The Conformational Change in Elongation Factor Tu Involves Separation of Its Domains
Lai, Jonathan; Ghaemi, Zhaleh; Luthey-Schulten, Zaida
2017-10-18
Elongation factor Tu (EF-Tu) is a highly conserved GTPase that is responsible for supplying the aminoacylated tRNA to the ribosome. Upon binding to the ribosome, EF-Tu undergoes GTP hydrolysis, which drives a major conformational change, triggering the release of aminoacylated tRNA to the ribosome. Using a combination of molecular simulation techniques, we studied the transition between the pre- and post-hydrolysis structures through two distinct pathways. Here, we show that the transition free energy is minimal along a non-intuitive pathway that involves “separation” of the GTP binding domain (domain 1) from the OB folds (domains 2 and 3), followed by domainmore » 1 rotation, and, eventually, locking the EF-Tu conformation in the post-hydrolysis state. The domain separation also leads to a slight extension of the linker connecting domain 1 to domain 2. Using docking tools and correlation-based analysis, we identified and characterized the EF-Tu conformations that release the tRNA. These calculations suggest that EF-Tu can release the tRNA before the domains separate and after domain 1 rotates by 25°. Lastly, we also examined the EF-Tu conformations in the context of the ribosome. Given the high degrees of sequence similarity with other translational GTPases, we predict a similar separation mechanism is followed.« less
The Conformational Change in Elongation Factor Tu Involves Separation of Its Domains
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lai, Jonathan; Ghaemi, Zhaleh; Luthey-Schulten, Zaida
Elongation factor Tu (EF-Tu) is a highly conserved GTPase that is responsible for supplying the aminoacylated tRNA to the ribosome. Upon binding to the ribosome, EF-Tu undergoes GTP hydrolysis, which drives a major conformational change, triggering the release of aminoacylated tRNA to the ribosome. Using a combination of molecular simulation techniques, we studied the transition between the pre- and post-hydrolysis structures through two distinct pathways. Here, we show that the transition free energy is minimal along a non-intuitive pathway that involves “separation” of the GTP binding domain (domain 1) from the OB folds (domains 2 and 3), followed by domainmore » 1 rotation, and, eventually, locking the EF-Tu conformation in the post-hydrolysis state. The domain separation also leads to a slight extension of the linker connecting domain 1 to domain 2. Using docking tools and correlation-based analysis, we identified and characterized the EF-Tu conformations that release the tRNA. These calculations suggest that EF-Tu can release the tRNA before the domains separate and after domain 1 rotates by 25°. Lastly, we also examined the EF-Tu conformations in the context of the ribosome. Given the high degrees of sequence similarity with other translational GTPases, we predict a similar separation mechanism is followed.« less
Phosphorylation decelerates conformational dynamics in bacterial translation elongation factors
Talavera, Ariel; Hendrix, Jelle; Versées, Wim; Jurėnas, Dukas; Van Nerom, Katleen; Vandenberk, Niels; Singh, Ranjan Kumar; Konijnenberg, Albert; De Gieter, Steven; Castro-Roa, Daniel; Barth, Anders; De Greve, Henri; Sobott, Frank; Hofkens, Johan; Zenkin, Nikolay; Loris, Remy; Garcia-Pino, Abel
2018-01-01
Bacterial protein synthesis is intricately connected to metabolic rate. One of the ways in which bacteria respond to environmental stress is through posttranslational modifications of translation factors. Translation elongation factor Tu (EF-Tu) is methylated and phosphorylated in response to nutrient starvation upon entering stationary phase, and its phosphorylation is a crucial step in the pathway toward sporulation. We analyze how phosphorylation leads to inactivation of Escherichia coli EF-Tu. We provide structural and biophysical evidence that phosphorylation of EF-Tu at T382 acts as an efficient switch that turns off protein synthesis by decoupling nucleotide binding from the EF-Tu conformational cycle. Direct modifications of the EF-Tu switch I region or modifications in other regions stabilizing the β-hairpin state of switch I result in an effective allosteric trap that restricts the normal dynamics of EF-Tu and enables the evasion of the control exerted by nucleotides on G proteins. These results highlight stabilization of a phosphorylation-induced conformational trap as an essential mechanism for phosphoregulation of bacterial translation and metabolism. We propose that this mechanism may lead to the multisite phosphorylation state observed during dormancy and stationary phase. PMID:29546243
Burnett, Benjamin J.; Altman, Roger B.; Ferrao, Ryan; Alejo, Jose L.; Kaur, Navdep; Kanji, Joshua; Blanchard, Scott C.
2013-01-01
Aminoacyl-tRNA enters the translating ribosome in a ternary complex with elongation factor Tu (EF-Tu) and GTP. Here, we describe bulk steady state and pre-steady state fluorescence methods that enabled us to quantitatively explore the kinetic features of Escherichia coli ternary complex formation and decay. The data obtained suggest that both processes are controlled by a nucleotide-dependent, rate-determining conformational change in EF-Tu. Unexpectedly, we found that this conformational change is accelerated by elongation factor Ts (EF-Ts), the guanosine nucleotide exchange factor for EF-Tu. Notably, EF-Ts attenuates the affinity of EF-Tu for GTP and destabilizes ternary complex in the presence of non-hydrolyzable GTP analogs. These results suggest that EF-Ts serves an unanticipated role in the cell of actively regulating the abundance and stability of ternary complex in a manner that contributes to rapid and faithful protein synthesis. PMID:23539628
Burnett, Benjamin J; Altman, Roger B; Ferrao, Ryan; Alejo, Jose L; Kaur, Navdep; Kanji, Joshua; Blanchard, Scott C
2013-05-10
Aminoacyl-tRNA (aa-tRNA) enters the ribosome in a ternary complex with the G-protein elongation factor Tu (EF-Tu) and GTP. EF-Tu·GTP·aa-tRNA ternary complex formation and decay rates are accelerated in the presence of the nucleotide exchange factor elongation factor Ts (EF-Ts). EF-Ts directly facilitates the formation and disassociation of ternary complex. This system demonstrates a novel function of EF-Ts. Aminoacyl-tRNA enters the translating ribosome in a ternary complex with elongation factor Tu (EF-Tu) and GTP. Here, we describe bulk steady state and pre-steady state fluorescence methods that enabled us to quantitatively explore the kinetic features of Escherichia coli ternary complex formation and decay. The data obtained suggest that both processes are controlled by a nucleotide-dependent, rate-determining conformational change in EF-Tu. Unexpectedly, we found that this conformational change is accelerated by elongation factor Ts (EF-Ts), the guanosine nucleotide exchange factor for EF-Tu. Notably, EF-Ts attenuates the affinity of EF-Tu for GTP and destabilizes ternary complex in the presence of non-hydrolyzable GTP analogs. These results suggest that EF-Ts serves an unanticipated role in the cell of actively regulating the abundance and stability of ternary complex in a manner that contributes to rapid and faithful protein synthesis.
Thirup, Søren S; Van, Lan Bich; Nielsen, Tine K; Knudsen, Charlotte R
2015-07-01
Translation elongation factor EF-Tu belongs to the superfamily of guanine-nucleotide binding proteins, which play key cellular roles as regulatory switches. All G-proteins require activation via exchange of GDP for GTP to carry out their respective tasks. Often, guanine-nucleotide exchange factors are essential to this process. During translation, EF-Tu:GTP transports aminoacylated tRNA to the ribosome. GTP is hydrolyzed during this process, and subsequent reactivation of EF-Tu is catalyzed by EF-Ts. The reaction path of guanine-nucleotide exchange is structurally poorly defined for EF-Tu and EF-Ts. We have determined the crystal structures of the following reaction intermediates: two structures of EF-Tu:GDP:EF-Ts (2.2 and 1.8Å resolution), EF-Tu:PO4:EF-Ts (1.9Å resolution), EF-Tu:GDPNP:EF-Ts (2.2Å resolution) and EF-Tu:GDPNP:pulvomycin:Mg(2+):EF-Ts (3.5Å resolution). These structures provide snapshots throughout the entire exchange reaction and suggest a mechanism for the release of EF-Tu in its GTP conformation. An inferred sequence of events during the exchange reaction is presented. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
Michalska, Karolina; Gucinski, Grant C.; Garza-Sanchez, Fernando; ...
2017-08-11
Contact-dependent growth inhibition (CDI) is a mechanism of inter-cellular competition in which Gram-negative bacteria exchange polymorphic toxins using type V secretion systems. Here, we present structures of the CDI toxin from Escherichia coli NC101 in ternary complex with its cognate immunity protein and elongation factor Tu (EF-Tu). The toxin binds exclusively to domain 2 of EF-Tu, partially overlapping the site that interacts with the 3'-end of aminoacyl-tRNA (aa-tRNA). The toxin exerts a unique ribonuclease activity that cleaves the single-stranded 3'-end from tRNAs that contain guanine discriminator nucleotides. EF-Tu is required to support this tRNase activity in vitro, suggesting the toxinmore » specifically cleaves substrate in the context of GTP·EF-Tu·aa-tRNA complexes. However, superimposition of the toxin domain onto previously solved GTP·EF-Tu·aa-tRNA structures reveals potential steric clashes with both aa-tRNA and the switch I region of EF-Tu. Further, the toxin induces conformational changes in EF-Tu, displacing a β-hairpin loop that forms a critical salt-bridge contact with the 3'-terminal adenylate of aa-tRNA. Altogether, these observations suggest that the toxin remodels GTP·EF-Tu·aa-tRNA complexes to free the 3'-end of aa-tRNA for entry into the nuclease active site.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Michalska, Karolina; Gucinski, Grant C.; Garza-Sanchez, Fernando
Contact-dependent growth inhibition (CDI) is a mechanism of inter-cellular competition in which Gram-negative bacteria exchange polymorphic toxins using type V secretion systems. Here, we present structures of the CDI toxin from Escherichia coli NC101 in ternary complex with its cognate immunity protein and elongation factor Tu (EF-Tu). The toxin binds exclusively to domain 2 of EF-Tu, partially overlapping the site that interacts with the 3'-end of aminoacyl-tRNA (aa-tRNA). The toxin exerts a unique ribonuclease activity that cleaves the single-stranded 3'-end from tRNAs that contain guanine discriminator nucleotides. EF-Tu is required to support this tRNase activity in vitro, suggesting the toxinmore » specifically cleaves substrate in the context of GTP·EF-Tu·aa-tRNA complexes. However, superimposition of the toxin domain onto previously solved GTP·EF-Tu·aa-tRNA structures reveals potential steric clashes with both aa-tRNA and the switch I region of EF-Tu. Further, the toxin induces conformational changes in EF-Tu, displacing a β-hairpin loop that forms a critical salt-bridge contact with the 3'-terminal adenylate of aa-tRNA. Altogether, these observations suggest that the toxin remodels GTP·EF-Tu·aa-tRNA complexes to free the 3'-end of aa-tRNA for entry into the nuclease active site.« less
Crepin, Thibaut; Shalak, Vyacheslav F.; Yaremchuk, Anna D.; Vlasenko, Dmytro O.; McCarthy, Andrew; Negrutskii, Boris S.; Tukalo, Michail A.; El'skaya, Anna V.
2014-01-01
Eukaryotic elongation factor eEF1A transits between the GTP- and GDP-bound conformations during the ribosomal polypeptide chain elongation. eEF1A*GTP establishes a complex with the aminoacyl-tRNA in the A site of the 80S ribosome. Correct codon–anticodon recognition triggers GTP hydrolysis, with subsequent dissociation of eEF1A*GDP from the ribosome. The structures of both the ‘GTP’- and ‘GDP’-bound conformations of eEF1A are unknown. Thus, the eEF1A-related ribosomal mechanisms were anticipated only by analogy with the bacterial homolog EF-Tu. Here, we report the first crystal structure of the mammalian eEF1A2*GDP complex which indicates major differences in the organization of the nucleotide-binding domain and intramolecular movements of eEF1A compared to EF-Tu. Our results explain the nucleotide exchange mechanism in the mammalian eEF1A and suggest that the first step of eEF1A*GDP dissociation from the 80S ribosome is the rotation of the nucleotide-binding domain observed after GTP hydrolysis. PMID:25326326
Crepin, Thibaut; Shalak, Vyacheslav F; Yaremchuk, Anna D; Vlasenko, Dmytro O; McCarthy, Andrew; Negrutskii, Boris S; Tukalo, Michail A; El'skaya, Anna V
2014-11-10
Eukaryotic elongation factor eEF1A transits between the GTP- and GDP-bound conformations during the ribosomal polypeptide chain elongation. eEF1A*GTP establishes a complex with the aminoacyl-tRNA in the A site of the 80S ribosome. Correct codon-anticodon recognition triggers GTP hydrolysis, with subsequent dissociation of eEF1A*GDP from the ribosome. The structures of both the 'GTP'- and 'GDP'-bound conformations of eEF1A are unknown. Thus, the eEF1A-related ribosomal mechanisms were anticipated only by analogy with the bacterial homolog EF-Tu. Here, we report the first crystal structure of the mammalian eEF1A2*GDP complex which indicates major differences in the organization of the nucleotide-binding domain and intramolecular movements of eEF1A compared to EF-Tu. Our results explain the nucleotide exchange mechanism in the mammalian eEF1A and suggest that the first step of eEF1A*GDP dissociation from the 80S ribosome is the rotation of the nucleotide-binding domain observed after GTP hydrolysis. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.
Structure of the OsSERK2 leucine-rich repeat extracellular domain.
McAndrew, Ryan; Pruitt, Rory N; Kamita, Shizuo G; Pereira, Jose Henrique; Majumdar, Dipali; Hammock, Bruce D; Adams, Paul D; Ronald, Pamela C
2014-11-01
Somatic embryogenesis receptor kinases (SERKs) are leucine-rich repeat (LRR)-containing integral membrane receptors that are involved in the regulation of development and immune responses in plants. It has recently been shown that rice SERK2 (OsSERK2) is essential for XA21-mediated resistance to the pathogen Xanthomonas oryzae pv. oryzae. OsSERK2 is also required for the BRI1-mediated, FLS2-mediated and EFR-mediated responses to brassinosteroids, flagellin and elongation factor Tu (EF-Tu), respectively. Here, crystal structures of the LRR domains of OsSERK2 and a D128N OsSERK2 mutant, expressed as hagfish variable lymphocyte receptor (VLR) fusions, are reported. These structures suggest that the aspartate mutation does not generate any significant conformational change in the protein, but instead leads to an altered interaction with partner receptors.
NASA Astrophysics Data System (ADS)
Dehipawala, Sunil; Nguyen, A.; Tremberger, G.; Cheung, E.; Schneider, P.; Lieberman, D.; Holden, T.; Cheung, T.
2013-09-01
A paleo-experimental evolution report on elongation factor EF-Tu structural stability results has provided an opportunity to rewind the tape of life using the ancestral protein sequence reconstruction modeling approach; consistent with the book of life dogma in current biology and being an important component in the astrobiology community. Fractal dimension via the Higuchi fractal method and Shannon entropy of the DNA sequence classification could be used in a diagram that serves as a simple summary. Results from biomedical gene research provide examples on the diagram methodology. Comparisons between biomedical genes such as EEF2 (elongation factor 2 human, mouse, etc), WDR85 in epigenetics, HAR1 in human specificity, DLG1 in cognitive skill, and HLA-C in mosquito bite immunology with EF Tu DNA sequences have accounted for the reported circular dichroism thermo-stability data systematically; the results also infer a relatively less volatility geologic time period from 2 to 3 Gyr from adaptation viewpoint. Comparison to Thermotoga maritima MSB8 and Psychrobacter shows that Thermus thermophilus HB8 EF-Tu calibration sequence could be an outlier, consistent with free energy calculation by NUPACK. Diagram methodology allows computer simulation studies and HAR1 shows about 0.5% probability from chimp to human in terms of diagram location, and SNP simulation results such as amoebic meningoencephalitis NAF1 suggest correlation. Extensions to the studies of the translation and transcription elongation factor sequences in Megavirus Chiliensis, Megavirus Lba and Pandoravirus show that the studied Pandoravirus sequence could be an outlier with the highest fractal dimension and lowest entropy, as compared to chicken as a deviant in the DNMT3A DNA methylation gene sequences from zebrafish to human and to the less than one percent probability in computer simulation using the HAR1 0.5% probability as reference. The diagram methodology would be useful in ancestral gene reconstruction studies in astrobiology and also be applicable to the study of point mutation in conformational thermostabilization research with Synchrotron based X-ray data for drug applications such as Parkinson's disease.
Ensemble cryo-EM elucidates the mechanism of translation fidelity
Loveland, Anna B.; Demo, Gabriel; Grigorieff, Nikolaus; Korostelev, Andrei A.
2017-01-01
SUMMARY Faithful gene translation depends on accurate decoding, whose structural mechanism remains a matter of debate. Ribosomes decode mRNA codons by selecting cognate aminoacyl-tRNAs delivered by EF-Tu. We present high-resolution structural ensembles of ribosomes with cognate or near-cognate aminoacyl-tRNAs delivered by EF-Tu. Both cognate and near-cognate tRNA anticodons explore the A site of an open 30S subunit, while inactive EF-Tu is separated from the 50S subunit. A transient conformation of decoding-center nucleotide G530 stabilizes the cognate codon-anticodon helix, initiating step-wise “latching” of the decoding center. The resulting 30S domain closure docks EF-Tu at the sarcin-ricin loop of the 50S subunit, activating EF-Tu for GTP hydrolysis and ensuing aminoacyl-tRNA accommodation. By contrast, near-cognate complexes fail to induce the G530 latch, thus favoring open 30S pre-accommodation intermediates with inactive EF-Tu. This work unveils long-sought structural differences between the pre-accommodation of cognate and near-cognate tRNA that elucidate the mechanism of accurate decoding. PMID:28538735
Paleskava, Alena; Konevega, Andrey L.; Rodnina, Marina V.
2012-01-01
SelB is a specialized translation factor that binds GTP and GDP and delivers selenocysteyl-tRNA (Sec-tRNASec) to the ribosome. By analogy to elongation factor Tu (EF-Tu), SelB is expected to control the delivery and release of Sec-tRNASec to the ribosome by the structural switch between GTP- and GDP-bound conformations. However, crystal structures of SelB suggested a similar domain arrangement in the apo form and GDP- and GTP-bound forms of the factor, raising the question of how SelB can fulfill its delivery function. Here, we studied the thermodynamics of guanine nucleotide binding to SelB by isothermal titration calorimetry in the temperature range between 10 and 25 °C using GTP, GDP, and two nonhydrolyzable GTP analogs, guanosine 5′-O-(γ-thio)triphosphate (GTPγS) and guanosine 5′-(β,γ-imido)-triphosphate (GDPNP). The binding of SelB to either guanine nucleotide is characterized by a large heat capacity change (−621, −467, −235, and −275 cal × mol−1 × K−1, with GTP, GTPγS, GDPNP, and GDP, respectively), associated with compensatory changes in binding entropy and enthalpy. Changes in heat capacity indicate a large decrease of the solvent-accessible surface area in SelB, amounting to 43 or 32 amino acids buried upon binding of GTP or GTPγS, respectively, and 15–19 amino acids upon binding GDP or GDPNP. The similarity of the GTP and GDP forms in the crystal structures can be attributed to the use of GDPNP, which appears to induce a structure of SelB that is more similar to the GDP than to the GTP-bound form. PMID:22740700
Paleskava, Alena; Konevega, Andrey L; Rodnina, Marina V
2012-08-10
SelB is a specialized translation factor that binds GTP and GDP and delivers selenocysteyl-tRNA (Sec-tRNA(Sec)) to the ribosome. By analogy to elongation factor Tu (EF-Tu), SelB is expected to control the delivery and release of Sec-tRNA(Sec) to the ribosome by the structural switch between GTP- and GDP-bound conformations. However, crystal structures of SelB suggested a similar domain arrangement in the apo form and GDP- and GTP-bound forms of the factor, raising the question of how SelB can fulfill its delivery function. Here, we studied the thermodynamics of guanine nucleotide binding to SelB by isothermal titration calorimetry in the temperature range between 10 and 25 °C using GTP, GDP, and two nonhydrolyzable GTP analogs, guanosine 5'-O-(γ-thio)triphosphate (GTPγS) and guanosine 5'-(β,γ-imido)-triphosphate (GDPNP). The binding of SelB to either guanine nucleotide is characterized by a large heat capacity change (-621, -467, -235, and -275 cal × mol(-1) × K(-1), with GTP, GTPγS, GDPNP, and GDP, respectively), associated with compensatory changes in binding entropy and enthalpy. Changes in heat capacity indicate a large decrease of the solvent-accessible surface area in SelB, amounting to 43 or 32 amino acids buried upon binding of GTP or GTPγS, respectively, and 15-19 amino acids upon binding GDP or GDPNP. The similarity of the GTP and GDP forms in the crystal structures can be attributed to the use of GDPNP, which appears to induce a structure of SelB that is more similar to the GDP than to the GTP-bound form.
Kirromycin, an Inhibitor of Protein Biosynthesis that Acts on Elongation Factor Tu
Wolf, Heinz; Chinali, Gianni; Parmeggiani, Andrea
1974-01-01
Kirromycin, a new inhibitor of protein synthesis, is shown to interfere with the peptide transfer reaction by acting on elongation factor Tu (EF-Tu). All the reactions associated with this elongation factor are affected. Formation of the EF-Tu·GTP complex is strongly stimulated. Peptide bond formation is prevented only when Phe-tRNAPhe is bound enzymatically to ribosomes, presumably because GTP hydrolysis associated with enzymatic binding of Phe-tRNAPhe is not followed by release of EF-Tu·GDP from the ribosome. This antibiotic also enables EF-Tu to catalyze the binding of Phe-tRNAPhe to the poly(U)·ribosome complex even in the absence of GTP. EF-Tu activity in the GTPase reaction is dramatically affected by kirromycin: GTP hydrolysis, which normally requires ribosomes and aminoacyl-tRNA, takes place with the elongation factor alone. This GTPase shows the same Km for GTP as the one dependent on Phe-tRNAPhe and ribosomes in the absence of the antibiotic. Ribosomes and Phe-tRNAPhe, but not tRNAPhe or Ac-Phe-tRNAPhe, stimulate the kirromycin-induced EF-Tu GTPase. These results indicate that the catalytic center of EF-Tu GTPase that is dependent upon aminoacyl-tRNA and ribosomes is primarily located on the elongation factor. In conclusion, kirromycin can substitute for GTP, aminoacyl-tRNA, or ribosomes in various reactions involving EF-Tu, apparently by affecting the allosteric controls between the sites on the EF-Tu molecule interacting with these components. PMID:4373734
Biswas, Subir; Lim, Erin E; Gupta, Ankit; Saqib, Uzma; Mir, Snober S; Siddiqi, Mohammad Imran; Ralph, Stuart A; Habib, Saman
2011-03-01
Protein translation in the plastid (apicoplast) of Plasmodium spp. is of immense interest as a target for potential anti-malarial drugs. However, the molecular data on apicoplast translation needed for optimisation and development of novel inhibitors is lacking. We report characterisation of two key translation elongation factors in Plasmodium falciparum, apicoplast-encoded elongation factor PfEF-Tu and nuclear-encoded PfEF-Ts. Recombinant PfEF-Tu hydrolysed GTP and interacted with its presumed nuclear-encoded partner PfEF-Ts. The EF-Tu inhibitor kirromycin affected PfEF-Tu activity in vitro, indicating that apicoplast EF-Tu is indeed the target of this drug. The predicted PfEF-Ts leader sequence targeted GFP to the apicoplast, confirming that PfEF-Ts functions in this organelle. Recombinant PfEF-Ts mediated nucleotide exchange on PfEF-Tu and homology modeling of the PfEF-Tu:PfEF-Ts complex revealed PfEF-Ts-induced structural alterations that would expedite GDP release from PfEF-Tu. Our results establish functional interaction between two apicoplast translation factors encoded by genes residing in different cellular compartments and highlight the significance of their sequence/structural differences from bacterial elongation factors in relation to inhibitor activity. These data provide an experimental system to study the effects of novel inhibitors targeting PfEF-Tu and PfEF-Tu.PfEF-Ts interaction. Our finding that apicoplast EF-Tu possesses chaperone-related disulphide reductase activity also provides a rationale for retention of the tufA gene on the plastid genome. Copyright © 2010 Australian Society for Parasitology Inc. All rights reserved.
USDA-ARS?s Scientific Manuscript database
Clostridium related poultry diseases such as necrotic enteritis (NE) and gangrenous dermatitis (GD) cause substantial economic losses on a global scale. Two antigenic C. perfringens proteins, elongation factor Tu (EF-Tu) and pyruvate:ferredoxin oxidoreductase (PFO), were identified by reaction with...
Abe, Cecília M.; Monaris, Denize; Morais, Zenaide M.; Souza, Gisele O.; Vasconcellos, Sílvio A.; Isaac, Lourdes; Abreu, Patrícia A. E.; Barbosa, Angela S.
2013-01-01
The elongation factor Tu (EF-Tu), an abundant bacterial protein involved in protein synthesis, has been shown to display moonlighting activities. Known to perform more than one function at different times or in different places, it is found in several subcellular locations in a single organism, and may serve as a virulence factor in a range of important human pathogens. Here we demonstrate that Leptospira EF-Tu is surface-exposed and performs additional roles as a cell-surface receptor for host plasma proteins. It binds plasminogen in a dose-dependent manner, and lysine residues are critical for this interaction. Bound plasminogen is converted to active plasmin, which, in turn, is able to cleave the natural substrates C3b and fibrinogen. Leptospira EF-Tu also acquires the complement regulator Factor H (FH). FH bound to immobilized EF-Tu displays cofactor activity, mediating C3b degradation by Factor I (FI). In this manner, EF-Tu may contribute to leptospiral tissue invasion and complement inactivation. To our knowledge, this is the first description of a leptospiral protein exhibiting moonlighting activities. PMID:24312361
Defeu Soufo, Hervé Joël; Reimold, Christian; Linne, Uwe; Knust, Tobias; Gescher, Johannes; Graumann, Peter L
2010-02-16
We show that translation initiation factor EF-Tu plays a second important role in cell shape maintenance in the bacterium Bacillus subtilis. EF-Tu localizes in a helical pattern underneath the cell membrane and colocalizes with MreB, an actin-like cytoskeletal element setting up rod cell shape. The localization of MreB and of EF-Tu is interdependent, but in contrast to the dynamic MreB filaments, EF-Tu structures are more static and may serve as tracks for MreB filaments. In agreement with this idea, EF-Tu and MreB interact in vivo and in vitro. Lowering of the EF-Tu levels had a minor effect on translation but a strong effect on cell shape and on the localization of MreB, and blocking of the function of EF-Tu in translation did not interfere with the localization of MreB, showing that, directly or indirectly, EF-Tu affects the cytoskeletal MreB structure and thus serves two important functions in a bacterium.
USDA-ARS?s Scientific Manuscript database
Clostridium-related poultry diseases such as necrotic enteritis (NE) and gangrenous dermatitis (GD) cause substantial economic losses on a global scale. Two antigenic Clostridium perfringens proteins, elongation factor Tu (EF-Tu) and pyruvate:ferredoxin oxidoreductase (PFO), were identified by react...
Direct evidence of an elongation factor-Tu/Ts·GTP·Aminoacyl-tRNA quaternary complex.
Burnett, Benjamin J; Altman, Roger B; Ferguson, Angelica; Wasserman, Michael R; Zhou, Zhou; Blanchard, Scott C
2014-08-22
During protein synthesis, elongation factor-Tu (EF-Tu) bound to GTP chaperones the entry of aminoacyl-tRNA (aa-tRNA) into actively translating ribosomes. In so doing, EF-Tu increases the rate and fidelity of the translation mechanism. Recent evidence suggests that EF-Ts, the guanosine nucleotide exchange factor for EF-Tu, directly accelerates both the formation and dissociation of the EF-Tu-GTP-Phe-tRNA(Phe) ternary complex (Burnett, B. J., Altman, R. B., Ferrao, R., Alejo, J. L., Kaur, N., Kanji, J., and Blanchard, S. C. (2013) J. Biol. Chem. 288, 13917-13928). A central feature of this model is the existence of a quaternary complex of EF-Tu/Ts·GTP·aa-tRNA(aa). Here, through comparative investigations of phenylalanyl, methionyl, and arginyl ternary complexes, and the development of a strategy to monitor their formation and decay using fluorescence resonance energy transfer, we reveal the generality of this newly described EF-Ts function and the first direct evidence of the transient quaternary complex species. These findings suggest that EF-Ts may regulate ternary complex abundance in the cell through mechanisms that are distinct from its guanosine nucleotide exchange factor functions. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.
Elongation factor Tu resistant to kirromycin in an Esherichia coli mutant altered in both tuf genes
Fischer, Eckhard; Wolf, Heinz; Hantke, Klaus; Parmeggiani, Andrea
1977-01-01
A mutant of Escherichia coli is described that displays kirromycin resistance in a cell-free system by virtue of an altered elongation factor Tu (EF-Tu). In poly(U)-directed poly(Phe) synthesis the kirromycin resistance of the crystallized enzyme ranged between a factor of 80 and 700, depending on temperature. Similarly, kirromycin-induced EF-Tu GTPase activity uncoupled from ribosomes and aminoacyl-tRNA required correspondingly higher concentrations of the antibiotic. Resistance of EF-Tu to kirromycin is a consequence of a modified enzyme structure as indicated by its altered fingerprint pattern. P1 transduction experiments showed that the kirromycin-resistant EF-Tu is coded by an altered tufB gene (tufB1). The known existence of two genes coding for EF-Tu would interfere with the recognition of a mutant altered in only one of those genes, if the mutation were recessive. Because kirromycin blocks EF-Tu release from the ribosome, kirromycin sensitivity is dominant, as shown by the failure of a mixed EF-Tu population to express resistance in vitro. Therefore, phenotypic expression of kirromycin resistance in vivo appears to be only possible if the EF-Tu mutant lacks an active tufA gene, a property likely to be inherited from the parental D22 strain. The observations that introduction of a tufA+ region makes the resistant strain sensitive to the antibiotic and that transduction of tufB1 into a recipient other than E. coli D22 yields kirromycin-sensitive progeny support these conclusions. Images PMID:337296
USDA-ARS?s Scientific Manuscript database
Protein elongation factors, EF-Tu and EF-1a, have been implicated in cell response to heat stress. In spring wheat, EF-Tu displays chaperone activity and reduces thermal aggregation of Rubisco activase. Similarly, in mammalian cells, EF-1a displays chaperone-like activity and regulates the expressio...
Assembly of Q{beta} viral RNA polymerase with host translational elongation factors EF-Tu and -Ts.
Takeshita, Daijiro; Tomita, Kozo
2010-09-07
Replication and transcription of viral RNA genomes rely on host-donated proteins. Qbeta virus infects Escherichia coli and replicates and transcribes its own genomic RNA by Qbeta replicase. Qbeta replicase requires the virus-encoded RNA-dependent RNA polymerase (beta-subunit), and the host-donated translational elongation factors EF-Tu and -Ts, as active core subunits for its RNA polymerization activity. Here, we present the crystal structure of the core Qbeta replicase, comprising the beta-subunit, EF-Tu and -Ts. The beta-subunit has a right-handed structure, and the EF-Tu:Ts binary complex maintains the structure of the catalytic core crevasse of the beta-subunit through hydrophobic interactions, between the finger and thumb domains of the beta-subunit and domain-2 of EF-Tu and the coiled-coil motif of EF-Ts, respectively. These hydrophobic interactions are required for the expression and assembly of the Qbeta replicase complex. Thus, EF-Tu and -Ts have chaperone-like functions in the maintenance of the structure of the active Qbeta replicase. Modeling of the template RNA and the growing RNA in the catalytic site of the Qbeta replicase structure also suggests that structural changes of the RNAs and EF-Tu:Ts should accompany processive RNA polymerization and that EF-Tu:Ts in the Qbeta replicase could function to modulate the RNA folding and structure.
Cabillic, F; Bouet-Toussaint, F; Toutirais, O; Rioux-Leclercq, N; Fergelot, P; de la Pintière, C Thomas; Genetet, N; Patard, J-J; Catros-Quemener, V
2006-12-01
Anti-tumour T cell response requires antigen presentation via efficient immunological synapse between antigen presenting cells, e.g. dendritic cells (DC), and specific T cells in an adapted Th1 cytokine context. Nine renal cell carcinoma (RCC) primary culture cells were used as sources of tumour antigens which were loaded on DC (DC-Tu) for autologous T cell activation assays. Cytotoxic activity of lymphocytes stimulated with DC-Tu was evaluated against autologous tumour cells. Assays were performed with 75 grays irradiated tumour cells (Tu irr) and with hydrogen peroxide +/- heat shock (Tu H(2)O(2) +/- HS) treated cells. DC-Tu irr failed to enhance cytotoxic activity of autologous lymphocytes in seven of 13 assays. In all these defective assays, irradiated tumour cells displayed high interleukin (IL)-6 and vascular endothelial growth factor (VEGF) release. Conversely, when tumour cells released low IL-6 levels (n = 4), DC-Tu irr efficiently enhanced CTL activity. When assays were performed with the same RCC cells treated with H(2)O(2) + HS, DC-Tu stimulation resulted in improved CTL activity. H(2)O(2) + HS treatment induced post-apoptotic cell necrosis of tumour cells, totally abrogated their cytokine release [IL-6, VEGF, transforming growth factor (TGF)-beta1] and induced HSP70 expression. Taken together, data show that reduction in IL-6 and VEGF release in the environment of the tumour concomitantly to tumour cell HSP expression favours induction of a stronger anti-tumour CTL response.
Förster, C; Limmer, S; Zeidler, W; Sprinzl, M
1994-01-01
tRNA(Val) from Escherichia coli was aminoacylated with [1-13C]valine and its complex with Thermus thermophilus elongation factor EF-Tu.GTP was analyzed by 13C NMR spectroscopy. The results suggest that the aminoacyl residue of the valyl-tRNA in ternary complex with bacterial EF-Tu and GTP is not attached to tRNA by a regular ester bond to either a 2'- or 3'-hydroxyl group; instead, an intermediate orthoester acid structure with covalent linkage to both vicinal hydroxyls of the terminal adenosine-76 is formed. Mutation of arginine-59 located in the effector region of EF-Tu, a conserved residue in protein elongation factors and the alpha subunits of heterotrimeric guanine nucleotide-binding regulatory proteins (G proteins), abolishes the stabilization of the orthoester acid structure of aminoacyl-tRNA. PMID:8183898
Sato, Aya; Suematsu, Takuma; Aihara, Koh-Ki; Kita, Kiyoshi; Suzuki, Tsutomu; Watanabe, Kimitsuna; Ohtsuki, Takashi; Watanabe, Yoh-Ichi
2017-03-07
Translation elongation factor Tu (EF-Tu) delivers aminoacyl-tRNA (aa-tRNA) to ribosomes in protein synthesis. EF-Tu generally recognizes aminoacyl moieties and acceptor- and T-stems of aa-tRNAs. However, nematode mitochondrial (mt) tRNAs frequently lack all or part of the T-arm that is recognized by canonical EF-Tu. We previously reported that two distinct EF-Tu species, EF-Tu1 and EF-Tu2, respectively, recognize mt tRNAs lacking T-arms and D-arms in the mitochondria of the chromadorean nematode Caenorhabditis elegans C. elegans EF-Tu2 specifically recognizes the seryl moiety of serylated D-armless tRNAs. Mitochondria of the enoplean nematode Trichinella possess three structural types of tRNAs: T-armless tRNAs, D-armless tRNAs, and cloverleaf tRNAs with a short T-arm. Trichinella mt EF-Tu1 binds to all three types and EF-Tu2 binds only to D-armless Ser-tRNAs, showing an evolutionary intermediate state from canonical EF-Tu to chromadorean nematode (e.g. C. elegans ) EF-Tu species. We report here that two EF-Tu species also participate in Drosophila melanogaster mitochondria. Both D. melanogaster EF-Tu1 and EF-Tu2 bound to cloverleaf and D-armless tRNAs. D. melanogaster EF-Tu1 has the ability to recognize T-armless tRNAs that do not evidently exist in D. melanogaster mitochondria, but do exist in related arthropod species. In addition, D. melanogaster EF-Tu2 preferentially bound to aa-tRNAs carrying small amino acids, but not to aa-tRNAs carrying bulky amino acids. These results suggest that the Drosophila mt translation system could be another intermediate state between the canonical and nematode mitochondria-type translation systems. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.
Structural insights into translational fidelity.
Ogle, James M; Ramakrishnan, V
2005-01-01
The underlying basis for the accuracy of protein synthesis has been the subject of over four decades of investigation. Recent biochemical and structural data make it possible to understand at least in outline the structural basis for tRNA selection, in which codon recognition by cognate tRNA results in the hydrolysis of GTP by EF-Tu over 75 A away. The ribosome recognizes the geometry of codon-anticodon base pairing at the first two positions but monitors the third, or wobble position, less stringently. Part of the additional binding energy of cognate tRNA is used to induce conformational changes in the ribosome that stabilize a transition state for GTP hydrolysis by EF-Tu and subsequently result in accelerated accommodation of tRNA into the peptidyl transferase center. The transition state for GTP hydrolysis is characterized, among other things, by a distorted tRNA. This picture explains a large body of data on the effect of antibiotics and mutations on translational fidelity. However, many fundamental questions remain, such as the mechanism of activation of GTP hydrolysis by EF-Tu, and the relationship between decoding and frameshifting.
Chen, Yu-Wen; Tzeng, Jann-Inn; Huang, Po-Ching; Hung, Ching-Hsia; Shao, Dong-Zi; Wang, Jhi-Joung
2015-01-01
We studied the mechanisms and impact of therapeutic ultrasound (TU) for pain caused by nerve injury. TU began on post-operative day 5 (POD5) and then continued daily for the next 22 d. Sensitivity to thermal and mechanical stimuli and levels of neurokinin-1 receptor, substance P, tumor necrosis factor-α and interleukin-6 in the sciatic nerve were examined. On POD7, chronic constriction injury rats undergoing TU at an intensity of 1 W/cm(2), but not 0.25 or 0.5 W/cm(2), had increases in both the mechanical withdrawal threshold and the thermal withdrawal latency compared with the chronic constriction injury group. Moreover, chronic constriction injury rats exhibited upregulation of neurokinin-1 receptor, substance P, tumor necrosis factor-α and interleukin-6 in the sciatic nerve on PODs 14 and 28, whereas TU inhibited their increased expression. We suggest that the efficacy of TU is dependent on its ability to limit the upregulation of neurokinin-1 receptor, substance P, tumor necrosis factor-α and interleukin-6 around the injured sciatic nerve. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.
Studies of elongation factor Tu in Streptococcus faecium (ATCC 9790)
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bourbeau, P.P.
1986-01-01
It has been known for over twenty years that elongation factor Tu (Ef-Tu) is one of the proteins involved in protein synthesis in bacteria. Several years ago, it was proposed that Ef-Tu may, in addition, have other structural functions in bacterial. The author's research has examined the function of Ef-Tu in Streptococcus faecium. Using an antibiotic kirromycin, which specifically inhibits Ef-Tu function, the effects upon a number of cellular parameters were determined. Inhibition of both protein and RNA synthesis was found to be similar to the effect of chloramphenicol. Using the residual division technique for the determination of cell cyclemore » events with both heterogeneous and sucrose gradient fractionated cell populations, a kirromycin sensitive event was detected between 8 min. (Td = 30 min.) and 19 min. (Td = 175 min.) later in the cell cycle than the chloramphenical sensitive event. This suggests that kirromycin is inhibiting a terminal cell cycle event which is in addition to the inhibition of protein synthesis. Purification of Ef-Tu was performed using two different methods: ion exchange and molecular exclusion chromatography; and GDP affinity chromatography. Various schemes were employed to try and obtain optimum cellular fractionation, allowing for both proper separation of ribosomes from the other cellular fractions and retention of enzymatic activity by Ef-Tu as determined by a /sup 3/H-GDP binding assay. Analysis of the cell cycle of S. faecium using the residual division technique was also performed. In addition, certain cell wall antibiotics were used to determine if other cell cycle events could be determined using the residual division technique.« less
Premkumar, Lakshmanane; Kurth, Fabian; Duprez, Wilko; Grøftehauge, Morten K.; King, Gordon J.; Halili, Maria A.; Heras, Begoña; Martin, Jennifer L.
2014-01-01
The multidrug resistant bacterium Acinetobacter baumannii is a significant cause of nosocomial infection. Biofilm formation, that requires both disulfide bond forming and chaperone-usher pathways, is a major virulence trait in this bacterium. Our biochemical characterizations show that the periplasmic A. baumannii DsbA (AbDsbA) enzyme has an oxidizing redox potential and dithiol oxidase activity. We found an unexpected non-covalent interaction between AbDsbA and the highly conserved prokaryotic elongation factor, EF-Tu. EF-Tu is a cytoplasmic protein but has been localized extracellularly in many bacterial pathogens. The crystal structure of this complex revealed that the EF-Tu switch I region binds to the non-catalytic surface of AbDsbA. Although the physiological and pathological significance of a DsbA/EF-Tu association is unknown, peptides derived from the EF-Tu switch I region bound to AbDsbA with submicromolar affinity. We also identified a seven-residue DsbB-derived peptide that bound to AbDsbA with low micromolar affinity. Further characterization confirmed that the EF-Tu- and DsbB-derived peptides bind at two distinct sites. These data point to the possibility that the non-catalytic surface of DsbA is a potential substrate or regulatory protein interaction site. The two peptides identified in this work together with the newly characterized interaction site provide a novel starting point for inhibitor design targeting AbDsbA. PMID:24860094
Premkumar, Lakshmanane; Kurth, Fabian; Duprez, Wilko; Grøftehauge, Morten K; King, Gordon J; Halili, Maria A; Heras, Begoña; Martin, Jennifer L
2014-07-18
The multidrug resistant bacterium Acinetobacter baumannii is a significant cause of nosocomial infection. Biofilm formation, that requires both disulfide bond forming and chaperone-usher pathways, is a major virulence trait in this bacterium. Our biochemical characterizations show that the periplasmic A. baumannii DsbA (AbDsbA) enzyme has an oxidizing redox potential and dithiol oxidase activity. We found an unexpected non-covalent interaction between AbDsbA and the highly conserved prokaryotic elongation factor, EF-Tu. EF-Tu is a cytoplasmic protein but has been localized extracellularly in many bacterial pathogens. The crystal structure of this complex revealed that the EF-Tu switch I region binds to the non-catalytic surface of AbDsbA. Although the physiological and pathological significance of a DsbA/EF-Tu association is unknown, peptides derived from the EF-Tu switch I region bound to AbDsbA with submicromolar affinity. We also identified a seven-residue DsbB-derived peptide that bound to AbDsbA with low micromolar affinity. Further characterization confirmed that the EF-Tu- and DsbB-derived peptides bind at two distinct sites. These data point to the possibility that the non-catalytic surface of DsbA is a potential substrate or regulatory protein interaction site. The two peptides identified in this work together with the newly characterized interaction site provide a novel starting point for inhibitor design targeting AbDsbA. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.
Weiser, Brian; Gonye, Gregory; Sykora, Peter; Crumm, Sara; Cahill, Alan
2011-05-01
Chronic ethanol feeding is known to negatively impact hepatic energy metabolism. Previous studies have indicated that the underlying lesion responsible for this may lie at the level of the mitoribosome. The aim of this study was to characterize the structure of the hepatic mitoribosome in alcoholic male rats and their isocalorically paired controls. Our experiments revealed that chronic ethanol feeding resulted in a significant depletion of both structural (death-associated protein 3) and functional [elongation factor thermo unstable (EF-Tu)] mitoribosomal proteins. In addition, significant increases were found in nucleotide elongation factor thermo stable (EF-Ts) and structural mitochondrial ribosomal protein L12 (MRPL12). The increase in MRPL12 was found to correlate with an increase in the levels of the 39S large mitoribosomal subunit. These changes were accompanied by decreased levels of nuclear- and mitochondrially encoded respiratory subunits, decreased amounts of intact respiratory complexes, decreased hepatic ATP levels, and depressed mitochondrial translation. Mathematical modeling of ethanol-mediated changes in EF-Tu and EF-Ts using prederived kinetic data predicted that the ethanol-mediated decrease in EF-Tu levels could completely account for the impaired mitochondrial protein synthesis. In conclusion, chronic ethanol feeding results in a depletion of mitochondrial EF-Tu levels within the liver that is mathematically predicted to be responsible for the impaired mitochondrial protein synthesis seen in alcoholic animals.
Pod Corn Is Caused by Rearrangement at the Tunicate1 Locus[W][OA
Han, Jong-Jin; Jackson, David; Martienssen, Robert
2012-01-01
Pod corn (Zea mays var tunicata) was once regarded as ancestral to cultivated maize, and was prized by pre-Columbian cultures for its magical properties. Tunicate1 (Tu1) is a dominant pod corn mutation in which kernels are completely enclosed in leaflike glumes. Here we show that Tu1 encodes a MADS box transcription factor expressed in leaves whose 5′ regulatory region is fused by a 1.8-Mb chromosomal inversion to the 3′ region of a gene expressed in the inflorescence. Both genes are further duplicated, accounting for classical derivative alleles isolated by recombination, and Tu1 transgenes interact with these derivative alleles in a dose-dependent manner. In young ear primordia, TU1 proteins are nuclearly localized in specific cells at the base of spikelet pair meristems. Tu1 branch determination defects resemble those in ramosa mutants, which encode regulatory proteins expressed in these same cells, accounting for synergism in double mutants discovered almost 100 years ago. The Tu1 rearrangement is not found in ancestral teosinte and arose after domestication of maize. PMID:22829149
Wang, Dongxian; Luo, Benping; Shan, Weiran; Hao, Mingcong; Sun, Xuesong; Ge, Ruiguang
2013-06-01
Helicobacter pylori is a common human pathogen responsible for various gastric diseases. Bismuth can effectively inhibit the growth of this bacterium and is commonly recommended for the treatment of the related diseases. Translation elongation factors EF-Tu and EF-Ts are two important components of the protein translation system. EF-Ts has inhibitory effects on the GTPase activity of EF-Tu and enhances GDP release, a hint that careful timing for the introduction of EF-Ts in the elongation should be accomplished to prevent the complete inhibition of the elongation process. Bismuth inhibits the chaperone activity of EF-Tu, and has opposite effects on the elongation activity: inhibitory effects on the intrinsic GTPase activity and stimulation of GDP release. The present work deepens our understanding of the bacterial elongation process as mediated by EF-Tu and EF-Ts and extends our knowledge about the inhibitory effects of bismuth-based drugs against Helicobacter pylori.
De Laurentiis, Evelina Ines; Mercier, Evan; Wieden, Hans-Joachim
2016-10-28
Little is known about the conservation of critical kinetic parameters and the mechanistic strategies of elongation factor (EF) Ts-catalyzed nucleotide exchange in EF-Tu in bacteria and particularly in clinically relevant pathogens. EF-Tu from the clinically relevant pathogen Pseudomonas aeruginosa shares over 84% sequence identity with the corresponding elongation factor from Escherichia coli Interestingly, the functionally closely linked EF-Ts only shares 55% sequence identity. To identify any differences in the nucleotide binding properties, as well as in the EF-Ts-mediated nucleotide exchange reaction, we performed a comparative rapid kinetics and mutagenesis analysis of the nucleotide exchange mechanism for both the E. coli and P. aeruginosa systems, identifying helix 13 of EF-Ts as a previously unnoticed regulatory element in the nucleotide exchange mechanism with species-specific elements. Our findings support the base side-first entry of the nucleotide into the binding pocket of the EF-Tu·EF-Ts binary complex, followed by displacement of helix 13 and rapid binding of the phosphate side of the nucleotide, ultimately leading to the release of EF-Ts. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
Ramiah, K; van Reenen, C A; Dicks, L M T
2007-05-30
Expression of the mucus adhesion genes Mub and MapA, adhesion-like factor EF-Tu and bacteriocin gene plaA by Lactobacillus plantarum 423, grown in the presence of bile, pancreatin and at low pH, was studied by real-time PCR. Mub, MapA and EF-Tu were up-regulated in the presence of mucus, proportional to increasing concentrations. Expression of MapA was up-regulated in the presence of 3.0 g/l bile and 3.0 g/l pancreatin at pH 6.5. Similar results were recorded in the presence of 10.0 g/l bile and 10.0 g/l pancreatin at pH 6.5. Expression of Mub was down-regulated in the presence of bile and pancreatin, whilst the expression of EF-Tu and plaA remained unchanged. Expression of Mub and MapA remained unchanged at pH 4.0, whilst expression of EF-Tu and plaA were up-regulated. Expression of MapA was down-regulated in the presence of 1.0 g/l l-cysteine HCl, suggesting that the gene is regulated by transcription attenuation that involves cysteine.
Cloning and characterization of EF-Tu and EF-Ts from Pseudomonas aeruginosa.
Palmer, Stephanie O; Rangel, Edna Y; Montalvo, Alberto E; Tran, Alexis T; Ferguson, Kate C; Bullard, James M
2013-01-01
We have cloned genes encoding elongation factors EF-Tu and EF-Ts from Pseudomonas aeruginosa and expressed and purified the proteins to greater than 95% homogeneity. Sequence analysis indicated that P. aeruginosa EF-Tu and EF-Ts are 84% and 55% identical to E. coli counterparts, respectively. P. aeruginosa EF-Tu was active when assayed in GDP exchange assays. Kinetic parameters for the interaction of EF-Tu with GDP in the absence of EF-Ts were observed to be K M = 33 μM, k cat (obs) = 0.003 s(-1), and the specificity constant k cat (obs)/K M was 0.1 × 10(-3) s(-1) μM(-1). In the presence of EF-Ts, these values were shifted to K M = 2 μM, k cat (obs) = 0.005 s(-1), and the specificity constant k(cat)(obs)/K M was 2.5 × 10(-3) s(-1) μM(-1). The equilibrium dissociation constants governing the binding of EF-Tu to GDP (K GDP) were 30-75 nM and to GTP (K GTP) were 125-200 nM. EF-Ts stimulated the exchange of GDP by EF-Tu 10-fold. P. aeruginosa EF-Tu was active in forming a ternary complex with GTP and aminoacylated tRNA and was functional in poly(U)-dependent binding of Phe-tRNA(Phe) at the A-site of P. aeruginosa ribosomes. P. aeruginosa EF-Tu was active in poly(U)-programmed polyphenylalanine protein synthesis system composed of all P. aeruginosa components.
Defeu Soufo, Hervé Joël; Reimold, Christian; Breddermann, Hannes; Mannherz, Hans G; Graumann, Peter L
2015-04-24
EF-Tu has been shown to interact with actin-like protein MreB and to affect its localization in Escherichia coli and in Bacillus subtilis cells. We have purified YFP-MreB in an active form, which forms filaments on glass slides in vitro and was active in dynamic light-scattering assays, polymerizing in milliseconds after addition of magnesium. Purified EF-Tu enhanced the amount of MreB filaments, as seen by sedimentation assays, the speed of filament formation and the length of MreB filaments in vitro. EF-Tu had the strongest impact on MreB filaments in a 1:1 ratio, and EF-Tu co-sedimented with MreB filaments, revealing a stoichiometric interaction between both proteins. This was supported by cross-linking assays where 1:1 species were well detectable. When expressed in E. coli cells, B. subtilis MreB formed filaments and induced the formation of co-localizing B. subtilis EF-Tu structures, indicating that MreB can direct the positioning of EF-Tu structures in a heterologous cell system. Fluorescence recovery after photobleaching analysis showed that MreB filaments have a higher turnover in B. subtilis cells than in E. coli cells, indicating different filament kinetics in homologous or heterologous cell systems. The data show that MreB can direct the localization of EF-Tu in vivo, which in turn positively affects the formation and dynamics of MreB filaments. Thus, EF-Tu is a modulator of the activity of a bacterial actin-like protein. Copyright © 2015. Published by Elsevier Ltd.
