PgeIF4A2 protein using the crystal structure of Homo sapiens eIF4A3 (PDB ID: 2J0S) as template by Modeller 9.12. The resultant PgeIF4A2 model structure was refined by PROCHECK, ProSA, Verify3D and RMSD that showed the model structure is reliable with 77 % amino acid sequence identity with template. Investigation revealed two conserved signatures for ATP-dependent RNA Helicase DEAD-box conserved site (VLDEADEML) and RNA helicase DEAD-box type, Q-motif in sheet-turn-helix and α-helical region respectively. All these conserved motifs are responsible for response during developmental stages and stress tolerance in plants.

30 CFR 250.136 - How will MMS determine if my operating performance is unacceptable?

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 2 2010-07-01 2010-07-01 false How will MMS determine if my operating... Disqualification § 250.136 How will MMS determine if my operating performance is unacceptable? In determining if your operating performance is unacceptable, MMS will consider, individually or collectively: (a...

Rapid kinetics of iron responsive element (IRE) RNA/iron regulatory protein 1 and IRE-RNA/eIF4F complexes respond differently to metal ions.

Science.gov (United States)

Khan, Mateen A; Ma, Jia; Walden, William E; Merrick, William C; Theil, Elizabeth C; Goss, Dixie J

2014-06-01

Metal ion binding was previously shown to destabilize IRE-RNA/IRP1 equilibria and enhanced IRE-RNA/eIF4F equilibria. In order to understand the relative importance of kinetics and stability, we now report rapid rates of protein/RNA complex assembly and dissociation for two IRE-RNAs with IRP1, and quantitatively different metal ion response kinetics that coincide with the different iron responses in vivo. kon, for FRT IRE-RNA binding to IRP1 was eight times faster than ACO2 IRE-RNA. Mn(2+) decreased kon and increased koff for IRP1 binding to both FRT and ACO2 IRE-RNA, with a larger effect for FRT IRE-RNA. In order to further understand IRE-mRNA regulation in terms of kinetics and stability, eIF4F kinetics with FRT IRE-RNA were determined. kon for eIF4F binding to FRT IRE-RNA in the absence of metal ions was 5-times slower than the IRP1 binding to FRT IRE-RNA. Mn(2+) increased the association rate for eIF4F binding to FRT IRE-RNA, so that at 50 µM Mn(2+) eIF4F bound more than 3-times faster than IRP1. IRP1/IRE-RNA complex has a much shorter life-time than the eIF4F/IRE-RNA complex, which suggests that both rate of assembly and stability of the complexes are important, and that allows this regulatory system to respond rapidly to change in cellular iron. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Esophageal cancer alters the expression of nuclear pore complex binding protein Hsc70 and eIF5A-1.

Science.gov (United States)

Moghanibashi, Mehdi; Rastgar Jazii, Ferdous; Soheili, Zahra-Soheila; Zare, Maryam; Karkhane, Aliasghar; Parivar, Kazem; Mohamadynejad, Parisa

2013-06-01

Nuclear pore complex (NPC) is the only corridor for macromolecules exchange between nucleus and cytoplasm. NPC and its components, nucleoporins, play important role in the diverse physiological processes including macromolecule exchange, chromosome segregation, apoptosis and gene expression. Recent reports also suggest involvement of nucleoporins in carcinogenesis. Applying proteomics, we analyzed expression pattern of the NPC components in a newly established esophageal cancer cell line from Persia (Iran), the high-risk region for esophageal cancer. Our results indicate overexpression of Hsc70 and downregulation of subunit alpha type-3 of proteasome, calpain small subunit 1, and eIF5A-1. Among these proteins, Hsc70 and eIF5A-1 are in direct interaction with NPC and involved in the nucleocytoplasmic exchange. Hsc70 plays a critical role as a chaperone in the formation of a cargo-receptor complex in nucleocytoplasmic transport. On the other hand, it is an NPC-associated protein that binds to nucleoporins and contributes in recycling of the nucleocytoplasmic transport receptors in mammals and affects transport of proteins between nucleus and cytoplasm. The other nuclear pore interacting protein: eIF5A-1 binds to the several nucleoporins and participates in nucleocytoplasmic transport. Altered expression of Hsc70 and eIF5A-1 may cause defects in nucleocytoplasmic transport and play a role in esophageal carcinogenesis.

Diversity of Eukaryotic Translational Initiation Factor eIF4E in Protists.

Science.gov (United States)

Jagus, Rosemary; Bachvaroff, Tsvetan R; Joshi, Bhavesh; Place, Allen R

2012-01-01

The greatest diversity of eukaryotic species is within the microbial eukaryotes, the protists, with plants and fungi/metazoa representing just two of the estimated seventy five lineages of eukaryotes. Protists are a diverse group characterized by unusual genome features and a wide range of genome sizes from 8.2 Mb in the apicomplexan parasite Babesia bovis to 112,000-220,050 Mb in the dinoflagellate Prorocentrum micans. Protists possess numerous cellular, molecular and biochemical traits not observed in "text-book" model organisms. These features challenge some of the concepts and assumptions about the regulation of gene expression in eukaryotes. Like multicellular eukaryotes, many protists encode multiple eIF4Es, but few functional studies have been undertaken except in parasitic species. An earlier phylogenetic analysis of protist eIF4Es indicated that they cannot be grouped within the three classes that describe eIF4E family members from multicellular organisms. Many more protist sequences are now available from which three clades can be recognized that are distinct from the plant/fungi/metazoan classes. Understanding of the protist eIF4Es will be facilitated as more sequences become available particularly for the under-represented opisthokonts and amoebozoa. Similarly, a better understanding of eIF4Es within each clade will develop as more functional studies of protist eIF4Es are completed.

Origins of robustness in translational control via eukaryotic translation initiation factor (eIF) 2.

Science.gov (United States)

Khan, Mohammad Farhan; Spurgeon, Sarah; von der Haar, Tobias

2018-05-14

Phosphorylation of eukaryotic translation initiation factor 2 (eIF2) is one of the best studied and most widely used means for regulating protein synthesis activity in eukaryotic cells. This pathway regulates protein synthesis in response to stresses, viral infections, and nutrient depletion, among others. We present analyses of an ordinary differential equation-based model of this pathway, which aim to identify its principal robustness-conferring features. Our analyses indicate that robustness is a distributed property, rather than arising from the properties of any one individual pathway species. However, robustness-conferring properties are unevenly distributed between the different species, and we identify a guanine nucleotide dissociation inhibitor (GDI) complex as a species that likely contributes strongly to the robustness of the pathway. Our analyses make further predictions on the dynamic response to different types of kinases that impinge on eIF2. Copyright © 2018 Elsevier Ltd. All rights reserved.

30 CFR 250.135 - What will MMS do if my operating performance is unacceptable?

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 2 2010-07-01 2010-07-01 false What will MMS do if my operating performance is....135 What will MMS do if my operating performance is unacceptable? If your operating performance is unacceptable, MMS may disapprove or revoke your designation as operator on a single facility or multiple...

Helper component proteinase of the genus Potyvirus is an interaction partner of translation initiation factors eIF(iso)4E and eIF4E and contains a 4E binding motif.

Science.gov (United States)

Ala-Poikela, Marjo; Goytia, Elisa; Haikonen, Tuuli; Rajamäki, Minna-Liisa; Valkonen, Jari P T

2011-07-01

The multifunctional helper component proteinase (HCpro) of potyviruses (genus Potyvirus; Potyviridae) shows self-interaction and interacts with other potyviral and host plant proteins. Host proteins that are pivotal to potyvirus infection include the eukaryotic translation initiation factor eIF4E and the isoform eIF(iso)4E, which interact with viral genome-linked protein (VPg). Here we show that HCpro of Potato virus A (PVA) interacts with both eIF4E and eIF(iso)4E, with interactions with eIF(iso)4E being stronger, as judged by the data of a yeast two-hybrid system assay. A bimolecular fluorescence complementation assay on leaves of Nicotiana benthamiana showed that HCpro from three potyviruses (PVA, Potato virus Y, and Tobacco etch virus) interacted with the eIF(iso)4E and eIF4E of tobacco (Nicotiana tabacum); interactions with eIF(iso)4E and eIF4E of potato (Solanum tuberosum) were weaker. In PVA-infected cells, interactions between HCpro and tobacco eIF(iso)4E were confined to round structures that colocalized with 6K2-induced vesicles. Point mutations introduced to a 4E binding motif identified in the C-terminal region of HCpro debilitated interactions of HCpro with translation initiation factors and were detrimental to the virulence of PVA in plants. The 4E binding motif conserved in HCpro of potyviruses and HCpro-initiation factor interactions suggest new roles for HCpro and/or translation factors in the potyvirus infection cycle.

20 CFR 408.1226 - What happens if you are underpaid?

Science.gov (United States)

2010-04-01

... Section 408.1226 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SPECIAL BENEFITS FOR CERTAIN WORLD WAR II VETERANS Federal Administration of State Recognition Payments § 408.1226 What happens if you are underpaid? If we determine that you are due an underpayment of State recognition payments, we will pay the...

Targeting eukaryotic translation in mesothelioma cells with an eIF4E-specific antisense oligonucleotide.

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Blake A Jacobson

Full Text Available BACKGROUND: Aberrant cap-dependent translation is implicated in tumorigenesis in multiple tumor types including mesothelioma. In this study, disabling the eIF4F complex by targeting eIF4E with eIF4E-specific antisense oligonucleotide (4EASO is assessed as a therapy for mesothelioma. METHODS: Mesothelioma cells were transfected with 4EASO, designed to target eIF4E mRNA, or mismatch-ASO control. Cell survival was measured in mesothelioma treated with 4EASO alone or combined with either gemcitabine or pemetrexed. Levels of eIF4E, ODC, Bcl-2 and β-actin were assessed following treatment. Binding to a synthetic cap-analogue was used to study the strength of eIF4F complex activation following treatment. RESULTS: eIF4E level and the formation of eIF4F cap-complex decreased in response to 4EASO, but not mismatch control ASO, resulting in cleavage of PARP indicating apoptosis. 4EASO treatment resulted in dose dependent decrease in eIF4E levels, which corresponded to cytotoxicity of mesothelioma cells. 4EASO resulted in decreased levels of eIF4E in non-malignant LP9 cells, but this did not correspond to increased cytotoxicity. Proteins thought to be regulated by cap-dependent translation, Bcl-2 and ODC, were decreased upon treatment with 4EASO. Combination therapy of 4EASO with pemetrexed or gemcitabine further reduced cell number. CONCLUSION: 4EASO is a novel drug that causes apoptosis and selectively reduces eIF4E levels, eIF4F complex formation, and proliferation of mesothelioma cells. eIF4E knockdown results in decreased expression of anti-apoptotic and pro-growth proteins and enhances chemosensitivity.

Translation initiation complex eIF4F is a therapeutic target for dual mTOR kinase inhibitors in non-Hodgkin lymphoma

Science.gov (United States)

Stenson, Mary J.; Maurer, Matthew J.; Wellik, Linda E.; Link, Brian; Hege, Kristen; Dogan, Ahmet; Sotomayor, Eduardo; Witzig, Thomas; Gupta, Mamta

2015-01-01

Deregulated mRNA translation has been implicated in disease development and in part is controlled by a eukaryotic initiation complex eIF4F (composed of eIF4E, eIF4G and eIF4A). We demonstrate here that the cap bound fraction from lymphoma cells was enriched with eIF4G and eIF4E indicating that lymphoma cells exist in an activated translational state. Moreover, 77% (110/142) of diffuse large B cell lymphoma tumors expressed eIF4E and this was associated with an inferior event free survival. Over-expression of wild-type eIF4E (eIF4EWT) but not cap-mutant eIF4E (eIF4Ecap mutant) increased the activation of the eIF4F complex. Treatment with the active-site dual mTOR inhibitor CC214-1 reduced the level of the eIF4F complex by decreasing the cap bound fraction of eIF4G and increasing the levels of 4E-BP1. CC214-1 inhibited both the cap dependent and global protein translation. CC214-1 inhibited c-Myc, and cyclin D3 translation by decreasing polysomal fractions from lymphoma cells. Inhibition of eIF4E with shRNA further decreased the CC214-1 induced inhibition of the eIF4F complex, c-Myc, cyclin D3 translation, and colony formation. These studies demonstrate that the eIF4F complex is deregulated in aggressive lymphoma and that dual mTOR therapy has therapeutic potential in these patients. PMID:25839159

The RNA Polymerase II C-Terminal Domain Phosphatase-Like Protein FIERY2/CPL1 Interacts with eIF4AIII and Is Essential for Nonsense-Mediated mRNA Decay in Arabidopsis

KAUST Repository

Cui, Peng; Chen, Tao; Qin, Tao; Ding, Feng; Wang, Zhenyu; Chen, Hao; Xiong, Liming

2016-01-01

© 2016 American Society of Plant Biologists. All rights reserved. Nonsense-mediated decay (NMD) is a posttranscriptional surveillance mechanism in eukaryotes that recognizes and degrades transcripts with premature translation-termination codons. The RNA polymerase II C-terminal domain phosphatase-like protein FIERY2 (FRY2; also known as C-TERMINAL DOMAIN PHOSPHATASE-LIKE1 [CPL1]) plays multiple roles in RNA processing in Arabidopsis thaliana. Here, we found that FRY2/CPL1 interacts with two NMD factors, eIF4AIII and UPF3, and is involved in the dephosphorylation of eIF4AIII. This dephosphorylation retains eIF4AIII in the nucleus and limits its accumulation in the cytoplasm. By analyzing RNA-seq data combined with quantitative RT-PCR validation, we found that a subset of alternatively spliced transcripts and 59-extended mRNAs with NMD-eliciting features accumulated in the fry2-1 mutant, cycloheximidetreated wild type, and upf3 mutant plants, indicating that FRY2 is essential for the degradation of these NMD transcripts.

The RNA Polymerase II C-Terminal Domain Phosphatase-Like Protein FIERY2/CPL1 Interacts with eIF4AIII and Is Essential for Nonsense-Mediated mRNA Decay in Arabidopsis

KAUST Repository

Cui, Peng

2016-02-18

© 2016 American Society of Plant Biologists. All rights reserved. Nonsense-mediated decay (NMD) is a posttranscriptional surveillance mechanism in eukaryotes that recognizes and degrades transcripts with premature translation-termination codons. The RNA polymerase II C-terminal domain phosphatase-like protein FIERY2 (FRY2; also known as C-TERMINAL DOMAIN PHOSPHATASE-LIKE1 [CPL1]) plays multiple roles in RNA processing in Arabidopsis thaliana. Here, we found that FRY2/CPL1 interacts with two NMD factors, eIF4AIII and UPF3, and is involved in the dephosphorylation of eIF4AIII. This dephosphorylation retains eIF4AIII in the nucleus and limits its accumulation in the cytoplasm. By analyzing RNA-seq data combined with quantitative RT-PCR validation, we found that a subset of alternatively spliced transcripts and 59-extended mRNAs with NMD-eliciting features accumulated in the fry2-1 mutant, cycloheximidetreated wild type, and upf3 mutant plants, indicating that FRY2 is essential for the degradation of these NMD transcripts.

Translation initiation factor AteIF(iso4E is involved in selective mRNA translation in Arabidopsis thaliana seedlings.

Directory of Open Access Journals (Sweden)

Ana Valeria Martínez-Silva

Full Text Available One of the most regulated steps of translation initiation is the recruitment of mRNA by the translation machinery. In eukaryotes, this step is mediated by the 5'end cap-binding factor eIF4E bound to the bridge protein eIF4G and forming the eIF4F complex. In plants, different isoforms of eIF4E and eIF4G form the antigenically distinct eIF4F and eIF(iso4F complexes proposed to mediate selective translation. Using a microarray analysis of polyribosome- and non-polyribosome-purified mRNAs from 15 day-old Arabidopsis thaliana wild type [WT] and eIF(iso4E knockout mutant [(iso4E-1] seedlings we found 79 transcripts shifted from polyribosomes toward non-polyribosomes, and 47 mRNAs with the opposite behavior in the knockout mutant. The translationally decreased mRNAs were overrepresented in root-preferentially expressed genes and proteins from the endomembrane system, including several transporters such as the phosphate transporter PHOSPHATE1 (PHO1, Sucrose transporter 3 (SUC3, ABC transporter-like with ATPase activity (MRP11 and five electron transporters, as well as signal transduction-, protein modification- and transcription-related proteins. Under normal growth conditions, eIF(iso4E expression under the constitutive promoter 35 S enhanced the polyribosomal recruitment of PHO1 supporting its translational preference for eIF(iso4E. Furthermore, under phosphate deficiency, the PHO1 protein increased in the eIF(iso4E overexpressing plants and decreased in the knockout mutant as compared to wild type. In addition, the knockout mutant had larger root, whereas the 35 S directed expression of eIF(iso4E caused shorter root under normal growth conditions, but not under phosphate deficiency. These results indicate that selective translation mediated by eIF(iso4E is relevant for Arabidopsis root development under normal growth conditions.

Modulation of translation-initiation in CHO-K1 cells by rapamycin-induced heterodimerization of engineered eIF4G fusion proteins.

Science.gov (United States)

Schlatter, Stefan; Senn, Claudia; Fussenegger, Martin

2003-07-20

Translation-initiation is a predominant checkpoint in mammalian cells which controls protein synthesis and fine-tunes the flow of information from gene to protein. In eukaryotes, translation-initiation is typically initiated at a 7-methyl-guanylic acid cap posttranscriptionally linked to the 5' end of mRNAs. Alternative cap-independent translation-initiation involves 5' untranslated regions (UTR) known as internal ribosome entry sites, which adopt a particular secondary structure. Translation-initiating ribosome assembly at cap or IRES elements is mediated by a multiprotein complex of which the initiation factor 4F (eIF4F) consisting of eIF4A (helicase), eIF4E (cap-binding protein), and eIF4G is a major constituent. eIF4G is a key target of picornaviral protease 2A, which cleaves this initiation factor into eIF4G(Delta) and (Delta)eIF4G to redirect the cellular translation machinery exclusively to its own IRES-containing transcripts. We have designed a novel translation control system (TCS) for conditional as well as adjustable translation of cap- and IRES-dependent transgene mRNAs in mammalian cells. eIF4G(Delta) and (Delta)eIF4G were fused C- and N-terminally to the FK506-binding protein (FKBP) and the FKBP-rapamycin-binding domain (FRB) of the human FKBP-rapamycin-associated protein (FRAP), respectively. Rapamycin-induced heterodimerization of eIF4G(Delta)-FKBP and FRB-(Delta)eIF4G fusion proteins reconstituted a functional chimeric elongation factor 4G in a dose-dependent manner. Rigorous quantitative expression analysis of cap- and IRES-dependent SEAP- (human placental secreted alkaline phosphatase) and luc- (Photinus pyralis luciferase) encoding reporter constructs confirmed adjustable translation control and revealed increased production of desired proteins in response to dimerization-induced heterologous eIF4G in Chinese hamster ovary (CHO-K1) cells. Copyright 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 83: 210-225, 2003.

FUS-DDIT3 prevents the development of adipocytic precursors in liposarcoma by repressing PPARgamma and C/EBPalpha and activating eIF4E.

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Pedro A Pérez-Mancera

Full Text Available BACKGROUND: FUS-DDIT3 is a chimeric protein generated by the most common chromosomal translocation t(12;16(q13;p11 linked to liposarcomas, which are characterized by the accumulation of early adipocytic precursors. Current studies indicate that FUS-DDIT3- liposarcoma develops from uncommitted progenitors. However, the precise mechanism whereby FUS-DDIT3 contributes to the differentiation arrest remains to be elucidated. METHODOLOGY/PRINCIPAL FINDINGS: Here we have characterized the adipocyte regulatory protein network in liposarcomas of FUS-DITT3 transgenic mice and showed that PPARgamma2 and C/EBPalpha expression was altered. Consistent with in vivo data, FUS-DDIT3 MEFs and human liposarcoma cell lines showed a similar downregulation of both PPARgamma2 and C/EBPalpha expression. Complementation studies with PPARgamma but not C/EBPalpha rescued the differentiation block in committed adipocytic precursors expressing FUS-DDIT3. Our results further show that FUS-DDIT3 interferes with the control of initiation of translation by upregulation of the eukaryotic translation initiation factors eIF2 and eIF4E both in FUS-DDIT3 mice and human liposarcomas cell lines, explaining the shift towards the truncated p30 isoform of C/EBPalpha in liposarcomas. Suppression of the FUS-DDIT3 transgene did rescue this adipocyte differentiation block. Moreover, eIF4E was also strongly upregulated in normal adipose tissue of FUS-DDIT3 transgenic mice, suggesting that overexpression of eIF4E may be a primary event in the initiation of liposarcomas. Reporter assays showed FUS-DDIT3 is involved in the upregulation of eIF4E in liposarcomas and that both domains of the fusion protein are required for affecting eIF4E expression. CONCLUSIONS/SIGNIFICANCE: Taken together, this study provides evidence of the molecular mechanisms involve in the disruption of normal adipocyte differentiation program in liposarcoma harbouring the chimeric gene FUS-DDIT3.

Signalling in IF-games : a tricky business

NARCIS (Netherlands)

Janssen, T.M.V.; Dechesne, F.; Benthem, van J.F.A.K.; Heinzmann, G.; Rebuschi, M.; Visser, H.

2006-01-01

The paper studies the phenomenon of signalling in logics for imperfect information, such as Hintikka’s IF logic. It is shown that signalling is a phenomenon that at the one hand is essential for the semantics, but at the other hand is a source of tricky phenomena. Several properties which in the

Immunogenicity and efficacy of a bivalent DNA vaccine containing LeIF and TSA genes against murine cutaneous leishmaniasis.

Science.gov (United States)

Maspi, Nahid; Ghaffarifar, Fatemeh; Sharifi, Zohreh; Dalimi, Abdolhossein; Dayer, Mohammad Saaid

2017-03-01

There is no effective vaccine for the prevention and elimination of leishmaniasis. For this reason, we assessed the protective effects of DNA vaccines containing LeIF, TSA genes alone, or LeIF-TSA fusion against cutaneous leishmaniasis pEGFP-N1 plasmid (empty vector) and phosphate buffer saline (PBS) were used as control groups. Therefore, cellular and humoral immune responses were evaluated before and after the challenge with Leishmania major. Lesion diameter was also measured 3-12 weeks after challenge. All immunized mice with plasmid DNA encoding Leishmania antigens induced the partial immunity characterized by increased IFN-γ and IgG2a levels compared with control groups (p TSA, and LeIF-TSA, respectively, than in PBS group at 12th week post infection. IFN/IL-4 and IgG2a/IgG1 ratios indicated that group receiving LeIF-TSA fusion had the highest IFN-γ and IgG2a levels. In this study, DNA immunization promoted Th1 immune response characterized by higher IFN-γ and IgG2a levels and also reduction in lesion size. These results showed that a bivalent vaccine containing two distinct antigens may induce more potent immune responses against leishmaniasis. © 2017 APMIS. Published by John Wiley & Sons Ltd.

41 CFR 102-33.125 - If we use Federal aircraft, what are our management responsibilities?

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2010-07-01

... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false If we use Federal aircraft, what are our management responsibilities? 102-33.125 Section 102-33.125 Public Contracts and... Parts Overview § 102-33.125 If we use Federal aircraft, what are our management responsibilities? If you...

A note on 'Some results on the IF-normed spaces'

International Nuclear Information System (INIS)

Saadati, Reza

2009-01-01

Recently, Lael and Nourouzi [Some results on the IF-normed spaces. Chaos, Solitons and Fractals 2006; doi:10.1016/j.chaos.2006.10.019] introduced and studied a new notation of IF-normed spaces by using the idea of intuitionistic fuzzy normed spaces due to Saadati and Park [On the intuitionistic fuzzy topological spaces. Chaos, Solitons and Fractals 2006;27:331-44], a special continuous t-norm i.e. min and a special continuous s-norm i.e. max. In this note, we consider the modified definition of IF-normed space i.e. LF-normed spaces and prove the open mapping and closed graph theorems for this space using arbitrary continuous t-norm.

On Determining if Tree-based Networks Contain Fixed Trees.

Science.gov (United States)

Anaya, Maria; Anipchenko-Ulaj, Olga; Ashfaq, Aisha; Chiu, Joyce; Kaiser, Mahedi; Ohsawa, Max Shoji; Owen, Megan; Pavlechko, Ella; St John, Katherine; Suleria, Shivam; Thompson, Keith; Yap, Corrine

2016-05-01

We address an open question of Francis and Steel about phylogenetic networks and trees. They give a polynomial time algorithm to decide if a phylogenetic network, N, is tree-based and pose the problem: given a fixed tree T and network N, is N based on T? We show that it is [Formula: see text]-hard to decide, by reduction from 3-Dimensional Matching (3DM) and further that the problem is fixed-parameter tractable.

IfA Catalogs of Solar Data Products

Science.gov (United States)

Habbal, Shadia R.; Scholl, I.; Morgan, H.

2009-05-01

This paper presents a new set of online catalogs of solar data products. The IfA Catalogs of Solar Data Products were developed to enhance the scientific output of coronal images acquired from ground and space, starting with the SoHO era. Image processing tools have played a significant role in the production of these catalogs [Morgan et al. 2006, 2008, Scholl and Habbal 2008]. Two catalogs are currently available at http://alshamess.ifa.hawaii.edu/ : 1) Catalog of daily coronal images: One coronal image per day from EIT, MLSO and LASCO/C2 and C3 have been processed using the Normalizing Radial-Graded-Filter (NRGF) image processing tool. These images are available individually or as composite images. 2) Catalog of LASCO data: The whole LASCO dataset has been re-processed using the same method. The user can search files by dates and instruments, and images can be retrieved as JPEG or FITS files. An option to make on-line GIF movies from selected images is also available. In addition, the LASCO data set can be searched from existing CME catalogs (CDAW and Cactus). By browsing one of the two CME catalogs, the user can refine the query and access LASCO data covering the time frame of a CME. The catalogs will be continually updated as more data become publicly available.

Characterization of the Expression of the RNA Binding Protein eIF4G1 and Its Clinicopathological Correlation with Serous Ovarian Cancer.

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Lanfang Li

Full Text Available Ovarian cancer is the most lethal type of malignant tumor in gynecological cancers and is associated with a high percentage of late diagnosis and chemotherapy resistance. Thus, it is urgent to identify a tumor marker or a molecular target that allows early detection and effective treatment. RNA-binding proteins (RBPs are crucial in various cellular processes at the post-transcriptional level. The eukaryotic translation initiation factor 4 gamma, 1(eIF4G1, an RNA-binding protein, facilitates the recruitment of mRNA to the ribosome, which is a rate-limiting step during the initiation phase of protein synthesis. However, little is known regarding the characteristics of eIF4G1 expression and its clinical significance in ovarian cancer. Therefore, we propose to investigate the expression and clinicopathological significance of eIF4G1 in ovarian cancer patients.We performed Real-time PCR in 40 fresh serous ovarian cancer tissues and 27 normal ovarian surface epithelial cell specimens to assess eIF4G1mRNA expression. Immunohistochemistry (IHC was used to examine the expression of eIF4G1 at the protein level in 134 patients with serous ovarian cancer and 18 normal ovarian tissues. Statistical analysis was conducted to determine the correlation of the eIF4G1 protein levels with the clinicopathological characteristics and prognosis in ovarian cancer.The expression of eIF4G1 was upregulated in serous ovarian cancer tissues at both the mRNA (P = 0.0375 and the protein (P = 0.0007 levels. The eIF4G1 expression was significantly correlated with the clinical tumor stage (P = 0.0004 and omentum metastasis (P = 0.024. Moreover, patients with low eIF4G1 protein expression had a longer overall survival time (P = 0.026.These data revealed that eIF4G1 is markedly expressed in serous ovarian cancer and that upregulation of the eIF4G1 protein expression is significantly associated with an advanced tumor stage. Besides, the patients with lower expression of eIF4G1 tend

40 CFR Table 1 to Subpart Ssss of... - Operating Limits if Using Add-on Control Devices and Capture System

Science.gov (United States)

2010-07-01

... Using Add-on Control Devices and Capture System If you are required to comply with operating limits by... 40 Protection of Environment 12 2010-07-01 2010-07-01 true Operating Limits if Using Add-on Control Devices and Capture System 1 Table 1 to Subpart SSSS of Part 63 Protection of Environment...

Hydroxychloroquine reduces heart rate by modulating the hyperpolarization-activated current If: Novel electrophysiological insights and therapeutic potential

Science.gov (United States)

Capel, Rebecca A.; Herring, Neil; Kalla, Manish; Yavari, Arash; Mirams, Gary R.; Douglas, Gillian; Bub, Gil; Channon, Keith; Paterson, David J.; Terrar, Derek A.; Burton, Rebecca-Ann B.

2015-01-01

Background Bradycardic agents are of interest for the treatment of ischemic heart disease and heart failure, as heart rate is an important determinant of myocardial oxygen consumption. Objectives The purpose of this study was to investigate the propensity of hydroxychloroquine (HCQ) to cause bradycardia. Methods We assessed the effects of HCQ on (1) cardiac beating rate in vitro (mice); (2) the “funny” current (If) in isolated guinea pig sinoatrial node (SAN) myocytes (1, 3, 10 µM); (3) heart rate and blood pressure in vivo by acute bolus injection (rat, dose range 1–30 mg/kg), (4) blood pressure and ventricular function during feeding (mouse, 100 mg/kg/d for 2 wk, tail cuff plethysmography, anesthetized echocardiography). Results In mouse atria, spontaneous beating rate was significantly (P < .05) reduced (by 9% ± 3% and 15% ± 2% at 3 and 10 µM HCQ, n = 7). In guinea pig isolated SAN cells, HCQ conferred a significant reduction in spontaneous action potential firing rate (17% ± 6%, 1 μM dose) and a dose-dependent reduction in If (13% ± 3% at 1 µM; 19% ± 2% at 3 µM). Effects were also observed on L-type calcium ion current (ICaL) (12% ± 4% reduction) and rapid delayed rectifier potassium current (IKr) (35% ± 4%) at 3 µM. Intravenous HCQ decreased heart rate in anesthetized rats (14.3% ± 1.1% at 15mg/kg; n = 6) without significantly reducing mean arterial blood pressure. In vivo feeding studies in mice showed no significant change in systolic blood pressure nor left ventricular function. Conclusions We have shown that HCQ acts as a bradycardic agent in SAN cells, in atrial preparations, and in vivo. HCQ slows the rate of spontaneous action potential firing in the SAN through multichannel inhibition, including that of If. PMID:26025323

Ectopic expression of eIF4E-transporter triggers the movement of eIF4E into P-bodies, inhibiting steady-state translation but not the pioneer round of translation

International Nuclear Information System (INIS)

Lee, Hyung Chul; Cho, Hana; Kim, Yoon Ki

2008-01-01

Nonsense-mediated mRNA decay (NMD) is the best-characterized mRNA surveillance mechanism; this process removes faulty mRNAs harboring premature termination codons (PTCs). NMD targets newly synthesized mRNAs bound by nuclear cap-binding proteins 80/20 (CBP80/20) and exon junction complex (EJC), the former of which is thought to recruit the ribosome to initiate the pioneer round of translation. After completion of the pioneer round of translation, CBP80/20 is replaced by the cytoplasmic cap-binding protein eIF4E, which mediates steady-state translation in the cytoplasm. Here, we show that overexpression of eIF4E-T preferentially inhibits cap-dependent steady-state translation, but not the pioneer round of translation. We also demonstrate that overexpression of eIF4E-T or Dcp1a triggers the movement of eIF4E into the processing bodies. These results suggest that the pioneer round of translation differs from steady-state translation in terms of ribosome recruitment

Does eIF3 promote reinitiation after translation of short upstream ORFs also in mammalian cells?

Czech Academy of Sciences Publication Activity Database

Hronová, Vladislava; Mohammad, Mahabub Pasha; Wagner, Susan; Pánek, Josef; Gunišová, Stanislava; Zeman, Jakub; Poncová, Kristýna; Valášek, Leoš Shivaya

2017-01-01

Roč. 14, č. 12 (2017), s. 1660-1667 ISSN 1547-6286 R&D Projects: GA ČR GA15-10116S Institutional support: RVO:61388971 Keywords : ATF4 * eIF3 * GCN4 Subject RIV: EE - Microbiology, Virology OBOR OECD: Developmental biology Impact factor: 3.900, year: 2016

No longer "if," but "when": the coming abbreviated approval pathway for follow-on biologics.

Science.gov (United States)

Kelly, Jeremiah J; David, Michael

2009-01-01

Abbreviated approval of follow-on biologics involves answering complex scientific, legal, and policy questions. The Food and Drug Administration (FDA or the Agency) asserts that it lacks the statutory authority to approve follow-on versions of biologics licensed under Section 351 of the Public Health Service Act (PHSA). Despite persuasive arguments to the contrary the one hundred and tenth Congress entertained four legislative proposals to give FDA this authority, each markedly different. It is no longer a question of "if," but "when" FDA will receive authority to review and license abbreviated applications for follow-on biologics. Any legislation in the one hundred and eleventh Congress must determine: (1) if FDA should be granted authority to develop an abbreviated pathway through rulemaking or guidance; (2) if human clinical trials should be mandatory or discretionary; (3) the feasibility of interchangeability determinations in light of patient safety concerns; (4) the duration of marketing exclusivity for associated products; (5) which products are eligible for follow-on approval; and (6) the degree to which uniformity is achievable between the FD&C Act and the PHSA. This paper recommends the one hundred and eleventh Congress strike a balance between patient safety, incentives for product innovation, price competition, and the need for a flexible, transparent process that capitalizes on FDA's growing expertise with follow-on biologics approvals under Section 505(b)(2) of the FD&C Act.

A biochemical framework for eIF4E-dependent mRNA export and nuclear recycling of the export machinery.