Yang, Xuqin; Zhang, Weiwei; He, Huanle; Nie, Jingtao; Bie, Beibei; Zhao, Junlong; Ren, Guoliang; Li, Yue; Zhang, Dabing; Pan, Junsong; Cai, Run
2014-06-01
Cucumber fruits that have tubercules and spines (trichomes) are known to possess a warty (Wty) phenotype. In this study, the tuberculate fruit gene Tu was identified by map-based cloning, and was found to encode a transcription factor (TF) with a single C2 H2 zinc finger domain. Tu was identified in all 38 Wty lines examined, and was completely absent from all 56 non-warty (nWty) lines. Cucumber plants transgenic for Tu (TCP) revealed that Tu was required for the Wty fruit phenotype. Subcellular localization showed that the fusion protein GFP-Tu was localized mainly to the nucleus. Based on analyses of semi-quantitative and quantitative reverse transcription polymerase chain reaction (RT-PCR), and mRNA in situ hybridization, we found that Tu was expressed specifically in fruit spine cells during development of fruit tubercules. Moreover, cytokinin (CTK) content measurements and cytological observations in Wty and nWty fruits revealed that the Wty fruit phenotype correlated with high endogenous CTK concentrations. As a result of further analyses on the transcriptomic profile of the nWty fruit epidermis and TCP fruit warts, expression of CTK-associated genes, and hormone content in nWty fruit epidermis, Wty fruit warts and epidermis, and TCP fruit warts and epidermis, we found that Tu probably promoted CTK biosynthesis in fruit warts. Here we show that Tu could not be expressed in the glabrous and tubercule-free mutant line gl that contained Tu, this result that futher confirmed the epistatic effect of the trichome (spine) gene Gl over Tu. Taken together, these data led us to propose a genetic pathway for the Wty fruit trait that could guide future mechanistic studies. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.
Federal Logistics Information System (FLIS) Procedures Manual. Volume 13. Change 1.
1997-01-01
BD 06 TA 67 BD BD TU BD TU BD FBDA DF BD 06 TA 96 BD BD TU BD TU BD FBDD DF BD 06 TD 96 BD BD TU BD TU BD FBDE DF BD 06 SE 96 BD BD TU BD TU BD FBDG...XN TD FAZD DF AZ 06 TD 96 AZ AZ TU AZ TU TD FAZ7 DF AZ 22 TD 97 AZ AZ TU AZ TU TD FBDD DF BD 06 TD 96 BD BD TU BD TU TD FBD7 DF BD 22 TD 97 BD BD TU...48 TU TU FBDA DF BD 06 TA 96 BD BD TU BD TU TU FBDD DF BD 06 TD 96 BD BD TU BD TU TU FBDE DF BD 06 SE 96 BD BD TU BD TU TU FBDG DF BD 06 TG 96 BD BD TU
FLIS Procedures Manual. Materiel Management Decision Rule Tables.
1996-10-01
U5 C PA FAPA DF PA 06 TA 67 PA PA TU PA TU PA FEPA DF PA 06 SE 67 PA PA TU PA TU PA FGPA DF PA 06 TG 67 PA PA TU PA TU PA FJPA DF PA 06 SJ 67 PA PA SJ...AJ TU AJ TU TA FAJ4 DF AJ 22 TA 97 AJ AJ TU AJ TU TA FAKE DF KE 06 TA 67 KE KE TU KE TU TA FAKZ DF KZ 01 TA 5D KZ KZ TU KZ TU I TA FAPA DF PA 06 TA...AJ TU TU FAJ5 DF AJ 22 TG 97 AJ AJ TU AJ TU TU FAKE DF KE 06 TA 67 KE KE TU KE TU TU FAPA DF PA 01 TA 67 PA PA TU PA TU TU FATC DF AZ 22 TA 8D AZ AZ
Ott, G; Faulhammer, H G; Sprinzl, M
1989-09-15
Transfer ribonucleic acids containing 2-thiocytidine in position 75 ([s2C]tRNAs) were prepared by incorporation of the corresponding cytidine analogue into 3'-shortened tRNA using ATP(CTP):tRNA nucleotidyltransferase. [s2C]tRNA was selectively alkylated with fluorescent N-iodoacetyl-N'-(5-sulfo-1-naphthyl)ethylenediamine (1,5-I-AEDANS) on the 2-thiocytidine residue. The product [AEDANS-s2C]aminoacyl-tRNA, forms a ternary complex with Escherichia coli elongation factor Tu and GTP, leading to up to 130% fluorescence enhancement of the AEDANS chromophore. From fluorescence titration experiments, equilibrium dissociation constants of 0.24 nM, 0.22 nM and 0.60 nM were determined for yeast [AEDANS-s2C]Tyr-tRNATyr, yeast Tyr-tRNATyr, and the homologous E. coli Phe-tRNAPhe, respectively, interacting with E. coli elongation factor Tu.GTP. The measurement of the association and dissociation rates of the interaction of [AEDANS-s2C]Tyr-tRNATyr with EF-Tu.GTP and the temperature dependence of the resulting dissociation constants gave values of 55 J mol-1 K-1 for delta S degrees' and -34.7 kJ mol-1 for delta H degrees' of this reaction.
International Symposium on Molecular Spectroscopy (70th)
2015-06-22
N DAY June 22 8:30 AM TU ESDAY June 23 8:30 AM W EDN ESDAY June 24 8:30 AM THU RSDAY June 25 8:30 AM FRIDAY June 26 8:30 AM Foellinger Auditorium M A...energy surfaces Room 100 N oyes Laboratory TB M ini-sym posium : Accelerator-Based Spectroscopy RB M ini-sym posium : Accelerator-Based...Conform ers, isom ers, chirality, stereochem istry RD Astronom y FD Atm ospheric science Room 217 N oyes Laboratory TE Instrum
López-Ochoa, Jaqueline; Montes-García, J Fernando; Vázquez, Candelario; Sánchez-Alonso, Patricia; Pérez-Márquez, Victor M; Blackall, Patrick J; Vaca, Sergio; Negrete-Abascal, Erasmo
2017-09-01
Gallibacterium, which is a bacterial pathogen in chickens, can form biofilms. Amyloid proteins present in biofilms bind Congo red dye. The aim of this study was to characterize the cell-surface amyloid-like protein expressed in biofilms formed by Gallibacterium strains and determine the relationship between this protein and curli, which is an amyloid protein that is commonly expressed by members of the Enterobacteriaceae family. The presence of amyloid-like proteins in outer membrane protein samples from three strains of G. anatis and one strain of Gallibacterium genomospecies 2 was evaluated. A protein identified as elongation factor-Tu (EF-Tu) by mass spectrometric analysis and in silico analysis was obtained from the G. anatis strain F149 T . This protein bound Congo red dye, cross-reacted with anti-curli polyclonal serum, exhibited polymerizing properties and was present in biofilms. This protein also reacted with pooled serum from chickens that were experimentally infected with G. anatis, indicating the in vivo immunogenicity of this protein. The recombinant EF-Tu purified protein, which was prepared from G. anatis 12656-12, polymerizes under in vitro conditions, forms filaments and interacts with fibronectin and fibrinogen, all of which suggest that this protein functions as an adhesin. In summary, EF-Tu from G. anatis presents amyloid characteristics, is present in biofilms and could be relevant for the pathogenesis of G. anatis.
USDA-ARS?s Scientific Manuscript database
Clostridium-related diseases such as gangrenous dermatitis (GD) and necrotic enteritis (NE) are increasingly emerging as major diseases in recent years with high economic loss around the world. In this report, we characterized two immunogenic Clostridium perfringens (CP) proteins (e.g., elongation f...
Palade, Elena Alina; Demeter, Zoltán; Hornyák, Akos; Nemes, Csaba; Kisary, János; Rusvai, Miklós
2011-09-01
Samples collected in 2008 and 2009, from 49 turkey flocks of 6 to 43 days in age and presenting clinical signs of enteric disease and high mortality, were tested by polymerase chain reaction and reverse transcription-polymerase chain reaction for the presence of viruses currently associated with enteric disease (ED) syndromes: astrovirus, reovirus, rotavirus, coronavirus, adenovirus, and parvovirus. Turkey astroviruses were found in 83.67% of the cases and turkey astrovirus 2 (TAst-2) in 26.53%. The investigations directly demonstrated the high prevalence of turkey parvovirus (TuPV) in 23 flocks (46.9%) experiencing signs of ED, making this pathogen the second most identified after astroviruses. Phylogenetic analysis on a 527 base pair-long region from the NS1 gene revealed two main clusters, a chicken parvovirus (ChPV) and a TuPV group, but also the presence of a divergent branch of tentatively named "TuPV-like ChPV" strains. The 23 Hungarian TuPV strains were separately positioned in two groups from the American origin sequences in the TuPV cluster. An Avail-based restriction fragment length polymorphism assay has also been developed for the quick differentiation of TuPV, ChPV, and divergent TuPV-like ChPV strains. As most detected enteric viruses have been directly demonstrated in healthy turkey flocks as well, the epidemiology of this disease complex remains unclear, suggesting that a certain combination of pathogens, environmental factors, or both are necessary for the development of clinical signs.
Inhibition by Siomycin and Thiostrepton of Both Aminoacyl-tRNA and Factor G Binding to Ribosomes
Ll, Juan Modole; Cabrer, Bartolomé; Parmeggiani, Andrea; Azquez, David V
1971-01-01
Siomycin, a peptide antibiotic that interacts with the 50S ribosomal subunit and inhibits binding of factor G, is shown also to inhibit binding of aminoacyl-tRNA; however, it does not impair binding of fMet-tRNA and completion of the initiation complex. Moreover, unlike other inhibitors of aminoacyl-tRNA binding (tetracycline, sparsomycin, and streptogramin A), siomycin completely abolishes the GTPase activity associated with the binding of aminoacyl-tRNA catalyzed by factor Tu. A single-site interaction of siomycin appears to be responsible for its effect on both the binding of the aminoacyl-tRNA-Tu-GTP complex and that of factor G. PMID:4331558
Nonrandom γ-TuNA-dependent spatial pattern of microtubule nucleation at the Golgi
Sanders, Anna A. W. M.; Chang, Kevin; Zhu, Xiaodong; Thoppil, Roslin J.; Holmes, William R.; Kaverina, Irina
2017-01-01
Noncentrosomal microtubule (MT) nucleation at the Golgi generates MT network asymmetry in motile vertebrate cells. Investigating the Golgi-derived MT (GDMT) distribution, we find that MT asymmetry arises from nonrandom nucleation sites at the Golgi (hotspots). Using computational simulations, we propose two plausible mechanistic models of GDMT nucleation leading to this phenotype. In the “cooperativity” model, formation of a single GDMT promotes further nucleation at the same site. In the “heterogeneous Golgi” model, MT nucleation is dramatically up-regulated at discrete and sparse locations within the Golgi. While MT clustering in hotspots is equally well described by both models, simulating MT length distributions within the cooperativity model fits the data better. Investigating the molecular mechanism underlying hotspot formation, we have found that hotspots are significantly smaller than a Golgi subdomain positive for scaffolding protein AKAP450, which is thought to recruit GDMT nucleation factors. We have further probed potential roles of known GDMT-promoting molecules, including γ-TuRC-mediated nucleation activator (γ-TuNA) domain-containing proteins and MT stabilizer CLASPs. While both γ-TuNA inhibition and lack of CLASPs resulted in drastically decreased GDMT nucleation, computational modeling revealed that only γ-TuNA inhibition suppressed hotspot formation. We conclude that hotspots require γ-TuNA activity, which facilitates clustered GDMT nucleation at distinct Golgi sites. PMID:28931596
Fu, Jianming; Momcilović, Ivana; Clemente, Thomas E; Nersesian, Natalya; Trick, Harold N; Ristic, Zoran
2008-10-01
Heat stress is a major constraint to wheat production and negatively impacts grain quality, causing tremendous economic losses, and may become a more troublesome factor due to global warming. At the cellular level, heat stress causes denaturation and aggregation of proteins and injury to membranes leading to alterations in metabolic fluxes. Protein aggregation is irreversible, and protection of proteins from thermal aggregation is a strategy a cell uses to tolerate heat stress. Here we report on the development of transgenic wheat (Triticum aestivum) events, expressing a maize gene coding for plastidal protein synthesis elongation factor (EF-Tu), which, compared to non-transgenic plants, display reduced thermal aggregation of leaf proteins, reduced heat injury to photosynthetic membranes (thylakoids), and enhanced rate of CO(2) fixation after exposure to heat stress. The results support the concept that EF-Tu ameliorates negative effects of heat stress by acting as a molecular chaperone. This is the first demonstration of the introduction of a plastidal EF-Tu in plants that leads to protection against heat injury and enhanced photosynthesis after heat stress. This is also the first demonstration that a gene other than HSP gene can be used for improvement of heat tolerance and that the improvement is possible in a species that has a complex genome, hexaploid wheat. The results strongly suggest that heat tolerance of wheat, and possibly other crop plants, can be improved by modulating expression of plastidal EF-Tu and/or by selection of genotypes with increased endogenous levels of this protein.
Copper(I), silver(I) and gold(I) halide complexes with the dithioformamidinium dihalides
NASA Astrophysics Data System (ADS)
Peyronel, Giorgio; Malavasi, Wanda; Pignedoli, Anna
Some copper(I), silver(I) and gold(I) halide complexes with the dithioformamidinium dihalides (Tu 2X 2) were prepared and studied by infrared spectroscopy and conductometry: 3CuX.2Tu 2X 2(XCl,I), CuBr.Tu 2Br 2, 4CuBr.3.5Tu 2Br 2.MeOH, 2CuBr.Tu 2Br 2.0.66EtOH, 3CuI.2Tu 2I 2, 2AgCl.2.5Tu 2Cl 2, 3AgCl.2Tu 2Cl 2.0.5EtOH, 3AgCl.Tu 2Cl 2, 2AgBr.2Tu 2Br 2.0.5Tu 2(NO 3) 2.H 2O, AgBr.Tu 2Br 2, 4AgBr.Tu 2Br 2, 4AgI.0.5Tu 2I 2.EtOH, AuCl.1.5Tu 2Cl 2, 4AuCl.3.5Tu 2Cl 2.2DMF, AuBr.4Tu 2Br 2, AuBr.2Tu 2Br 2.1.5DMF, AuI.5Tu 2I 2, AuI.Tu 2I 2. A decrease of the ν(NH), δ(NH 2) and ν(CN 2) frequencies and an increase of the ν(CS) frequencies indicate an N-coordination of the dithioformamidinium cation to the metal ions; ν(MN) and ν(MX) frequencies are tentatively assigned in the far-infrared spectra.
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.
Wang, Deng-Liang; Song, Yan-Ling; Zhu, Zhi; Li, Xi-Lan; Zou, Yuan; Yang, Hai-Tao; Wang, Jiang-Jie; Yao, Pei-Sen; Pan, Ru-Jun; Yang, Chaoyong James; Kang, De-Zhi
2014-10-31
Epidermal growth factor receptor (EGFR/HER1/c-ErbB1), is overexpressed in many solid cancers, such as epidermoid carcinomas, malignant gliomas, etc. EGFR plays roles in proliferation, invasion, angiogenesis and metastasis of malignant cancer cells and is the ideal antigen for clinical applications in cancer detection, imaging and therapy. Aptamers, the output of the systematic evolution of ligands by exponential enrichment (SELEX), are DNA/RNA oligonucleotides which can bind protein and other substances with specificity. RNA aptamers are undesirable due to their instability and high cost of production. Conversely, DNA aptamers have aroused researcher's attention because they are easily synthesized, stable, selective, have high binding affinity and are cost-effective to produce. In this study, we have successfully identified DNA aptamers with high binding affinity and selectivity to EGFR. The aptamer named TuTu22 with Kd 56±7.3nM was chosen from the identified DNA aptamers for further study. Flow cytometry analysis results indicated that the TuTu22 aptamer was able to specifically recognize a variety of cancer cells expressing EGFR but did not bind to the EGFR-negative cells. With all of the aforementioned advantages, the DNA aptamers reported here against cancer biomarker EGFR will facilitate the development of novel targeted cancer detection, imaging and therapy. Copyright © 2014 Elsevier Inc. All rights reserved.
Wholey, Wei-Yun; Jakob, Ursula
2012-01-01
Summary The redox-regulated chaperone Hsp33 protects bacteria specifically against stress conditions that cause oxidative protein unfolding, such as treatment with bleach or exposure to peroxide at elevated temperatures. To gain insight into the mechanism by which expression of Hsp33 confers resistance to oxidative protein unfolding conditions, we made use of V. cholerae strain O395 lacking the Hsp33 gene hslO. We found that this strain, which is exquisitely bleach-sensitive, displays a temperature-sensitive (ts) phenotype during aerobic growth, implying that V. cholerae suffers from oxidative heat stress when cultivated at 43°C. We utilized this phenotype to select for E. coli genes that rescue the ts phenotype of V. cholerae ΔhslO when overexpressed. We discovered that expression of a single protein, the elongation factor EF-Tu, was sufficient to rescue both the ts and bleach-sensitive phenotypes of V. cholerae ΔhslO. In vivo studies revealed that V. cholerae EF-Tu is highly sensitive to oxidative protein degradation in the absence of Hsp33, indicating that EF-Tu is a vital chaperone substrate of Hsp33 in V. cholerae. These results suggest an “essential client protein” model for Hsp33’s chaperone action in Vibrio in which stabilization of a single oxidative stress-sensitive protein is sufficient to enhance the oxidative stress resistance of the whole organism. PMID:22296329
Khan, Farhan R; Keller, W Bill; Yan, Norman D; Welsh, Paul G; Wood, Chris M; McGeer, James C
2012-02-07
Using a 30-year record of biological and water chemistry data collected from seven lakes near smelters in Sudbury (Ontario, Canada) we examined the link between reductions of Cu, Ni, and Zn concentrations and zooplankton species richness. The toxicity of the metal mixtures was assessed using an additive Toxic Unit (TU) approach. Four TU models were developed based on total metal concentrations (TM-TU); free ion concentrations (FI-TU); acute LC50s calculated from the Biotic Ligand Model (BLM-TU); and chronic LC50s (acute LC50s adjusted by metal-specific acute-to-chronic ratios, cBLM-TU). All models significantly correlated reductions in metal concentrations to increased zooplankton species richness over time (p < 0.01) with a rank based on r(2) values of cBLM-TU > BLM-TU = FI-TU > TM-TU. Lake-wise comparisons within each model showed that the BLM-TU and cBLM-TU models provided the best description of recovery across all seven lakes. These two models were used to calculate thresholds for chemical and biological recovery using data from reference lakes in the same region. A threshold value of TU = 1 derived from the cBLM-TU provided the most accurate description of recovery. Overall, BLM-based TU models that integrate site-specific water chemistry-derived estimates of toxicity offer a useful predictor of biological recovery.
Fujimura, Masatoshi; Ideguchi, Mineo; Minami, Yuji; Watanabe, Keiichi; Tadera, Kenjiro
2004-03-01
Novel antimicrobial peptides (AMP), designated Tu-AMP 1 and Tu-AMP 2, were purified from the bulbs of tulip (Tulipa gesneriana L.) by chitin affinity chromatography and reverse-phase high-performance liquid chromatography (HPLC). They bind to chitin in a reversible way. They were basic peptides having isoelectric points of over 12. Tu-AMP 1 and Tu-AMP 2 had molecular masses of 4,988 Da and 5,006 Da on MALDI-TOF MS analysis, and their extinction coefficients of 1% aqueous solutions at 280 nm were 3.3 and 3.4, respectively. Half of all amino acid residues of Tu-AMP 1 and Tu-AMP 2 were occupied by cysteine, arginine, lysine, and proline. The concentrations of peptides required for 50% inhibition (IC(50)) of the growth of plant pathogenic bacteria and fungi were 2 to 20 microg/ml. The structural characteristics of Tu-AMP 1 and Tu-AMP 2 indicated that they were novel thionin-like antimicrobial peptides, though Tu-AMP 2 was a heterodimer composes of two short peptides joined with disulfide bonds.
Fu, Jianming; Ristic, Zoran
2010-06-01
We previously reported that transgenic wheat (Triticum aestivum L.) carrying a maize (Zea mays L.) gene (Zmeftu1) for chloroplast protein synthesis elongation factor, EF-Tu, displays reduced thermal aggregation of leaf proteins, reduced injury to photosynthetic membranes (thylakoids), and enhanced rate of CO(2) fixation following exposure to heat stress (18 h at 45 degrees C) [Fu et al. in Plant Mol Biol 68:277-288, 2008]. In the current study, we investigated the segregation pattern and expression of the transgene Zmeftu1 and determined the grain yield of transgenic plants after exposure to a brief heat stress (18 h at 45 degrees C). We also assessed thermal aggregation of soluble leaf proteins in transgenic plants, testing the hypothesis that increased levels of EF-Tu will lead to a non-specific protection of leaf proteins against thermal aggregation. The transgenic wheat displayed a single-gene pattern of segregation of Zmeftu1. Zmeftu1 was expressed, and the transgenic plants synthesized and accumulated three anti-EF-Tu cross-reacting polypeptides of similar molecular mass but different pI, suggesting the possibility of posttranslational modification of this protein. The transgenic plants also showed better grain yield after exposure to heat stress compared with their non-transgenic counterparts. Soluble leaf proteins of various molecular masses displayed lower thermal aggregation in transgenic than in non-transgenic wheat. The results suggest that overexpression of chloroplast EF-Tu can be beneficial to wheat tolerance to heat stress. Moreover, the results also support the hypothesis that EF-Tu contributes to heat tolerance by acting as a molecular chaperone and protecting heat-labile proteins from thermal aggregation in a non-specific manner.
Nonrandom γ-TuNA-dependent spatial pattern of microtubule nucleation at the Golgi.
Sanders, Anna A W M; Chang, Kevin; Zhu, Xiaodong; Thoppil, Roslin J; Holmes, William R; Kaverina, Irina
2017-11-07
Noncentrosomal microtubule (MT) nucleation at the Golgi generates MT network asymmetry in motile vertebrate cells. Investigating the Golgi-derived MT (GDMT) distribution, we find that MT asymmetry arises from nonrandom nucleation sites at the Golgi (hotspots). Using computational simulations, we propose two plausible mechanistic models of GDMT nucleation leading to this phenotype. In the "cooperativity" model, formation of a single GDMT promotes further nucleation at the same site. In the "heterogeneous Golgi" model, MT nucleation is dramatically up-regulated at discrete and sparse locations within the Golgi. While MT clustering in hotspots is equally well described by both models, simulating MT length distributions within the cooperativity model fits the data better. Investigating the molecular mechanism underlying hotspot formation, we have found that hotspots are significantly smaller than a Golgi subdomain positive for scaffolding protein AKAP450, which is thought to recruit GDMT nucleation factors. We have further probed potential roles of known GDMT-promoting molecules, including γ-TuRC-mediated nucleation activator (γ-TuNA) domain-containing proteins and MT stabilizer CLASPs. While both γ-TuNA inhibition and lack of CLASPs resulted in drastically decreased GDMT nucleation, computational modeling revealed that only γ-TuNA inhibition suppressed hotspot formation. We conclude that hotspots require γ-TuNA activity, which facilitates clustered GDMT nucleation at distinct Golgi sites. © 2017 Sanders et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).
Arita, Masashi; Suematsu, Takuma; Osanai, Arihiro; Inaba, Takashi; Kamiya, Haruo; Kita, Kiyoshi; Sisido, Masahiko; Watanabe, Yoh-ichi; Ohtsuki, Takashi
2006-01-01
EF-Tu delivers aminoacyl-tRNAs to ribosomes in the translation system. However, unusual truncations found in some animal mitochondrial tRNAs seem to prevent recognition by a canonical EF-Tu. We showed previously that the chromadorean nematode has two distinct EF-Tus, one of which (EF-Tu1) binds only to T-armless aminoacyl-tRNAs and the other (EF-Tu2) binds to D-armless Ser-tRNAs. Neither of the EF-Tus can bind to canonical cloverleaf tRNAs. In this study, by analyzing the translation system of enoplean nematode Trichinella species, we address how EF-Tus and tRNAs have evolved from the canonical structures toward those of the chromadorean translation system. Trichinella mitochondria possess three types of tRNAs: cloverleaf tRNAs, which do not exist in chromadorean nematode mitochondria; T-armless tRNAs; and D-armless tRNAs. We found two mitochondrial EF-Tu species, EF-Tu1 and EF-Tu2, in Trichinella britovi. T.britovi EF-Tu2 could bind to only D-armless Ser-tRNA, as Caenorhabditis elegans EF-Tu2 does. In contrast to the case of C.elegans EF-Tu1, however, T.britovi EF-Tu1 bound to all three types of tRNA present in Trichinella mitochondria. These results suggest that Trichinella mitochondrial translation system, and particularly the tRNA-binding specificity of EF-Tu1, could be an intermediate state between the canonical system and the chromadorean nematode mitochondrial system. PMID:17012285
Cui, Yugui; Zhu, Hui; Zhu, Yefei; Guo, Xuejiang; Huo, Ran; Wang, Xinghai; Tong, Jiansun; Qian, Lixin; Zhou, Zuomin; Jia, Yue; Lue, Yan-He; Hikim, Amiya Sinha; Wang, Christina; Swerdloff, Ronald S; Sha, Jiahao
2008-09-01
Treatment with injectable testosterone undecanoate (TU) alone or in combination with oral levonorgestrel (LNG) resulted in marked decreases in sperm concentrations. In this study, we used proteomic analyses to examine the cellular/molecular events occurring in the human testis after TU or TU + LNG treatment. We conducted a global proteomic analysis of the human testicular biopsies before and at 2 weeks after TU alone or TU + LNG treatment. Proteins showing significant changes in expression were identified and analyzed. As a result, 17 and 46 protein spots were found with significant differential expression after the treatment with TU alone and TU + LNG, respectively. TU treatment changed the expression of heterogeneous nuclear ribonucleoprotein K (hnRNP K), proteasome inhibitor PI31 subunit (PSMF1), and superoxide dismutase [Mn] mitochondrial precursor (SOD2). These proteins inhibit "assembly", induce cell death, and promote compensatory "cell survival" in the testis. After TU + LNG treatment, "proliferation/cell survival" and "apoptosis/death" were the predominant responses in the testis. TU + LNG treatment inhibited the expression of Prolyl 4-hydroxylase beta subunit (P4HB) and Annexin A2 (Annexin II). These proteins are involved in apoptosis and cell proliferation, respectively. TU + LNG treatment also enhanced the expression of SOD2 and Parvalbumin alpha (Pvalb). These two proteins may protect testicular cells against apoptosis/death and promote cell survival. In conclusion, TU and TU + LNG treatments suppress spermatogenesis through different pathways by changing the expression of different proteins. hnRNP K, PSMF1, SOD2, P4HB, Annexin II, and Pvalb, are key proteins that may be early molecular targets responsible for spermatogenesis suppression induced by hormone treatment.
ERIC Educational Resources Information Center
Lei, Hongde
2016-01-01
Youguang Tu is a contemporary Chinese philosopher of education. His course on philosophy of education had a significant impact on his students. This exploratory study examines how Tu designed and taught this course. Ultimately, there are two reasons why Tu's course had such a significant influence on his students. The first is that Tu used…
Need for Different Cutoff Values for Reading Mantoux Test with 2TU and 5TU PPD.
Ramaraj, Savitha M; Nagendra, K; Gopal, Girish; Majgi, Sumanth Mallikarjuna
2017-09-01
To compare the tuberculin reaction of 2 tuberculin unit (TU) with 5TU purified protein derivative (PPD) (both calibrated against RT 23) in healthy children. This was a cross sectional study done in the pediatric outpatient department of a tertiary care teaching hospital. Seventy healthy siblings of the children attending pediatric outpatient department in the age group of 1 to 12 y were enrolled. The exclusion criteria included previously diagnosed tuberculosis patients, malnutrition diagnosed according to the WHO classification, history of drug intake like steroids, recent history of measles, any skin lesions over forearm, history of fever, contact with tuberculosis and previous mantoux testing. The study was conducted wherein each child was subjected to simultaneous testing with 2TU and 5TU by standard technique. The reactions to both the tests was read at 48-72 h. Children with induration ≥10 mm were evaluated for tuberculosis by taking chest x-ray, gastric lavage or sputum smear examination for acid fast bacilli (AFB). Considering ≥10 mm induration as positive, subjects positive with 5TU were 7 (10%) and 2TU was 1(p value = 0.031); thus, there is no agreement between the two methods (McNemar's test). Comparing the mean diameter of induration of 2TU and 5TU (p < 0.001, Wilcoxon test), signified no agreement between the two strengths. Bland-Altman plot and kappa statistic showed no agreement between the two strengths. Cutaneous hypersensitivity to 2TU PPD is not comparable to that of 5TU PPD.
Two Novel Vesicle-Inducing Proteins in Plastids 1 Genes Cloned and Characterized in Triticum urartu
Chen, Bo; Jiao, Juan; Jia, Lijia; Liu, Cuimin
2017-01-01
Vesicle-inducing protein in plastids 1 (Vipp1) is thought to play an important role both in thylakoid biogenesis and chloroplast envelope maintenance during stress. Vipp1 is conserved in photosynthetic organisms and forms a high homo-oligomer complex structure that may help sustain the membrane integrity of chloroplasts. This study cloned two novel VIPP1 genes from Triticum urartu and named them TuVipp1 and TuVipp2. Both proteins shared high identity with the homologous proteins AtVipp1 and CrVipp1. TuVipp1 and TuVipp2 were expressed in various organs of common wheat, and both genes were induced by light and various stress treatments. Purified TuVipp1 and TuVipp2 proteins showed secondary and advanced structures similar to those of the homologous proteins. Similar to AtVipp1, TuVipp1 is a chloroplast target protein. Additionally, TuVipp1 was able to rescue the phenotypes of pale leaves, lethality, and disordered chloroplast structures of AtVipp1 (-/-) mutant lines. Collectively, our data demonstrate that TuVipp1 and TuVipp2 are functional proteins in chloroplasts in wheat and may be critical for maintaining the chloroplast envelope under stress and membrane biogenesis upon photosynthesis. PMID:28103282
Arabidopsis EF-Tu receptor enhances bacterial disease resistance in transgenic wheat.
Schoonbeek, Henk-Jan; Wang, Hsi-Hua; Stefanato, Francesca L; Craze, Melanie; Bowden, Sarah; Wallington, Emma; Zipfel, Cyril; Ridout, Christopher J
2015-04-01
Perception of pathogen (or microbe)-associated molecular patterns (PAMPs/MAMPs) by pattern recognition receptors (PRRs) is a key component of plant innate immunity. The Arabidopsis PRR EF-Tu receptor (EFR) recognizes the bacterial PAMP elongation factor Tu (EF-Tu) and its derived peptide elf18. Previous work revealed that transgenic expression of AtEFR in Solanaceae confers elf18 responsiveness and broad-spectrum bacterial disease resistance. In this study, we developed a set of bioassays to study the activation of PAMP-triggered immunity (PTI) in wheat. We generated transgenic wheat (Triticum aestivum) plants expressing AtEFR driven by the constitutive rice actin promoter and tested their response to elf18. We show that transgenic expression of AtEFR in wheat confers recognition of elf18, as measured by the induction of immune marker genes and callose deposition. When challenged with the cereal bacterial pathogen Pseudomonas syringae pv. oryzae, transgenic EFR wheat lines had reduced lesion size and bacterial multiplication. These results demonstrate that AtEFR can be transferred successfully from dicot to monocot species, further revealing that immune signalling pathways are conserved across these distant phyla. As novel PRRs are identified, their transfer between plant families represents a useful strategy for enhancing resistance to pathogens in crops. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.
Kankipati, Padmaja; Boninger, Michael L; Gagnon, Dany; Cooper, Rory A; Koontz, Alicia M
2015-07-01
Repeated measures design. This study compared the upper extremity (UE) joint kinetics between three transfer techniques. Research laboratory. Twenty individuals with spinal cord injury performed three transfer techniques from their wheelchair to a level tub bench. Two of the techniques involved a head-hips method with leading hand position close (HH-I) and far (HH-A) from the body, and the third technique with the trunk upright (TU) and hand far from body. Motion analysis equipment recorded upper body movements and force sensors recorded their hand and feet reaction forces during the transfers. Several significant differences were found between HH-A and HH-I and TU and HH-I transfers indicating that hand placement was a key factor influencing the UE joint kinetics. Peak resultant hand, elbow, and shoulder joint forces were significantly higher for the HH-A and TU techniques at the trailing arm (P < 0.036) and lower at the leading arm (P < 0.021), compared to the HH-I technique. Always trailing with the same arm if using HH-A or TU could predispose that arm to overuse related pain and injuries. Technique training should focus on initial hand placement close to the body followed by the amount of trunk flexion needed to facilitate movement.
Oegema, Karen; Wiese, Christiane; Martin, Ona C.; Milligan, Ronald A.; Iwamatsu, Akihiro; Mitchison, Timothy J.; Zheng, Yixian
1999-01-01
γ-tubulin exists in two related complexes in Drosophila embryo extracts (Moritz, M., Y. Zheng, B.M. Alberts, and K. Oegema. 1998. J. Cell Biol. 142:1– 12). Here, we report the purification and characterization of both complexes that we name γ-tubulin small complex (γTuSC; ∼280,000 D) and Drosophila γTuRC (∼2,200,000 D). In addition to γ-tubulin, the γTuSC contains Dgrip84 and Dgrip91, two proteins homologous to the Spc97/98p protein family. The γTuSC is a structural subunit of the γTuRC, a larger complex containing about six additional polypeptides. Like the γTuRC isolated from Xenopus egg extracts (Zheng, Y., M.L. Wong, B. Alberts, and T. Mitchison. 1995. Nature. 378:578–583), the Drosophila γTuRC can nucleate microtubules in vitro and has an open ring structure with a diameter of 25 nm. Cryo-electron microscopy reveals a modular structure with ∼13 radially arranged structural repeats. The γTuSC also nucleates microtubules, but much less efficiently than the γTuRC, suggesting that assembly into a larger complex enhances nucleating activity. Analysis of the nucleotide content of the γTuSC reveals that γ-tubulin binds preferentially to GDP over GTP, rendering γ-tubulin an unusual member of the tubulin superfamily. PMID:10037793
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wang, Deng-Liang; Department of Neurosurgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou; Song, Yan-Ling
2014-10-31
Highlights: • This is the first report of DNA aptamer against EGFR in vitro. • Aptamer can bind targets with high affinity and selectivity. • DNA aptamers are more stable, cheap and efficient than RNA aptamers. • Our selected DNA aptamer against EGFR has high affinity with K{sub d} 56 ± 7.3 nM. • Our selected DNA aptamer against EGFR has high selectivity. - Abstract: Epidermal growth factor receptor (EGFR/HER1/c-ErbB1), is overexpressed in many solid cancers, such as epidermoid carcinomas, malignant gliomas, etc. EGFR plays roles in proliferation, invasion, angiogenesis and metastasis of malignant cancer cells and is the idealmore » antigen for clinical applications in cancer detection, imaging and therapy. Aptamers, the output of the systematic evolution of ligands by exponential enrichment (SELEX), are DNA/RNA oligonucleotides which can bind protein and other substances with specificity. RNA aptamers are undesirable due to their instability and high cost of production. Conversely, DNA aptamers have aroused researcher’s attention because they are easily synthesized, stable, selective, have high binding affinity and are cost-effective to produce. In this study, we have successfully identified DNA aptamers with high binding affinity and selectivity to EGFR. The aptamer named TuTu22 with K{sub d} 56 ± 7.3 nM was chosen from the identified DNA aptamers for further study. Flow cytometry analysis results indicated that the TuTu22 aptamer was able to specifically recognize a variety of cancer cells expressing EGFR but did not bind to the EGFR-negative cells. With all of the aforementioned advantages, the DNA aptamers reported here against cancer biomarker EGFR will facilitate the development of novel targeted cancer detection, imaging and therapy.« less
Kostalas, M; Nageswaran, H; Froghi, S; Riga, A; Kumar, R; Menezes, N; Worthington, T R; Karanjia, N D
2017-08-19
To assess impact of centralisation on patients undergoing pancreatic head resections at a tertiary hepatobiliary (HPB) centre in the UK. Data were analysed from a prospectively maintained database from 1998 to 2014 on all patients undergoing pancreatic head resections. Two specific time periods were defined; these were the evolving unit phase (EU) from 1998 to 2009 and finally the established tertiary unit phase (TU) from 2010 to 2014. Peri-operative factors and post-operative outcomes were analysed. 395 resections were undertaken during the study period. Following establishment of our tertiary HPB unit, the volume of resections undertaken increased greater than three-fold with an associated increase in case-complexity (p = 0.004). Operating time was found to increase in the TU phase compared with EU phase (p=>0.0005) whilst there was no significant difference in the rate of peri-operative transfusion, or in post-operative morbidity rates. There was a significant reduction in the post-operative length of stay in the TU phase (p = 0.003) with a significantly higher proportion of patients being discharged within 9 days of their procedure (p=<0.0005). There was also a significant reduction in 30-day post-operative mortality in the TU phase (0.5%) compared with the EU phase (3%) (p = 0.029). Data from our series of 395 cases suggests that centralisation of pancreatic cancer services to a tertiary centre does result in improved patient outcomes. The benefits of a multi-disciplinary and specialist HPB service results in a high volume, high quality unit with improved patient outcomes. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.
Li, G D; Hu, X L; Xing, J F; Shi, R Y; Li, X; Li, J F; Li, T L
2018-04-07
Objective: To explore the effect of c-fos on multidrug resistance of laryngeal cancer TU177 cells. Method: Increasing drug concentration gradient is adopted to establish the stability of the laryngeal cancer drug resistance in cell line; RT-PCR and Western blot were used to detect difference of the c-fos between TU177 and TU177/VCR cells; plasmids with human c-fos knockdown or over expression were transfected into TU177/VCR and TU177 cells respectively, and the effects of different treatment on cell proliferation were investigated with MTT. Results: The drug resistance of TU177/VCR cells was 26.25-fold in vincristine (VCR), 7.33-fold in Paclitaxel (TAX), 2.41 in cisplatin (DDP), and 5.50 in 5-fluorouracil (5-FU), comparing with TU177( P <0.05). The TU177/VCR cells had significantly higher c-fos expression compared to TU177 cells( P <0.05). The results showed that the IC(50) values of 5-FU for the NC group and c-fos shRNA group were (306.2±6.3)μmol/L and (81.3±3.9)μmol/L, respectively, which was decreased by 73% in the c-fos shRNA group compared to that in the NC group ( P <0.05). Similarly, the results showed that the IC(50) values for 5-FU were (55.3±9.4) μmol/L in NC group and (288.1±7.3)μmol/L in c-fos WT group, which was increased 5.21-fold in c-fos WT cells. Conclusion: C-fos plays important role in multidrug resistance of larynx cancer cell TU177/VCR, and might become a new molecular target for laryngeal cancer treatment.
Gayed, Bishoy A; Gillen, Jessica; Christie, Alana; Peña-Llopis, Samuel; Xie, Xian-Jin; Yan, Jingsheng; Karam, Jose A; Raj, Ganesh; Sagalowsky, Arthur I; Lotan, Yair; Margulis, Vitaly; Brugarolas, James
2015-04-03
To assess pathological correlations and temporal trends of Angiopoietin-2 (ANGPT2), vascular endothelial growth factor (VEGF) and M2 Pyruvate kinase (TuM2PK), markers of tumor vascular development and metabolism, in patients with renal cell carcinoma (RCC). We prospectively collected plasma samples from 89 patients who underwent surgical/ablative therapy for RCC and 38 patients with benign disease (nephrolithiasis, hematuria without apparent neoplastic origin, or renal cysts). In RCC patients, marker levels were compared between at least 1 preoperative and 1 postoperative time point generally 3 weeks after surgery. Marker temporal trends were assessed using the Wilcoxon sign-rank test. Plasma VEGF, ANGPT2, and TuM2PK levels were determined by ELISA and tested for association with pathological variables. Median age was comparable between groups. 83/89 (93%) of the cohort underwent surgical extirpation. 82% of the tumors were organ confined (T ≤ 2, N0). Only ANGPT2 exhibited significantly elevated preoperative levels in patients with RCC compared to benign disease (p = 0.046). Elevated preoperative levels of ANGPT2 and TuM2PK significantly correlated with increased tumor size and advanced grade (p < 0.05). Chromophobe RCC exhibited higher levels of ANGPT2 compared to other histologies (p < 0.05). A decline in marker level after surgery was not observed, likely due to the timing of the analyses. Our results suggest that ANGPT2 is a marker of RCC. Additionally, ANGPT2 and TuM2PK significantly correlated with several adverse pathological features. Further studies are needed to determine clinical applicability.
A Grammar of Bao'an Tu, a Mongolic Language of Northwest China
ERIC Educational Resources Information Center
Fried, Robert Wayne
2010-01-01
The present study is a grammatical overview of the Bao'an Tu language (one of the varieties included in the designation "ISO6393-3:PEH", also known as "Tongren Monguor", "Southwestern Monguor", or "Tongren Tu"). Bao'an Tu is spoken by approximately 4,000 people who live on the Qinghai-Tibetan Plateau in…
Wolf, Jan; Keipert, Dieter; Motazedi, Heiko; Ernst, Michael; Nettleship, Joanne; Gooren, Louis
2017-12-01
This observational post-marketing study of parenteral testosterone undecanoate (TU) in a non-selected population aimed to: examine the effectiveness of TU as treatment of hypogonadism; record adverse drug reactions (ADR) quantitatively particularly regarding polycythemia, prostate safety and cardiovascular-related metabolic risk factors; and verify whether recommended injection intervals apply to routine clinical practice. Eight hundred and seventy subjects from 259 outpatient units scheduled to visit the clinic six times were included. Effectiveness and tolerability of TU administration were assessed on a 4-point scale. Body weight, waist girth, blood pressure, hemoglobin levels, hematocrit, prostate-specific antigen (PSA), and digital rectal prostate examination were assessed. Over 90% of subjects completed the observational duration of 52.8 ± 9.7 weeks (mean ± SD) and 56% judged effectiveness as very good, 30.8% as good. 63.1% judged tolerability as very good, and 24.4% as good. No adverse effects on indicators of cardiovascular risk were observed. Polycythemia occurred in one subject and a supranormal hematocrit in one subject. Four subjects developed supranormal PSA levels. Prostate carcinoma was found in one subject, one subject had recurrence of a previously surgically treated prostate carcinoma, and the other two showed no indication of malignancy. Parenteral TU is safe, effective, and well-tolerated in clinical practice proving a good therapeutic option for hypogonadism.
Kankipati, Padmaja; Boninger, Michael L.; Gagnon, Dany; Cooper, Rory A.; Koontz, Alicia M.
2015-01-01
Study design Repeated measures design. Objective This study compared the upper extremity (UE) joint kinetics between three transfer techniques. Setting Research laboratory. Methods Twenty individuals with spinal cord injury performed three transfer techniques from their wheelchair to a level tub bench. Two of the techniques involved a head–hips method with leading hand position close (HH-I) and far (HH-A) from the body, and the third technique with the trunk upright (TU) and hand far from body. Motion analysis equipment recorded upper body movements and force sensors recorded their hand and feet reaction forces during the transfers. Results Several significant differences were found between HH-A and HH-I and TU and HH-I transfers indicating that hand placement was a key factor influencing the UE joint kinetics. Peak resultant hand, elbow, and shoulder joint forces were significantly higher for the HH-A and TU techniques at the trailing arm (P < 0.036) and lower at the leading arm (P < 0.021), compared to the HH-I technique. Conclusion Always trailing with the same arm if using HH-A or TU could predispose that arm to overuse related pain and injuries. Technique training should focus on initial hand placement close to the body followed by the amount of trunk flexion needed to facilitate movement. PMID:25130053
Zhang, G Y; Gu, Y Q; Wang, X H; Cui, Y G; Bremner, W J
1999-10-01
This is a pilot dose-finding study of spermatogenic suppression using testosterone undecanoate (TU) injections alone in normal Chinese men. Thirty-two healthy men were recruited. Volunteers underwent pretreatment evaluation, then a treatment period in which group I (n = 13) received 500 mg TU, group II (n = 12) received 1000 mg TU, and group III (n = 7) received placebo, respectively, at monthly intervals during the treatment period (or until azoospermia was achieved). Thereafter, they underwent a recovery period until all parameters returned to pretreatment levels. Eleven of 12 volunteers in the 500-mg TU group, and all volunteers in the 1000-mg TU group became azoospermic. Faster suppression of spermatogenesis was achieved in the 1000-mg TU group. Serum testosterone increased significantly in the higher dose group at weeks 8 and 12, but remained within the normal range. Mean serum LH and FSH were profoundly suppressed by both doses to undetectable levels at week 16. TU injections did not cause a significant change in high density lipoprotein cholesterol levels. No serious side-effects were found. We conclude that both dosages of TU can effectively, safely, and reversibly suppress spermatogenesis in normal Chinese men.
Bateman, Randall J.; Benzinger, Tammie L.; Berry, Scott; Clifford, David B.; Duggan, Cynthia; Fagan, Anne M.; Fanning, Kathleen; Farlow, Martin R.; Hassenstab, Jason; McDade, Eric M.; Mills, Susan; Paumier, Katrina; Quintana, Melanie; Salloway, Stephen P.; Santacruz, Anna; Schneider, Lon S.; Wang, Guoqiao; Xiong, Chengjie
2016-01-01
INTRODUCTION The Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) trial is an adaptive platform trial testing multiple drugs to slow or prevent the progression of Alzheimer’s disease in autosomal dominant Alzheimer’s disease (ADAD) families. With completion of enrollment of the first two drug arms, the DIAN-TU now plans to add new drugs to the platform, designated as the Next Generation Prevention Trial (NexGen). METHODS In collaboration with ADAD families, philanthropic organizations, academic leaders, the DIAN-TU Pharma Consortium, the NIH, and regulatory colleagues, the DIAN-TU developed innovative clinical study designs for the DIAN-TU NexGen trial. RESULTS Our expanded trials toolbox consists of a Disease Progression Model for ADAD, primary endpoint DIAN-TU cognitive performance composite, biomarker development, self-administered cognitive assessments, adaptive dose adjustments, and blinded data collection through the last participant completion. CONCLUSION These steps represent elements to improve efficacy of the adaptive platform trial and a continued effort to optimize prevention and treatment trials in ADAD. PMID:27583651
Regulation of microtubule nucleation mediated by γ-tubulin complexes.
Sulimenko, Vadym; Hájková, Zuzana; Klebanovych, Anastasiya; Dráber, Pavel
2017-05-01
The microtubule cytoskeleton is critically important for spatio-temporal organization of eukaryotic cells. The nucleation of new microtubules is typically restricted to microtubule organizing centers (MTOCs) and requires γ-tubulin that assembles into multisubunit complexes of various sizes. γ-Tubulin ring complexes (TuRCs) are efficient microtubule nucleators and are associated with large number of targeting, activating and modulating proteins. γ-Tubulin-dependent nucleation of microtubules occurs both from canonical MTOCs, such as spindle pole bodies and centrosomes, and additional sites such as Golgi apparatus, nuclear envelope, plasma membrane-associated sites, chromatin and surface of pre-existing microtubules. Despite many advances in structure of γ-tubulin complexes and characterization of γTuRC interacting factors, regulatory mechanisms of microtubule nucleation are not fully understood. Here, we review recent work on the factors and regulatory mechanisms that are involved in centrosomal and non-centrosomal microtubule nucleation.
Stuart, R.; Bennett, N.; Forbes, A.; Grayson, M
2000-01-01
BACKGROUND—Historically, 10 TU has been employed in Australia and the United Kingdom to perform the tuberculin skin test (TST). However, this makes it difficult to compare the rates of TST positivity with other countries such as the USA who use 5 TU. To assess the impact of the dose of tuberculin on the TST a comparison was made of TST responses in health care workers given a TST with both 5 and 10 TU. METHODS—Two TSTs were performed simultaneously in each health care worker using 5 and 10 TU. Each dose was randomly assigned in a blinded manner to the right or left forearm and read at 48-72 hours by a single nurse who was blinded to the assignment of the 5 and 10 TU doses. RESULTS—A total of 128 health care workers were enrolled, 119 (93%) of whom had a past history of BCG vaccination. The overall mean difference in paired reaction sizes for the two doses was 1.5 mm with 95% limits of agreement of -3.6 to 6.5 mm. CONCLUSION—A slightly larger TST reading was seen with 10 TU than with 5 TU. The mean difference of 1.5 mm between the two doses should be considered when comparing rates of TST positivity between countries who use different doses of tuberculin to perform the tuberculin skin test. PMID:10899248
Inferring the palaeoenvironment of ancient bacteria on the basis of resurrected proteins
NASA Technical Reports Server (NTRS)
Gaucher, Eric A.; Thomson, J. Michael; Burgan, Michelle F.; Benner, Steven A.
2003-01-01
Features of the physical environment surrounding an ancestral organism can be inferred by reconstructing sequences of ancient proteins made by those organisms, resurrecting these proteins in the laboratory, and measuring their properties. Here, we resurrect candidate sequences for elongation factors of the Tu family (EF-Tu) found at ancient nodes in the bacterial evolutionary tree, and measure their activities as a function of temperature. The ancient EF-Tu proteins have temperature optima of 55-65 degrees C. This value seems to be robust with respect to uncertainties in the ancestral reconstruction. This suggests that the ancient bacteria that hosted these particular genes were thermophiles, and neither hyperthermophiles nor mesophiles. This conclusion can be compared and contrasted with inferences drawn from an analysis of the lengths of branches in trees joining proteins from contemporary bacteria, the distribution of thermophily in derived bacterial lineages, the inferred G + C content of ancient ribosomal RNA, and the geological record combined with assumptions concerning molecular clocks. The study illustrates the use of experimental palaeobiochemistry and assumptions about deep phylogenetic relationships between bacteria to explore the character of ancient life.