Science.gov (United States)

Volpon, Laurent; Culjkovic-Kraljacic, Biljana; Sohn, Hye Seon; Blanchet-Cohen, Alexis; Osborne, Michael J; Borden, Katherine L B

2017-06-01

The eukaryotic translation initiation factor eIF4E acts in the nuclear export and translation of a subset of mRNAs. Both of these functions contribute to its oncogenic potential. While the biochemical mechanisms that underlie translation are relatively well understood, the molecular basis for eIF4E's role in mRNA export remains largely unexplored. To date, over 3000 transcripts, many encoding oncoproteins, were identified as potential nuclear eIF4E export targets. These target RNAs typically contain a ∼50-nucleotide eIF4E sensitivity element (4ESE) in the 3' UTR and a 7-methylguanosine cap on the 5' end. While eIF4E associates with the cap, an unknown factor recognizes the 4ESE element. We previously identified cofactors that functionally interacted with eIF4E in mammalian cell nuclei including the leucine-rich pentatricopeptide repeat protein LRPPRC and the export receptor CRM1/XPO1. LRPPRC simultaneously interacts with both eIF4E bound to the 5' mRNA cap and the 4ESE element in the 3' UTR. In this way, LRPPRC serves as a specificity factor to recruit 4ESE-containing RNAs within the nucleus. Further, we show that CRM1 directly binds LRPPRC likely acting as the export receptor for the LRPPRC-eIF4E-4ESE RNA complex. We also found that Importin 8, the nuclear importer for cap-free eIF4E, imports RNA-free LRPPRC, potentially providing both coordinated nuclear recycling of the export machinery and an important surveillance mechanism to prevent futile export cycles. Our studies provide the first biochemical framework for the eIF4E-dependent mRNA export pathway. © 2017 Volpon et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

29 CFR 37.84 - What happens if CRC does not have jurisdiction over a complaint?

Science.gov (United States)

2010-07-01

... 29 Labor 1 2010-07-01 2010-07-01 true What happens if CRC does not have jurisdiction over a complaint? 37.84 Section 37.84 Labor Office of the Secretary of Labor IMPLEMENTATION OF THE... Procedures § 37.84 What happens if CRC does not have jurisdiction over a complaint? If CRC does not have...

Conservatism and "copy-if-better" in chimpanzees (Pan troglodytes).

Science.gov (United States)

van Leeuwen, Edwin J C; Call, Josep

2017-05-01

Social learning is predicted to evolve in socially living animals provided the learning process is not random but biased by certain socio-ecological factors. One bias of particular interest for the emergence of (cumulative) culture is the tendency to forgo personal behaviour in favour of relatively better variants observed in others, also known as the "copy-if-better" strategy. We investigated whether chimpanzees employ copy-if-better in a simple token-exchange paradigm controlling for individual and random social learning. After being trained on one token-type, subjects were confronted with a conspecific demonstrator who either received the same food reward as the subject (control condition) or a higher value food reward than the subject (test condition) for exchanging another token-type. In general, the chimpanzees persisted in exchanging the token-type they were trained on individually, indicating a form of conservatism consistent with previous studies. However, the chimpanzees were more inclined to copy the demonstrator in the test compared to the control condition, indicating a tendency to employ a copy-if-better strategy. We discuss the validity of our results by considering alternative explanations and relate our findings to the emergence of cumulative culture.

The IFS for WFIRST CGI: Science Requirements to Design

Science.gov (United States)

Groff, Tyler; Gong, Qian; Mandell, Avi M.; Zimmerman, Neil; Rizzo, Maxime; McElwain, Michael; harvey, david; Saxena, Prabal; cady, eric; mejia prada, camilo

2018-01-01

Direct Imaging of exoplanets using a coronagraph has become a major field of research both on the ground and in space. Key to the science of direct imaging is the spectroscopic capabilities of the instrument, our ability to extract spectra, and measure the abundance of molecular species such as Methane. To take these spectra, the WFIRST coronagraph instrument (CGI) uses an integral field spectrograph (IFS), which encodes the spectrum into a two-dimensional image on the detector. This results in more efficient detection and characterization of targets, and the spectral information is critical to achieving detection limits below the speckle floor of the imager. The CGI IFS operates in three 18% bands spanning 600nm to 970nm at a nominal spectral resolution of R50. We present the current science and engineering requirements for the IFS design, the instrument design, anticipated performance, and how the calibration is integrated into the focal plane wavefront control algorithms. We also highlight the role of the Prototype Imaging Spectrograph for Coronagraphic Exoplanet Studies (PISCES) at the JPL High Contrast Imaging Testbed to demonstrate performance and validate calibration methodologies for the flight instrument.

Man, You Might Look Like a Woman-If a Child Is Next to You.

Science.gov (United States)

Brielmann, Aenne A; Gaetano, Justin; Stolarova, Margarita

2015-01-01

Gender categorization seems prone to a pervasive bias: Persons about whom null or ambiguous gender information is available are more often considered male than female. Our study assessed whether such a male-bias is present in non-binary choice tasks and whether it can be altered by social contextual information. Participants were asked to report their perception of an adult figure's gender in three context conditions: (1) alone, (2) passively besides a child, or (3) actively helping a child (n = 10 pictures each). The response options male, female and I don't know were provided. As a result, participants attributed male gender to most figures and rarely used the I don't know option in all conditions, but were more likely to attribute female gender to the same adult figure if it was shown with a child. If such social contextual information was provided in the first rather than the second block of the experiment, subsequent female gender attributions increased for adult figures shown alone. Additionally, female gender attributions for actively helping relative to passive adults were made more often. Thus, we provide strong evidence that gender categorization can be altered by social context even if the subject of gender categorization remains identical.

And if we forget the talent detection… And if we individualize the development of his Talent

Directory of Open Access Journals (Sweden)

Alberto LORENZO

2015-10-01

Full Text Available For many years, it has been understood that the process of sport talent identification as a close to magic process (although it is understood in many cases as well, in which the coach was able, by some tests and test batteries, able to predict the future of athletes, and discern among them, who are the graceful people that would be World Champions. What ideas and arguments can lead to think that this is possible? Similarly, under the idea of talent development, it is also thought that, knowing how these athletes who have achieved the highest possible performance, it would also be possible to design a perfect process that allowed younger, if they met perfectly with the path set, reach or even exceed that performance. Do we really think this is possible?Far from accepting such ideas (and that support mainly, we must consider that there are many people who have the potential to produce high yields, in our case in sports. And far from thinking that you are just a graceful by grace of fate or the genetic lottery, we must understand that if we are able to monitor and facilitate the development process of a person, will be closer to being able to achieve the desired levels of performance. What is it that allows or causes an athlete to achieve the expected results when others do not? What factors favor the development of the athlete? How to design the development process of the athlete? We aim in this article summarize the main ideas and arguments with which the detection process and developing talent is addressed, and give the reader some ideas to help improve the learning process of any athlete who may fall into their hands.

Panel: If I Only Knew Then What I Know Now

Science.gov (United States)

Goals Recycling Green Purchasing Pollution Prevention Reusing Water Resources Environmental Management Discussion and Networking Event Panel: If I Only Knew Then What I Know Now WHEN: May 16, 2016 2:30 PM - 5:00 Alamos CONTACT: Veronika Mocko CATEGORY: Community INTERNAL: Calendar Login Event Description The LANL

30 CFR 203.66 - What happens if MMS does not act in the time allowed?

Science.gov (United States)

2010-07-01

... Relief for Pre-Act Deep Water Leases and for Development and Expansion Projects § 203.66 What happens if MMS does not act in the time allowed? If we do not act within the timeframes established under § 203... 30 Mineral Resources 2 2010-07-01 2010-07-01 false What happens if MMS does not act in the time...

Amino acid substrates impose polyamine, eIF5A, or hypusine requirement for peptide synthesis.

Science.gov (United States)

Shin, Byung-Sik; Katoh, Takayuki; Gutierrez, Erik; Kim, Joo-Ran; Suga, Hiroaki; Dever, Thomas E

2017-08-21

Whereas ribosomes efficiently catalyze peptide bond synthesis by most amino acids, the imino acid proline is a poor substrate for protein synthesis. Previous studies have shown that the translation factor eIF5A and its bacterial ortholog EF-P bind in the E site of the ribosome where they contact the peptidyl-tRNA in the P site and play a critical role in promoting the synthesis of polyproline peptides. Using misacylated Pro-tRNAPhe and Phe-tRNAPro, we show that the imino acid proline and not tRNAPro imposes the primary eIF5A requirement for polyproline synthesis. Though most proline analogs require eIF5A for efficient peptide synthesis, azetidine-2-caboxylic acid, a more flexible four-membered ring derivative of proline, shows relaxed eIF5A dependency, indicating that the structural rigidity of proline might contribute to the requirement for eIF5A. Finally, we examine the interplay between eIF5A and polyamines in promoting translation elongation. We show that eIF5A can obviate the polyamine requirement for general translation elongation, and that this activity is independent of the conserved hypusine modification on eIF5A. Thus, we propose that the body of eIF5A functionally substitutes for polyamines to promote general protein synthesis and that the hypusine modification on eIF5A is critically important for poor substrates like proline. Published by Oxford University Press on behalf of Nucleic Acids Research 2017.

2 CFR 180.360 - What happens if I fail to disclose information required under § 180.355?

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2010-01-01

... Doing Business With Other Persons Disclosing Information-Lower Tier Participants § 180.360 What happens... 2 Grants and Agreements 1 2010-01-01 2010-01-01 false What happens if I fail to disclose information required under § 180.355? 180.360 Section 180.360 Grants and Agreements OFFICE OF MANAGEMENT AND...

2 CFR 180.345 - What happens if I fail to disclose information required under § 180.335?

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2010-01-01

... Doing Business With Other Persons Disclosing Information-Primary Tier Participants § 180.345 What... 2 Grants and Agreements 1 2010-01-01 2010-01-01 false What happens if I fail to disclose information required under § 180.335? 180.345 Section 180.345 Grants and Agreements OFFICE OF MANAGEMENT AND...

Surface enrichment with chrome and nitriding of IF steel under an abnormal glow discharge

International Nuclear Information System (INIS)

Meira, S.R.; Borges, P.C.; Bernardelli, E.A.

2014-01-01

The objective of this work is to evaluate the influence of surface enrichment of IF steel with chrome, and nitriding, the formation of the nitrided layer. Thus, IF steel samples were subjected to surface enrichment process, using 409 stainless steel as a target for sputtering, followed by plasma nitriding, both under a dc abnormal glow discharge. The enrichment treatment was operated at 1200 ° C for 3h. The nitriding treatment was operated at 510 ° C for 2 h. The influence of the treatments on the layers formed was studied through optical microscopy (OM), scan electron microscopy (SEM), X-ray diffraction (XRD) and Vickers microindentation. The results show that the enrichment is effective to enrich the IF surface, furthermore, improves the characteristics of nitriding, comparing nitriding samples to nitriding and enriched, was observed needles of nitrides, as well as a higher hardness, which is associated with the nitrides of chrome, on the nitriding and enriched samples. (author)

Down-regulation of eIF4GII by miR-520c-3p represses diffuse large B cell lymphoma development.

Directory of Open Access Journals (Sweden)

Krystyna Mazan-Mamczarz

2014-01-01

Full Text Available Deregulation of the translational machinery is emerging as a critical contributor to cancer development. The contribution of microRNAs in translational gene control has been established however; the role of microRNAs in disrupting the cap-dependent translation regulation complex has not been previously described. Here, we established that elevated miR-520c-3p represses global translation, cell proliferation and initiates premature senescence in HeLa and DLBCL cells. Moreover, we demonstrate that miR-520c-3p directly targets translation initiation factor, eIF4GII mRNA and negatively regulates eIF4GII protein synthesis. miR-520c-3p overexpression diminishes cells colony formation and reduces tumor growth in a human xenograft mouse model. Consequently, downregulation of eIF4GII by siRNA decreases translation, cell proliferation and ability to form colonies, as well as induces cellular senescence. In vitro and in vivo findings were further validated in patient samples; DLBCL primary cells demonstrated low miR-520c-3p levels with reciprocally up-regulated eIF4GII protein expression. Our results provide evidence that the tumor suppressor effect of miR-520c-3p is mediated through repression of translation while inducing senescence and that eIF4GII is a key effector of this anti-tumor activity.

Blocking the eIF2α kinase (PKR) enhances positive and negative forms of cortex-dependent taste memory.

Science.gov (United States)

Stern, Elad; Chinnakkaruppan, Adaikkan; David, Orit; Sonenberg, Nahum; Rosenblum, Kobi

2013-02-06

Age-associated memory deterioration (and the decline in ability to acquire new information) is one of the major diseases of our era. Cognitive enhancement can be achieved by using psycho-stimulants, such as caffeine or nicotine, but very little is known about drugs that can enhance the consolidation phase of memories in the cortex, the brain structure considered to store, at least partially, long-term memories. We used cortex-dependent taste-learning paradigms to test the hypothesis that pharmacological manipulation of the translation initiation eIF2α, which plays a role in hippocampus-dependent memory, can enhance positive or negative forms of taste memories. We found that dephosphorylation (Ser51) of eIF2α, specifically in the cortex, is both correlated with and necessary for normal memory consolidation. To reduce eIF2α phosphorylation and improve memory consolidation, we pharmacologically inhibited one of the eIF2α kinases, PKR, which is known to be involved in brain aging and Alzheimer's disease. Systemic or local microinjection of PKR inhibitor to the gustatory cortex enhanced both positive and negative forms of taste memory in rats and mice. Our results provide clear evidence that PKR plays a major role in cortex-dependent memory consolidation and, therefore, that pharmacological inhibition of PKR is a potential target for drugs to enhance cognition.

What could family income be if health insurance were more affordable?

Science.gov (United States)

Young, Richard A; Devoe, Jennifer E

2012-10-01

Adjusted for inflation, household income has been relatively flat since the mid-1990s, but the inflation rate of employer-sponsored health insurance has been greater than both household income growth and general inflation for 50 years. We estimated the effect on average family income if health insurance inflation matched the general inflation rate since 1996, and those savings were given to employees as income. We used data from the Medical Expenditure Panel Survey, the Milliman Medical Index, and other federal sources to model the relationship between private health insurance costs and household income over the last 15 years. If the cost of family health care costs had kept pace with the Consumer Price Index (CPI) rate since 1996, the average family income could have been $8,410 higher in 2010 ($68,805 versus $60,395), 13.9% more than actual earnings. If health care costs had not exceeded the CPI rate since 1996 and if all the excess costs were converted into employee wages, median family income could be substantially higher today.

Identification of candidate children for maturity-onset diabetes of the young type 2 (MODY2 gene testing: a seven-item clinical flowchart (7-iF.

Directory of Open Access Journals (Sweden)

Michele Pinelli

Full Text Available MODY2 is the most prevalent monogenic form of diabetes in Italy with an estimated prevalence of about 0.5-1.5%. MODY2 is potentially indistinguishable from other forms of diabetes, however, its identification impacts on patients' quality of life and healthcare resources. Unfortunately, DNA direct sequencing as diagnostic test is not readily accessible and expensive. In addition current guidelines, aiming to establish when the test should be performed, proved a poor detection rate. Aim of this study is to propose a reliable and easy-to-use tool to identify candidate patients for MODY2 genetic testing. We designed and validated a diagnostic flowchart in the attempt to improve the detection rate and to increase the number of properly requested tests. The flowchart, called 7-iF, consists of 7 binary "yes or no" questions and its unequivocal output is an indication for whether testing or not. We tested the 7-iF to estimate its clinical utility in comparison to the clinical suspicion alone. The 7-iF, in a prospective 2-year study (921 diabetic children showed a precision of about the 76%. Using retrospective data, the 7-iF showed a precision in identifying MODY2 patients of about 80% compared to the 40% of the clinical suspicion. On the other hand, despite a relatively high number of missing MODY2 patients, the 7-iF would not suggest the test for 90% of the non-MODY2 patients, demonstrating that a wide application of this method might 1 help less experienced clinicians in suspecting MODY2 patients and 2 reducing the number of unnecessary tests. With the 7-iF, a clinician can feel confident of identifying a potential case of MODY2 and suggest the molecular test without fear of wasting time and money. A Qaly-type analysis estimated an increase in the patients' quality of life and savings for the health care system of about 9 million euros per year.

I/asterisk/ /6s 4P/ collisional quenching - Application to the IF 491-nm laser

Science.gov (United States)

Hutchison, S. B.; Verdeyen, J. T.; Eden, J. G.

1981-01-01

Measurements of the rate constants for quenching of the excited I (6s 4P) states by Ar, Xe, CF39I, UF6, and NF3 are described. Each rate constant is determined by recording the exponential time decay of the excited IF or excited I2 (342 nm) fluorescence in the afterglow of the e-beam-excited plasmas containing Ar, CF3I, NF3, and the desired quenching gas. In addition, further experimental evidence in support of neutral channel formation of excited IF in e-beam-pumped Ar/CF3I/NF3 mixtures is presented. Details of the experimental apparatus and gas handling procedures are given, and the kinetics model developed to interpret the experimental data is described.

40 CFR 141.561 - What happens if my system's turbidity monitoring equipment fails?

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 22 2010-07-01 2010-07-01 false What happens if my system's turbidity... Disinfection-Systems Serving Fewer Than 10,000 People Individual Filter Turbidity Requirements § 141.561 What happens if my system's turbidity monitoring equipment fails? If there is a failure in the continuous...

Foliated vector fields, the Godbillon-Vey invariant and the invariant I(F)

International Nuclear Information System (INIS)

Banyaga, A.; Landa, Alain Musesa

2004-03-01

We prove that if the invariant I(F) constructed in 'An invariant of contact structures and transversally oriented foliations', Ann. Global Analysis and Geom. 14(1996) 427-441 (A. Banyaga), through the Lie algebra of infinitesimal automorphisms of transversally oriented foliations F is trivial, then the Godbillon-Vey invariant GV (F) of F is also trivial, but that the converse is not true. For codimension one foliations, the restrictions I τ , (F) of I(F) to the Lie subalgebra of vector fields tangent to the leaves is the Reeb class R(F) of F. We also prove that if there exists a foliated vector field which is everywhere transverse to a codimension one foliation, then the Reeb class R(F) is trivial, hence so is the GV(F) invariant. (author)

The human Ago2 MC region does not contain an eIF4E-like mRNA cap binding motif

Directory of Open Access Journals (Sweden)

Grishin Nick V

2009-01-01

Full Text Available Abstract Background Argonaute (Ago proteins interact with small regulatory RNAs to mediate gene regulatory pathways. A recent report by Kiriakidou et al. 1 describes an MC sequence region identified in Ago2 that displays similarity to the cap-binding motif in translation initiation factor 4E (eIF4E. In a cap-bound eIF4E structure, two important aromatic residues of the motif stack on either side of a 7-methylguanosine 5'-triphosphate (m7Gppp base. The corresponding Ago2 aromatic residues (F450 and F505 were hypothesized to perform the same cap-binding function. However, the detected similarity between the MC sequence and the eIF4E cap-binding motif was questionable. Results A number of sequence-based and structure-based bioinformatics methods reveal the reported similarity between the Ago2 MC sequence region and the eIF4E cap-binding motif to be spurious. Alternatively, the MC sequence region is confidently assigned to the N-terminus of the Ago piwi module, within the mid domain of experimentally determined prokaryotic Ago structures. Confident mapping of the Ago2 MC sequence region to the piwi mid domain results in a homology-based structure model that positions the identified aromatic residues over 20 Å apart, with one of the aromatic side chains (F450 contributing instead to the hydrophobic core of the domain. Conclusion Correct functional prediction based on weak sequence similarity requires substantial evolutionary and structural support. The evolutionary context of the Ago mid domain suggested by multiple sequence alignment is limited to a conserved hydrophobicity profile required for the fold and a motif following the MC region that binds guide RNA. Mapping of the MC sequence to the mid domain structure reveals Ago2 aromatics that are incompatible with eIF4E-like mRNA cap-binding, yet display some limited local structure similarities that cause the chance sequence match to eIF4E. Reviewers This article was reviewed by Arcady Mushegian

The Probability Approach to English If-Conditional Sentences

Science.gov (United States)

Wu, Mei

2012-01-01

Users of the Probability Approach choose the right one from four basic types of conditional sentences--factual, predictive, hypothetical and counterfactual conditionals, by judging how likely (i.e. the probability) the event in the result-clause will take place when the condition in the if-clause is met. Thirty-three students from the experimental…

Unfinished Business: Writing as If You're Dying

Science.gov (United States)

Ardoin, Nicole; Dillon, Justin

2010-01-01

Participants in the 10th International Seminar in Health and Environmental Education Research Symposium in Montebello, Quebec were presented with the challenge of considering the question, "If you could only write one book and one paper in your life from now on, what would the titles be?" The task was structured to stimulate thought…

13 CFR 121.801 - May patent fees be reduced if a concern is small?

Science.gov (United States)

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false May patent fees be reduced if a concern is small? 121.801 Section 121.801 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION... for Paying Reduced Patent Fees § 121.801 May patent fees be reduced if a concern is small? These...

NEW LENSLET BASED IFS WITH HIGH DETECTOR PIXEL EFFICIENCY

Science.gov (United States)

Gong, Qian

2018-01-01

Three IFS types currently used for optical design are: lenslet array, imager slicer, and lenslet array and fiber combined. Lenslet array based Integral Field Spectroscopy (IFS) is very popular for many astrophysics applications due to its compactness, simplicity, as well as cost and mass savings. The disadvantage of lenslet based IFS is its low detector pixel efficiency. Enough spacing is needed between adjacent spectral traces in cross dispersion direction to avoid wavelength cross-talk, because the same wavelength is not aligned to the same column on detector. Such as on a recent exoplanet coronagraph instrument study to support the coming astrophysics decadal survey (LUVOIR), to cover a 45 λ/D Field of View (FOV) with a spectral resolving power of 200 at shortest wavelength, a 4k x 4k detector array is needed. This large format EMCCD pushes the detector into technology development area with a low TRL. Besides the future mission, it will help WFIRST coronagraph IFS by packing all spectra into a smaller area on detector, which will reduce the chance for electrons to be trapped in pixels, and slow the detector degradation during the mission.The innovation we propose here is to increase the detector packing efficiency by grouping a number of lenslets together to form many mini slits. In other words, a number of spots (Point Spread Function at lenslet focus) are aligned into a line to resemble a mini slit. Therefore, wavelength cross-talk is no longer a concern anymore. This combines the advantage of lenslet array and imager slicer together. The isolation rows between spectral traces in cross dispersion direction can be reduced or removed. So the packing efficiency is greatly increased. Furthermore, the today’s microlithography and etching technique is capable of making such a lenslet array, which will relax the detector demand significantly. It will finally contribute to the habitable exoplanets study to analyzing their spectra from direct images. Detailed theory

Disruption of genes encoding eIF4E binding proteins-1 and -2 does not alter basal or sepsis-induced changes in skeletal muscle protein synthesis in male or female mice.

Science.gov (United States)

Steiner, Jennifer L; Pruznak, Anne M; Deiter, Gina; Navaratnarajah, Maithili; Kutzler, Lydia; Kimball, Scot R; Lang, Charles H

2014-01-01

Sepsis decreases skeletal muscle protein synthesis in part by impairing mTOR activity and the subsequent phosphorylation of 4E-BP1 and S6K1 thereby controlling translation initiation; however, the relative importance of changes in these two downstream substrates is unknown. The role of 4E-BP1 (and -BP2) in regulating muscle protein synthesis was assessed in wild-type (WT) and 4E-BP1/BP2 double knockout (DKO) male mice under basal conditions and in response to sepsis. At 12 months of age, body weight, lean body mass and energy expenditure did not differ between WT and DKO mice. Moreover, in vivo rates of protein synthesis in gastrocnemius, heart and liver did not differ between DKO and WT mice. Sepsis decreased skeletal muscle protein synthesis and S6K1 phosphorylation in WT and DKO male mice to a similar extent. Sepsis only decreased 4E-BP1 phosphorylation in WT mice as no 4E-BP1/BP2 protein was detected in muscle from DKO mice. Sepsis decreased the binding of eIF4G to eIF4E in WT mice; however, eIF4E•eIF4G binding was not altered in DKO mice under either basal or septic conditions. A comparable sepsis-induced increase in eIF4B phosphorylation was seen in both WT and DKO mice. eEF2 phosphorylation was similarly increased in muscle from WT septic mice and both control and septic DKO mice, compared to WT control values. The sepsis-induced increase in muscle MuRF1 and atrogin-1 (markers of proteolysis) as well as TNFα and IL-6 (inflammatory cytokines) mRNA was greater in DKO than WT mice. The sepsis-induced decrease in myocardial and hepatic protein synthesis did not differ between WT and DKO mice. These data suggest overall basal protein balance and synthesis is maintained in muscle of mice lacking both 4E-BP1/BP2 and that sepsis-induced changes in mTOR signaling may be mediated by a down-stream mechanism independent of 4E-BP1 phosphorylation and eIF4E•eIF4G binding.

41 CFR 102-117.255 - What actions may I take if the TSP's performance is not satisfactory?

Science.gov (United States)

2010-07-01

... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false What actions may I take if the TSP's performance is not satisfactory? 102-117.255 Section 102-117.255 Public Contracts and... may I take if the TSP's performance is not satisfactory? If the TSP's performance is not satisfactory...

What If My Child Doesn't Take His or Her Asthma Medication?

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... My Child Doesn't Take His or Her Asthma Medication? KidsHealth / For Parents / What if My Child Doesn't Take His or Her Asthma Medication? ... When to Go to the ER if Your Child Has Asthma Asthma Managing Asthma Asthma Center How Do Asthma ...

34 CFR 472.34 - Under what circumstances may a project continue if a partner withdraws?

Science.gov (United States)

2010-07-01

... project continue if a partner withdraws? (a) A project may continue despite the withdrawal of a partner... the grant agreement by the partner that is withdrawing without a change in the project's scope or... 34 Education 3 2010-07-01 2010-07-01 false Under what circumstances may a project continue if a...

PKC δ Regulates Translation Initiation through PKR and eIF2 α in Response to Retinoic Acid in Acute Myeloid Leukemia Cells

OpenAIRE

Ozpolat, Bulent; Akar, Ugur; Tekedereli, Ibrahim; Alpay, S. Neslihan; Barria, Magaly; Gezgen, Baki; Zhang, Nianxiang; Coombes, Kevin; Kornblau, Steve; Lopez-Berestein, Gabriel

2012-01-01

Translation initiation and activity of eukaryotic initiation factor-alpha (eIF2 α ), the rate-limiting step of translation initiation, is often overactivated in malignant cells. Here, we investigated the regulation and role of eIF2 α in acute promyelocytic (APL) and acute myeloid leukemia (AML) cells in response to all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), the front-line therapies in APL. ATRA and ATO induce Ser-51 phosphorylation (inactivation) of eIF2 α , through the induct...

Narrowing the Transfer Gap: The Advantages of "as if" Situations in Training.

Science.gov (United States)

Vermeulen, Rita C. M.

2002-01-01

A schema a frame creates context and shapes interpretation. Using an "as if" framework can connect the contexts of training and job performance to improve transfer. Techniques that create "as if" situations include role playing, visualization, psychodrama, voice dialogue, improvisation, playback theatre, and six-steps reframing. (Contains 23…

The eIF4AIII RNA helicase is a critical determinant of human cytomegalovirus replication

Energy Technology Data Exchange (ETDEWEB)

Ziehr, Ben; Lenarcic, Erik; Cecil, Chad; Moorman, Nathaniel J., E-mail: nmoorman@med.unc.edu

2016-02-15

Human cytomegalovirus (HCMV) was recently shown to encode a large number of spliced mRNAs. While the nuclear export of unspliced viral transcripts has been extensively studied, the role of host mRNA export factors in HCMV mRNA trafficking remains poorly defined. We found that the eIF4AIII RNA helicase, a component of the exon junction complex, was necessary for efficient virus replication. Depletion of eIF4AIII limited viral DNA accumulation, export of viral mRNAs from the nucleus, and the production of progeny virus. However eIF4AIII was dispensable for the association of viral transcripts with ribosomes. We found that pateamine A, a natural compound that inhibits both eIF4AI/II and eIF4AIII, has potent antiviral activity and inhibits HCMV replication throughout the virus lytic cycle. Our results demonstrate that eIF4AIII is required for efficient HCMV replication, and suggest that eIF4A family helicases may be a new class of targets for the development of host-directed antiviral therapeutics. - Highlights: • The host eIF4AIII RNA helicase is required for efficient HCMV replication. • Depleting eIF4AIII inhibited the nuclear export of HCMV mRNAs. • HCMV mRNAs did not require eIF4AIII to associate with polyribosomes. • The eIF4A family helicases may be new targets for host-directed antiviral drugs.

The eIF4AIII RNA helicase is a critical determinant of human cytomegalovirus replication

International Nuclear Information System (INIS)

Ziehr, Ben; Lenarcic, Erik; Cecil, Chad; Moorman, Nathaniel J.

2016-01-01

Human cytomegalovirus (HCMV) was recently shown to encode a large number of spliced mRNAs. While the nuclear export of unspliced viral transcripts has been extensively studied, the role of host mRNA export factors in HCMV mRNA trafficking remains poorly defined. We found that the eIF4AIII RNA helicase, a component of the exon junction complex, was necessary for efficient virus replication. Depletion of eIF4AIII limited viral DNA accumulation, export of viral mRNAs from the nucleus, and the production of progeny virus. However eIF4AIII was dispensable for the association of viral transcripts with ribosomes. We found that pateamine A, a natural compound that inhibits both eIF4AI/II and eIF4AIII, has potent antiviral activity and inhibits HCMV replication throughout the virus lytic cycle. Our results demonstrate that eIF4AIII is required for efficient HCMV replication, and suggest that eIF4A family helicases may be a new class of targets for the development of host-directed antiviral therapeutics. - Highlights: • The host eIF4AIII RNA helicase is required for efficient HCMV replication. • Depleting eIF4AIII inhibited the nuclear export of HCMV mRNAs. • HCMV mRNAs did not require eIF4AIII to associate with polyribosomes. • The eIF4A family helicases may be new targets for host-directed antiviral drugs.

Dynamics of Networks if Everyone Strives for Structural Holes

NARCIS (Netherlands)

Buskens, Vincent; Rijt, Arnout van de

2008-01-01

When entrepreneurs enter structural holes in networks, they can exploit the related benefits. Evidence for these benefits has steadily accumulated. The authors ask whether those who strive for such structural advantages can maintain them if others follow their example. Burt speculates that they

Targeting Synthetic Lethal Interactions between Myc and the eIF4F Complex Impedes Tumorigenesis

Directory of Open Access Journals (Sweden)

Chen-Ju Lin

2012-04-01

Full Text Available The energetically demanding process of translation is linked to multiple signaling events through mTOR-mediated regulation of eukaryotic initiation factor (eIF4F complex assembly. Disrupting mTOR constraints on eIF4F activity can be oncogenic and alter chemotherapy response, making eIF4F an attractive antineoplastic target. Here, we combine a newly developed inducible RNAi platform and pharmacological targeting of eIF4F activity to define a critical role for endogenous eIF4F in Myc-dependent tumor initiation. We find elevated Myc levels are associated with deregulated eIF4F activity in the prelymphomatous stage of the Eμ-Myc lymphoma model. Inhibition of eIF4F is synthetic lethal with elevated Myc in premalignant pre-B/B cells resulting in reduced numbers of cycling pre-B/B cells and delayed tumor onset. At the organismal level, eIF4F suppression affected a subset of normal regenerating cells, but this was well tolerated and rapidly and completely reversible. Therefore, eIF4F is a key Myc client that represents a tumor-specific vulnerability.

Synthetic geology - Exploring the "what if?" in geology

Science.gov (United States)

Klump, J. F.; Robertson, J.

2015-12-01

The spatial and temporal extent of geological phenomena makes experiments in geology difficult to conduct, if not entirely impossible and collection of data is laborious and expensive - so expensive that most of the time we cannot test a hypothesis. The aim, in many cases, is to gather enough data to build a predictive geological model. Even in a mine, where data are abundant, a model remains incomplete because the information at the level of a blasting block is two orders of magnitude larger than the sample from a drill core, and we have to take measurement errors into account. So, what confidence can we have in a model based on sparse data, uncertainties and measurement error? Synthetic geology does not attempt to model the real world in terms of geological processes with all their uncertainties, rather it offers an artificial geological data source with fully known properties. On the basis of this artificial geology, we can simulate geological sampling by established or future technologies to study the resulting dataset. Conducting these experiments in silico removes the constraints of testing in the field or in production, and provides us with a known ground-truth against which the steps in a data analysis and integration workflow can be validated.Real-time simulation of data sources can be used to investigate crucial questions such as the potential information gain from future sensing capabilities, or from new sampling strategies, or the combination of both, and it enables us to test many "what if?" questions, both in geology and in data engineering. What would we be able to see if we could obtain data at higher resolution? How would real-time data analysis change sampling strategies? Does our data infrastructure handle many new real-time data streams? What feature engineering can be deducted for machine learning approaches? By providing a 'data sandbox' able to scale to realistic geological scenarios we hope to start answering some of these questions.

What if mankind warms the earth

International Nuclear Information System (INIS)

Kellogg, W.W.

1977-01-01

There are a variety of human activities that are being pursued on such a large scale that they may influence regional and global climate. Virtually all of these activities, including the addition of carbon dioxide and particles to the atmosphere, are expected on theoretical grounds to cause an increase in mean surface temperature in the decades ahead, and by 2000 AD the total warming effect will probably be larger than any of the natural climate fluctuations during the past 1,000 years or more. It is therefore pertinent ot inquire what a warmer earth might be like; and to obtain a first rough answer we turn to our mathematical models of the atmosphere, and also to the conditions that have been deduced for the period about 4,000 to 8,000 years ago when the earth was apparently several degress warmer the now. Atan now. At that time some areas that are now subtropical deserts received more rainfall, and there were other areas in the middle latitudes that were drier. There are several important implications for society if mankind does succeed in warming the earth - and a number of still unanswered questions as well. (orig.) [de

31 CFR 370.40 - Can I be held accountable if my negligence contributes to a forged signature?

Science.gov (United States)

2010-07-01

... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Can I be held accountable if my negligence contributes to a forged signature? 370.40 Section 370.40 Money and Finance: Treasury Regulations... if my negligence contributes to a forged signature? (a) General. If your failure to exercise ordinary...