Bateman, Randall J; Benzinger, Tammie L; Berry, Scott; Clifford, David B; Duggan, Cynthia; Fagan, Anne M; Fanning, Kathleen; Farlow, Martin R; Hassenstab, Jason; McDade, Eric M; Mills, Susan; Paumier, Katrina; Quintana, Melanie; Salloway, Stephen P; Santacruz, Anna; Schneider, Lon S; Wang, Guoqiao; Xiong, Chengjie
2017-01-01
The Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) trial is an adaptive platform trial testing multiple drugs to slow or prevent the progression of Alzheimer's disease in autosomal dominant Alzheimer's disease (ADAD) families. With completion of enrollment of the first two drug arms, the DIAN-TU now plans to add new drugs to the platform, designated as the Next Generation (NexGen) prevention trial. In collaboration with ADAD families, philanthropic organizations, academic leaders, the DIAN-TU Pharma Consortium, the National Institutes of Health, and regulatory colleagues, the DIAN-TU developed innovative clinical study designs for the DIAN-TU NexGen prevention trial. Our expanded trial toolbox consists of a disease progression model for ADAD, primary end point DIAN-TU cognitive performance composite, biomarker development, self-administered cognitive assessments, adaptive dose adjustments, and blinded data collection through the last participant completion. These steps represent elements to improve efficacy of the adaptive platform trial and a continued effort to optimize prevention and treatment trials in ADAD. Copyright © 2016 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
NASA Astrophysics Data System (ADS)
Liu, Zhen; Xing, Dong; Su, Qian Peter; Zhu, Yun; Zhang, Jiamei; Kong, Xinyu; Xue, Boxin; Wang, Sheng; Sun, Hao; Tao, Yile; Sun, Yujie
2014-07-01
Imaging the location and dynamics of individual interacting protein pairs is essential but often difficult because of the fluorescent background from other paired and non-paired molecules, particularly in the sub-diffraction cellular space. Here we develop a new method combining bimolecular fluorescence complementation and photoactivated localization microscopy for super-resolution imaging and single-molecule tracking of specific protein-protein interactions. The method is used to study the interaction of two abundant proteins, MreB and EF-Tu, in Escherichia coli cells. The super-resolution imaging shows interesting distribution and domain sizes of interacting MreB-EF-Tu pairs as a subpopulation of total EF-Tu. The single-molecule tracking of MreB, EF-Tu and MreB-EF-Tu pairs reveals intriguing localization-dependent heterogonous dynamics and provides valuable insights to understanding the roles of MreB-EF-Tu interactions.
Liu, Zhen; Xing, Dong; Su, Qian Peter; Zhu, Yun; Zhang, Jiamei; Kong, Xinyu; Xue, Boxin; Wang, Sheng; Sun, Hao; Tao, Yile; Sun, Yujie
2014-01-01
Imaging the location and dynamics of individual interacting protein pairs is essential but often difficult because of the fluorescent background from other paired and non-paired molecules, particularly in the sub-diffraction cellular space. Here we develop a new method combining bimolecular fluorescence complementation and photoactivated localization microscopy for super-resolution imaging and single-molecule tracking of specific protein–protein interactions. The method is used to study the interaction of two abundant proteins, MreB and EF-Tu, in Escherichia coli cells. The super-resolution imaging shows interesting distribution and domain sizes of interacting MreB–EF-Tu pairs as a subpopulation of total EF-Tu. The single-molecule tracking of MreB, EF-Tu and MreB–EF-Tu pairs reveals intriguing localization-dependent heterogonous dynamics and provides valuable insights to understanding the roles of MreB–EF-Tu interactions. PMID:25030837
Radioiodination and biodistribution of the monoclonal antibody TU-20 and its scFv fragment
NASA Astrophysics Data System (ADS)
Kubaštová, H.; Kleinova, V.; Seifert, D.; Fišer, M.; Kranda, K.
2006-01-01
The ability of the monoclonal antibody TU-20 and its scFv fragment to specifically bind to the C-end of the class III beta-tubulin makes these preparations useful as potential diagnostics for in vivo determination of neurodegenerative diseases that entail degradation of neuronal cytoskeleton. To examine this hypothesis, TU-20 and its scFv were labelled with 125I and their properties were extensively investigated. TU-20 and its scFv were labelled via chloramine-T with the yield 90 95% and 64 78%, respectively. Their quality control, performed by an ELISA and gel electrophoresis, determined adequate properties for further studies. The in vitro experiment, involving autoradiography and immunohistochemistry of mice’ brain slices, enabled confirmation of preserved immunospecificity of the radiolabelled substances. Finally, the in vivo biodistribution proved differences in elimination of either TU-20, scFv TU-20, or iodide from the mice.
Blood flow velocity in monocular retinoblastoma assessed by color doppler
Bonanomi, Maria Teresa B C; Saito, Osmar C; de Lima, Patricia Picciarelli; Bonanomi, Roberta Chizzotti; Chammas, Maria Cristina
2015-01-01
OBJECTIVE: To analyze the flow of retrobulbar vessels in retinoblastoma by color Doppler imaging. METHODS: A prospective study of monocular retinoblastoma treated by enucleation between 2010 and 2014. The examination comprised fundoscopy, magnetic resonance imaging, ultrasonography and color Doppler imaging. The peak blood velocities in the central retinal artery and central retinal vein of tumor-containing eyes (tuCRAv and tuCRVv, respectively) were assessed. The velocities were compared with those for normal eyes (nlCRAv and nlCRVv) and correlated with clinical and pathological findings. Tumor dimensions in the pathological sections were compared with those in magnetic resonance imaging and ultrasonography and were correlated with tuCRAv and tuCRVv. In tumor-containing eyes, the resistivity index in the central retinal artery and the pulse index in the central retinal vein were studied in relation to all variables. RESULTS: Eighteen patients were included. Comparisons between tuCRAv and nlCRAv and between tuCRVv and nlCRVv revealed higher velocities in tumor-containing eyes (p<0.001 for both), with a greater effect in the central retinal artery than in the central retinal vein (p=0.024). Magnetic resonance imaging and ultrasonography measurements were as reliable as pathology assessments (p=0.675 and p=0.375, respectively). A positive relationship was found between tuCRAv and the tumor volume (p=0.027). The pulse index in the central retinal vein was lower in male patients (p=0.017) and in eyes with optic nerve invasion (p=0.0088). CONCLUSIONS: TuCRAv and tuCRVv are higher in tumor-containing eyes than in normal eyes. Magnetic resonance imaging and ultrasonography measurements are reliable. The tumor volume is correlated with a higher tuCRAv and a reduced pulse in the central retinal vein is correlated with male sex and optic nerve invasion. PMID:26735219
Rodriguez-Medina, Caren; Boissinot, Sylvaine; Chapuis, Sophie; Gereige, Dalya; Rastegar, Maryam; Erdinger, Monique; Revers, Frédéric; Ziegler-Graff, Véronique; Brault, Véronique
2015-12-01
Turnip yellows virus (TuYV), a phloem-limited virus, encodes a 74kDa protein known as the readthrough protein (RT) involved in virus movement. We show here that a TuYV mutant deleted of the C-terminal part of the RT protein (TuYV-∆RTCter) was affected in long-distance trafficking in a host-specific manner. By using the C-terminal domain of the RT protein as a bait in a yeast two-hybrid screen of a phloem cDNA library from Arabidopsis thaliana we identified the calcineurin B-like protein-interacting protein kinase-7 (AtCIPK7). Transient expression of a GFP:CIPK7 fusion protein in virus-inoculated Nicotiana benthamiana leaves led to local increase of wild-type TuYV accumulation, but not that of TuYV-∆RTCter. Surprisingly, elevated virus titer in inoculated leaves did not result in higher TuYV accumulation in systemic leaves, which indicates that virus long-distance movement was not affected. Since GFP:CIPK7 was localized in or near plasmodesmata, CIPK7 could negatively regulate TuYV export from infected cells. Copyright © 2015 Elsevier Inc. All rights reserved.
Kiebooms, Julie A. L.; Wauters, Jella; Vanden Bussche, Julie; Houf, Kurt; De Vos, Paul; Van Trappen, Stefanie; Cleenwerck, Ilse
2014-01-01
In recent years, the frequent detection of the banned thyreostat thiouracil (TU) in livestock urine has been related to endogenous TU formation following digestion of glucosinolate-rich Brassicaceae crops. Recently, it was demonstrated that, upon in vitro digestion of Brassicaceae, fecal bacteria induce TU detection in livestock (porcine livestock > bovines). Therefore, the present study was intended to isolate and identify bacteria involved in this intestinal TU formation upon Brassicaceae digestion and to gain more insight into the underlying mechanism in porcine livestock. Twenty porcine fecal inocula (gilts and multiparous sows) were assessed through static in vitro colonic-digestion simulations with rapeseed. After derivatization and extraction of the fecal suspensions, TU was analyzed using liquid chromatography-tandem mass spectrometry (LC-MS2). On average, lower TU concentrations were observed in fecal colonic simulations in gilts (8.35 ng g−1 rapeseed ± 3.42 [mean ± standard deviation]) than in multiparous sows (52.63 ng g−1 ± 16.17), which correlates with maturation of the gut microbial population with age. Further exploration of the mechanism showed cell-dependent activity of the microbial conversion and sustained TU-forming activity after subjection of the fecal inoculum to moderate heat over a time span of up to 30 min. Finally, nine TU-producing bacterial species were successfully isolated and identified by a combination of biochemical and molecular techniques as Escherichia coli (n = 5), Lactobacillus reuteri (n = 2), Enterococcus faecium (n = 1), and Salmonella enterica subsp. arizonae (n = 1). This report demonstrates that endogenous formation of TU is Brassicaceae induced and occurs under colonic conditions most likely through myrosinase-like enzyme activity expressed by different common intestinal bacterial species. PMID:25261511
Kim, Tae-Kyu; Han, Taeman; Kim, Tae-Woo; Park, In Gyun; Kim, Seonghyun; Park, Haechul
2016-03-15
In Korea, members of the genus Tettigonia have been known as two species, T. ussuriana and T. dolichoptera dolichoptera. However, the taxonomic status of the Jeju Island population of T. ussuriana (JJ-TU) is in question, relative to the mainland population (ML-TU), because of their different body sizes and ratios of wing length. To clarify the relatedness of JJ-TU and ML-TU, we examined the genetic variation and phylogenetic relationships within and between T. ussuriana and related species collected in South Korea, using five genetic loci: three mitochondrial genes (cytochrome c oxidase subunit 1 [CO1], cytochrome c oxidase subunit 2 [CO2], NADH dehydrogenase 1 [ND1]) and two nuclear loci (second internal transcribed spacer [ITS2], and tubulin alpha-1 [TA1]). Unexpectedly, the JJ-TU population is explicitly sister to T. d. dolichoptera, with low genetic distance (0.76-1.22% in CO1), indicating no direct connection with the ML-TU population; this finding suggests a recent divergence involving rapid morphological change without gene flow between JJ-TU and mainland T. d. dolichoptera. The separation of these populations from their common ancestor was caused by geographical isolation during last glacial age. This finding indicates that the JJ-TU population should be elevated to the rank of subspecies, at the very least. Furthermore, the ML-TU population was also revealed to have four genetically divided groups (group A-D) from four localized populations, but no significant morphological differences exist among them. The genetic difference (range 3.19-4.10% in CO1) between group A + B and C + D was especially large, suggesting that cryptic speciation has widely occurred within the mainland areas, caused by allopatric isolations resulting from mountain barriers.
Observations on the TU/VOS Option in Guatemalan Ladino Spanish.
ERIC Educational Resources Information Center
Pinkerton, Anne
1986-01-01
Examines the usage of the "voseo" in Guatemalan Ladino Spanish. It is concluded that "vos" has not replaced "tu" in Guatemalan Ladino Spanish but rather has joined with "tu" and "usted" to form a tri-level second person singular address system. (SED)
Thawani, Akanksha; Kadzik, Rachel S; Petry, Sabine
2018-05-01
How microtubules (MTs) are generated in the cell is a major question in understanding how the cytoskeleton is assembled. For several decades, γ-tubulin has been accepted as the universal MT nucleator of the cell. Although there is evidence that γ-tubulin complexes are not the sole MT nucleators, identification of other nucleation factors has proven difficult. Here, we report that the well-characterized MT polymerase XMAP215 (chTOG/Msps/Stu2p/Alp14/Dis1 homologue) is essential for MT nucleation in Xenopus egg extracts. The concentration of XMAP215 determines the extent of MT nucleation. Even though XMAP215 and the γ-tubulin ring complex (γ-TuRC) possess minimal nucleation activity individually, together, these factors synergistically stimulate MT nucleation in vitro. The amino-terminal TOG domains 1-5 of XMAP215 bind to αβ-tubulin and promote MT polymerization, whereas the conserved carboxy terminus is required for efficient MT nucleation and directly binds to γ-tubulin. In summary, XMAP215 and γ-TuRC together function as the principal nucleation module that generates MTs in cells.
NASA Astrophysics Data System (ADS)
Fernandes, Adji Achmad Rinaldo; Solimun, Arisoesilaningsih, Endang
2017-12-01
The aim of this research is to estimate the spline in Path Analysis-based on Nonparametric Regression using Penalized Weighted Least Square (PWLS) approach. Approach used is Reproducing Kernel Hilbert Space at sobolev space. Nonparametric path analysis model on the equation y1 i=f1.1(x1 i)+ε1 i; y2 i=f1.2(x1 i)+f2.2(y1 i)+ε2 i; i =1 ,2 ,…,n Nonparametric Path Analysis which meet the criteria of minimizing PWLS min fw .k∈W2m[aw .k,bw .k], k =1 ,2 { (2n ) -1(y˜-f ˜ ) TΣ-1(y ˜-f ˜ ) + ∑k =1 2 ∑w =1 2 λw .k ∫aw .k bw .k [fw.k (m )(xi) ] 2d xi } is f ˜^=Ay ˜ with A=T1(T1TU1-1∑-1T1)-1T1TU1-1∑-1+V1U1-1∑-1[I-T1(T1TU1-1∑-1T1)-1T1TU1-1∑-1] columnalign="left">+T2(T2TU2-1∑-1T2)-1T2TU2-1∑-1+V2U2-1∑-1[I1-T2(T2TU2-1∑-1T2) -1T2TU2-1∑-1
40 CFR Appendixes T-U to Part 51 - [Reserved
Code of Federal Regulations, 2011 CFR
2011-07-01
... 40 Protection of Environment 2 2011-07-01 2011-07-01 false [Reserved] T Appendixes T-U to Part 51 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS REQUIREMENTS FOR PREPARATION, ADOPTION, AND SUBMITTAL OF IMPLEMENTATION PLANS Appendixes T-U to Part 51 [Reserved] ...
40 CFR Appendixes T-U to Part 51 - [Reserved
Code of Federal Regulations, 2010 CFR
2010-07-01
... 40 Protection of Environment 2 2010-07-01 2010-07-01 false [Reserved] T Appendixes T-U to Part 51 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS REQUIREMENTS FOR PREPARATION, ADOPTION, AND SUBMITTAL OF IMPLEMENTATION PLANS Appendixes T-U to Part 51 [Reserved] ...
40 CFR 264.553 - Temporary Units (TU).
Code of Federal Regulations, 2011 CFR
2011-07-01
... 40 Protection of Environment 26 2011-07-01 2011-07-01 false Temporary Units (TU). 264.553 Section 264.553 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED... Provisions for Cleanup § 264.553 Temporary Units (TU). (a) For temporary tanks and container storage areas...
40 CFR 264.553 - Temporary Units (TU).
Code of Federal Regulations, 2010 CFR
2010-07-01
... 40 Protection of Environment 25 2010-07-01 2010-07-01 false Temporary Units (TU). 264.553 Section 264.553 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED... Provisions for Cleanup § 264.553 Temporary Units (TU). (a) For temporary tanks and container storage areas...
Technology transfer and the NASA Technology Utilization Program - An overview
NASA Technical Reports Server (NTRS)
Clarks, Henry J.; Rose, James T.; Mangum, Stephen D.
1989-01-01
The goal of the NASA Technology Utilization (TU) Program is to broaden and accelerate the transfer of aerospace technology and to develop new commercial products and processes that represent additional return on the national investment in the U.S. space programs. The mechanisms established by the TU Program includes TU offices, publications, the information retrieval, software dissemination, and the NASA Applications Engineering Program. These mechanisms are implemented through a nationwide NASA TU Network, working closely with industry and public sector organizations to encourage and facilitate their access and utilization of the results of the U.S space programs. Examples of TU are described, including a method for the reduction of metal fatigue in textile equipment and a method for the management of wandering behavior in Alzheimer's patients.
Whitney, John C.; Quentin, Dennis; Sawai, Shin; ...
2015-10-08
Type VI secretion (T6S) influences the composition of microbial communities by catalyzing the delivery of toxins between adjacent bacterial cells. Here, we demonstrate that a T6S integral membrane toxin from Pseudomonas aeruginosa, Tse6, acts on target cells by degrading the universally essential dinucleotides NAD + and NADP +. Structural analyses of Tse6 show that it resembles mono-ADP-ribosyltransferase proteins, such as diphtheria toxin, with the exception of a unique loop that both excludes proteinaceous ADP-ribose acceptors and contributes to hydrolysis. We find that entry of Tse6 into target cells requires its binding to an essential housekeeping protein, translation elongation factor Tumore » (EF-Tu). These proteins participate in a larger assembly that additionally directs toxin export and provides chaperone activity. Lastly, visualization of this complex by electron microscopy defines the architecture of a toxin-loaded T6S apparatus and provides mechanistic insight into intercellular membrane protein delivery between bacteria.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Whitney, John C.; Quentin, Dennis; Sawai, Shin
2015-10-08
Type VI secretion (T6S) influences the composition of microbial communities by catalyzing the delivery of toxins between adjacent bacterial cells. Here, we demonstrate that a T6S integral membrane toxin from Pseudomonas aeruginosa, Tse6, acts on target cells by degrading the universally essential dinucleotides NAD + and NADP +. Structural analyses of Tse6 show that it resembles mono-ADP-ribosyltransferase proteins, such as diphtheria toxin, with the exception of a unique loop that both excludes proteinaceous ADP-ribose acceptors and contributes to hydrolysis. We find that entry of Tse6 into target cells requires its binding to an essential housekeeping protein, translation elongation factor Tumore » (EF-Tu). These proteins participate in a larger assembly that additionally directs toxin export and provides chaperone activity. Visualization of this complex by electron microscopy defines the architecture of a toxin-loaded T6S apparatus and provides mechanistic insight into intercellular membrane protein delivery between bacteria.« less
TU-FG-201-10: Quality Management of Accelerated Partial Breast Irradiation (APBI) Plans
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ji, H; Lorio, V; Cernica, G
2016-06-15
Purpose: Since 2008, over 700 patients received high dose rate (HDR) APBI treatment at Virginia Hospital Center. The complexity involved in the planning process demonstrated a broad variation between patient geometry across all applicators, in relation to anatomical regions of interest. A quality management program instituting various metrics was implemented in March 2013 with the goal of ensuring an optimal plan is achieved for each patient. Methods: For each plan, an in-house complexity index, geometric conformity index, and plan quality index were defined. These indices were obtained for all patients treated. For patients treated after the implementation, the conformity indexmore » and quality index were maximized while other dosimetric limits, such as maximum skin and rib doses, were strictly kept. Subsequently, all evaluation parameters and applicator information were placed in a database for cross-evaluation with similar complexity. Results: Both the conformity and quality indices show good correlation with the complexity index. They decrease as complexity increases for all applicators. Multi lumen type balloon applicators demonstrate a minimal advantage over single lumen applicators in increasingly complex patient geometries, as compared to SAVI applicators which showed considerably greater advantage in these circumstances. After the implementation of the in-house planning protocol, there is a direct improvement of quality for SAVI plans. Conclusion: Due to their interstitial nature, SAVI devices show a better conformity in comparison to balloon-based devices regardless of the number of lumens, especially in complex cases. The quality management program focuses on optimizing indices by utilizing prior planning knowledge based on complexity levels. The database of indices assists in decision making and has subsequently aided in balancing the experience level among planners. This approach has made APBI planning more robust for patient care, with a measurable improvement in the plan quality.« less
Tumor type M2 pyruvate kinase expression in advanced breast cancer.
Lüftner, D; Mesterharm, J; Akrivakis, C; Geppert, R; Petrides, P E; Wernecke, K D; Possinger, K
2000-01-01
Recently, a high validity correlation of the tumor M2 pyruvate kinase (Tu M2-PK) isoenzyme in comparison to standard tumor markers has been demonstrated in solid tumors. We investigated this marker in 67 patients with advanced breast cancer (ABC) in comparison to healthy controls. Plasma Tu M2-PK was measured using an ELISA assay (ScheBo Tech, Giessen, Germany) while serum CA27.29 was determined using a chemiluminescent immunoassay (Bayer Diagnostics, Tarrytown, USA). In a ROC analysis, the cut-off to discriminate patients from controls was established at 15 U/ml for Tu M2-PK (specificity 85%; positive predictive value 81%) and 30 U/ml for CA27.29 (specificity 91%; positive predictive value 92%). Median ABC baseline levels (ranges) in patients with ABC for Tu M2-PK and CA27.29 were 12.8 U/ml (4.8-252,495) and 130 U/ml (13.3-8130), respectively. Response assessment was done in 45 chemotherapy courses of 38 pts. In 13 out of 19 blocks (68.4%) with PD (progressive disease), an elevated level of Tu M2-PK at baseline or in the follow-up was found. In 17 out of 20 blocks (85%) with SD (stable disease), the Tu M2-PK level was normal at baseline or normalised within 4 weeks of treatment. All 6 patients with disease remission had a normal baseline Tu M2-PK level or the levels decreased promptly. Tu M2-PK gives additional information about ABC, indicating disease activity and sensitivity to chemotherapy while CA27.29 reflects tumor burden.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Rodriguez-Medina, Caren; Boissinot, Sylvaine; Chapuis, Sophie
Turnip yellows virus (TuYV), a phloem-limited virus, encodes a 74 kDa protein known as the readthrough protein (RT) involved in virus movement. We show here that a TuYV mutant deleted of the C-terminal part of the RT protein (TuYV-∆RT{sub Cter}) was affected in long-distance trafficking in a host-specific manner. By using the C-terminal domain of the RT protein as a bait in a yeast two-hybrid screen of a phloem cDNA library from Arabidopsis thaliana we identified the calcineurin B-like protein-interacting protein kinase-7 (AtCIPK7). Transient expression of a GFP:CIPK7 fusion protein in virus-inoculated Nicotiana benthamiana leaves led to local increase ofmore » wild-type TuYV accumulation, but not that of TuYV-∆RT{sub Cter}. Surprisingly, elevated virus titer in inoculated leaves did not result in higher TuYV accumulation in systemic leaves, which indicates that virus long-distance movement was not affected. Since GFP:CIPK7 was localized in or near plasmodesmata, CIPK7 could negatively regulate TuYV export from infected cells. - Highlights: • The C-terminal domain of TuYV-RT is required for long-distance movement. • CIPK7 from Arabidopsis interacts with RT{sub Cter} in yeast and in plants. • CIPK7 overexpression increases virus titer locally but not virus systemic movement. • CIPK7 localizes to plasmodesmata. • CIPK7 could be a defense protein regulating virus export.« less
Xia, Xi; Wu, Congming; Cui, Yaowen; Kang, Mengjiao; Li, Xiaowei; Ding, Shuangyang; Shen, Jianzhong
2015-11-20
Mycoplasma gallisepticum is a significant pathogenic bacterium that infects poultry, causing chronic respiratory disease and sinusitis in chickens and turkeys, respectively. M. gallisepticum infection poses a substantial economic threat to the poultry industry, and this threat is made worse by the emergence of antibiotic-resistant strains. The mechanisms of resistance are often difficult to determine; for example, little is known about antibiotic resistance of M. gallisepticum at the proteome level. In this study, we performed comparative proteomic analyses of an antibiotic (tylosin)-resistant M. gallisepticum mutant and a susceptible parent strain using a combination of two-dimensional differential gel electrophoresis and nano-liquid chromatography-quadrupole-time of flight mass spectrometry. Thirteen proteins were identified as differentially expressed in the resistant strain compared to the susceptible strain. Most of these proteins were related to catalytic activity, including catalysis that promotes the formylation of initiator tRNA and energy production. Elongation factors Tu and G were over-expressed in the resistant strains, and this could promote the binding of tRNA to ribosomes and catalyze ribosomal translocation, the coordinated movement of tRNA, and conformational changes in the ribosome. Taken together, our results indicate that M. gallisepticum develops resistance to tylosin by regulating associated enzymatic activities.
ERIC Educational Resources Information Center
Bustin-Lekeu, Francine
1973-01-01
Surveys conducted among secondary school students in Toulon, France in choice of personal pronouns indicate more prevalent use of tu''. Students consider widespread use of tu'' to be more democratic and thought employment of vous'' on certain occasions is a hypocritical and bourgeois habit. (DS)
Wistuba, Joachim; Marc Luetjens, C; Kamischke, Axel; Gu, Yi-Qun; Schlatt, Stefan; Simoni, Manuela; Nieschlag, Eberhard
2005-08-01
Testosterone undecanoate (TU) dissolved in soybean oil was developed in China to improve the pharmacokinetics of this testosterone ester in comparison with TU in castor or tea seed oil. As a pre-clinical primate model, three groups of five castrated cynomolgus macaques received either a single intramuscular injection of 10 mg/kg body weight TU in soybean oil, in tea seed oil, or in castor oil (equals 6.3 mg pure T/kg body weight for all preparations). Testosterone, estradiol, luteinizing hormone, and follicle-stimulating hormone as well as prostate volume, body weight and ejaculate weight were evaluated. After injection supraphysiological testosterone levels were induced. There were no significant differences in the pharmacokinetics of the three TU preparations for testosterone and estradiol. The gonadotropin levels showed a high individual variation. Prostate volumes increased equally in all groups after administration and declined to castrate level afterwards. The results suggest that TU in soybean oil produces similar effects as TU in the other vehicles. This study in non-human primates provides no objection to testing of this new preparation in humans.
TAKAGI, Risa; TSUJIKAWA, Yuji; NOMOTO, Ryohei; OSAWA, Ro
2014-01-01
Lactobacillus delbrueckii TU-1, which apparently takes intact inulin into its cells and then degrades it intracellularly, was co-cultured in vitro with L. paracasei KTN-5, an extracellular inulin degrader; or L. plantarum 22A-3, a strain that is able to utilize fructose but not inulin; or both in order to prequalify inulin as a prebiotic agent in vivo. When L. delbrueckii TU-1 was co-cultured with L. paracasei KTN-5 on fructose or inulin, the growth of L. delbrueckii TU-1 on inulin was markedly higher than that of L. paracasei KTN-5, whereas the growth of L. delbrueckii TU-1 on fructose was much lower than that of L. paracasei KTN-5. These results suggest that L. delbrueckii TU-1 and L. paracasei KTN-5 were efficient at utilizing inulin and fructose, respectively. When L. plantarum 22A-3 was co-cultured with L. delbrueckii TU-1 on inulin, the growth of L. plantarum 22A-3 was enhanced by L. paracasei KTN-5 but not by L. delbrueckii TU-1, suggesting that the fructose moiety that L. paracasei KTN-5 released temporarily into the medium was “scavenged” by L. plantarum 22A-3. Thus, L. delbrueckii TU-1, L. paracasei KTN-5, and L. plantarum 22A-3 were then cultured altogether on inulin. The growth of L. delbrueckii TU-1 was unaffected but that of L. paracasei KTN-5 was markedly suppressed. This evidence suggests that prebiotic use of inulin supported the selective growth of intracellular inulin degraders such as L. delbrueckii rather than extracellular inulin degraders such as L. paracasei in the host microbiota. PMID:25379361
Takagi, Risa; Tsujikawa, Yuji; Nomoto, Ryohei; Osawa, Ro
2014-01-01
Lactobacillus delbrueckii TU-1, which apparently takes intact inulin into its cells and then degrades it intracellularly, was co-cultured in vitro with L. paracasei KTN-5, an extracellular inulin degrader; or L. plantarum 22A-3, a strain that is able to utilize fructose but not inulin; or both in order to prequalify inulin as a prebiotic agent in vivo. When L. delbrueckii TU-1 was co-cultured with L. paracasei KTN-5 on fructose or inulin, the growth of L. delbrueckii TU-1 on inulin was markedly higher than that of L. paracasei KTN-5, whereas the growth of L. delbrueckii TU-1 on fructose was much lower than that of L. paracasei KTN-5. These results suggest that L. delbrueckii TU-1 and L. paracasei KTN-5 were efficient at utilizing inulin and fructose, respectively. When L. plantarum 22A-3 was co-cultured with L. delbrueckii TU-1 on inulin, the growth of L. plantarum 22A-3 was enhanced by L. paracasei KTN-5 but not by L. delbrueckii TU-1, suggesting that the fructose moiety that L. paracasei KTN-5 released temporarily into the medium was "scavenged" by L. plantarum 22A-3. Thus, L. delbrueckii TU-1, L. paracasei KTN-5, and L. plantarum 22A-3 were then cultured altogether on inulin. The growth of L. delbrueckii TU-1 was unaffected but that of L. paracasei KTN-5 was markedly suppressed. This evidence suggests that prebiotic use of inulin supported the selective growth of intracellular inulin degraders such as L. delbrueckii rather than extracellular inulin degraders such as L. paracasei in the host microbiota.
Evolution of tuf genes: ancient duplication, differential loss and gene conversion.
Lathe, W C; Bork, P
2001-08-03
The tuf gene of eubacteria, encoding the EF-tu elongation factor, was duplicated early in the evolution of the taxon. Phylogenetic and genomic location analysis of 20 complete eubacterial genomes suggests that this ancient duplication has been differentially lost and maintained in eubacteria.
Forms of Address in Chilean Spanish
ERIC Educational Resources Information Center
Bishop, Kelley; Michnowicz, Jim
2010-01-01
The present investigation examines possible social and linguistic factors that influence forms of address used in Chilean Spanish with various interlocutors. A characteristic of the Spanish of Chile is the use of a variety of forms of address for the second person singular, "tu", "vos", and "usted", with corresponding…
Co-ordination of Mobile Information Agents in TuCSoN.
ERIC Educational Resources Information Center
Omicini, Andrea; Zambonelli, Franco
1998-01-01
Examines mobile agent coordination and presents TuCSoN, a coordination model for Internet applications based on mobile information agents that uses a tuple centre, a tuple space enhanced with the capability of programming its behavior in response to communication events. Discusses the effectiveness of the TuCSoN model in the contexts of Internet…
USDA-ARS?s Scientific Manuscript database
In 2014, we performed a nationwide survey in Korean radish fields to investigate the distribution of Turnip mosaic virus (TuMV). Brassica chinensis sap-inoculated with TuMV-infected radish tissue showed different symptom severity with three isolates. In order to investigate variation among Korean Tu...
DOE Office of Scientific and Technical Information (OSTI.GOV)
Pang, Yuan-Ping, E-mail: pang@mayo.edu
Highlights: • 1–4 interaction scaling factors are used to adjust conformational energy. • This article reports the effects of these factors on protein conformations. • Reducing these factors changes a helix to a strand in molecular dynamics simulation. • Increasing these factors causes the reverse conformational change. • These factors control the conformational equilibrium between helix and strand. - Abstract: 1–4 interaction scaling factors are used in AMBER forcefields to reduce the exaggeration of short-range repulsion caused by the 6–12 Lennard-Jones potential and a nonpolarizable charge model and to obtain better agreements of small-molecule conformational energies with experimental data. However,more » the effects of these scaling factors on protein secondary structure conformations have not been investigated until now. This article reports the finding that the 1–4 interactions among the protein backbone atoms separated by three consecutive covalent bonds are more repulsive in the α-helix conformation than in two β-strand conformations. Therefore, the 1–4 interaction scaling factors of protein backbone torsions ϕ and ψ control the conformational equilibrium between α-helix and β-strand. Molecular dynamics simulations confirm that reducing the ϕ and ψ scaling factors readily converts the α-helix conformation of AcO-(AAQAA){sub 3}-NH{sub 2} to a β-strand conformation, and the reverse occurs when these scaling factors are increased. These results suggest that the ϕ and ψ scaling factors can be used to generate the α-helix or β-strand conformation in situ and to control the propensities of a forcefield for adopting secondary structure elements.« less
Effects of testosterone undecanoate as a male contraceptive candidate on rat immunological features.
Yu, Mingcan; Cao, Xiaomei; Xu, Jinju; Wang, Xiaolei; Yang, Jing; Wang, Xinghai; Ben, Kunlong
2003-11-01
Testosterone undecanoate (TU) is under phase III clinical trial as a hormonal male contraceptive in China. Sex hormones can modulate the immune system. Female hormonal contraceptives may affect SIV/HIV-1 transmission. To evaluate the safety of TU and to understand whether long-term use of TU for a male contraceptive affects users' immunological features, adult male rats were treated for a 32-week TU-treated phase at the dose of 20 mg TU/kg body weight and a 24-week recovery phase. The reproductive and immunological parameters of 4-6 rats in each subgroup were examined at the stated time point. The mean sperm count and viability in the treated rats were significantly suppressed (p < 0.01). In the TU-treated group: the mean blood leukocyte and lymphocyte counts; the proliferation indexes of T cells from peripheral blood mononuclear cells (PBMC) and spleen; and, of B cells from spleen, as well as the mean counts of blood T, NK, and B cells decreased in comparison with those of control group. These decreases were not significant (p > 0.01). Similarly, the mean serum IgM, IgG, and IgA levels and complement activity in TU-treated rats were lower than those in control group (p > 0.01), and the changes in the antibody levels of the examined genital secretions were not significant (p > 0.01). The changes in the thickness of urethra epithelium, and in secretory component (SC) expression in genitals were not observed in the treated group. These results demonstrated that long-term supraphysiological TU injection did not obviously affect the examined rat immunological parameters.
NASA Astrophysics Data System (ADS)
Ramaroson, Voahirana; Rakotomalala, Christian Ulrich; Rajaobelison, Joel; Fareze, Lahimamy Paul; Razafitsalama, Falintsoa A.; Rasolofonirina, Mamiseheno
2018-05-01
This study aims to understand the extension of groundwater pollution downstream of a landfill, Andralanitra-Antananarivo-Madagascar. Twenty-one samples, composed of dug well waters, spring waters, river, and lake, were measured in stable isotopes ( δ 2H, δ 18O) and tritium. Results showed that only two dug well waters, collected at the immediate vicinity of the landfill, have high tritium activities (22.82 TU and 10.43 TU), probably of artificial origin. Both upstream and further downstream of the landfill, tritium activities represent natural source, with values varying from 0.17 TU to 1.46 TU upstream and from 0.88 TU to 1.88 TU further downstream. Stable isotope data suggest that recharge occurs through infiltration of slightly evaporated rainfall. Using the radioactive decay equation, the calculated tracer ages related to two recent ground water samples collected down gradient of the landfill lay between [8-15] years and [4-7] years, taking into account the uncertainty of tritium measurements. For the calculation, a value of 2.36 TU was taken as A o. The latter was estimated based on similarity between stable isotope compositions of nearby spring and dug well waters as well as tritium activities of the local precipitation. Calculation of the tritium activities from the contaminated water point having 22.82 TU to further downstream using the calculated tracer ages showed values of one order of magnitude higher than the measured values. The absence of hydrological connection from the contaminated water point to further downstream the landfill would explain the lower tritium activities measured. Groundwater pollution seems to be limited to the closest proximity of the landfill.
Submission of nucleotide sequence clostridium perfringens elongation factor-tu to genbank database
USDA-ARS?s Scientific Manuscript database
Clostridium perfringens (CP) is ubiquitous in the nature, and a normal inhabitant in the intestinal tracts of animals and humans. However, pathogenic CP is also a causative agent of poultry disease necrotic enteritis (NE). Clostridium-related poultry diseases such as necrotic enteritis (NE) and gang...
Crystal structures and vibrational spectroscopy of copper(I) thiourea complexes.
Bowmaker, Graham A; Hanna, John V; Pakawatchai, Chaveng; Skelton, Brian W; Thanyasirikul, Yupa; White, Allan H
2009-01-05
Several synthetic strategies using copper(I) starting materials or copper(II) compounds and an in situ sulfite reductant have been used to systematically explore the chemistry of copper(I) complexes with thiourea and substituted thiourea ligands. This has resulted in the discovery of several new complexes and methods for the bulk synthesis of some previously reported complexes that had been prepared adventitiously in small quantity. The new complexes are (tu = thiourea, dmtu = N,N'-dimethylthiourea, etu = ethylenethiourea): [I(4)Cu(4)(tu)(6)].H(2)O, [Cu(4)(tu)(10)](NO(3)).tu.3H(2)O, [BrCu(dmtu)(3)], [ICu(dmtu)(3)](2), [BrCu(etu)(2)](2), [ICu(etu)(2)], [ICu(etu)(2)](3). [I(4)Cu(4)(tu)(6)].H(2)O has an adamantanoid structure, with four terminal iodide ligands and six doubly bridging tu ligands. In contrast to this, [Cu(4)(tu)(10)](NO(3)).tu.3H(2)O contains a tetranuclear cluster in which four of the tu ligands are terminal and the other six are doubly bridging. [BrCu(dmtu)(3)] is a mononuclear complex with tetrahedral coordination of copper by one bromide and three dmtu ligands, whereas [Cu(dmtu)(3)](2)I(2) has a centrosymmetric dimeric cation with two uncoordinated iodides, four terminal dmtu and two doubly bridging dmtu ligands, [(dmtu)(2)Cu(mu-S-dmtu)(2)Cu(dmtu)(2)]I(2). A reversal of this monomer to dimer trend from bromide to iodide is seen for the etu counterparts: [BrCu(etu)(2)](2) is a centrosymmetric dimer with two doubly bridging etu ligands, [(etu)BrCu(mu-S-etu)(2)CuBr(etu)], whereas [ICu(etu)(2)] is a trigonal planar monomer, although the novel [I(3)Cu(3)(etu)(6)] is also defined. Infrared and Raman spectra of the synthesized complexes were recorded and the metal-ligand vibrational frequencies have been assigned in many cases. The results confirm previously observed correlations between the vibrational frequencies and the corresponding bond lengths for complexes of the unsubstituted tu ligand. A mechanochemical/infrared method was used to synthesize [I(3)Cu(3)(etu)(6)] from CuI and etu, and to demonstrate the polymorphic transition from [ICu(etu)(2)] to [I(3)Cu(3)(etu)(6)].
Delvecchio, Vito G; Connolly, Joseph P; Alefantis, Timothy G; Walz, Alexander; Quan, Marian A; Patra, Guy; Ashton, John M; Whittington, Jessica T; Chafin, Ryan D; Liang, Xudong; Grewal, Paul; Khan, Akbar S; Mujer, Cesar V
2006-09-01
Differentially expressed and immunogenic spore proteins of the Bacillus cereus group of bacteria, which includes Bacillus anthracis, Bacillus cereus, and Bacillus thuringiensis, were identified. Comparative proteomic profiling of their spore proteins distinguished the three species from each other as well as the virulent from the avirulent strains. A total of 458 proteins encoded by 232 open reading frames were identified by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry analysis for all the species. A number of highly expressed proteins, including elongation factor Tu (EF-Tu), elongation factor G, 60-kDa chaperonin, enolase, pyruvate dehydrogenase complex, and others exist as charge variants on two-dimensional gels. These charge variants have similar masses but different isoelectric points. The majority of identified proteins have cellular roles associated with energy production, carbohydrate transport and metabolism, amino acid transport and metabolism, posttranslational modifications, and translation. Novel vaccine candidate proteins were identified using B. anthracis polyclonal antisera from humans postinfected with cutaneous anthrax. Fifteen immunoreactive proteins were identified in B. anthracis spores, whereas 7, 14, and 7 immunoreactive proteins were identified for B. cereus and in the virulent and avirulent strains of B. thuringiensis spores, respectively. Some of the immunodominant antigens include charge variants of EF-Tu, glyceraldehyde-3-phosphate dehydrogenase, dihydrolipoamide acetyltransferase, Delta-1-pyrroline-5-carboxylate dehydrogenase, and a dihydrolipoamide dehydrogenase. Alanine racemase and neutral protease were uniquely immunogenic to B. anthracis. Comparative analysis of the spore immunome will be of significance for further nucleic acid- and immuno-based detection systems as well as next-generation vaccine development.
DelVecchio, Vito G.; Connolly, Joseph P.; Alefantis, Timothy G.; Walz, Alexander; Quan, Marian A.; Patra, Guy; Ashton, John M.; Whittington, Jessica T.; Chafin, Ryan D.; Liang, Xudong; Grewal, Paul; Khan, Akbar S.; Mujer, Cesar V.
2006-01-01
Differentially expressed and immunogenic spore proteins of the Bacillus cereus group of bacteria, which includes Bacillus anthracis, Bacillus cereus, and Bacillus thuringiensis, were identified. Comparative proteomic profiling of their spore proteins distinguished the three species from each other as well as the virulent from the avirulent strains. A total of 458 proteins encoded by 232 open reading frames were identified by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry analysis for all the species. A number of highly expressed proteins, including elongation factor Tu (EF-Tu), elongation factor G, 60-kDa chaperonin, enolase, pyruvate dehydrogenase complex, and others exist as charge variants on two-dimensional gels. These charge variants have similar masses but different isoelectric points. The majority of identified proteins have cellular roles associated with energy production, carbohydrate transport and metabolism, amino acid transport and metabolism, posttranslational modifications, and translation. Novel vaccine candidate proteins were identified using B. anthracis polyclonal antisera from humans postinfected with cutaneous anthrax. Fifteen immunoreactive proteins were identified in B. anthracis spores, whereas 7, 14, and 7 immunoreactive proteins were identified for B. cereus and in the virulent and avirulent strains of B. thuringiensis spores, respectively. Some of the immunodominant antigens include charge variants of EF-Tu, glyceraldehyde-3-phosphate dehydrogenase, dihydrolipoamide acetyltransferase, Δ-1-pyrroline-5-carboxylate dehydrogenase, and a dihydrolipoamide dehydrogenase. Alanine racemase and neutral protease were uniquely immunogenic to B. anthracis. Comparative analysis of the spore immunome will be of significance for further nucleic acid- and immuno-based detection systems as well as next-generation vaccine development. PMID:16957262
Zhou, Qing; Li, Ziyin
2015-11-01
γ-Tubulin complex constitutes a key component of the microtubule-organizing center and nucleates microtubule assembly. This complex differs in complexity in different organisms: the budding yeast contains the γ-tubulin small complex (γTuSC) composed of γ-tubulin, gamma-tubulin complex protein (GCP)2 and GCP3, whereas animals contain the γ-tubulin ring complex (γTuRC) composed of γTuSC and three additional proteins, GCP4, GCP5 and GCP6. In Trypanosoma brucei, the composition of the γ-tubulin complex remains elusive, and it is not known whether it also regulates assembly of the subpellicular microtubules and the spindle microtubules. Here we report that the γ-tubulin complex in T. brucei is composed of γ-tubulin and three GCP proteins, GCP2-GCP4, and is primarily localized in the basal body throughout the cell cycle. Depletion of GCP2 and GCP3, but not GCP4, disrupted the axonemal central pair microtubules, but not the subpellicular microtubules and the spindle microtubules. Furthermore, we showed that the γTuSC is required for assembly of two central pair proteins and that γTuSC subunits are mutually required for stability. Together, these results identified an unusual γ-tubulin complex in T. brucei, uncovered an essential role of γTuSC in central pair protein assembly, and demonstrated the interdependence of individual γTuSC components for maintaining a stable complex. © 2015 John Wiley & Sons Ltd.
Zhou, Qing; Li, Ziyin
2015-01-01
The γ-tubulin complex constitutes a key component of the microtubule-organizing center and nucleates microtubule assembly. This complex differs in complexity in different organisms: the budding yeast contains the γ-tubulin small complex (γTuSC) composed of γ-tubulin, GCP2 and GCP3, whereas animals contain the γ-tubulin ring complex (γTuRC) composed of γTuSC and three additional proteins, GCP4, GCP5 and GCP6. In Trypanosoma brucei, the composition of the γ-tubulin complex remains elusive, and it is not known whether it also regulates assembly of the subpellicular microtubules and the spindle microtubules. Here we report that the γ-tubulin complex in T. brucei is composed of γ-tubulin and three GCP proteins, GCP2-GCP4, and is primarily localized in the basal body throughout the cell cycle. Depletion of GCP2 and GCP3, but not GCP4, disrupted the axonemal central pair microtubules, but not the subpellicular microtubules and the spindle microtubules. Furthermore, we showed that the γTuSC is required for assembly of two central pair proteins and that γTuSC subunits are mutually required for stability. Together, these results identified an unusual γ-tubulin complex in T. brucei, uncovered an essential role of γTuSC in central pair protein assembly, and demonstrated the interdependence of individual γTuSC components for maintaining a stable complex. PMID:26224545
ERIC Educational Resources Information Center
Coveney, Aidan
2003-01-01
Presents a survey of the French indefinite "tu/vous" in in earlier periods and in a range of varieties. Draws on a corpus of French spoken in Picardy in Northern France to investigate the extent to which this use of second person pronouns helps to avoid ambiguity and co-occurs with another grammatical variable. (Author/VWL)
Schmidt, T.S.; Church, S.E.; Clements, W.H.; Mitchell, K.A.; Fey, D. L.; Wanty, R.B.; Verplanck, P.L.; San, Juan C.A.; Klein, T.L.; deWitt, E.H.; Rockwell, B.W.
2009-01-01
Stream water and sediment toxicity to aquatic insects were quantified from central Colorado catchments to distinguish the effect of geologic processes which result in high background metals concentrations from historical mining. Our sampling design targeted small catchments underlain by rocks of a single lithology, which allowed the development of biological and geochemical baselines without the complication of multiple rock types exposed in the catchment. By accounting for geologic sources of metals to the environment, we were able to distinguish between the environmental effects caused by mining and the weathering of different mineralized areas. Elevated metal concentrations in water and sediment were not restricted to mined catchments. Impairment of aquatic communities also occurred in unmined catchments influenced by hydrothermal alteration. Hydrothermal alteration style, deposit type, and mining were important determinants of water and sediment quality and aquatic community structure. Weathering of unmined porphyry Cu-Mo occurrences resulted in water (median toxic unit (TU) = 108) and sediment quality (TU = 1.9) that exceeded concentrations thought to be safe for aquatic ecosystems (TU = 1). Metalsensitive aquatic insects were virtually absent from streams draining catchments with porphyry Cu-Mo occurrences (1.1 individuals/0.1 m2 ). However, water and sediment quality (TU = 0.1, 0.5 water and sediment, respectively) and presence of metalsensitive aquatic insects (204 individuals/0.1 m2 ) for unmined polymetallic vein occurrences were indistinguishable from that for unmined and unaltered streams (TU = 0.1, 0.5 water and sediment, respectively; 201 individuals/0.1 m2 ). In catchments with mined quartz-sericite-pyrite altered polymetallic vein deposits, water (TU = 8.4) and sediment quality (TU = 3.1) were degraded and more toxic to aquatic insects (36 individuals/0.1 m2 ) than water (TU = 0.4) and sediment quality (TU = 1.7) from mined propylitically altered polymetallic vein deposits. The sampling approach taken in this study distinguishes the effects of different mineral deposits on ecosystems and can be used to more accurately quantify the effect of mining on the environment.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gonzalez-Sprinberg, G; Piriz, G
Purpose: To optimize the dose in bladder and rectum and show the different shapes of the isodose volumes in Co60-HDR brachytherapy, considering different utero and vaginal sources dwell ratio times (TU:TV). Methods: Besides Ir192-HDR, new Co60-HDR sources are being incorporated. We considered different TU:TV times and computed the dosis in bladder, rectum and at the reference points of the Manchester system. Also, we calculated the isodose volume and shape in each case. We used a EZAG-BEBIG Co0.A86 model with TPS HDRplus3.0.4. and LCT42-7, LCT42-2(R,L) applicators. A reference dose RA= 1.00 Gy was given to the A-right point. We considered themore » TU:TV dwell time ratios 1:0.25, 1:0.33, 1:0.5, 1:1, 1:2, 1:3, and 1:4. Given TU:TV, the stop time at each dwell position is fixed for each applicator. Results: Increasing TU:TV systematically results in a decreasing of the dose in bladder and rectum, e.g. 9% and 27% reduction were found in 1:0.25 with respect to 1:1, while 12% and 34% increase were found in 1:4 with respect to 1:1. Also, the isodose volume parameters height (h), width (w), thickness (t) and volume (hwt) increased from the 1:0.25 case to the 1:4 value: hwt is 25% lower and 31% higher than the 1:1 reference volume in these cases. Also w decreased for higher TU:TV and may compromise the tumoral volume coverage, decreasing 17% in the 1:0.25 case compared to the 1:1 case. The shape of the isodose volume was obtained for the different TU:TV considered. Conclusion: We obtained the shape of isodose volumes for different TU:TV values in gynecological Co60-HDR. We studied the dose reduction in bladder and rectum for different TU:TV ratios. The volume parameters and hwt are strongly dependent on this ratio. This information is useful for a quantitative check of the TPS and as a starting point towards optimization.« less
NASA Astrophysics Data System (ADS)
Sharma, A.; Tapadia, K.
2017-01-01
A rapid and low-cost nano-drop spectrophotometric method using citrate-modified silver nanoparticles (Ag NPs) for the determination of thiol-containing toxicants was developed. The introduction of thioglycolic acid (TGA) and thiourea (TU) reduced the overall surface charge of Ag NPs, resulting in aggregation of Ag NPs, and a colorimetric response that was individually correlated with the concentration of TGA and TU. Under optimum experimental conditions, the maximum molar absorptivity values for TGA and TU were 1.04 × 105 and 2.13 × 105 L × mol-1 × cm-1, respectively, at λmax of 415 nm. The linear range used was 0.5-2.5 mg/L for TGA, and 0.3-1.5 mg/L for TU. The detection limits (3S) and % relative standard deviation (RSD) for the method were found to be 3 ppb, 2 ppb, and ±1.13%, ±0.96% for TGA and TU, respectively. This new chromogenic method provided a facile and sensitive scheme for the determination of TGA and TU, and could be applied for the determination of thiol-containing biomolecules. This scheme was tested for the analysis of real samples such as urine, blood, and environmental samples.
Theoretical Construction of Freedom and Pluralism Education in Pastoral Areas
ERIC Educational Resources Information Center
Zhao, Shuyan
2009-01-01
At beginning of the article, the author has a brief introduction of basic conditions in pastoral areas of Imperial Town, and interprets ethnic relations among Han, Tibetan, Mongolian, Yugur, Hui, Manchu and Tu mixed residence. After analysis of the internal and external factors that affect the specificity of pastoral education, the author…
Kinoshita, Michiyo; Pfeiffer, Keram; Homberg, Uwe
2007-04-01
Many migrating animals employ a celestial compass mechanism for spatial navigation. Behavioral experiments in bees and ants have shown that sun compass navigation may rely on the spectral gradient in the sky as well as on the pattern of sky polarization. While polarized-light sensitive interneurons (POL neurons) have been identified in the brain of several insect species, there are at present no data on the neural basis of coding the spectral gradient of the sky. In the present study we have analyzed the chromatic properties of two identified POL neurons in the brain of the desert locust. Both neurons, termed TuTu1 and LoTu1, arborize in the anterior optic tubercle and respond to unpolarized light as well as to polarized light. We show here that the polarized-light response of both types of neuron relies on blue-sensitive photoreceptors. Responses to unpolarized light depended on stimulus position and wavelength. Dorsal unpolarized blue light inhibited the neurons, while stimulation from the ipsilateral side resulted in opponent responses to UV light and green light. While LoTu1 was inhibited by UV light and was excited by green light, one subtype of TuTu1 was excited by UV and inhibited by green light. In LoTu1 the sensitivity to polarized light was at least 2 log units higher than the response to unpolarized light stimuli. Taken together, the spatial and chromatic properties of the neurons may be suited to signal azimuthal directions based on a combination of the spectral gradient and the polarization pattern of the sky.
NASA Astrophysics Data System (ADS)
Wang, Yu; Zhao, Yan-Jiao; Huang, Ji-Ping
2012-07-01
The detection of macromolecular conformation is particularly important in many physical and biological applications. Here we theoretically explore a method for achieving this detection by probing the electricity of sequential charged segments of macromolecules. Our analysis is based on molecular dynamics simulations, and we investigate a single file of water molecules confined in a half-capped single-walled carbon nanotube (SWCNT) with an external electric charge of +e or -e (e is the elementary charge). The charge is located in the vicinity of the cap of the SWCNT and along the centerline of the SWCNT. We reveal the picosecond timescale for the re-orientation (namely, from one unidirectional direction to the other) of the water molecules in response to a switch in the charge signal, -e → +e or +e → -e. Our results are well understood by taking into account the electrical interactions between the water molecules and between the water molecules and the external charge. Because such signals of re-orientation can be magnified and transported according to Tu et al. [2009 Proc. Natl. Acad. Sci. USA 106 18120], it becomes possible to record fingerprints of electric signals arising from sequential charged segments of a macromolecule, which are expected to be useful for recognizing the conformations of some particular macromolecules.
Srivastava, A. K.; Ramaswamy, N. K.; Mukopadhyaya, R.; Jincy, M. G. Chiramal; D'Souza, S. F.
2009-01-01
Background and Aims Large areas of the globe are becoming saline due to evapotranspiration and poor irrigation practices, and sustainability of agriculture is being seriously affected. Thiourea (TU) has been identified as an effective bioregulator imparting stress tolerance to crops. The molecular mechanisms involved in the TU-mediated response are considered in this study. Methods Differential display was performed in order to identify TU-modulated transcripts in Brassica juncea seeds exposed to various treatments (distilled water; 1 m NaCl; 1 m NaCl + 500 p.p.m. TU). The differential regulation of these transcripts was validated by quantitative real-time PCR. Key Results Thiourea treatment maintained the viability of seeds exposed to NaCl for 6 h. Expression analysis showed that the transcript level of alpha, beta, gamma, delta and epsilon subunits of mitochondrial ATPase (mtATPase) varied in seeds subjected to the different treatments for 1 h: expression level was significantly altered by 1 m NaCl relative to controls; however, in the NaCl + TU treatment it reverted back in an integrated manner. Similar results were obtained from time-kinetics studies of beta and delta subunits in roots of 8-d-old seedlings. These observations were also confirmed by the mtATPase activity from isolated mitochondria. The reversal in the expression and activity profile of mtATPase through the application of a bioregulator such as TU is a novel finding for any plant system. Conclusions The results suggest that TU treatment maintains the integrity and functioning of mitochondria in seeds as well as seedlings exposed to salinity. Thus, TU has the potential to be used as an effective bioregulator to impart salinity tolerance under field conditions, and might prove to be of high economic importance by opening new avenues for both basic and applied research. PMID:19033283
Kamischke, Axel; Heuermann, Tanja; Krüger, Kathrin; von Eckardstein, Sigrid; Schellschmidt, Ilka; Rübig, Alexander; Nieschlag, Eberhard
2002-02-01
Suppression of spermatogenesis to azoospermia is the goal of hormonal male contraception based on T combined with gestagens. The combination of the long-acting T, ester testosterone undecanoate (TU), with norethisterone (NET) enanthate (E) showed high efficacy. In the present study, we tested the validity of this approach by varying the NET dose and mode of application. The aim of the study was to achieve high rates of suppression of spermatogenesis as reflected by sperm counts, monitor gonadotropins as well as other hormones, and evaluate any possible side effects. In a phase II clinical trial, groups of normal volunteers received: 1000 mg TU im at wk 2, 6, 12, and 18 combined with 200 mg NETE im at wk 0, 6, 12, and 18 (group I); 1000 mg TU im and 400 mg NETE im at wk 0, 6, 12, and 18 (group II); and 1000 mg TU im at wk 0, 6, 12, and 18 with daily oral NET acetate (NETA) from wk 0 to 24 (group III). In all groups marked suppression of gonadotropins resulted in a significant decrease of spermatogenesis and azoospermia in 13/14, 11/12, and 12/14 men in groups I to III, respectively. The remaining men all had less than 1 million sperm/ml. Reversible side effects included increase in body weight, erythrocytes, hemoglobin, and hematocrit and decrease in high-density lipoprotein cholesterol and alkaline phosphatase in all groups and increase in liver enzymes in the oral NETA group. This study documents the high efficacy of TU in combination with NET and confirms that this dose and mode of application (1000 mg TU im every 6 wk plus 400 mg NETE im every 6 wk or plus 10 mg daily oral NETA) is as effective as the previously reported regimen containing 1000 mg TU + 200 mg NETE im every 6 wk. The contraceptive efficacy of this combination of TU and NETE should be evaluated in further clinical trials.
A PRELIMINARY assessment of BCG vacination in India.
1955-01-01
A NEW ASSESSMENT ACTIVITY IN RELATION TO THE WHO/UNICEF BCG VACCINATION PROGRAMME IS DESCRIBED IN THIS REPORT: according to a detailed plan special field teams collect data on tuberculin sensitivity to determine how efficiently children are being selected for vaccination and to appraise the allergy produced by the mass vaccinations. Results of nine months' work in India have important implications for the practical BCG work.Testing of unvaccinated groups of schoolchildren shows that the pattern of tuberculin sensitivity differs in different parts of India. Specific tuberculin sensitivity is found in all areas, as evidenced by strong reactions to the 5 TU test. Many children had a low-grade non-specific sensitivity, evidenced by small reactions to 5 TU and large reactions to 100 TU. This non-specific tuberculin sensitivity was less frequent at high altitudes, and most common in low-lying humid areas: in all areas it was more prevalent than specific sensitivity.In some areas non-specific tuberculin sensitivity is so strong that it cannot be effectively distinguished from specific sensitivity: consequently, many children not infected with tuberculosis are undoubtedly being excluded from vaccination.Sample retesting of children vaccinated in the mass campaign revealed variable levels of allergy, in many instances much lower than had been expected. These results cannot be explained by a native incapacity of the Indian children to develop strong allergy-nor presumably by the vaccine used. Impairment of the vaccine by exposure to light could be no more than a contributory factor. The marked variability of the campaign results suggests that some factor connected with the handling or application of the vaccine (or possibly of the tuberculin) is involved.
2014-01-01
Background Pancreatic cancer is one of the most aggressive human malignancies with a extremely low 5-year survival rate. Hence, the search for more effective anti-pancreatic cancer agents is urgent. Methods PaTu8988 pancreatic cancer cells were treated with different concentrations of suberoylanilide hydroxamic acid (SAHA), cell survival, proliferation, migration and vasculogenic mimicry (VM) were analyzed. Associated signaling changes were also analyzed by RT-PCR and Western blots. Results Here, we reported that SAHA, a histone deacetylase inhibitor (HDACi), exerted significant inhibitory efficiency against pancreatic cancer cell survival, proliferation, migration and VM. SAHA dose-dependently inhibited PaTu8988 pancreatic cancer cell growth with the IC-50 of 3.4 ± 0. 7 μM. Meanwhile, SAHA suppressed PaTu8988 cell cycle progression through inducing G2/M arrest, which was associated with cyclin-dependent kinase 1 (CDK-1)/cyclin-B1 degradation and p21/p27 upregulation. Further, SAHA induced both apoptotic and non-apoptotic death of PaTu8988 cells. Significantly, SAHA suppressed PaTu8988 cell in vitro migration and cell-dominant tube formation or VM, which was accompanied by semaphorin-4D (Sema-4D) and integrin-β5 down-regulation. Our evidences showed that Akt activation might be important for Sema-4D expression in PaTu8988 cells, and SAHA-induced Sema-4D down-regulation might be associated with Akt inhibition. Conclusions This study is among the first to report the VM formation in cultured human pancreatic cancer cells. And we provided strong evidence to suggest that SAHA executes significant anti-VM efficiency in the progressive pancreatic cancer cells. Thus, SAHA could be further investigated as a promising anti-pancreatic cancer agent. PMID:24886166
Zhu, Fuxiang; Sun, Ying; Wang, Yan; Pan, Hongyu; Wang, Fengting; Zhang, Xianghui; Zhang, Yanhua; Liu, Jinliang
2016-06-04
Turnip mosaic virus (TuMV) infects crops of plant species in the family Brassicaceae worldwide. TuMV isolates were clustered to five lineages corresponding to basal-B, basal-BR, Asian-BR, world-B and OMs. Here, we determined the complete genome sequences of three TuMV basal-BR isolates infecting radish from Shandong and Jilin Provinces in China. Their genomes were all composed of 9833 nucleotides, excluding the 3'-terminal poly(A) tail. They contained two open reading frames (ORFs), with the large one encoding a polyprotein of 3164 amino acids and the small overlapping ORF encoding a PIPO protein of 61 amino acids, which contained the typically conserved motifs found in members of the genus Potyvirus. In pairwise comparison with 30 other TuMV genome sequences, these three isolates shared their highest identities with isolates from Eurasian countries (Germany, Italy, Turkey and China). Recombination analysis showed that the three isolates in this study had no "clear" recombination. The analyses of conserved amino acids changed between groups showed that the codons in the TuMV out group (OGp) and OMs group were the same at three codon sites (852, 1006, 1548), and the other TuMV groups (basal-B, basal-BR, Asian-BR, world-B) were different. This pattern suggests that the codon in the OMs progenitor did not change but that in the other TuMV groups the progenitor sequence did change at divergence. Genetic diversity analyses indicate that the PIPO gene was under the highest selection pressure and the selection pressure on P3N-PIPO and P3 was almost the same. It suggests that most of the selection pressure on P3 was probably imposed through P3N-PIPO.
Pandey, Manish; Srivastava, Ashish Kumar; D'Souza, Stanislaus Francis; Penna, Suprasanna
2013-01-01
In the present agricultural scenario, the major thrust is to increase crop productivity so as to ensure sustainability. In an earlier study, foliar application of thiourea (TU; a non physiological thiol based ROS scavenger) has been demonstrated to enhance the stress tolerance and yield of different crops under field condition. Towards this endeavor, present work deals with the effect of TU on photosynthetic efficiency and source-to-sink relationship of Indian mustard (Brassica juncea) for understanding its mode of action. The application of TU increased the efficiency of both PSI and PSII photosystems and vegetative growth of plant. The comparative analysis of sucrose to starch ratio and expression level of sugar transporters confirmed the higher source and sink strength in response to TU treatment. The biochemical evidence in support of this was derived from higher activities of sucrose phosphate synthase and fructose-1,6-bis-phosphatase at source; and sucrose synthase and different classes of invertases at both source and sink. This indicated an overall increase in photoassimilate level at sink. An additional contribution through pod photosynthesis was confirmed through the analysis of phosphoenol pyruvate carboxylase enzyme activity and level of organic acids. The increased photoassimilate level was also co-ordinated with acetyl coA carboxylase mediated oil biosynthesis. All these changes were ultimately reflected in the form of 10 and 20% increase in total yield and oil content, respectively under TU treatment as compared to control. Additionally, no change was observed in oil composition of seeds derived from TU treated plants. The study thus signifies the co-ordinated regulation of key steps of photosynthesis and source-to-sink relationship through the external application of TU resulting in increased crop yield and oil content.
Cai, Hui-hua; Liu, Mu-biao; He, Yuan-li
2016-01-01
Abstract To compare the outcomes of transumbilical laparoendoscopic single-site surgery (TU-LESS) versus traditional laparoscopic surgery (TLS) for early stage endometrial cancer (EC). We retrospectively reviewed the medical records of patients with early stage EC who were surgically treated by TU-LESS or TLS between 2011 and 2014 in a tertiary care teaching hospital. We identified 18 EC patients who underwent TU-LESS. Propensity score matching was used to match this group with 18 EC patients who underwent TLS. All patients underwent laparoscopic-assisted vaginal hysterectomy, bilateral salpingo-oophorectomy, and systematic pelvic lymphadenectomy by TU-LESS or TLS without conversion to laparoscopy or laparotomy. Number of pelvic lymph nodes retrieved, operative time and estimated blood loss were comparable between 2 groups. Satisfaction values of the cosmetic outcome evaluated by the patient at day 30 after surgery were significantly higher in TU-LESS group than that in TLS group (9.6 ± 0.8 vs 7.5 ± 0.7, P < 0.001), while there was no statistical difference in postoperative complications within 30 days after surgery, postoperative hospital stay, and hospital cost. For the surgical management of early stage EC, TU-LESS may be a feasible alternative approach to TLS, with comparable short-term surgical outcomes and superior cosmetic outcome. Future large-scale prospective studies are needed to identify these benefits. PMID:27057851
Ganbold, Erdene-Ochir; Yoon, Jinha; Cho, Kwang-Hwi; Joo, Sang-Woo
2015-01-01
The adsorption structures of 2-thiocytosine (2TC) on gold surfaces were examined by means of vibrational Raman spectroscopy and quantum mechanical density functional theory calculations. The 1H-thione-amino form was calculated to be most stable among the six examined tautomers. The three plausible binding geometries of sulfur, pyrimidine nitrogen, and amino group binding modes were calculated to estimate the binding energies of the 1H-thione-amino form with six gold cluster atoms. Thiouracils including 2-thiouracil (2TU), 4-thiouracil (4TU), and 6-methyl-2-thiouracil (6M2TU) were also studied to compare their relative binding energies on gold atoms. The intracellular localization of a DNA base analog of 2TC on gold nanoparticles (AuNPs) in HeLa cells was identified by means of surface-enhanced Raman scattering. AuNPs were modified with 2TC by self-assembly. Our dark-field microscopy and z-depth-dependent confocal Raman spectroscopy indicated that 2TC-assembled AuNPs could be found inside cancer cells. On the other hand, we did not observe noticeably strong Raman peaks in the cases of thiouracils including 2TU, 4TU, and 6M2TU. This may be due to the additional amino group of 2TC, which can lead to a stronger binding of adsorbates on AuNPs. Copyright © 2015. Published by Elsevier B.V.
Structural analysis of the role of TPX2 in branching microtubule nucleation
Thawani, Akanksha
2017-01-01
The mitotic spindle consists of microtubules (MTs), which are nucleated by the γ-tubulin ring complex (γ-TuRC). How the γ-TuRC gets activated at the right time and location remains elusive. Recently, it was uncovered that MTs nucleate from preexisting MTs within the mitotic spindle, which requires the protein TPX2, but the mechanism basis for TPX2 action is unknown. Here, we investigate the role of TPX2 in branching MT nucleation. We establish the domain organization of Xenopus laevis TPX2 and define the minimal TPX2 version that stimulates branching MT nucleation, which we find is unrelated to TPX2’s ability to nucleate MTs in vitro. Several domains of TPX2 contribute to its MT-binding and bundling activities. However, the property necessary for TPX2 to induce branching MT nucleation is contained within newly identified γ-TuRC nucleation activator motifs. Separation-of-function mutations leave the binding of TPX2 to γ-TuRC intact, whereas branching MT nucleation is abolished, suggesting that TPX2 may activate γ-TuRC to promote branching MT nucleation. PMID:28264915
Atypical archaeal tRNA pyrrolysine transcript behaves towards EF-Tu as a typical elongator tRNA
Théobald-Dietrich, Anne; Frugier, Magali; Giegé, Richard; Rudinger-Thirion, Joëlle
2004-01-01
The newly discovered tRNAPyl is involved in specific incorporation of pyrrolysine in the active site of methylamine methyltransferases in the archaeon Methanosarcina barkeri. In solution probing experiments, a transcript derived from tRNAPyl displays a secondary fold slightly different from the canonical cloverleaf and interestingly similar to that of bovine mitochondrial tRNASer(uga). Aminoacylation of tRNAPyl transcript by a typical class II synthetase, LysRS from yeast, was possible when its amber anticodon CUA was mutated into a lysine UUU anticodon. Hydrolysis protection assays show that lysylated tRNAPyl can be recognized by bacterial elongation factor. This indicates that no antideterminant sequence is present in the body of the tRNAPyl transcript to prevent it from interacting with EF-Tu, in contrast with the otherwise functionally similar tRNASec that mediates selenocysteine incorporation. PMID:14872064
2012-10-01
8217 Affiliatio athology an e, Philadelp ponding Au ysiology, D MS 488, P 2-2299; E-m .1158/1078- American A ancer Respose : Platelet-derived growth factor...their metastatic growth. The resulting increase in tu- ass will recruit and activate a progressively higher er of osteoclasts, thereby generating a self
2001-10-01
tu- vation of transcription and deregulated cell mors and may eventually regress through growth (18). The importance of APC and [- cat - apoptosis (25...receptors, fibrosarcoma cells transfected to express 10ng/ml TPRII [621, ALK-1 [63], and endoglin [64], and one of its TGF-131 in vitro are unable to
Permpongkosol, Sompol; Khupulsup, Kalayanee; Leelaphiwat, Supatra; Pavavattananusorn, Sarawan; Thongpradit, Supranee; Petchthong, Thanom
2016-08-01
The long-term effects of long-acting testosterone undecanoate (TU) and androgen receptor CAG repeat lengths in Thai men with late-onset hypogonadism (LOH) have not been reported. To analyze the 8-year follow-up effects of intramuscular TU therapy on metabolic parameters, urinary symptoms, bone mineral density, and sexual function and investigate CAG repeat lengths in men with LOH. We reviewed the medical records of 428 men with LOH who had been treated with TU and 5 patients were diagnosed with prostate cancer during TU therapy. There were 120 patients (mean age = 65.6 ± 8.9 years) who had 5 to 8 years of continuous TU supplementation and sufficiently completed records for analysis. Genomic DNA was extracted from peripheral blood and the CAG repeat region was amplified by polymerase chain reaction. Fragment analysis, sequencing, electropherography, and chromatography were performed. The main outcome measure was dynamic parameter changes during testosterone supplementation. TU did not improve all obesity parameters. A statistically significant decrease was found in waist circumference, percentage of body fat, glycated hemoglobin, cholesterol, low-density lipoprotein, and International Prostate Symptom Score (P < .05). TU did not produce differences in body mass index, high-density lipoprotein, triglyceride, or the Aging Male Symptoms score from baseline. However, a statistically significant increase was found in the level of testosterone, prostate-specific antigen, hematocrit, International Index of Erectile Function score, and vertebral and femoral bone mineral density (P < .05). No major adverse cardiovascular events or prostate cancer occurred during this study. The CAG repeat length was 14 to 28 and the median CAG length was 22. There was no association between CAG repeat length and any of the anthropometric measurements. Long-term TU treatment in men with LOH for up to 8 years appears to be safe, tolerable, and effective in correcting obesity parameters. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.
Historically Speaking, "Tu" or "Vocus"?
ERIC Educational Resources Information Center
Maley, Catherine A.
1972-01-01
Comments on the usage of the second person pronouns of address ( tu" and vous") in French, and traces the usage from the fifteenth century to present day, reflecting social, religious, and political attitudes. (DS)
Dai, Yaozhang; Liu, Yong; Tian, Xiufen; Zhang, Xin
2015-02-01
To explore the RCP protein expression and its clinicopathological significance in laryngeal squamous cell carcinoma (LSCC). RCP protein expression in human head and neck squamous cell carcinoma cell lines (NP-69, Tu686, Tu212, M2 and M4) was analyzed by Western blotting. Besides, its expression in 87 cases of LSCC, 18 cases of adjacent epithelial mucosa and 16 cases of vocal cord leukoplakia was detected by immunohistochemistry, and their correlation with clinicopathological parameters and patients' outcome was analyzed. The NP-69, Tu212 Tu686, M2 and M4 cells showed a gradual increase in the expression of RCP protein. The average relative expression levels of RCP protein in the NP-69, Tu212, Tu686, M2 and M4 cells were 0.05±0.01, 0.38±0.05, 0.63±0.02, 0.84±0.06 and 0.96±0.04, respectively. The same situation occurred in the adjacent mucosa, vocal cord leukoplakia and LSCC. Specifically, only 3 of 18 adjacent mucosa showed a low RCP expression (scored 0-2). Although the 16 cases of vocal cord leukoplakia had a low RCP expression, all their scores ranged from 0 to 3. While in the LSCC specimens, 59 (67.8%) cases demonstrated a high RCP expression (scored 8-15), 18 cases showed a lower RCP expression (scored 4-7), and only 10 cases were scored 2-3. Among the 87 LSCC cases, there were 28 cases (32.2%) of low RCP expression and 59 cases of high RCP expression. All the 18 cases of cancer-adjacent tissues and 16 cases of vocal cord leukoplakia were of low RCP expression. RCP overexpression was significantly associated with T classification, clinical staging, lymph node metastasis and recurrence (P<0.05 for all). Survival analysis revealed that the 5-year survival rate was 40.0% in the patients with high RCP expression and 75.0% in the patients with low RCP expression, the tumor-free 5-year survival rate was 30.7% and 64.0%, respectively, both showing a significant difference between the two subgroups (P<0.05). Univariate analysis revealed that alcohol history; smoking, T classification, clinical staging, lymph node metastasis and RCP expression were significantly associated with a poor prognosis (P<0.05 for all). The multivariate analysis showed that only recurrence and RCP expression were independent prognostic factors affecting the prognosis for patients with LSCC (P<0.05 for both). Expression of RCP protein may contribute to the malignant progression of LSCC, and may become a novel marker predicting tumor recurrence, cervical lymph node metastasis and prognosis for patients with laryngeal squamous cell carcinoma.
DNA methylation of miRNA-encoding genes in non-small cell lung cancer patients.
Heller, Gerwin; Altenberger, Corinna; Steiner, Irene; Topakian, Thais; Ziegler, Barbara; Tomasich, Erwin; Lang, György; End-Pfützenreuter, Adelheid; Zehetmayer, Sonja; Döme, Balazs; Arns, Britt-Madeleine; Klepetko, Walter; Zielinski, Christoph C; Zöchbauer-Müller, Sabine
2018-03-23
De-regulated DNA methylation leading to transcriptional inactivation of certain genes occurs frequently in non-small cell lung cancers (NSCLC). Besides protein-encoding genes also microRNA (miRNA)-encoding genes may be targets for methylation in NSCLCs, however, the number of known methylated miRNA genes is still small. Thus, we investigated methylation of miRNA genes in primary tumours (TU) and corresponding non-malignant lung tissue samples (NL) of 50 NSCLC patients using methylated DNA immunoprecipitation followed by custom designed tiling microarray analyses (MeDIP-chip) and 252 differentially methylated probes between TU and NL samples were identified. These probes were annotated which resulted in the identification of 34 miRNA-encoding genes with increased methylation in TU specimens. While some of these miRNA-encoding genes were already known to be methylated in NSCLCs (e.g. miR-9-3, miR-124), methylation of the vast majority of them was unknown so far. We selected six miRNA genes (miR-10b, miR-1179, miR-137, miR-572, miR-3150b and miR-129-2) for gene-specific methylation analyses in TU and corresponding NL samples of 104 NSCLC patients and observed a statistically significant increase of methylation of these miRNA genes in TU samples (p<0.0001, respectively). In silico target prediction of the six miRNAs identified several oncogenic/cell proliferation promoting factors (e.g. CCNE1 as miR-1179 target). To investigate if miR-1179 indeed targets CCNE1, we transfected miR-1179 mimics into CCNE1 expressing NSCLC cells and observed down-regulated CCNE1 mRNA expression in these cells compared to control cells. Similar effects on Cyclin E1 expression were seen in Western blot analyses. In addition, we found a statistically significant growth reduction of NSCLC cells transfected with miR-1179 mimics compared to control cells. In conclusion, we identified many methylated miRNA genes in NSCLC patients and found that miR-1179 is a potential tumour cell growth suppressor in NSCLCs. Overall, our findings emphasize the impact of miRNA gene methylation on the pathogenesis of NSCLCs. This article is protected by copyright. All rights reserved.
Tritium in water vapor in the shallow unsaturated zone at the Amargosa Desert Research Site
Healy, Richard W.; Striegl, Robert G.; Michel, Robert L.; Prudic, David E.; Andraski, Brian J.; Morganwalp, David W.; Buxton, Herbert T.
1999-01-01
Samples of water vapor in soil gas were obtained at the U.S. Geological Survey's Amargosa Desert Research Site in 1997 and 1998 from a depth of 1.5 m (meters) within a 300 m by 300 m grid that lies immediately to the south and west of a low-level radioactive-waste disposal site. The gas samples were analyzed for tritium. Fifty-eight samples were collected in May 1997; 61 samples were collected in June 1998. Measured tritium concentrations ranged from 16 ± 9 TU (tritium units) to 36,900 ± 300 TU in 1997, and from 6 ± 6 TU to 37,360 ± 450 TU in 1998. Concentrations decreased from northeast to southwest across the grid. In general, there was very little difference in tritium concentrations between the two sampling periods.
Chiba, Yohei; Sato, Seiya; Itamochi, Hiroaki; Suga, Yasuko; Fukagawa, Tomoyuki; Oumi, Nao; Oishi, Tetsuro; Harada, Tasuku; Sugai, Tamotsu; Sugiyama, Toru
2017-04-01
A new human uterine carcinosarcoma (UCS) cell line, TU-ECS-1, was established and characterized. The morphological appearance of the cultured cells was an insular of epithelial-like cells arranged in the form of a jigsaw puzzle and mesenchymal-like cells with a spindle-shaped or fibroblast-like morphology. A relatively high proliferation rate was observed with a doubling time of 18.2 h. The chromosome number ranged from 44 to 49 and had an extra chromosome 12 (trisomy 12). The respective half-maximal inhibitory concentrations of cisplatin, paclitaxel, and doxorubicin were 2.9 µM, 154 nM, and 219 ng/mL, respectively. Mutational analysis revealed that TU-ECS-1 cells have mutations of TP53 in exons 4, 6, and 8 and of KRAS at codon 12 (G12D) in exon 2, which is a mutation hot spot on this gene. Western blot analysis showed that p53 protein was overexpressed in TU-ECS-1 cells. Immunostaining of the cultured cells and in vivo tumors showed that the TU-ECS-1 cells and xenografts were positive for epithelial marker cytokeratin AE1/3 and mesenchymal marker vimentin. These results suggested that TU-ECS-1 cells might have both epithelial and mesenchymal characteristics. This cell line may be useful to study the carcinogenesis of UCS and contribute to the development of novel treatment strategies.
Masuda, Hirohisa; Mori, Risa; Yukawa, Masashi; Toda, Takashi
2013-01-01
γ-Tubulin plays a universal role in microtubule nucleation from microtubule organizing centers (MTOCs) such as the animal centrosome and fungal spindle pole body (SPB). γ-Tubulin functions as a multiprotein complex called the γ-tubulin complex (γ-TuC), consisting of GCP1–6 (GCP1 is γ-tubulin). In fungi and flies, it has been shown that GCP1–3 are core components, as they are indispensable for γ-TuC complex assembly and cell division, whereas the other three GCPs are not. Recently a novel conserved component, MOZART1, was identified in humans and plants, but its precise functions remain to be determined. In this paper, we characterize the fission yeast homologue Mzt1, showing that it is essential for cell viability. Mzt1 is present in approximately equal stoichiometry with Alp4/GCP2 and localizes to all the MTOCs, including the SPB and interphase and equatorial MTOCs. Temperature-sensitive mzt1 mutants display varying degrees of compromised microtubule organization, exhibiting multiple defects during both interphase and mitosis. Mzt1 is required for γ-TuC recruitment, but not sufficient to localize to the SPB, which depends on γ-TuC integrity. Intriguingly, the core γ-TuC assembles in the absence of Mzt1. Mzt1 therefore plays a unique role within the γ-TuC components in attachment of this complex to the major MTOC site. PMID:23885124
Asea, Philip E; MacNeil, James D; Boison, Joe O
2006-01-01
A method was developed and validated to screen for residues of the thyreostatic drugs, tapazole (TAP), mercaptobenzimidazole (MBI), thiouracil (TU), methylthiouracil (MTU), propylthiouracil (PrTU), and phenylthiouracil (PhTU) in bovine, equine, ovine, and porcine thyroid and muscle tissues at concentrations > or = 5 ng/g using 2-methoxy-mercaptobenzimidazole (MeMBI) and dimethylthiouracil (DMTU) as internal standards. In this method, the drugs were solvent extracted from thyroid and muscle tissue and cleaned up on an amino-propyl solid-phase extraction (SPE) cartridge. The unretained fraction containing TAP and MBI and the internal standard, MeMBI, was collected as Fraction 1. The retained fraction containing TU, MTU, PrTU, PhTU, and the internal standard, DMTU, was eluted with 3% acetic acid-isopropanol as Fraction 2. Fraction 1 was further cleaned up on an alumina B SPE cartridge and analyzed by gradient elution on a C18 high-performance liquid chromatography (HPLC) column with ultraviolet detection at wavelengths of 255 and 300 nm. Fraction 2 was taken to dryness, derivatized with 4-chloro-7-nitrobenzo-2-furazan at pH 8, and analyzed by gradient elution on a C18 LC column with mass spectrometry (MS) detection. Any "presumptive positive" test results were submitted for further analysis by LC/MS/MS. The validated method was applied to the analysis of over 300 thyroid tissue samples.
Trim25 Is an RNA-Specific Activator of Lin28a/TuT4-Mediated Uridylation.
Choudhury, Nila Roy; Nowak, Jakub S; Zuo, Juan; Rappsilber, Juri; Spoel, Steven H; Michlewski, Gracjan
2014-11-20
RNA binding proteins have thousands of cellular RNA targets and often exhibit opposite or passive molecular functions. Lin28a is a conserved RNA binding protein involved in pluripotency and tumorigenesis that was previously shown to trigger TuT4-mediated pre-let-7 uridylation, inhibiting its processing and targeting it for degradation. Surprisingly, despite binding to other pre-microRNAs (pre-miRNAs), only pre-let-7 is efficiently uridylated by TuT4. Thus, we hypothesized the existence of substrate-specific cofactors that stimulate Lin28a-mediated pre-let-7 uridylation or restrict its functionality on non-let-7 pre-miRNAs. Through RNA pull-downs coupled with quantitative mass spectrometry, we identified the E3 ligase Trim25 as an RNA-specific cofactor for Lin28a/TuT4-mediated uridylation. We show that Trim25 binds to the conserved terminal loop (CTL) of pre-let-7 and activates TuT4, allowing for more efficient Lin28a-mediated uridylation. These findings reveal that protein-modifying enzymes, only recently shown to bind RNA, can guide the function of canonical ribonucleoprotein (RNP) complexes in cis, thereby providing an additional level of specificity.
Artemisinin and Chinese Medicine as Tu Science.
Fu, Jia-Chen
2017-09-01
The story of discovery of artemisinin highlights the diversity of scientific values across time and space. Resituating artemisinin research within a broader temporal framework allows us to understand how Chinese drugs like qinghao came to articulate a space for scientific experimentation and innovation through its embodiment of alternating clusters of meanings associated with tu and yang within scientific discourse. Tu science, which was associated with terms like native, Chinese, local, rustic, mass, and crude, articulated a radical vision of science in the service of socialist revolutionary ideals. Yang science, which signified foreign, Western, elite, and professional, tended to bear the hallmarks of professionalism, transnational networks in education and training, and an emphasis on basic or foundational research. With respect to medical research, the case of artemisinin highlights how the constitution of socialist science as an interplay of tu and yang engendered different scientific values and parameters for scientific endeavor. Modern medical research in Maoist China could harness the productive energies of mass participation to technical expertise in its investigations of Chinese drugs, and under the banner of tu science, it became possible and scientifically legitimate to research Chinese drugs in ways that had previously provoked resistance and controversy. Copyright © 2017 Elsevier Ltd. All rights reserved.
RNA-Seq reveals virus–virus and virus–plant interactions in nature
Kamitani, Mari; Nagano, Atsushi J.; Honjo, Mie N.; Kudoh, Hiroshi
2016-01-01
Abstract As research on plant viruses has focused mainly on crop diseases, little is known about these viruses in natural environments. To understand the ecology of viruses in natural systems, comprehensive information on virus–virus and virus–host interactions is required. We applied RNA-Seq to plants from a natural population of Arabidopsis halleri subsp. gemmifera to simultaneously determine the presence/absence of all sequence-reported viruses, identify novel viruses and quantify the host transcriptome. By introducing the criteria of read number and genome coverage, we detected infections by Turnip mosaic virus (TuMV), Cucumber mosaic virus and Brassica yellows virus. Active TuMV replication was observed by ultramicroscopy. De novo assembly further identified a novel partitivirus, Arabidopsis halleri partitivirus 1. Interestingly, virus reads reached a maximum level that was equivalent to that of the host's total mRNA, although asymptomatic infection was common. AhgAGO2, a key gene in host defence systems, was upregulated in TuMV-infected plants. Multiple infection was frequent in TuMV-infected leaves, suggesting that TuMV facilitates multiple infection, probably by suppressing host RNA silencing. Revealing hidden plant–virus interactions in nature can enhance our understanding of biological interactions and may have agricultural applications. PMID:27549115
Recent trends in the treatment of testosterone deficiency syndrome.
Hong, Bum Sik; Ahn, Tai Young
2007-11-01
Testosterone deficiency syndrome (TDS) is defined as a clinical and biochemical syndrome associated with advancing age and is characterized by typical symptoms and deficiency in serum testosterone levels. TDS is a result of the interaction of hypothalamo-pituitary and testicular factors. Now, treatment of TDS with testosterone is still controversial due to a lack of large, controlled clinical trials on efficacy. The risks of treatment with testosterone appear to be minimal, although long-term studies on the safety of testosterone therapy are lacking. The aim of the therapy is to establish a physiological concentration of serum testosterone in order to correct the androgen deficiency, relieve its symptoms and prevent long-term sequelae. All of the available products, despite their varying pharmacodynamic and pharmacokinetic profiles, are able to reach this goal. Newer testosterone patches seem not to cause severe skin irritation. Testosterone gels minimize the skin irritation while providing flexibility in dosing and a low discontinuation rate. Oral testosterone undecanoate (TU) is free of liver toxicity. Recent formulation of oral TU markedly increased shelf-live, a major drawback in the older preparation. Producing swings in testosterone levels rising rapidly to the supraphysiological range is not the case with the new injectable long-acting preparation of TU. To be able to rapidly react and stop treatment in cases where side-effects and contraindications are detected, the short-acting transdermal and oral delivery modes have certain advantages. However, there is no evidence that the use of an injectable long-acting TU in men with TDS has limitations in clinical application for this reason. The use of dehydroepiandrosterone is still controversial because of a lack of well designed long-term trials, although some recent studies suggest positive effects on various body systems. Only a few studies have been carried out to investigate the effect of hCG (human chorionic gonadotropin) in TDS with some positive results on various body systems.
A novel plant protection strategy for transient reactors
NASA Astrophysics Data System (ADS)
Bhattacharyya, Samit K.; Lipinski, Walter C.; Hanan, Nelson A.
A novel plant protection system designed for use in the TREAT Upgrade (TU) reactor is described. The TU reactor is designed for controlled transient operation in the testing of reactor fuel behavior under simulated reactor accident conditions. Safe operation of the reactor is of paramount importance and the Plant Protection System (PPS) had to be designed to exacting requirements. Researchers believe that the strategy developed for the TU has potential application to the multimegawatt space reactors and represents the state of the art in terrestrial transient reactor protection systems.
Molecular insight into γ-γ tubulin lateral interactions within the γ-tubulin ring complex (γ-TuRC)
NASA Astrophysics Data System (ADS)
Suri, Charu; Hendrickson, Triscia W.; Joshi, Harish C.; Naik, Pradeep Kumar
2014-09-01
γ-tubulin is essential for the nucleation and organization of mitotic microtubules in dividing cells. It is localized at the microtubule organizing centers and mitotic spindle fibres. The most well accepted hypothesis for the initiation of microtubule polymerization is that α/β-tubulin dimers add onto a γ-tubulin ring complex (γTuRC), in which adjacent γ-tubulin subunits bind to the underlying non-tubulin components of the γTuRC. This template thus determines the resulting microtubule lattice. In this study we use molecular modelling and molecular dynamics simulations, combined with computational MM-PBSA/MM-GBSA methods, to determine the extent of the lateral atomic interaction between two adjacent γ-tubulins within the γTuRC. To do this we simulated a γ-γ homodimer for 10 ns and calculated the ensemble average of binding free energies of -107.76 kcal/mol by the MM-PBSA method and of -87.12 kcal/mol by the MM-GBSA method. These highly favourable binding free energy values imply robust lateral interactions between adjacent γ-tubulin subunits in addition to their end-interactions longitudinally with other proteins of γTuRC. Although the functional reconstitution of γ-TuRC subunits and their stepwise in vitro assembly from purified components is not yet feasible, we nevertheless wanted to recognize hotspot amino acids responsible for key γ-γ interactions. Our free energy decomposition data from converting a compendium of amino acid residues identified an array of hotspot amino acids. A subset of such mutants can be expressed in vivo in living yeast. Because γTuRC is important for the growth of yeast, we could test whether this subset of the hotspot mutations support growth of yeast. Consistent with our model, γ-tubulin mutants that fall into our identified hotspot do not support yeast growth.
Conformal Nets II: Conformal Blocks
NASA Astrophysics Data System (ADS)
Bartels, Arthur; Douglas, Christopher L.; Henriques, André
2017-08-01
Conformal nets provide a mathematical formalism for conformal field theory. Associated to a conformal net with finite index, we give a construction of the `bundle of conformal blocks', a representation of the mapping class groupoid of closed topological surfaces into the category of finite-dimensional projective Hilbert spaces. We also construct infinite-dimensional spaces of conformal blocks for topological surfaces with smooth boundary. We prove that the conformal blocks satisfy a factorization formula for gluing surfaces along circles, and an analogous formula for gluing surfaces along intervals. We use this interval factorization property to give a new proof of the modularity of the category of representations of a conformal net.
Alibardi, Lorenzo
2014-01-01
The corneous layer of the epidermis in hard-shelled turtles largely derives from the accumulation of beta-proteins as indicated by microscopic, in situ hybridization, and immunocytochemical and Western blotting analysis. The expression of mRNAs of one of the most common type of beta-proteins shows higher expression in upper spinosus and pre-corneous keratinocytes of growing scutes. Two beta-proteins of 14-16 kDa, indicated as Tu2 and Tu17 and representing two subtypes of beta-proteins co-accumulate in the thick corneous layer of the epidermis in hard-shelled turtle. The two beta-proteins apparently mix in differentiating and mature corneocytes although Tu2 appears more prevalent than Tu17. The specific role of the different subtypes in the formation of the hard corneous material of the carapace and plastron is not clear. It is hypothesized that the relative amount of beta-proteins belonging to the two subclasses in relation to the alpha-keratin meshwork present in keratinocytes contributes to the formation of a variably resistant and inflexible corneous layer. Tu17 may have a more globular structure than Tu2 and is likely present in denser areas of the corneous layer containing also alpha-keratin. The increase of cysteine-glycine-rich beta-proteins in the matrix located among alpha-keratin filaments may allow the formation of a hard corneous material, probably through increase of cross-bridge formation and hydrophobicity. © 2013 Wiley Periodicals, Inc.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Aranda, J. I.; Ramirez-Zavaleta, F.; Tututi, E. S.
The rare top quark couplings tu{sub i{gamma}} and tu{sub i{gamma}{gamma}} (u{sub i}=u, c) induced at the one-loop level by a flavor violating tu{sub i}H vertex are studied within the context of an effective Yukawa sector that incorporates SU{sub L}(2)xU{sub Y}(1)-invariant operators of up to dimension six. Data on the recently observed D{sup 0}-D{sup 0} mixing are employed to constrain the tu{sub i}H vertex, which is then used to predict the t{yields}u{sub i}H, t{yields}u{sub i{gamma}}, and t{yields}u{sub i{gamma}{gamma}} decays, as well as the {gamma}{gamma}{yields}tu{sub i}+tu{sub i} reaction in the context of the ILC. It is found that the t{yields}cH and t{yields}c{gamma}{gamma}more » decays can reach sizable branching ratios as high as 5x10{sup -3} and 10{sup -4}, respectively. As for the t{yields}c{gamma} decay, it can have a branching ratio of 5x10{sup -8} that is about 6 orders of magnitude larger than the standard model prediction, which, however, is still very small to be detected. As for tc production, it is found that, due to the presence of a resonant effect in the convoluted cross section {sigma}(e{sup +}e{sup -{yields}{gamma}{gamma}{yields}}tc+tc), about (0.5-2.7)x10{sup 3} tc events may be produced at the ILC for a value of the Higgs mass near to the top mass.« less
Tunable Light-Guide Image Processing Snapshot Spectrometer (TuLIPSS) for Earth and Moon Observations
NASA Astrophysics Data System (ADS)
Tkaczyk, T. S.; Alexander, D.; Luvall, J. C.; Wang, Y.; Dwight, J. G.; Pawlowsk, M. E.; Howell, B.; Tatum, P. F.; Stoian, R.-I.; Cheng, S.; Daou, A.
2018-02-01
A tunable light-guide image processing snapshot spectrometer (TuLIPSS) for Earth science research and observation is being developed through a NASA instrument incubator project with Rice University and Marshall Space Flight Center.
TU Berlin Rover Family for Terrestrial Testing of Complex Planetary Mission Scenarios
NASA Astrophysics Data System (ADS)
Kryza, L.; Brieß, K.
2018-04-01
The TU Berlin has developed a family of planetary rovers for educational use and research activities. The paper will introduce these cost-effective systems, which can be used for analogue mission demonstration on Earth.
Understanding and Assessing Risk of Intrastate Conflict: Human Development Theory and Practice
2004-04-01
R es ou rc es O pp or tu ni ty S ec ur ity V io le nc e Le ve l To ta l R is k R es...ou rc es O pp or tu ni ty S ec ur ity V io le nc e Le ve l To ta l R is k R es ou rc es O pp or tu ni ty S ec ur ity V io le nc e Le ve...l To ta l R is k R es ou rc es O pp or
1989-03-01
characteristics of the plasma. (p. 75) xi Hx transition at 54.19 A is reported. (p. 86) TuC20 Quantum Mechanical Interference in Four-Wave TuC28 Gain Measurement...E.MixingtK.ctivH.iBaldwinenAustralean Ntwoiofenal untue Miura. Y. Kitagawa, K. Nishihara, Y. Kato. H. Nishimura. C. and destructive interference between...Incidence Optics for Synchrotron TuC25 Spectra of Lead, Bismuth, Thorium, and Uranium X-Ray Lithography , R. J. Rosser, P. M. J. H. Wormell, R
Trim25 Is an RNA-Specific Activator of Lin28a/TuT4-Mediated Uridylation
Choudhury, Nila Roy; Nowak, Jakub S.; Zuo, Juan; Rappsilber, Juri; Spoel, Steven H.; Michlewski, Gracjan
2014-01-01
Summary RNA binding proteins have thousands of cellular RNA targets and often exhibit opposite or passive molecular functions. Lin28a is a conserved RNA binding protein involved in pluripotency and tumorigenesis that was previously shown to trigger TuT4-mediated pre-let-7 uridylation, inhibiting its processing and targeting it for degradation. Surprisingly, despite binding to other pre-microRNAs (pre-miRNAs), only pre-let-7 is efficiently uridylated by TuT4. Thus, we hypothesized the existence of substrate-specific cofactors that stimulate Lin28a-mediated pre-let-7 uridylation or restrict its functionality on non-let-7 pre-miRNAs. Through RNA pull-downs coupled with quantitative mass spectrometry, we identified the E3 ligase Trim25 as an RNA-specific cofactor for Lin28a/TuT4-mediated uridylation. We show that Trim25 binds to the conserved terminal loop (CTL) of pre-let-7 and activates TuT4, allowing for more efficient Lin28a-mediated uridylation. These findings reveal that protein-modifying enzymes, only recently shown to bind RNA, can guide the function of canonical ribonucleoprotein (RNP) complexes in cis, thereby providing an additional level of specificity. PMID:25457611
SeqTU: A web server for identification of bacterial transcription units
DOE Office of Scientific and Technical Information (OSTI.GOV)
Chen, Xin; Chou, Wen -Chi; Ma, Qin
A transcription unit (TU) consists of K ≥ 1 consecutive genes on the same strand of a bacterial genome that are transcribed into a single mRNA molecule under certain conditions. Their identification is an essential step in elucidation of transcriptional regulatory networks. We have recently developed a machine-learning method to accurately identify TUs from RNA-seq data, based on two features of the assembled RNA reads: the continuity and stability of RNA-seq coverage across a genomic region. While good performance was achieved by the method on Escherichia coli and Clostridium thermocellum, substantial work is needed to make the program generally applicablemore » to all bacteria, knowing that the program requires organism specific information. A web server, named SeqTU, was developed to automatically identify TUs with given RNA-seq data of any bacterium using a machine-learning approach. The server consists of a number of utility tools, in addition to TU identification, such as data preparation, data quality check and RNA-read mapping. SeqTU provides a user-friendly interface and automated prediction of TUs from given RNA-seq data. Furthermore, the predicted TUs are displayed intuitively using HTML format along with a graphic visualization of the prediction.« less
SeqTU: A web server for identification of bacterial transcription units
Chen, Xin; Chou, Wen -Chi; Ma, Qin; ...
2017-03-07
A transcription unit (TU) consists of K ≥ 1 consecutive genes on the same strand of a bacterial genome that are transcribed into a single mRNA molecule under certain conditions. Their identification is an essential step in elucidation of transcriptional regulatory networks. We have recently developed a machine-learning method to accurately identify TUs from RNA-seq data, based on two features of the assembled RNA reads: the continuity and stability of RNA-seq coverage across a genomic region. While good performance was achieved by the method on Escherichia coli and Clostridium thermocellum, substantial work is needed to make the program generally applicablemore » to all bacteria, knowing that the program requires organism specific information. A web server, named SeqTU, was developed to automatically identify TUs with given RNA-seq data of any bacterium using a machine-learning approach. The server consists of a number of utility tools, in addition to TU identification, such as data preparation, data quality check and RNA-read mapping. SeqTU provides a user-friendly interface and automated prediction of TUs from given RNA-seq data. Furthermore, the predicted TUs are displayed intuitively using HTML format along with a graphic visualization of the prediction.« less
Sakurai, Rakusa; Nomura, Hideo; Moriyam, Yohsuke; Kawano, Shigeyuki
2004-08-01
Mitochondrial DNA (mtDNA) is inherited maternally in most eukaryotes. Linear mitochondrial plasmids in higher plants and fungi are also transmitted from the maternal parent to the progeny. However, mF, which is a mitochondrial linear plasmid of Physarum polycephalum, evades uniparental mitochondrial inheritance. We examined 36 myxamoebal strains of Physarum and isolated three novel mF+ strains (JE8, TU111, NG111) that harbored free mF plasmids. These strains were mated with the mF- strain KM88. Of the three mF- x mF+ crosses, only KM88 x JE8 displayed complete uniparental inheritance. However, in KM88 x TU111 and KM88 x NG111, the mtDNA of KM88 and mF of TU111 and NG111 were inherited by the plasmodia and showed recombination. For example, although the mtDNA of TU111 was eliminated, the mF of TU111 persisted and became inserted into the mtDNA of KM88, such that recombinant mtDNA represented 80% of the total mtDNA. The parental mitochondria fused to yield giant mitochondria with two or more mitochondrial nucleoids. The mF appears to exchange mitochondria from the recipient (paternal) to the donor (maternal) by promoting mitochondrial fusion.
2'-O-methylation in mRNA disrupts tRNA decoding during translation elongation.
Choi, Junhong; Indrisiunaite, Gabriele; DeMirci, Hasan; Ieong, Ka-Weng; Wang, Jinfan; Petrov, Alexey; Prabhakar, Arjun; Rechavi, Gideon; Dominissini, Dan; He, Chuan; Ehrenberg, Måns; Puglisi, Joseph D
2018-03-01
Chemical modifications of mRNA may regulate many aspects of mRNA processing and protein synthesis. Recently, 2'-O-methylation of nucleotides was identified as a frequent modification in translated regions of human mRNA, showing enrichment in codons for certain amino acids. Here, using single-molecule, bulk kinetics and structural methods, we show that 2'-O-methylation within coding regions of mRNA disrupts key steps in codon reading during cognate tRNA selection. Our results suggest that 2'-O-methylation sterically perturbs interactions of ribosomal-monitoring bases (G530, A1492 and A1493) with cognate codon-anticodon helices, thereby inhibiting downstream GTP hydrolysis by elongation factor Tu (EF-Tu) and A-site tRNA accommodation, leading to excessive rejection of cognate aminoacylated tRNAs in initial selection and proofreading. Our current and prior findings highlight how chemical modifications of mRNA tune the dynamics of protein synthesis at different steps of translation elongation.
A Whitham-Theory Sonic-Boom Analysis of the TU-144 Aircraft at a Mach Number of 2.2
NASA Technical Reports Server (NTRS)
Mack, Robert J.
1999-01-01
Officially, the Tu-144 was the first supersonic-cruise, passenger-carrying aircraft to enter commercial service. Design, construction, and testing were carried out by the Soviet Union, flight certification was by the Soviet Union, and the only regular passenger flights were scheduled and flown across the territory of the Soviet Union. Although it was not introduced to international passenger service, there were many significant engineering accomplishments achieved in the design, production, and flight of this aircraft. Development of the aircraft began with a prototype stage. Systematic testing and redesign led to a production aircraft in discrete stages that measurably improved the performance of the aircraft from the starting concept to final aircraft certification. It flew in competition with the English-French Concorde for a short time, but was withdrawn from national commercial service due to a lack of interest by airlines outside the Soviet Union. NASA became interested in the Tu- 144 aircraft when it was offered for use as a flying "testbed" in the study of operating characteristics of a supersonic-cruise commercial airplane. Since it had been in supersonic-cruise service, the Tu- 144 had operational characteris'tics similar to those anticipated in the conceptual aircraft designs being studied by the United States aircraft companies. In addition to the other operational tests being conducted on the Tu-144 aircraft, it was proposed that two sets of sonic-boom pressure signature measurements be made. The first set would be made on the ground, using techniques and devices similar to those in reference I and many other subsequent studies. A second set would be made in the air with an instrumented aircraft flying close under the Tu-144 in supersonic flight. Such in-flight measurements would require pressure gages that were capable of accurately recording the flow-field overpressures generated by the Tu- 144 at relatively close distances under the vehicle. Therefore, an analysis of the Tu-144 was made to obtain predictions of pressure signature shape and shock strengths at cruise conditions so that the range and characteristics of the required pressure gages could be determined well in advance of the tests. Cancellation of the sonic-boom signature measurement part of the tests removed the need for these pressure gages. Since CFD methods would be used to analyze the aerodynamic performance of the Tu-144 and make similar pressure signature predictions, the relatively quick and simple Whitham-theory pressure signature predictions presented in this paper could be used for comparisons. Pressure signature predictions of sonic-boom disturbances from the Tu- 144 aircraft were obtained from geometry derived from a three-view description of the production aircraft. The geometry was used to calculate aerodynamic performance characteristics at supersonic-cruise conditions. These characteristics and Whitham/Walkden sonic-boom theory were employed to obtain F-functions and flow-field pressure signature predictions at a Mach number of 2.2, at a cruise altitude of 61000 feet, and at a cruise weight of 350000 pounds.
Knutson, Stacy T.; Westwood, Brian M.; Leuthaeuser, Janelle B.; Turner, Brandon E.; Nguyendac, Don; Shea, Gabrielle; Kumar, Kiran; Hayden, Julia D.; Harper, Angela F.; Brown, Shoshana D.; Morris, John H.; Ferrin, Thomas E.; Babbitt, Patricia C.