Potyviral resistance derived from cultivars of Phaseolus vulgaris carrying bc-3 is associated with homozygotic presence of a mutated eIF4E allele

DEFF Research Database (Denmark)

Naderpour, Masoud; Lund, Ole Søgaard; Larsen, Richard

2010-01-01

-3 and bc-u, have been proposed to control resistance to the potyviruses Bean common mosaic virus (BCMV) and Bean common mosaic necrosis virus. In order to identify molecular entities for these genes, we cloned and sequenced P. vulgaris homologues of genes encoding the eIF proteins eIF4E, eIF(iso)4E...

Building "the Yoruba truth" An afroepistemologic reading of the Ifá system

OpenAIRE

de Diego González, Antonio

2012-01-01

Este artículo propone una lectura afroepistemológica del sistema de Ifá. Las políticas de la epistemología académica europea han despreciado el conocimiento tradicional africano. Ifá no ha sido una excepción. Pero a través de este método se han configurado gran parte de las normas socio-culturales y epistemológicas de la sociedad yorùbá. Así Ifá se convierte en algo más importante que un rito de adivinación, pues representa la cohesión político-social y epistemológica de una gran parte de los...

43 CFR 30.128 - What happens if an error in BIA's estate inventory is alleged?

Science.gov (United States)

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false What happens if an error in BIA's estate... INDIAN PROBATE HEARINGS PROCEDURES Judicial Authority and Duties § 30.128 What happens if an error in BIA's estate inventory is alleged? This section applies when, during a probate proceeding, an interested...

If It's Part Broke Half Fix It / Virginija Januskeviciute

Index Scriptorium Estoniae

Januskeviciute, Virginija, 1979-

2011-01-01

Kaasaegse Kunsti Eesti Keskuse ja Vilniuse Kaasaegse Kunsti Keskuse korraldatud näitus "If It's Part Broke, Half Fix It" Kaasaegse Kunsti Keskuses Vilniuses 28.01.-13.03.2011, kuraator Margit Säde Lehni. Osalesid kunstnikud Eestist, Leedust, Saksamaalt, Rootsist, Soomest, Inglismaalt ja Hollandist, osalejad loetletud

Presence of Type I-F CRISPR/Cas systems is associated with antimicrobial susceptibility in Escherichia coli.

Science.gov (United States)

Aydin, Seyid; Personne, Yoann; Newire, Enas; Laverick, Rebecca; Russell, Oliver; Roberts, Adam P; Enne, Virve I

2017-08-01

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and their associated cas genes are sequence-specific DNA nuclease systems found in bacteria and archaea. CRISPR/Cas systems use RNA transcripts of previously acquired DNA (spacers) to target invading genetic elements with the same sequence, including plasmids. In this research we studied the relationship between CRISPR/Cas systems and multidrug resistance in Escherichia coli . The presence of Type I-E and Type I-F CRISPR systems was investigated among 82 antimicrobial-susceptible and 96 MDR clinical E. coli isolates by PCR and DNA sequencing. Phylogrouping and MLST were performed to determine relatedness of isolates. RT-PCR was performed to ascertain the expression of associated cas genes. Type I-F CRISPR was associated with the B2 phylogroup and was significantly overrepresented in the susceptible group (22.0%) compared with the MDR group (2.1%). The majority of CRISPR I-F-containing isolates had spacer sequences that matched IncF and IncI plasmids. RT-PCR demonstrated that Type I-F cas genes were expressed and therefore potentially functional. The CRISPR I-F system is more likely to be found in antimicrobial-susceptible E. coli . Given that the Type I-F system is expressed in WT isolates, we suggest that this difference could be due to the CRISPR system potentially interfering with the acquisition of antimicrobial resistance plasmids, maintaining susceptibility in these isolates. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Targeting the eIF4F translation initiation complex: a critical nexus for cancer development.

Science.gov (United States)

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

2015-01-15

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 4F (eIF4F), the key regulator of the mRNA-ribosome recruitment phase of translation initiation. In many cellular and preclinical 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 antineoplastic agents. ©2014 American Association for Cancer Research.

Insulin Signaling Augments eIF4E-Dependent Nonsense-Mediated mRNA Decay in Mammalian Cells.

Science.gov (United States)

Park, Jungyun; Ahn, Seyoung; Jayabalan, Aravinth K; Ohn, Takbum; Koh, Hyun Chul; Hwang, Jungwook

2016-07-01

Nonsense-mediated mRNA decay (NMD) modulates the level of mRNA harboring a premature termination codon (PTC) in a translation-dependent manner. Inhibition of translation is known to impair NMD; however, few studies have investigated the correlation between enhanced translation and increased NMD. Here, we demonstrate that insulin signaling events increase translation, leading to an increase in NMD of eIF4E-bound transcripts. We provide evidence that (i) insulin-mediated enhancement of translation augments NMD and rapamycin abrogates this enhancement; (ii) an increase in AKT phosphorylation due to inhibition of PTEN facilitates NMD; (iii) insulin stimulation increases the binding of up-frameshift factor 1 (UPF1), most likely to eIF4E-bound PTC-containing transcripts; and (iv) insulin stimulation induces the colocalization of UPF1 and eIF4E in processing bodies. These results illustrate how extracellular signaling promotes the removal of eIF4E-bound NMD targets. Copyright © 2015 Elsevier B.V. All rights reserved.

Biochemical quantitation of the eIF5A hypusination in Arabidopsis thaliana uncovers ABA-dependent regulation

Science.gov (United States)

Belda-Palazón, Borja; Nohales, María A.; Rambla, José L.; Aceña, José L.; Delgado, Oscar; Fustero, Santos; Martínez, M. Carmen; Granell, Antonio; Carbonell, Juan; Ferrando, Alejandro

2014-01-01

The eukaryotic translation elongation factor eIF5A is the only protein known to contain the unusual amino acid hypusine which is essential for its biological activity. This post-translational modification is achieved by the sequential action of the enzymes deoxyhypusine synthase (DHS) and deoxyhypusine hydroxylase (DOHH). The crucial molecular function of eIF5A during translation has been recently elucidated in yeast and it is expected to be fully conserved in every eukaryotic cell, however the functional description of this pathway in plants is still sparse. The genetic approaches with transgenic plants for either eIF5A overexpression or antisense have revealed some activities related to the control of cell death processes but the molecular details remain to be characterized. One important aspect of fully understanding this pathway is the biochemical description of the hypusine modification system. Here we have used recombinant eIF5A proteins either modified by hypusination or non-modified to establish a bi-dimensional electrophoresis (2D-E) profile for the three eIF5A protein isoforms and their hypusinated or unmodified proteoforms present in Arabidopsis thaliana. The combined use of the recombinant 2D-E profile together with 2D-E/western blot analysis from whole plant extracts has provided a quantitative approach to measure the hypusination status of eIF5A. We have used this information to demonstrate that treatment with the hormone abscisic acid produces an alteration of the hypusine modification system in Arabidopsis thaliana. Overall this study presents the first biochemical description of the post-translational modification of eIF5A by hypusination which will be functionally relevant for future studies related to the characterization of this pathway in Arabidopsis thaliana. PMID:24904603

“If you drink alcohol, drink sensibly.” Is this guideline still appropriate?

African Journals Online (AJOL)

Food-Based Dietary Guidelines for South Africa: “If you drink alcohol, drink sensibly.” - Is this guideline ... alcohol-consumption guideline to be adopted by the general public: “If .... Survey of 20038 and the Youth Risk Behaviour Study of 20029.

29 CFR 4000.28 - What if I send a computer disk?

Science.gov (United States)

2010-07-01

... 29 Labor 9 2010-07-01 2010-07-01 false What if I send a computer disk? 4000.28 Section 4000.28... I send a computer disk? (a) In general. We determine your filing or issuance date for a computer... paragraph (b) of this section. (1) Filings. For computer-disk filings, we may treat your submission as...

What happens if you single out? An experiment

OpenAIRE

Galeotti, Fabio; Zizzo, Daniel John

2014-01-01

We present an experiment investigating the effects of singling out an individual on trust and trustworthiness. We find that (a) trustworthiness falls if there is a singled out subject; (b) non-singled out subjects discriminate against the singled out subject when they are not responsible of the distinct status of this person; (c) under a negative frame, the singled out subject returns significantly less; (d) under a positive frame, the singled out subject behaves bimodally, either selecting v...

A IF Signal Precessing System Design Based on Software Radio Platform

Directory of Open Access Journals (Sweden)

Zhao Jing

2018-01-01

Full Text Available Software radio is a definition of a design thought about how to implement flexible functions by using fixed hardware platform. Any platform based on this is characterized to be universal, standardized, modular, open and highly flexible. Due to some realistic reasons, a software radio platform is hard to be realized. So, most signal processing is operated after mixing. According to software radio requirements, a “FPGA+ADC+DAC” structure is designed. Compared with former processors, this module has broad application prospects with the small size, low power, configurable and programmable feathers. It has multifunction, such as generating IF signals, performing digital down conversion and realizing the synchronous demodulation and the other functions. This module also provides the extended host interface to communicate with upper computers. According to the practical test, take MSK signal for example, if the bit rate is 1Mb/s, bit error rate is lower than 10-6.

41 CFR 102-117.285 - What are my choices if a TSP's performance is not satisfactory?

Science.gov (United States)

2010-07-01

... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false What are my choices if a TSP's performance is not satisfactory? 102-117.285 Section 102-117.285 Public Contracts and Property... are my choices if a TSP's performance is not satisfactory? You may choose to place a TSP in temporary...

Remote MINOS Shift Station at IF-UFG

International Nuclear Information System (INIS)

Tognini, Stefano Castro; Gomes, Ricardo Avelino

2011-01-01

Full text: MINOS is a very well known neutrino experiment mainly designed to study neutrino oscillations and measure the parameters that rule the phenomena. The experiment uses an intense neutrino beam provided by the NuMI (Neutrinos at the Main Injector) beamline at Fermilab and two similar magnetized detectors - the Near Detector located at Fermilab, 1 km downstream the target and 94 m underground; and the Far Detector located in the Soudan Mine in northern Minnesota, 734 km downstream the Near Detector and 713 m underground. The MINOS control room is consisted of four main systems used to monitor the beam, the detectors and the data acquisition process: the Beam Monitoring System - a set of tools used to monitor the status of the NuMI beam, such as its intensity, its alignment with the target and beamline and if the beam data acquisition is working properly; the Online Monitoring System (OM) - responsible for monitoring the electronics of both detectors, which determines the quality of the data; the Detector Control System (DCS) - which monitors the detectors information, such as the high voltage systems, state of the rack protection system, the magnet control, chiller monitor, coil current, humidity and environmental temperatures; and the Data Acquisition System (DAQ) - used to control the runs/subruns and monitor the recording process. The experiment is taking data with the Far Detector since 2003 and with the Near Detector since 2005. The Physics Institute of the Federal University of Goias (IF-UFG) is joining the MINOS Collaboration since June 2009 and this work describes the configuration of our Remote MINOS Shift Station. In order to accomplish the shift tasks with minimum expenditure of time and money efforts, MINOS decided to authorize remote shifts on January 2011. Apart of being able to realize remote shifts, the main goals of our shift station are to allow the training of new users, in particular graduate students; to allow our real-time monitoring of

Characterization of the domains of E. coli initiation factor IF2 responsible for recognition of the ribosome

DEFF Research Database (Denmark)

Manuel Palacios Moreno, Juan; Andersen, Lars Dyrskjøt; Egebjerg Kristensen, Janni

1999-01-01

We have studied the interactions between the ribosome and the domains of Escherichia coli translation initiation factor 2, using an in vitro ribosomal binding assay with wild-type forms, N- and C-terminal truncated forms of IF2 as well as isolated structural domains. A deletion mutant of the factor...

Characterization of the domains of E. coli initiation factor IF2 responsible for recognition of the ribosome

DEFF Research Database (Denmark)

Manuel Palacios Moreno, Juan; Andersen, Lars Dyrskjøt; Egebjerg Kristensen, Janni

1999-01-01

We have studied the interactions between the ribosome and the domains of Escherichia coli translation initiation factor 2, using an in vitro ribosomal binding assay with wild-type forms, N- and C-terminal truncated forms of IF2 as well as isolated structural domains. A deletion mutant of the fact...

5 CFR 919.325 - What happens if I do business with an excluded person in a covered transaction?

Science.gov (United States)

2010-01-01

... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false What happens if I do business with an... Persons § 919.325 What happens if I do business with an excluded person in a covered transaction? If as a... PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) GOVERNMENTWIDE DEBARMENT AND...

The eIF4E-binding proteins are modifiers of cytoplasmic eIF4E relocalization during the heat shock response

OpenAIRE

Sukarieh, R.; Sonenberg, N.; Pelletier, J.

2009-01-01

Stress granules (SGs) arise as a consequence of cellular stress, contain stalled translation preinitiation complexes, and are associated with cell survival during environmental insults. SGs are dynamic entities with proteins relocating into and out of them during stress. Among the repertoire of proteins present in SGs is eukaryotic initiation factor 4E (eIF4E), a translation factor required for cap-dependent translation and that regulates a rate-limiting step for protein synthesis. Herein, we...

If You or Someone You Love is Very Ill...Ask Tough Questions

Science.gov (United States)

If you or someone you love is very ill... ask tough questions* Ask Your Doctor... 1 Will you talk openly and candidly with me and my family ... make decisions about my care? 7 Will you still be available to me even when I’m ...

13 CFR 127.403 - What happens if SBA verifies the concern's eligibility?

Science.gov (United States)

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false What happens if SBA verifies the concern's eligibility? 127.403 Section 127.403 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION WOMEN-OWNED SMALL BUSINESS FEDERAL CONTRACT ASSISTANCE PROCEDURES Eligibility Examinations § 127...

"If It's Not in English, It's Not Worth Reading!"

Science.gov (United States)

Durand, Charles Xavier

2006-01-01

A policy favouring one foreign language can only be imposed if measures are taken to make it accepted. Therefore, the development of perceptions about the policy takes on as much importance as the measures taken for promoting its use. This paper aims to demonstrate the cogency of this assertion particularly in the area of science and technology…

A role for eukaryotic translation initiation factor 2B (eIF2B) in taste memory consolidation and in thermal control establishment during the critical period for sensory development.

Science.gov (United States)

Tirosh, Sharon; Elkobi, Alina; Rosenblum, Kobi; Meiri, Noam

2007-05-01

All species exhibit critical periods for sensory development, yet very little is known about the molecules involved in the changes in the network wiring that underlies this process. Here the role of transcription regulation of the translation machinery was determined by evaluating the expression of eIF2Bepsilon, an essential component of translation initiation, in both taste-preference development and thermal control establishment in chicks. Analysis of the expression pattern of this gene after passive-avoidance training revealed clear induction of eIF2Bepsilon in both the mesopallium intermediomediale (IMM) and in the striatum mediale (StM). In addition, a correlation was found between the concentration of methylanthranilate (MeA), which was the malaise substrate in the passive-avoidance training procedure, the duration of memory, and the expression level of eIF2Bepsilon. Training chicks on a low concentration of MeA induced short-term memory and low expression level of eIF2Bepsilon, whereas a high concentration of MeA induced long-term memory and a high expression level of eIF2Bepsilon in both the IMM and StM. Furthermore, eIF2Bepsilon-antisense "knock-down" not only reduced the amount of eIF2Bepsilon but also attenuated taste memory formation. In order to determine whether induction of eIF2Bepsilon is a general feature of neuronal plasticity, we checked whether it was induced in other forms of neuronal plasticity, with particular attention to its role in temperature control establishment, which represents hypothalamic-related plasticity. It was established that eIF2Bepsilon-mRNA was induced in the preopotic anterior hypothalamus during heat conditioning. Taken together, these results correlate eIF2Bepsilon with sensory development.

Depletion of eIF4G from yeast cells narrows the range of translational efficiencies genome-wide

Directory of Open Access Journals (Sweden)

Hinnebusch Alan G

2011-01-01

Full Text Available Abstract Background Eukaryotic translation initiation factor 4G (eIF4G is thought to influence the translational efficiencies of cellular mRNAs by its roles in forming an eIF4F-mRNA-PABP mRNP that is competent for attachment of the 43S preinitiation complex, and in scanning through structured 5' UTR sequences. We have tested this hypothesis by determining the effects of genetically depleting eIF4G from yeast cells on global translational efficiencies (TEs, using gene expression microarrays to measure the abundance of mRNA in polysomes relative to total mRNA for ~5900 genes. Results Although depletion of eIF4G is lethal and reduces protein synthesis by ~75%, it had small effects (less than a factor of 1.5 on the relative TE of most genes. Within these limits, however, depleting eIF4G narrowed the range of translational efficiencies genome-wide, with mRNAs of better than average TE being translated relatively worse, and mRNAs with lower than average TE being translated relatively better. Surprisingly, the fraction of mRNAs most dependent on eIF4G display an average 5' UTR length at or below the mean for all yeast genes. Conclusions This finding suggests that eIF4G is more critical for ribosome attachment to mRNAs than for scanning long, structured 5' UTRs. Our results also indicate that eIF4G, and the closed-loop mRNP it assembles with the m7 G cap- and poly(A-binding factors (eIF4E and PABP, is not essential for translation of most (if not all mRNAs but enhances the differentiation of translational efficiencies genome-wide.

A 10.7 MHz CMOS SC radio IF filter using orthogonal hardware modulation

NARCIS (Netherlands)

Quinn, P.J.; Hartingsveldt, van K.; Roermund, van A.H.M.

2000-01-01

FM radio receivers require an IF filter for channel selection, customarily set at an IF center frequency of 10.7 MHz. Up until now, the limitations of integrated radio selectivity filters in terms of power dissipation, dynamic range, and cost are such that it is still required to use an external

13 CFR 123.412 - What happens if SBA declines your business' pre-disaster mitigation loan request?

Science.gov (United States)

2010-01-01

...' loan request, SBA will notify your business in writing giving specific reasons for decline. If your... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false What happens if SBA declines your business' pre-disaster mitigation loan request? 123.412 Section 123.412 Business Credit and Assistance...

30 CFR 250.116 - How do I determine producibility if my well is in the Gulf of Mexico?

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 2 2010-07-01 2010-07-01 false How do I determine producibility if my well is in the Gulf of Mexico? 250.116 Section 250.116 Mineral Resources MINERALS MANAGEMENT SERVICE... Performance Standards § 250.116 How do I determine producibility if my well is in the Gulf of Mexico? If your...

20 CFR 220.184 - If the annuitant becomes disabled by another impairment(s).

Science.gov (United States)

2010-04-01

... impairment(s). 220.184 Section 220.184 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE... Activity or Medical Improvement § 220.184 If the annuitant becomes disabled by another impairment(s). If a new severe impairment(s) begins in or before the month in which the last impairment(s) ends, the Board...

40 CFR 59.506 - How do I demonstrate compliance if I manufacture multi-component kits?

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 5 2010-07-01 2010-07-01 false How do I demonstrate compliance if I manufacture multi-component kits? 59.506 Section 59.506 Protection of Environment ENVIRONMENTAL PROTECTION... § 59.506 How do I demonstrate compliance if I manufacture multi-component kits? (a) If you manufacture...

Structural changes of eIF4E upon binding to the mRNA 5' monomethylguanosine and trimethylguanosine Cap.

Science.gov (United States)

Rutkowska-Wlodarczyk, Izabela; Stepinski, Janusz; Dadlez, Michal; Darzynkiewicz, Edward; Stolarski, Ryszard; Niedzwiecka, Anna

2008-03-04

Recognition of the 5' cap by the eukaryotic initiation factor 4E (eIF4E) is the rate-limiting step in the ribosome recruitment to mRNAs. The regular cap consists of 7-monomethylguanosine (MMG) linked by a 5'-5' triphosphate bridge to the first transcribed nucleoside, while some primitive eukaryotes possess a N (2), N (2),7-trimethylguanosine (TMG) cap structure as a result of trans splicing. Mammalian eIF4E is highly specific to the MMG form of the cap in terms of association constants and thermodynamic driving force. We have investigated conformational changes of eIF4E induced by interaction with two cap analogues, 7-methyl-GTP and N (2), N (2),7-trimethyl-GTP. Hydrogen-deuterium exchange and electrospray mass spectrometry were applied to probe local dynamics of murine eIF4E in the apo and cap-bound forms. The data show that the cap binding induces long-range conformational changes in the protein, not only in the cap-binding pocket but also in a distant region of the 4E-BP/eIF4G binding site. Formation of the complex with 7-methyl-GTP makes the eIF4E structure more compact, while binding of N (2), N (2),7-trimethyl-GTP leads to higher solvent accessibility of the protein backbone in comparison with the apo form. The results suggest that the additional double methylation at the N (2)-amino group of the cap causes sterical effects upon binding to mammalian eIF4E which influence the overall solution dynamics of the protein, thus precluding formation of a tight complex.

Damned if you do, damned if you do not - Reduced Climate Impact vs. Sustainable Forests in Sweden

International Nuclear Information System (INIS)

Geijer, Erik; Bostedt, Goeran; Braennlund, Runar

2011-01-01

The main objective of this paper is to analyze the potential goal conflict between two of Sweden's environmental objectives: Sustainable Forests and Reduced Climate Impact - or, more precisely, the conflict between forest conservation and the supply of wood fuel. To accomplish this, we use a forest sector model that includes the suppliers and major users of roundwood. The econometric results, based on a data set that spans 40 years, show that all the own price elasticities have the expected signs. Among the three forestry products, the supply and (long-term) demand of forest fuel seems to be most sensitive to a price change. In a second step, the estimated model is used to simulate the effect of increased forest conservation - the Sustainable Forest objective - on the supply of wood fuel. If oil is used as a substitute, Swedish emissions of greenhouse gases will increase by almost 0.92 percent, which indicates a clear conflict with the Reduced Climate Impact objective. (author)

Nuclear assortment of eIF4E coincides with shut-off of host protein synthesis upon poliovirus infection.

Science.gov (United States)

Sukarieh, R; Sonenberg, N; Pelletier, J

2010-05-01

Eukaryotic initiation factor (eIF) 4E is a subunit of the cap-binding protein complex, eIF4F, which recognizes the cap structure of cellular mRNAs to facilitate translation initiation. eIF4E is assembled into the eIF4F complex via its interaction with eIF4G, an event that is under Akt/mTOR regulation. The eIF4E-eIF4G interaction is regulated by the eIF4E binding partners, eIF4E-binding proteins and eIF4E-transporter. Cleavage of eIF4G occurs upon poliovirus infection and is responsible for the shut-off of host-cell protein synthesis observed early in infection. Here, we document that relocalization of eIF4E to the nucleus occurs concomitantly with cleavage of eIF4G upon poliovirus infection. This event is not dependent upon virus replication, but is dependent on eIF4G cleavage. We postulate that eIF4E nuclear relocalization may contribute to the shut-off of host protein synthesis that is a hallmark of poliovirus infection by perturbing the circular status of actively translating mRNAs.

50 CFR 86.73 - What if I do not spend all the money?

Science.gov (United States)

2010-10-01

... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 false What if I do not spend all the money? 86.73 Section 86.73 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE... GRANT (BIG) PROGRAM How States Manage Grants § 86.73 What if I do not spend all the money? Funds not...

41 CFR 105-68.325 - What happens if I do business with an excluded person in a covered transaction?

Science.gov (United States)

2010-07-01

... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false What happens if I do business with an excluded person in a covered transaction? 105-68.325 Section 105-68.325 Public Contracts...-68.325 What happens if I do business with an excluded person in a covered transaction? If as a...

20 CFR 416.1142 - If you live in a public assistance household.

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false If you live in a public assistance household... and Emergency Assistance Act; (5) General assistance programs of the Bureau of Indian Affairs; (6) State or local government assistance programs based on need (tax credits or refunds are not assistance...

32 CFR 37.805 - If I am awarding a TIA, what payment methods may I specify?

Science.gov (United States)

2010-07-01

... 32 National Defense 1 2010-07-01 2010-07-01 false If I am awarding a TIA, what payment methods may... Administrative Matters Payments § 37.805 If I am awarding a TIA, what payment methods may I specify? Your TIA may... measure of progress. Fixed-support TIAs must use this payment method and each measure of progress...

32 CFR 37.230 - May I use a TIA if a participant is to receive fee or profit?

Science.gov (United States)

2010-07-01

... 32 National Defense 1 2010-07-01 2010-07-01 false May I use a TIA if a participant is to receive... Investment Agreements § 37.230 May I use a TIA if a participant is to receive fee or profit? In accordance with 32 CFR 22.205(b), you may not use a TIA if any participant is to receive fee or profit. Note that...

If My Child Has Asthma, Can We Keep Our Pet?

Science.gov (United States)

... your only choice might be to find a new home for your pet. If so, be sure to discuss this with your child. Reassure your child that this isn't his or her "fault" — and make sure siblings don't blame the child. Losing a pet, ...

Negative masses, even if isolated, imply self-acceleration, hence a catastrophic world

International Nuclear Information System (INIS)

Cavalleri, G.; Tonni, E.

1997-01-01

The conjecture of the existence of negative masses together with ordinary positive masses leads to runaway motions even if no self-reaction is considered. Pollard and Dunning-Davies have shown other constraints as a modification of the principle of least action and that negative masses can only exist at negative temperature, and must be adiabatically separate from positive masses. They show here that the self-reaction on a single isolated negative mass implies a runaway motion. Consequently, the consideration of self-fields and relevant self-reaction excludes negative masses even if isolated

Heterogeneous multi-layered IF steel with simultaneous high strength and good ductility

Science.gov (United States)

Zhang, Ling; Jiang, Xiaojuan; Wang, Yuhui; Chen, Qiang; Chen, Zhen; Zhang, Yonghong; Huang, Tianlin; Wu, Guilin

2017-07-01

Multi-layered IF steel samples were designed and fabricated by hot compression followed by cold forging of an alternating stack of cold-rolled and annealed IF steel sheets, with an aim to improve the strength of the material without losing much ductility. A very good combination of strength and ductility was achieved by proper annealing after deformation. Microstructural analysis by electron back-scatter diffraction revealed that the good combination of strength and ductility is related to a characteristic hierarchical structure that is characterized by layered and lamella structures with different length scales.

Crystal structure of an eIF4G-like protein from Danio rerio

Energy Technology Data Exchange (ETDEWEB)

Bae, Euiyoung; Bitto, Eduard; Bingman, Craig A.; McCoy, Jason G.; Wesenberg, Gary E.; Phillips, Jr., George N. (UW)

2012-04-18

The gene LOC 91917 Danio rerio (zebrafish) encodes a protein annotated in the UniProt knowledgebase as the middle domain of eukaryotic initiation factor 4G domain containing protein b (MIF4Gdb). Its molecular weight is 25.8 kDa, and it comprises 222 amino acid residues. BLAST searches revealed homologues of D. rerio MIF4Gdb in many eukaryotes including humans. The homologue sand MIF4Gdb were identified as members of the Pfam family, MIF4G (PF2854), which is named after the middle domain of eukaryotic initiation factor 4G (eIF4G). eIF4G is a component of eukaryotic translational initiation complex, and contains binding sites for other initiation factors, suggesting its critical role in translational initiation. The MIF4G domain also occurs in several other proteins involved in RNA metabolism, including the Nonsense-mediated mRNA decay 2 protein (NMD2/UPF2), and the nuclear cap-binding protein 80-kDa subunit (CBP80). Sequence and structure analysis of the MIF4G domains in many proteins indicate that the domain assumes an all helical fold and has tandem repeated motifs. The zebrafish protein described here has homology to domains of other proteins variously referred to as NIC-containing proteins (NMD2, eIF4G, CBP80). The biological function of D. rerio MIF4Gdb has not yet been experimentally characterized, and the annotation is based on amino acid sequence comparison. D. rerio MIF4Gdb did not share more than 25% sequence identity with any protein for which the three-dimensional structure is known and was selected as a target for structure determination by the Center for Eukaryotic Structural Genomics (CESG). Here, they report the crystal structure of D. rerio MIF4Gdb (UniGene code Dr.79360, UniProt code Q5EAQ1, CESG target number GO.79294).

Mutational analysis of the EMCV 2A protein identifies a nuclear localization signal and an eIF4E binding site

International Nuclear Information System (INIS)

Groppo, Rachel; Brown, Bradley A.; Palmenberg, Ann C.

2011-01-01

Cardioviruses have a unique 2A protein (143 aa). During genome translation, the encephalomyocarditis virus (EMCV) 2A is released through a ribosome skipping event mitigated through C-terminal 2A sequences and by subsequent N-terminal reaction with viral 3C pro . Although viral replication is cytoplasmic, mature 2A accumulates in nucleoli shortly after infection. Some protein also transiently associates with cytoplasmic 40S ribosomal subunits, an activity contributing to inhibition of cellular cap-dependent translation. Cardiovirus sequences predict an eIF4E binding site (aa 126-134) and a nuclear localization signal (NLS, aa 91-102), within 2A, both of which are functional during EMCV infection. Point mutations preventing eIF4E:2A interactions gave small-plaque phenotype viruses, but still inhibited cellular cap-dependent translation. Deletions within the NLS motif relocalized 2A to the cytoplasm and abrogated the inhibition of cap-dependent translation. A fusion protein linking the 2A NLS to eGFP was sufficient to redirect the reporter to the nucleus but not into nucleoli.

2002/2003 IfSAR data for Southern California: Radar Reflectance Image

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — This metadata document describes the collection and processing of topographic elevation point data derived from Interferometric Synthetic Aperture Radar (IfSAR)...

Design and implementation of quadrature bandpass sigma-delta modulator used in low-IF RF receiver

Science.gov (United States)

Ge, Binjie; Li, Yan; Yu, Hang; Feng, Xiaoxing

2018-05-01

This paper presents the design and implementation of quadrature bandpass sigma-delta modulator. A pole movement method for transforming real sigma-delta modulator to a quadrature one is proposed by detailed study of the relationship of noise-shaping center frequency and integrator pole position in sigma-delta modulator. The proposed modulator uses sampling capacitor sharing switched capacitor integrator, and achieves a very small feedback coefficient by a series capacitor network, and those two techniques can dramatically reduce capacitor area. Quantizer output-dependent dummy capacitor load for reference voltage buffer can compensate signal-dependent noise that is caused by load variation. This paper designs a quadrature bandpass Sigma-Delta modulator for 2.4 GHz low IF receivers that achieve 69 dB SNDR at 1 MHz BW and -1 MHz IF with 48 MHz clock. The chip is fabricated with SMIC 0.18 μm CMOS technology, it achieves a total power current of 2.1 mA, and the chip area is 0.48 mm2. Project supported by the National Natural Science Foundation of China (Nos. 61471245, U1201256), the Guangdong Province Foundation (No. 2014B090901031), and the Shenzhen Foundation (Nos. JCYJ20160308095019383, JSGG20150529160945187).

EBSD characterization of deformed lath martensite in if steel

DEFF Research Database (Denmark)

Lv, Z.A.; Zhang, Xiaodan; Huang, Xiaoxu

2017-01-01

Rolling deformation results in the transformation of a lath martensite structure to a lamellar structure characteristic to that of IF steel cold-rolled to medium and high strains. The structural transition takes place from low to medium strain, and electron backscatter diffraction analysis shows...... and the strength are characterized for lath martensite rolled to a thickness reduction of 30%, showing that large changes in the misorientation take place, while the strain hardening rate is low....

25 CFR 170.811 - What happens if lack of funds results in inadequate maintenance?

Science.gov (United States)

2010-04-01

... maintenance? 170.811 Section 170.811 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER INDIAN RESERVATION ROADS PROGRAM BIA Road Maintenance § 170.811 What happens if lack of funds results in inadequate maintenance? If BIA determines that an IRR transportation facility is not being...

Adult Health: Discover if You're at Risk of Job Burnout

Science.gov (United States)

... solutions. Is job sharing an option? What about telecommuting or flexing your time? Would it help to ... and collaboration might help you cope with job stress and feelings of burnout. If you have access ...

Transgenic Brassica rapa plants over-expressing eIF(iso)4E variants show broad-spectrum Turnip mosaic virus (TuMV) resistance.

Science.gov (United States)

Kim, Jinhee; Kang, Won-Hee; Hwang, Jeena; Yang, Hee-Bum; Dosun, Kim; Oh, Chang-Sik; Kang, Byoung-Cheorl

2014-08-01

The protein-protein interaction between VPg (viral protein genome-linked) of potyviruses and eIF4E (eukaryotic initiation factor 4E) or eIF(iso)4E of their host plants is a critical step in determining viral virulence. In this study, we evaluated the approach of engineering broad-spectrum resistance in Chinese cabbage (Brassica rapa) to Turnip mosaic virus (TuMV), which is one of the most important potyviruses, by a systematic knowledge-based approach to interrupt the interaction between TuMV VPg and B. rapa eIF(iso)4E. The seven amino acids in the cap-binding pocket of eIF(iso)4E were selected on the basis of other previous results and comparison of protein models of cap-binding pockets, and mutated. Yeast two-hybrid assay and co-immunoprecipitation analysis demonstrated that W95L, K150L and W95L/K150E amino acid mutations of B. rapa eIF(iso)4E interrupted its interaction with TuMV VPg. All eIF(iso)4E mutants were able to complement an eIF4E-knockout yeast strain, indicating that the mutated eIF(iso)4E proteins retained their function as a translational initiation factor. To determine whether these mutations could confer resistance, eIF(iso)4E W95L, W95L/K150E and eIF(iso)4E wild-type were over-expressed in a susceptible Chinese cabbage cultivar. Evaluation of the TuMV resistance of T1 and T2 transformants demonstrated that the over-expression of the eIF(iso)4E mutant forms can confer resistance to multiple TuMV strains. These data demonstrate the utility of knowledge-based approaches for the engineering of broad-spectrum resistance in Chinese cabbage. © 2014 BSPP AND JOHN WILEY & SONS LTD.

2 CFR 180.440 - What action may I take if a primary tier participant knowingly does business with an excluded or...

Science.gov (United States)

2010-01-01

... 2 Grants and Agreements 1 2010-01-01 2010-01-01 false What action may I take if a primary tier participant knowingly does business with an excluded or disqualified person? 180.440 Section 180.440 Grants and Agreements OFFICE OF MANAGEMENT AND BUDGET GOVERNMENTWIDE GUIDANCE FOR GRANTS AND AGREEMENTS...

40 CFR 1051.325 - What happens if an engine family fails the production-line testing requirements?

Science.gov (United States)

2010-07-01

... ENGINES AND VEHICLES Testing Production-Line Vehicles and Engines § 1051.325 What happens if an engine... for an engine family if it fails under § 1051.315. The suspension may apply to all facilities producing vehicles or engines from an engine family, even if you find noncompliant vehicles or engines only...

A case if dysphagia lusoria | Fynn | SA Journal of Radiology

African Journals Online (AJOL)

SA Journal of Radiology. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 8, No 4 (2004) >. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register. A case if dysphagia lusoria. E Fynn, NZ Makhanya, Lm Ntlhe ...

31 CFR 363.38 - What happens if my financial institution returns an ACH debit?

Science.gov (United States)

2010-07-01

... TreasuryDirect § 363.38 What happens if my financial institution returns an ACH debit? If your designated financial institution returns an ACH debit, we reserve the right to reinitiate the debit at our option. We.... We are not responsible for any fees your financial institution may charge relating to returned ACH...

Pumpkin eIF5A isoforms interact with components of the translational machinery in the cucurbit sieve tube system.

Science.gov (United States)

Ma, Yi; Miura, Eriko; Ham, Byung-Kook; Cheng, Hao-Wen; Lee, Young-Jin; Lucas, William J

2010-11-01

In yeast, eIF5A, in combination with eEF2, functions at the translation step, during the protein elongation cycle. This result is of significance with respect to functioning of the enucleate sieve tube system, as eIF5A was recently detected in Cucurbita maxima (pumpkin) phloem sap. In the present study, we further characterized four CmeIF5A isoforms, encoding three proteins, all of which were present in the phloem sap. Although hypusination of CmeIF5A was not necessary for entry into the sieve elements, this unique post-translational modification was necessary for RNA binding. The two enzymes required for hypusination were detected in pumpkin phloem sap, where presumably this modification takes place. A combination of gel-filtration chromatography and protein overlay assays demonstrated that, as in yeast, CmeIF5A interacts with phloem proteins, like eEF2, known to be involved in protein synthesis. These findings are discussed in terms of a potential role for eIF5A in regulating protein synthesis within the enucleate sieve tube system of the angiosperms. © 2010 The Authors. Journal compilation © 2010 Blackwell Publishing Ltd.

40 CFR 1045.415 - What happens if in-use engines do not meet requirements?

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 32 2010-07-01 2010-07-01 false What happens if in-use engines do not... VESSELS In-Use Testing § 1045.415 What happens if in-use engines do not meet requirements? (a) Determine... families showing that you designed them to exceed the minimum requirements for controlling emissions. We...

40 CFR 1048.415 - What happens if in-use engines do not meet requirements?

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 32 2010-07-01 2010-07-01 false What happens if in-use engines do not... Testing In-use Engines § 1048.415 What happens if in-use engines do not meet requirements? (a) Determine... families showing that you designed them to exceed the minimum requirements for controlling emissions. We...

"What If" Analyses: Ways to Interpret Statistical Significance Test Results Using EXCEL or "R"

Science.gov (United States)

Ozturk, Elif

2012-01-01

The present paper aims to review two motivations to conduct "what if" analyses using Excel and "R" to understand the statistical significance tests through the sample size context. "What if" analyses can be used to teach students what statistical significance tests really do and in applied research either prospectively to estimate what sample size…

"Capture" Me if You Can: Estimating Abundance of Dolphin Populations

Science.gov (United States)

Thompson, Jessica; Curran, Mary Carla; Cox, Tara

2016-01-01

Animal populations are monitored over time to assess the effects of environmental disaster and disease, as well as the efficacy of laws designed to protect them. Determining the abundance of a species within a defined area is one method of monitoring a population. In "Capture" Me if You Can, middle school students will use data collected…

Should doctors provide futile medical treatment if patients or their ...

African Journals Online (AJOL)

Ethically and legally doctors are not obliged to provide futile treatment to patients, even if the patient or their proxies are prepared to pay for it. However, it may be justified where such treatment is harmless and has a placebo effect. In deciding about a request for futile treatment, doctors should be guided by the ethical ...

What if there were no significance tests?

CERN Document Server

Harlow, Lisa L; Steiger, James H

2013-01-01

This book is the result of a spirited debate stimulated by a recent meeting of the Society of Multivariate Experimental Psychology. Although the viewpoints span a range of perspectives, the overriding theme that emerges states that significance testing may still be useful if supplemented with some or all of the following -- Bayesian logic, caution, confidence intervals, effect sizes and power, other goodness of approximation measures, replication and meta-analysis, sound reasoning, and theory appraisal and corroboration. The book is organized into five general areas. The first presents an overview of significance testing issues that sythesizes the highlights of the remainder of the book. The next discusses the debate in which significance testing should be rejected or retained. The third outlines various methods that may supplement current significance testing procedures. The fourth discusses Bayesian approaches and methods and the use of confidence intervals versus significance tests. The last presents the p...

40 CFR 63.1087 - What actions must I take if a leak is detected?

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 10 2010-07-01 2010-07-01 false What actions must I take if a leak is... leak is detected? If a leak is detected, you must comply with the requirements in paragraphs (a) and (b) of this section unless repair is delayed according to § 63.1088. (a) Repair the leak as soon as...

19 CFR 351.406 - Calculation of normal value if sales are made at less than cost of production.

Science.gov (United States)

2010-04-01

... Price, Fair Value, and Normal Value § 351.406 Calculation of normal value if sales are made at less than cost of production. (a) Introduction. In determining normal value, the Secretary may disregard sales of... 19 Customs Duties 3 2010-04-01 2010-04-01 false Calculation of normal value if sales are made at...

Getting past yes: negotiating as if implementation mattered.

Science.gov (United States)

Ertel, Danny

2004-11-01

Many deals that look good on paper never materialize into value-creating endeavors. Often, the problem begins at the negotiating table. In fact, the very person everyone thinks is pivotal to a deal's success--the negotiator--is often the one who undermines it. That's because most negotiators have a deal maker mind-set: They see the signed contract as the final destination rather than the start of a cooperative venture. What's worse, most companies reward negotiators on the basis of the number and size of the deals they're signing, giving them no incentive to change. The author asserts that organizations and negotiators must transition from a deal maker mentality--which involves squeezing your counterpart for everything you can get--to an implementation mind-set--which sets the stage for a healthy working relationship long after the ink has dried. Achieving an implementation mind-set demands five new approaches. First, start with the end in mind: Negotiation teams should carry out a "benefit of hindsight" exercise to imagine what sorts of problems they'll have encountered 12 months down the road. Second, help your counterpart prepare. Surprise confers advantage only because the other side has no time to think through all the implications of a proposal. If they agree to something they can't deliver, it will affect you both. Third, treat alignment as a shared responsibility. After all, if the other side's interests aren't aligned, it's your problem, too. Fourth, send one unified message. Negotiators should brief implementation teams on both sides together so everyone has the same information. And fifth, manage the negotiation like a business exercise: Combine disciplined negotiation preparation with post-negotiation reviews. Above all, companies must remember that the best deals don't end at the negotiating table--they begin there.

An experimental vital signs detection radar using low-IF heterodyne architecture and single-sideband transmission

DEFF Research Database (Denmark)

Jensen, Brian Sveistrup; Johansen, Tom Keinicke; Yan, Lei

2013-01-01

In this paper an experimental X-band radar system, called DTU-VISDAM, developed for the detection and monitoring of human vital signs is described. The DTU-VISDAM radar exploits a low intermediate frequency (IF) heterodyne RF front-end architecture and single-sideband (SSB) transmission for easier...... and more reliable extraction of the vital signs. The hardware implementation of the proposed low-IF RF front-end architecture and associated IF circuitry is discussed. Furthermore, the signal processing and calibration steps necessary to extract the vital signs information measured on a human subject...

31 CFR 19.430 - How do I check to see if a person is excluded or disqualified?

Science.gov (United States)

2010-07-01

... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false How do I check to see if a person is excluded or disqualified? 19.430 Section 19.430 Money and Finance: Treasury Office of the Secretary of the... disqualified? You check to see if a person is excluded or disqualified in two ways: (a) You as an agency...

Mitochondrial dysfunction enhances cisplatin resistance in human gastric cancer cells via the ROS-activated GCN2-eIF2α-ATF4-xCT pathway.

Science.gov (United States)

Wang, Sheng-Fan; Chen, Meng-Shian; Chou, Yueh-Ching; Ueng, Yune-Fang; Yin, Pen-Hui; Yeh, Tien-Shun; Lee, Hsin-Chen

2016-11-08

Mitochondrial DNA mutations and defects in mitochondrial enzymes have been identified in gastric cancers, and they might contribute to cancer progression. In previous studies, mitochondrial dysfunction was induced by oligomycin-enhanced chemoresistance to cisplatin. Herein, we dissected the regulatory mechanism for mitochondrial dysfunction-enhanced cisplatin resistance in human gastric cancer cells. Repeated cisplatin treatment-induced cisplatin-resistant cells exhibited high SLC7A11 (xCT) expression, and xCT inhibitors (sulfasalazine or erastin), xCT siRNA, or a GSH synthesis inhibitor (buthionine sulphoximine, BSO) could sensitize these cells to cisplatin. Clinically, the high expression of xCT was associated with a poorer prognosis for gastric cancer patients under adjuvant chemotherapy. Moreover, we found that mitochondrial dysfunction enhanced cisplatin resistance and up-regulated xCT expression, as well as intracellular glutathione (GSH). The xCT inhibitors, siRNA against xCT or BSO decreased mitochondrial dysfunction-enhanced cisplatin resistance. We further demonstrated that the upregulation of the eIF2α-ATF4 pathway contributed to mitochondrial dysfunction-induced xCT expression, and activated eIF2α kinase GCN2, but not PERK, stimulated the eIF2α-ATF4-xCT pathway in response to mitochondrial dysfunction-increased reactive oxygen species (ROS) levels. In conclusion, our results suggested that the ROS-activated GCN2-eIF2α-ATF4-xCT pathway might contribute to mitochondrial dysfunction-enhanced cisplatin resistance and could be a potential target for gastric cancer therapy.

12 CFR 502.75 - What if I do not pay my fees on time?

Science.gov (United States)

2010-01-01

... 12 Banks and Banking 5 2010-01-01 2010-01-01 false What if I do not pay my fees on time? 502.75 Section 502.75 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY ASSESSMENTS AND FEES Fees § 502.75 What if I do not pay my fees on time? (a) Interest. An examination or investigation...

PENERAPAN FUZZY IF-THEN RULES UNTUK PENINGKATAN KONTRAS PADA CITRA HASIL MAMMOGRAFI

Directory of Open Access Journals (Sweden)

Helmy Thendean

2008-01-01

Full Text Available In medical area, the quality of an image which is acquired from mammography often has a poor contrast. The poor quality image leads a difficulty for a radiologist to analyze the image. The problem becomes bigger when the image contains a cancer or tumor. There are some methods in image processing technique to increase the contrast quality of an image. This paper presents Fuzzy IF-THEN Rules method which has four knowledge base approaches to increase the contrast quality of the image, especially breast images from mammography. To determine the success rate, this experiment tries to compare this method with a standard contrast improvement such as histogram equalization. The quantity parameters to compare these methods are linier index of fuzziness and fuzzy entropy. The result shows that Fuzzy IF-THEN Rules offers better result to improve the contrast quality than standard method. The result of this experiment is validated by an expert from radiology department from Husada Hospital, Jakarta. Abstract in Bahasa Indonesia : Citra hasil dari mammografi dalam dunia kedokteran sering memiliki kualitas yang buruk dari sisi kontras. Hal ini mengakibatkan kesulitan bagi seorang radiolog untuk menganalisis citra tersebut. Tingkat kesulitan bertambah apabila citra yang harus dianalisis tersebut mengandung kanker atau tumor. Terdapat beberapa metode untuk peningkatan kualitas kontras sebuah citra. Penelitian ini menggunakan metode Fuzzy IF-THEN Rules dengan empat pendekatan basis pengetahuan untuk meningkatkan kualitas kontras citra, khususnya citra payudara yang diperoleh dari hasil mammografi. Untuk menentukan tingkat keberha-silannya, metode tersebut akan dibandingkan dengan metode standar untuk peningkatan kontras seperti Histogram Equalization. Parameter yang digunakan untuk membandingkan setiap metode tersebut adalah linier index of fuzziness dan fuzzy entropy. Hasil percobaan menunjukkan bahwa Fuzzy IF-THEN Rules mampu menghasilkan hasil peningkatan

What to Do If Your Appliances Are Wet After a Disaster

Centers for Disease Control (CDC) Podcasts

2006-08-10

If your home was flooded, look for signs that your appliances have gotten wet. Throw away wet or flooded appliances to protect from shock and fire.  Created: 8/10/2006 by Emergency Communications System.   Date Released: 7/30/2008.

Rift Valley fever virus NSs protein promotes post-transcriptional downregulation of protein kinase PKR and inhibits eIF2alpha phosphorylation.

Science.gov (United States)

Ikegami, Tetsuro; Narayanan, Krishna; Won, Sungyong; Kamitani, Wataru; Peters, C J; Makino, Shinji

2009-02-01

Rift Valley fever virus (RVFV) (genus Phlebovirus, family Bunyaviridae) is a negative-stranded RNA virus with a tripartite genome. RVFV is transmitted by mosquitoes and causes fever and severe hemorrhagic illness among humans, and fever and high rates of abortions in livestock. A nonstructural RVFV NSs protein inhibits the transcription of host mRNAs, including interferon-beta mRNA, and is a major virulence factor. The present study explored a novel function of the RVFV NSs protein by testing the replication of RVFV lacking the NSs gene in the presence of actinomycin D (ActD) or alpha-amanitin, both of which served as a surrogate of the host mRNA synthesis suppression function of the NSs. In the presence of the host-transcriptional inhibitors, the replication of RVFV lacking the NSs protein, but not that carrying NSs, induced double-stranded RNA-dependent protein kinase (PKR)-mediated eukaryotic initiation factor (eIF)2alpha phosphorylation, leading to the suppression of host and viral protein translation. RVFV NSs promoted post-transcriptional downregulation of PKR early in the course of the infection and suppressed the phosphorylated eIF2alpha accumulation. These data suggested that a combination of RVFV replication and NSs-induced host transcriptional suppression induces PKR-mediated eIF2alpha phosphorylation, while the NSs facilitates efficient viral translation by downregulating PKR and inhibiting PKR-mediated eIF2alpha phosphorylation. Thus, the two distinct functions of the NSs, i.e., the suppression of host transcription, including that of type I interferon mRNAs, and the downregulation of PKR, work together to prevent host innate antiviral functions, allowing efficient replication and survival of RVFV in infected mammalian hosts.

30 CFR 243.201 - How will MMS determine if I am financially solvent?

Science.gov (United States)

2010-07-01

... Section by one of the methods in § 243.200(a): (1) A written request asking us to consult a business... active appeals. (d) If you request that we consult a business-information or credit-reporting service or... solvent? 243.201 Section 243.201 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR...

30 CFR 203.45 - If I drill a certified unsuccessful well, what royalty relief will my lease earn?

Science.gov (United States)

2010-07-01

... than 200 meters but less than 400 meters deep; or (ii) On or after May 3, 2004, if your lease is located in water partly or entirely less than 200 meters deep. (2) Production to which an RSV applies...

An anti-image interference quadrature IF architecture for satellite receivers

Directory of Open Access Journals (Sweden)

He Weidong

2014-08-01

Full Text Available Since Global Navigation Satellite System (GNSS signals span a wide range of frequency, wireless signals coming from other communication systems may be aliased and appear as image interference. In quadrature intermediate frequency (IF receivers, image aliasing due to in-phase and quadrature (I/Q channel mismatches is always a big problem. I/Q mismatches occur because of gain and phase imbalances between quadrature mixers and capacitor mismatches in analog-to-digital converters (ADC. As a result, the dynamic range and performance of a receiver are severely degraded. In this paper, several popular receiver architectures are summarized and the image aliasing problem is investigated in detail. Based on this analysis, a low-IF architecture is proposed for a single-chip solution and a novel and feasible anti-image algorithm is investigated. With this anti-image digital processing, the image reject ratio (IRR can reach approximately above 50 dB, which relaxes image rejection specific in front-end circuit designs and allows cheap and highly flexible analog front-end solutions. Simulation and experimental data show that the anti-image algorithm can work effectively, robustly, and steadily.

Treatnebt if Addiction - Clinical and Judicial Perspectives: Two Case Reports

Directory of Open Access Journals (Sweden)

Sofia Fonseca

2013-12-01

Full Text Available The sporadic or chronic use of drugs and alcohol is directly related to conduct disorders and to the triggering of psychopathological states of sub-acute or chronic course. The excessive consumption of alcohol and excessive traffic/consumption of illicit drugs by individuals without mental illness or disability are actions of free will; they are therefore criminally responsible for their behaviour, even if they commit a crime during the state of intoxication, which the individual chose voluntarily to experience. In clinical practice, it is widely accepted that the treatment of these disorders is only effective when the patient accepts it voluntarily and that involuntary commitment (compulsive treatment is only carried out when the psychopathological state associated justifies the presuppositions of Article 12 of the Mental Health Law. However, if the compulsive treatment is of a penal character, mandated by a judge, the individual is obligated to accept treatment, independent of whether or not he suffers from mental illness. The authors present two case studies, one of drug addiction, the other of alcoholism, and discuss the clinical and judicial perspectives on the treatment of these clinical entities.

25 CFR 161.610 - What will BIA do if livestock is not removed when a permit expires or is cancelled?

Science.gov (United States)

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false What will BIA do if livestock is not removed when a permit expires or is cancelled? 161.610 Section 161.610 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF... will BIA do if livestock is not removed when a permit expires or is cancelled? If the livestock is not...

Programmed cell death in the leaves of the Arabidopsis spontaneous necrotic spots (sns-D mutant correlates with increased expression of the eukaryotic translation initiation factor eIF4B2

Directory of Open Access Journals (Sweden)

Gwenael M.D.J.-M. Gaussand

2011-04-01

Full Text Available From a pool of transgenic Arabidopsis (Arabidopsis thaliana plants harboring an activator T-DNA construct, one mutant was identified that developed spontaneous necrotic spots (sns-D on the rosette leaves under aseptic conditions. The sns-D mutation is dominant and homozygous plants are embryo lethal. The mutant produced smaller rosettes with a different number of stomata than the wild-type. DNA fragmentation in the nuclei of cells in the necrotic spots and a significant increase of caspase-3 and caspase-6 like activities in sns-D leaf extracts indicated that the sns-D mutation caused programmed cell death (PCD. The integration of the activator T-DNA caused an increase of the expression level of At1g13020, which encodes the eukaryotic translation initiation factor eIF4B2. The expression level of eIF4B2 was positively correlated with the severity of sns-D mutant phenotype. Overexpression of the eIF4B2 cDNA mimicked phenotypic traits of the sns-D mutant indicating that the sns-D mutant phenotype is indeed caused by activation tagging of eIF4B2. Thus, incorrect regulation of translation initiation may result in PCD.

TRBP and eIF6 homologue in Marsupenaeus japonicus play crucial roles in antiviral response.

Directory of Open Access Journals (Sweden)

Shuai Wang

Full Text Available Plants and invertebrates can suppress viral infection through RNA silencing, mediated by RNA-induced silencing complex (RISC. Trans-activation response RNA-binding protein (TRBP, consisting of three double-stranded RNA-binding domains, is a component of the RISC. In our previous paper, a TRBP homologue in Fenneropenaeus chinensis (Fc-TRBP was reported to directly bind to eukaryotic initiation factor 6 (Fc-eIF6. In this study, we further characterized the function of TRBP and the involvement of TRBP and eIF6 in antiviral RNA interference (RNAi pathway of shrimp. The double-stranded RNA binding domains (dsRBDs B and C of the TRBP from Marsupenaeus japonicus (Mj-TRBP were found to mediate the interaction of TRBP and eIF6. Gel-shift assays revealed that the N-terminal of Mj-TRBP dsRBD strongly binds to double-stranded RNA (dsRNA and that the homodimer of the TRBP mediated by the C-terminal dsRBD increases the affinity to dsRNA. RNAi against either Mj-TRBP or Mj-eIF6 impairs the dsRNA-induced sequence-specific RNAi pathway and facilitates the proliferation of white spot syndrome virus (WSSV. These results further proved the important roles of TRBP and eIF6 in the antiviral response of shrimp.

25 CFR 1000.276 - Does FTCA apply to a self-governance AFA if FTCA is not referenced in the AFA?

Science.gov (United States)

2010-04-01

...-governance AFA if FTCA is not referenced in the AFA? Yes, FTCA applies even if the AFA does not mention it. ... 25 Indians 2 2010-04-01 2010-04-01 false Does FTCA apply to a self-governance AFA if FTCA is not referenced in the AFA? 1000.276 Section 1000.276 Indians OFFICE OF THE ASSISTANT SECRETARY, INDIAN AFFAIRS...

Would You Say You "Had Masturbated" If … ?: The Influence of Situational and Individual Factors on Labeling a Behavior as Masturbation.

Science.gov (United States)

Kirschbaum, Allison L; Peterson, Zoë D

2018-02-01

The term masturbation is often not clearly defined despite its prevalent use in sex education, sex research, and clinical settings. The purpose of this study was to understand what behaviors are typically considered to be masturbation as well as the situational and individual variables that may affect the labeling of a behavior as such. An online study of 564 individuals demonstrated that a wide variety of behaviors were considered to be masturbation by a majority of participants. No difference was found between men and women in the total number of behaviors labeled as masturbation. Both men and women were more likely to label a behavior as masturbation (1) if there was no sexual partner present than if there was and (2) if an orgasm occurred than if it did not. In addition, women were more likely than men to label a behavior as masturbation if they were alone and if no orgasm occurred. Younger age was associated with labeling more behaviors as masturbation, but sexual identity, self-pleasuring experience, partnered sexual experience, and attitudes toward masturbation were not related to the number of behaviors labeled as masturbation. Results speak to the importance of behavioral specificity when discussing masturbation with students, clients, and in sex research.

After the Shots... What to Do If Your Child Has Discomfort

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... about or if you have questions, call your healthcare provider. Here are some things you can do to help reduce fever: n ... what is on the label, check with a healthcare professional before ... sources such as the Internet, old dosing charts, or family members. It is ...

20 CFR 416.974 - Evaluation guides if you are an employee.

Science.gov (United States)

2010-04-01

....974 Section 416.974 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL SECURITY INCOME... you have done shows that you are able to do substantial gainful activity. If you are working or have... relevant to your work activity. We will use these provisions whenever they are appropriate in connection...

eIF4E Phosphorylation Influences Bdnf mRNA Translation in Mouse Dorsal Root Ganglion Neurons

Directory of Open Access Journals (Sweden)

Jamie K. Moy

2018-02-01

Full Text Available Plasticity in dorsal root ganglion (DRG neurons that promotes pain requires activity-dependent mRNA translation. Protein synthesis inhibitors block the ability of many pain-promoting molecules to enhance excitability in DRG neurons and attenuate behavioral signs of pain plasticity. In line with this, we have recently shown that phosphorylation of the 5′ cap-binding protein, eIF4E, plays a pivotal role in plasticity of DRG nociceptors in models of hyperalgesic priming. However, mRNA targets of eIF4E phosphorylation have not been elucidated in the DRG. Brain-derived neurotrophic factor (BDNF signaling from nociceptors in the DRG to spinal dorsal horn neurons is an important mediator of hyperalgesic priming. Regulatory mechanisms that promote pain plasticity via controlling BDNF expression that is involved in promoting pain plasticity have not been identified. We show that phosphorylation of eIF4E is paramount for Bdnf mRNA translation in the DRG. Bdnf mRNA translation is reduced in mice lacking eIF4E phosphorylation (eIF4ES209A and pro-nociceptive factors fail to increase BDNF protein levels in the DRGs of these mice despite robust upregulation of Bdnf-201 mRNA levels. Importantly, bypassing the DRG by giving intrathecal injection of BDNF in eIF4ES209A mice creates a strong hyperalgesic priming response that is normally absent or reduced in these mice. We conclude that eIF4E phosphorylation-mediated translational control of BDNF expression is a key mechanism for nociceptor plasticity leading to hyperalgesic priming.

Opportunities that abound for British coal--if only

Energy Technology Data Exchange (ETDEWEB)

1984-04-01

The chairman of the National Coal Board discusses primary-energy consumption from 1965, with major emphasis on coal. He points out that coal consumption showed growth after 1975, but before then - except for a boost in 1973 - real expansion has been quite slow. World coal resources and reserves are presented. Because several countries are able to deliver coal into Europe at prices which are lower than the National Coal Board's average cost, Britain must reduce production costs in order to compete more effectively worldwide. Patterns of costs could be improved if more output was to be concentrated at the modern, more-productive collieries. Investment in coal mining is at one of the highest levels of investment of any industry in Britain today.

40 CFR 1042.320 - What happens if one of my production-line engines fails to meet emission standards?

Science.gov (United States)

2010-07-01

... an initial failed test if all of the following are true: (1) The catalyst was in a green condition... 40 Protection of Environment 32 2010-07-01 2010-07-01 false What happens if one of my production... MARINE COMPRESSION-IGNITION ENGINES AND VESSELS Testing Production-line Engines § 1042.320 What happens...

Potyviral resistance derived from cultivars of Phaseolus vulgaris carrying bc-3 co-segregates with homozygotic presence of a mutated eIF4E allele

DEFF Research Database (Denmark)

Naderpour, M; Lund, O Søgaard; Larsen, R

2008-01-01

-binding proteins, eIF4E, eIF(iso)4E and nCBP. In cultivars reported to carry bc-3 resistance, eIF4E was found to display non-silent mutations at codons 53, 65, 76 and 111 closely resembling a pattern of eIF4E mutations determining potyvirus resistance in other plant species. By application of a molecular marker...

Formation of Outburst Structure in Hot Dip Galvannealed Coatings on IF Steels

Directory of Open Access Journals (Sweden)

Kollárová, M.

2007-01-01

Full Text Available Outburst structure in two industrially produced hot dip galvanized interstitial free steel sheets for automotive industry after additional annealing has been examined. Ti IF steel was found to form weak outburst structure in the early stage of annealing, followed by frontal growth of Fe-Zn phases during further heating. The high reactivity of this steel was confirmed by rapid G-phase formation. Under the same conditions, Ti-Nb-P IF steel exhibited frontal growth of Fe-Zn compounds without G-phase formation due to relatively high phosphorous content, which is known as inhibitor of Fe-Zn reaction, but simultaneously significant occurrence of undesired outburst structures was recorded. It was assumed that the phosphorous content was insufficient and/or ferrite grain was very fine.

Translational Control of the SigR-Directed Oxidative Stress Response in Streptomyces via IF3-Mediated Repression of a Noncanonical GTC Start Codon.

Science.gov (United States)

Feeney, Morgan A; Chandra, Govind; Findlay, Kim C; Paget, Mark S B; Buttner, Mark J

2017-06-13

The major oxidative stress response in Streptomyces is controlled by the sigma factor SigR and its cognate antisigma factor RsrA, and SigR activity is tightly controlled through multiple mechanisms at both the transcriptional and posttranslational levels. Here we show that sigR has a highly unusual GTC start codon and that this leads to another level of SigR regulation, in which SigR translation is repressed by translation initiation factor 3 (IF3). Changing the GTC to a canonical start codon causes SigR to be overproduced relative to RsrA, resulting in unregulated and constitutive expression of the SigR regulon. Similarly, introducing IF3* mutations that impair its ability to repress SigR translation has the same effect. Thus, the noncanonical GTC sigR start codon and its repression by IF3 are critical for the correct and proper functioning of the oxidative stress regulatory system. sigR and rsrA are cotranscribed and translationally coupled, and it had therefore been assumed that SigR and RsrA are produced in stoichiometric amounts. Here we show that RsrA can be transcribed and translated independently of SigR, present evidence that RsrA is normally produced in excess of SigR, and describe the factors that determine SigR-RsrA stoichiometry. IMPORTANCE In all sigma factor-antisigma factor regulatory switches, the relative abundance of the two proteins is critical to the proper functioning of the system. Many sigma-antisigma operons are cotranscribed and translationally coupled, leading to a generic assumption that the sigma and antisigma factors are produced in a fixed 1:1 ratio. In the case of sigR - rsrA , we show instead that the antisigma factor is produced in excess over the sigma factor, providing a buffer to prevent spurious release of sigma activity. This excess arises in part because sigR has an extremely rare noncanonical GTC start codon, and as a result, SigR translation initiation is repressed by IF3. This finding highlights the potential significance

49 CFR 23.57 - What happens if a recipient falls short of meeting its overall goals?

Science.gov (United States)

2010-10-01

... PARTICIPATION OF DISADVANTAGED BUSINESS ENTERPRISE IN AIRPORT CONCESSIONS Goals, Good Faith Efforts, and... if you have failed to administer your ACDBE program in good faith. (b) If your ACDBE participation...

Chronic copper exposure causes spatial memory impairment, selective loss of hippocampal synaptic proteins, and activation of PKR/eIF2α pathway in mice.

Science.gov (United States)

Ma, Quan; Ying, Ming; Sui, Xiaojing; Zhang, Huimin; Huang, Haiyan; Yang, Linqing; Huang, Xinfeng; Zhuang, Zhixiong; Liu, Jianjun; Yang, Xifei

2015-01-01

Copper is an essential element for human growth and development; however, excessive intake of copper could contribute to neurotoxicity. Here we show that chronic exposure to copper in drinking water impaired spatial memory with simultaneous selective loss of hippocampal pre-synaptic protein synapsin 1, and post-synaptic density protein (PSD)-93/95 in mice. Copper exposure was shown to elevate the levels of nitrotyrosine and 8-hydroxydeoxyguanosine (8-OHdG) in hippocampus, two markers of oxidative stress. Concurrently, we also found that copper exposure activated double stranded RNA-dependent protein kinase (PKR) as evidenced by increased ratio of phosphorylated PKR at Thr451 and total PKR and increased the phosphorylation of its downstream signaling molecule eukaryotic initiation factor 2α (eIF2α) at Ser51 in hippocampus. Consistent with activation of PKR/eIF2α signaling pathway which was shown to mediate synaptic deficit and cognitive impairment, the levels of activating transcription factor 4 (ATF-4), a downstream signaling molecule of eIF2α and a repressor of CREB-mediated gene expression, were significantly increased, while the activity of cAMP response elements binding protein (CREB) was inactivated as suggested by decreased phosphorylation of CREB at Ser133 by copper exposure. In addition, the expression of the pro-apoptotic target molecule C/EBP homology protein (CHOP) of ATF-4 was upregulated and hippocampal neuronal apoptosis was induced by copper exposure. Taken together, we propose that chronic copper exposure might cause spatial memory impairment, selective loss of synaptic proteins, and neuronal apoptosis through the mechanisms involving activation of PKR/eIF2α signaling pathway.

Rift Valley fever virus NSs protein promotes post-transcriptional downregulation of protein kinase PKR and inhibits eIF2alpha phosphorylation.

Directory of Open Access Journals (Sweden)

Tetsuro Ikegami

2009-02-01

Full Text Available Rift Valley fever virus (RVFV (genus Phlebovirus, family Bunyaviridae is a negative-stranded RNA virus with a tripartite genome. RVFV is transmitted by mosquitoes and causes fever and severe hemorrhagic illness among humans, and fever and high rates of abortions in livestock. A nonstructural RVFV NSs protein inhibits the transcription of host mRNAs, including interferon-beta mRNA, and is a major virulence factor. The present study explored a novel function of the RVFV NSs protein by testing the replication of RVFV lacking the NSs gene in the presence of actinomycin D (ActD or alpha-amanitin, both of which served as a surrogate of the host mRNA synthesis suppression function of the NSs. In the presence of the host-transcriptional inhibitors, the replication of RVFV lacking the NSs protein, but not that carrying NSs, induced double-stranded RNA-dependent protein kinase (PKR-mediated eukaryotic initiation factor (eIF2alpha phosphorylation, leading to the suppression of host and viral protein translation. RVFV NSs promoted post-transcriptional downregulation of PKR early in the course of the infection and suppressed the phosphorylated eIF2alpha accumulation. These data suggested that a combination of RVFV replication and NSs-induced host transcriptional suppression induces PKR-mediated eIF2alpha phosphorylation, while the NSs facilitates efficient viral translation by downregulating PKR and inhibiting PKR-mediated eIF2alpha phosphorylation. Thus, the two distinct functions of the NSs, i.e., the suppression of host transcription, including that of type I interferon mRNAs, and the downregulation of PKR, work together to prevent host innate antiviral functions, allowing efficient replication and survival of RVFV in infected mammalian hosts.

Muckraking Free Speech: I.F. Stone and the Trial of Socrates.

Science.gov (United States)

Birkhead, Douglas

1989-01-01

Reviews I.F. Stone's "The Trial of Socrates," discussing the application of Stone's particular perspective (vintage American liberalism) and method (the muckraking tradition) to his reassessment of democracy and free speech in ancient Athens via Socrates' trial and condemnation. Compares Ancient Greek and modern concepts of free speech…

20 CFR 404.1574 - Evaluation guides if you are an employee.

Science.gov (United States)

2010-04-01

....1574 Section 404.1574 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND... shows that you are able to do substantial gainful activity. If you are working or have worked as an... your work activity. We will use these provisions whenever they are appropriate, whether in connection...