2017-01-01
Abstract Protein function identification remains a significant problem. Solving this problem at the molecular functional level would allow mechanistic determinant identification—amino acids that distinguish details between functional families within a superfamily. Active site profiling was developed to identify mechanistic determinants. DASP and DASP2 were developed as tools to search sequence databases using active site profiling. Here, TuLIP (Two‐Level Iterative clustering Process) is introduced as an iterative, divisive clustering process that utilizes active site profiling to separate structurally characterized superfamily members into functionally relevant clusters. Underlying TuLIP is the observation that functionally relevant families (curated by Structure‐Function Linkage Database, SFLD) self‐identify in DASP2 searches; clusters containing multiple functional families do not. Each TuLIP iteration produces candidate clusters, each evaluated to determine if it self‐identifies using DASP2. If so, it is deemed a functionally relevant group. Divisive clustering continues until each structure is either a functionally relevant group member or a singlet. TuLIP is validated on enolase and glutathione transferase structures, superfamilies well‐curated by SFLD. Correlation is strong; small numbers of structures prevent statistically significant analysis. TuLIP‐identified enolase clusters are used in DASP2 GenBank searches to identify sequences sharing functional site features. Analysis shows a true positive rate of 96%, false negative rate of 4%, and maximum false positive rate of 4%. F‐measure and performance analysis on the enolase search results and comparison to GEMMA and SCI‐PHY demonstrate that TuLIP avoids the over‐division problem of these methods. Mechanistic determinants for enolase families are evaluated and shown to correlate well with literature results. PMID:28054422
Knutson, Stacy T; Westwood, Brian M; Leuthaeuser, Janelle B; Turner, Brandon E; Nguyendac, Don; Shea, Gabrielle; Kumar, Kiran; Hayden, Julia D; Harper, Angela F; Brown, Shoshana D; Morris, John H; Ferrin, Thomas E; Babbitt, Patricia C; Fetrow, Jacquelyn S
2017-04-01
Protein function identification remains a significant problem. Solving this problem at the molecular functional level would allow mechanistic determinant identification-amino acids that distinguish details between functional families within a superfamily. Active site profiling was developed to identify mechanistic determinants. DASP and DASP2 were developed as tools to search sequence databases using active site profiling. Here, TuLIP (Two-Level Iterative clustering Process) is introduced as an iterative, divisive clustering process that utilizes active site profiling to separate structurally characterized superfamily members into functionally relevant clusters. Underlying TuLIP is the observation that functionally relevant families (curated by Structure-Function Linkage Database, SFLD) self-identify in DASP2 searches; clusters containing multiple functional families do not. Each TuLIP iteration produces candidate clusters, each evaluated to determine if it self-identifies using DASP2. If so, it is deemed a functionally relevant group. Divisive clustering continues until each structure is either a functionally relevant group member or a singlet. TuLIP is validated on enolase and glutathione transferase structures, superfamilies well-curated by SFLD. Correlation is strong; small numbers of structures prevent statistically significant analysis. TuLIP-identified enolase clusters are used in DASP2 GenBank searches to identify sequences sharing functional site features. Analysis shows a true positive rate of 96%, false negative rate of 4%, and maximum false positive rate of 4%. F-measure and performance analysis on the enolase search results and comparison to GEMMA and SCI-PHY demonstrate that TuLIP avoids the over-division problem of these methods. Mechanistic determinants for enolase families are evaluated and shown to correlate well with literature results. © 2017 The Authors Protein Science published by Wiley Periodicals, Inc. on behalf of The Protein Society.
Schnabel, Peter G; Bagchus, Wilma; Lass, Holger; Thomsen, Torben; Geurts, T B Paul
2007-01-01
Objective Andriol® Testocaps® is a new oral formulation of testosterone undecanoate (TU) for treatment of hypogonadism. As TU is taken up by the intestinal lymphatic system, both the presence and the composition of food influence the absorption. The aim of this study was to investigate the effect of food composition on the pharmacokinetics of oral TU. Design An open-label, single-centre, four-way crossover study. With a washout period of 6–7 days, 80 mg TU was administered in the morning 5 min after consuming each of four different meals in a randomized order (A: 230 kcal, 0·6 g lipid; B: 220 kcal, 5 g lipid; C: 474 kcal, 19 g lipid; D: 837 kcal, 44 g lipid). Patients Twenty-four postmenopausal volunteers. Measurements Serial blood samples were collected until 24 h after dosing to determine testosterone and dihydrotestosterone (DHT) by gas chromatography-mass spectroscopy (GC-MS). Results The bioavailability of testosterone after a low-calorie meal containing 0·6 g lipid or 5 g lipid was relatively low, the area under the concentration–time curve (AUC0–tlast) for testosterone being 30·7 and 43·5 nmol h/l, respectively. The bioavailability of testosterone after a meal containing 19 g lipid was considerably higher (AUC0–tlast = 146 nmol h/l), whereas increasing the lipid content to 44 g lipid did not further increase the bioavailability of testosterone (AUC0–tlast = 154 nmol h/l). Conclusion Approximately 19 g of lipid per meal efficiently increases absorption of testosterone from oral TU. Therefore, coadministration with a normal rather than a fatty meal is sufficient to increase serum testosterone levels when using oral TU. PMID:17371478
The Dual Function of "usted:" Forms of Address in Bogota, Colombia.
ERIC Educational Resources Information Center
Uber, Diane Ringer
1985-01-01
Shows that "usted" has two functions: showing lack of solidarity and showing extreme solidarity, with "tu" falling somewhere in between on the continuum. Discusses the increasing use of "tu," especially among younger people, and presents some possible reasons for this. (SED)
Conformations of Substituted Ethanes.
ERIC Educational Resources Information Center
Kingsbury, Charles A.
1979-01-01
Reviews state-of-the-art of conformational analysis and factors which affect it. Emphasizes sp-3 hybridized acrylic molecules. Provides examples on the importance of certain factors in determining conformation. Purpose, is to provide examples for examination questions. (Author/SA)
Manchester, Keith L
2004-01-30
An analysis is made of the rate constants for the reactions involving the interactions of EF-Tu, EF-Ts, GDP, and GTP recently derived by Gromadski et al. [Biochemistry 41 (2002) 162]. Though their measured values appear to allow a reasonable rate of nucleotide exchange sufficient to support rates of protein synthesis in vivo, their data underestimate the thermodynamic barrier involved in nucleotide exchange and therefore cannot be considered definitive. A kinetic scheme consistent with the thermodynamic barrier can be achieved by modification of various rate constants, particularly of those involving the release of EF-Ts from EF-Tu.GTP.EF-Ts, but such constants are markedly different from what are experimentally observed. It thus remains impossible at present satisfactorily to model guanine nucleotide exchange on EF-Tu, catalysed by EF-Ts by a double displacement mechanism, with experimentally derived rate constants. Metabolic control analysis has been applied to determine the degree of flux control of the different steps in the pathway.
A Satellite Imagery Approach to Monitor Turbidity and Total Suspended Sediments in Green Bay, WI
NASA Astrophysics Data System (ADS)
Khazaei, B.; Hamidi, S.; Hosseiny, S. M. H.; Ekhtari, N.
2017-12-01
Fox River is a major source of land-based pollutants, nutrients, and sediment that flows into the southern Green Bay (GB). GB supplies one-third of the total nutrient loading to Lake Michigan. This can play a significant role in the biological functioning of the Bay and development of managerial scenarios. To name a few, it can degrade the quality of the aquatic life, add to the costs for treatment processes, and reduce coastal quality. Water quality evaluation is a time consuming and costly process. Spaceborne imagery data provides a cheap and valuable source of information as an alternative for field monitoring of the water resources. Sediment is an optically active variable; hence; remote sensing techniques can be utilized to estimate Total Suspended Sediments (TSS) and Turbidity (TU) of water. In this study, we developed relationships between remote sensing imagery data with daily in situ measurements of TSS and TU in the summers of 2011 to 2014. Surface reflectance (SR) values obtained from Band 1 of MYD09GQ dataset-a level 2 product of MODerate Resolution Imaging Spectroradiometer (MODIS). This band covers SR between 620 and 670nm, in which, the wavelength is sensitive to mineral suspended matters most. After elimination of days with cloud contamination, 118 pairs of data remained for analysis. Several possible functions were tested and exponential function was the best estimator of the SR-TSS and SR-TU relationships with R2 values of 0.8269 and 0.8688, respectively. We then used 2014 data to validate the proposed functions. The model was able to estimate TSS and TU with NRMSE values of 0.36 and 0.30. It indicates that the model can be well-applied to predict TSS and TU within a reasonable margin of error. Then, equations were used to map the spatiotemporal dynamics of sediment in GB. Area of the plume ranges between 12 to 180 km2 while 50% of the time the area of the turbid plume is more than 106 km2. Expectedly, the concentration of sediment is much higher near the Fox River mouth. It suggests that the main source of sediment in the southern GB is river discharge, even though other factors such as wind driven wave, gyres, and circulation affect the TSS concentration. The proposed approach can be extended to other coastal regions of the Great Lakes and provides a framework to study pollution transportation in coastal areas.
Youyou Tu: significance of winning the 2015 Nobel Prize in Physiology or Medicine.
Liu, Wenxiu; Liu, Yue
2016-02-01
Youyou Tu, a female scientist at the China Academy of Traditional Chinese Medicine in Beijing, is the first Chinese winner of the Nobel Prize in Physiology or Medicine. Based on the study of recipes which had been used for thousands of years to treat fever, Tu's group discovered that the plant artemesia annua, sweet wormwood, showed substantial inhibition of rodent malaria parasites. Her achievement and experience have inspired other researchers and emphasized the development of traditional Chinese medicine. Her award has led to a heated discussion about scientific research investment, fair treatment of research staff, and intellectual property right (IPR) protection in China.
Nanjyo, S
1994-09-01
In order to evaluate left ventricular regional wall motion and regional myocardial perfusion, 99mTc-HSAD multigated cardiac blood pool emission computed tomography (cardiac pool SPECT) and 201Tl myocardial SPECT (Tl) were performed on 12 patients with acute myocardial infarction (AMI), 6 patients had treated with only thrombolysis in group I and 6 patients had treated with thrombolysis and selective PTCA in group II, 17 patients with old myocardial infarction (OMI) in group III and 5 normal volunteers (controls). The relationship between left ventricular regional wall motion and regional myocardial perfusion was estimated. The relationship between % length shortening (%LS) by cardiac pool SPECT and %Tl uptake (%TU) was good (r = 0.820) in group III. The value for %TU in the segments of akinesia was low (35%) and in the those of severe hypokinesia was higher (48%). In all phases, two groups showed significant relationships between %LS and %TU in group I and II. The %TU was unchanged in the akinetic segment, the %LS changed 30% in group I and the %LS changed to 49% in group II. If the %TU is more than 50% (AMI) or 40% (OMI), we would observe viable muscle. The combination of Tl and cardiac pool SPECT are useful for evaluating myocardial viability in the patients with AMI.
Roth, M. Y.; Dudley, R. E.; Hull, L.; Leung, A.; Christenson, P.; Wang, C.; Swerdloff, R.; Amory, J. K.
2014-01-01
Summary Oral testosterone undecanoate (TU) is used to treat testosterone deficiency; however, oral TU treatment elevates dihydrotestosterone (DHT), which may be associated with an increased risk of acne, male pattern baldness and prostate hyperplasia. Co-administration of 5α-reductase inhibitors with other formulations of oral testosterone suppresses DHT production and increases serum testosterone. We hypothesized that finasteride would increase serum testosterone and lower DHT during treatment with oral TU. Therefore, we studied the steady-state pharmacokinetics of oral TU, 200 mg equivalents of testosterone twice daily for 7 days, alone and with finasteride 0.5 and 1.0 mg po twice daily in an open-label, three-way crossover study in 11 young men with experimentally induced hypogonadism. On the seventh day of each dosing period, serum testosterone, DHT and oestradiol were measured at baseline and 1, 2, 4, 8, 12, 13, 14, 16, 20 and 24 h after the morning dose. Serum testosterone and DHT were significantly increased into and above their normal ranges similarly by all three treatments. Co-administration of finasteride at 0.5 and 1.0 mg po twice daily had no significant effect on either serum testosterone or DHT. Oral TU differs from other formulations of oral testosterone in its response to concomitant inhibition of 5α-reductase, perhaps because of its unique lymphatic route of absorption. PMID:20969601
We incorporate the recently developed Regional Atmospheric Chemistry Mechanism (version 2, RACM2) into the Community Multiscale Air Quality modeling system for comparison with the existing 2005 Carbon Bond mechanism with updated toluene chemistry (CB05TU). Compared to CB05TU, RAC...
Faced with Returnees, I Am Very Confident
ERIC Educational Resources Information Center
Song, Xiao; Yan, Long
2004-01-01
This article is an interview with Tu Hui regarding the relative merits of "returnees" and "indigens". Tu Hui is currently chief products inspector at the Anyi Software company and one of the many indigens engaged in Information Technology. In this article, he states that, "the weakness of the indigens sometimes lies in…
CCD Photometry of 967 Helionape, 3415 Danby, (85275) 1994 LY, 2007 DT103, and 2007 TU24
NASA Astrophysics Data System (ADS)
Apostolovska, Gordana; Ivanova, Violeta; Kostov, Andon
2009-01-01
The R-band lightcurves of asteroids 967 Helionape, 3415 Danby, (85275) 1994 LY, 2007 DT103 and 2007 TU24 are presented. The observations were obtained at the Bulgarian National Astronomical Observatory Rozhen (MPC Code 071) from 2007 August through 2008 February.
2013-05-01
N A E P -Q A S co rin g S p ecial S tu d y F Y 0 5 — D R A F T REPORT DOCUMENTATION PAGE Form...Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std. Z39.18 iv N A E P -Q A S co rin g S p ecial S tu d y F Y 0 5 — D R A F T...admissions. 3 N A E P -Q A S co rin g S p ecial S tu d y F Y 0 5 — D R A F T Method
Stability, Higgs boson mass, and new physics.
Branchina, Vincenzo; Messina, Emanuele
2013-12-13
Assuming that the particle with mass ∼126 GeV discovered at LHC is the standard model Higgs boson, we find that the stability of the electroweak (EW) vacuum strongly depends on new physics interaction at the Planck scale MP, despite of the fact that they are higher-dimensional interactions, apparently suppressed by inverse powers of MP. In particular, for the present experimental values of the top and Higgs boson masses, if τ is the lifetime of the EW vacuum, new physics can turn τ from τ≫TU to τ≪TU, where TU is the age of the Universe, thus, weakening the conclusions of the so called metastability scenario.
ERIC Educational Resources Information Center
Shen, Xiao-nan
This study explores the relationship between question intonation patterns in French using dislocated questions and question-focus (Q- focus). A dislocated question is defined as an interrogative sentence whose sequence is interrupted by the topicalization of a constituent at the left ("Toi, tu viens?"), at the right (Tu viens,…
Evaluation of the Sustainable Development Graduation Track at Delft University of Technology
ERIC Educational Resources Information Center
De Werk, G.; Kamp, L. M.
2008-01-01
This paper evaluates the sustainable development graduation track at TU Delft. This track can be followed by all students of TU Delft. It consists of an interdisciplinary colloquium "Technology in Sustainable Development", 300 h of self-chosen courses on sustainable development and a graduation project in which sustainable development is…
Teaching Tu Fu on the Night Shift.
ERIC Educational Resources Information Center
Brady, Philip
1995-01-01
Describes a teacher's unsuccessful attempt to introduce the poetry of Tu Fu, a wayward bureaucrat of the T'ang dynasty, to a class of part-time students. Uses his students' resistance to this poetry as an occasion to discuss the importance of personal responses to poetry, as opposed to "correct" academic responses. (TB)
The Impending Demise of "tu" in Montevideo, Uruguay
ERIC Educational Resources Information Center
Weyers, Joseph R.
2009-01-01
Since the early 1960s, the "tuteo" (T-T), and particularly the use of tonic "tu" with the "vos" verbal morphology (T-V) has been accepted as typical of the speech of Montevideo, Uruguay, a region generally classified as "voseante". This paper reports on the results of 117 rapid anonymous interviews conducted…
The Effects of a Multiple-Talent Teaching Program.
ERIC Educational Resources Information Center
Gordon, H. James; Shaver, James P.
1985-01-01
A study of 450 elementary students was made to examine the effects of Talents Unlimited (TU) teaching on students' productive and creative thinking scores. Results were not consistent across grade levels, nor from class to class. There seemed to be small to moderate associations between TU teaching and test scores. (Author/MT)
We employ the Community Multiscale Air Quality model to examine tropospheric sulfateproduction in the northern hemisphere using the Carbon Bond 2005 chemical mechanism withupdated toluene chemistry (CB05TU) and the Regional Atmospheric Chemistry Mechanism(RACM2) without and with ...
How EF-Tu can contribute to efficient proofreading of aa-tRNA by the ribosome
Noel, Jeffrey K.; Whitford, Paul C.
2016-01-01
It has long been recognized that the thermodynamics of mRNA–tRNA base pairing is insufficient to explain the high fidelity and efficiency of aminoacyl-tRNA (aa-tRNA) selection by the ribosome. To rationalize this apparent inconsistency, Hopfield proposed that the ribosome may improve accuracy by utilizing a multi-step kinetic proofreading mechanism. While biochemical, structural and single-molecule studies have provided a detailed characterization of aa-tRNA selection, there is a limited understanding of how the physical–chemical properties of the ribosome enable proofreading. To this end, we probe the role of EF-Tu during aa-tRNA accommodation (the proofreading step) through the use of energy landscape principles, molecular dynamics simulations and kinetic models. We find that the steric composition of EF-Tu can reduce the free-energy barrier associated with the first step of accommodation: elbow accommodation. We interpret this effect within an extended kinetic model of accommodation and show how EF-Tu can contribute to efficient and accurate proofreading. PMID:27796304
Boissinot, Sylvaine; Pichon, Elodie; Sorin, Céline; Piccini, Céline; Scheidecker, Danièle; Ziegler-Graff, Véronique; Brault, Véronique
2017-01-01
A fluorescent viral clone of the polerovirus Turnip yellows virus (TuYV) was engineered by introducing the Enhanced Green Fluorescent Protein (EGFP) sequence into the non-structural domain sequence of the readthrough protein, a minor capsid protein. The resulting recombinant virus, referred to as TuYV-RTGFP, was infectious in several plant species when delivered by agroinoculation and invaded efficiently non-inoculated leaves. As expected for poleroviruses, which infect only phloem cells, the fluorescence emitted by TuYV-RTGFP was restricted to the vasculature of infected plants. In addition, TuYV-RTGFP was aphid transmissible and enabled the observation of the initial sites of infection in the phloem after aphid probing in epidermal cells. The aphid-transmitted virus moved efficiently to leaves distant from the inoculation sites and importantly retained the EGFP sequence in the viral genome. This work reports on the first engineered member in the Luteoviridae family that can be visualized by fluorescence emission in systemic leaves of different plant species after agroinoculation or aphid transmission. PMID:28661469
Boissinot, Sylvaine; Pichon, Elodie; Sorin, Céline; Piccini, Céline; Scheidecker, Danièle; Ziegler-Graff, Véronique; Brault, Véronique
2017-06-29
A fluorescent viral clone of the polerovirus Turnip yellows virus (TuYV) was engineered by introducing the Enhanced Green Fluorescent Protein (EGFP) sequence into the non-structural domain sequence of the readthrough protein, a minor capsid protein. The resulting recombinant virus, referred to as TuYV-RT GFP , was infectious in several plant species when delivered by agroinoculation and invaded efficiently non-inoculated leaves. As expected for poleroviruses, which infect only phloem cells, the fluorescence emitted by TuYV-RT GFP was restricted to the vasculature of infected plants. In addition, TuYV-RT GFP was aphid transmissible and enabled the observation of the initial sites of infection in the phloem after aphid probing in epidermal cells. The aphid-transmitted virus moved efficiently to leaves distant from the inoculation sites and importantly retained the EGFP sequence in the viral genome. This work reports on the first engineered member in the Luteoviridae family that can be visualized by fluorescence emission in systemic leaves of different plant species after agroinoculation or aphid transmission.
Sobrino-Figueroa, Alma S; Cáceres-Martínez, Carlos; Botello, Alfonso V; Nunez-Nogueira, G
2007-08-01
The effects of Cd, Cr, Pb and their mixtures on the growth and sensitivity of the scallop Argopecten ventricosus were analyzed in this study. Cadmium showed to be more toxic metal to juveniles (96 hour median lethal concentration (LC(50)) = 0.396 mg Cd/L), followed by lead (LC(50) = 0.830 mg Pb/L) and chromium (LC(50) = 3.430 mg Cr/L). Cadmium toxicity was 8 times higher than chromium and 2 times than lead. The most toxic combination was Cd + Cr + Pb. (LC(50) = 0.302 mg/L). Based on toxic units analyses (T.U.), a synergistic effect was observed for Cr + Pb and Cd + Cr + Pb. (T.U. = 0.374; T.U. = 0.403), and antagonic effects for Cd + Cr and Cd + Pb (T.U. = 1.26; T.U. = 1.43) respectively. The level of effect (from high to low) on the growth of A. ventricosus juveniles was: Cd > Cd + Cr + Pb > Cr > Pb. The EC(50) (metal concentration where a reduction of 50% growing rate is observed) obtained were: Cd = 0.018 mg/L, Cd + Cr + Pb = 0.104 mg/L, Cr = 0.51 mg/L and Pb = 4.21 mg/L. These results suggest that A. ventricosus juveniles are more sensitive to these metals in comparison to other juveniles from other bivalve species (e.g., A. irradians, Mytillus edulis, Crassostrea virginica).
BnSGS3 Has Differential Effects on the Accumulation of CMV, ORMV and TuMV in Oilseed Rape
Chen, Quan; Wang, Jie; Hou, Mingsheng; Liu, Shengyi; Huang, Junyan; Cai, Li
2015-01-01
Virus diseases greatly affect oilseed rape (Brassica napus) production. Investigating antiviral genes may lead to the development of disease-resistant varieties of oilseed rape. In this study, we examined the effects of the suppressor of gene silencing 3 in Brassica napus (BnSGS3, a putative antiviral gene) with different genus viruses by constructing BnSGS3-overexpressing (BnSGS3-Ov) and BnSGS3-silenced (BnSGS3-Si) oilseed rape (cv. Zhongshuang No. 6) plants. These three viruses are Oilseed rape mosaic virus (ORMV), Turnip mosaic virus (TuMV) and Cucumber mosaic virus (CMV). The native BnSGS3 expressed in all examined tissues with the highest expression in siliques. All three viruses induced BnSGS3 expression, but ORMV induced a dramatic increase in the BnSGS3-Ov plants, followed by TuMV and CMV. Upon inoculation with three different viruses, transcript abundance of BnSGS3 gene follows: BnSGS3-Ov > non-transgenic plants > BnSGS3-Si. The accumulation quantities of ORMV and TuMV exhibited a similar trend. However, CMV accumulation showed an opposite trend where virus accumulations were negatively correlated with BnSGS3 expression. The results suggest that BnSGS3 selectively inhibits CMV accumulation but promotes ORMV and TuMV accumulation. BnSGS3 should be used in different ways (up- and down-regulation) for breeding virus-resistant oilseed rape varieties. PMID:26225990
Misro, Man M; Chaki, Shankar P; Kaushik, Mahesh C; Nandan, Deoki
2009-06-01
The study was conducted to test the potential of using dienogest (DNG) plus testosterone undecanoate (TU) in rats for development of a once-a-month injectable male hormonal contraceptive. Dose selection studies were initiated with administration of DNG in three different doses of 20, 30 and 40 mg/kg body weight (bw) per week plus TU 25 mg/kg bw once in every 6 weeks. Status of spermatogenesis and sperm count in epididymis was evaluated. The frequency of DNG intervention was later extended to every 2- and 4-week intervals. Mating studies, toxicity and reversibility of spermatogenesis following stoppage of treatment were carried out with DNG 40 mg/kg bw at 4-week intervals. Complete arrest of spermatogenesis was observed after 60 days of treatment at all doses of DNG (20, 30 and 40 mg/kg bw per week)+TU. However, weights of testis and accessory sex organs (epididymis, prostate and seminal vesicle) declined significantly 60 days post treatment compared to vehicle-treated controls. Epididymis in the treated animals was completely devoid of sperm. When the frequency of DNG injection (20 mg/kg bw) was extended to once every 15 days, a few immotile and decapitated sperm were observed in the epididymis. With TU treatment unchanged, animals receiving DNG (40 mg/kg bw) once either every 2- or 4-week intervals demonstrated good and uniform arrest of spermatogenesis. DNG 40 mg/kg per 4 weeks+TU also demonstrated a significant rise in germ cell apoptosis in the seminiferous epithelium. There was no significant increase in the serum high-density lipoprotein and low-density lipoprotein levels at the end of 120 days of treatment. Following withdrawal of treatment after 60 or 120 days, qualitative restoration of spermatogenesis was rapid in the former compared to the latter. Dienogest plus TU has the potential for development as a monthly injectable showing reversible hormonal male contraception with good efficacy.
Peterson, Mark E; Guterl, Jade N; Rishniw, Mark; Broome, Michael R
2016-07-01
Thyroid scintigraphy is commonly used for evaluation of cats with hyperthyroidism, with the thyroid-to-salivary ratio (T/S) being the most common method to quantify the degree of thyroid activity and disease. Calculation of thyroid-to-background ratios (T/B) or percent thyroidal uptake of (99m) TcO(-) 4 (TcTU) has only been reported in a few studies. The purpose of this prospective, cross-sectional study was to evaluate a number of quantitative scintigraphic indices as diagnostic tests for hyperthyroidism, including the T/S, three different T/B, TcTU, and estimated thyroid volume. Of 524 cats referred to our clinic for evaluation of suspected hyperthyroidism, the diagnosis was confirmed (n = 504) or excluded (n = 20) based on results of a serum thyroid panel consisting of thyroxine (T4 ), triiodothyronine (T3 ), free T4 (fT4 ), and thyroid-stimulating hormone (TSH) concentrations. In the hyperthyroid cats, median values for TcTU, T/S, and three T/B ratios were all significantly higher (P < 0.001) than values in euthyroid suspect cats or clinically normal cats. All scintigraphic parameters were relatively sensitive and specific as diagnostic tests for hyperthyroidism, but the T/S ratio had the highest test accuracy. The T/S ratio correlated strongly with the TcTU (r = 0.85). However, the TcTU had a higher and more significant correlation (P < 0.01) with serum T4 (r = 0.76 vs. 0.64), T3 (r = 0.77 vs. 0.64), and estimated thyroid volume (r = 0.62 vs. 0.38). Overall, calculation of TcTU is an accurate diagnostic test, but also appears to be the best parameter to predict the functional volume and metabolic activity of the feline adenomatous thyroid gland. © 2016 American College of Veterinary Radiology.
Hasenbein, Simone; Lawler, Sharon P; Geist, Juergen; Connon, Richard E
2015-05-01
Aquatic communities are often subject to complex contaminant mixtures, usually at sublethal concentrations, that can cause long-term detrimental effects. Chemicals within mixtures can effectively interact, resulting in synergism, antagonism or additivity. We investigated the tertiary mixture effects of two pyrethroids, lambda-cyhalothrin and permethrin, and the organophosphate chlorpyrifos, evaluating sublethal endpoints; immobility and growth, on Chironomus dilutus in 10-day exposures. We utilized a toxic units (TU) approach, based on median lethal concentrations (LC50) for each compound. The concepts of independent action and concentration addition were used to compare predicted mixture toxicity to observed mixture toxicity. Increased immobility resulted from mixture concentrations ≥1 TU (7.45 ng/L lambda-cyhalothrin × 24.90 ng/L permethrin × 129.70 ng/L chlorpyrifos), and single pesticides concentrations ≥0.25 TU (5.50 ng/L lambda-cyhalothrin, 24.23 ng/L permethrin, 90.92 ng/L chlorpyrifos, respectively). Growth was inhibited by pesticide mixtures ≥0.125 TU (1.04 ng/L lambda-cyhalothrin × 3.15 ng/L permethrin × 15.47 ng/L chlorpyrifos), and singly by lambda-cyhalothrin ≥0.25 TU (5.50 ng/L), and permethrin ≥0.167 TU (18.21 ng/L). The no observed effect concentrations (NOEC) for immobility and growth, for both mixture and single-pyrethroid exposure, were up to 8.0 and 12.0 times respectively lower than the corresponding NOEC for survival. The median effective concentrations (EC50) for growth (mixture and single-pyrethroid exposure) were up to 7.0 times lower than the respective LC50. This study reinforces that the integration of sublethal endpoints in monitoring efforts is powerful in discerning toxic effects that would otherwise be missed by solely utilizing traditional toxicity assessments.
Conformational effect of dicyclo-hexano-18-crown-6 on isotopic fractionation of zinc: DFT approach
DOE Office of Scientific and Technical Information (OSTI.GOV)
Boda, A.; Singha Deb, A. K.; Ali, Sk. M.
2014-04-24
Generalized gradient approximated BP86 density functional employing triple zeta valence plus polarization (TZVP) basis set has been used to compute the reduced partition function ratio and isotopic separation factor for zinc isotopes. The isotopic separation factor was found to be in good agreement with the experimental results. The isotopic separation factor was found to depend on the conformation of the crown ether ligand. The trans-trans conformation shows the highest fractionation compared to cis-cis conformer. The present theoretical results can thus be used to plan the isotope separation experiments.
Mirzaei, Reza; Saei, Azad; Torkashvand, Fatemeh; Azarian, Bahareh; Jalili, Ahmad; Noorbakhsh, Farshid; Vaziri, Behrouz; Hadjati, Jamshid
2016-08-01
Dendritic cells (DCs) are potent antigen-presenting cells (APCs) that can promote antitumor immunity when pulsed with tumor antigens and then matured by stimulatory agents. Despite apparent progress in DC-based cancer immunotherapy, some discrepancies were reported in generating potent DCs. Listeria monocytogenes as an intracellular microorganism is able to effectively activate DCs through engaging pattern-recognition receptors (PRRs). This study aimed to find the most potent components derived from L. monocytogenes inducing DC maturation. The preliminary results demonstrated that the ability of protein components is higher than DNA components to promote DC maturation and activation. Protein lysate fractionation demonstrated that fraction 2 HIC (obtained by hydrophobic interaction chromatography) was able to efficiently mature DCs. F2HIC-matured DCs are able to induce allogeneic CD8(+) T cells proliferation better than LPS-matured DCs and induce IFN-γ producing CD8(+) T cells. Mass spectrometry results showed that F2HIC contains 109 proteins. Based on the bioinformatics analysis for these 109 proteins, elongation factor Tu (EF-Tu) could be considered as a PRR ligand for stimulating DC maturation.
Proteomic Investigation of Aphid Honeydew Reveals an Unexpected Diversity of Proteins
Haubruge, Eric; Hance, Thierry; Thonart, Philippe; De Pauw, Edwin; Francis, Frédéric
2013-01-01
Aphids feed on the phloem sap of plants, and are the most common honeydew-producing insects. While aphid honeydew is primarily considered to comprise sugars and amino acids, its protein diversity has yet to be documented. Here, we report on the investigation of the honeydew proteome from the pea aphid Acyrthosiphon pisum. Using a two-Dimensional Differential in-Gel Electrophoresis (2D-Dige) approach, more than 140 spots were isolated, demonstrating that aphid honeydew also represents a diverse source of proteins. About 66% of the isolated spots were identified through mass spectrometry analysis, revealing that the protein diversity of aphid honeydew originates from several organisms (i.e. the host aphid and its microbiota, including endosymbiotic bacteria and gut flora). Interestingly, our experiments also allowed to identify some proteins like chaperonin, GroEL and Dnak chaperones, elongation factor Tu (EF-Tu), and flagellin that might act as mediators in the plant-aphid interaction. In addition to providing the first aphid honeydew proteome analysis, we propose to reconsider the importance of this substance, mainly acknowledged to be a waste product, from the aphid ecology perspective. PMID:24086359
Federal Register 2010, 2011, 2012, 2013, 2014
2013-09-18
... detect and correct discrepancies of the battery wiring installation inside the TU, which could result in... TUs revealed battery wiring installation discrepancies inside the TU that may result in an electrical short. The AAIB noted that in case of an electrical short, the ELT battery could provide the energy for...
"The Et Tu Brute Complex" Compulsive Self Betrayal
ERIC Educational Resources Information Center
Antus, Robert Lawrence
2006-01-01
In this article, the author discusses "The Et Tu Brute Complex." More specifically, this phenomenon occurs when a person, instead of supporting and befriending himself, orally condemns himself in front of other people and becomes his own worst enemy. This is a form of compulsive self-hatred. Most often, the victim of this complex is unaware of the…
“Impact of CB6 and CB05TU chemical mechanisms on air quality”
“Impacts of CB6 and CB05TU chemical mechanisms on air quality”In this study, we incorporate the newly developed Carbon Bond chemical mechanism (CB6) into the Community Multiscale Air Quality modeling system (CMAQv5.0.1) and perform air quality model simulations with the CB6 and t...
Marcinkiewicz, C; Gajko, A; Gałasiński, W
1991-01-01
Elongation factor EF-1 from Guerin epithelioma was separated into two subunit forms EF-1A and EF-1B by chromatography in the presence of 25% glycerol, successively on CM-Sephadex and DEAE-Sephadex. It was shown that EF-1A is a thermolabile, single polypeptide which catalyses the binding of aminoacyl-tRNA to ribosomes, similarly as eukaryotic EF-1 alpha or prokaryotic EF-Tu. EF-1B was characterized as a complex composed of at least two polypeptides. One of them is EF-1A, the other EF-1C, which stimulates EF-1A activity and protects this elongation factor from thermal inactivation.
Performance and Preference with Various VDT (Video Display Terminal) Phosphors
1987-04-24
Unit M\\100.001-1302. was submitted for review on 13 March 1987, approved for publication on 24 April 1987, and has been designated as Naval Submarine... designed to investigate reading fatigue, Nordqvist et al. (1986) had their subjects read texts for 15 minutes, followed by 5 minutes of performance tests...Doc, Ophthalmol. 3: 138-163. Tu-lis, T.S. (1981). An evaluation of alphanumeric, graphic , and color information displays. -_pman Factors 23: 541-550
McGivney, C L; Gough, K F; McGivney, B A; Farries, G; Hill, E W; Katz, L M
2018-06-23
Conflicting results have been reported for risk factors for recurrent laryngeal neuropathy (RLN) based on resting endoscopic evaluation and comparison of single conformation traits, with many traits correlated to one another. To simplify identification of signalment and conformation traits (i.e. variables) associated with RLN cases and controls diagnosed with exercising overground endoscopy (OGE) using exploratory factor analysis (EFA). Prospective cohort. Pearson's rank correlation was used to establish significance and association between variables collected from n = 188 Thoroughbreds from one stable by observers blinded to OGE results. Exploratory factor analysis was conducted on 9 variables for cases and controls; common elements between variables developed a factor, with variables grouped into 3 factors for cases and controls, respectively. Correlation (loading) between each variable and factor was calculated to rank relationships between variables and cases/controls, with factors retrospectively named based on their underlying correlations with variables. Numerous inter-correlations were present between variables. Most strongly correlated in cases were wither height with body weight (r = 0.70) and ventral neck length (r = 0.68) and in controls body weight with rostral neck circumference (r = 0.58). Wither height (r = 0.61) significantly loaded the top-ranked factor for cases ('height RLN '), explaining 25% of conformational variance. Ventral neck length (r = 0.69) and age (r = 0.57) significantly loaded the second-ranked factor for cases ('neck length RLN '), explaining 16% of conformational variance. Rostral neck circumference (r = 0.86) and body weight (r = 0.6) significantly loaded the top-ranked factor for controls ('body size CON '), explaining 19% of the variance. Wither height (r = 0.84) significantly loaded the second-ranked factor for controls ('height CON '), explaining 13% of the variance. Horses had not reached skeletal maturity. Exploratory factor analysis allowed weightings to be determined for each variable. Wither height was the predominant conformational feature associated with RLN. Exploratory factor analysis confirms aggregated conformational differences exist between RLN cases and controls, suitable for future evaluations. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Impact of population growth and population ethics on climate change mitigation policy
Scovronick, Noah; Budolfson, Mark B.; Dennig, Francis; Fleurbaey, Marc; Siebert, Asher; Socolow, Robert H.; Spears, Dean; Wagner, Fabian
2017-01-01
Future population growth is uncertain and matters for climate policy: higher growth entails more emissions and means more people will be vulnerable to climate-related impacts. We show that how future population is valued importantly determines mitigation decisions. Using the Dynamic Integrated Climate-Economy model, we explore two approaches to valuing population: a discounted version of total utilitarianism (TU), which considers total wellbeing and is standard in social cost of carbon dioxide (SCC) models, and of average utilitarianism (AU), which ignores population size and sums only each time period’s discounted average wellbeing. Under both approaches, as population increases the SCC increases, but optimal peak temperature decreases. The effect is larger under TU, because it responds to the fact that a larger population means climate change hurts more people: for example, in 2025, assuming the United Nations (UN)-high rather than UN-low population scenario entails an increase in the SCC of 85% under TU vs. 5% under AU. The difference in the SCC between the two population scenarios under TU is comparable to commonly debated decisions regarding time discounting. Additionally, we estimate the avoided mitigation costs implied by plausible reductions in population growth, finding that large near-term savings ($billions annually) occur under TU; savings under AU emerge in the more distant future. These savings are larger than spending shortfalls for human development policies that may lower fertility. Finally, we show that whether lowering population growth entails overall improvements in wellbeing—rather than merely cost savings—again depends on the ethical approach to valuing population. PMID:29087298
Impact of population growth and population ethics on climate change mitigation policy.
Scovronick, Noah; Budolfson, Mark B; Dennig, Francis; Fleurbaey, Marc; Siebert, Asher; Socolow, Robert H; Spears, Dean; Wagner, Fabian
2017-11-14
Future population growth is uncertain and matters for climate policy: higher growth entails more emissions and means more people will be vulnerable to climate-related impacts. We show that how future population is valued importantly determines mitigation decisions. Using the Dynamic Integrated Climate-Economy model, we explore two approaches to valuing population: a discounted version of total utilitarianism (TU), which considers total wellbeing and is standard in social cost of carbon dioxide (SCC) models, and of average utilitarianism (AU), which ignores population size and sums only each time period's discounted average wellbeing. Under both approaches, as population increases the SCC increases, but optimal peak temperature decreases. The effect is larger under TU, because it responds to the fact that a larger population means climate change hurts more people: for example, in 2025, assuming the United Nations (UN)-high rather than UN-low population scenario entails an increase in the SCC of 85% under TU vs. 5% under AU. The difference in the SCC between the two population scenarios under TU is comparable to commonly debated decisions regarding time discounting. Additionally, we estimate the avoided mitigation costs implied by plausible reductions in population growth, finding that large near-term savings ($billions annually) occur under TU; savings under AU emerge in the more distant future. These savings are larger than spending shortfalls for human development policies that may lower fertility. Finally, we show that whether lowering population growth entails overall improvements in wellbeing-rather than merely cost savings-again depends on the ethical approach to valuing population. Copyright © 2017 the Author(s). Published by PNAS.
Faria-E-Silva, André L; Pfeifer, Carmem S
2017-10-01
1) to determine the moment during the redox polymerization reaction of dual cure cements at which to photo-activate the material in order to reduce the polymerization stress, and 2) to evaluate possible synergistic effects between adding chain transfer agents and delayed photo-activation. The two pastes of an experimental dual-cure material were mixed, and the polymerization kinetics of the redox phase was followed. The moment when the material reached its maximum rate of redox polymerization (MRRP) of cement was determined. The degree of conversion (DC) and maximum rates of polymerization (Rp max ) were assessed for materials where: the photoactivation immediately followed material mixing, at MRRP, 1min before and 1min after MRRP. Thio-urethane (TU) additives were synthesized and added to the cement (20% wt), which was then cured under the same conditions. The polymerization kinetics was evaluated for both cements photo-activated immediately or at MRRP, followed by measurements of polymerization stress, flexural strength (FS) and elastic modulus (EM). Knoop hardness was measured before and after ethanol storage. Photo-activating the cement at or after MRRP reduced the Rp max and the polymerization stress. Addition of TU promoted additional and more significant reduction, while not affecting the Rp max . Greater hardness loss was observed for cements with TU, but the final hardness was similar for all experimental conditions. Addition of TU slightly reduced the EM and did not affect the FS. Delayed photo-activation and addition of TU significantly reduce the polymerization stress of dual-cured cements. Copyright © 2017 Elsevier Ltd. All rights reserved.
Reactivity of Metal Oxide Sorbents for Removal of H{sub 2}S
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kwon, K.C.; Crowe, E.R.
1996-12-31
Removal of hydrogen sulfide contained in hot coal gases produced from integrated gasification combined cycle power generation systems is required to protect downstream combustion turbines from being corroded with sulfur compounds. Removal of sulfur compounds from hot coal gas products is investigated by using various metal oxide sorbents and membrane separation methods. The main requirements of these metal oxide sorbents are durability and high sulfur loading capacity during absorption-regeneration cycles. In this research, durable metal oxide sorbents were formulated. Reactivity of the formulated metal oxide sorbents with simulated coal gas mixtures was examined to search for an ideal sorbent formulationmore » with a high-sulfur loading capacity suitable for removal of hydrogen sulfide from coal gases. The main objectives of this research are to formulate durable metal oxide sorbents with high-sulfur loading capacity by a physical mixing method, to investigate reaction kinetics on the removal of sulfur compounds from coal gases at high temperature and pressure, to study reaction kinetics on the regeneration of sulfided sorbents, to identify effects of hydrogen partial pressures and moisture on equilibrium/dynamic absorption of hydrogen sulfide into formulated metal oxide sorbents as well as initial reaction rates of H{sub 2}S with formulated metal oxide sorbents, and to evaluate intraparticular diffusivity of H{sub 2}S into formulated sorbents at various reaction conditions. The metal oxide sorbents such as TU-1, TU-19, TU-24, TU-25 and TU-28 were formulated with zinc oxide powder as an active sorbent ingredient, bentonite as a binding material and titanium oxide as a supporting metal oxide.« less
Yonezawa, Yasushige
2014-05-01
The carboxyl-terminal domain (CTD) of RNA polymerase II in eukaryotes regulates mRNA processing processes by recruiting various regulation factors. A main function of the CTD relies on the heptad consensus sequence (YSPTSPS). The CTD dynamically changes its conformational state to recognize and bind different regulation factors. The dynamical conformation changes are caused by modifications, mainly phosphorylation and dephosphorylation, to the serine residues. In this study, we investigate the conformational states of the unit consensus CTD peptide with various phosphorylation patterns of the serine residues by extended ensemble simulations. The results show that the CTD without phosphorylation has a flexible disordered structure distributed between twisted and extended states, but phosphorylation tends to reduce the conformational space. It was found that phosphorylation induces a β-turn around the phosphorylated serine residue and the cis conformation of the proline residue significantly inhibits the β-turn formation. The β-turn should contribute to specific CTD binding of the different regulation factors by changing the conformation propensity combined with induced fit.
Critical analysis of world uranium resources
Hall, Susan; Coleman, Margaret
2013-01-01
The U.S. Department of Energy, Energy Information Administration (EIA) joined with the U.S. Department of the Interior, U.S. Geological Survey (USGS) to analyze the world uranium supply and demand balance. To evaluate short-term primary supply (0–15 years), the analysis focused on Reasonably Assured Resources (RAR), which are resources projected with a high degree of geologic assurance and considered to be economically feasible to mine. Such resources include uranium resources from mines currently in production as well as resources that are in the stages of feasibility or of being permitted. Sources of secondary supply for uranium, such as stockpiles and reprocessed fuel, were also examined. To evaluate long-term primary supply, estimates of uranium from unconventional and from undiscovered resources were analyzed. At 2010 rates of consumption, uranium resources identified in operating or developing mines would fuel the world nuclear fleet for about 30 years. However, projections currently predict an increase in uranium requirements tied to expansion of nuclear energy worldwide. Under a low-demand scenario, requirements through the period ending in 2035 are about 2.1 million tU. In the low demand case, uranium identified in existing and developing mines is adequate to supply requirements. However, whether or not these identified resources will be developed rapidly enough to provide an uninterrupted fuel supply to expanded nuclear facilities could not be determined. On the basis of a scenario of high demand through 2035, 2.6 million tU is required and identified resources in operating or developing mines is inadequate. Beyond 2035, when requirements could exceed resources in these developing properties, other sources will need to be developed from less well-assured resources, deposits not yet at the prefeasibility stage, resources that are currently subeconomic, secondary sources, undiscovered conventional resources, and unconventional uranium supplies. This report’s analysis of 141 mines that are operating or are being actively developed identifies 2.7 million tU of in-situ uranium resources worldwide, approximately 2.1 million tU recoverable after mining and milling losses were deducted. Sixty-four operating mines report a total of 1.4 million tU of in-situ RAR (about 1 million tU recoverable). Seventy-seven developing mines/production centers report 1.3 million tU in-situ Reasonably Assured Resources (RAR) (about 1.1 million tU recoverable), which have a reasonable chance of producing uranium within 5 years. Most of the production is projected to come from conventional underground or open pit mines as opposed to in-situ leach mines. Production capacity in operating mines is about 76,000 tU/yr, and in developing mines is estimated at greater than 52,000 tU/yr. Production capacity in operating mines should be considered a maximum as mines seldom produce up to licensed capacity due to operational difficulties. In 2010, worldwide mines operated at 70 percent of licensed capacity, and production has never exceeded 89 percent of capacity. The capacity in developing mines is not always reported. In this study 35 percent of developing mines did not report a target licensed capacity, so estimates of future capacity may be too low. The Organisation for Economic Co-operation and Development’s Nuclear Energy Agency (NEA) and International Atomic Energy Agency (IAEA) estimate an additional 1.4 million tU economically recoverable resources, beyond that identified in operating or developing mines identified in this report. As well, 0.5 million tU in subeconomic resources, and 2.3 million tU in the geologically less certain inferred category are identified worldwide. These agencies estimate 2.2 million tU in secondary sources such as government and commercial stockpiles and re-enriched uranium tails. They also estimate that unconventional uranium supplies (uraniferous phosphate and black shale deposits) may contain up to 7.6 million tU. Although unconventional resources are currently subeconomic, the improvement of extraction techniques or the production of coproducts may make extraction of uranium from these types of deposits profitable. A large undiscovered resource base is reported by these agencies, however this class of resource should be considered speculative and will require intensive exploration programs to adequately define them as mineable. These resources may all contribute to uranium supply that would fuel the world nuclear fleet well beyond that calculated in this report. Production of resources in both operating and developing uranium mines is subject to uncertainties caused by technical, legal, regulatory, and financial challenges that combined to create long timelines between deposit discovery and mine production. This analysis indicates that mine development is proceeding too slowly to fully meet requirements for an expanded nuclear power reactor fleet in the near future (to 2035), and unless adequate secondary or unconventional resources can be identified, imbalances in supply and demand may occur.
Duary, Raj Kumar; Batish, Virender Kumar; Grover, Sunita
2012-03-01
Probiotic bacteria must overcome the toxicity of bile salts secreted in the gut and adhere to the epithelial cells to enable their better colonization with extended transit time. Expression of bile salt hydrolase and other proteins on the surface of probiotic bacteria can help in better survivability and optimal functionality in the gut. Two putative Lactobacillus plantarum isolates i.e., Lp9 and Lp91 along with standard strain CSCC5276 were used. A battery of six housekeeping genes viz. gapB, dnaG, gyrA, ldhD, rpoD and 16S rRNA were evaluated by using geNorm 3.4 excel based application for normalizing the expression of bile salt hydrolase (bsh), mucus-binding protein (mub), mucus adhesion promoting protein (mapA), and elongation factor thermo unstable (EF-Tu) in Lp9 and Lp91. The maximal level of relative bsh gene expression was recorded in Lp91 with 2.89 ± 0.14, 4.57 ± 0.37 and 6.38 ± 0.19 fold increase at 2% bile salt concentration after 1, 2 and 3 h, respectively. Similarly, mub and mapA genes were maximally expressed in Lp9 at the level of 20.07 ± 1.28 and 30.92 ± 1.51 fold, when MRS was supplemented with 0.05% mucin and 1% each of bile and pancreatin (pH 6.5). However, in case of EF-Tu, the maximal expression of 42.84 ± 5.64 fold was recorded in Lp91 in the presence of mucin alone (0.05%). Hence, the expression of bsh, mub, mapA and EF-Tu could be considered as prospective biomarkers for screening of novel probiotic lactobacillus strains for optimal functionality in the gut.
USDA-ARS?s Scientific Manuscript database
Sclerotinia sclerotiorum causes serious yield losses in crops in The People’s Republic of China. Two formulations of oilseed rape seed containing the endophytic bacterium Bacillus subtilis Tu-100 were evaluated for suppression of this pathogen in field trials conducted at two independent locations....
Linking Student Engagement and Strategic Initiatives: Using NSSE Results to Inform Campus Action
ERIC Educational Resources Information Center
Doherty, Kathryn
2007-01-01
Towson University (TU) is in a period of growth in both students and facilities. To guide this growth, TU relies on its strategic plan, Towson 2010, to focus its strategic decisions through 2010. Release of the National Survey of Student Engagement (NSSE) data for 2005 coincided with a call for academic excellence and accelerated growth at Towson…
"Vous" or "tu"? Native and Non-Native Speakers of French on a Sociolinguistic Tightrope
ERIC Educational Resources Information Center
Dewaele, Jean-Marc
2004-01-01
Sociolinguistic rules governing choice of pronouns of address are notoriously difficult in French, despite the fact that the number of variants is rather limited: the more formal "vous" versus the more informal "tu." Children with French as L1 learn to use pronouns of address appropriately as part of their socialization process. The learning curve…
ERIC Educational Resources Information Center
Loomis, Michael J.
2009-01-01
This research uses the Defining Issues Test-2 (DIT-2) to investigate the cognitive moral development of college seniors in adult degree completion (ADC) programs and traditional undergraduate (TU) programs at three Council of Christian College and University institutions. Overall, TU students had significantly higher scores on the DIT-2, TU…
On-line pre-reduction of Se(VI) by thiourea for selenium speciation by hydride generation
NASA Astrophysics Data System (ADS)
Qiu, Jianhua; Wang, Qiuquan; Ma, Yuning; Yang, Limin; Huang, Benli
2006-07-01
In this study, thiourea (TU) was novelly developed as a reduction reagent for on-line pre-reduction of selenium(VI) before conventional hydride generation (HG) by KBH 4/NaOH-HCl. After TU on-line pre-reduction, the HG efficiency of Se(VI) has been greatly improved and because even higher than that of the same amount of Se(IV) obtained in the conventional HG system. The possible pre-reduction mechanism is discussed. The detection limit (DL) of selenate reaches 10 pg mL - 1 when using on-line TU pre-reduction followed by HG atomic fluorescence detection. When TU pre-reduction followed by HG is used as an interface between ion-pair high performance liquid chromatography and atomic fluorescence spectrometry, selenocystine, selenomethionine, selenite and selenate can be measured simultaneously and quantitatively. The DLs of these are 0.06, 0.08, 0.05 and 0.04 ng mL - 1 , respectively, and the relative standard deviations of 9 duplicate runs for all the 4 species are less than 5%. Furthermore, it was successfully applied to Se speciation analysis of cultured garlic samples, and validated by determination of total selenium and selenium species in certified reference material NIST 1946.