EBSD characterization of an IF steel processed by Accumulative Roll Bonding

International Nuclear Information System (INIS)

Cruz-Gandarilla, F; Salcedo-Garrido, A M; Avalos, M; Bolmaro, R; Baudin, T; Cabañas-Moreno, J G; Dorantes-Rosales, H J

2015-01-01

The objective of this work is to study the texture and microstructure evolution of an IF steel deformed by Accumulative Roll Bonding (ARB) using Electron Backscatter Diffraction. Texture changes occur with increasing number of ARB cycles. For the early cycles, the main components are the α and γ fiber components characteristic of steels. With increasing the number of ARB cycles a tendency towards a random texture is obtained. In the initial state, the mean grain size is 30 μm and after 5 cycles it decreases to 1.2 μm. For the first ARB cycles, the fraction of high angle grain boundary is low but it increases with the number of cycles to about 80% for 5 cycles. The Kernel Average Misorientation (KAM) has no appreciable changes with the number of ARB cycles for all the texture components. (paper)

Simulation Kinetics of Austenitic Phase Transformation in Ti+Nb Stabilized IF and Microalloyed Steels

Science.gov (United States)

Ghosh, Sumit; Dasharath, S. M.; Mula, Suhrit

2018-05-01

In the present study, the influence of cooling rates (low to ultrafast) on diffusion controlled and displacive transformation of Ti-Nb IF and microalloyed steels has been thoroughly investigated. Mechanisms of nucleation and formation of non-equiaxed ferrite morphologies (i.e., acicular ferrite and bainitic ferrite) have been analyzed in details. The continuous cooling transformation behavior has been studied in a thermomechanical simulator (Gleeble 3800) using the cooling rates of 1-150 °C/s. On the basis of the dilatometric analysis of each cooling rate, continuous cooling transformation (CCT) diagrams have been constructed for both the steels to correlate the microstructural features at each cooling rate in different critical zones. In the case of the IF steel, massive ferrite grains along with granular bainite structures have been developed at cooling rates > 120 °C/s. On the other hand, a mixture of lath bainitic and lath martensite structures has been formed at a cooling rate of 80 °C/s in the microalloyed steel. A strong dependence of the cooling rates and C content on the microstructures and mechanical properties has been established. The steel samples that were fast cooled to a mixture of bainite ferrite and martensite showed a significant improvement of impact toughness and hardness (157 J, for IF steel and 174 J for microalloyed steel) as compared to that of the as-received specimens (133 J for IF steel and 116 J for microalloyed steel). Thus, it can be concluded that the hardness and impact toughness properties are correlated well with the microstructural constituents as indicated by the CCT diagram. Transformation mechanisms and kinetics of austenitic transformation to different phase morphologies at various cooling rates have been discussed in details to correlate microstructural evolution and mechanical properties.

40 CFR 1068.430 - What happens if a family fails an SEA?

Science.gov (United States)

2010-07-01

... POLLUTION CONTROLS GENERAL COMPLIANCE PROVISIONS FOR ENGINE PROGRAMS Selective Enforcement Auditing § 1068... family if it fails the SEA under § 1068.420. The suspension may apply to all facilities producing engines...

It helps to untangle really complicated situations: 'AS IF' supervision for working with complexity

OpenAIRE

Haydon-Laurelut, Mark; Millett, E.; Bissmire, D.; Doswell, S.; Heneage, C.

2012-01-01

Working effectively with people with learning disabilities may well involve negotiating complex systems of relationships. Negotiating a network - particularly in the context of risk, anxiety, and conflict - is a common task for clinical psychologists and systemic psychotherapists in Community Learning Disability Teams (CLDT's). In this paper we describe our use of the 'AS IF' consultation exercise (Anderson, 1987) as a tool for addressing complexity and stuck-ness. We have employed 'AS IF' in...

41 CFR 102-85.205 - What happens if a customer agency continues occupancy after the expiration of an OA?

Science.gov (United States)

2010-07-01

... assignments. However, provisions are necessary to cover the GSA and customer relationship if an OA expires... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false What happens if a customer agency continues occupancy after the expiration of an OA? 102-85.205 Section 102-85.205 Public...

41 CFR 102-75.130 - If hazardous substance activity took place on the property, what specific information must an...

Science.gov (United States)

2010-07-01

... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false If hazardous substance... Utilization of Excess Real Property Title Report § 102-75.130 If hazardous substance activity took place on... quantity of such hazardous substance and the time at which such storage, release, or disposal took place...

31 CFR 19.325 - What happens if I do business with an excluded person in a covered transaction?

Science.gov (United States)

2010-07-01

... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false What happens if I do business with an excluded person in a covered transaction? 19.325 Section 19.325 Money and Finance: Treasury Office of the... Participants Regarding Transactions Doing Business with Other Persons § 19.325 What happens if I do business...

Interpreting Statistical Significance Test Results: A Proposed New "What If" Method.

Science.gov (United States)

Kieffer, Kevin M.; Thompson, Bruce

As the 1994 publication manual of the American Psychological Association emphasized, "p" values are affected by sample size. As a result, it can be helpful to interpret the results of statistical significant tests in a sample size context by conducting so-called "what if" analyses. However, these methods can be inaccurate…

A high linearity current mode second IF CMOS mixer for a DRM/DAB receiver

International Nuclear Information System (INIS)

Xu Jian; Zhou Zheng; Wu Yiqiang; Wang Zhigong; Chen Jianping

2015-01-01

A passive current switch mixer was designed for the second IF down-conversion in a DRM/DAB receiver. The circuit consists of an input transconductance stage, a passive current switching stage, and a current amplifier stage. The input transconductance stage employs a self-biasing current reusing technique, with a resistor shunt feedback to increase the gain and output impedance. A dynamic bias technique is used in the switching stage to ensure the stability of the overdrive voltage versus the PVT variations. A current shunt feedback is introduced to the conventional low-voltage second-generation fully balanced multi-output current converter (FBMOCCII), which provides very low input impedance and high output impedance. With the circuit working in current mode, the linearity is effectively improved with low supply voltages. Especially, the transimpedance stage can be removed, which simplifies the design considerably. The design is verified with a SMIC 0.18 μm RF CMOS process. The measurement results show that the voltage conversation gain is 1.407 dB, the NF is 16.22 dB, and the IIP3 is 4.5 dBm, respectively. The current consumption is 9.30 mA with a supply voltage of 1.8 V. This exhibits a good compromise among the gain, noise, and linearity for the second IF mixer in DRM/DAB receivers. (paper)

Chilean version of the INECO Frontal Screening (IFS-Ch: Psychometric properties and diagnostic accuracy

Directory of Open Access Journals (Sweden)

Josefina Ihnen

Full Text Available ABSTRACT Objective: This study sought to analyze the psychometric properties and diagnostic accuracy of the Chilean version of the INECO Frontal Screening (IFS-Ch in a sample of dementia patients and control Methods: After adapting the instrument to the Chilean context and obtaining content validity evidence through expert consultation, the IFS-Ch was administered to 31 dementia patients and 30 control subjects together with other executive assessments (Frontal Assessment Battery [FAB], Modified version of the Wisconsin Card Sorting Test [MCST], phonemic verbal fluencies [letters A and P] and semantic verbal fluency [animals] and global cognitive efficiency tests (Mini mental State Examination [MMSE] and Addenbrooke's Cognitive Examination-Revised [ACE-R]. Caregivers of dementia patients and proxies of control subjects were interviewed with instruments measuring dysexecutive symptoms (Dysexecutive Questionnaire [DEX], dementia severity (Clinical Dementia Rating Scale [CDR] and functional status in activities of daily living (Activities of Daily Living Scale [IADL] and Technology-Activities of Daily Living Questionnaire [T-ADLQ]. Convergent and discriminant validity, internal consistency reliability, cut-off points, sensitivity and specificity for the IFS-Ch were estimated. Results: Evidence of content validity was obtained. Evidence of convergent validity was also found showing significant correlations (p<0.05 between the IFS-Ch and the other instruments measuring: executive functions (FAB, r=0.935; categories achieved in the MCST, r=0.791; perseverative errors in the MCST, r= -0.617; animal verbal fluency, r=0.728; A verbal fluency, r=0.681; and P verbal fluency, r=0.783, dysexecutive symptoms in daily living (DEX, r= -0.494, dementia severity (CDR, r= -0.75 and functional status in activities of daily living (T-ADLQ, r= -0.745; IADL, r=0.717. Regarding reliability, a Cronbach's alpha coefficient of 0.905 was obtained. For diagnostic accuracy

May the Soul of the IFS Financial System Definition RIP in Developing Countries

Directory of Open Access Journals (Sweden)

Simplice A. Asongu

2015-03-01

Full Text Available In this paper, we dissect with great acuteness contemporary insufficiencies of the IFS (2008 definition of the financial system and conclude from sound theoretical underpinnings and empirical justifications that the foundation, on which it is based, while solid for developed countries, holds less ground in developing countries. Perhaps one of the deepest empirical hollows in the financial development literature has been the equation of financial depth in the perspective of money supply to liquid liabilities. This equation has put on the margin (and skewed burgeoning phenomena of mobile banking, knowledge economy (KE, inequality…etc. We conclude that the informal financial sector, a previously missing component in the IFS conception and definition of the financial system can only be marginalized at the cost of misunderstanding recent burgeoning trends in mobile phone penetration, KE and poverty. Hence, the IFS definition has incontrovertibly fought its final dead battle and lost in the face of soaring trends highlighted above. Despite the plethora of econometric and policy-making sins the definition has committed in developing countries through bias estimates and misleading inferences, may its soul RIP.

Molecular modeling of the human eukaryotic translation initiation factor 5A (eIF5A) based on spectroscopic and computational analyses

International Nuclear Information System (INIS)

Costa-Neto, Claudio M.; Parreiras-e-Silva, Lucas T.; Ruller, Roberto; Oliveira, Eduardo B.; Miranda, Antonio; Oliveira, Laerte; Ward, Richard J.

2006-01-01

The eukaryotic translation initiation factor 5A (eIF5A) is a protein ubiquitously present in archaea and eukarya, which undergoes a unique two-step post-translational modification called hypusination. Several studies have shown that hypusination is essential for a variety of functional roles for eIF5A, including cell proliferation and synthesis of proteins involved in cell cycle control. Up to now neither a totally selective inhibitor of hypusination nor an inhibitor capable of directly binding to eIF5A has been reported in the literature. The discovery of such an inhibitor might be achieved by computer-aided drug design based on the 3D structure of the human eIF5A. In this study, we present a molecular model for the human eIF5A protein based on the crystal structure of the eIF5A from Leishmania brasiliensis, and compare the modeled conformation of the loop bearing the hypusination site with circular dichroism data obtained with a synthetic peptide of this loop. Furthermore, analysis of amino acid variability between different human eIF5A isoforms revealed peculiar structural characteristics that are of functional relevance

30 CFR 250.235 - If a State objects to the EP's coastal zone consistency certification, what can I do?

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 2 2010-07-01 2010-07-01 false If a State objects to the EP's coastal zone... EP's coastal zone consistency certification, what can I do? If an affected State objects to the coastal zone consistency certification accompanying your proposed EP within the timeframe prescribed in...

Do I put Solar Panels on My Roof If My Neighbors Can See Them?

DEFF Research Database (Denmark)

Ørding Olsen, Anders; Claussen, Jörg; Tumlinson, Justin

if they want to conform to their peers. We study in how far the potential visibility of solar panels from the street influences the adoption decision of 122,349 Danish households and find that conformity motivations seem to dominate, i.e. the average household is less likely to adopt if solar panels...... are visible from the street, but less wealthy households are more likely to adopt of solar panels are visible. These findings generate policy implications for supporting the adoption of sustainable technologies....

Knowledge Management: “What If That’s Not True?”

International Nuclear Information System (INIS)

Barnes, S.

2016-01-01

Full text: Knowledge management, critical thinking, creativity, and innovation would seem to be different ideas and disciplines, but in fact they can and do enable and enrich each other as in the process of addressing the question: what if that’s not true. This technical brief explores the connections between critical thinking, creativity, innovation, and knowledge management. The result of this interconnectedness is observed in efficiency and effectiveness, competitive advantage as well as in risk informed decision making. (author

What if the Doha Round Fails? Implications for Canadian Agriculture

OpenAIRE

Gifford, Michael N.; McCalla, Alex F.; Meilke, Karl D.

2008-01-01

Many commentators assume that the WTO Doha Round negotiations have already failed and that this failure will not matter for Canadian agriculture. Neither view is correct. Most countries appear willing to make the effort needed to bring the negotiations to a make or break point in early 2008. If the Doha Round does eventually fail, an important opportunity to make the agricultural trading system significantly less distorted, more open and fair will have been lost. For Canadian agriculture, the...

25 CFR 900.48 - If the Indian tribe or tribal organization does not propose different standards, what basic...

Science.gov (United States)

2010-04-01

... EDUCATION ASSISTANCE ACT Standards for Tribal or Tribal Organization Management Systems Procurement... procurement supported by Federal funds if a conflict of interest, real or apparent, would be involved. (2) An... that is not substantial or a gift that is an unsolicited item of nominal value. (3) These standards...

Internal and overall motions of the translation factor eIF4E: Cap binding and insertion in a CHAPS detergent micelle

International Nuclear Information System (INIS)

McGuire, Abigail Manson; Matsuo, Hiroshi; Wagner, Gerhard

1998-01-01

The mRNA cap-binding protein eIF4E is the limiting factor in the eIF4F translation initiation complex, which mediates the binding of the 40S ribosome to the mRNA. 15 N relaxation studies have been used to characterize the backbone dynamics of deuterated eIF4E in a CHAPS micelle for the apoprotein, the m 7 GDP-bound form, and the dinucleotide (m 7 GpppA)-bound form, as well as for CHAPS-free eIF4E. Large differences in overall correlation time between the CHAPS-free form (11.8 ns) and samples containing different concentrations of CHAPS (15.9-19.4 ns) indicate that eIF4E is embedded in a large micelle in the presence of CHAPS, with a total molecular weight in the range of 40-60 kDa. CHAPS seems to restrict the mobility of the a2-b3 and a4-b5 loops which are thought to be embedded in the micelle. No significant changes in overall mobility were seen between the m 7 GDP-bound form, the m 7 GpppA-bound form, and the apoprotein. Amide hydrogen exchange data indicate the presence of slowly exchanging amides in two surface-exposed helices (a2 and a4), as well as the a4-b5 loop, indicating protection by the CHAPS micelle. The micelle covers the convex side of the protein away from the cap-binding site

The effect of metformin treatment on endoplasmic reticulum (ER stress induced by status epilepticus (SE via the PERK-eIF2α-CHOP pathway

Directory of Open Access Journals (Sweden)

Jing Chen

2018-02-01

Full Text Available Status epilepticus (SE is defined as continuous seizure activity lasting more than 5 minutes. It results in neuronal cell death, mediated by endoplasmic reticulum (ER stress response. Previously, metformin demonstrated neuroprotective effects in primary cortical neurons. In this study, we analyzed the effect of metformin on ER stress via the pro-apoptotic protein kinase RNA-like endoplasmic reticulum kinase (PERK-eukaryotic initiation factor 2α (eIF2α-C/EBP homologous protein (CHOP pathway. SE was induced in rats by pentylenetetrazole. Following SE, the rats were treated with salubrinal, GSK2656157, or metformin. In a control group (normal saline SE was not induced. CHOP, eIF2α, and PERK expression was determined by Western blot; apoptosis was analyzed by TUNEL assay. CHOP expression was significantly increased at 6 and 24 hours following SE. At both time points, eIF2α and PERK levels were also increased. At 6 hours, CHOP expression was significantly reduced in salubrinal, GSK2656157 and metformin groups versus SE group. eIF2α and PERK levels were decreased in metformin compared to SE group. eIF2α expression was markedly decreased in salubrinal versus SE group, while PERK expression was markedly reduced in GSK2656157 versus SE group. At 6 and 24 hours, the apoptosis rate was significantly increased in SE versus control group, while it was significantly reduced in salubrinal, GSK2656157, and metformin groups compared to SE group. The apoptosis rate also decreased in salubrinal group at 24 hours, although not to the extent observed in metformin group. Overall, CHOP expression and apoptosis induced by SE in rats were reduced with metformin. Further studies are required to evaluate the clinical relevance of metformin for patients with SE.

21 CFR 111.77 - What must you do if established specifications are not met?

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 2 2010-04-01 2010-04-01 false What must you do if established specifications are not met? 111.77 Section 111.77 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION CURRENT GOOD MANUFACTURING PRACTICE IN...

Essential role of eIF5-mimic protein in animal development is linked to control of ATF4 expression

Science.gov (United States)

Translational control of ATF4 through upstream ORFs (uORFs) plays an important role in eukaryotic gene regulation. While ATF4 translation is typically induced by inhibitory phosphorylation of eIF2, ATF4 translation can be also induced by expression of a new translational inhibitor protein, eIF5-mimi...

Sapovirus translation requires an interaction between VPg and the cap binding protein eIF4E.

Science.gov (United States)

Hosmillo, Myra; Chaudhry, Yasmin; Kim, Deok-Song; Goodfellow, Ian; Cho, Kyoung-Oh

2014-11-01

Sapoviruses of the Caliciviridae family of small RNA viruses are emerging pathogens that cause gastroenteritis in humans and animals. Molecular studies on human sapovirus have been hampered due to the lack of a cell culture system. In contrast, porcine sapovirus (PSaV) can be grown in cell culture, making it a suitable model for understanding the infectious cycle of sapoviruses and the related enteric caliciviruses. Caliciviruses are known to use a novel mechanism of protein synthesis that relies on the interaction of cellular translation initiation factors with the virus genome-encoded viral protein genome (VPg) protein, which is covalently linked to the 5' end of the viral genome. Using PSaV as a representative member of the Sapovirus genus, we characterized the role of the viral VPg protein in sapovirus translation. As observed for other caliciviruses, the PSaV genome was found to be covalently linked to VPg, and this linkage was required for the translation and the infectivity of viral RNA. The PSaV VPg protein was associated with the 4F subunit of the eukaryotic translation initiation factor (eIF4F) complex in infected cells and bound directly to the eIF4E protein. As has been previously demonstrated for feline calicivirus, a member of the Vesivirus genus, PSaV translation required eIF4E and the interaction between eIF4E and eIF4G. Overall, our study provides new insights into the novel mechanism of sapovirus translation, suggesting that sapovirus VPg can hijack the cellular translation initiation mechanism by recruiting the eIF4F complex through a direct eIF4E interaction. Sapoviruses, which are members of the Caliciviridae family, are one of the causative agents of viral gastroenteritis in humans. However, human sapovirus remains noncultivable in cell culture, hampering the ability to characterize the virus infectious cycle. Here, we show that the VPg protein from porcine sapovirus, the only cultivatable sapovirus, is essential for viral translation and

25 CFR 39.219 - What happens if a residential program does not maintain residency levels required by this subpart?

Science.gov (United States)

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false What happens if a residential program does not maintain residency levels required by this subpart? 39.219 Section 39.219 Indians BUREAU OF INDIAN AFFAIRS..., Student Counts, and Verifications Residential Programs § 39.219 What happens if a residential program does...

41 CFR 102-75.135 - If no hazardous substance activity took place on the property, what specific information must an...

Science.gov (United States)

2010-07-01

... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false If no hazardous... DISPOSAL Utilization of Excess Real Property Title Report § 102-75.135 If no hazardous substance activity... hazardous substance activity took place, the reporting agency must include the following statement: The...

41 CFR 102-75.930 - What happens if there is no objection by an appropriate committee or subcommittee of Congress...

Science.gov (United States)

2010-07-01

... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false What happens if there is no objection by an appropriate committee or subcommittee of Congress concerning the proposed... happens if there is no objection by an appropriate committee or subcommittee of Congress concerning the...

Identification of residues within the African swine fever virus DP71L protein required for dephosphorylation of translation initiation factor eIF2α and inhibiting activation of pro-apoptotic CHOP

Energy Technology Data Exchange (ETDEWEB)

Barber, Claire; Netherton, Chris; Goatley, Lynnette [The Pirbright Institute, Ash Road, Pirbright, Woking, Surrey GU24 0NF (United Kingdom); Moon, Alice; Goodbourn, Steve [Institute for Infection and Immunity, St. George' s, University of London, London SW17 0RE (United Kingdom); Dixon, Linda, E-mail: linda.dixon@pirbright.ac.uk [The Pirbright Institute, Ash Road, Pirbright, Woking, Surrey GU24 0NF (United Kingdom)

2017-04-15

The African swine fever virus DP71L protein recruits protein phosphatase 1 (PP1) to dephosphorylate the translation initiation factor 2α (eIF2α) and avoid shut-off of global protein synthesis and downstream activation of the pro-apoptotic factor CHOP. Residues V16 and F18A were critical for binding of DP71L to PP1. Mutation of this PP1 binding motif or deletion of residues between 52 and 66 reduced the ability of DP71L to cause dephosphorylation of eIF2α and inhibit CHOP induction. The residues LSAVL, between 57 and 61, were also required. PP1 was co-precipitated with wild type DP71L and the mutant lacking residues 52- 66 or the LSAVL motif, but not with the PP1 binding motif mutant. The residues in the LSAVL motif play a critical role in DP71L function but do not interfere with binding to PP1. Instead we propose these residues are important for DP71L binding to eIF2α. - Highlights: •The African swine fever virus DP71L protein recruits protein phosphatase 1 (PP1) to dephosphorylate translation initiation factor eIF2α (eIF2α). •The residues V{sup 16}, F{sup 18} of DP71L are required for binding to the α, β and γ isoforms of PP1 and for DP71L function. •The sequence LSAVL downstream from the PP1 binding site (residues 57–61) are also important for DP71L function. •DP71L mutants of the LSAVL sequence retain ability to co-precipitate with PP1 showing these sequences have a different role to PP1 binding.

What does society owe me if I am responsible for being worse off?

DEFF Research Database (Denmark)

Andersen, Martin Marchman

2014-01-01

Luck egalitarians need to address the question of cost-responsibility: If an indi- vidual is responsible for being worse off than others, then what benefits, if any, is that individual uniquely cost-responsible for? By applying luck egalitarianism to justice in health I discuss different answers...... to this question inspired by two different interpretations of luck egalitarianism, namely ‘standard luck egalitarianism’ and ‘all luck egalitarianism’, respectively. Even though I argue that the latter is more plausible than the former, I ultimately suggest and defend a third interpretation of luck egalitarianism......, which I label ‘universal luck egalitarianism’. Finally, I adjust my findings to a (all things considered) more plausible currency, namely welfare....

Involved field (IF) irradiation with or without chemotherapy in the management of children with Hodgkin's disease

International Nuclear Information System (INIS)

Jereb, B.; Tan, C.; Bretsky, S.; He, S.Q.; Exelby, P.

1984-01-01

The present policy at Memorial Sloan Kettering Cancer Center (MSKCC) of treating children with Hodgkin's disease [HD] is as follows: involved field (IF) irradiation only (3,600 rad) for Stages IA and IIA; IF irradiation (2,400 or 2,000 rad) combined with multidrug chemotherapy (MDP) protocol for all other stages. A somewhat higher recurrence rate is accepted for Stages IA and IIA in view of the good salvage rate for these recurrences and in view of side effects of more aggressive types of radiation treatment. One hundred forty-two patients with HD, 2-19 years of age, were treated at MSKCC between 1970 and 1981; 98 of these were treated according to the present policy (SP group), and 44 (NP group) were treated differently. All SP patients underwent staging laparotomy. The follow-up time was 12 to 146 months with a median of 65 months; two patients were lost to follow-up. For the SP group, all stages, 10-year disease-free survival is 77%, and 10-year survival is 93%. By comparison, in the NP group 10-year disease-free survival is 64%, and 10-year survival is 80%. The disease-free survival of SP patients in Stages IA and IIA treated with IF radiation alone is 72%, and survival is 95%. The disease-free survival of SP patients in advanced stages treated with combined radiation and chemotherapy is 87%; the salvage rate of recurrent disease in these stages is poor. The survival was apparently better in the SP group as compared to the NP group. All 6 patients of the SP group who died had a nodular sclerosing type of HD. None of the patients in the SP group have developed secondary malignancies, and no severe bone growth retardations or late effects to other organs were observed

Investigation of long-term retention of unchanged (-)-N-{2-[(R)-3-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)piperidino]ethyl}-4-fluorobenzamide, a novel "funny" If current channel inhibitor, and its metabolites in the eyeball and thoracic aorta of rats.

Science.gov (United States)

Umehara, Ken-ichi; Nakada, Naoyuki; Noguchi, Kiyoshi; Iwatsubo, Takafumi; Usui, Takashi; Kamimura, Hidetaka

2009-11-01

(-)-N-{2-[(R)-3-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)piperidino]ethyl}-4-fluorobenzamide (YM758), a novel "funny" If current channel inhibitor, was being developed as a treatment for stable angina and atrial fibrillation. After a single oral administration of (14)C-YM758, extensive accumulation and long-term retention of radioactivity were observed in the eyeballs of nonalbino rats and in the thoracic aorta of albino/nonalbino rats. Radioluminograms of the eyeballs of nonalbino rats indicated that the radioactivity was localized to the uveal tract, which suggests that the radioactivity may be positively charged and bound mainly to the melanins. Treatment with a mixture of 2 mol/l hydrochloric acid and methanol (5:95, v/v) allowed for the recovery of the major portion of radioactivity from the eyeball, which suggests reversible binding. The radioactive constituents in eyeballs consisted of the unchanged drug (YM758) and three metabolites [mainly 6,7-dimethoxy-2-[(3R)-piperidin-3-ylcarbonyl]-1,2,3,4-tetrahydroisoquinoline (YM-252124)]. Using the organic solvent mixture described above, almost all of the radioactivity was not collected from the thoracic aorta, and approximately 90% was recovered by treatment with elastase, which suggests that some metabolites covalently bind to the elastin fiber localized in the tunica media.

29 CFR 37.99 - If the Director concludes that compliance cannot be secured by voluntary means, what actions must...

Science.gov (United States)

2010-07-01

... 29 Labor 1 2010-07-01 2010-07-01 true If the Director concludes that compliance cannot be secured by voluntary means, what actions must he or she take? 37.99 Section 37.99 Labor Office of the... INVESTMENT ACT OF 1998 (WIA) Compliance Procedures § 37.99 If the Director concludes that compliance cannot...

Would we have had this crisis if women had been running the financial sector?

OpenAIRE

Staveren, Irene

2010-01-01

textabstractIntroduction In popular media and debates, both men and women sometimes utter the words that “if women had run the financial sector, we would not have found ourselves in this crisis” – or, the Lehman Sisters hypothesis. This paper will not go into the various views of sex and gender that may go behind this statement. But we do recognize the problem of natural fallacy here: if the statement would be based on a belief in some natural differences between women and men, it would imply...

43 CFR 30.267 - What if I disagree with the probate decision regarding tribal purchase option?

Science.gov (United States)

2010-10-01

... decision regarding tribal purchase option? 30.267 Section 30.267 Public Lands: Interior Office of the Secretary of the Interior INDIAN PROBATE HEARINGS PROCEDURES Tribal Purchase of Interests Under Special Statutes § 30.267 What if I disagree with the probate decision regarding tribal purchase option? If you are...

Antibiotic drug rifabutin is effective against lung cancer cells by targeting the eIF4E-β-catenin axis

Energy Technology Data Exchange (ETDEWEB)

Li, Ji; Huang, Yijiang [Department of Respiratory Medicine, Hainan General Hospital, Hainan Province (China); Gao, Yunsuo [Equipment Division, Hainan General Hospital, Hainan Province (China); Wu, Haihong; Dong, Wen [Department of Respiratory Medicine, Hainan General Hospital, Hainan Province (China); Liu, Lina, E-mail: echoliun@hotmail.com [Department of Ophthalmology, Hainan Eye Hospital, ZhongShan Ophthalmic Centre, Sun Yat-Sen University, Hainan Province (China)

2016-04-01

The essential roles of overexpression of eukaryotic translation initiation factor 4E (eIF4E) and aberrant activation of β-catenin in lung cancer development have been recently identified. However, whether there is a direct connection between eIF4E overexpression and β-catenin activation in lung cancer cells is unknown. In this study, we show that antibiotic drug rifabutin targets human lung cancer cells via inhibition of eIF4E-β-catenin axis. Rifabutin is effectively against lung cancer cells in in vitro cultured cells and in vivo xenograft mouse model through inhibiting proliferation and inducing apoptosis. Mechanistically, eIF4E regulates β-catenin activity in lung cancer cells as shown by the increased β-catenin phosphorylation and activity in cells overexpressing eIF4E, and furthermore that the regulation is dependent on phosphorylation at S209. Rifabutin suppresses eIF4E phosphorylation, leads to decreased β-catenin phosphorylation and its subsequent transcriptional activities. Depletion of eIF4E abolishes the inhibitory effects of rifabutin on β-catenin activities and overexpression of β-catenin reverses the inhibitory effects of rifabutin on cell growth and survival, further confirming that rifabutin acts on lung cancer cells via targeting eIF4E- β-catenin axis. Our findings identify the eIF4E- β-catenin axis as a critical regulator of lung cancer cell growth and survival, and suggest that its pharmacological inhibition may be therapeutically useful in lung cancer. - Highlights: • Rifabutin targets EGFR-mutated lung cancer cells in vitro and in vivo. • eIF4E phosphorylation regulates β-catenin activity in lung cancer cells. • Rifabutin acts on lung cancer cells via eIF4E- β-catenin axis. • Rifabutin can be repurposed for lung cancer treatment.

Antibiotic drug rifabutin is effective against lung cancer cells by targeting the eIF4E-β-catenin axis

International Nuclear Information System (INIS)

Li, Ji; Huang, Yijiang; Gao, Yunsuo; Wu, Haihong; Dong, Wen; Liu, Lina

2016-01-01

The essential roles of overexpression of eukaryotic translation initiation factor 4E (eIF4E) and aberrant activation of β-catenin in lung cancer development have been recently identified. However, whether there is a direct connection between eIF4E overexpression and β-catenin activation in lung cancer cells is unknown. In this study, we show that antibiotic drug rifabutin targets human lung cancer cells via inhibition of eIF4E-β-catenin axis. Rifabutin is effectively against lung cancer cells in in vitro cultured cells and in vivo xenograft mouse model through inhibiting proliferation and inducing apoptosis. Mechanistically, eIF4E regulates β-catenin activity in lung cancer cells as shown by the increased β-catenin phosphorylation and activity in cells overexpressing eIF4E, and furthermore that the regulation is dependent on phosphorylation at S209. Rifabutin suppresses eIF4E phosphorylation, leads to decreased β-catenin phosphorylation and its subsequent transcriptional activities. Depletion of eIF4E abolishes the inhibitory effects of rifabutin on β-catenin activities and overexpression of β-catenin reverses the inhibitory effects of rifabutin on cell growth and survival, further confirming that rifabutin acts on lung cancer cells via targeting eIF4E- β-catenin axis. Our findings identify the eIF4E- β-catenin axis as a critical regulator of lung cancer cell growth and survival, and suggest that its pharmacological inhibition may be therapeutically useful in lung cancer. - Highlights: • Rifabutin targets EGFR-mutated lung cancer cells in vitro and in vivo. • eIF4E phosphorylation regulates β-catenin activity in lung cancer cells. • Rifabutin acts on lung cancer cells via eIF4E- β-catenin axis. • Rifabutin can be repurposed for lung cancer treatment.

5 CFR 839.1114 - Will OPM actuarially reduce my benefit if I elect to change my retirement coverage under these...

Science.gov (United States)

2010-01-01

... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Will OPM actuarially reduce my benefit if... General Provisions § 839.1114 Will OPM actuarially reduce my benefit if I elect to change my retirement... Basic Employee Death Benefit (see § 839.1121). ...

40 CFR 60.4335 - How do I demonstrate compliance for NOX if I use water or steam injection?

Science.gov (United States)

2010-07-01

... if I use water or steam injection? 60.4335 Section 60.4335 Protection of Environment ENVIRONMENTAL... compliance for NOX if I use water or steam injection? (a) If you are using water or steam injection to... monitor and record the fuel consumption and the ratio of water or steam to fuel being fired in the turbine...

2002/2003 IfSAR data for Southern California: Digital Elevation Model (NAVD88)

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — This metadata document describes the collection and processing of topographic elevation point data derived from Interferometric Synthetic Aperture Radar (IfSAR)...

ERK 1/2 kinase metabolic pathway is responsible for phosphorylation of translation initiation factor eIF4E during in vitro maturation of pig oocytes

Czech Academy of Sciences Publication Activity Database

Ellederová, Zdeňka; Cais, Ondřej; Šušor, Andrej; Uhlířová, Kateřina; Kovářová, Hana; Jelínková, Lucie; Tomek, W.; Kubelka, Michal

2008-01-01

Roč. 75, č. 2 (2008), s. 309-317 ISSN 1040-452X R&D Projects: GA ČR GA524/04/0104 Grant - others:Deutsche Forschungsgemeinschaft(DE) 463 TSE 113/28 Institutional research plan: CEZ:AV0Z50450515; CEZ:AV0Z50110509 Keywords : meiosis * translation initiation * eIF4E Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.287, year: 2008

20 CFR 1002.265 - If the employee is reemployed with his or her pre-service employer, is the employee's pension...

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false If the employee is reemployed with his or her pre-service employer, is the employee's pension benefit the same as if he or she had remained continuously employed? 1002.265 Section 1002.265 Employees' Benefits OFFICE OF THE ASSISTANT SECRETARY FOR VETERANS' EMPLOYMENT AND TRAINING SERVICE,...

What if simulation for a Brazilian company regarding marketing budget

Directory of Open Access Journals (Sweden)

Diogo André PINTO

2016-06-01

Full Text Available The article research is a case study regarding how to design the marketing budget for a small Brazilian company that started the activity one year ago. Taking into account the data that we gather, we decided to use What-if simulation. The case study is a simplified model representation of a company, adjusted according to the data that is released as target for the following year. In practice, the formulation of a scenario allows the construction of a hypothetical world that the analyst can see and navigate.

40 CFR 35.4090 - If my group is eligible for an advance payment, how do we get our funds?

Science.gov (United States)

2010-07-01

... approval of your request, EPA will advance cash (in the form of a check or electronic funds transfer) to... 40 Protection of Environment 1 2010-07-01 2010-07-01 false If my group is eligible for an advance... Assistance How You Get the Money § 35.4090 If my group is eligible for an advance payment, how do we get our...

What You Should Know and Do This Flu Season If You Are 65 Years and Older

Science.gov (United States)

... Pandemic Other What You Should Know and Do this Flu Season If You Are 65 Years and Older Language: English (US) Español Recommend on ... for people 65 and older. Actions To Take This Flu Season: Get Your ... get a seasonal flu vaccine each year by the end of October if possible. However, ...

If the renewable energy saves a collective memory

Energy Technology Data Exchange (ETDEWEB)

Ratiba Wided, Biara; Boumediene, Touati [Laboratory of energy in Arid Zones, Faculty of Science and Technology, University of Bechar (Algeria)], email: halilouwided@yahoo.fr, email: btouatidz@yahoo.fr

2011-07-01

This paper presents a strategy of using renewable energies (solar and ground water in particular), to create a climate of well-being in the southern part of the Algerian Sahara, a vast territory, where nodal points are disparate and isolated, and where the electrification of houses and infrastructure is very difficult, if not virtually impossible. These oases are home to people with a particular culture and a rich literature which are unfortunately at risk of extinction. To protect this heritage requires that a balance be struck between the preservation of a historical and cultural identity and the improvement of the living conditions of the people in the oases, to which they are attached; this means pleasant temperatures, controlled humidity levels and abundant natural lighting. This requires providing renewable energy for the people, whether to supply drinking water or irrigation for farming and palm culture. Better integrating these people into their surrounding contexts would help stabilize them, safeguard their vernacular heritage, and facilitate transmission of their collective memory.

Estimando a necessidade: os oráculos de ifá e a verdade em Havana

Directory of Open Access Journals (Sweden)

Martin Holbraad

2003-10-01

Full Text Available O objeto deste artigo é o conceito de verdade tal como se articula no oráculo de Ifá cubano; seu objetivo é ilustrar a fecundidade de um "método ontográfico" que procure mapear as premissas ontológicas do discurso nativo por meio da produção de conceitos que, não sendo os conceitos nativos eles mesmos, constituam equivalentes aproximados destes. Enfatizando a afirmação dos praticantes de que o Ifá é infalível, propõe-se que os vereditos divinatórios devem ser entendidos como verdades necessárias, isto é, como enunciados que não poderiam não ser verdadeiros. Em seguida, mostrando que, do ponto de vista das concepções comuns de verdade, a necessidade modal dos oráculos só pode parecer um absurdo dogmático, procura-se avançar uma conceitualização alternativa que concorde com as convicções dos informantes, examinando um complexo de conceitos e práticas associados ao oráculo a fim de avaliar as premissas que garantem a verdade e sua emergência na prática do Ifá.This article analyzes the concept of truth as employed by Ifá oracles in Cuba; its aim is to illustrate the fertility of an 'ontographic method' dedicated to mapping the ontological premises of native discourse through the production of concepts which, while not the native concepts themselves, comprise close equivalents to them. Emphasizing practitioners claims that the Ifá is infallible, it is proposed that divinatory verdicts should be understood as necessary truths, that is, as statements which cannot not be true. Then, after showing that from the viewpoint of common place conceptions of truth, the modal necessity of oracles can only appear a dogmatic absurdity, I propose an alternative conceptualization which agrees with the convictions of informants. This involves examining a complex of concepts and practices linked to the oracle in order to evaluate the premises which ensure truth and its emergence in Ifá practice.

25 CFR 1000.227 - What happens if the Secretary denies the waiver request?

Science.gov (United States)

2010-04-01

... INTERIOR ANNUAL FUNDING AGREEMENTS UNDER THE TRIBAL SELF-GOVERNMENT ACT AMENDMENTS TO THE INDIAN SELF-DETERMINATION AND EDUCATION ACT Waiver of Regulations § 1000.227 What happens if the Secretary denies the waiver...

A surrogate p53 reporter in Drosophila reveals the interaction of eIF4E and p53

International Nuclear Information System (INIS)

Corujo, G.; Campagno, R.; Rivera Pomar, R.; Ferrero, P.; Lu, W.J.

2011-01-01

eIF4E promotes translation upon binding the mRNA 5'cap and it is required for cell proliferation. p53 is a proapoptotic protein which is activated in response to DNA damage. There is evidence that suggests that eIF4E and p53 are connected in a mechanism that regulates their function. We propose a model for that such a mechanism to explain the equilibrium between apoptosis and cell proliferation. Our data shows a correlation between the overexpression of eIF4E and the suppression of apoptosis triggered by the overexpression of p53 in Drosophila imaginal discs. We also studied a reporter transgene which expresses GFP in response to p53 activation by gamma radiation. We could confirm that this p53 surrogate works in imaginal discs as well as in embryos. This provided us a tool to quantify the effect on the GFP signal by overexpression of eIF4E to confirm how these two proteins could interact in vivo. Our results suggest that p53 and eIF4E are indeed in an equilibrium that decides if a cell shall proliferate or die. (authors)

45 CFR 284.21 - What will we do if the State's child poverty rate increased five percent or more over the two...

Science.gov (United States)

2010-10-01

... 45 Public Welfare 2 2010-10-01 2010-10-01 false What will we do if the State's child poverty rate... IN A STATE OR TERRITORY'S CHILD POVERTY RATE IS THE RESULT OF THE TANF PROGRAM § 284.21 What will we do if the State's child poverty rate increased five percent or more over the two-year period? (a) If...

49 CFR 40.295 - May employees or employers seek a second SAP evaluation if they disagree with the first SAP's...

Science.gov (United States)

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false May employees or employers seek a second SAP evaluation if they disagree with the first SAP's recommendations? 40.295 Section 40.295 Transportation Office... seek a second SAP evaluation if they disagree with the first SAP's recommendations? (a) As an employee...

13 CFR 127.404 - What happens if SBA is unable to verify a concern's eligibility?

Science.gov (United States)

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false What happens if SBA is unable to verify a concern's eligibility? 127.404 Section 127.404 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION WOMEN-OWNED SMALL BUSINESS FEDERAL CONTRACT ASSISTANCE PROCEDURES Eligibility Examinations § 127...

42 CFR 137.444 - If a Self-Governance Tribe objects to the recommended decision, what action will the Secretary take?

Science.gov (United States)

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false If a Self-Governance Tribe objects to the... SERVICES TRIBAL SELF-GOVERNANCE Appeals Appeals of An Immediate Reassumption of A Self-Governance Program § 137.444 If a Self-Governance Tribe objects to the recommended decision, what action will the Secretary...

If Gravity is Geometry, is Dark Energy just Arithmetic?

Science.gov (United States)

Czachor, Marek

2017-04-01

Arithmetic operations (addition, subtraction, multiplication, division), as well as the calculus they imply, are non-unique. The examples of four-dimensional spaces, R+4 and (- L/2, L/2)4, are considered where different types of arithmetic and calculus coexist simultaneously. In all the examples there exists a non-Diophantine arithmetic that makes the space globally Minkowskian, and thus the laws of physics are formulated in terms of the corresponding calculus. However, when one switches to the `natural' Diophantine arithmetic and calculus, the Minkowskian character of the space is lost and what one effectively obtains is a Lorentzian manifold. I discuss in more detail the problem of electromagnetic fields produced by a pointlike charge. The solution has the standard form when expressed in terms of the non-Diophantine formalism. When the `natural' formalsm is used, the same solution looks as if the fields were created by a charge located in an expanding universe, with nontrivially accelerating expansion. The effect is clearly visible also in solutions of the Friedman equation with vanishing cosmological constant. All of this suggests that phenomena attributed to dark energy may be a manifestation of a miss-match between the arithmetic employed in mathematical modeling, and the one occurring at the level of natural laws. Arithmetic is as physical as geometry.

Laser cladding Co-based alloy/SiCp composite coatings on IF steel

International Nuclear Information System (INIS)

Li Mingxi; He Yizhu; Sun Guoxiong

2004-01-01

Hardfacing coatings, made of Co-Cr-W-Ni-Si alloy + 20% SiCp, deposited by laser cladding on IF steel is introduced. Cross-section of such coatings has been examined to reveal their microstructure using optical microscope, scanning electron microscope (SEM) and X-ray diffractometer (XRD). MM-200 type wear tester is used to examine wear resistance of the coatings. The results showed that SiCp is dissolved completely during laser cladding process under this conditions, the primary phase γ-Co dendrite and Si 2 W, CoWSi, Cr 3 Si, CoSi 2 formed by C, Si reacting with other elements existed in the coatings. There existed some crystallization morphologies in different regions, such as planar (at the interface), followed cellular and dendrite crystallization from interface to the surface. The direction of solidification changes from one direction perpendicular to interface to multi-directions at the central and upper regions of the clad. The results also showed that the wear resistance of the clad improved by adding SiCp

25 CFR 166.307 - Will the grazing capacity be increased if I graze adjacent trust or non-trust rangelands not...

Science.gov (United States)

2010-04-01

... § 166.307 Will the grazing capacity be increased if I graze adjacent trust or non-trust rangelands not... trust or non-trust rangeland in common with the permitted land. Grazing capacity will be established... 25 Indians 1 2010-04-01 2010-04-01 false Will the grazing capacity be increased if I graze...

31 CFR 19.645 - Do other Federal agencies know if the Department of the Treasury agrees to a voluntary exclusion?

Science.gov (United States)

2010-07-01

... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Do other Federal agencies know if the Department of the Treasury agrees to a voluntary exclusion? 19.645 Section 19.645 Money and Finance: Treasury... Principles Relating to Suspension and Debarment Actions § 19.645 Do other Federal agencies know if the...

Fixed-Tuned Waveguide 0.6 THz SIS Mixer with Wide Band IF

NARCIS (Netherlands)

Baryshev, A.; Lauria, E.; Hesper, R.; Zijistra, T.; Wild, W.

2002-01-01

The Atacama Large Millimeter Array (ALMA) requires low noise SIS receivers for frequencies from about 80 GHz to 950 GHz with a very large IF bandwidth (8 GHz SSB upper or lower sideband, 8 GHz DSB or 4 GHz dual sideband, upper and lower sideband). Since there will be a large number of antennas in

High-resolution crystal structure of Streptococcus pyogenes β-NAD+ glycohydrolase in complex with its endogenous inhibitor IFS reveals a highly water-rich interface

International Nuclear Information System (INIS)

Yoon, Ji Young; An, Doo Ri; Yoon, Hye-Jin; Kim, Hyoun Sook; Lee, Sang Jae; Im, Ha Na; Jang, Jun Young; Suh, Se Won

2013-01-01

The crystal structure of the complex between the C-terminal domain of Streptococcus pyogenes β-NAD + glycohydrolase and an endogenous inhibitor for SPN was determined at 1.70 Å. It reveals that the interface between the two proteins is highly rich in water molecules. One of the virulence factors produced by Streptococcus pyogenes is β-NAD + glycohydrolase (SPN). S. pyogenes injects SPN into the cytosol of an infected host cell using the cytolysin-mediated translocation pathway. As SPN is toxic to bacterial cells themselves, S. pyogenes possesses the ifs gene that encodes an endogenous inhibitor for SPN (IFS). IFS is localized intracellularly and forms a complex with SPN. This intracellular complex must be dissociated during export through the cell envelope. To provide a structural basis for understanding the interactions between SPN and IFS, the complex was overexpressed between the mature SPN (residues 38–451) and the full-length IFS (residues 1–161), but it could not be crystallized. Therefore, limited proteolysis was used to isolate a crystallizable SPN ct –IFS complex, which consists of the SPN C-terminal domain (SPN ct ; residues 193–451) and the full-length IFS. Its crystal structure has been determined by single anomalous diffraction and the model refined at 1.70 Å resolution. Interestingly, our high-resolution structure of the complex reveals that the interface between SPN ct and IFS is highly rich in water molecules and many of the interactions are water-mediated. The wet interface may facilitate the dissociation of the complex for translocation across the cell envelope

32 CFR 37.1015 - How do I decide who must sign the TIA if the recipient is an unincorporated consortium?

Science.gov (United States)

2010-07-01

... 32 National Defense 1 2010-07-01 2010-07-01 false How do I decide who must sign the TIA if the recipient is an unincorporated consortium? 37.1015 Section 37.1015 National Defense Department of Defense... Executing the Award The Award Document § 37.1015 How do I decide who must sign the TIA if the recipient is...

Equal-channel angular sheet extrusion of interstitial-free (IF) steel: Microstructural evolution and mechanical properties

International Nuclear Information System (INIS)

Saray, O.; Purcek, G.; Karaman, I.; Neindorf, T.; Maier, H.J.

2011-01-01

Highlights: → IF-steel sheets can successfully be processed in the continuous manner using the equal-channel angular sheet extrusion (ECASE). → The ECASE produces the microstructures including dislocation cell and micro-shear bands inside the grains with mainly low-angle grain boundaries. → The ECASE results in a considerable increase in the strength but limited ductility. → A good strength-ductility balance in the ECASE-processed IF-steel sheets can be managed with a suitable annealing parameters. - Abstract: Interstitial-free steel (IF-steel) sheets were processed at room temperature using a continuous severe plastic deformation (SPD) technique called equal-channel angular sheet extrusion (ECASE). After processing, the microstructural evolution and mechanical properties have been systematically investigated. To be able to directly compare the results with those from the same material processed using discontinuous equal channel angular extrusion, the sheets were ECASE processed up to eight passes. The microstructural investigations revealed that the processed sheets exhibited a dislocation cell and/or subgrain structures with mostly low angle grain boundaries. The grains after processing have relatively high dislocation density and intense micro-shear band formation. The electron backscattering diffraction (EBSD) examination showed that the processed microstructure is not fully homogeneous along the sheet thickness due probably to the corner angle of 120 deg. in the ECASE die. It was also observed that the strengths of the processed sheets increase with the number of ECASE passes, and after eight passes following route-A and route-C, the yield strengths reach 463 MPa and 459 MPa, respectively, which is almost 2.5 times higher than that of the initial material. However, the tensile ductility considerably dropped after the ECASE. The limited ductility was attributed to the early plastic instability in the tensile samples due to the inhomogeneous

Beyond FMEA: the structured what-if technique (SWIFT).

Science.gov (United States)

Card, Alan J; Ward, James R; Clarkson, P John

2012-01-01

Although it is probably the best-known prospective hazard analysis (PHA) tool, failure mode and effects analysis (FMEA) is far from the only option available. This article introduces one of the alternatives: The structured what-if technique (SWIFT). SWIFT is a flexible, high-level risk identification technique that can be used on a stand-alone basis, or as part of a staged approach to make more efficient use of bottom-up methods like FMEA. In this article we describe the method, assess the evidence related to its use in healthcare with the use of a systematic literature review, and suggest ways in which it could be better adapted for use in the healthcare industry. Based on the limited evidence available, it appears that healthcare workers find it easy to learn, easy to use, and credible. Especially when used as part of a staged approach, SWIFT appears capable of playing a useful role as component of the PHA armamentarium. © 2012 American Society for Healthcare Risk Management of the American Hospital Association.

Pharmacogenetic Inhibition of eIF4E-Dependent Mmp9 mRNA Translation Reverses Fragile X Syndrome-like Phenotypes

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Christos G. Gkogkas

2014-12-01

Full Text Available Summary: Fragile X syndrome (FXS is the leading genetic cause of autism. Mutations in Fmr1 (fragile X mental retardation 1 gene engender exaggerated translation resulting in dendritic spine dysmorphogenesis, synaptic plasticity alterations, and behavioral deficits in mice, which are reminiscent of FXS phenotypes. Using postmortem brains from FXS patients and Fmr1 knockout mice (Fmr1−/y, we show that phosphorylation of the mRNA 5′ cap binding protein, eukaryotic initiation factor 4E (eIF4E, is elevated concomitant with increased expression of matrix metalloproteinase 9 (MMP-9 protein. Genetic or pharmacological reduction of eIF4E phosphorylation rescued core behavioral deficits, synaptic plasticity alterations, and dendritic spine morphology defects via reducing exaggerated translation of Mmp9 mRNA in Fmr1−/y mice, whereas MMP-9 overexpression produced several FXS-like phenotypes. These results uncover a mechanism of regulation of synaptic function by translational control of Mmp-9 in FXS, which opens the possibility of new treatment avenues for the diverse neurological and psychiatric aspects of FXS. : Fragile X syndrome (FXS is caused by dysregulation of translation in the brain. Gkogkas et al. show that phosphorylation of eukaryotic translation initiation factor 4E (eIF4E is increased in FXS postmortem brains and Fmr1−/y mice. Downregulation of eIF4E phosphorylation in Fmr1−/y mice rescues defects in dendritic spine morphology, synaptic plasticity, and social interaction via normalization of MMP-9 expression.

Investigation of the translation-initiation factor IF2 gene, infB, as a tool to study the population structure of Streptococcus agalactiae

DEFF Research Database (Denmark)

Hedegaard, J; Hauge, M; Fage-Larsen, J

2000-01-01

The sequence of infB, encoding the prokaryotic translation-initiation factor 2 (IF2), was determined in eight strains of Streptococcus agalactiae (group B streptococcus) and an alignment revealed limited intraspecies diversity within S. agalactiae. The amino acid sequence of IF2 from S. agalactiae...... and from related species were aligned and revealed an interspecies conserved central and C-terminal part, and an N-terminal part that is highly variable in length and amino acid sequence. The diversity and relationships in a collection of 58 genetically distinct strains of S. agalactiae were evaluated...... by comparing a partial sequence of infB. A total of six alleles were detected for the region of infB analysed. The alleles correlated with the separation of the same strains of S. agalactiae into major evolutionary lineages, as shown in previous work. The partial sequences of infB were furthermore used...

Evaluation of the effect of Chrysin and Caffeic acid phenethyl ester on eIF4E expression in AGS cell line

Directory of Open Access Journals (Sweden)

Abolhasani Marziyeh

2014-04-01

Full Text Available Introduction: The Ras/Akt/mTORC1 signal transduction pathways play a critical role in regulating translation and converge on initiation factor eukaryotic translation initiation factor 4E (eIF4E which is overexpressed in various malignancies. In the current study we aimed to assess the effect of chrysin and caffeic acid phenethyl ester (CAPE on eIF4E expression level in human stomach cancer AGS cell line. Methods: AGS cells were treated with 15, 20, 30 and 40 μM concentration of chrysin and CAPE separately, then eIF4E expression was evaluated in treated cells using real time-PCR method. Results: A significant decrease in eIF4E expression in the cells following 40 μM chrysin treatment was observed (p<0.05. There was a significant decrease in CAPE-treated cells in a dose dependent manner. Indeed the cells treated with 30 and 40 μM concentrations of CAPE, showed a significant decline in eIF4E expression (p<0.05. Conclusion: Our results suggest that CAPE and chrysin may be useful as a potential therapeutic agent for treatment of gastric cancers with an elevated eIF4E expression level.

Are carrots, corn and cattle really provided by Nature- If not ...

Science.gov (United States)

People harbor different perspectives regarding the aspects of agroecosystems or cultivated lands that are or could be considered ecosystem services. The first issues that need to be addressed in this regard are to define agro-ecosystem services and to establish their potential purpose (or use) to human beneficiaries. This early decision provides the foundation for what ecosystem services are, who uses them, and if or how they can be quantified. An important point to consider is that agricultural activities, while performed in and on environments provided by nature, are characterized by human labor and capital originating in the human economy. There are inherent reasons to quantify (i.e., measure) ecosystem services in a relatively standard way across landscapes and even within political units, such as counties or nations. Standard approaches to defining and measuring can underpin a multitude of accounting activities such as assigning value to them using either monetary or non-monetary approaches. The ecosystem services community could benefit by applying an ecosystem services definition that embodies from where in the environment the “service” originates and, equally as important, the user or beneficiary of this service. If we focus on the subset of ecosystem services which are Final Ecosystem Goods and Services by adopting the definition of Final Ecosystem Goods and Services (or FEGS), “components of nature, directly enjoyed, consumed or used to yi

Mapping polar bear maternal denning habitat in the National Petroleum Reserve -- Alaska with an IfSAR digital terrain model

Science.gov (United States)

Durner, George M.; Simac, Kristin S.; Amstrup, Steven C.

2013-01-01

The National Petroleum Reserve–Alaska (NPR-A) in northeastern Alaska provides winter maternal denning habitat for polar bears (Ursus maritimus) and also has high potential for recoverable hydrocarbons. Denning polar bears exposed to human activities may abandon their dens before their young are able to survive the severity of Arctic winter weather. To ensure that wintertime petroleum activities do not threaten polar bears, managers need to know the distribution of landscape features in which maternal dens are likely to occur. Here, we present a map of potential denning habitat within the NPR-A. We used a fine-grain digital elevation model derived from Interferometric Synthetic Aperture Radar (IfSAR) to generate a map of putative denning habitat. We then tested the map’s ability to identify polar bear denning habitat on the landscape. Our final map correctly identified 82% of denning habitat estimated to be within the NPR-A. Mapped denning habitat comprised 19.7 km2 (0.1% of the study area) and was widely dispersed. Though mapping denning habitat with IfSAR data was as effective as mapping with the photogrammetric methods used for other regions of the Alaskan Arctic coastal plain, the use of GIS to analyze IfSAR data allowed greater objectivity and flexibility with less manual labor. Analytical advantages and performance equivalent to that of manual cartographic methods suggest that the use of IfSAR data to identify polar bear maternal denning habitat is a better management tool in the NPR-A and wherever such data may be available.

I-F starting method with smooth transition to EMF based motion-sensorless vector control of PM synchronous motor/generator

DEFF Research Database (Denmark)

Blaabjerg, Frede; Teodorescu, Remus; Fatu, M.

2008-01-01

This paper proposes a novel hybrid motion- sensorless control system for permanent magnet synchronous motors (PMSM) using a new robust start-up method called I-f control, and a smooth transition to emf-based vector control. The I-f method is based on separate control of id, iq currents with the r......This paper proposes a novel hybrid motion- sensorless control system for permanent magnet synchronous motors (PMSM) using a new robust start-up method called I-f control, and a smooth transition to emf-based vector control. The I-f method is based on separate control of id, iq currents......-adaptive compensator to eliminate dc-offset and phase-delay. Digital simulations for PMSM start-up with full load torque are presented for different initial rotor-positions. The transitions from I-f to emf motion-sensorless vector control and back as well, at very low-speeds, are fully validated by experimental...

Microstructural characterization of IF steel after severe plastic deformation via ARB and subsequent heat treatment; Caracterizacao microestrutural de um aco IF apos deformacao plastica severa via ARB e posterior recozimento

Energy Technology Data Exchange (ETDEWEB)

Oliveira, F.C.; Abrantes, A.L.A.; Lins, J.F.C., E-mail: cristinafo2@hotmail.co [Universidade Federal Fluminense (PPGEM/UFF), Volta Redonda, RJ (Brazil). Programa de Pos-graduacao em Engenharia Metalurgica

2010-07-01

This study aimed to evaluate the microstructural evolution of a titanium stabilized IF steel deformed to warm through the ARB process for 5 consecutive cycles and then annealing at 600 deg C for 1 h. The material was characterized with the aid of the techniques of scanning electron microscopy and electron backscatter diffraction (Electron Backscatter Diffraction - EBSD). An intense process of microstructural refinement was observed in the deformed material and the phenomenon of dynamic recovery was predominant. It can be concluded that the annealing of severely deformed material was not sufficient for a complete recrystallization of the microstructure. (author)

20 CFR 411.205 - What if I disagree with the PM's decision about whether I am making timely progress toward self...

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2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false What if I disagree with the PM's decision... What if I disagree with the PM's decision about whether I am making timely progress toward self... decision to you. We will consider you to be making timely progress toward self-supporting employment until...

40 CFR 63.7291 - What work practice standards must I meet for fugitive pushing emissions if I have a by-product...

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2010-07-01

... meet for fugitive pushing emissions if I have a by-product coke oven battery with vertical flues? 63... meet for fugitive pushing emissions if I have a by-product coke oven battery with vertical flues? (a... existing by-product coke oven battery with vertical flues. (1) Observe and record the opacity of fugitive...

25 CFR 30.116 - If a school fails to achieve its annual measurable objectives, what other methods may it use to...

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2010-04-01

... participated in the assessment. (b) Method B—Uniform Averaging Procedure. A school may use uniform averaging... 25 Indians 1 2010-04-01 2010-04-01 false If a school fails to achieve its annual measurable... Adequate Yearly Progress § 30.116 If a school fails to achieve its annual measurable objectives, what other...

40 CFR 310.24 - What happens if I provide incorrect or false information?

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2010-07-01

... false information? 310.24 Section 310.24 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... § 310.24 What happens if I provide incorrect or false information? (a) You must not knowingly or recklessly make any statement or provide any information in your reimbursement application that is false...

State of the art of the KFUE and IfR radioactivity measurement systems

International Nuclear Information System (INIS)

Faleschini, H.; Mozer, W.

1992-01-01

A brief account is given of the KFUe and IfR measurement systems (Kernreaktor-FernUeberwachungssystem - nuclear reactor telemonitoring system/Immissionsmessnetz fuer Radioaktivitaet - radioactive-contamination monitoring system) operated by Bayerisches Landesamt fuer Umweltschutz (LfU). The corresponding measuring instruments and measuring points are described. (BBR) [de

Activist or Terrorist? Negotiating Discourses of Eco-Terror in "If a Tree Falls"

Science.gov (United States)

Olson, Jade

2018-01-01

Environmentalist voices like the Earth Liberation Front have been labeled "eco-terrorists." The 2011 documentary film "If a Tree Falls" explores how "eco-terrorism" troubles the unstable border between activism and terrorism. This essay offers a textual analysis of the film's negotiation of the activism/terrorism…

2 CFR 180.325 - What happens if I do business with an excluded person in a covered transaction?

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2010-01-01

... person, the Federal agency responsible for your transaction may disallow costs, annul or terminate the... excluded person in a covered transaction? 180.325 Section 180.325 Grants and Agreements OFFICE OF... Regarding Transactions Doing Business With Other Persons § 180.325 What happens if I do business with an...

Methodology if inspections to carry out the nuclear outages model

International Nuclear Information System (INIS)

Aycart, J.; Mortenson, S.; Fourquet, J. M.

2005-01-01

Before the nuclear generation industry was deregulated in the United States, refueling and maintenance outages in nuclear power plants usually lasted orotund 100 days. After deregulation took effect, improved capability factors and performances became more important. As a result, it became essential to reduce the critical path time during the outage, which meant that activities that had typically been done in series had to be executed in parallel. The new outage model required the development of new tools and new processes, The 360-degree platform developed by GE Energy has made it possible to execute multiple activities in parallel. Various in-vessel visual inspection (IVVI) equipments can now simultaneously perform inspections on the pressurized reactor vessel (RPV) components. The larger number of inspection equipments in turn results in a larger volume of data, with the risk of increasing the time needed for examining them and postponing the end of the analysis phase, which is critical for the outage. To decrease data analysis times, the IVVI Digitalisation process has been development. With this process, the IVVI data are sent via a high-speed transmission line to a site outside the Plant called Center of Excellence (COE), where a team of Level III experts is in charge of analyzing them. The tools for the different product lines are being developed to interfere with each other as little as possible, thus minimizing the impact of the critical path on plant refueling activities. Methods are also being developed to increase the intervals between inspection. In accordance with the guidelines of the Boiling Water Reactor Vessel and Internals project (BWRVIP), the intervals between inspections are typically longer if ultrasound volumetric inspections are performed than if the scope is limited to IVVI. (Author)

20 CFR 411.555 - Can the EN keep the milestone and outcome payments even if the beneficiary does not achieve all...

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Can the EN keep the milestone and outcome payments even if the beneficiary does not achieve all outcome months? 411.555 Section 411.555 Employees... Payment Systems § 411.555 Can the EN keep the milestone and outcome payments even if the beneficiary does...

42 CFR 137.325 - What does a Self-Governance Tribe do if it wants to perform a construction project under section...

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2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false What does a Self-Governance Tribe do if it wants to..., DEPARTMENT OF HEALTH AND HUMAN SERVICES TRIBAL SELF-GOVERNANCE Construction Project Assumption Process § 137.325 What does a Self-Governance Tribe do if it wants to perform a construction project under section...

43 CFR 30.127 - What happens if property was improperly included in the inventory?

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2010-10-01

... Interior INDIAN PROBATE HEARINGS PROCEDURES Judicial Authority and Duties § 30.127 What happens if property... proceeding, it is found that property has been improperly included in the inventory of an estate, the...

25 CFR 518.7 - If a tribe holds a certificate of self-regulation, is it required to report information to the...

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2010-04-01

... 25 Indians 2 2010-04-01 2010-04-01 false If a tribe holds a certificate of self-regulation, is it... REGULATION OF CLASS II GAMING § 518.7 If a tribe holds a certificate of self-regulation, is it required to... certificate of self-regulation shall be required to submit a self-regulation report annually to the Commission...

Answers to if the lead aprons are really helpful in nuclear medicine from the perspective of spectroscopy

International Nuclear Information System (INIS)

He, X.; Zhao, R.; Rong, L.; Yao, K.; Wei, B.; Chen, S.

2017-01-01

Wearing lead X-ray-protective aprons is a routine in nuclear medicine department in parts of China. However, the staff are often perplexed by questions such as if it is imperative to wear aprons when injecting radioactive drugs, how much radiation dosage can be shielded and if the apron will produce secondary radiation instead? To answer these questions, a semiconductor detector was employed to record different gamma and X-ray spectra with and without the lead apron or lead sheet. Then, we could estimate the signal shielding ratio to different photons for the lead apron and compare with the hospitals measured data. In general, the two results coincided well. The spectral results showed that the detrimental secondary X-rays irradiation rises when the energy of gamma rays exceeds the K absorption edge of lead (88 keV). Moreover, the aprons are not so effective for gamma rays of 364 keV emitted from "1"3"1I and 511 keV emitted from the positron radioactive nuclides. This work is purely a physical measurement in the laboratory. To the best of our knowledge, this is the first quantitative study on the level of gamma rays protection offered by the medical lead aprons and the importance of the spectroscopic measurements is discussed in this paper. (authors)

The bacterial parasite Pasteuria ramosa is not killed if it fails to infect: implications for coevolution.

Science.gov (United States)

King, Kayla C; Auld, Stuart K J R; Wilson, Philip J; James, Janna; Little, Tom J

2013-02-01

Strong selection on parasites, as well as on hosts, is crucial for fueling coevolutionary dynamics. Selection will be especially strong if parasites that encounter resistant hosts are destroyed and diluted from the local environment. We tested whether spores of the bacterial parasite Pasteuria ramosa were passed through the gut (the route of infection) of their host, Daphnia magna, and whether passaged spores remained viable for a "second chance" at infecting a new host. In particular, we tested if this viability (estimated via infectivity) depended on host genotype, whether or not the genotype was susceptible, and on initial parasite dose. Our results show that Pasteuria spores generally remain viable after passage through both susceptible and resistant Daphnia. Furthermore, these spores remained infectious even after being frozen for several weeks. If parasites can get a second chance at infecting hosts in the wild, selection for infection success in the first instance will be reduced. This could also weaken reciprocal selection on hosts and slow the coevolutionary process.

eIF5A: uma proteína essencial para a viabilidade celular cuja função permanece obscura

Directory of Open Access Journals (Sweden)

S. R. Valentini

2009-01-01

Full Text Available

O provável fator de início de tradução 5A (eIF5A é uma proteína abundante e altamente conservada em todos os organismos eucarióticos observados e também está presente em arquebactérias. eIF5A é essencial para a viabilidade celular e esse fator é a única proteína descrita que contém o resíduo de aminoácido hipusina. Em Saccharomyces cerevisiae, eIF5A é expressa em condições aeróbicas pelo gene TIF51A. Apesar de eIF5A ser conhecida há quase 30 anos, a sua função biológica ainda é obscura. Este artigo revisa os estudos de caracterização funcional de eIF5A, evidenciando como esse fator foi envolvido com diferentes etapas do metabolismo de RNA mensageiro (mRNA, como o início de tradução, o transporte nucleocitoplasmático e o decaimento de RNA mensageiro. Ainda, estudos que evidenciaram o envolvimento de eIF5A com a proliferação celular e progressão no ciclo celular também foram abordados. Finalmente, esse artigo apresenta os resultados recentes dos experimentos que colocam eIF5A novamente no cenário da tradução. Novos experimentos serão necessários para definir o papel desempenhado por eIF5A na maquinaria de tradução. Palavras-chave: eIF5A; tradução; proliferação celular; hipusina; síntese protéica

41 CFR 302-2.9 - If I am furloughed to perform active military duty, will I have to complete all aspects of the...

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2010-07-01

... 41 Public Contracts and Property Management 4 2010-07-01 2010-07-01 false If I am furloughed to... limitation? 302-2.9 Section 302-2.9 Public Contracts and Property Management Federal Travel Regulation System RELOCATION ALLOWANCES INTRODUCTION 2-EMPLOYEES ELIGIBILITY REQUIREMENTS General Rules Time Limits § 302-2.9...

41 CFR 102-75.420 - What happens if the FAA informs the disposal agency that it does not recommend disposal of the...

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2010-07-01

... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false What happens if the FAA... Real Property Disposal Property for Public Airports § 102-75.420 What happens if the FAA informs the... property that the FAA does not recommend for disposal as a public airport must be disposed of in accordance...