NASA Astrophysics Data System (ADS)
Wang, Sijia; Hüttmann, Gereon; Hasan, Tayyaba; Rahmanzadeh, Ramtin
2016-03-01
Light-induced inhibition of intracellular molecules holds great promise for a selective treatment of cancer and other diseases. Challenges for the targeting of intracellular proteins are the synthesis of effective photoimmuno-conjugates and their functional delivery inside living cells. In earlier studies we have shown, that photodynamic inactivation of the nuclear Ki-67 protein leads to an effective elimination of proliferating tumor cells. Here we show a selective treatment for EGFR and Ki-67 positive cancer cells after light-controlled delivery of indocyanine green (ICG) photo-immunoconjugates. The Ki-67 antibody TuBB-9, which recognizes an active state of the protein, was labeled with different ratios of ICG and encapsulated into immuno-liposomes that selectively deliver the conjugates to EGFR overexpressing cells. To overcome endosomal entrapment of the delivered agents, ovarian carcinoma cells were treated with the photosensitizer benzoporphyrin monoacid derivative (BPD) and irradiated first for endosomal escape of the TuBB-9-ICG constructs. 24 h after irradiation TuBB-9-ICG antibodies showed a relocalization from spots in the cytoplasm to the cell nucleus. A second irradiation of the delivered TuBB-9-ICG led to a significant elimination of cells after Ki-67 inactivation.
DNA-binding studies and biological activities of new nitrosubstituted acyl thioureas
NASA Astrophysics Data System (ADS)
Tahir, Shaista; Badshah, Amin; Hussain, Raja Azadar; Tahir, Muhammad Nawaz; Tabassum, Saira; Patujo, Jahangir Ali; Rauf, Muhammad Khawar
2015-11-01
Four new nitrosubstituted acylthioureas i.e. 1-acetyl-3-(4-nitrophenyl)thiourea (TU1), 1-acetyl-3-(2-methyl-4-nitrophenyl)thiourea (TU2), 1-acetyl-3-(2-methoxy-4-nitrophenyl)thiourea (TU3) and 1-acetyl-3-(4-chloro-3-nitrophenyl)thiourea (TU4) have been synthesized and characterized (by C13 and H1 nuclear magnetic resonance, Fourier transform infrared spectroscopy and single crystal X-ray diffraction). As a preliminary investigation of the anti-cancer potencies of the said compounds, DNA interaction studies have been carried out using cyclic voltammetry and UV-vis spectroscopy along with verification from computational studies. The drug-DNA binding constants are found to be in the order, KTU3 9.04 × 106 M-1 > KTU4 8.57 × 106 M-1 > KTU2 6.05 × 106 M-1 > KTU1 1.16 × 106 M-1. Furthermore, the antioxidant, cytotoxic, antibacterial and antifungal activities have been carried out against DPPH (1,1-diphenyl-2-dipicrylhydrazyl), Brine shrimp eggs, gram positive (Micrococcus luteus, Staphylococcus aureus) and gram negative (Bordetella bronchiseptica, Salmonella typhimurium, Enterobacter aerogens) and fungal cultures (Aspergillus fumigatus, Mucor species, Aspergillus niger, Aspergillus flavus) respectively.
NASA Astrophysics Data System (ADS)
Kostyuk, A. G.; Volokhovskaya, O. A.
2017-01-01
The work is dedicated to the study of vibration activity of double-span rotor of turbine unit (TU) consisting of a high-pressure rotor and a rotor of medium-low pressure rotor combined with it (HPR—MLPR system) at the lowest critical rotational frequencies at rundown. When using the design model of the system, it was assumed that the rotors were installed on anisotropic elastic-damper supports, tied among themselves by a rigid clutch, and having the initial curvature (nonremovable initial deflection) and the residual unbalances in both spans. Two types of bearings were considered-elliptical and six-shoe segmental bearings. It was believed that the initial deflection during operation or as a result of noncompliance of start-up conditions initially gets only HPR and the axis shape of unloaded HPR is known and it is a flat curve. The resultant curve of nonremovable deflection of the HPR-MLPR system occurring after installing the shafting into the bearings was also considered flat and located in the same plane as the initial deflection of HPR. The cases of additional presence with the rotors of concentrated residual unbalances in the middle of each span are considered. The case of availability with both rotors of the shafting antisymmetric point unbalances on each of the spans was not considered in this work. The values of each of the factors of vibration activity (of the initial deflection of HPR and residual unbalances of both rotors) were chosen to be equal to the maximum permissible established by the active in the practice of TU operation limitations on the maximum values of the initial deflection of thermally unstable rotor and its residual unbalances. The influence of location of residual unbalances in relation to the initial deflection curve of HPR-MLPR system on the total amplitudes of transient vibrations caused by both excitation factors in the reference points of the system at TU rundown was investigated. It was established that, at the unfavorable relations between directions of curvature of the rotors of HPR-MLPR system and their residual unbalances with segmental bearings, touching in the diaphragm seals in the middle of HPR span is possible.
Karlsson, Mattias; Scherbak, Nikolai; Khalaf, Hazem; Olsson, Per-Erik; Jass, Jana
2012-11-01
Lactobacillus rhamnosus GR-1 is a probiotic bacterium used to maintain urogenital health. The putative mechanism for its probiotic effect is by modulating the host immunity. Urinary tract infections (UTI) are often caused by uropathogenic Escherichia coli that frequently evade or suppress immune responses in the bladder and can target pathways, including nuclear factor-kappaB (NF-κB). We evaluated the role of L. rhamnosus GR-1 on NF-κB activation in E. coli-stimulated bladder cells. Viable L. rhamnosus GR-1 was found to potentiate NF-κB activity in E. coli-stimulated T24 bladder cells, whereas heat-killed lactobacilli demonstrated a marginal increase in NF-κB activity. Surface components released by trypsin- or LiCl treatment, or the resultant heat-killed shaved lactobacilli, had no effect on NF-κB activity. Isolation of released products from L. rhamnosus GR-1 demonstrated that the induction of NF-κB activity was owing to released product(s) with a relatively large native size. Several putative immunomodulatory proteins were identified, namely GroEL, elongation factor Tu and NLP/P60. GroEL and elongation factor Tu have previously been shown to elicit immune responses from human cells. Isolating and using immune-augmenting substances produced by lactobacilli is a novel strategy for the prevention or treatment of UTI caused by immune-evading E. coli. © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.
Dunoyer, P; Thomas, C; Harrison, S; Revers, F; Maule, A
2004-03-01
We have identified a cellular factor that interacts with the virus genome-linked proteins (VPgs) of a diverse range of potyviruses. The factor, called Potyvirus VPg-interacting protein (PVIP), is a plant-specific protein with homologues in all the species examined, i.e., pea, Arabidopsis thaliana, and Nicotiana benthamiana. The sequence of PVIP does not identify a specific function, although the existence of a "PHD finger" domain may implicate the protein in transcriptional control through chromatin remodeling. Deletion analysis using the yeast two-hybrid system showed that the determinants of the interaction lay close to the N terminus of VPg; indeed, the N-terminal 16 amino acids were shown to be both necessary and sufficient for the interaction with at least one PVIP protein. From a sequence comparison of different potyvirus VPg proteins, a specific amino acid at position 12 was directly implicated in the interaction. This part of VPg is distinct from regions associated with other functional roles of VPg. Through mutation of Turnip mosaic virus (TuMV) at VPg position 12, we showed that the interaction with PVIP affected systemic symptoms in infected plants. This resulted from reduced cell-to-cell and systemic movement more than reduced virus replication, as visualized by comparing green fluorescent protein-tagged wild-type and mutant viruses. Furthermore, by using RNA interference of PVIP in Arabidopsis, we showed that reduced expression of PVIP genes reduced susceptibility to TuMV infection. We conclude that PVIP functions as an ancillary factor to support potyvirus movement in plants.
Horiuchi, Takayuki; Taoka, Masato; Isobe, Toshiaki; Komano, Teruya; Inouye, Sumiko
2002-07-26
Two genes, fruA and csgA, encoding a putative transcription factor and C-factor, respectively, are essential for fruiting body formation of Myxococcus xanthus. To investigate the role of fruA and csgA genes in developmental gene expression, developing cells as well as vegetative cells of M. xanthus wild-type, fruA::Tc, and csgA731 strains were pulse-labeled with [(35)S]methionine, and the whole cell proteins were analyzed using two-dimensional immobilized pH gradient/SDS-PAGE. Differences in protein synthesis patterns among more than 700 protein spots were detected during development of the three strains. Fourteen proteins showing distinctly different expression patterns in mutant cells were analyzed in more detail. Five of the 14 proteins were identified as elongation factor Tu (EF-Tu), Dru, DofA, FruA, and protein S by immunoblot analysis and mass spectroscopy. A gene encoding DofA was cloned and sequenced. Although both fruA and csgA genes regulate early development of M. xanthus, they were found to differently regulate expression of several developmental genes. The production of six proteins, including DofA and protein S, was dependent on fruA, whereas the production of two proteins was dependent on csgA, and one protein was dependent on both fruA and csgA. To explain the present findings, a new model was presented in which different levels of FruA phosphorylation may distinctively regulate the expression of two groups of developmental genes.
Yu, Feng; Liu, Wei; Gong, Xiao Rong; Zhou, Yi Bo; Lin, Ying
2018-03-01
To investigate the effect of Procyanidins (OPCs) on the autophagy of laryngeal cancer cell line TU686 and to explore the effect of OPCs on the chemosensitivity of laryngeal cancer cells to DDP in terms of autophagy and apoptosis. CCK-8 was used to detected the effect of different concentrations of OPC and DDP on TU686 cell viability. Experimental grouping: Both kinds of cells were divided into CON group, DDP group, OPC group and MIX group. Annexin-V-FITC/PI double staining of flow cytometry was used to detect the effect of each experimental group on the apoptosis. Cell immunofluorescence staining was used to detect the formation of autophagy. Western blot was used to detect the expression of autophagy-related and apoptosis-related proteins. Autophagy inhibitors (3-MA) were used to study the effect of autophagy on apoptosis. The results of CCK-8 showed that TU686 cells were inhibited by OPC and DDP in a concentration-dependent manner for 24 hours. LC3-Ⅱ protein staining showed that compared with CON group, DDP group and OPC group, MIX group significantly induced autophagy formation in TU686 cells ( P <0.05). Flow cytometry showed that compared with CON group, apoptosis of TU686 cells was induced in DDP group, OPC group and MIX group. And the effect of MIX on apoptosis was significantly higher than that of OPC and DDP groups ( P <0.05). After pretreatment with 3-MA, the apoptotic effect of OPC group and MIX group on TU686 cells was significantly decreased ( P <0.05). Western blot results showed that the expression of LC3-Ⅱ and Caspase-3 in DDP, OPC and MIX groups was significantly higher than that in CON group ( P <0.05). In MIX group, the expression of LC3-Ⅱ and Caspase-3 also had significant difference ( P <0.05) compared with single drug group. After using 3-MA to inhibit autophagy, the expression of LC3-Ⅱ was significantly decreased ( P <0.05), and the expression of Caspase-3 was decreased along with LC3-Ⅱ, but the decrease of Caspase-3 expression was only significant in OPC and MIX group ( P <0.05). OPC can induce autophagy in laryngeal carcinoma TU686 cells and promote its apoptosis, which in turn enhances sensitivity of laryngeal cancer cells to cisplatin chemotherapy. Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.
Response to 'pervasive sequence patents cover the entire human genome' - authors' reply.
Rosenfeld, Jeffrey; Mason, Christopher
2014-01-01
An author reply to the Letter to the Editor from Tu et al. regarding Pervasive sequence patents cover the entire human genome by J Rosenfeld and C Mason. Genome Med 2013, 5:27. See related Correspondence by Rosenfeld and Mason, http://genomemedicine.com/content/5/3/27, and related letter by Tu et al., http://genomemedicine.com/content/6/2/14.
NASA Technical Reports Server (NTRS)
Flegel, Ashlie Brynn; Giel, Paul W.; Welch, Gerard E.
2014-01-01
The effects of inlet turbulence intensity on the aerodynamic performance of a variable speed power turbine blade are examined over large incidence and Reynolds number ranges. Both high and low turbulence studies were conducted in the NASA Glenn Research Center Transonic Turbine Blade Cascade Facility. The purpose of the low inlet turbulence study was to examine the transitional flow effects that are anticipated at cruise Reynolds numbers. The high turbulence study extends this to LPT-relevant turbulence levels while perhaps sacrificing transitional flow effects. Downstream total pressure and exit angle data were acquired for ten incidence angles ranging from +15.8 to 51.0. For each incidence angle, data were obtained at five flow conditions with the exit Reynolds number ranging from 2.12105 to 2.12106 and at a design exit Mach number of 0.72. In order to achieve the lowest Reynolds number, the exit Mach number was reduced to 0.35 due to facility constraints. The inlet turbulence intensity, Tu, was measured using a single-wire hotwire located 0.415 axial-chord upstream of the blade row. The inlet turbulence levels ranged from 0.25 - 0.4 for the low Tu tests and 8- 15 for the high Tu study. Tu measurements were also made farther upstream so that turbulence decay rates could be calculated as needed for computational inlet boundary conditions. Downstream flow field measurements were obtained using a pneumatic five-hole pitchyaw probe located in a survey plane 7 axial chord aft of the blade trailing edge and covering three blade passages. Blade and endwall static pressures were acquired for each flow condition as well. The blade loading data show that the suction surface separation that was evident at many of the low Tu conditions has been eliminated. At the extreme positive and negative incidence angles, the data show substantial differences in the exit flow field. These differences are attributable to both the higher inlet Tu directly and to the thinner inlet endwall boundary layer that the turbulence grid imposes.
Yim, Jin Hee; Kim, Kyoung W; Kim, Sang D
2006-11-02
In this study, the effect of hardness on the combined outcome of metal mixtures was investigated using Daphnia magna. The toxic unit (TU) was calculated using modified LC(50) values based on the hardness (i.e., LC(50-soft) and LC(50-hard)). From a bioassay test, the degree of sensitivity to hardness on the toxicity changes was in the order: Cd
1987-09-01
from studies of met expectations: (1) The decision to participate or withdraw from an organization may be looked upon as a process of balancing ...was included in this study tu provide some balance and because a large number of Air Force contract specialists are employed at Aeronautical Systems...thirteen days of sick leave per year. Vacation or leave is accrued constantly with an updated balance provided at the end of each pay period
Comparison of twinning rates for villages in Makarska region, Croatia.
Sunde, Jadranka; Borić, Matija; Urlić, Natalija; Urlić, Lara
2013-11-01
A detailed database on the genealogy of the Makarska region in Croatia has been created. The twinning rate for three villages in the region (Podgora, Tučepi and Brela) were analysed over the period 1870 to 1940 and factors such as mother's age and birth order are discussed. Of the three villages, Podgora was identified as having the highest twinning rate and consequently records for Podgora were examined further to include almost 400 years of historical data (from 1621 to 1950).
Jandric, Ivan; Vrcic, Hrvoje; Jandric Balen, Marica; Kolenc, Danijela; Brcic, Luka; Radic, Bozo; Drmic, Domagoj; Seiwerth, Sven; Sikiric, Predrag
2013-03-12
Since an originally anti-ulcer stable gastric pentadecapeptide BPC 157 (PL 14736) was shown to promote healing of injured striated muscle and smooth muscle in the gastrointestinal tract, we explored its therapeutic potentials for leak point pressure (LPP) recovery in rat stress urinary incontinence (SUI) after transabdominal urethrolysis (TU) and prolonged vaginal dilatation (VD). During a 7-day period, TU-rats and VD-rats (or healthy rats) received BPC 157, either (i) intraperitoneally, 10 µg/kg or 10 ng/kg, once daily (first administration 30 min after surgery, last 24 h before LPP-testing and sacrifice), or (ii) per-orally, 10 µg/kg in drinking water (0.16 µg/mL, 12 mL/rat/day). Vesicourethral segments were harvested for immunohistochemical evaluation. All BPC 157 regimens counteracted decrease of LPP values in TU-rats and VD-rats. Additionally, BPC 157-TU rats (µg-intraperitoneally or per-orally) and BPC 157-VD rats (µg intraperitoneally) reached LPP values originally noted in healthy rats. Conversely, in healthy rats, BPC 157 did not alter LPP. Immunohistochemical studies revealed higher desmin (delineates striated organization of skeletal muscle), smooth muscle actin, and CD34 (angiogenic marker) positivity within the urethral wall in BPC 157-treated rats vs. controls, as well as overall preserved muscle/connective tissue ratio assessed with Mallory's trichrome staining. Pentadecapeptide BPC 157, applied parenterally or per-orally, appears to ameliorate the SUI in rat models, improving the otherwise detrimental course of healing after VD and TU, which may be analogous to human injury. These beneficial effects may possibly be selectively used in future strategies for treatment of SUI.
Jandric, Ivan; Vrcic, Hrvoje; Balen, Marica Jandric; Kolenc, Danijela; Brcic, Luka; Radic, Bozo; Drmic, Domagoj; Seiwerth, Sven; Sikiric, Predrag
2013-01-01
Background Since an originally anti-ulcer stable gastric pentadecapeptide BPC 157 (PL 14736) was shown to promote healing of injured striated muscle and smooth muscle in the gastrointestinal tract, we explored its therapeutic potentials for leak point pressure (LPP) recovery in rat stress urinary incontinence (SUI) after transabdominal urethrolysis (TU) and prolonged vaginal dilatation (VD). Material/Methods During a 7-day period, TU-rats and VD-rats (or healthy rats) received BPC 157, either (i) intraperitoneally, 10 μg/kg or 10 ng/kg, once daily (first administration 30 min after surgery, last 24 h before LPP-testing and sacrifice), or (ii) per-orally, 10 μg/kg in drinking water (0.16 μg/mL, 12 mL/rat/day). Vesicourethral segments were harvested for immunohistochemical evaluation. Results All BPC 157 regimens counteracted decrease of LPP values in TU-rats and VD-rats. Additionally, BPC 157-TU rats (μg-intraperitoneally or per-orally) and BPC 157-VD rats (μg intraperitoneally) reached LPP values originally noted in healthy rats. Conversely, in healthy rats, BPC 157 did not alter LPP. Immunohistochemical studies revealed higher desmin (delineates striated organization of skeletal muscle), smooth muscle actin, and CD34 (angiogenic marker) positivity within the urethral wall in BPC 157-treated rats vs. controls, as well as overall preserved muscle/connective tissue ratio assessed with Mallory’s trichrome staining. Conclusions Pentadecapeptide BPC 157, applied parenterally or per-orally, appears to ameliorate the SUI in rat models, improving the otherwise detrimental course of healing after VD and TU, which may be analogous to human injury. These beneficial effects may possibly be selectively used in future strategies for treatment of SUI. PMID:23478678
Molecular genetic basis of pod corn (Tunicate maize)
Wingen, Luzie U.; Münster, Thomas; Faigl, Wolfram; Deleu, Wim; Sommer, Hans; Saedler, Heinz; Theißen, Günter
2012-01-01
Pod corn is a classic morphological mutant of maize in which the mature kernels of the cob are covered by glumes, in contrast to generally grown maize varieties in which kernels are naked. Pod corn, known since pre-Columbian times, is the result of a dominant gain-of-function mutation at the Tunicate (Tu) locus. Some classic articles of 20th century maize genetics reported that the mutant Tu locus is complex, but molecular details remained elusive. Here, we show that pod corn is caused by a cis-regulatory mutation and duplication of the ZMM19 MADS-box gene. Although the WT locus contains a single-copy gene that is expressed in vegetative organs only, mutation and duplication of ZMM19 in Tu lead to ectopic expression of the gene in the inflorescences, thus conferring vegetative traits to reproductive organs. PMID:22517751
A divergent picornavirus from a turkey with gastro-intestinal disease
USDA-ARS?s Scientific Manuscript database
A novel picornavirus, turkey avisivirus (TuASV), was identified from the feces of turkeys (Meleagris gallopavo) with gastro-intestinal disease from a farm in Indiana, USA. Its genome organization is 5’UTR**IRES-II[VP0,VP3,VP1,2A,2B,2C,3A,3B,3Cpro,3Dpol]3’UTR-poly(A). TuASV only shares 34% (P1), 36% ...
Response to ‘pervasive sequence patents cover the entire human genome’ - authors’ reply
2014-01-01
An author reply to the Letter to the Editor from Tu et al. regarding Pervasive sequence patents cover the entire human genome by J Rosenfeld and C Mason. Genome Med 2013, 5:27. See related Correspondence by Rosenfeld and Mason, http://genomemedicine.com/content/5/3/27, and related letter by Tu et al., http://genomemedicine.com/content/6/2/14 PMID:24764495
Metal sulfide thin films by chemical spray pyrolysis
NASA Astrophysics Data System (ADS)
Krunks, Malle; Mellikov, Enn
2001-04-01
CdS, ZnS and CuS thin films were prepared by spray pyrolysis method using metal chlorides and thiourea (tu) as starting materials. Metal sulfide films form as products of thermal decomposition of complexes Cd(tu)2Cl2, Zn(tu)2Cl2 and Cu(tu)Cl(DOT)1/2H2O, originally formed in aqueous solution at precursors molar ratio 1:2. The metal-ligand bonding is thermally stable up to 220 degrees Celsius, followed by multistep degradation process of complexes. The TG/DTA analysis show similar thermal behavior of complexes up to 300 degrees Celsius with the formation of metal sulfides in this decomposition step. In air intensive oxidation processes are detected close to 400, 600 and 720 degrees Celsius for Cu, Cd and Zn complexes, respectively. The results of thermoanalytical study and XRD of sprayed films show that CdS and ZnS films could be grown at 450 degrees Celsius even in air while deposition of copper sulfide films should be performed in an inert atmosphere. High total impurities content of 10 wt% in CdS films prepared at 240 degrees Celsius is originated from the precursor and reduced to 2 wt% by increasing the growth temperature up to 400 degrees Celsius.
Formation of virions is strictly required for turnip yellows virus long-distance movement in plants.
Hipper, Clémence; Monsion, Baptiste; Bortolamiol-Bécet, Diane; Ziegler-Graff, Véronique; Brault, Véronique
2014-02-01
Viral genomic RNA of the Turnip yellows virus (TuYV; genus Polerovirus; family Luteoviridae) is protected in virions formed by the major capsid protein (CP) and the minor component, the readthrough (RT*) protein. Long-distance transport, used commonly by viruses to systemically infect host plants, occurs in phloem sieve elements and two viral forms of transport have been described: virions and ribonucleoprotein (RNP) complexes. With regard to poleroviruses, virions have always been presumed to be the long-distance transport form, but the potential role of RNP complexes has not been investigated. Here, we examined the requirement of virions for polerovirus systemic movement by analysing CP-targeted mutants that were unable to form viral particles. We confirmed that TuYV mutants that cannot encapsidate into virions are not able to reach systemic leaves. To completely discard the possibility that the introduced mutations in CP simply blocked the formation or the movement of RNP complexes, we tested in trans complementation of TuYV CP mutants by providing WT CP expressed in transgenic plants. WT CP was able to facilitate systemic movement of TuYV CP mutants and this observation was always correlated with the formation of virions. This demonstrated clearly that virus particles are essential for polerovirus systemic movement.
NASA Astrophysics Data System (ADS)
Sossa, Viviana; Assunção, Sonia; Pérez, Vega
2017-04-01
The STSM, Short-Term Missions, was carried out with the support of Murphy Survey company from Dublin - Ireland, was proposed for to Develop a module "GPR Applications in Archaeology" of the educational pack defined in the different meetings of the Cost Action TU 1208. The employ of GPR is mainly determined by the limits and uncertainties associated to this technique that affects to the measurements and the results. Private companies and end-users are highly interested in known the limits associated to particular cases and the advantages of the methodology compared to other studies. During this STSM, we plan to prepare a field survey, analyzing the possible problems and defining the objectives, and to acquire data to assess the structure. This data will be analyzed and processed in order to determine the limits of the technique in the particular case. The results will be compared to other surveys, in order to determine some clear restrictions that the company need to take into account in further works. Aknowledgments: This work has been partially funded by the EU COST Action TU1208, "Civil Engineering Applications of Ground Penetrating Radar", and it is a contribution to the working group 2.2 tasks in the COST Action TU1208.
Pavlov, Michael Y; Ehrenberg, Måns
2018-05-20
Accurate translation of genetic information is crucial for synthesis of functional proteins in all organisms. We use recent experimental data to discuss how induced fit affects accuracy of initial codon selection on the ribosome by aminoacyl transfer RNA in ternary complex ( T 3 ) with elongation factor Tu (EF-Tu) and guanosine-5'-triphosphate (GTP). We define actual accuracy ([Formula: see text]) of a particular protein synthesis system as its current accuracy and the effective selectivity ([Formula: see text]) as [Formula: see text] in the limit of zero ribosomal binding affinity for T 3 . Intrinsic selectivity ([Formula: see text]), defined as the upper thermodynamic limit of [Formula: see text], is determined by the free energy difference between near-cognate and cognate T 3 in the pre-GTP hydrolysis state on the ribosome. [Formula: see text] is much larger than [Formula: see text], suggesting the possibility of a considerable increase in [Formula: see text] and [Formula: see text] at negligible kinetic cost. Induced fit increases [Formula: see text] and [Formula: see text] without affecting [Formula: see text], and aminoglycoside antibiotics reduce [Formula: see text] and [Formula: see text] at unaltered [Formula: see text].
Salman, Mahmoud; Yassin, Dany-Jan; Shoukfeh, Huda; Nettleship, Joanne Elisabeth; Yassin, Aksam
2017-03-01
We and others have previously shown that testosterone replacement therapy (TRT) results in sustained weight loss in the majority of middle-aged hypogonadal men. Previously, however, a small proportion failed to lose at least 5% of their baseline weight. The reason for this is not yet understood. In the present study, we sought to identify early indicators that may predict successful long-term weight loss, defined as a reduction of at least 5% of total body weight relative to baseline weight (T0), in men with hypogonadism undergoing TRT. Eight parameters measured were assessed as potential predictors of sustained weight loss: loss of 3% or more of baseline weight after 1 year of TU treatment, severe hypogonadism, BMI, waist circumference, International Prostate Symptom Score (IPSS), glycated hemoglobin (HbA 1C ), age and use of vardenafil. Among the eight measured parameters, three factors were significantly associated with sustained weight loss over the entire period of TU treatment: (1) a loss of 3% of the baseline body weight after 1 year of TRT; (2) baseline BMI over 30; and (3) a waist circumference >102 cm. Age was not a predictor of weight loss.
Javornik, Uroš; Plavec, Janez; Wang, Baifan; Graham, Steven M
2018-01-02
A combined variable temperature 600 MHz NMR/molecular dynamics study of the Ca 2+ -release agent cyclic adenosine 5'-diphosphate ribose (cADPR) was conducted. In addition to elucidating the major and minor orientations of the conformationally flexible furanose rings, γ- (C4'-C5'), and β- (C5'-O5') bonds, the thermodynamics (ΔH o , ΔS o ) associated with each of these conformational equilibria were determined. Both furanose rings were biased towards a south conformation (64-74%) and both β-bonds heavily favored trans conformations. The R-ring γ-bond was found to exist almost exclusively as the γ + conformer, whereas the A-ring γ-bond was a mixture of the γ + and γ t conformers, with the trans conformer being slightly favored. Enthalpic factors accounted for most of the observed conformational preferences, although the R-ring furanose exists as its major conformation based solely on entropic factors. There was excellent agreement between the NMR and MD results, particularly with regard to the conformer identities, but the MD showed a bias towards γ + conformers. The MD results showed that both N-glycosidic χ-bonds are exclusively syn. Collectively the data allowed for the construction of a model for cADPR in which many of the conformationally flexible units in fact effectively adopt single orientations and where most of the conformational diversity resides in its A-ring furanose and γ-bond. Copyright © 2017 Elsevier Ltd. All rights reserved.
NASA Astrophysics Data System (ADS)
Gusyev, Maksym A.; Morgenstern, Uwe; Stewart, Michael K.; Yamazaki, Yusuke; Kashiwaya, Kazuhisa; Nishihara, Terumasa; Kuribayashi, Daisuke; Sawano, Hisaya; Iwami, Yoichi
2016-07-01
In this study, we demonstrate the application of tritium in precipitation and baseflow to estimate groundwater transit times and storage volumes in Hokkaido, Japan. To establish the long-term history of tritium concentration in Japanese precipitation, we used tritium data from the global network of isotopes in precipitation and from local studies in Japan. The record developed for Tokyo area precipitation was scaled for Hokkaido using tritium values for precipitation based on wine grown at Hokkaido. Then, tritium concentrations measured with high accuracy in river water from Hokkaido, Japan, were compared to this scaled precipitation record and used to estimate groundwater mean transit times (MTTs). A total of 16 river water samples in Hokkaido were collected in June, July, and October 2014 at 12 locations with altitudes between 22 and 831 m above sea level and catchment areas between 14 and 377 km2. Measured tritium concentrations were between 4.07 (± 0.07) TU and 5.29 (± 0.09) TU in June, 5.06 (± 0.09) TU in July, and between 3.75 (± 0.07) TU and 4.85 (± 0.07) TU in October. We utilised TracerLPM (Jurgens et al., 2012) for MTT estimation and introduced a Visual Basic module to automatically simulate tritium concentrations and relative errors for selected ranges of MTTs, exponential-piston ratios, and scaling factors of tritium input. Using the exponential (70 %) piston flow (30 %) model (E70 %PM), we simulated unique MTTs for seven river samples collected in six Hokkaido headwater catchments because their low tritium concentrations were no longer ambiguous. These river catchments are clustered in similar hydrogeological settings of Quaternary lava as well as Tertiary propylite formations near Sapporo city. However, nine river samples from six other catchments produced up to three possible MTT values with E70 % PM due to the interference by the tritium from the atmospheric hydrogen bomb testing 5-6 decades ago. For these catchments, we show that tritium in Japanese groundwater will reach natural levels in a decade, when one tritium measurement will be sufficient to estimate a unique MTT. Using a series of tritium measurements over the next few years with 3-year intervals will enable us to estimate the correct MTT without ambiguity in this period. These unique MTTs will allow estimation of groundwater storage volumes for water resources management during droughts and improvement of numerical model simulations. For example, the groundwater storage ranges between 0.013 and 5.07 km3 with saturated water thickness from 0.2 and 24 m. In summary, we emphasise three important points from our findings: (1) one tritium measurement is already sufficient to estimate MTTs for some Japanese catchments, (2) the hydrogeological settings control the tritium transit times of subsurface groundwater storage during baseflow, and (3) in the future, one tritium measurement will be sufficient to estimate MTTs in most Japanese watersheds.
Proper Conformal Killing Vectors in Kantowski-Sachs Metric
NASA Astrophysics Data System (ADS)
Hussain, Tahir; Farhan, Muhammad
2018-04-01
This paper deals with the existence of proper conformal Killing vectors (CKVs) in Kantowski-Sachs metric. Subject to some integrability conditions, the general form of vector filed generating CKVs and the conformal factor is presented. The integrability conditions are solved generally as well as in some particular cases to show that the non-conformally flat Kantowski-Sachs metric admits two proper CKVs, while it admits a 15-dimensional Lie algebra of CKVs in the case when it becomes conformally flat. The inheriting conformal Killing vectors (ICKVs), which map fluid lines conformally, are also investigated.
He, Xianghui; Yang, Wenzhi; Ye, Min; Wang, Qing; Guo, Dean
2011-11-01
Cuscuta chinensis and Cuscuta australis, the two botanical sources of the Chinese herbal medicine Tu-Si-Zi, were distinguished from each other based on qualitative and quantitative chemical analysis. By HPLC‑DAD‑MS, a total of 36 compounds were characterized from these two Cuscuta species, including 14 flavonoids, 17 quinic acid derivatives, and 5 lignans. In addition, HPLC‑UV was applied to determine seven major compounds (6 flavonoids plus chlorogenic acid) in 27 batches of Tu-Si-Zi. The results revealed that the amounts of the three classes of compounds varied significantly between the species. C. australis contained more flavonoids but less quinic acid derivatives and lignans than C. chinensis. Particularly, the amounts of kaempferol and astragalin in C. australis were remarkably higher than in C. chinensis. This finding could be valuable for the quality control of Tu-Si-Zi. © Georg Thieme Verlag KG Stuttgart · New York.
Kong, B H; Hanifah, Y A; Yusof, M Y; Thong, K L
2011-12-01
Acinetobacter baumannii, genomic species 3 and 13TU are being increasingly reported as the most important Acinetobacter species that cause infections in hospitalized patients. These Acinetobacter species are grouped in the Acinetobacter calcoaceticus- Acinetobacter baumannii (Acb) complex. Differentiation of the species in the Acb-complex is limited by phenotypic methods. Therefore, in this study, amplified ribosomal DNA restriction analysis (ARDRA) was applied to confirm the identity A. baumannii strains as well as to differentiate between the subspecies. One hundred and eighty-five strains from Intensive Care Unit, Universiti Malaya Medical Center (UMMC) were successfully identified as A. baumannii by ARDRA. Acinetobacter genomic species 13TU and 15TU were identified in 3 and 1 strains, respectively. ARDRA provides an accurate, rapid and definitive approach towards the identification of the species level in the genus Acinetobacter. This paper reports the first application ARDRA in genospecies identification of Acinetobacter in Malaysia.
Hatzitaki, Vassilia; Pavlou, Marousa; Bronstein, Adolfo M
2004-02-01
Previous studies have looked at co-processing of multiple proprioceptive inputs but few have investigated the effect of separate dynamic and tonic predominantly proprioceptive disruptions applied concurrently at the same segment. The purpose of the present study was to investigate how simultaneous ankle tendon vibration, a tonic stimulus, with a dynamic toes-up (TU) or toes-down (TD) platform perturbation (1) affects postural stability and (2) influences the adaptation process. Sixteen normal subjects (ten male, six female, mean age 26 +/- 4.8 years) stood blindfolded on a moving platform with vibrators attached bilaterally over the Achilles tendons. Participants were tested in quiet stance (QS), and with five successive TU and TD tilts. All tests were conducted both with (QS+V, TU+V, TD+V) and without vibration. Centre of pressure (CoP) displacements and pitch angular trunk velocity were recorded. Results for QS+V showed a significant 1.02-cm backward CoP displacement (P<0.01) and a significant increase in trunk velocity (peak-to-peak amplitude, P<0.05; SD of trunk velocity, P<0.05). TU+V resulted in a non-significant increase of maximum backwards CoP displacement when compared to TU alone. In addition, no notable effect of vibration on other measures of CoP (pre-tilt position, SD and area of sway) and trunk velocity (peak-to-peak, SD and area of sway) indicates that TU+V does not introduce significantly greater instability compared to tilt alone. In the TD condition, vibration was found to be a stabilising influence, causing a significant shift of the mean pre-tilt position 0.85 cm backwards (P<0.01) and a substantial decrease in the area of forward CoP displacement (P<0.01). However, maximum forwards CoP displacement and trunk velocity measures were not significantly altered during TD+V. Furthermore, in neither TU nor TD was the time-course or pattern of adaptation disrupted by the additional application of vibration. In conclusion, although vibration significantly affects postural measures when applied in isolation, this finding does not hold when it is applied in combination with a more dynamic stimulus. Instead it seems that once postural stability has been disrupted the central nervous system can rapidly assess information from a weaker tonic input and utilise or suppress it appropriately, depending on its effect towards overall postural control. It can be concluded that postural responses to the concurrent application of different predominantly proprioceptive stimuli are dependent upon the type of stimulus and the ability of the central nervous system to rapidly assess and re-weigh available sensory inputs.
Taylor, Eric S; Pol-Fachin, Laercio; Lins, Roberto D; Lower, Steven K
2017-04-01
The epidermal growth factor receptor (EGFR) is an important transmembrane glycoprotein kinase involved the initiation or perpetuation of signal transduction cascades within cells. These processes occur after EGFR binds to a ligand [epidermal growth factor (EGF)], thus inducing its dimerization and tyrosine autophosphorylation. Previous publications have highlighted the importance of glycosylation and dimerization for promoting proper function of the receptor and conformation in membranes; however, the effects of these associations on the protein conformational stability have not yet been described. Molecular dynamics simulations were performed to characterize the conformational preferences of the monomeric and dimeric forms of the EGFR extracellular domain upon binding to EGF in the presence and absence of N-glycan moieties. Structural stability analyses revealed that EGF provides the most conformational stability to EGFR, followed by glycosylation and dimerization, respectively. The findings also support that EGF-EGFR binding takes place through a large-scale induced-fitting mechanism. Proteins 2017; 85:561-570. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Renormalization, conformal ward identities and the origin of a conformal anomaly pole
NASA Astrophysics Data System (ADS)
Corianò, Claudio; Maglio, Matteo Maria
2018-06-01
We investigate the emergence of a conformal anomaly pole in conformal field theories in the case of the TJJ correlator. We show how it comes to be generated in dimensional renormalization, using a basis of 13 form factors (the F-basis), where only one of them requires renormalization (F13), extending previous studies. We then combine recent results on the structure of the non-perturbative solutions of the conformal Ward identities (CWI's) for the TJJ in momentum space, expressed in terms of a minimal set of 4 form factors (A-basis), with the properties of the F-basis, and show how the singular behaviour of the corresponding form factors in both basis can be related. The result proves the centrality of such massless effective interactions induced by the anomaly, which have recently found realization in solid state, in the theory of topological insulators and of Weyl semimetals. This pattern is confirmed in massless abelian and nonabelian theories (QED and QCD) investigated at one-loop.
Borisova, Tatiana; Dekaliuk, Mariia; Pozdnyakova, Natalia; Pastukhov, Artem; Dudarenko, Marina; Borysov, Arsenii; Vari, Sandor G; Demchenko, Alexander P
2017-07-01
Carbon nanoparticles that may be potent air pollutants with adverse effects on human health often contain heteroatoms including sulfur. In order to study in detail their effects on different physiological and biochemical processes, artificially produced carbon dots (CDs) with well-controlled composition that allows fluorescence detection may be of great use. Having been prepared from different types of organic precursors, CDs expose different atoms at their surface suggesting a broad variation of functional groups. Recently, we demonstrated neurotoxic properties of CDs synthesized from the amino acid β-alanine, and it is of importance to analyze whether CDs obtained from different precursors and particularly those exposing sulfur atoms induce similar neurotoxic effects. This study focused on synthesis of CDs from the sulfur-containing precursor thiourea-CDs (TU-CDs) with a size less than 10 nm, their characterization, and neuroactivity assessment. Neuroactive properties of TU-CDs were analyzed based on their effects on the key characteristics of glutamatergic and γ-aminobutyric acid (GABA) neurotransmission in isolated rat brain nerve terminals. It was observed that TU-CDs (0.5-1.0 mg/ml) attenuated the initial velocity of Na + -dependent transporter-mediated uptake and accumulation of L-[ 14 C]glutamate and [ 3 H]GABA by nerve terminals in a dose-dependent manner and increased the ambient level of the neurotransmitters. Starting from the concentration of 0.2 mg/ml, TU-CDs evoked a gradual dose-dependent depolarization of the plasma membrane of nerve terminals measured with the cationic potentiometric dye rhodamine 6G. Within the concentration range of 0.1-0.5 mg/ml, TU-CDs caused an "unphysiological" step-like increase in fluorescence intensity of the рН-sensitive fluorescent dye acridine orange accumulated by synaptic vesicles. Therefore, despite different surface properties and fluorescent features of CDs prepared from different starting materials (thiourea and β-alanine), their principal neurotoxic effects are analogous but displayed at a different level of efficiency. Sulfur-containing TU-CDs exhibit lower effects (by ~30%) on glutamate and GABA transport in the nerve terminals in comparison with sulfur-free β-alanine CDs. Our results suggest considering that an uncontrolled presence of carbon-containing particulate matter in the human environment may pose a toxicity risk for the central nervous system.
CTC Sentinel. Volume 6, Issue 3
2013-03-01
rac- ism. Locals reported that “light- skinned ” Arabs, Tu- aregs, and sub-Saharan Africans from Niger, Nigeria, Mali and other countries fought...Wadud), the amir of AQIM, to his lieutenants in the Sahara and to the Islamist militant group Ansar Eddine’s2 leader, Iyad ag Ghaly (also known as...2013. 2 Ansar Eddine, which means “Defenders of the Faith,” is a homegrown Islamist movement led by renowned Tu- areg rebel leader Iyad ag Ghaly
Integrable Rosochatius deformations of the restricted soliton flows
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zhou Ruguang
2007-10-15
A method to construct integrable Rosochatius deformations of the restricted soliton flows in the setup of Lax formulation is presented. The integrable Rosochatius deformations of the restricted soliton flows such as the restricted Ablowitz-Kaup-Newell-Segur flow, the restricted Tu-Meng flow, the restricted Tu flow with Neumann-type constraints, and the restricted modified Korteweg-de Vries flow, together with their Lax representations, are presented. In addition, a Lax representation of the Jacobi-Rosochatius system is obtained.
NASA Technical Reports Server (NTRS)
Cox, Timothy H.; Marshall, Alisa
2000-01-01
Four flights have been conducted using the Tu-144LL supersonic transport aircraft with the dedicated objective of collecting quantitative data and qualitative pilot comments. These data are compared with the following longitudinal flying qualities criteria: Neal-Smith, short-period damping, time delay, control anticipation parameter, phase delay (omega(sp)*T(theta(2))), pitch bandwidth as a function of time delay, and flight path as a function of pitch bandwidth. Determining the applicability of these criteria and gaining insight into the flying qualities of a large, supersonic aircraft are attempted. Where appropriate, YF-12, XB-70, and SR-71 pilot ratings are compared with the Tu-144LL results to aid in the interpretation of the Tu-144LL data and to gain insight into the application of criteria. The data show that approach and landing requirements appear to be applicable to the precision flightpath control required for up-and-away flight of large, supersonic aircraft. The Neal-Smith, control anticipation parameter, and pitch-bandwidth criteria tend to correlate with the pilot comments better than the phase delay criterion, omega(sp)*T(theta(2)). The data indicate that the detrimental flying qualities implication of decoupled pitch-attitude and flightpath responses occurring for high-speed flight may be mitigated by requiring the pilot to close the loop on flightpath or vertical speed.
Rosado, Daniel; Usero, José; Morillo, José
2016-06-01
Relationship between toxicity and bioavailable metals in sediments from the Huelva estuary and its littoral of influence was analyzed. Toxicity was assessed with Microtox® bioassay using a marine luminescent bacterium: Vibrio fischeri. Bioavailable metals were considered as both, acid extractable fraction of BCR procedure and the sum of exchangeable and bound to carbonates fractions of Tessier sequential extraction. A bioavailable metals index was calculated to integrate results in a single figure. Toxicity and bioavailable metals showed a similar pattern. Higher levels were found in the estuary than in the littoral (140 TU/g). In Huelva estuary, highest levels were found in the Tinto estuary (5725 TU/g), followed by the Odiel estuary (5100 TU/g) and the Padre Santo Canal (2500 TU/g). Results in this area were well over than those in nearby estuaries. Furthermore, they are similar to or even higher than those in other polluted sediments around the world. Bioavailable metal index showed a stronger correlation with acid extractable fraction of BCR (R(2) = 0.704) than that for the sum of exchangeable and bound to carbonates fractions of Tessier (R(2) = 0.661). These results suggest that bioavailable metals are an important source of sediment toxicity in the Huelva estuary and its littoral of influence, an area with one of the highest mortality risks of Spain. Copyright © 2016 Elsevier Ltd. All rights reserved.
A novel patient-derived xenograft model for claudin-low triple-negative breast cancer.
Matossian, Margarite D; Burks, Hope E; Bowles, Annie C; Elliott, Steven; Hoang, Van T; Sabol, Rachel A; Pashos, Nicholas C; O'Donnell, Benjamen; Miller, Kristin S; Wahba, Bahia M; Bunnell, Bruce A; Moroz, Krzysztof; Zea, Arnold H; Jones, Steven D; Ochoa, Augusto C; Al-Khami, Amir A; Hossain, Fokhrul; Riker, Adam I; Rhodes, Lyndsay V; Martin, Elizabeth C; Miele, Lucio; Burow, Matthew E; Collins-Burow, Bridgette M
2018-06-01
Triple-negative breast cancer (TNBC) subtypes are clinically aggressive and cannot be treated with targeted therapeutics commonly used in other breast cancer subtypes. The claudin-low (CL) molecular subtype of TNBC has high rates of metastases, chemoresistance and recurrence. There exists an urgent need to identify novel therapeutic targets in TNBC; however, existing models utilized in target discovery research are limited. Patient-derived xenograft (PDX) models have emerged as superior models for target discovery experiments because they recapitulate features of patient tumors that are limited by cell-line derived xenograft methods. We utilize immunohistochemistry, qRT-PCR and Western Blot to visualize tumor architecture, cellular composition, genomic and protein expressions of a new CL-TNBC PDX model (TU-BcX-2O0). We utilize tissue decellularization techniques to examine extracellular matrix composition of TU-BcX-2O0. Our laboratory successfully established a TNBC PDX tumor, TU-BCX-2O0, which represents a CL-TNBC subtype and maintains this phenotype throughout subsequent passaging. We dissected TU-BCx-2O0 to examine aspects of this complex tumor that can be targeted by developing therapeutics, including the whole and intact breast tumor, specific cell populations within the tumor, and the extracellular matrix. Here, we characterize a claudin-low TNBC patient-derived xenograft model that can be utilized for therapeutic research studies.
Choy, John S.; O'Toole, Eileen; Schuster, Breanna M.; Crisp, Matthew J.; Karpova, Tatiana S.; McNally, James G.; Winey, Mark; Gardner, Melissa K.; Basrai, Munira A.
2013-01-01
How subunit dosage contributes to the assembly and function of multimeric complexes is an important question with implications in understanding biochemical, evolutionary, and disease mechanisms. Toward identifying pathways that are susceptible to decreased gene dosage, we performed a genome-wide screen for haploinsufficient (HI) genes that guard against genome instability in Saccharomyces cerevisiae. This led to the identification of all three genes (SPC97, SPC98, and TUB4) encoding the evolutionarily conserved γ-tubulin small complex (γ-TuSC), which nucleates microtubule assembly. We found that hemizygous γ-TuSC mutants exhibit higher rates of chromosome loss and increases in anaphase spindle length and elongation velocities. Fluorescence microscopy, fluorescence recovery after photobleaching, electron tomography, and model convolution simulation of spc98/+ mutants revealed improper regulation of interpolar (iMT) and kinetochore (kMT) microtubules in anaphase. The underlying cause is likely due to reduced levels of Tub4, as overexpression of TUB4 suppressed the spindle and chromosome segregation defects in spc98/+ mutants. We propose that γ-TuSC is crucial for balanced assembly between iMTs and kMTs for spindle organization and accurate chromosome segregation. Taken together, the results show how gene dosage studies provide critical insights into the assembly and function of multisubunit complexes that may not be revealed by using traditional studies with haploid gene deletion or conditional alleles. PMID:23825022
Choy, John S; O'Toole, Eileen; Schuster, Breanna M; Crisp, Matthew J; Karpova, Tatiana S; McNally, James G; Winey, Mark; Gardner, Melissa K; Basrai, Munira A
2013-09-01
How subunit dosage contributes to the assembly and function of multimeric complexes is an important question with implications in understanding biochemical, evolutionary, and disease mechanisms. Toward identifying pathways that are susceptible to decreased gene dosage, we performed a genome-wide screen for haploinsufficient (HI) genes that guard against genome instability in Saccharomyces cerevisiae. This led to the identification of all three genes (SPC97, SPC98, and TUB4) encoding the evolutionarily conserved γ-tubulin small complex (γ-TuSC), which nucleates microtubule assembly. We found that hemizygous γ-TuSC mutants exhibit higher rates of chromosome loss and increases in anaphase spindle length and elongation velocities. Fluorescence microscopy, fluorescence recovery after photobleaching, electron tomography, and model convolution simulation of spc98/+ mutants revealed improper regulation of interpolar (iMT) and kinetochore (kMT) microtubules in anaphase. The underlying cause is likely due to reduced levels of Tub4, as overexpression of TUB4 suppressed the spindle and chromosome segregation defects in spc98/+ mutants. We propose that γ-TuSC is crucial for balanced assembly between iMTs and kMTs for spindle organization and accurate chromosome segregation. Taken together, the results show how gene dosage studies provide critical insights into the assembly and function of multisubunit complexes that may not be revealed by using traditional studies with haploid gene deletion or conditional alleles.
Sun, Ying; Gu, Lianhong; Dickinson, Robert E; Pallardy, Stephen G; Baker, John; Cao, Yonghui; DaMatta, Fábio Murilo; Dong, Xuejun; Ellsworth, David; Van Goethem, Davina; Jensen, Anna M; Law, Beverly E; Loos, Rodolfo; Martins, Samuel C Vitor; Norby, Richard J; Warren, Jeffrey; Weston, David; Winter, Klaus
2014-04-01
Worldwide measurements of nearly 130 C3 species covering all major plant functional types are analysed in conjunction with model simulations to determine the effects of mesophyll conductance (g(m)) on photosynthetic parameters and their relationships estimated from A/Ci curves. We find that an assumption of infinite g(m) results in up to 75% underestimation for maximum carboxylation rate V(cmax), 60% for maximum electron transport rate J(max), and 40% for triose phosphate utilization rate T(u) . V(cmax) is most sensitive, J(max) is less sensitive, and T(u) has the least sensitivity to the variation of g(m). Because of this asymmetrical effect of g(m), the ratios of J(max) to V(cmax), T(u) to V(cmax) and T(u) to J(max) are all overestimated. An infinite g(m) assumption also limits the freedom of variation of estimated parameters and artificially constrains parameter relationships to stronger shapes. These findings suggest the importance of quantifying g(m) for understanding in situ photosynthetic machinery functioning. We show that a nonzero resistance to CO2 movement in chloroplasts has small effects on estimated parameters. A non-linear function with gm as input is developed to convert the parameters estimated under an assumption of infinite gm to proper values. This function will facilitate gm representation in global carbon cycle models. © 2013 John Wiley & Sons Ltd.
ERIC Educational Resources Information Center
Parent, Mike C.; Moradi, Bonnie
2011-01-01
The Conformity to Feminine Norms Inventory-45 (CFNI-45; Parent & Moradi, 2010) is an important tool for assessing level of conformity to feminine gender norms and for investigating the implications of such norms for women's functioning. The authors of the present study assessed the factor structure, measurement invariance, reliability, and…
Basheer Ahamed, Shadir Bughari; Vanajassun, Purushothaman Pranav; Rajkumar, Kothandaraman; Mahalaxmi, Sekar
2018-04-01
Single cross-sectional nickel-titanium (NiTi) rotary instruments during continuous rotations are subjected to constant and variable stresses depending on the canal anatomy. This study was intended to create 2 new experimental, theoretic single-file designs with combinations of triple U (TU), triangle (TR), and convex triangle (CT) cross sections and to compare their bending stresses in simulated root canals with a single cross-sectional instrument using finite element analysis. A 3-dimensional model of the simulated root canal with 45° curvature and NiTi files with 5 cross-sectional designs were created using Pro/ENGINEER Wildfire 4.0 software (PTC Inc, Needham, MA) and ANSYS software (version 17; ANSYS, Inc, Canonsburg, PA) for finite element analysis. The NiTi files of 3 groups had single cross-sectional shapes of CT, TR, and TU designs, and 2 experimental groups had a CT, TR, and TU (CTU) design and a TU, TR, and CT (UTC) design. The file was rotated in simulated root canals to analyze the bending stress, and the von Mises stress value for every file was recorded in MPa. Statistical analysis was performed using the Kruskal-Wallis test and the Bonferroni-adjusted Mann-Whitney test for multiple pair-wise comparison with a P value <.05 (95 %). The maximum bending stress of the rotary file was observed in the apical third of the CT design, whereas comparatively less stress was recorded in the CTU design. The TU and TR designs showed a similar stress pattern at the curvature, whereas the UTC design showed greater stress in the apical and middle thirds of the file in curved canals. All the file designs showed a statistically significant difference. The CTU designed instruments showed the least bending stress on a 45° angulated simulated root canal when compared with all the other tested designs. Copyright © 2017 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.