High-resolution crystal structure of Streptococcus pyogenes β-NAD{sup +} glycohydrolase in complex with its endogenous inhibitor IFS reveals a highly water-rich interface

Energy Technology Data Exchange (ETDEWEB)

Yoon, Ji Young; An, Doo Ri; Yoon, Hye-Jin [Seoul National University, Seoul 151-747 (Korea, Republic of); Kim, Hyoun Sook [Seoul National University, Seoul 151-747 (Korea, Republic of); Seoul National University, Seoul 151-742 (Korea, Republic of); Lee, Sang Jae [Seoul National University, Seoul 151-742 (Korea, Republic of); Im, Ha Na; Jang, Jun Young [Seoul National University, Seoul 151-747 (Korea, Republic of); Suh, Se Won, E-mail: sewonsuh@snu.ac.kr [Seoul National University, Seoul 151-747 (Korea, Republic of); Seoul National University, Seoul 151-747 (Korea, Republic of)

2013-11-01

The crystal structure of the complex between the C-terminal domain of Streptococcus pyogenes β-NAD{sup +} glycohydrolase and an endogenous inhibitor for SPN was determined at 1.70 Å. It reveals that the interface between the two proteins is highly rich in water molecules. One of the virulence factors produced by Streptococcus pyogenes is β-NAD{sup +} glycohydrolase (SPN). S. pyogenes injects SPN into the cytosol of an infected host cell using the cytolysin-mediated translocation pathway. As SPN is toxic to bacterial cells themselves, S. pyogenes possesses the ifs gene that encodes an endogenous inhibitor for SPN (IFS). IFS is localized intracellularly and forms a complex with SPN. This intracellular complex must be dissociated during export through the cell envelope. To provide a structural basis for understanding the interactions between SPN and IFS, the complex was overexpressed between the mature SPN (residues 38–451) and the full-length IFS (residues 1–161), but it could not be crystallized. Therefore, limited proteolysis was used to isolate a crystallizable SPN{sub ct}–IFS complex, which consists of the SPN C-terminal domain (SPN{sub ct}; residues 193–451) and the full-length IFS. Its crystal structure has been determined by single anomalous diffraction and the model refined at 1.70 Å resolution. Interestingly, our high-resolution structure of the complex reveals that the interface between SPN{sub ct} and IFS is highly rich in water molecules and many of the interactions are water-mediated. The wet interface may facilitate the dissociation of the complex for translocation across the cell envelope.

20 CFR 408.234 - Can you continue to receive SVB payments if you stay in the United States for more than 1 full...

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2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Can you continue to receive SVB payments if...' Benefits SOCIAL SECURITY ADMINISTRATION SPECIAL BENEFITS FOR CERTAIN WORLD WAR II VETERANS SVB... family, a transportation strike, etc.); or (2) Are exercising your option to be personally present in the...

41 CFR 105-64.502 - How do I find out if my record has been disclosed?

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2010-07-01

... Subpart 105-64.2, providing no restrictions to disclosure or accounting of disclosures applies. ... Services Administration 64-GSA PRIVACY ACT RULES 64.5-Disclosure of Records § 105-64.502 How do I find out if my record has been disclosed? You may request an accounting of the persons or agencies to whom...

45 CFR 264.72 - What requirements are imposed on a State if it receives contingency funds?

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2010-10-01

... receives contingency funds? 264.72 Section 264.72 Public Welfare Regulations Relating to Public Welfare... Contingency Fund? § 264.72 What requirements are imposed on a State if it receives contingency funds? (a)(1) A State must meet a Contingency Fund MOE level of 100 percent of historic State expenditures for FY 1994...

ITIL Based Service Level Management if SLAs Cover Security

Directory of Open Access Journals (Sweden)

Tomas Feglar

2005-08-01

Full Text Available Current level of information technology creates new perspectives for more IT service oriented market. Quality of these services requires slightly different approach then was applied for products including software. No IT services are delivered and supported in risk free environment. Risks would be considered consistently with IT services quality gaps from Service Level Management (SLM perspective. SLM is one of ITIL modules that are widely used within the IT service industry. We identified some weaknesses in how SLM is developed in ITIL environment if service level agreement (SLA has cover Security. We argue that in such cases Architecture modeling and risk assessment approach let us effectively control analytical effort that relates to risks identification and understanding. Risk driven countermeasures designed in a next step (Risk treatment have significant impact to the SLM especially from responsibility perspective. To demonstrate SLM's importance in real practice we analyze SLA synthesize process in CCI (Cyber Critical Infrastructure environment.

12 CFR 340.3 - What are the restrictions on the sale of assets by the FDIC if the buyer wants to finance the...

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2010-01-01

... 12 Banks and Banking 4 2010-01-01 2010-01-01 false What are the restrictions on the sale of assets by the FDIC if the buyer wants to finance the purchase with a loan from the FDIC? 340.3 Section 340.3 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION REGULATIONS AND STATEMENTS OF GENERAL POLICY RESTRICTIONS ON SALE OF ASSETS BY THE FEDERAL...

Prioritizing treatment outcomes: How people with acne vulgaris decide if their treatment is working.

Science.gov (United States)

Layton, Alison M; Whitehouse, Heather; Eady, E Anne; Cowdell, Fiona; Warburton, Katharine L; Fenton, Mark

2017-08-01

To collect information about how people with acne make day-to-day decisions concerning the effectiveness of their treatment. Between May and August 2013, an optional question was embedded in the James Lind Alliance Acne Priority Setting Partnership's online survey to collect treatment uncertainties. The question asked people with acne to "Tell us in your own words how you decide if your treatment has been effective." A total of 742 respondents specified at least one outcome or means of assessing change (outcome measure). Fewer spots were the most commonly cited outcome, identified by 272 respondents (36.7%). Other frequently mentioned outcomes were in descending order: less redness (19.4%), reduction in spot size (12.1%), and less pain/discomfort (11.4%). Signs were much more commonly used than symptoms and surrogate outcomes such as changes in aspects of life quality were infrequently mentioned. Visual inspection of the skin was the most widely adopted outcome measure (16.3%). Although the most frequently used methods map well onto the outcome measures adopted in the majority of acne trials, namely physician-assessed changes in lesion counts and global acne severity, people with acne often take into account several factors that cannot be assessed by a third party at a single point in time. The minimal use of changes in psychosocial wellbeing and mood may reflect that these are regarded as secondary consequences of improvements in appearance. The robustness of these findings now requires independent evaluation. If confirmed, they could form the basis of a new patient-reported outcome measure. © 2017 Chinese Cochrane Center, West China Hospital of Sichuan University and John Wiley & Sons Australia, Ltd.

If You're Concerned - Act Early

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... visit this page: About CDC.gov . Learn the Signs Home Milestones 2 months 4 months 6 months 9 months 1 year 18 months 2 years 3 years 4 years 5 years Milestone Tracker App Milestones in Action: Photos & Videos 2 months ...

How Can We Change Our Habits if We Don't Talk about Them?

Science.gov (United States)

Mantie, Roger; Talbot, Brent C.

2015-01-01

For the late nineteenth century pragmatists, habits were of great interest. Habits, and the habit of changing habits, they believed, reflected if not defined human rationality, leading William James to describe habit as "the enormous fly-wheel of society." What the pragmatists did not adequately address (at least for us) is the role of…

Downregulation of eIF4G by microRNA-503 enhances drug sensitivity of MCF-7/ADR cells through suppressing the expression of ABC transport proteins.

Science.gov (United States)

Pan, Xia; Yang, Xiaoyan; Zang, Jinglei; Zhang, Si; Huang, Nan; Guan, Xinxin; Zhang, Jianhua; Wang, Zhihui; Li, Xi; Lei, Xiaoyong

2017-06-01

Overexpression of adenosine triphosphate-binding cassette (ABC) transport protein is emerging as a critical contributor to anticancer drug resistance. The eukaryotic translation initiation factor (eIF) 4F complex, the key modulator of mRNA translation, is regulated by the phosphoinositide 3-kinase-AKT-mammalian target of rapamycin pathway in anticancer drug-resistant tumors. The present study demonstrated the roles of ABC translation protein alterations in the acquisition of the Adriamycin (ADM)-resistant phenotype of MCF-7 human breast cells. Quantitative polymerase chain reaction and western blot analysis were applied to examine the differences in mRNA and protein levels, respectively. It was found that the expression of the ABC sub-family B member 1, ABC sub-family C member 1 and ABC sub-family G member 2 transport proteins were upregulated in MCF-7/ADR cells. An MTT assay was used to detect the cell viability, from the results MCF-7/ADR cells were less sensitive to ADM, tamoxifen (TAM) and taxol (TAX) treatment compared with MCF-7 cells. We predicted that the 3'-untranslated region of eukaryotic translation initiation factor 4-γ 1 (eIF4G) contains a potential miRNA binding site for microRNA (miR)-503 through using computational programs. These binding sites were confirmed by luciferase reporter assays. eIF4G mRNA degradation was accelerated in cells transfected with miR-503 mimics. Furthermore, it was demonstrated that eIF4G and ABC translation proteins were significantly downregulated in MCF-7/ADR cells after transfection with miR-503. It was found that miR-503 mimics could sensitize the cells to treatment with ADM, TAM and TAX. These findings demonstrated for the first time that eIF4G acted as a key factor in MCF-7/ADR cells, and may be an efficient agent for preventing and reversing multi-drug resistance in breast cancer.

Multiple-Choice Testing Using Immediate Feedback--Assessment Technique (IF AT®) Forms: Second-Chance Guessing vs. Second-Chance Learning?

Science.gov (United States)

Merrel, Jeremy D.; Cirillo, Pier F.; Schwartz, Pauline M.; Webb, Jeffrey A.

2015-01-01

Multiple choice testing is a common but often ineffective method for evaluating learning. A newer approach, however, using Immediate Feedback Assessment Technique (IF AT®, Epstein Educational Enterprise, Inc.) forms, offers several advantages. In particular, a student learns immediately if his or her answer is correct and, in the case of an…

The Triticum Mosaic Virus 5' Leader Binds to Both eIF4G and eIFiso4G for Translation.

Directory of Open Access Journals (Sweden)

Robyn Roberts

Full Text Available We recently identified a remarkably strong (739 nt-long IRES-like element in the 5' untranslated region (UTR of Triticum mosaic virus (TriMV, Potyviridae. Here, we define the components of the cap-binding translation initiation complex that are required for TriMV translation. Using bio-layer interferometry and affinity capture of the native translation apparatus, we reveal that the viral translation element has a ten-fold greater affinity for the large subunit eIF4G/eIFiso4G than to the cap binding protein eIF4E/eIFiso4E. This data supports a translation mechanism that is largely dependent on eIF4G and its isoform. The binding of both scaffold isoforms requires an eight base-pair-long hairpin structure located 270 nucleotides upstream of the translation initiation site, which we have previously shown to be crucial for IRES activity. Despite a weak binding affinity to the mRNA, eIFiso4G alone or in combination with eIFiso4E supports TriMV translation in a cap-binding factor-depleted wheat germ extract. Notably, TriMV 5' UTR-mediated translation is dependent upon eIF4A helicase activity, as the addition of the eIF4A inhibitor hippuristanol inhibits 5' UTR-mediated translation. This inhibition is reversible with the addition of recombinant wheat eIF4A. These results and previous observations demonstrate a key role of eIF4G and eIF4A in this unique mechanism of cap-independent-translation. This work provides new insights into the lesser studied translation mechanisms of plant virus-mediated internal translation initiation.

A Concrete Psychological Investigation of Ifá Divination

Directory of Open Access Journals (Sweden)

Martin J. Packer

2012-01-01

Full Text Available La adivinación -consulta de un oráculo con el fin de determinar acciones futuras- se ha considerado una práctica característica de la "mentalidad primitiva". A continuación se presenta una investigación con los babalawos de la santería: los expertos en el sistema de adivinación de Ifá. El primer objetivo fue dar un ejemplo de lo que Vygotsky llamó "psicología concreta": el estudio de sistemas de funciones psicológicas particulares dentro de las circunstancias concretas de complejos profesionales específicos. El segundo objetivo fue explorar la adivinación como proceso psicológico y social, examinando las nociones, un tanto negativas, que han expresado algunos científicos sociales sobre este concepto, incluyendo a Lévy-Bruhl y al mismo Vygotsky. Algunos rasgos característicos del discurso institucional se identificaron a través del análisis de registros de audio de consultas al oráculo por parte de los autores. En este trabajo se argumentó que los aspectos institucionales de la adivinación pueden constituir una ontología poco común, pero una epistemología familiar.

Low phase noise microwave extraction from femtosecond laser by frequency conversion pair and IF-domain processing.

Science.gov (United States)

Dai, Yitang; Cen, Qizhuang; Wang, Lei; Zhou, Yue; Yin, Feifei; Dai, Jian; Li, Jianqiang; Xu, Kun

2015-12-14

Extraction of a microwave component from a low-time-jitter femtosecond pulse train has been attractive for current generation of spectrally pure microwave. In order to avoid the transfer from the optical amplitude noise to microwave phase noise (AM-PM), we propose to down-convert the target component to intermediate frequency (IF) before the opto-electronic conversion. Due to the much lower carrier frequency, the AM-PM is greatly suppressed. The target is then recovered by up-conversion with the same microwave local oscillation (LO). As long as the time delay of the second LO matches that of the IF carrier, the phase noise of the LO shows no impact on the extraction process. The residual noise of the proposed extraction is analyzed in theory, which is also experimentally demonstrated as averagely around -155 dBc/Hz under offset frequency larger than 1 kHz when 10-GHz tone is extracted from a home-made femtosecond fiber laser. Large tunable extraction from 1 GHz to 10 GHz is also reported.

40 CFR 1068.425 - What happens if one of my production-line engines/equipment exceeds the emission standards?

Science.gov (United States)

2010-07-01

... FOR ENGINE PROGRAMS Selective Enforcement Auditing § 1068.425 What happens if one of my production... engine/equipment to show it complies with all emission standards. (2) Include in your written report a...

21 CFR 822.26 - If my company changes ownership, what must I do?

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false If my company changes ownership, what must I do? 822.26 Section 822.26 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... my company changes ownership, what must I do? You must notify us within 30 days of any change in...

Requirements for Pseudomonas aeruginosa Type I-F CRISPR-Cas Adaptation Determined Using a Biofilm Enrichment Assay.

Science.gov (United States)

Heussler, Gary E; Miller, Jon L; Price, Courtney E; Collins, Alan J; O'Toole, George A

2016-11-15

CRISPR (clustered regularly interspaced short palindromic repeat)-Cas (CRISPR-associated protein) systems are diverse and found in many archaea and bacteria. These systems have mainly been characterized as adaptive immune systems able to protect against invading mobile genetic elements, including viruses. The first step in this protection is acquisition of spacer sequences from the invader DNA and incorporation of those sequences into the CRISPR array, termed CRISPR adaptation. Progress in understanding the mechanisms and requirements of CRISPR adaptation has largely been accomplished using overexpression of cas genes or plasmid loss assays; little work has focused on endogenous CRISPR-acquired immunity from viral predation. Here, we developed a new biofilm-based assay system to enrich for Pseudomonas aeruginosa strains with new spacer acquisition. We used this assay to demonstrate that P. aeruginosa rapidly acquires spacers protective against DMS3vir, an engineered lytic variant of the Mu-like bacteriophage DMS3, through primed CRISPR adaptation from spacers present in the native CRISPR2 array. We found that for the P. aeruginosa type I-F system, the cas1 gene is required for CRISPR adaptation, recG contributes to (but is not required for) primed CRISPR adaptation, recD is dispensable for primed CRISPR adaptation, and finally, the ability of a putative priming spacer to prime can vary considerably depending on the specific sequences of the spacer. Our understanding of CRISPR adaptation has expanded largely through experiments in type I CRISPR systems using plasmid loss assays, mutants of Escherichia coli, or cas1-cas2 overexpression systems, but there has been little focus on studying the adaptation of endogenous systems protecting against a lytic bacteriophage. Here we describe a biofilm system that allows P. aeruginosa to rapidly gain spacers protective against a lytic bacteriophage. This approach has allowed us to probe the requirements for CRISPR adaptation in

21 CFR 822.28 - If I stop marketing the device subject to postmarket surveillance, what must I do?

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false If I stop marketing the device subject to postmarket surveillance, what must I do? 822.28 Section 822.28 Food and Drugs FOOD AND DRUG ADMINISTRATION... of Manufacturers § 822.28 If I stop marketing the device subject to postmarket surveillance, what...

41 CFR 302-12.9 - What are the income tax consequences if I use a relocation services company?

Science.gov (United States)

2010-07-01

... the income tax consequences if I use a relocation services company? You may incur income taxes on... 41 Public Contracts and Property Management 4 2010-07-01 2010-07-01 false What are the income tax consequences if I use a relocation services company? 302-12.9 Section 302-12.9 Public Contracts and Property...

What if Dutch investors started worrying about flood risk? Implications for disaster risk reduction

NARCIS (Netherlands)

Husby, T.G.; Mechler, R.; Jongman, B.

2016-01-01

Increasingly, roles and responsibilities of the public sector in flood risk management are receiving attention in research and policy. Part of the debate suggests that allocating risk to the private sector increases efficiency as it promotes individual adaptation, thereby reducing the impact if a

Analysing the World Population: Using Population Pyramids and "If the World Were a Village"

Science.gov (United States)

Caniglia, Joanne; Leapard, Barbara

2010-01-01

The book "If the World Were a Village," by David J. Smith, is the context for analysing and creating graphs of the world's demographic information. Students examine numerical information regarding the more than six billion world inhabitants by imagining the world's population as 100 people.

20 CFR 30.312 - What will the FAB do if the claimant objects to the recommended decision but does not request a...

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false What will the FAB do if the claimant objects....312 What will the FAB do if the claimant objects to the recommended decision but does not request a... period of time allotted in § 30.310 but does not request a hearing, the FAB will consider any objections...

13 CFR 123.505 - What if you are both an essential employee and the owner of the small business and you started...

Science.gov (United States)

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false What if you are both an essential... DISASTER LOAN PROGRAM Military Reservist Economic Injury Disaster Loans § 123.505 What if you are both an essential employee and the owner of the small business and you started active duty before applying for a...

14 CFR 61.429 - May I exercise the privileges of a flight instructor certificate with a sport pilot rating if I...

Science.gov (United States)

2010-01-01

... instructor certificate with a sport pilot rating if I hold a flight instructor certificate with another... Instructors With a Sport Pilot Rating § 61.429 May I exercise the privileges of a flight instructor certificate with a sport pilot rating if I hold a flight instructor certificate with another rating? If you...

ESONANCE--IF-eb-rua

Indian Academy of Sciences (India)

would undertake to defeat any definition of chair or chairishness ... red light, you must advise a driving student to apply the brakes. ... uncertainty because of their ability to put together uncertain .... Coordinate (1, I) is interpreted as All + BII, where both A and ... represents a fuzzy set S = AIO.75 +BIO.3 with the connotation:.

40 CFR 60.4340 - How do I demonstrate continuous compliance for NOX if I do not use water or steam injection?

Science.gov (United States)

2010-07-01

... compliance for NOX if I do not use water or steam injection? 60.4340 Section 60.4340 Protection of....4340 How do I demonstrate continuous compliance for NOX if I do not use water or steam injection? (a) If you are not using water or steam injection to control NOX emissions, you must perform annual...

The consumption discount rate for the distant future (if we do not die out)

NARCIS (Netherlands)

Vermeylen, K.

2013-01-01

Gollier and Weitzman (2010) show that if future consumption discount rates are uncertain and persistent, the consumption discount rate should decline to its lowest possible value for events in the most distant future. In this paper, I argue that the lowest possible growth rate of consumption per

If I had a magic wand....Wish list of a dermatologist (Conference Presentation)

Science.gov (United States)

Kelly, Kristen M.

2016-02-01

Challenges in dermatology that can be addressed by photonics research will be explored. Non-invasive, real-time diagnosis of skin lesions would eliminate biopsy risks, minimize patient anxiety by providing more rapid answers and allow diagnosis and treatment in a single visit. Multiple approaches have been tried, but significant limitations of current technologies make them impractical for routine clinic implementation. Photonics can also be used for treatment assessment to determine if intervention is adequate or if further treatment is needed. Ideal feedback should be non-invasive, rapid and accurate. Monitoring for potential adverse effects can greatly improve treatment safety, allowing clinicians to push the limits of therapy while preventing serious complications. Light based therapies can also be improved by increasing photon penetration and selectivity for targeted cells or skin structures. Current light based treatments are in many cases limited by photon penetration. In addition, we often seek to damage a specific chromophore but are not able to distinguish between targeted disease and non-targeted normal structures such as the cells of a melanoma and normal melanocytes and port wine stain versus normal vasculature. Scientist and clinician collaboration can address these and other issues and greatly improve patient care.

A comparison of photograph-interpreted and IfSAR-derived maps of polar bear denning habitat for the 1002 Area of the Arctic National Wildlife Refuge, Alaska

Science.gov (United States)

Durner, George M.; Atwood, Todd C.

2018-05-11

Polar bears (Ursus maritimus) in Alaska use the Arctic National Wildlife Refuge (ANWR) for maternal denning. Pregnant bears den in snow banks for more than 3 months in winter during which they give birth to and nurture young. Denning is one of the most vulnerable times in polar bear life history as the family group cannot simply walk away from a disturbance without jeopardizing survival of newly born cubs. The ANWR includes the “1002 Area”, a region recently opened for oil and gas exploration by the U.S. Department of the Interior (DOI). As a part of its mission, the DOI “… protects and manages the Nation's natural resources …” and is therefore responsible for conserving polar bears and encouraging development of energy potential. Because future industrial activities could overlap habitats used by denning polar bears, identifying these habitats can inform the decisions of resource managers tasked to develop resources and protect polar bears. To help inform these efforts, we qualitatively compared the distribution of denning habitat identified by two different methods: previously published habitat from manual interpretation of aerial photographs, and habitat derived by computer interrogation of interferometric synthetic aperture radar (IfSAR) digital terrain models (DTM). Because photograph-interpreted methods depicted denning habitat as a line and IfSAR-derived methods depicted habitat as a polygon, we assessed agreement between the two methods with distance measurements. We found that 77.5 percent of IfSAR-derived denning habitat (79.6 km2 ; 1.2 percent of the 6,837.0 km2 1002 Area) was within 600 m of photograph-interpreted habitat (3,026.9 km), including 53.9 percent within 200 m. This distribution differed from that of randomly distributed points, as only 49.4 percent of these occurred within 600 m of photograph-interpreted habitat, including 18.3 percent within 200 m. Both methods appear to identify the major physiographic features that polar bears

31 CFR 380.3 - What collateral may I pledge if I am a Treasury Tax and Loan depositary under 31 CFR part 203...

Science.gov (United States)

2010-07-01

... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false What collateral may I pledge if I am a Treasury Tax and Loan depositary under 31 CFR part 203, and what value will you assign to it? 380...) FISCAL SERVICE, DEPARTMENT OF THE TREASURY BUREAU OF THE PUBLIC DEBT COLLATERAL ACCEPTABILITY AND...

The Riemann Problem for the Multidimensional Isentropic System of Gas Dynamics is Ill-Posed if It Contains a Shock

Science.gov (United States)

Markfelder, Simon; Klingenberg, Christian

2018-03-01

In this paper we consider the isentropic compressible Euler equations in two space dimensions together with particular initial data. This data consists of two constant states, where one state lies in the lower and the other state in the upper half plane. The aim is to investigate whether there exists a unique entropy solution or if the convex integration method produces infinitely many entropy solutions. For some initial states this question has been answered by Feireisl and Kreml (J Hyperbolic Differ Equ 12(3):489-499, 2015), and also Chen and Chen (J Hyperbolic Differ Equ 4(1):105-122, 2007), where there exists a unique entropy solution. For other initial states Chiodaroli and Kreml (Arch Ration Mech Anal 214(3):1019-1049, 2014) and Chiodaroli et al. (Commun Pure Appl Math 68(7):1157-1190, 2015), showed that there are infinitely many entropy solutions. For still other initial states the question on uniqueness remained open and this will be the content of this paper. This paper can be seen as a completion of the aforementioned papers by showing that the solution is non-unique in all cases (except if the solution is smooth).

40 CFR 63.2166 - How do I demonstrate initial compliance with the emission limitations if I monitor brew ethanol?

Science.gov (United States)

2010-07-01

... with the emission limitations if I monitor brew ethanol? 63.2166 Section 63.2166 Protection of... demonstrate initial compliance with the emission limitations if I monitor brew ethanol? (a) You must... subpart. (b) You must establish the brew-to-exhaust correlation for each fermentation stage according to...

Translation Initiation Factor eIF4E and eIFiso4E Are Both Required for Peanut stripe virus Infection in Peanut (Arachis hypogaea L.).

Science.gov (United States)

Xu, Manlin; Xie, Hongfeng; Wu, Juxiang; Xie, Lianhui; Yang, Jinguang; Chi, Yucheng

2017-01-01

Peanut stripe virus (PStV) belongs to the genus Potyvirus and is the most important viral pathogen of cultivated peanut ( Arachis hypogaea L.). The eukaryotic translation initiation factor, eIF4E, and its isoform, eIF(iso)4E, play key roles during virus infection in plants, particularly Potyvirus . In the present study, we cloned the eIF4E and eIF(iso)4E homologs in peanut and named these as PeaeIF4E and PeaeIF(iso)4E , respectively. Quantitative real-time PCR (qRT-PCR) analysis showed that these two genes were expressed during all growth periods and in all peanut organs, but were especially abundant in young leaves and roots. These also had similar expression levels. Yeast two-hybrid analysis showed that PStV multifunctional helper component proteinase (HC-Pro) and viral protein genome-linked (VPg) both interacted with PeaeIF4E and PeaeIF(iso)4E. Bimolecular fluorescence complementation assay showed that there was an interaction between HC-Pro and PeaeIF4E/PeaeIF(iso)4E in the cytoplasm and between VPg and PeaeIF4E/PeaeIF(iso)4E in the nucleus. Silencing either PeaeIF4E or PeaeIF(iso)4E using a virus-induced gene silencing system did not significantly affect PStV accumulation. However, silencing both PeaeIF4E and PeaeIF(iso)4E genes significantly weakened PStV accumulation. The findings of the present study suggest that PeaeIF4E and PeaeIF(iso)4E play important roles in the PStV infection cycle and may potentially contribute to PStV resistance.

What if LIGO's gravitational wave detections are strongly lensed by massive galaxy clusters?

Science.gov (United States)

Smith, Graham P.; Jauzac, Mathilde; Veitch, John; Farr, Will M.; Massey, Richard; Richard, Johan

2018-04-01

Motivated by the preponderance of so-called `heavy black holes' in the binary black hole (BBH) gravitational wave (GW) detections to date, and the role that gravitational lensing continues to play in discovering new galaxy populations, we explore the possibility that the GWs are strongly lensed by massive galaxy clusters. For example, if one of the GW sources were actually located at z = 1, then the rest-frame mass of the associated BHs would be reduced by a factor of ˜2. Based on the known populations of BBH GW sources and strong-lensing clusters, we estimate a conservative lower limit on the number of BBH mergers detected per detector year at LIGO/Virgo's current sensitivity that are multiply-imaged, of Rdetect ≃ 10-5 yr-1. This is equivalent to rejecting the hypothesis that one of the BBH GWs detected to date was multiply-imaged at ≲4σ. It is therefore unlikely, but not impossible, that one of the GWs is multiply-imaged. We identify three spectroscopically confirmed strong-lensing clusters with well-constrained mass models within the 90 per cent credible sky localizations of the BBH GWs from LIGO's first observing run. In the event that one of these clusters multiply-imaged one of the BBH GWs, we predict that 20-60 per cent of the putative next appearances of the GWs would be detectable by LIGO, and that they would arrive at Earth within 3yr of first detection.

A Simple Method to Determine if a Music Information Retrieval System is a "Horse"

DEFF Research Database (Denmark)

Sturm, Bob L.

2014-01-01

We propose and demonstrate a simple method to determine if a music information retrieval (MIR) system is using factors irrelevant to the task for which it is designed. This is of critical importance to certain use cases, but cannot be accomplished using standard approaches to evaluation in MIR...

If this then that: an introduction to automated task services.

Science.gov (United States)

Hoy, Matthew B

2015-01-01

This article explores automated task services, a type of website that allows users to create rules that are triggered by activity on one website and perform a task on another site. The most well-known automated task service is If This Then That (IFTTT), but recently a large number of these services have sprung up. These services can be used to connect websites, apps, business services, and even devices such as phones and home automation equipment. This allows for millions of possible combinations of rules, triggers, and actions. Librarians can put these services to use in many ways, from automating social media postings to remembering to bring their umbrella when rain is in the forecast. A list of popular automated task services is included, as well as a number of ideas for using these services in libraries.

20 CFR 10.812 - If OWCP reduces a fee, may a provider request reconsideration of the reduction?

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false If OWCP reduces a fee, may a provider request reconsideration of the reduction? 10.812 Section 10.812 Employees' Benefits OFFICE OF WORKERS' COMPENSATION.... Department of Labor, Office of Workers' Compensation Programs, Washington, DC 20210, or from the Internet at...

The mechanical design of CHARIS: an exoplanet IFS for the Subaru Telescope

Science.gov (United States)

Galvin, Michael B.; Carr, Michael A.; Groff, Tyler D.; Kasdin, N. Jeremy; Fagan, Radford; Hayashi, Masahiko; Takato, Naruhisa

2014-07-01

Princeton University is designing and building an integral field spectrograph (IFS), the Coronagraphic High Angular Resolution Imaging Spectrograph (CHARIS), for integration with the Subaru Corona Extreme Adaptive Optics (SCExAO) system and the AO188 adaptive optics system on the Subaru Telescope. CHARIS and SCExAO will measure spectra of hot, young Jovian planets in a coronagraphic image across J, H, and K bands down to an 80 milliarcsecond inner working angle. Here we present the current status of the mechanical design of the CHARIS instrument.

37 CFR 10.66 - Refusing to accept or continue employment if the interests of another client may impair the...

Science.gov (United States)

2010-07-01

... continue employment if the interests of another client may impair the independent professional judgment of... employment if the interests of another client may impair the independent professional judgment of the... independent professional judgment in behalf of a client will be or is likely to be adversely affected by the...

The retinamide VNLG-152 inhibits f-AR/AR-V7 and MNK-eIF4E signaling pathways to suppress EMT and castration-resistant prostate cancer xenograft growth.

Science.gov (United States)

Ramamurthy, Vidya P; Ramalingam, Senthilmurugan; Gediya, Lalji K; Njar, Vincent C O

2018-03-01

VNLG-152 is a novel retinamide (NR) shown to suppress growth and progression of genetically diverse prostate cancer cells via inhibition of androgen receptor signaling and eukaryotic initiation factor 4E (eIF4E) translational machinery. Herein, we report therapeutic effects of VNLG-152 on castration-resistant prostate cancer (CRPC) growth and metastatic phenotype in a CRPC tumor xenograft model. Administration of VNLG-152 significantly and dose-dependently suppressed the growth of aggressive CWR22Rv1 tumors by 63.4% and 76.3% at 10 and 20 mg·kg -1 bw, respectively (P AR)/androgen receptor splice variant-7 (AR-V7), mitogen-activated protein kinase-interacting kinases 1 and 2 (MNK1/2), phosphorylated eIF4E and their associated target proteins, including prostate-specific antigen, cyclin D1 and Bcl-2, were strongly decreased in VNLG-152-treated tumors signifying inhibition of f-AR/AR-V7 and MNK-eIF4E signaling in VNLG-152-treated CWR22Rv1 tumors as observed in vitro. VNLG-152 also suppressed the epithelial to mesenchymal transition in CWR22Rv1 tumors as evidenced by repression of N-cadherin, β-catenin, claudin, Slug, Snail, Twist, vimentin and matrix metalloproteinases (MMP-2 and MMP-9) with upsurge in E-cadherin. These results highlight the promising use of VNLG-152 in CRPC therapy and justify its further development towards clinical trials. © 2018 Federation of European Biochemical Societies.

High eIF4E Overexpression in Node Negative Breast Cancer as Predictor for Recurrence

National Research Council Canada - National Science Library

Li, Benjamin

2002-01-01

.... EIF4E overexpression has been found in human malignancies (Li, 1997; Nathan, 1997). Furthermore, there appears to be an association of eIF4E overexpression and clinical outcomes (Li, 1998; Nathan, 1997; Li, 2001...

50 CFR 84.49 - What if the project costs more or less than originally expected?

Science.gov (United States)

2010-10-01

... monies for approved coastal wetland grants will be subject to the entire review process along with new grants. Any monies left over after the project is complete, or if the project is not completed, should be...

13 CFR 126.308 - What happens if SBA inadvertently omits a qualified HUBZone SBC from the List?

Science.gov (United States)

2010-01-01

... writing at U.S. Small Business Administration, 409 Third Street, SW., Washington, DC 20416 or via e-mail... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false What happens if SBA inadvertently omits a qualified HUBZone SBC from the List? 126.308 Section 126.308 Business Credit and Assistance...

Would we have had this crisis if women had been running the financial sector?

NARCIS (Netherlands)

I.P. van Staveren (Irene)

2010-01-01

textabstractIntroduction In popular media and debates, both men and women sometimes utter the words that “if women had run the financial sector, we would not have found ourselves in this crisis” – or, the Lehman Sisters hypothesis. This paper will not go into the various views of sex and gender

20 CFR 30.712 - If OWCP reduces a fee, may a provider request reconsideration of the reduction?

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false If OWCP reduces a fee, may a provider request reconsideration of the reduction? 30.712 Section 30.712 Employees' Benefits OFFICE OF WORKERS' COMPENSATION... Internet at http://www.dol.gov/esa/regs/compliance/owcp/eeoicp/main.htm. Within 30 days of receiving the...

Analysing student written solutions to investigate if problem-solving processes are evident throughout

Science.gov (United States)

Kelly, Regina; McLoughlin, Eilish; Finlayson, Odilla E.

2016-07-01

An interdisciplinary science course has been implemented at a university with the intention of providing students the opportunity to develop a range of key skills in relation to: real-world connections of science, problem-solving, information and communications technology use and team while linking subject knowledge in each of the science disciplines. One of the problems used in this interdisciplinary course has been selected to evaluate if it affords students the opportunity to explicitly display problem-solving processes. While the benefits of implementing problem-based learning have been well reported, far less research has been devoted to methods of assessing student problem-solving solutions. A problem-solving theoretical framework was used as a tool to assess student written solutions to indicate if problem-solving processes were present. In two academic years, student problem-solving processes were satisfactory for exploring and understanding, representing and formulating, and planning and executing, indicating that student collaboration on problems is a good initiator of developing these processes. In both academic years, students displayed poor monitoring and reflecting (MR) processes at the intermediate level. A key impact of evaluating student work in this way is that it facilitated meaningful feedback about the students' problem-solving process rather than solely assessing the correctness of problem solutions.