Lamb, John R.; Zhang, Chunsheng; Xie, Tao; Wang, Kai; Zhang, Bin; Hao, Ke; Chudin, Eugene; Fraser, Hunter B.; Millstein, Joshua; Ferguson, Mark; Suver, Christine; Ivanovska, Irena; Scott, Martin; Philippar, Ulrike; Bansal, Dimple; Zhang, Zhan; Burchard, Julja; Smith, Ryan; Greenawalt, Danielle; Cleary, Michele; Derry, Jonathan; Loboda, Andrey; Watters, James; Poon, Ronnie T. P.; Fan, Sheung T.; Yeung, Chun; Lee, Nikki P. Y.; Guinney, Justin; Molony, Cliona; Emilsson, Valur; Buser-Doepner, Carolyn; Zhu, Jun; Friend, Stephen; Mao, Mao; Shaw, Peter M.; Dai, Hongyue; Luk, John M.; Schadt, Eric E.
2011-01-01
Background In hepatocellular carcinoma (HCC) genes predictive of survival have been found in both adjacent normal (AN) and tumor (TU) tissues. The relationships between these two sets of predictive genes and the general process of tumorigenesis and disease progression remains unclear. Methodology/Principal Findings Here we have investigated HCC tumorigenesis by comparing gene expression, DNA copy number variation and survival using ∼250 AN and TU samples representing, respectively, the pre-cancer state, and the result of tumorigenesis. Genes that participate in tumorigenesis were defined using a gene-gene correlation meta-analysis procedure that compared AN versus TU tissues. Genes predictive of survival in AN (AN-survival genes) were found to be enriched in the differential gene-gene correlation gene set indicating that they directly participate in the process of tumorigenesis. Additionally the AN-survival genes were mostly not predictive after tumorigenesis in TU tissue and this transition was associated with and could largely be explained by the effect of somatic DNA copy number variation (sCNV) in cis and in trans. The data was consistent with the variance of AN-survival genes being rate-limiting steps in tumorigenesis and this was confirmed using a treatment that promotes HCC tumorigenesis that selectively altered AN-survival genes and genes differentially correlated between AN and TU. Conclusions/Significance This suggests that the process of tumor evolution involves rate-limiting steps related to the background from which the tumor evolved where these were frequently predictive of clinical outcome. Additionally treatments that alter the likelihood of tumorigenesis occurring may act by altering AN-survival genes, suggesting that the process can be manipulated. Further sCNV explains a substantial fraction of tumor specific expression and may therefore be a causal driver of tumor evolution in HCC and perhaps many solid tumor types. PMID:21750698
Arver, Stefan; Luong, Ba; Fraschke, Anina; Ghatnekar, Ola; Stanisic, Sanja; Gultyev, Dmitry; Müller, Elvira
2014-01-01
Testosterone replacement therapy (TRT) has been recommended for the treatment of primary and secondary hypogonadism. However, long-term implications of TRT have not been investigated extensively. The aim of this analysis was to evaluate health outcomes and costs associated with life-long TRT in patients suffering from Klinefelter syndrome and late-onset hypogonadism (LOH). A Markov model was developed to assess cost-effectiveness of testosterone undecanoate (TU) depot injection treatment compared with no treatment. Health outcomes and associated costs were modeled in monthly cycles per patient individually along a lifetime horizon. Modeled health outcomes included development of type 2 diabetes, depression, cardiovascular and cerebrovascular complications, and fractures. Analysis was performed for the Swedish health-care setting from health-care payer's and societal perspective. One-way sensitivity analyses evaluated the robustness of results. The main outcome measures were quality-adjusted life-years (QALYs) and total cost in TU depot injection treatment and no treatment cohorts. In addition, outcomes were also expressed as incremental cost per QALY gained for TU depot injection therapy compared with no treatment (incremental cost-effectiveness ratio [ICER]). TU depot injection compared to no-treatment yielded a gain of 1.67 QALYs at an incremental cost of 28,176 EUR (37,192 USD) in the Klinefelter population. The ICER was 16,884 EUR (22,287 USD) per QALY gained. Outcomes in LOH population estimated benefits of TRT at 19,719 EUR (26,029 USD) per QALY gained. Results showed to be considerably robust when tested in sensitivity analyses. Variation of relative risk to develop type 2 diabetes had the highest impact on long-term outcomes in both patient groups. This analysis suggests that lifelong TU depot injection therapy of patients with hypogonadism is a cost-effective treatment in Sweden. Hence, it can support clinicians in decision making when considering appropriate treatment strategies for patients with testosterone deficiency. © 2013 International Society for Sexual Medicine.
Conformal invariance and conserved quantities of mechanical system with unilateral constraints
NASA Astrophysics Data System (ADS)
Wang, Peng
2018-06-01
By distinguishing the different constraint cases, the whole course and piecewise conserved quantities, which deduced from conformal invariance of mechanical systems with unilateral constraints, are given. The determining equation of conformal invariance of the system is obtained. The sufficient and necessary conditions for the conformal invariance must be Lie symmetry of the system are given. The forms of conformal factors are obtained. An example is given to illustrate the results in this paper.
Anomalous conformer dependent S 1 lifetime of L-phenylalanine
NASA Astrophysics Data System (ADS)
Hashimoto, Takayo; Takasu, Yuichi; Yamada, Yuji; Ebata, Takayuki
2006-04-01
The fluorescence lifetimes were measured for six conformers of L-phenylalanine cooled in a supersonic jet. It was found that the S 1 state lifetimes differ by a factor of three among the conformers. Especially, the most stable conformer (intramolecular hydrogen-bonded form) in S 0 had the shortest lifetime. Time-dependent DFT calculation suggested an importance of the mixing of the nπ ∗ character to S 1(ππ ∗) in this conformer dependent dynamics.
Carbon, Claus-Christian; Hecht, Heiko
2017-01-01
The present study is a first attempt to experimentally test the impact of two specific social factors, namely social conformity pressure and a sense of being watched, on participants’ judgments of the artistic quality of aesthetic objects. We manipulated conformity pressure with a test form in which a photograph of each stimulus was presented together with unanimously low (downward pressure) or high quality ratings (upward pressure) of three would-be previous raters. Participants’ sense of being watched was manipulated by testing each of them in two settings, one of which contained an eyespots stimulus. Both social factors significantly affected the participants’ judgments—unexpectedly, however, with conformity pressure only working in the downward direction and eyespots leading to an overall downward shift in participants’ judgments. Our findings indicate the relevance of including explicit and implicit social factors in aesthetics research, thus also reminding us of the limitations of overly reductionist approaches to investigating aesthetic perception and experience. PMID:29201336
Hesslinger, Vera M; Carbon, Claus-Christian; Hecht, Heiko
2017-01-01
The present study is a first attempt to experimentally test the impact of two specific social factors, namely social conformity pressure and a sense of being watched, on participants' judgments of the artistic quality of aesthetic objects. We manipulated conformity pressure with a test form in which a photograph of each stimulus was presented together with unanimously low (downward pressure) or high quality ratings (upward pressure) of three would-be previous raters. Participants' sense of being watched was manipulated by testing each of them in two settings, one of which contained an eyespots stimulus. Both social factors significantly affected the participants' judgments-unexpectedly, however, with conformity pressure only working in the downward direction and eyespots leading to an overall downward shift in participants' judgments. Our findings indicate the relevance of including explicit and implicit social factors in aesthetics research, thus also reminding us of the limitations of overly reductionist approaches to investigating aesthetic perception and experience.
A Theory of Cramer-Rao Bounds for Constrained Parametric Models
2010-01-01
reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of...overly optimistic. This occurs frequently in communications when the signal- to-noise ratio (SNR) or data transmission size decreases. 43 3.1, then U ?(φ...space of UTHT , the LSE is BLUE and is given by dT θ̂CLS(x) = d Tθ1 + d TU ( UTQU )† UTHTC−1 ( x−Hθ1 ) (3.28) similar to (3.27) with variance dTU
China Report, Science and Technology
1986-01-27
Technology Assessment Reviewed (Huang Qingming; JISHU JINGJI YU GUANLI YANJIU, No 4, 31 Aug 85) 19 - a - Editorial Explores Technology Importation...JPRS-CST-86-003 27 January 1986 NATIONAL DEVELOPMENTS TECHNOLOGY ASSESSMENT REVIEWED Shanxi JISHU JINGJI YU GUANLI YANJIU [RESEARCH ON THE...derived based on the theory of least squares: where: and x0=l(MN-U 2)Q+(UV-NT)R + (TU-MV)Sl/D y0 = ZOJV-NT)Q + (LN-V 1)R + (TV- LU )Sn/D 20 = L(TU-VM)Q
Translations on North Korea. Number 616.
1978-09-20
Chin-u, Kye Ung -tae, Kim -hwan, Kim Man-kum, Ho Tam, Chong Chun-ki and Kong Chin-tae. Attending the soiree were Comrade Han Tok-su, chairman of the...Committee which was held on 10 June under the leadership of Kim Il-song; listed ninth, after Kim Tu- yong and before No T’ae-sok (NODONG SINMUN 12 Jun...Province KWP Committee which was held on 10 June under the leadership of Kim Il-song; listed seventh, after Kang Song-san and before Kim Tu- yong
Yuan, Da; Yang, Xue; Guo, Jun-Chao
2016-05-01
Public excitement over the award of the 2015 Nobel Prize in Physiology or Medicine to the Chinese medical scientist You-you TU for the discovery of a herbal anti-malarial, may mislead the Chinese people into believing that traditional Chinese herbal medi-cine can be used to cure all disease without any ad-verse effects. The aim of this paper is to explain the advantages and disadvantages of herbal traditional Chinese medicine (TCM) objectively.
Air Weapon Systems in the Third World: A Combat Potential Assessment Technique.
1986-06-01
VALUE LABEL BMAT BOMBER-GROUND ATTACK FTAT FIGHTER-GROUND ATTACK FTTA FIGHTER/TRAINER-GROUND ATTACK FTIN FIGHTER-INTERCEPTOR FTTI FIGHTER/TRAINER...260 2.91 10900 5440 17720 24540 TORADV FTIN 46 400 5.20 31500 15632 41392 60000 TORIDS FTAT 46 400 5.20 31065 14000 47985 60000 TU16AG BMAT 108 1772...6.58 82000 56870 130235 158730 TU22BD BMAT 91 1451 5. 69 80400 81600 147650 185000 ACFT MAXPWR TWPWR ASPD SPECENA LSPD SPECENS CSPD SCEI ALPHAMSI 5952
Conformal anomaly of generalized form factors and finite loop integrals
NASA Astrophysics Data System (ADS)
Chicherin, Dmitry; Sokatchev, Emery
2018-04-01
We reveal a new mechanism of conformal symmetry breaking at Born level. It occurs in generalized form factors with several local operators and an on-shell state of massless particles. The effect is due to hidden singularities on collinear configurations of the momenta. This conformal anomaly is different from the holomorphic anomaly of amplitudes. We present a number of examples in four and six dimensions. We find an application of the new conformal anomaly to finite loop momentum integrals with one or more massless legs. The collinear region around a massless leg creates a contact anomaly, made visible by the loop integration. The anomalous conformal Ward identity for an ℓ-loop integral is a 2nd-order differential equation whose right-hand side is an (ℓ - 1)-loop integral. It could serve as a new useful tool to find/test analytic expressions for conformal integrals. We illustrate this point with several examples of known integrals. We propose a new differential equation for the four-dimensional scalar double box.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Schueler, E; Loo, B; Maxim, P
2016-06-15
Purpose: The aim of this study was to evaluate the performance of very high-energy electron (VHEE) beams in comparison to clinically delivered treatment plans generated with volumetric modulated arc therapy (VMAT) and proton pencil beam scanning (PBS) technology. Methods: Three clinical cases were selected (prostate, lung, and pediatric CNS). The VHEE plans were calculated in the Monte Carlo EGSnrc code and pencil beam doses were calculated using the DOSxyznrc MC code for 100 and 200 MeV beams. Treatment plans with VHEE, VMAT, and PBS were optimized in a research version of RayStation using an in house build script in ordermore » to minimize operator bias between the different techniques. Results: For the prostate cancer case, the PBS plan showed lower mean organ at risk (OAR) doses compared to the other modalities. An exception was the femoral heads, due to the lateral beam arrangements. The VMAT plan showed lower mean doses to the rectum and the bladder compared to the 100 MeV VHEE plan. The lung cancer case showed minor differences between the three modalities. However, the PBS plan showed a lower contralateral lung dose. The pediatric CNS case showed a better conformity and lower spinal cord dose for the 100 MeV VHEE plan. For all cases, the 200 MeV VHEE plans were found to be similar to or better than the 100 MeV VHEE plans. Conclusion: The present study showed that VHEE plans are similar or superior to VMAT plans with reduced mean OAR dose and increased target conformity for a variety of clinical cases. With increased VHEE energy, better conformity and even higher reductions in mean OAR doses can be achieved. Funding: DoD, Award#:W81XWH-13-1-0165, Weston Havens Foundation, Bio-X (Stanford University), the Office of the Dean of the Medical School, the Office of the Provost (Stanford University), and the Swedish Childhood Cancer Foundation. BL and PM are founders of TibaRay,Inc. BL and PM have received research grants from Varian and RaySearch Laboratory.« less
Synthesis and characterization of hydrolysed starch-g-poly(methacrylic acid) composite.
Zahran, Magdy K; Ahmed, Enas M; El-Rafie, Mohamed H
2016-06-01
A novel method for the synthesis of starch-g-poly(methacrylic acid) composite was adopted by graft polymerization of hydrolysed starch (HS) and methacrylic acid (MAA) in aqueous medium using an efficient sodium perborate (SPB)-thiourea (TU) redox initiation system. The parameters influencing the redox system efficiency and thence the polymerization method were considered. These parameters comprehended the concentrations of MAA, SPB, TU and SPB/TU molar ratio as well as the polymerization temperature. The polymerization reaction was scrutinized through calculation of the MAA total conversion percent (TC%). The resultant poly(MAA-HS) composite was assessed by evaluating the polymer criteria (the graft yield, GY%; the grafting efficiency, GE%; the homopolymer, HP%; and the total conversion). The comportment of the apparent viscosity of the cooked poly(MAA)-starch composite paste, obtained under diverse polymerization conditions, was examined. Tentative mechanisms, which depict all occasions that happen amid the entire course of the polymerization reaction, have been proffered. Copyright © 2016 Elsevier B.V. All rights reserved.
Glazer, I.; Orion, D.
1984-01-01
Urea (U), hydroxyurea (HU), and thiourea (TU), in various concentrations, were added to chemically defined plant tissue culture medium on which Meloidogyne javanica was reared on excised tomato roots. Concentrations as low as 3 ppm HU or 12 ppm TU inhibited nematode maturation by 70-90% 4 weeks after inoculation, and the coenocytes in the parasitized tissue were poorly developed. Gall weight was also inhibited by 50% in cultures treated with 3 and 6 ppm HU. However, exposing juveniles of M. javanica and Tylenchulus semipenetrans or juveniles and adults of Pratylenchus thornei to increasing concentrations of HU or TU, up to 100 ppm, was not lethal. These two urea derivatives still inhibited nematode maturation when the infected region of the root was not in direct contact with the chemicals. Therefore, we suggest that these urea derivatives inhibit nematode development by affecting the plant metabolism essential to coenocyte formation, an occurrence similar to the hypersensitive reaction in a naturally resistant plant. PMID:19295888
Ventura, Marco; Canchaya, Carlos; Meylan, Valèrie; Klaenhammer, Todd R.; Zink, Ralf
2003-01-01
We analyzed the tuf gene, encoding elongation factor Tu, from 33 strains representing 17 Lactobacillus species and 8 Bifidobacterium species. The tuf sequences were aligned and used to infer phylogenesis among species of lactobacilli and bifidobacteria. We demonstrated that the synonymous substitution affecting this gene renders elongation factor Tu a reliable molecular clock for investigating evolutionary distances of lactobacilli and bifidobacteria. In fact, the phylogeny generated by these tuf sequences is consistent with that derived from 16S rRNA analysis. The investigation of a multiple alignment of tuf sequences revealed regions conserved among strains belonging to the same species but distinct from those of other species. PCR primers complementary to these regions allowed species-specific identification of closely related species, such as Lactobacillus casei group members. These tuf gene-based assays developed in this study provide an alternative to present methods for the identification for lactic acid bacterial species. Since a variable number of tuf genes have been described for bacteria, the presence of multiple genes was examined. Southern analysis revealed one tuf gene in the genomes of lactobacilli and bifidobacteria, but the tuf gene was arranged differently in the genomes of these two taxa. Our results revealed that the tuf gene in bifidobacteria is flanked by the same gene constellation as the str operon, as originally reported for Escherichia coli. In contrast, bioinformatic and transcriptional analyses of the DNA region flanking the tuf gene in four Lactobacillus species indicated the same four-gene unit and suggested a novel tuf operon specific for the genus Lactobacillus. PMID:14602655
Functional Properties of Lactobacillus mucosae Strains Isolated from Brazilian Goat Milk.
de Moraes, Georgia Maciel Dias; de Abreu, Louricélia Rodrigues; do Egito, Antônio Silvio; Salles, Hévila Oliveira; da Silva, Liana Maria Ferreira; Nero, Luís Augusto; Todorov, Svetoslav Dimitrov; Dos Santos, Karina Maria Olbrich
2017-09-01
The search for probiotic candidates among lactic acid bacteria (LAB) isolated from food may uncover new strains with promising health and technological properties. Lactobacillus mucosae strains attracted recent research attention due to their ability to adhere to intestinal mucus and to inhibit pathogens in the gastrointestinal tract, both related to a probiotic potential. Properties of interest and safety aspects of three Lb. mucosae strains (CNPC006, CNPC007, and CNPC009) isolated from goat milk were investigated employing in vitro tests. The presence of genetic factors related to bile salt hydrolase production (bsh), intestinal adhesion properties (msa, map, mub, and ef-tu), virulence, and biogenic amine production were also verified. All strains exhibited the target map, mub, and ef-tu sequences; the msa gene was detected in CNPC006 and CNPC007 strains. Some of the searched sequences for virulence factors were detected, especially in the CNPC009 strain; all strains carried the hyl gene, related to the production of hyaluronidase. Lb. mucosae CNPC007 exhibited a high survival rate in simulated gastric and enteric conditions. Besides, all strains exhibited the bsh sequence, and CNPC006 and CNPC007 were able to deconjugate salts of glycodeoxycholic acid (GDC). Regarding technological properties for dairy product applications, a relatively higher milk acidification and clotting capacity, diacetyl production, and proteolytic activity were registered for CNPC007 in comparison to the other strains. Collectively, the results aim at Lb. mucosae CNPC007 as a promising probiotic candidate for application in dairy products, deserving further studies to confirm and explore its potential.
Stability of dilute solutions of tuberculin purified protein derivative.
Landi, S; Held, H R
1978-06-01
The biological potency of 15 commercially available tuberculin solutions prepared from a master batch of tuberculin purified protein derivative (PPD) (PPD-CT68) and using a newly formulated diluent (Connaught diluent) containing 0.0005% Tween 80 as an anti-adsorption agent and 0.3% phenol as a preservative, was determined after storage for various intervals at 4, 24 and 37 degrees C. The 5 tuberculin units (TU) per 0.1 ml dose solutions were bioequivalent to a non-stabilized solution of PPD-S whereas the 1 TU and 250 TU per dose solutions were equivalent by calculation to a non-stabilized solution of PPD-S. It was found that the PPD solutions of all 3 strengths, 1, 5 and 250 TU per dose, were stable for at least 3 years at 4 degrees C and for 2 years at room temperature (24 degrees C). Even at 37 degrees C the solutions of all 3 strengths were stable for at least 1 year. The stability of Connaught tuberculin PPD solutions has not been affected by the changes in formulation. The stability data suggest that the expiry date of the newly formulated tuberculin products could be at least two years from the data of the last satisfactory potency test. Although these products are stable for at least 1 year even at 37 degrees C, we nonetheless agree with the Canadian and U.S. regulations that they be stored at 2 to 8 degrees C in their original containers.
Shiri, Mahdi; Navaei-Nigjeh, Mona; Baeeri, Maryam; Rahimifard, Mahban; Mahboudi, Hossein; Shahverdi, Ahmad Reza; Kebriaeezadeh, Abbas; Abdollahi, Mohammad
Diazinon (DZ) is an organophosphorus insecticide that acts as an acetylcholinesterase inhibitor. It is important to note that it can induce oxidative stress, lipid peroxidation, diabetic disorders, and cytotoxicity. Magnesium oxide (MgO) and selenium nanoparticles (Se NPs) showed promising protection against oxidative stress, lipid peroxidation, cytotoxicity, and diabetic disorders. Therefore, this study was conducted to explore the possible protective mechanisms of MgO and Se NPs against DZ-induced cytotoxicity in PaTu cell line. Cytotoxicity of DZ, in the presence or absence of effective doses of MgO and Se NPs, was determined in human pancreatic cancer cell line (PaTu cells) after 24 hours of exposure by using mitochondrial activity and mitochondrial membrane potential assays. Then, the insulin, proinsulin, and C-peptide release; caspase-3 and -9 activities; and total thiol molecule levels were assessed. Determination of cell viability, including apoptotic and necrotic cells, was assessed via acridine orange/ethidium bromide double staining. Furthermore, expression of 15 genes associated with cell death/apoptosis in various phenomena was examined after 24 hours of contact with DZ and NPs by using real-time polymerase chain reaction. Compared to the individual cases, the group receiving the combination of MgO and Se NPs showed more beneficial effects in reducing the toxicity of DZ. Cotreatment of PaTu cell lines with MgO and Se NPs counteracts the toxicity of DZ on insulin-producing cells.
Chen, Hui-Xing; Yang, Shi; Ning, Ye; Shao, Hai-Hao; Ma, Meng; Tian, Ru-Hui; Liu, Yu-Fei; Gao, Wei-Qiang; Li, Zheng; Xia, Wei-Liang
2017-01-01
Testicular prostheses have been used to deal with anorchia for nearly 80 years. Here, we evaluated a novel testicular prosthesis that can controllably release hormones to maintain physiological levels of testosterone in vivo for a long time. Silastic testicular prostheses with controlled release of testosterone (STPT) with different dosages of testosterone undecanoate (TU) were prepared and implanted into castrated Sprague-Dawley rats. TU oil was applied by oral administration to a separate group of castrated rats. Castrated untreated and sham-operated groups were used as controls. Serum samples from every group were collected to measure the levels of testosterone (T), follicle-stimulating hormone and luteinizing hormone (LH). Maximum intracavernous penile pressure (ICPmax) was recorded. The prostates and seminal vesicles were weighed and subjected to histology, and a terminal dexynucleotidyl transferase-mediated UTP nick end labeling (TUNEL) assay was used to evaluate apoptosis. Our results revealed that the weights of these tissues and the levels of T and LH showed significant statistical differences in the oral administration and TU replacement groups compared with the castrated group (P < 0.05). Compared with the sham-operated group, the ICPmax, histology and TUNEL staining for apoptosis, showed no significant differences in the hormone replacement groups implanted with medium and high doses of STPT. Our results suggested that this new STPT could release TU stably through its double semi-permeable membranes with excellent biocompatibility. The study provides a new approach for testosterone replacement therapy. PMID:27174160
Tracing nuclear elements released by Fukushima Nuclear Power Plant accident
NASA Astrophysics Data System (ADS)
Tsujimura, M.; Onda, Y.; Abe, Y.; Hada, M.; Pun, I.
2011-12-01
Radioactive contamination has been detected in Fukushima and the neighboring regions due to the nuclear accident at Fukushima Daiichi Nuclear Power Plant (NPP) following the earthquake and tsunami occurred on 11th March 2011. The small experimental catchments have been established in Yamakiya district, Kawamata Town, Fukushima Prefecture, located approximately 35 km west from the Fukushima NPP. The tritium (3H) concentration and stable isotopic compositions of deuterium and oxygen-18 have been determined on the water samples of precipitation, soil water at the depths of 10 to 30 cm, groundwater at the depths of 5 m to 50 m, spring water and stream water taken at the watersheds in the recharge and discharge zones from the view point of the groundwater flow system. The tritium concentration of the rain water fell just a few days after the earthquake showed a value of approximately 17 Tritium Unit (T.U.), whereas the average concentration of the tritium in the precipitation was less than 5 T.U. before the Fukushima accident. The spring water in the recharge zone showed a relatively high tritium concentration of approximately 12 T.U., whereas that of the discharge zone showed less than 5 T.U. Thus, the artificial tritium was apparently injected in the groundwater flow system due to the Fukushima NPP accident, whereas that has not reached at the discharge zone yet. The monitoring of the nuclear elements is now on going from the view points of the hydrological cycles and the drinking water security.
Chou, Wen-Chi; Ma, Qin; Yang, Shihui; ...
2015-03-12
The identification of transcription units (TUs) encoded in a bacterial genome is essential to elucidation of transcriptional regulation of the organism. To gain a detailed understanding of the dynamically composed TU structures, we have used four strand-specific RNA-seq (ssRNA-seq) datasets collected under two experimental conditions to derive the genomic TU organization of Clostridium thermocellum using a machine-learning approach. Our method accurately predicted the genomic boundaries of individual TUs based on two sets of parameters measuring the RNA-seq expression patterns across the genome: expression-level continuity and variance. A total of 2590 distinct TUs are predicted based on the four RNA-seq datasets.more » Moreover, among the predicted TUs, 44% have multiple genes. We assessed our prediction method on an independent set of RNA-seq data with longer reads. The evaluation confirmed the high quality of the predicted TUs. Functional enrichment analyses on a selected subset of the predicted TUs revealed interesting biology. To demonstrate the generality of the prediction method, we have also applied the method to RNA-seq data collected on Escherichia coli and achieved high prediction accuracies. The TU prediction program named SeqTU is publicly available athttps://code.google.com/p/seqtu/. We expect that the predicted TUs can serve as the baseline information for studying transcriptional and post-transcriptional regulation in C. thermocellum and other bacteria.« less
Multichannel conformal blocks for scattering amplitudes
NASA Astrophysics Data System (ADS)
Belitsky, A. V.
2018-05-01
By performing resummation of small fermion-antifermion pairs within the pentagon form factor program to scattering amplitudes in planar N = 4 superYang-Mills theory, we construct multichannel conformal blocks within the flux-tube picture for N-sided NMHV polygons. This procedure is equivalent to summation of descendants of conformal primaries in the OPE framework. The resulting conformal partial waves are determined by multivariable hypergeometric series of Lauricella-Saran type.
Conformity Behavior and Self-Consciousness.
ERIC Educational Resources Information Center
Froming, William J.
Compliance, conforming behavior as a response to social influences, is affected by a variety of factors within the self. Some of these factors pertain to one's perceived place in the social context; others pertain to the salience of one's immediate affective and perceptual experience. The self-aspect chosen as the object of one's attention can…
1989-03-01
00 PM oleton Laboratory, U K. Stripe. foil. and fiber targets were ir- TuC, SESSION 7: POSTER SESSION radiated ,vith high intensity line-focused laser...Interference in Four-Wave TuC28 Gain Measurement on a 18.2-nm Carbon Recombin- Mixing, K. G. H. Baldwin. Australian National U. Constructive ation Laser...mixing in sodium vapor. (p. 76) cylindrical wall confined carbon recombination laser produc- ed by a high power CO laser are presented. A maximum gain
Volkov, A V; Kolkutin, V V; Klevno, V A; Shkol'nikov, B V; Kornienko, I V
2008-01-01
Managerial experience is described that was gained during the large-scale work on victim identification following mass casualties in the Tu 154-M and Airbus A310 passenger plane crashes. The authors emphasize the necessity to set up a specialized agency of constant readiness meeting modern requirements for the implementation of a system of measures for personality identification. This agency must incorporate relevant departments of the Ministries of Health, Defense, and Emergency Situations as well as investigative authorities and other organizations.
A Qualitative Piloted Evaluation of the Tupolev Tu-144 Supersonic Transport
NASA Technical Reports Server (NTRS)
Rivers, Robert A.; Jackson, E. Bruce; Fullerton, C. Gordon; Cox, Timothy H.; Princen, Norman H.
2000-01-01
Two U.S. research pilots evaluated the Tupolev Tu-144 supersonic transport aircraft on three dedicated flights: one subsonic and two supersonic profiles. The flight profiles and maneuvers were developed jointly by Tupolev and U.S. engineers. The vehicle was found to have unique operational and flight characteristics that serve as lessons for designers of future supersonic transport aircraft. Vehicle subsystems and observed characteristics are described as are flight test planning and ground monitoring facilities. Maneuver descriptions and extended pilot narratives for each flight are included as appendices.
1985-09-01
Strypi rocket, XM-33 ’"’" 22 1.3 Nike -Hercules missile 23 2.1 Staff organization, TU 8.1.3- 34 2.2 Control diagram, TU 8.1.3 2.3...DAMPshlp lf 6.3 General experimental plan, radar attenuation I69 6.4 Nike -Apache rockets with C-band beacon payloads - I™ 6.5 Shipboard antenna...Shot Star Fish 198 6.34 Blast instrument installation, Project 1.1 199 6.35 Accelerometer installation, Project 1.1 199 6.36 Nike -Cajun rocket
An Investigation of Large Tilt-Rotor Hover and Low Speed Handling Qualities
2011-05-01
de (d B) 10 1 100 101 102 360 180 0 180 360 Frequency (rad...sec) Ph as e (d eg ) CAMRAD Reduced order 150 100 50 0 50 M ag ni tu de (d B) 10 1 100 101 102 360 180 0 180 360 Frequency (rad/sec) Ph as e...time specifications defined in ADS-33. Additionally, the 0 10 20 30 40 50 M ag ni tu de (d B) 10 2 10 1 100 101 102 360 180 0 180 360
NASA Astrophysics Data System (ADS)
Hudson, Brian D.; George, Ashley R.; Ford, Martyn G.; Livingstone, David J.
1992-04-01
Molecular dynamics simulations have been performed on a number of conformationally flexible pyrethroid insecticides. The results indicate that molecular dynamics is a suitable tool for conformational searching of small molecules given suitable simulation parameters. The structures derived from the simulations are compared with the static conformation used in a previous study. Various physicochemical parameters have been calculated for a set of conformations selected from the simulations using multivariate analysis. The averaged values of the parameters over the selected set (and the factors derived from them) are compared with the single conformation values used in the previous study.
Water - Isotope - Map (δ 18O, δ 2H, 3H) of Austria: Applications, Extremes and Trends
NASA Astrophysics Data System (ADS)
Wyhlidal, Stefan; Kralik, Martin; Benischke, Ralf; Leis, Albrecht; Philippitsch, Rudolf
2016-04-01
The isotopic ratios of oxygen and hydrogen in water (2H/1H and 18O/16O) are important tools to characterise waters and their cycles. This starts in the atmosphere as rain or snow and continues in surface water and ends in shallow groundwater as well as in deep groundwater. Tritium formed by natural cosmic radiation in the upper atmosphere and in the last century by tests of thermonuclear bombs in the atmosphere, is characterised by its radioactive decay with a half-life of 12.32 years and is an ideal age-marker during the last 60 years. To determine the origin and mean age of waters in many projects concerning water supply, engineering and scientific projects in the last 45 years on more than 1,350 sites, more than 40,000 isotope measurements were performed in Austria. The median value of all sites of oxygen-18 is δ 18O -10.7 ‰ and for hydrogen-2 δ 2H -75 ‰. As the fractionation is mainly temperature dependent the lowest negative values are observed in winter precipitation (oxygen-18 as low as δ 18O -23 ‰) and in springs in the mountain regions (δ 18O -15.1 ‰). In contrast the highest values were observed in summer precipitation (up to δ 18O - 0.5 ‰) and in shallow lakes in the Seewinkel (up to δ 18O + 5 ‰). The isotopic ratios of the Austrian waters are also influenced by the origin of the evaporated water masses. Therefore the precipitation in the region south of the main Alpine crest (East-Tyrol, Carinthia and South-East Styria) is approximately 1 ‰ higher in δ 18O-values than sites at the same altitude in the northern part. This is most probably caused by the stronger influence of precipitation from the mediterranean area. The median value of all 1,120 sampling sites of decay corrected (2015) tritium measurements is 6.2 tritium units (TU). This is somewhat smaller than the median value of all precipitation stations with 7.2 TU. This can be explained by the fact that in most cases in groundwater the median value has been reduced by decay according to the residence time underground. The tritium concentration increases in the summer up to 10 - 11 TU and decreases in winter down to 3 - 4 TU. This is due to the better circulation in the atmosphere in spring which brings the tritium formed by cosmic radiation down to the lower atmosphere and precipitation. A smaller mean tritium concentration in aquifers than approximately 3.5 TU indicates large amounts of water older than 60 years. Waters with approximately more than 12 TU contain still tritium from the 1960s and 1970s formed originally by thermonuclear bomb experiments. In Austria the highest Tritium values can be observed in the rivers Danube and March which show periodic or permanent tritium contamination up to 70 TU coming from nuclear power plants in the neighbouring countries.
Chioccioli, Matteo; Marsili, Simone; Bonaccini, Claudia; Procacci, Piero; Gratteri, Paola
2012-02-27
Human vascular endothelial growth factor receptor type 2 (h-VEFGR2) is a receptor tyrosine kinase involved in the angiogenesis process and regarded as an interesting target for the design of anticancer drugs. Its activation/inactivation mechanism is related to conformational changes in its cytoplasmatic kinase domain, involving first among all the αC-helix in N-lobe and the A-loop in C-lobe. Affinity of inhibitors for the active or inactive kinase form could dictate the open or closed conformation of the A-loop, thus making the different conformations of the kinase domain receptor (KDR) domain different drug targets in drug discovery. In this view, a detailed knowledge of the conformational landscape of KDR domain is of central relevance to rationalize the efficiency and selectivity of kinase inhibitors. Here, molecular dynamics simulations were used to gain insight into the conformational switching activity of the KDR domain and to identify intermediate conformations between the two limiting active and inactive conformations. Specific energy barriers have been selectively removed to induce, and hence highlight at the atomistic level, the regulation mechanism of the A-loop opening. The proposed strategy allowed to repeatedly observe the escape of the KDR domain from the DFG-out free energy basin and to identify rare intermediate conformations between the DFG-out and the DFG-in structures to be employed in a structure-based drug discovery process.
Rosa Salazar, V; Bernal Martínez, L; García Pino, M J; Hernández Contreras, M E; García Méndez, M M; García Pérez, B; Marras Fernández-Cid, C
2016-01-01
To determine the mean stay (MS) of patients with pulmonary embolism (PE) in a thrombosis unit (TU) with a short stay unit (SSU) in a tertiary hospital. To compare the data collected with those of other hospitals in the same region, of other regions (Autonomous Communities [AACC]), and within the same hospital in the year before the SSU opened. A descriptive retrospective observational study that included patients with a diagnosis of PE in the University Hospital Virgen de la Arrixaca (HCUVA) in 2012. These data were classified by hospital department, and used for calculating the mean stay. This was then compared with that of other hospitals in our region, with the rest of the regions, and with the data in 2007 (the last year without a TU). A total of 113patients with PE were included, 60 (53%) in the TU with an MS of 4.39, in Oncology, 7.45, and Internal Medicine (IM), 15.38days. There were no deaths in the TU and only 3 (5%) readmissions. Published data showed that the MS in all hospitals in our region was 8.25, 5.18 in our hospital, and higher in the rest of hospitals. The best AACC was the Basque Country with an MS of 6.85days. In 2007, there were 70patients with PE in the HCUVA, 34 (49%) in IM, with an MS of 8.50, Oncology 11 (31%) with an MS 9.64, and Chest Diseases 3 (4.3%) with an MS 19days, and with an overall mortality of 11% and a rate of readmissions in IM of 6%. The mean stay for a PE in the SSU of a TU was lower than in the rest of the hospital departments, lower than the rest hospitals of our region, lower than the rest of the regions, and lower than any department of our hospital before the SSU existed, without increasing the readmission or mortality rate. Copyright © 2015 SECA. Publicado por Elsevier España, S.L.U. All rights reserved.
NASA Astrophysics Data System (ADS)
Taylor, Robert A.
2010-09-01
These conference proceedings contain the written papers of the contributions presented at Quantum Dot 2010 (QD2010). The conference was held in Nottingham, UK, on 26-30 April 2010. The conference addressed topics in research on: 1. Epitaxial quantum dots (including self-assembled and interface structures, dots defined by electrostatic gates etc): optical properties and electron transport quantum coherence effects spin phenomena optics of dots in cavities interaction with surface plasmons in metal/semiconductor structures opto-electronics applications 2. Novel QD structures: fabrication and physics of graphene dots, dots in nano-wires etc 3. Colloidal quantum dots: growth (shape control and hybrid nanocrystals such as metal/semiconductor, magnetic/semiconductor) assembly and surface functionalisation optical properties and spin dynamics electrical and magnetic properties applications (light emitting devices and solar cells, biological and medical applications, data storage, assemblers) The Editors Acknowledgements Conference Organising Committee: Maurice Skolnick (Chair) Alexander Tartakovskii (Programme Chair) Pavlos Lagoudakis (Programme Chair) Max Migliorato (Conference Secretary) Paola Borri (Publicity) Robert Taylor (Proceedings) Manus Hayne (Treasurer) Ray Murray (Sponsorship) Mohamed Henini (Local Organiser) International Advisory Committee: Yasuhiko Arakawa (Tokyo University, Japan) Manfred Bayer (Dortmund University, Germany) Sergey Gaponenko (Stepanov Institute of Physics, Minsk, Belarus) Pawel Hawrylak (NRC, Ottawa, Canada) Fritz Henneberger (Institute for Physics, Berlin, Germany) Atac Imamoglu (ETH, Zurich, Switzerland) Paul Koenraad (TU Eindhoven, Nethehrlands) Guglielmo Lanzani (Politecnico di Milano, Italy) Jungil Lee (Korea Institute of Science and Technology, Korea) Henri Mariette (CNRS-CEA, Grenoble, France) Lu Jeu Sham (San Diego, USA) Andrew Shields (Toshiba Research Europe, Cambridge, UK) Yoshihisa Yamamoto (Stanford University, USA) Artur Zrenner (Paderborn University, Germany) International Programme Committee: Alexander Eychmüller (TU Dresden, Germany) Jonathan Finley (TU Munich, Germany) Dan Gammon (NRL, Washington, USA) Alexander Govorov (Ohio University, USA) Neil Greenham (Cavendish Laboratory, UK) Vladimir Korenev (Ioffe Institute, Russia) Leo Kouwenhoven (TU Delft, Netherlands) Wolfgang Langbein (Cardiff University, UK) Xavier Marie (CNRS Toulouse, France) David Ritchie (Cambridge, UK) Andrew Sachrajda (IMS, Ottawa, Canada) Katerina Soulantica (University of Toulouse, France) Seigo Tarucha (University of Tokyo, Japan) Carlos Tejedor (UAM, Madrid, Spain) Euijoon Yoon (Seoul National University, Korea) Ulrike Woggon (Tu Berlin, Germany) Proceedings edited and compiled by Profesor Robert A Taylor, University of Oxford
Scale factor duality for conformal cyclic cosmologies
NASA Astrophysics Data System (ADS)
Camara da Silva, U.; Alves Lima, A. L.; Sotkov, G. M.
2016-11-01
The scale factor duality is a symmetry of dilaton gravity which is known to lead to pre-big-bang cosmologies. A conformal time version of the scale factor duality (SFD) was recently implemented as a UV/IR symmetry between decelerated and accelerated phases of the post-big-bang evolution within Einstein gravity coupled to a scalar field. The problem investigated in the present paper concerns the employment of the conformal time SFD methods to the construction of pre-big-bang and cyclic extensions of these models. We demonstrate that each big-bang model gives rise to two qualitatively different pre-big-bang evolutions: a contraction/expansion SFD model and Penrose's Conformal Cyclic Cosmology (CCC). A few examples of SFD symmetric cyclic universes involving certain gauged Kähler sigma models minimally coupled to Einstein gravity are studied. We also describe the specific SFD features of the thermodynamics and the conditions for validity of the generalized second law in the case of Gauss-Bonnet (GB) extension of these selected CCC models.
Prevalence of parvovirus in Minnesota turkeys.
Sharafeldin, T A; Singh, A; Abdel-Glil, M Y; Mor, S K; Porter, R E; Goyal, S M
2017-02-01
Poult enteritis syndrome (PES) is characterized by enteritis and decreased body weight gain in growing turkey poults between one d and 7 wk of age. Another syndrome called light turkey syndrome (LTS) causes a decrease in body weight of adult tom turkeys in Minnesota leading to huge economic losses. Reovirus, rotavirus, and astrovirus have been found in LTS and PES flocks in Minnesota. We tested 80 fecal pools collected from four LTS flocks and 35 fecal pools from non-LTS flocks for the presence of parvovirus. In addition, 116 fecal and meconium samples from turkeys submitted to the Minnesota Veterinary Diagnostic Laboratory (MVDL) also were tested. The samples were tested by PCR using primers for the non-structural 1 (NS1) gene of parvovirus. Of the 80 samples from LTS flocks, 41 were positive for parvovirus while 20 of 35 samples from non-LTS flocks were positive. The prevalence of parvovirus in fecal samples submitted to MVDL was relatively low; only five of the 116 pools were positive. The partial NS1 gene sequences from LTS and non-LTS samples showed 98 to 100% nt identity except for one divergent turkey parvovirus (TuPV) strain that revealed 90% identity and clustered with chicken-like parvoviruses. The presence of this divergent strain suggests circulation of a recombinant strain of TuPV in Minnesota turkeys. Our results indicate that TuPVs are circulating in both LTS and non-LTS flocks of turkeys in Minnesota, and further experimental studies are indicated to study the role of TuPV in LTS. © 2016 Poultry Science Association Inc.
Rennick, Linda J; Duprex, W Paul; Rima, Bert K
2007-10-01
Transcription from morbillivirus genomes commences at a single promoter in the 3' non-coding terminus, with the six genes being transcribed sequentially. The 3' and 5' untranslated regions (UTRs) of the genes (mRNA sense), together with the intergenic trinucleotide spacer, comprise the non-coding sequences (NCS) of the virus and contain the conserved gene end and gene start signals, respectively. Bicistronic minigenomes containing transcription units (TUs) encoding autofluorescent reporter proteins separated by measles virus (MV) NCS were used to give a direct estimation of gene expression in single, living cells by assessing the relative amounts of each fluorescent protein in each cell. Initially, five minigenomes containing each of the MV NCS were generated. Assays were developed to determine the amount of each fluorescent protein in cells at both cell population and single-cell levels. This revealed significant variations in gene expression between cells expressing the same NCS-containing minigenome. The minigenome containing the M/F NCS produced significantly lower amounts of fluorescent protein from the second TU (TU2), compared with the other minigenomes. A minigenome with a truncated F 5' UTR had increased expression from TU2. This UTR is 524 nt longer than the other MV 5' UTRs. Insertions into the 5' UTR of the enhanced green fluorescent protein gene in the minigenome containing the N/P NCS showed that specific sequences, rather than just the additional length of F 5' UTR, govern this decreased expression from TU2.
Toxicity and photoactivation of PAH mixtures in marine sediment
DOE Office of Scientific and Technical Information (OSTI.GOV)
Swartz, R.; Ferraro, S.; Lamberson, J.
1995-12-31
The toxicity and toxicological photoactivation of mixtures of sediment-associated fluoranthene, phenanthrene, pyrene, and acenaphthene were determined using standard 10 d sediment toxicity tests with the marine amphipod, Rhepoxynius abronius. The four PAHs were spiked into sediment in a concentration series of either single compounds or an equitoxic mixture. Spiked sediment was stored at 4 C for 28 d before testing. Toxicity tests were conducted under fluorescent lighting. Survivors after 10 d in PAH-contaminated sediment were exposed for 1 h to UV light in the absence of sediment and then tested for their ability to bury in clean sediment. The 10more » d LC50s for single PAHs were 3.3, 2.2, 2.8, and 2.3 mg/g oc for fluoranthene, phenanthrene, pyrene, and acenaphthene, respectively. These LC50s were used to calculate the sum of toxic units ({Sigma}TU) of the four PAHs in the equitoxic mixture treatments. The {Sigma}TU LC50 was then calculated for the mixture treatments. If the toxicological interaction of the four PAHs in the mixture was additive, the {Sigma}TU LC50 should equal 1.0. The observed {Sigma}TU LC50 in the mixture was 1.55, indicating the interaction was slightly less than additive. UV enhancement of toxic effects of individual PAHs was correctly predicted by photophysical properties, i.e. pyrene and fluoranthene were photoactivated and phenanthrene and acenaphthene were not. UV effects in the mixture of four PAHs can be explained by the photoactivation of pyrene and fluoranthene alone.« less
Future use of tritium in mapping pre-bomb groundwater volumes.
Eastoe, C J; Watts, C J; Ploughe, M; Wright, W E
2012-01-01
The tritium input to groundwater, represented as volume-weighted mean tritium concentrations in precipitation, has been close to constant in Tucson and Albuquerque since 1992, and the decrease in tritium concentrations at the tail end of the bomb tritium pulse has ceased. To determine the future usefulness of tritium measurements in southwestern North America, volume-weighted mean tritium levels in seasonal aggregate precipitation samples have been gathered from 26 sites. The averages range from 2 to 9 tritium units (TU). Tritium concentrations increase with site latitude, and possibly with distance from the coast and with site altitude, reflecting local ratios of combination of low-tritium moisture advected from the oceans with high-tritium moisture originating near the tropopause. Tritium used alone as a tool for mapping aquifer volumes containing only pre-bomb recharge to groundwater will become ambiguous when the tritium in precipitation at the end of the bomb tritium pulse decays to levels close to the analytical detection limit. At such a time, tritium in precipitation from the last one to two decades of the bomb pulse will become indistinguishable from pre-bomb recharge. The threshold of ambiguity has already arrived in coastal areas with a mean of 2 TU in precipitation and will follow in the next three decades throughout the study region. Where the mean tritium level is near 5 TU, the threshold will occur between 2025 and 2030, given a detection limit of 0.6 TU. Similar thresholds of ambiguity, with different local timing possible, apply globally. © 2011, The Author(s). Ground Water © 2011, National Ground Water Association.
The Conformal Factor and the Cosmological Constant
NASA Astrophysics Data System (ADS)
Giddings, Steven B.
The issue of the conformal factor in quantum gravity is examined for Lorentzian signature spacetimes. In Euclidean signature, the “wrong” sign of the conformal action makes the path integral undefined, but in Lorentzian signature this sign is tied to the instability of gravity and once this is accounted for the path integral should be well-defined. In this approach it is not obvious that the Baum-Hawking-Coleman mechanism for suppression of the cosmological constant functions. It is conceivable that since the multiuniverse system exhibits an instability for positive cosmological constant, the dynamics should force the system to zero cosmological constant.
Pilot Non-Conformance to Alerting System Commands
NASA Technical Reports Server (NTRS)
Pritchett, Amy R.; Hansman, R. John
1997-01-01
Instances of pilot non-conformance to alerting system commands have been identified in previous studies. Pilot non-conformance changes the final behavior of the system, and therefore may reduce actual performance from that anticipated. A simulator study has examined pilot non-conformance, using the task of collision avoidance during closely spaced parallel approaches as a case study. Consonance between the display and the alerting system was found to significantly improve subject agreement with automatic alerts. Based on these results, a more general discussion of the factors involved in pilot conformance is given, and design guidelines for alerting systems are given.
Effect of low-purity Fenton reagents on toxicity of textile dyeing effluent to Daphnia magna.
Na, Joorim; Yoo, Jisu; Nam, Gwiwoong; Jung, Jinho
2017-09-20
This study aimed to identify the source of toxicity in textile dyeing effluent collected from February to July 2016, using Daphnia magna as a test organism. Toxicity identification evaluation (TIE) procedures were used to identify the toxicants in textile dyeing effluent, and Jar testing to simulate the Fenton process was conducted to identify the source of toxicants. Textile dyeing effluent was acutely toxic to D. magna [from 1.5 to 9.7 toxic units (TU)] during the study period. TIE results showed that Zn derived from the Fenton process was a key toxicant in textile dyeing effluent. Additionally, Jar testing revealed that low-purity Fenton reagents (FeCl 2 and FeSO 4 ), which contained large amounts of Zn (89 838 and 610 mg L -1 , respectively), were the source of toxicity. Although we were unable to conclusively identify the residual toxicity (approx. 1.4 TU of 9.71 TU) attributable to unknown toxicants in textile dyeing effluent, the findings of this study suggest that careful operation of the Fenton treatment process could contribute to eliminating its unintended toxic effects on aquatic organisms.
Huang, L X
2017-11-28
This compilation process of Mian xue tang zhen jiu ji cheng ( Mian Xuetang ' s Synthetic Work of Acu - moxibustion )was quite mysterious, the book's advent coincidentally met with several major historical events which made its value of decoding its historical functions far beyond its academic value. The editor of this book is Le Xianyang, the founder of Tong Ren Tang. While compiling this book, he also made a replica of Ming-Dynasty's Zhengtong bronze statue. More than 200 years later, Le Jingyu, the 12th generation of the Le family revised Ming Tang Tu inherited from his ancestors and engraved Ming Tang Tu on the stone for its standardization. This great achievement of Le family was no less than the recasting of the Tiansheng bronze statue and the reengraving Tong ren shu xue zhen jiu tu jing ( Illustrated Manual of Acupuncture Points of the Bronze Figure ) by support of state power for building the Beijing Imperial Hospital in the eighth year of the Zhengtong reign (1443).
Conformational and stereoelectronic investigation in 1,2-difluoropropane: The gauche effect
NASA Astrophysics Data System (ADS)
Bitencourt, Michelle; Freitas, Matheus P.; Rittner, Roberto
2007-09-01
The effect of attaching an additional fluorine atom at C-2 in 1-fluoropropane (FP), giving 1,2-difluoropropane (DFP), on its conformational equilibrium, is theoretically evaluated. This substitution causes critical implications on the conformer stabilities of DFP (TG, GT and GG conformations) and the steric and electrostatic interactions should favor the conformer with fluorine atoms trans. However, the gauche effect plays a major role in describing the energies balance in DFP, shifting the equilibrium towards the conformation in which the two fluorine atoms are gauche. The origin of this effect is discussed through an NBO analysis, which allows the evaluation of both classical and non-classical (hyperconjugation and bent bonds) interactions as the prevailing factors governing the conformational equilibrium of molecules containing the 1,2-difluoroethane fragment.
Kumar, B; Han, L-F; Wassenaar, L I; Klaus, P M; Kainz, G G; Hillegonds, D; Brummer, D; Ahmad, M; Belachew, D L; Araguás, L; Aggarwal, P
2016-12-01
Tritium ( 3 H) in natural waters is a powerful tracer of hydrological processes, but its low concentrations require electrolytic enrichment before precise measurements can be made with a liquid scintillation counter. Here, we describe a newly developed, compact tritium enrichment unit which can be used to enrich up to 2L of a water sample. This allows a high enrichment factor (>100) for measuring low 3 H contents of <0.05TU. The TEU uses a small cell (250mL) with automated re-filling and a CO 2 bubbling technique to neutralize the high alkalinity of enriched samples. The enriched residual sample is retrieved from the cell under vacuum by cryogenic distillation at -20°C and the tritium enrichment factor for each sample is accurately determined by measuring pre- and post- enrichment 2 H concentrations with laser spectrometry. Copyright © 2016. Published by Elsevier Ltd.