“It would have been better if I had never known”: why Swazi women ...

International Development Research Centre (IDRC) Digital Library (Canada)

2017-08-17

Aug 17, 2017 ... “It would have been better if I had never known”: why Swazi women avoid cancer screening ... telling me they would not attend cervical screening due to the lack of ... long enough to appreciate the complex web of political, economic, ... In S. Lindenbaum & M. Lock (Eds.), Knowledge, power and practice: the ...

'Like Playing with Fire Under a Hut' - You Will Get Burnt If You Do ...

African Journals Online (AJOL)

'Like Playing with Fire Under a Hut' - You Will Get Burnt If You Do Not Adjust: Reflections of Social Work Students on Adjusting to University Life. ... High dropout rates in first year and the enculturation into the academic literacies essential in promoting a successful academic adjustment are some of the challenges faced by ...

NO CHANGES IN SERUM CONCENTRATIONS OF INTERLEUKIN 10 (IL-10) AND INTERFERON γ (IF-γ) BEFORE AND AFTER TREATMENT OF THE THYROID EYE DISEASE (TED)

Science.gov (United States)

Laban-Gučeva, Nevenka; Antova, Magdalena; Bogoev, Milco

2007-01-01

TED is a severe eye disease leading in rare cases to decrease of sight, optic nerve compression and blindness. Recently, significant progresses in understanding the disease have been done. Nevertheless, the treatment of the disease, especially in its severe form remains challenging. Glucocorticoids (GC) have been the basis of the treatment for a long time. Orbital irradiation (OI) and optical decompression (OD) are also used in managing the severe forms of TED. Somatostatin, intravenous immunoglobulin have been also used, with conflicting results. Regarding the potential for the treatment of TED with cytokine antagonists, controlled clinical studies are not available. Since cytokines play an important role in the pathogenesis of the TED, they seemed to be logical choice for modern TED treatment. It has been shown that both Th1 (interleukin-2, tumor necrosis factor γ, interleukin γ) and Th2 (interleukin-4,-5-,-10) profile T cells are activated in the TED. We therefore measured interleukin-γ, IF-γ and interleukin -10 (IL-10)(Th1 and Th2 pattern) to assess its relationship to the course of the disease. This paper shows that both Th1 (Il-2) and Th2 (If-γ) pathways represented by those two cytokines are not involved (Il-10 before 2,29±5,23 and after treatment 3,77±8,44; IF γ before 0,50±0,24 and after treatment 0,35±0,19). No relationship to the response to treatment was found. GC resulted in positive response in 8/22 patients, OI (12 patients) given after CS therapy, resulted in a response in all patients. Increase in proptosis, loss of visual acuity is spite of CS treatment prompted OD in two patients, who both recovered visual acuity and proptosis fell under 25mm Hertel. PMID:18039196

No changes in serum concentrations of interleukin 10 (IL-10) and interferon gamma (IF-gamma) before and after treatment of the thyroid eye disease (TED).

Science.gov (United States)

Laban-Guceva, Nevenka; Antova, Magdalena; Bogoev, Milco

2007-11-01

TED is a severe eye disease leading in rare cases to decrease of sight, optic nerve compression and blindness. Recently, significant progresses in understanding the disease have been done. Nevertheless, the treatment of the disease, especially in its severe form remains challenging. Glucocorticoids (GC) have been the basis of the treatment for a long time. Orbital irradiation (OI) and optical decompression (OD) are also used in managing the severe forms of TED. Somatostatin, intravenous immunoglobulin have been also used, with conflicting results. Regarding the potential for the treatment of TED with cytokine antagonists, controlled clinical studies are not available. Since cytokines play an important role in the pathogenesis of the TED, they seemed to be logical choice for modern TED treatment. It has been shown that both Th1 (interleukin-2, tumor necrosis factor gamma, interleukin gamma) and Th2 (interleukin -4, -5, -10) profile T cells are activated in the TED. We therefore measured interleukin-gamma, IF-gamma and interleukin -10 (IL-10)(Th1 and Th2 pattern) to assess its relationship to the course of the disease. This paper shows that both Th1 (IL-2) and Th2 (IF-gamma) pathways represented by those two cytokines are not involved (IL-10 before 2.29+/-5.23 and after treatment 3.77+/-8.44; IF gamma before 0.50+/-0.24 and after treatment 0.35+/-0.19). No relationship to the response to treatment was found. GC resulted in positive response in 8/22 patients, OI (12 patients) given after CS therapy, resulted in a response in all patients. Increase in proptosis, loss of visual acuity is spite of CS treatment prompted OD in two patients, who both recovered visual acuity and proptosis fell under 25 mm Hertel.

No Changes in Serum Concentrations of Interleukin 10 (IL-10 and Interferon γ (IF-γ Before and After Treatment of the Thyroid Eye Disease (TED

Directory of Open Access Journals (Sweden)

Nevenka Laban-Gučeva

2008-11-01

Full Text Available TED is a severe eye disease leading in rare cases to decrease of sight, optic nerve compression and blindness. Recently, significant progresses in understanding the disease have been done. Nevertheless, the treatment of the disease, especially in its severe form remains challenging. Glucocorticoids (GC have been the basis of the treatment for a long time. Orbital irradiation (OI and optical decompression (OD are also used in managing the severe forms of TED. Somatostatin, intravenous immunoglobulin have been also used, with conflicting results. Regarding the potential for the treatment of TED with cytokine antagonists, controlled clinical studies are not available. Since cytokines play an important role in the pathogenesis of the TED, they seemed to be logical choice for modern TED treatment. It has been shown that both Th1 (interleukin-2, tumor necrosis factor γ, interleukin γ and Th2 (interleukin-4,-5-,-10 profile T cells are activated in the TED. We therefore measured interleukin-γ, IF-γ and interleukin -10 (IL-10(Th1 and Th2 pattern to assess its relationship to the course of the disease. This paper shows that both Th1 (Il-2 and Th2 (If-γ pathways represented by those two cytokines are not involved (Il-10 before 2,29±5,23 and after treatment 3,77±8,44; IF γ before 0,50±0,24 and after treatment 0,35±0,19. No relationship to the response to treatment was found. GC resulted in positive response in 8/22 patients, OI (12 patients given after CS therapy, resulted in a response in all patients. Increase in proptosis, loss of visual acuity is spite of CS treatment prompted OD in two patients, who both recovered visual acuity and proptosis fell under 25mm Hertel.

Genome-wide analyses and functional classification of proline repeat-rich proteins: potential role of eIF5A in eukaryotic evolution.

Directory of Open Access Journals (Sweden)

Ajeet Mandal

Full Text Available The eukaryotic translation factor, eIF5A has been recently reported as a sequence-specific elongation factor that facilitates peptide bond formation at consecutive prolines in Saccharomyces cerevisiae, as its ortholog elongation factor P (EF-P does in bacteria. We have searched the genome databases of 35 representative organisms from six kingdoms of life for PPP (Pro-Pro-Pro and/or PPG (Pro-Pro-Gly-encoding genes whose expression is expected to depend on eIF5A. We have made detailed analyses of proteome data of 5 selected species, Escherichia coli, Saccharomyces cerevisiae, Drosophila melanogaster, Mus musculus and Homo sapiens. The PPP and PPG motifs are low in the prokaryotic proteomes. However, their frequencies markedly increase with the biological complexity of eukaryotic organisms, and are higher in newly derived proteins than in those orthologous proteins commonly shared in all species. Ontology classifications of S. cerevisiae and human genes encoding the highest level of polyprolines reveal their strong association with several specific biological processes, including actin/cytoskeletal associated functions, RNA splicing/turnover, DNA binding/transcription and cell signaling. Previously reported phenotypic defects in actin polarity and mRNA decay of eIF5A mutant strains are consistent with the proposed role for eIF5A in the translation of the polyproline-containing proteins. Of all the amino acid tandem repeats (≥3 amino acids, only the proline repeat frequency correlates with functional complexity of the five organisms examined. Taken together, these findings suggest the importance of proline repeat-rich proteins and a potential role for eIF5A and its hypusine modification pathway in the course of eukaryotic evolution.

50 CFR 23.91 - How do I find out if a species is listed?

Science.gov (United States)

2010-10-01

... FAUNA AND FLORA (CITES) Lists of Species § 23.91 How do I find out if a species is listed? (a) CITES list. The official CITES list includes species of wildlife and plants placed in Appendix I, II, and III... the CITES Secretariat based on decisions of the Parties. You may access the official list from the...

eIF4A inhibition allows translational regulation of mRNAs encoding proteins involved in Alzheimer's disease.

Directory of Open Access Journals (Sweden)

Andrew Bottley

2010-09-01

Full Text Available Alzheimer's disease (AD is the main cause of dementia in our increasingly aging population. The debilitating cognitive and behavioral symptoms characteristic of AD make it an extremely distressing illness for patients and carers. Although drugs have been developed to treat AD symptoms and to slow disease progression, there is currently no cure. The incidence of AD is predicted to increase to over one hundred million by 2050, placing a heavy burden on communities and economies, and making the development of effective therapies an urgent priority. Two proteins are thought to have major contributory roles in AD: the microtubule associated protein tau, also known as MAPT; and the amyloid-beta peptide (A-beta, a cleavage product of amyloid precursor protein (APP. Oxidative stress is also implicated in AD pathology from an early stage. By targeting eIF4A, an RNA helicase involved in translation initiation, the synthesis of APP and tau, but not neuroprotective proteins, can be simultaneously and specifically reduced, representing a novel avenue for AD intervention. We also show that protection from oxidative stress is increased upon eIF4A inhibition. We demonstrate that the reduction of these proteins is not due to changes in mRNA levels or increased protein degradation, but is a consequence of translational repression conferred by inhibition of the helicase activity of eIF4A. Inhibition of eIF4A selectively and simultaneously modulates the synthesis of proteins involved in Alzheimer's disease: reducing A-beta and tau synthesis, while increasing proteins predicted to be neuroprotective.

45 CFR 73.735-903 - Action if conflicts of interest or possible conflicts are noted.

Science.gov (United States)

2010-10-01

... GENERAL ADMINISTRATION STANDARDS OF CONDUCT Reporting Financial Interests § 73.735-903 Action if conflicts... a financial interest statement, a reviewing official believes that additional information is needed... the basis of information submitted, the reporting individual is not in compliance with applicable laws...

Recognizing Risk and Vulnerability in Research Ethics: Imagining the "What Ifs?"

Science.gov (United States)

Peter, Elizabeth; Friedland, Judith

2017-04-01

Research ethics committees (RECs) may misunderstand the vulnerability of participants, given their distance from the field. What RECs identify as the vulnerabilities that were not adequately recognized in protocols and how they attempt to protect the perceived vulnerability of participants and mitigate risks were examined using the response letters sent to researchers by three university-based RECs. Using a critical qualitative method informed by feminist ethics, we identified an overarching theme of recognizing and responding to cascading vulnerabilities and four subthemes: identifying vulnerable groups, recognizing potentially risky research, imagining the "what ifs," and mitigating perceived risks. An ethics approach that is up-close, as opposed to distant, is needed to foster closer relationships among participants, researchers, and RECs and to understand participant vulnerability and strength better.

A Wide-Band High-Gain Compact SIS Receiver Utilizing a 300-μW SiGe IF LNA

Science.gov (United States)

Montazeri, Shirin; Grimes, Paul K.; Tong, Cheuk-Yu Edward; Bardin, Joseph C.

2017-06-01

Low-power low-noise amplifiers integrated with superconductor-insulator-superconductor (SIS) mixers are required to enable implementation of large-scale focal plane arrays. In this work, a 220-GHz SIS mixer has been integrated with a high-gain broad-band low-power IF amplifier into a compact receiver module. The low noise amplifier (LNA) was specifically designed to match to the SIS output impedance and contributes less than 7 K to the system noise temperature over the 4-8 GHz IF frequency range. A receiver noise temperature of 30-45 K was measured for a local oscillator frequency of 220 GHz over an IF spanning 4-8 GHz. The LNA power dissipation was only 300-μW. To the best of the authors' knowledge, this is the lowest power consumption reported for a high-gain wide-band LNA directly integrated with an SIS mixer.

49 CFR 381.410 - What may I do if I have an idea or suggestion for a pilot program?

Science.gov (United States)

2010-10-01

... 49 Transportation 5 2010-10-01 2010-10-01 false What may I do if I have an idea or suggestion for... may I do if I have an idea or suggestion for a pilot program? (a) You may send a written statement...) Principal place of business for the motor carrier (street address, city, State, and zip code); and (4) The...

49 CFR 40.303 - What happens if the SAP believes the employee needs additional treatment, aftercare, or support...

Science.gov (United States)

2010-10-01

... recommended services. You may also make use of SAP and employee assistance program (EAP) services in assisting... 49 Transportation 1 2010-10-01 2010-10-01 false What happens if the SAP believes the employee needs additional treatment, aftercare, or support group services even after the employee returns to...

Mechanical properties and corrosion resistance of nitrided or oxinitrided, and powder painted regular and interstitial free (IF) drawing steel sheet

Energy Technology Data Exchange (ETDEWEB)

Rogalski, Z.; Latas, Z. [Instytut Mechaniki Precyzyjnej, ul. Duchnicka 3, 01-796 Warszawa (Poland)

2004-06-01

Specimens of 0.8 mm thick regular and interstitial free (IF) drawing steel sheet have been nitrided in fluidised bed for 2 hours at 620 C and 560 C with and without a post-oxidation, and slow and accelerated cooling. As a result, surface hardness, yield and tensile strength of the sheets increased considerably without a critical loss of ductility. Resistance welds between the sheets did not lose their original strength after nitriding-oxinitriding. Nitrided-oxinitrided at 620 C and then powder painted sheets, as compared with powder painted raw sheets, were more corrosion resistant in neutral salt spray and climatic tests. Some mechanical and anticorrosion properties of the IF steel sheet that had undergone the nitriding-oxinitriding processes were definitely better than those of equally processed regular steel sheet. (Abstract Copyright [2004], Wiley Periodicals, Inc.) [German] Proben aus 0,8 mm dickem Blech aus Ziehmassenstahl sowie aus Ziehstahl ohne interstitiel geloeste Legierungsanteile (IF), werden im Wirbelbett in 2 Stunden bei 620 und 560 {sup o}C nitriert mit nachfolgenden Oxidierung sowie alternativ ohne Oxidierung und mit langsamer und beschleunigter Abkuehlung. Infolge dessen nehmen die Haerte, die Dehngrenze und die Zugfestigkeit der Bleche zu, ohne kritischen Zaehigkeitsverlust. Die Widerstandsschweisswulste zwischen den Blechen nach dem Nitrieren-Oxinitrieren haben nicht an Festigkeit verloren. Die bei 620 {sup o}C nitrierten-oxinitrierten und nachfolgend mit Pulverlack beschichteten Bleche sind bei den Versuchen in Salznebel und bei klimatischen Versuchen korrosionbestaendiger im Vergleich mit den mit nur Pulverlack beschichteten Rohblechen. Manche der mechanischen und korrosionsverhalten betreffenden Eigenschaften der Bleche aus IF-Staehle sind entscheidend besser als fuer das ebenso behandelte Blech aus Ziehmassenstahl. (Abstract Copyright [2004], Wiley Periodicals, Inc.)

21 CFR 822.27 - If I go out of business, what must I do?

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false If I go out of business, what must I do? 822.27 Section 822.27 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... business, what must I do? You must notify us within 30 days of the date of your decision to close your...

Pigment and Lovastatin content on the Red Rice cultivar Bah Butong and BP 1804 IF 9 which Fermented by Monascus purpureus Jmba

Directory of Open Access Journals (Sweden)

ERNAWATI KASIM

2006-01-01

Full Text Available Research on the red rice fermented by Monascus purpureus had been done. The rice consisted of 2 cultivars such as Bah Butong and BP 1804 IF 9. The aim of the research was to know the content of the pigment and lovastatin of the fermentation result/ angkak. Angkak was powdered by using blender. To measure the content of pigment, the powder was extracted by methanol. By using spectrophotometer the content of the pigment could be measured with 390 nm wave lengths for yellow pigment and 500 nm for the red pigment. For lovastatin the powder was extracted by acetonitrile and H2SO4. By using HPLC the content of lovastatin could be measured. The results showed that the highest pigment content for yellow pigment was on the PB 1804 IF 9 cultivar, and red pigment was on the Bah Butong cultivar. The highest lovastatin content was on the BP 1804 IF 9.

40 CFR 63.11087 - What requirements must I meet for gasoline storage tanks if my facility is a bulk gasoline...

Science.gov (United States)

2010-07-01

... gasoline storage tanks if my facility is a bulk gasoline terminal, pipeline breakout station, or pipeline... CATEGORIES (CONTINUED) National Emission Standards for Hazardous Air Pollutants for Source Category: Gasoline... § 63.11087 What requirements must I meet for gasoline storage tanks if my facility is a bulk gasoline...

25 CFR 224.138 - What must the Director do if a tribe's noncompliance has caused imminent jeopardy to a physical...

Science.gov (United States)

2010-04-01

... noncompliance with the TERA or a Federal law has caused imminent jeopardy to a physical trust asset. ... caused imminent jeopardy to a physical trust asset? 224.138 Section 224.138 Indians BUREAU OF INDIAN... the Director do if a tribe's noncompliance has caused imminent jeopardy to a physical trust asset? If...

41 CFR 301-71.206 - What must we do if we disallow a travel claim?

Science.gov (United States)

2010-07-01

... disallow a travel claim? 301-71.206 Section 301-71.206 Public Contracts and Property Management Federal Travel Regulation System TEMPORARY DUTY (TDY) TRAVEL ALLOWANCES AGENCY RESPONSIBILITIES 71-AGENCY TRAVEL ACCOUNTABILITY REQUIREMENTS Travel Claims for Reimbursement § 301-71.206 What must we do if we disallow a travel...

"If a Lion Could Speak ...": Online Sensitivity to Propositional Truth-Value of Unrealistic Counterfactual Sentences

Science.gov (United States)

Nieuwland, Mante S.

2013-01-01

People can establish whether a sentence is hypothetically true even if what it describes can never be literally true given the laws of the natural world. Two event-related potential (ERP) experiments examined electrophysiological responses to sentences about unrealistic counterfactual worlds that require people to construct novel conceptual…

25 CFR 166.819 - What happens if the BIA does not collect enough money to satisfy the penalty?

Science.gov (United States)

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false What happens if the BIA does not collect enough money to... does not collect enough money to satisfy the penalty? We will send written notice to the trespasser demanding immediate settlement and advising the trespasser that unless settlement is received within five...

41 CFR 102-75.105 - What responsibility does the Department of the Interior have if it determines that minerals in...

Science.gov (United States)

2010-07-01

... the Department of the Interior have if it determines that minerals in the land are unsuitable for disposition under the public land mining and mineral leasing laws? 102-75.105 Section 102-75.105 Public... Interior have if it determines that minerals in the land are unsuitable for disposition under the public...

40 CFR 63.11088 - What requirements must I meet for gasoline loading racks if my facility is a bulk gasoline...

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 14 2010-07-01 2010-07-01 false What requirements must I meet for gasoline loading racks if my facility is a bulk gasoline terminal, pipeline breakout station, or pipeline... § 63.11088 What requirements must I meet for gasoline loading racks if my facility is a bulk gasoline...

20 CFR 411.582 - Can a State VR agency receive payment under the cost reimbursement payment system if a continuous...

Science.gov (United States)

2010-04-01

... the cost reimbursement payment system if a continuous 9-month period of substantial gainful activity... Systems § 411.582 Can a State VR agency receive payment under the cost reimbursement payment system if a... under the cost reimbursement payment system under subpart V of part 404 (or subpart V of part 416) of...

41 CFR 105-68.310 - What must I do if a Federal agency excludes a person with whom I am already doing business in a...

Science.gov (United States)

2010-07-01

... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false What must I do if a Federal agency excludes a person with whom I am already doing business in a covered transaction? 105-68... Regarding Transactions Doing Business with Other Persons § 105-68.310 What must I do if a Federal agency...

Space Station Freedom - What if...?

Science.gov (United States)

Grey, Jerry

1992-10-01

The use of novel structural designs and the Energia launch system of the Commonwealth of Independent States for the Space Station Freedom (SSF) program is evaluated by means of a concept analysis. The analysis assumes that: (1) Energia is used for all cargo and logistics resupply missions; (2) the shuttles are launched from the U.S.; and (3) an eight-person assured crew return vehicle is available. This launch/supply scenario reduces the deployment risk from 30 launches to a total of only eight launches reducing the cost by about 15 billion U.S. dollars. The scenario also significantly increases the expected habitable and storage volumes and decreases the deployment time by three years over previous scenarios. The specific payloads are given for Energia launches emphasizing a proposed design for the common module cluster that incorporates direct structural attachment to the truss at midspan. The design is shown to facilitate the accommodation of additional service hangars and to provide a more efficient program for spacecraft habitable space.

49 CFR 40.105 - What happens if the laboratory reports a result different from that expected for a blind specimen?

Science.gov (United States)

2010-10-01

... different from that expected for a blind specimen? 40.105 Section 40.105 Transportation Office of the... for a blind specimen? (a) If you are an employer, MRO, or C/TPA who submits a blind specimen, and if... expected results (obtained from the supplier of the blind specimen), and direct the laboratory to determine...

Cap-proximal nucleotides via differential eIF4E binding and alternative promoter usage mediate translational response to energy stress.

Science.gov (United States)

Tamarkin-Ben-Harush, Ana; Vasseur, Jean-Jacques; Debart, Françoise; Ulitsky, Igor; Dikstein, Rivka

2017-02-08

Transcription start-site (TSS) selection and alternative promoter (AP) usage contribute to gene expression complexity but little is known about their impact on translation. Here we performed TSS mapping of the translatome following energy stress. Assessing the contribution of cap-proximal TSS nucleotides, we found dramatic effect on translation only upon stress. As eIF4E levels were reduced, we determined its binding to capped-RNAs with different initiating nucleotides and found the lowest affinity to 5'cytidine in correlation with the translational stress-response. In addition, the number of differentially translated APs was elevated following stress. These include novel glucose starvation-induced downstream transcripts for the translation regulators eIF4A and Pabp, which are also translationally-induced despite general translational inhibition. The resultant eIF4A protein is N-terminally truncated and acts as eIF4A inhibitor. The induced Pabp isoform has shorter 5'UTR removing an auto-inhibitory element. Our findings uncovered several levels of coordination of transcription and translation responses to energy stress.

40 CFR 63.6604 - What fuel requirements must I meet if I own or operate an existing stationary CI RICE?

Science.gov (United States)

2010-07-01

... I own or operate an existing stationary CI RICE? 63.6604 Section 63.6604 Protection of Environment....6604 What fuel requirements must I meet if I own or operate an existing stationary CI RICE? If you own or operate an existing non-emergency CI stationary RICE with a site rating of more than 300 brake HP...

36 CFR 1011.19 - Will the Presidio Trust issue a refund if money is erroneously collected on a debt?

Science.gov (United States)

2010-07-01

... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Will the Presidio Trust issue... Public Property PRESIDIO TRUST DEBT COLLECTION Procedures To Collect Presidio Trust Debts § 1011.19 Will the Presidio Trust issue a refund if money is erroneously collected on a debt? The Presidio Trust will...

Microstructural characterization of IF steel after severe plastic deformation via ARB and subsequent heat treatment

International Nuclear Information System (INIS)

Oliveira, F.C.; Abrantes, A.L.A.; Lins, J.F.C.

2010-01-01

This study aimed to evaluate the microstructural evolution of a titanium stabilized IF steel deformed to warm through the ARB process for 5 consecutive cycles and then annealing at 600 deg C for 1 h. The material was characterized with the aid of the techniques of scanning electron microscopy and electron backscatter diffraction (Electron Backscatter Diffraction - EBSD). An intense process of microstructural refinement was observed in the deformed material and the phenomenon of dynamic recovery was predominant. It can be concluded that the annealing of severely deformed material was not sufficient for a complete recrystallization of the microstructure. (author)

If they succeed, they will be on the lead

International Nuclear Information System (INIS)

Pinter, G.

1999-01-01

In this paper the supply of the Slovak Power Machine Works, plc. (SES), based in Tlmace, which are among the top designers and producers of steam boilers for power and heating plants using fossil, liquid and gas fuels, are described. A team engineers of SES took part at the technical contract discussions in China at the end of 1998. If they win the tender they will be awarded a contract to supply two Shen Tou (China) power plant units. The Shen Tou project will represent together with the fluid boiler for the Ukrainian power plant Starobesevo the two most important activities of the company over the next years. The joint supply of this type boiler with Germany's Lurgi and Lentjes will mean a significant point of reference for the SES as in terms of performance the fluid boiler layer boiler produced in Tlmace ever. The fluid boilers guarantee a reduced level of sulfur and nitrogen emissions in the boiler flue gas, complying thus with one of the crucial requirements for the ecological approach in production of the power and heating plants. They mastered the fluid lair combustion of fossil fuels in Tlmace with flying flags. This technology means a step up in quantity, as a guarantee for high efficiency and ecologically acceptable combustion with substantially reduced emissions and with no need for auxiliary equipment. The fluid layer combustion and desulfuring process takes place in a combustion chamber as a circulating fluid stream of flue gas, ashes, fuel and additives. Other strong points of the Tlmace approach to design, limiting not only SO 2 , NO x and chlorine effluents, but also reducing the space requirements, operation costs, simplified fuel transport, and in general shorter pipe routes, forming thus an advanced and progressive compact fluid boiler structure. (author)

Using codon optimization, chaperone co-expression, and rational mutagenesis for production and NMR assignments of human eIF2α

International Nuclear Information System (INIS)

Ito, Takuhiro; Wagner, Gerhard

2004-01-01

Producing a well behaved sample at high concentration is one of the main hurdles when starting a new project on an interesting protein. Especially when one attempts to overexpress a eukaryotic protein in bacteria, some difficulties are encountered, such as low expression level, low solubility, or even lack of folded structure. Overexpression in prokaryotic systems is highly desirable for cost-effective production of different isotope-labeled samples needed for NMR studies. Here we describe generally applicable methods for obtaining highly concentrated protein samples efficiently. This approach was developed as we tried to produce a NMR-suitable sample of the 35 kDa human translation initiation factor eIF2α, a protein that expresses poorly in E. coli and has very low solubility. First, an E. coli codon-optimized gene was synthesized on a thermal cycler, which increased the expression level by a factor of two. Second, we used co-expression of bacterial chaperone proteins, which largely increased the fraction of correctly folded protein found in the soluble phase. Third, we used rational mutagenesis guided by both the sequence alignment among homologues and the homology of one domain to a known fold for improving solubility and stability of the target protein by tenfold. Combining all these methods made it possible to produce from a one-liter preparation a 0.5 mM sample of human eIF2α that showed well-resolved NMR spectra and enabled nearly complete assignment of the protein. These methods may be generally useful for studies of other eukaryotic proteins that are otherwise difficult to express and exhibit poor solubility

29 CFR 778.320 - Hours that would not be hours worked if not paid for.

Science.gov (United States)

2010-07-01

... working hours fall in this category. The agreement of the parties to provide compensation for such hours... regular rate of an employee if the hours are compensated at the same rate as other working hours. The.... Activities of this type include eating meals between working hours. Where it appears from all the pertinent...

NETmundial: only a landmark event if 'Digital Cold War' rhetoric abandoned

Directory of Open Access Journals (Sweden)

Francesca Musiani

2014-03-01

Full Text Available While internet privacy has been a central concern for quite a long time, the revelations by Edward Snowden about the US National Security Agency’s massive surveillance programme have highlighted the extent to which it is a core political issue. The privacy-surveillance controversy has prompted what is perhaps the most prominent and ambitious call in internet governance history to break the dominance of the United States' control over internet infrastructure: the Global Multistakeholder Meeting on the Future of Internet Governance, or NETmundial (April 2014. The article analyses the current state of multi-stakeholderism in internet governance in light of this event. In particular, it argues for the necessity to leave the ‘Digital Cold War’ rhetoric behind if the internationalisation and the globalisation of internet governance is to move to the next level.

13 CFR 126.609 - What must the contracting officer do if a contracting opportunity does not exist for competition...

Science.gov (United States)

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false What must the contracting officer do if a contracting opportunity does not exist for competition among qualified HUBZone SBCs? 126.609 Section 126.609 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION HUBZONE PROGRAM Contractual...

What if Astyanax had survived? War, children, and youth.

Science.gov (United States)

Allen, J R; Pfefferbaum, B

1998-01-01

What, then, might have happened to Astyanax had he survived? He might have become a Greek slave and accepted his lot, or he might have felt loyalty and an obligation to his Trojan ancestry and organized acts of revenge. Depending on his personal characteristics and the people and the community that raised him, a number of outcomes are possible. The fact that after 3000 years we know little more than did the Homeric bards, however, gives us reason to be humble. There is evidence that each experience of loss or violence is additive and reduces coping ability. Although the psychologic disturbances of children and youth exposed to war do appear less intense than might have been expected, as Garmezy and Rutter noted in 1985, it is impossible to know the cost, the vulnerabilities that have been veiled, and what might have been. Perhaps the most remarkable thing is how some children seem able to transcend their misfortunes and even to be steeled by them. Coles has recorded how a 6-year-old, African-American girl, initiating school desegregation in New Orleans in the face of mob violence and daily threats to her life, told him that if she managed to get through with some success, she had an explanation: "It will be because there is more to me than I ever realized."

Myositis with endomysial cell invasion indicates inclusion body myositis even if other criteria are not fulfilled

NARCIS (Netherlands)

Van de Vlekkert, J.; Hoogendijk, J. E.; de Visser, M.

2015-01-01

The objective of this study was to investigate if patients with endomysial mononuclear cell infiltrates invading non-necrotic fibers have a disease course consistent with inclusion body myositis (IBM), irrespective of other histopathological and clinical characteristics. All patients with a muscle

Proposal of method for quantifying uranium weight in the interior of gas centrifuge, and performance evaluation of IF7 treatment reaction product separation and refinement

International Nuclear Information System (INIS)

Ema, Akira; Kado, Kazumi; Suzuki, Kazuhiko

2011-01-01

In uranium enrichment plant decommissioning, it is important to treat and dispose the gas centrifuge reasonably. At the Ningyo-Toge Environmental Engineering Center of JAEA, it has been planned to carry out IF 7 treatment for the gas centrifuge in the uranium enrichment plant for decontamination before dismantling. In order to carry out this IF 7 treatment, a nondestructive measurement technology to estimate the uranium weight in the interior of the gas centrifuge was needed. However, it was difficult to estimate exactly uranium weight using former methods. Therefore, in this study, we investigated a new nondestructive measurement. As a result, we succeeded in constructing theoretically the methodology using γ-ray intensity measured outside the gas centrifuge and MCNP code. Furthermore, the UF 6 and IF 5 mixture was recovered by IF 7 treatment. A technology to separate and refine IF 5 from this mixture was needed in order to use as a material of IF 7 gas. Therefore, in this study, we carried out IF 5 separation and refinement examination. This paper shows the investigation result of reasonable separation condition and the full-scale examination result. As a result, it could be proved that 86% of IF 5 was separated and refined from UF 6 and IF 5 mixture. (author)

TEXTURE AND MECHANICAL BEHAVIOUR OF Ti AND Nb-Ti STABILIZED IF STEELS

Directory of Open Access Journals (Sweden)

Fabio Moreira da Silva Dias

2013-12-01

Full Text Available An analysis of the crystallographic texture and mechanical behavior of two types of IF steels is presented. Two steels, Ti and Nb-Ti, were submitted to different thermal annealing cycles in a continuous hot-dip galvanizing line, heat treated at temperatures of 860°C and 760°C. The more relevant characteristics of mechanical properties are evaluated. The crystallographic texture of the samples is determined by electron diffraction technique of back-scattering (SEM-EBSD. The intensity of orientation //ND is evaluated and compared. Metallographic characterization is done, and the ferritic grain size is measured with optical microscopy. The mechanical behavior of materials is characterized in the tensile test with 80 mm gauge length.

40 CFR 63.5150 - If I use a control device to comply with the emission standards, what monitoring must I do?

Science.gov (United States)

2010-07-01

.... Calculate the temperature difference across the catalyst. If you are demonstrating continuous compliance... of the catalyst bed. (4) Capture system monitoring. If you are complying with the requirements of the... with the emission standards, what monitoring must I do? 63.5150 Section 63.5150 Protection of...

Functional Characterization of the Canine Heme-Regulated eIF2α Kinase: Regulation of Protein Synthesis

Directory of Open Access Journals (Sweden)

Kimon C. Kanelakis

2009-01-01

Full Text Available The heme-regulated inhibitor (HRI negatively regulates protein synthesis by phosphorylating eukaryotic initiation factor-2α (eIF2α thereby inhibiting protein translation. The importance of HRI in regulating hemoglobin synthesis in erythroid cells makes it an attractive molecular target in need of further characterization. In this work, we have cloned and expressed the canine form of the HRI kinase. The canine nucleotide sequence has 86%, 82%, and 81% identity to the human, mouse, and rat HRI, respectively. It was noted that an isoleucine residue in the ATP binding site of human, rat, and mouse HRI is replaced by a valine in the canine kinase. The expression of canine HRI protein by in vitro translation using wheat germ lysate or in Sf9 cells using a baculovirus expression system was increased by the addition of hemin. Following purification, the canine protein was found to be 72 kD and showed kinase activity determined by its ability to phosphorylate a synthetic peptide substrate. Quercetin, a kinase inhibitor known to inhibit mouse and human HRI, inhibits canine HRI in a concentration-dependent manner. Additionally, quercetin is able to increase de novo protein synthesis in canine reticulocytes. We conclude that the canine is a suitable model species for studying the role of HRI in erythropoiesis.