Bacillus anthracis Prolyl 4-Hydroxylase Interacts with and Modifies Elongation Factor Tu
DOE Office of Scientific and Technical Information (OSTI.GOV)
Schnicker, Nicholas J.; Razzaghi, Mortezaali; Guha Thakurta, Sanjukta
Prolyl hydroxylation is a very common post-translational modification and plays many roles in eukaryotes such as collagen stabilization, hypoxia sensing, and controlling protein transcription and translation. There is a growing body of evidence that suggests that prokaryotes contain prolyl 4-hydroxylases (P4Hs) homologous to the hypoxia-inducible factor (HIF) prolyl hydroxylase domain (PHD) enzymes that act on elongation factor Tu (EFTu) and are likely involved in the regulation of bacterial translation. Recent biochemical and structural studies with a PHD from Pseudomonas putida (PPHD) determined that it forms a complex with EFTu and hydroxylates a prolyl residue of EFTu. Moreover, while animal, plant,more » and viral P4Hs act on peptidyl proline, most prokaryotic P4Hs have been known to target free l-proline; the exceptions include PPHD and a P4H from Bacillus anthracis (BaP4H) that modifies collagen-like proline-rich peptides. Here we use biophysical and mass spectrometric methods to demonstrate that BaP4H recognizes full-length BaEFTu and a BaEFTu 9-mer peptide for site-specific proline hydroxylation. Using size-exclusion chromatography coupled small-angle X-ray scattering (SEC–SAXS) and binding studies, we determined that BaP4H forms a 1:1 heterodimeric complex with BaEFTu. The SEC–SAXS studies reveal dissociation of BaP4H dimeric subunits upon interaction with BaEFTu. While BaP4H is unusual within bacteria in that it is structurally and functionally similar to the animal PHDs and collagen P4Hs, respectively, this work provides further evidence of its promiscuous substrate recognition. It is possible that the enzyme might have evolved to hydroxylate a universally conserved protein in prokaryotes, similar to the PHDs, and implies a functional role in B. anthracis.« less
Radiation-Resistant Micrococcus luteus SC1204 and Its Proteomics Change Upon Gamma Irradiation.
Deng, Wuyuan; Yang, Yang; Gao, Peng; Chen, Hao; Wen, Wenting; Sun, Qun
2016-06-01
To explore the radiation-resistance mechanisms in bacteria, a radiation-resistant strain SC1204 was isolated from the surrounding area of a (60)Co-γ radiation facility. SC1204 could survive up to 8 kGy dose of gamma irradiation and was identified as Micrococcus luteus by phylogenetic analysis of 16S rRNA gene sequences. Its proteomic changes under 2-kGy irradiation were examined by two-dimensional electrophoresis followed by MALDI-TOF-TOF/MS analysis. The results showed that at least 24 proteins displayed significant changes (p < 0.05) at expression level under the radiation stress, among which 22 were successfully identified and classified into the major functional categories of metabolism, energy production and conservation, translation, ribosomal structure, and biogenesis. Among these proteins, leucyl aminopeptidase involved in synthesis of glutathione was the most abundant induced protein during postirradiation recovery, indicating that anti-oxidation protection was the most important line of defense in SC1204 against radiation. The next abundant protein was phosphoribosyl aminoimidazole carboxamide formyltransferase/IMP cyclohydrolase (AICAR Tfase/IMPCH), the key enzyme in the biosynthetic pathway of purine that is anti-radiation compound. Other proteins changing significantly (p < 0.05) after radiation exposure included urocanate hydratase, dihydrolipoyl dehydrogenase, succinyl-CoA synthetase subunit alpha, phosphoglycerate kinase, cell division protein FtsZ, elongation factor Ts and Tu, translation elongation factor Tu and G, 30S ribosomal protein S1, histidyl-tRNA synthetase, and arginyl-tRNA synthetase, which were considered to be the key proteins in urocanate metabolism, tricarboxylic acid cycle, glycolysis, cell division process, and synthesis process of proteins. Therefore, these proteins may also play important roles in radiation resistance in M. luteus.
The Measure your World / Mide tu Mundo Project
NASA Astrophysics Data System (ADS)
Hojman, S.; Johnson, R. M.; Meymaris, K. K.; Ward, D. L.; Russell, R.; Genyuk, J.; Lagrave, M.; Henderson, S.; Ostrosky, J.; Martinez, M.
2007-12-01
Over 22 centuries ago Erathostenes devised a method to determine the Earth radius. Measure your World / Mide tu Mundo is a joint venture lead by Windows to the Universe/Ventanas al Universo in the United States of America, EducaRed in Chile and RedEscolar in Mexico seeking to partner teams of students, teachers and parents from the three countries in a collaborative effort to determine the Earth circumference by sharing the results of their measurements, and exchanging cultural information. Data are collected from September 29 through October 7, 2007. A report of the whole experience will be presented.
The Japanese Space Program (Le Programme Spatial Japonais),
1982-04-22
three-axis stabilization, study of vertical * structure of the earth); --series of probes for exploration of the moon and the planets. Future Missions...in foreground and 7 rr IArk j I, I *151 Fig. 9. Structural detail of the MU 3S (rear skirt) Fi. 1. St u tu a de ai of MU 3S..’’ ’ -, t r-’ ,’ s:,ru...ture) The total l t of te M I is 2-8. 2 m, - . The Fig. i. Structural detail of tU S (ri er sit)ctre 1.65 mthiamr. ach bfotitaniu wll have a
Shen, Li-Fang; Zhao, Xin; Zhou, Shui-Hong; Lu, Zhong-Jie; Zhao, Kui; Fan, Jun; Zhou, Min-Li
2017-01-01
Purpose Hypoxia-inducible factor 1α (HIF-1α) and glucose transporter-1 (GLUT-1) are two important hypoxic markers associated with the radioresistance of cancers including laryngeal carcinoma. We evaluated whether the simultaneous inhibition of GLUT-1 and HIF-1α expression improved the radiosensitivity of laryngeal carcinoma. We explored whether the expression of HIF-1α and GLUT-1 was correlated with 2′-deoxy-2’-[18F]fluoro-D-glucose (18F-FDG) uptake and whether 18F-FDG positron emission tomography-computed tomography (PET/CT) was appropriate for early evaluation of the response of laryngeal carcinoma to targeted treatment in vivo. Materials and Methods To verify the above hypotheses, an in vivo model was applied by subcutaneously injecting Hep-2 (2 × 107/mL × 0.2 mL) and Tu212 cells (2 × 107/mL × 0.2 mL) into nude mice. The effects of HIF-1α antisense oligodeoxynucleotides (AS-ODNs) (100 μg) and GLUT-1 AS-ODNs (100 μg) on the radiosensitivity of laryngeal carcinoma were assessed by tumor volume and weight, microvessel density (MVD), apoptosis index (AI) and necrosis in vivo based on a full factorial (23) design. 18F-FDG-PET/CT was taken before and after the treatment of xenografts. The relationships between HIF-1α and GLUT-1 expression and 18F-FDG uptake in xenografts were estimated and the value of 18F-FDG-PET/CT was assessed after treating the xenografts. Results 10 Gy X-ray irradiation decreased the weight of Hep-2 xenografts 8 and 12 days after treatment, and the weights of Tu212 xenografts 8 days after treatment. GLUT-1 AS-ODNs decreased the weight of Tu212 xenografts 12 days after treatment. There was a synergistic interaction among the three treatments (GLUT-1 AS-ODNs, HIF-1α AS-ODNs and 10Gy X-ray irradiation) in increasing apoptosis, decreasing MVD, and increasing necrosis in Hep-2 xenografts 8 days after treatment (p < 0.05) and in Tu212 xenografts 12 days after treatment (p < 0.001). Standardized uptake value (tumor/normal tissue)( SUVmaxT/N) did not show a statistically significant correlation with GLUT1 and HIF-1α expression and therapeutic effect (necrosis, apoptosis). Conclusions Simultaneous inhibition of HIF-1α and GLUT-1 expression might increase the radiosensitivity of laryngeal carcinoma, decreasing MVD, and promoting apoptosis and necrosis. 18F-FDG-PET/CT wasn't useful in evaluating the therapeutic effect on laryngeal cancer in this animal study. PMID:28410229
Shen, Li-Fang; Zhao, Xin; Zhou, Shui-Hong; Lu, Zhong-Jie; Zhao, Kui; Fan, Jun; Zhou, Min-Li
2017-05-23
Hypoxia-inducible factor 1α (HIF-1α) and glucose transporter-1 (GLUT-1) are two important hypoxic markers associated with the radioresistance of cancers including laryngeal carcinoma. We evaluated whether the simultaneous inhibition of GLUT-1 and HIF-1α expression improved the radiosensitivity of laryngeal carcinoma. We explored whether the expression of HIF-1α and GLUT-1 was correlated with 2'-deoxy-2'-[18F]fluoro-D-glucose (18F-FDG) uptake and whether 18F-FDG positron emission tomography-computed tomography (PET/CT) was appropriate for early evaluation of the response of laryngeal carcinoma to targeted treatment in vivo. To verify the above hypotheses, an in vivo model was applied by subcutaneously injecting Hep-2 (2 × 107/mL × 0.2 mL) and Tu212 cells (2 × 107/mL × 0.2 mL) into nude mice. The effects of HIF-1α antisense oligodeoxynucleotides (AS-ODNs) (100 μg) and GLUT-1 AS-ODNs (100 μg) on the radiosensitivity of laryngeal carcinoma were assessed by tumor volume and weight, microvessel density (MVD), apoptosis index (AI) and necrosis in vivo based on a full factorial (23) design. 18F-FDG-PET/CT was taken before and after the treatment of xenografts. The relationships between HIF-1α and GLUT-1 expression and 18F-FDG uptake in xenografts were estimated and the value of 18F-FDG-PET/CT was assessed after treating the xenografts. 10 Gy X-ray irradiation decreased the weight of Hep-2 xenografts 8 and 12 days after treatment, and the weights of Tu212 xenografts 8 days after treatment. GLUT-1 AS-ODNs decreased the weight of Tu212 xenografts 12 days after treatment. There was a synergistic interaction among the three treatments (GLUT-1 AS-ODNs, HIF-1α AS-ODNs and 10Gy X-ray irradiation) in increasing apoptosis, decreasing MVD, and increasing necrosis in Hep-2 xenografts 8 days after treatment (p < 0.05) and in Tu212 xenografts 12 days after treatment (p < 0.001). Standardized uptake value (tumor/normal tissue)( SUVmaxT/N) did not show a statistically significant correlation with GLUT1 and HIF-1α expression and therapeutic effect (necrosis, apoptosis). Simultaneous inhibition of HIF-1α and GLUT-1 expression might increase the radiosensitivity of laryngeal carcinoma, decreasing MVD, and promoting apoptosis and necrosis. 18F-FDG-PET/CT wasn't useful in evaluating the therapeutic effect on laryngeal cancer in this animal study.
NASA Astrophysics Data System (ADS)
Ogura, Kenji; Okamura, Hideyasu
2013-10-01
Growth factor receptor-bound protein 2 (Grb2) is a small adapter protein composed of a single SH2 domain flanked by two SH3 domains. The N-terminal SH3 (nSH3) domain of Grb2 binds a proline-rich region present in the guanine nucleotide releasing factor, son of sevenless (Sos). Using NMR relaxation dispersion and chemical shift analysis methods, we investigated the conformational change of the Sos-derived proline-rich peptide during the transition between the free and Grb2 nSH3-bound states. The chemical shift analysis revealed that the peptide does not present a fully random conformation but has a relatively rigid structure. The relaxation dispersion analysis detected conformational exchange of several residues of the peptide upon binding to Grb2 nSH3.
Pilot Non-Conformance to Alerting System Commands During Closely Spaced Parallel Approaches
NASA Technical Reports Server (NTRS)
Pritchett, Amy R.; Hansman, R. John
1997-01-01
Pilot non-conformance to alerting system commands has been noted in general and to a TCAS-like collision avoidance system in a previous experiment. This paper details two experiments studying collision avoidance during closely-spaced parallel approaches in instrument meteorological conditions (IMC), and specifically examining possible causal factors of, and design solutions to, pilot non-conformance.
TU-AB-BRB-01: Coverage Evaluation and Probabilistic Treatment Planning as a Margin Alternative
DOE Office of Scientific and Technical Information (OSTI.GOV)
Siebers, J.
The accepted clinical method to accommodate targeting uncertainties inherent in fractionated external beam radiation therapy is to utilize GTV-to-CTV and CTV-to-PTV margins during the planning process to design a PTV-conformal static dose distribution on the planning image set. Ideally, margins are selected to ensure a high (e.g. >95%) target coverage probability (CP) in spite of inherent inter- and intra-fractional positional variations, tissue motions, and initial contouring uncertainties. Robust optimization techniques, also known as probabilistic treatment planning techniques, explicitly incorporate the dosimetric consequences of targeting uncertainties by including CP evaluation into the planning optimization process along with coverage-based planning objectives. Themore » treatment planner no longer needs to use PTV and/or PRV margins; instead robust optimization utilizes probability distributions of the underlying uncertainties in conjunction with CP-evaluation for the underlying CTVs and OARs to design an optimal treated volume. This symposium will describe CP-evaluation methods as well as various robust planning techniques including use of probability-weighted dose distributions, probability-weighted objective functions, and coverage optimized planning. Methods to compute and display the effect of uncertainties on dose distributions will be presented. The use of robust planning to accommodate inter-fractional setup uncertainties, organ deformation, and contouring uncertainties will be examined as will its use to accommodate intra-fractional organ motion. Clinical examples will be used to inter-compare robust and margin-based planning, highlighting advantages of robust-plans in terms of target and normal tissue coverage. Robust-planning limitations as uncertainties approach zero and as the number of treatment fractions becomes small will be presented, as well as the factors limiting clinical implementation of robust planning. Learning Objectives: To understand robust-planning as a clinical alternative to using margin-based planning. To understand conceptual differences between uncertainty and predictable motion. To understand fundamental limitations of the PTV concept that probabilistic planning can overcome. To understand the major contributing factors to target and normal tissue coverage probability. To understand the similarities and differences of various robust planning techniques To understand the benefits and limitations of robust planning techniques.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Xu, H.
The accepted clinical method to accommodate targeting uncertainties inherent in fractionated external beam radiation therapy is to utilize GTV-to-CTV and CTV-to-PTV margins during the planning process to design a PTV-conformal static dose distribution on the planning image set. Ideally, margins are selected to ensure a high (e.g. >95%) target coverage probability (CP) in spite of inherent inter- and intra-fractional positional variations, tissue motions, and initial contouring uncertainties. Robust optimization techniques, also known as probabilistic treatment planning techniques, explicitly incorporate the dosimetric consequences of targeting uncertainties by including CP evaluation into the planning optimization process along with coverage-based planning objectives. Themore » treatment planner no longer needs to use PTV and/or PRV margins; instead robust optimization utilizes probability distributions of the underlying uncertainties in conjunction with CP-evaluation for the underlying CTVs and OARs to design an optimal treated volume. This symposium will describe CP-evaluation methods as well as various robust planning techniques including use of probability-weighted dose distributions, probability-weighted objective functions, and coverage optimized planning. Methods to compute and display the effect of uncertainties on dose distributions will be presented. The use of robust planning to accommodate inter-fractional setup uncertainties, organ deformation, and contouring uncertainties will be examined as will its use to accommodate intra-fractional organ motion. Clinical examples will be used to inter-compare robust and margin-based planning, highlighting advantages of robust-plans in terms of target and normal tissue coverage. Robust-planning limitations as uncertainties approach zero and as the number of treatment fractions becomes small will be presented, as well as the factors limiting clinical implementation of robust planning. Learning Objectives: To understand robust-planning as a clinical alternative to using margin-based planning. To understand conceptual differences between uncertainty and predictable motion. To understand fundamental limitations of the PTV concept that probabilistic planning can overcome. To understand the major contributing factors to target and normal tissue coverage probability. To understand the similarities and differences of various robust planning techniques To understand the benefits and limitations of robust planning techniques.« less
TU-AB-BRB-02: Stochastic Programming Methods for Handling Uncertainty and Motion in IMRT Planning
DOE Office of Scientific and Technical Information (OSTI.GOV)
Unkelbach, J.
The accepted clinical method to accommodate targeting uncertainties inherent in fractionated external beam radiation therapy is to utilize GTV-to-CTV and CTV-to-PTV margins during the planning process to design a PTV-conformal static dose distribution on the planning image set. Ideally, margins are selected to ensure a high (e.g. >95%) target coverage probability (CP) in spite of inherent inter- and intra-fractional positional variations, tissue motions, and initial contouring uncertainties. Robust optimization techniques, also known as probabilistic treatment planning techniques, explicitly incorporate the dosimetric consequences of targeting uncertainties by including CP evaluation into the planning optimization process along with coverage-based planning objectives. Themore » treatment planner no longer needs to use PTV and/or PRV margins; instead robust optimization utilizes probability distributions of the underlying uncertainties in conjunction with CP-evaluation for the underlying CTVs and OARs to design an optimal treated volume. This symposium will describe CP-evaluation methods as well as various robust planning techniques including use of probability-weighted dose distributions, probability-weighted objective functions, and coverage optimized planning. Methods to compute and display the effect of uncertainties on dose distributions will be presented. The use of robust planning to accommodate inter-fractional setup uncertainties, organ deformation, and contouring uncertainties will be examined as will its use to accommodate intra-fractional organ motion. Clinical examples will be used to inter-compare robust and margin-based planning, highlighting advantages of robust-plans in terms of target and normal tissue coverage. Robust-planning limitations as uncertainties approach zero and as the number of treatment fractions becomes small will be presented, as well as the factors limiting clinical implementation of robust planning. Learning Objectives: To understand robust-planning as a clinical alternative to using margin-based planning. To understand conceptual differences between uncertainty and predictable motion. To understand fundamental limitations of the PTV concept that probabilistic planning can overcome. To understand the major contributing factors to target and normal tissue coverage probability. To understand the similarities and differences of various robust planning techniques To understand the benefits and limitations of robust planning techniques.« less
TU-AB-BRB-00: New Methods to Ensure Target Coverage
DOE Office of Scientific and Technical Information (OSTI.GOV)
NONE
2015-06-15
The accepted clinical method to accommodate targeting uncertainties inherent in fractionated external beam radiation therapy is to utilize GTV-to-CTV and CTV-to-PTV margins during the planning process to design a PTV-conformal static dose distribution on the planning image set. Ideally, margins are selected to ensure a high (e.g. >95%) target coverage probability (CP) in spite of inherent inter- and intra-fractional positional variations, tissue motions, and initial contouring uncertainties. Robust optimization techniques, also known as probabilistic treatment planning techniques, explicitly incorporate the dosimetric consequences of targeting uncertainties by including CP evaluation into the planning optimization process along with coverage-based planning objectives. Themore » treatment planner no longer needs to use PTV and/or PRV margins; instead robust optimization utilizes probability distributions of the underlying uncertainties in conjunction with CP-evaluation for the underlying CTVs and OARs to design an optimal treated volume. This symposium will describe CP-evaluation methods as well as various robust planning techniques including use of probability-weighted dose distributions, probability-weighted objective functions, and coverage optimized planning. Methods to compute and display the effect of uncertainties on dose distributions will be presented. The use of robust planning to accommodate inter-fractional setup uncertainties, organ deformation, and contouring uncertainties will be examined as will its use to accommodate intra-fractional organ motion. Clinical examples will be used to inter-compare robust and margin-based planning, highlighting advantages of robust-plans in terms of target and normal tissue coverage. Robust-planning limitations as uncertainties approach zero and as the number of treatment fractions becomes small will be presented, as well as the factors limiting clinical implementation of robust planning. Learning Objectives: To understand robust-planning as a clinical alternative to using margin-based planning. To understand conceptual differences between uncertainty and predictable motion. To understand fundamental limitations of the PTV concept that probabilistic planning can overcome. To understand the major contributing factors to target and normal tissue coverage probability. To understand the similarities and differences of various robust planning techniques To understand the benefits and limitations of robust planning techniques.« less
NASA Astrophysics Data System (ADS)
Abadi Berhe, Berihu; Erdem Dokuz, Uğur; Çelik, Mehmet
2017-10-01
The aim of the present work is to determine the geochemical processes that control the nature of the groundwater and assess the quality of water for drinking and public health purposes. Surface and groundwater samples of Kütahya plain were analyzed for their physio-chemical and environmental isotope properties. The relative concentrations of the water ions were found to occur in the order of Ca2+>Mg2+>(K+ + Na+) and HCO3->SO42->Cl-. Piper diagram shows that Ca-Mg/Mg-Ca-HCO3 was the dominant water types. Waters in the area were super-saturated with respect to carbonates. However, they were under-saturated with respect to sulphate minerals. The groundwaters had a mean isotopic composition of -67.32 δ2H and -9.72 δ18O and were comparatively lower than surface waters -64.64 δ2H and -9.25 δ18O. Tritium activities in groundwater from the wells ranged from 1.00 to 8.38 TU with a mean value of 4.37 TU. The impact of agricultural practices and poor sanitation conditions is indicated by the positive correlation between K+ - NO3-, K+- NO2- and HCO3- - Cl- ions as well as Na+ and Mg2+ ions with SO42-ion. The groundwater quality of Kütahya plain is influenced by various natural and anthropogenic factors.
Rotationally resolved electronic spectroscopy study of the conformational space of 3-methoxyphenol
NASA Astrophysics Data System (ADS)
Wilke, Martin; Schneider, Michael; Wilke, Josefin; Ruiz-Santoyo, José Arturo; Campos-Amador, Jorge J.; González-Medina, M. Elena; Álvarez-Valtierra, Leonardo; Schmitt, Michael
2017-07-01
Conformational preferences are determined by (de-)stabilization effects like intramolecular hydrogen bonds or steric hindrance of adjacent substituents and thus, influence the stability and reactivity of the conformers. In the present contribution, we investigate the conformational landscape of 3-methoxyphenol using a combination of high resolution electronic spectroscopy and ab initio calculations. Three of the four possible conformational isomers were characterized in their electronic ground and lowest excited singlet states on the basis of their rotational constants and other molecular parameters. The absence of one conformer in molecular beam studies can be explained by its non-planar structure in the excited state, which leads to a vanishingly small Franck-Condon factor of the respective origin excitation.
Poltev, V; Anisimov, V M; Dominguez, V; Gonzalez, E; Deriabina, A; Garcia, D; Rivas, F; Polteva, N A
2018-02-01
Deciphering the mechanism of functioning of DNA as the carrier of genetic information requires identifying inherent factors determining its structure and function. Following this path, our previous DFT studies attributed the origin of unique conformational characteristics of right-handed Watson-Crick duplexes (WCDs) to the conformational profile of deoxydinucleoside monophosphates (dDMPs) serving as the minimal repeating units of DNA strand. According to those findings, the directionality of the sugar-phosphate chain and the characteristic ranges of dihedral angles of energy minima combined with the geometric differences between purines and pyrimidines determine the dependence on base sequence of the three-dimensional (3D) structure of WCDs. This work extends our computational study to complementary deoxydinucleotide-monophosphates (cdDMPs) of non-standard conformation, including those of Z-family, Hoogsteen duplexes, parallel-stranded structures, and duplexes with mispaired bases. For most of these systems, except Z-conformation, computations closely reproduce experimental data within the tolerance of characteristic limits of dihedral parameters for each conformation family. Computation of cdDMPs with Z-conformation reveals that their experimental structures do not correspond to the internal energy minimum. This finding establishes the leading role of external factors in formation of the Z-conformation. Energy minima of cdDMPs of non-Watson-Crick duplexes demonstrate different sequence-dependence features than those known for WCDs. The obtained results provide evidence that the biologically important regularities of 3D structure distinguish WCDs from duplexes having non-Watson-Crick nucleotide pairing.
NASA Astrophysics Data System (ADS)
Pajewski, Lara; Benedetto, Andrea; Loizos, Andreas; Slob, Evert; Tosti, Fabio
2015-04-01
This work aims at presenting the ongoing activities and mid-term results of the COST (European COoperation in Science and Technology) Action TU1208 'Civil Engineering Applications of Ground Penetrating Radar.' Almost three hundreds experts are participating to the Action, from 28 COST Countries (Austria, Belgium, Croatia, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Ireland, Italy, Latvia, Malta, Macedonia, The Netherlands, Norway, Poland, Portugal, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey, United Kingdom), and from Albania, Armenia, Australia, Egypt, Hong Kong, Jordan, Israel, Philippines, Russia, Rwanda, Ukraine, and United States of America. In September 2014, TU1208 has been praised among the running Actions as 'COST Success Story' ('The Cities of Tomorrow: The Challenges of Horizon 2020,' September 17-19, 2014, Torino, IT - A COST strategic workshop on the development and needs of the European cities). The principal goal of the COST Action TU1208 is to exchange and increase scientific-technical knowledge and experience of GPR techniques in civil engineering, whilst simultaneously promoting throughout Europe the effective use of this safe and non-destructive technique in the monitoring of infrastructures and structures. Moreover, the Action is oriented to the following specific objectives and expected deliverables: (i) coordinating European scientists to highlight problems, merits and limits of current GPR systems; (ii) developing innovative protocols and guidelines, which will be published in a handbook and constitute a basis for European standards, for an effective GPR application in civil- engineering tasks; safety, economic and financial criteria will be integrated within the protocols; (iii) integrating competences for the improvement and merging of electromagnetic scattering techniques and of data- processing techniques; this will lead to a novel freeware tool for the localization of buried objects, shape-reconstruction and estimation of geophysical parameters useful for civil engineering needs; (iv) networking for the design, realization and optimization of innovative GPR equipment; (v) comparing GPR with different NDT techniques, such as ultrasonic, radiographic, liquid-penetrant, magnetic-particle, acoustic-emission and eddy-current testing; (vi) comparing GPR technology and methodology used in civil engineering with those used in other fields; (vii) promotion of a more widespread, advanced and efficient use of GPR in civil engineering; and (viii) organization of a high-level modular training program for GPR European users. Four Working Groups (WGs) carry out the research activities. WG 1 focuses on the design of innovative GPR equipment, on the building of prototypes and on the testing and optimisation of new systems. WG 2 focuses on the GPR surveying of pavement, bridges, tunnels and buildings, as well as on the sensing of underground utilities and voids. WG 3 deals with the development of electromagnetic forward and inverse scattering methods, for the characterization of GPR scenarios, as well as with data- processing algorithms for the elaboration of the data collected during GPR surveys. WG 4 works on the use of GPR in fields different from the civil engineering, as well as on the integration of GPR with other non-destructive testing techniques. Each WG includes several Projects. COST Action TU1208 is active through a range of networking tools: meetings, workshops, conferences, training schools, short-term scientific missions, dissemination activities. The Action is still open to the participation of new parties and it is possible to include, in the scientific work plan, new perspectives and activities. Scientists and scientific institutions willing to join are encouraged to contact the Chair of the Action and to follow the procedure described at http://www.cost.eu/participate/join_action. For more information on COST Action TU1208, please visit www.GPRadar.eu. Acknowledgement The Authors thank COST, for funding the Action TU1208 "Civil Engineering Applications of Ground Penetrating Radar." References [1] L. Pajewski, A. Benedetto, X. Dérobert, A. Giannopoulos, A. Loizos, G. Manacorda, M. Marciniak, C. Plati, G. Schettini, I. Trinks, "Applications of Ground Penetrating Radar in Civil Engineering - COST Action TU1208," Proc. 7th International Workshop on Advanced Ground Penetrating Radar (IWAGPR), 2-5 July 2013, Nantes, France, pp. 1-6 (INVITED). ISBN 978-1-4799-0937-7, doi:10.1109/ IWAGPR.2013.6601528). [2] L. Pajewski, A. Benedetto, "Advanced Ground Penetrating Radar: open issues and new research opportunities in Europe," Proc. 10th European Radar Conference (EuRad), 2013 European Microwave Week (EuMW), 6-11 October 2013, Nuremberg, Germany, pp. 1847-1850. [3] 'Proceedings of the First Action's General Meeting - Rome, Italy, July 2013' 1st edition, COST Action TU1208, Aracne, L. Pajewski and A. Benedetto, Eds., Rome, Italy, July 2013, ISBN 978-88-548-6191-6, available online at www.GPRadar.eu. [4] 'Booklet of Participants and Institutions,' 1st edition, COST Action TU1208, Aracne, L. Pajewski and A. Benedetto, Eds., Rome, Italy, July 2013, ISBN 978-88-548-6192-3, available online at www.GPRadar.eu. [5] 'Proceedings of the 2014 Working Group Progress Meeting - Nantes, France, February 2014,' COST Action TU1208, Aracne, L. Pajewski and X. Derobert, Eds., Rome, Italy, May 2014, ISBN 978-88-548-7223-3, available online at www.GPRadar.eu. [6] 'Proceedings of the Second Action's General Meeting - Vienna, Austria, April-May 2014,' COST Action TU1208, Aracne, L. Pajewski and A. Benedetto, Eds., Rome, Italy, 2014, ISBN 978-88-548-7224-0. [7] 'Short Term Scientific Missions and Training Schools - Year 1,' COST Action TU1208, Aracne, L. Pajewski and M. Marciniak, Eds., Rome, Italy, 2014, ISBN 978-88-548-7225-7. [8] 'Civil Engineering Applications of Ground Penetrating Radar,' A. Benedetto and L. Pajewski Eds., Springer, July 2015, ISBN 978-3-319-04812-3 (in press). [9] 'Proceedings of the 15th International Conference on Ground Penetrating Radar - GPR2014, June 30 - July 4, 2014, Bruxelles, Belgium,' S. Lambot, A. Giannopoulos, L. Pajewski, F. De André, E. Slob, and C. Craeye, Eds., IEEE Conference Record Number: 35163, ISBN: 978-1-4799-6789-6, IEEE Part Number: CFP14538-ART, October 2014. [10] 'Near Surface Geophysics' Special Issue on 'Civil and Environmental Engineering Applications of Ground Penetrating Radar,' A. Benedetto, A. Loizos, L. Pajewski, and F. Tosti, Guest Eds., publication planned for Spring 2015. [11] IEEE Journal of Selected Topics in Applied Earth Observations and Remote Sensing (JSTARS) Special Issue on 'Ground Penetrating Radar', S. Lambot, A. Giannopoulos, L. Pajewski, E. Slob, Guest Eds., publication planned for December 2015.
NASA Astrophysics Data System (ADS)
Pajewski, Lara; Benedetto, Andrea; Loizos, Andreas; Tosti, Fabio
2016-04-01
This work aims at disseminating the ongoing research activities and third-year results of the COST (European COoperation in Science and Technology) Action TU1208 "Civil Engineering Applications of Ground Penetrating Radar." About 350 experts are participating to the Action, from 28 COST Countries (Austria, Belgium, Croatia, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Ireland, Italy, Latvia, Malta, Macedonia, The Netherlands, Norway, Poland, Portugal, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey, United Kingdom), and from Albania, Armenia, Australia, Colombia, Egypt, Hong Kong, Jordan, Israel, Philippines, Russia, Rwanda, Ukraine, and United States of America. In September 2014, TU1208 has been recognised among the running Actions as "COST Success Story" ("The Cities of Tomorrow: The Challenges of Horizon 2020," September 17-19, 2014, Torino, IT - A COST strategic workshop on the development and needs of the European cities). The principal goal of the COST Action TU1208 is to exchange and increase scientific-technical knowledge and experience of GPR techniques in civil engineering, whilst simultaneously promoting throughout Europe the effective use of this safe and non-destructive technique in the monitoring of infrastructures and structures. Moreover, the Action is oriented to the following specific objectives and expected deliverables: (i) coordinating European scientists to highlight problems, merits and limits of current GPR systems; (ii) developing innovative protocols and guidelines, which will be published in a handbook and constitute a basis for European standards, for an effective GPR application in civil- engineering tasks; safety, economic and financial criteria will be integrated within the protocols; (iii) integrating competences for the improvement and merging of electromagnetic scattering techniques and of data- processing techniques; this will lead to a novel freeware tool for the localization of buried objects, shape-reconstruction and estimation of geophysical parameters useful for civil engineering needs; (iv) networking for the design, realization and optimization of innovative GPR equipment; (v) comparing GPR with different NDT techniques, such as ultrasonic, radiographic, liquid-penetrant, magnetic-particle, acoustic-emission and eddy-current testing; (vi) comparing GPR technology and methodology used in civil engineering with those used in other fields; (vii) promotion of a more widespread, advanced and efficient use of GPR in civil engineering; and (viii) organization of a high-level modular training program for GPR European users. Four Working Groups (WGs) carry out the research activities. WG 1 focuses on the design of innovative GPR equipment, on the building of prototypes and on the testing and optimisation of new systems. WG 2 focuses on the GPR surveying of pavement, bridges, tunnels and buildings, as well as on the sensing of underground utilities and voids. WG 3 deals with the development of electromagnetic forward and inverse scattering methods, for the characterization of GPR scenarios, as well as with data-processing algorithms for the elaboration of the data collected during GPR surveys. WG 4 works on the use of GPR in fields different from the civil engineering, as well as on the integration of GPR with other non-destructive testing techniques. Each WG includes several Projects. COST Action TU1208 is active through a range of networking tools: meetings, workshops, conferences, training schools, short-term scientific missions, dissemination activities. For more information on COST Action TU1208, please visit www.GPRadar.eu and www.cost.eu. Acknowledgement The Authors wish to thank COST, for funding the COST Action TU1208 "Civil engineering applications of Ground Penetrating Radar."
Tu-144LL SST Flying Laboratory on Taxiway at Zhukovsky Air Development Center near Moscow, Russia
NASA Technical Reports Server (NTRS)
1998-01-01
The sleek lines of the Tupolev Tu-144LL are evident as it sits on the taxiway at the Zhukovsky Air Development Center near Moscow, Russia. NASA teamed with American and Russian aerospace industries for an extended period in a joint international research program featuring the Russian-built Tu-144LL supersonic aircraft. The object of the program was to develop technologies for a proposed future second-generation supersonic airliner to be developed in the 21st Century. The aircraft's initial flight phase began in June 1996 and concluded in February 1998 after 19 research flights. A shorter follow-on program involving seven flights began in September 1998 and concluded in April 1999. All flights were conducted in Russia from Tupolev's facility at the Zhukovsky Air Development Center near Moscow. The centerpiece of the research program was the Tu 144LL, a first-generation Russian supersonic jetliner that was modified by its developer/builder, Tupolev ANTK (aviatsionnyy nauchno-tekhnicheskiy kompleks-roughly, aviation technical complex), into a flying laboratory for supersonic research. Using the Tu-144LL to conduct flight research experiments, researchers compared full-scale supersonic aircraft flight data with results from models in wind tunnels, computer-aided techniques, and other flight tests. The experiments provided unique aerodynamic, structures, acoustics, and operating environment data on supersonic passenger aircraft. Data collected from the research program was being used to develop the technology base for a proposed future American-built supersonic jetliner. Although actual development of such an advanced supersonic transport (SST) is currently on hold, commercial aviation experts estimate that a market for up to 500 such aircraft could develop by the third decade of the 21st Century. The Tu-144LL used in the NASA-sponsored research program was a 'D' model with different engines than were used in production-model aircraft. Fifty experiments were proposed for the program and eight were selected, including six flight and two ground (engine) tests. The flight experiments included studies of the aircraft's exterior surface, internal structure, engine temperatures, boundary-layer airflow, the wing's ground-effect characteristics, interior and exterior noise, handling qualities in various flight profiles, and in-flight structural flexibility. The ground tests studied the effect of air inlet structures on airflow entering the engine and the effect on engine performance when supersonic shock waves rapidly change position in the engine air inlet. A second phase of testing further studied the original six in-flight experiments with additional instrumentation installed to assist in data acquisition and analysis. A new experiment aimed at measuring the in-flight deflections of the wing and fuselage was also conducted. American-supplied transducers and sensors were installed to measure nose boom pressures, angle of attack, and sideslip angles with increased accuracy. Two NASA pilots, Robert Rivers of Langley Research Center, Hampton, Virginia, and Gordon Fullerton from Dryden Flight Research Center, Edwards, California, assessed the aircraft's handling at subsonic and supersonic speeds during three flight tests in September 1998. The program concluded after four more data-collection flights in the spring of 1999. The Tu-144LL model had new Kuznetsov NK-321 turbofan engines rated at more than 55,000 pounds of thrust in full afterburner. The aircraft is 215 feet, 6 inches long and 42 feet, 2 inches high with a wingspan of 94 feet, 6 inches. The aircraft is constructed mostly of light aluminum alloy with titanium and stainless steel on the leading edges, elevons, rudder, and the under-surface of the rear fuselage.
Tu-144LL SST Flying Laboratory Lifts off Runway on a High-Speed Research Flight
NASA Technical Reports Server (NTRS)
1998-01-01
The Tupolev Tu-144LL lifts off from the Zhukovsky Air Development Center near Moscow, Russia, on a 1998 test flight. NASA teamed with American and Russian aerospace industries for an extended period in a joint international research program featuring the Russian-built Tu-144LL supersonic aircraft. The object of the program was to develop technologies for a proposed future second-generation supersonic airliner to be developed in the 21st Century. The aircraft's initial flight phase began in June 1996 and concluded in February 1998 after 19 research flights. A shorter follow-on program involving seven flights began in September 1998 and concluded in April 1999. All flights were conducted in Russia from Tupolev's facility at the Zhukovsky Air Development Center near Moscow. The centerpiece of the research program was the Tu 144LL, a first-generation Russian supersonic jetliner that was modified by its developer/builder, Tupolev ANTK (aviatsionnyy nauchno-tekhnicheskiy kompleks-roughly, aviation technical complex), into a flying laboratory for supersonic research. Using the Tu-144LL to conduct flight research experiments, researchers compared full-scale supersonic aircraft flight data with results from models in wind tunnels, computer-aided techniques, and other flight tests. The experiments provided unique aerodynamic, structures, acoustics, and operating environment data on supersonic passenger aircraft. Data collected from the research program was being used to develop the technology base for a proposed future American-built supersonic jetliner. Although actual development of such an advanced supersonic transport (SST) is currently on hold, commercial aviation experts estimate that a market for up to 500 such aircraft could develop by the third decade of the 21st Century. The Tu-144LL used in the NASA-sponsored research program was a 'D' model with different engines than were used in production-model aircraft. Fifty experiments were proposed for the program and eight were selected, including six flight and two ground (engine) tests. The flight experiments included studies of the aircraft's exterior surface, internal structure, engine temperatures, boundary-layer airflow, the wing's ground-effect characteristics, interior and exterior noise, handling qualities in various flight profiles, and in-flight structural flexibility. The ground tests studied the effect of air inlet structures on airflow entering the engine and the effect on engine performance when supersonic shock waves rapidly change position in the engine air inlet. A second phase of testing further studied the original six in-flight experiments with additional instrumentation installed to assist in data acquisition and analysis. A new experiment aimed at measuring the in-flight deflections of the wing and fuselage was also conducted. American-supplied transducers and sensors were installed to measure nose boom pressures, angle of attack, and sideslip angles with increased accuracy. Two NASA pilots, Robert Rivers of Langley Research Center, Hampton, Virginia, and Gordon Fullerton from Dryden Flight Research Center, Edwards, California, assessed the aircraft's handling at subsonic and supersonic speeds during three flight tests in September 1998. The program concluded after four more data-collection flights in the spring of 1999. The Tu-144LL model had new Kuznetsov NK-321 turbofan engines rated at more than 55,000 pounds of thrust in full afterburner. The aircraft is 215 feet, 6 inches long and 42 feet, 2 inches high with a wingspan of 94 feet, 6 inches. The aircraft is constructed mostly of light aluminum alloy with titanium and stainless steel on the leading edges, elevons, rudder, and the under-surface of the rear fuselage.
The gammaTuRC Nanomachine Mechanism and Future Applications
NASA Astrophysics Data System (ADS)
Riehlman, Timothy D.
The complexity and precision of the eukaryotic cell's cytoskeletal network is unrivaled by any man-made systems, perfected by billions of years of evolution, mastering elegant processes of self-assembly, error correction, and self-repair. Understanding the capabilities of these networks will have important and far reaching applications in human medicine by aiding our understanding of developmental processes, cellular division, and disease mechanisms, and through biomimicry will provide insights for biosynthetic manufacturing at the nanoscale and across scales. My research utilizes cross species techniques from Human to the model organism of Fission Yeast to investigate the structure and mechanisms of the g-tubulin ring complex (gTuRC). The gTuRC is a highly conserved eukaryotic multiprotein complex serving as a microtubule organizing center (MTOC) responsible for microtubule nucleation through templating, regulation of dynamics, and establishment of microtubule polarity. Microtubules are 25 nm diameter dynamic flexible polymers of a/b-tubulin heterodimers that function as scaffolds, force generators, distributors, and intracellular highways. The microtubule cytoskeleton is essential for numerous fundamental cellular processes such as mitotic division of chromosomes and cell division, organelle distribution within the cell, cell signaling, and cell shape. This incredible diversity in functions is made possible in part due to molecular motor Kinesin-like proteins (Klps), which allow expansion into more specialized neural, immune, and ciliated cell functions. Combined, the MTOC, microtubules, and Klps represent ideal microtubule cytoskeleton protein (MCP) modular components for in vitro biomimicry towards generation of adaptable patterned networks for human designed applications. My research investigates the hypothesis that a mechanistic understanding of conserved MTOC gTuRC mechanisms will help us understand dynamic cellular nanomachines and their ability to self-assemble complex structures for applications in biomedicine and new roles in biomimetic nanotechnologies.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Yarde, Richard
2003-06-13
BPA proposes to fund several water rights acquisition projects proposed by Trout Unlimited Montana Water Project (TU). The funding will be administered by the National Fish and Wildlife Foundation, the entity administering the Columbia Basin Water Transactions Program, initiated under RPA 151 of the National Marine Fisheries Service’s 2000 Biological Opinion on the Operation of the Federal Columbia River Power System. The water rights acquired by TU will be left instream to increase flow and improve water quality. Increasing instream flow of water-limited streams benefits fish listed under the Endangered Species Act. The three projects proposed by TU include: amore » Diversion Reduction Agreement, where the landowner agrees to leave up to 4 cubic feet per second (cfs) of water in Rock Creek for the 2003 irrigation season; another Diversion Reduction Agreement for the latter part of the 2003 irrigation season, under which the landowner would agree to cease diverting 1.65 cfs on Rock Creek and between 3 to 6 cfs from the North Fork Blackfoot River; the final proposal is one piece of a larger project in conjunction with other local, federal and state entities, to install a pipeline and sprinkler system to replace a ditch and flood irrigation system, which will result in the conversion of 15.11 cfs of water rights to instream flow. TU's contribution to the proposal (and BPA’s funding) is limited to working with the landowner to convert the water rights to instream flow; all other components of the project, including the irrigation efficiency work, is being done in conjunction with other federal agencies with independent NEPA and other environmental review and consultation obligations.« less
Mandl, Kenneth D; McNabb, Marion; Marks, Norman; Weitzman, Elissa R; Kelemen, Skyler; Eggleston, Emma M; Quinn, Maryanne
2014-01-01
Malfunctions or poor usability of devices measuring glucose or delivering insulin are reportable to the FDA. Manufacturers submit 99.9% of these reports. We test online social networks as a complementary source to traditional FDA reporting of device-related adverse events. Participatory surveillance of members of a non-profit online social network, TuDiabetes.org, from October 2011 to September 2012. Subjects were volunteers from a group within TuDiabetes, actively engaged online in participatory surveillance. They used the free TuAnalyze app, a privacy-preserving method to report detailed clinical information, available through the network. Network members were polled about finger-stick blood glucose monitors, continuous glucose monitors, and insulin delivery devices, including insulin pumps and insulin pens. Of 549 participants, 75 reported device-related adverse events, nearly half (48.0%) requiring intervention from another person to manage the event. Only three (4.0%) of these were reported by participants to the FDA. All TuAnalyze reports contained outcome information compared with 22% of reports to the FDA. Hypoglycemia and hyperglycemia were experienced by 48.0% and 49.3% of participants, respectively. Members of an online community readily engaged in participatory surveillance. While polling distributed online populations does not yield generalizable, denominator-based rates, this approach can characterize risk within online communities using a bidirectional communication channel that enables reach-back and intervention. Engagement of distributed communities in social networks is a viable complementary approach to traditional public health surveillance for adverse events related to medical devices. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Swartz, R.C.; Ferraro, S.P.; Lamberson, J.O.
1997-10-01
The direct toxicity and photoinduced toxicity of sediment-associated acenaphthene, phenanthrene, fluoranthene, and pyrene were determined for the marine amphipod Rhepoxynius abronius. The four polycyclic aromatic hydrocarbons (PAHs) were spiked into sediment in a concentration series of either single compounds or as approximately equitoxic mixtures of all four compounds. Standard 10-d sediment toxicity tests were conducted under fluorescent lighting. After 10 d, survivors were exposed for 1 h to ultraviolet (UV) radiation in the absence of sediment and then tested for their ability to bury in uncontaminated sediment. The 10-d median lethal concentrations (LC50s) were 2.31 mg acenaphthene/g organic carbon (OC),more » 2.22 mg phenanthrene/g OC, 3.31 mg fluoranthene/g OC, and 2.81 mg pyrene/g OC. These LC50s were used to calculate the sum of toxic units ({Sigma}TU) of the four PAHs in the approximately equitoxic mixtures. The {Sigma}TU LC50 was then calculated for the mixture treatments. If the toxicologic interaction of a mixture of contaminants is additive, {Sigma}TU LC50 = 1.0. The observed LC50 (1.55 {Sigma}TU) was slightly, but significantly, greater than unity, indicating that the interaction of PAHs in the mixture was less than additive. Exposure to UV radiation enhanced the toxic effects of fluoranthene and pyrene, but did not affect the toxicity of acenaphthene and phenanthrene. Effects of UV radiation on the toxicity of the mixture of four PAHs could be explained by the photoactivation of fluoranthene and pyrene alone. These results are consistent with predictions based on photophysical properties of PAH compounds.« less
Mulot, Michaël; Monsion, Baptiste; Boissinot, Sylvaine; Rastegar, Maryam; Meyer, Sophie; Bochet, Nicole; Brault, Véronique
2018-01-01
Aphid-transmitted plant viruses are a threat for major crops causing massive economic loss worldwide. Members in the Luteoviridae family are transmitted by aphids in a circulative and non-replicative mode. Virions are acquired by aphids when ingesting sap from infected plants and are transported through the gut and the accessory salivary gland (ASG) cells by a transcytosis mechanism relying on virus-specific receptors largely unknown. Once released into the salivary canal, virions are inoculated to plants, together with saliva, during a subsequent feeding. In this paper, we bring in vivo evidence that the membrane-bound Ephrin receptor (Eph) is a novel aphid protein involved in the transmission of the Turnip yellows virus (TuYV, Polerovirus genus, Luteoviridae family) by Myzus persicae. The minor capsid protein of TuYV, essential for aphid transmission, was able to bind the external domain of Eph in yeast. Feeding M. persicae on in planta- or in vitro-synthesized dsRNA targeting Eph-mRNA (dsRNAEph) did not affect aphid feeding behavior but reduced accumulation of TuYV genomes in the aphid's body. Consequently, TuYV transmission efficiency by the dsRNAEph-treated aphids was reproducibly inhibited and we brought evidence that Eph is likely involved in intestinal uptake of the virion. The inhibition of virus uptake after dsRNAEph acquisition was also observed for two other poleroviruses transmitted by M. persicae, suggesting a broader role of Eph in polerovirus transmission. Finally, dsRNAEph acquisition by aphids did not affect nymph production. These results pave the way toward an ecologically safe alternative of insecticide treatments that are used to lower aphid populations and reduce polerovirus damages. PMID:29593696
Mulot, Michaël; Monsion, Baptiste; Boissinot, Sylvaine; Rastegar, Maryam; Meyer, Sophie; Bochet, Nicole; Brault, Véronique
2018-01-01
Aphid-transmitted plant viruses are a threat for major crops causing massive economic loss worldwide. Members in the Luteoviridae family are transmitted by aphids in a circulative and non-replicative mode. Virions are acquired by aphids when ingesting sap from infected plants and are transported through the gut and the accessory salivary gland (ASG) cells by a transcytosis mechanism relying on virus-specific receptors largely unknown. Once released into the salivary canal, virions are inoculated to plants, together with saliva, during a subsequent feeding. In this paper, we bring in vivo evidence that the membrane-bound Ephrin receptor (Eph) is a novel aphid protein involved in the transmission of the Turnip yellows virus (TuYV, Polerovirus genus, Luteoviridae family) by Myzus persicae . The minor capsid protein of TuYV, essential for aphid transmission, was able to bind the external domain of Eph in yeast. Feeding M. persicae on in planta - or in vitro -synthesized dsRNA targeting Eph -mRNA (dsRNA Eph ) did not affect aphid feeding behavior but reduced accumulation of TuYV genomes in the aphid's body. Consequently, TuYV transmission efficiency by the dsRNA Eph -treated aphids was reproducibly inhibited and we brought evidence that Eph is likely involved in intestinal uptake of the virion. The inhibition of virus uptake after dsRNA Eph acquisition was also observed for two other poleroviruses transmitted by M. persicae , suggesting a broader role of Eph in polerovirus transmission. Finally, dsRNA Eph acquisition by aphids did not affect nymph production. These results pave the way toward an ecologically safe alternative of insecticide treatments that are used to lower aphid populations and reduce polerovirus damages.
Lefevre, S; Findorf, I; Bayley, M; Huong, D T T; Wang, T
2016-01-01
This study investigated the hypothesis that in the Asian swamp eel Monopterus albus, an air-breathing fish from south-east Asia that uses the buccopharyngeal cavity for oxygen uptake, the upper critical temperature (TU) is increased by acclimation to higher temperature, and that the increased TU is associated with improved cardiovascular and respiratory function. Monopterus albus were therefore acclimated to 27° C (current average) and 32° C (current maximum temperature as well as projected average within 100-200 years), and both the effect of acclimation and acute temperature increments on cardiovascular and respiratory functions were investigated. Two weeks of heat acclimation increased upper tolerated temperature (TU ) by 2° C from 36·9 ± 0·1° C to 38·9 ± 0·1° C (mean ± s.e.). Oxygen uptake (M˙O2) increased with acclimation temperature, accommodated by increases in both aerial and aquatic respiration. Overall, M˙O2 from air (M˙O2a ) was predominant, representing 85% in 27° C acclimated fish and 80% in 32° C acclimated fish. M˙O2 increased with acute increments in temperature and this increase was entirely accommodated by an increase in air-breathing frequency and M˙O2a . Monopterus albus failed to upregulate stroke volume; rather, cardiac output was maintained through increased heart rate with rising temperature. Overall, acclimation of M. albus to 32° C did not improve its cardiovascular and respiratory performance at higher temperatures, and cardiovascular adaptations, therefore, do not appear to contribute to the observed increase in TU. © 2015 The Fisheries Society of the British Isles.
The Shock and Vibration Digest. Volume 16, Number 12
1984-12-01
speed, spring constant of meshing gear teeth, and mass of the Dept. of Applied Mathematical Studies , Univ of rotating years. All of these factors are...interest that stress concentration factors in civil, mechanical, naval, and aeronautical Most graduate engineers have learned that conformal structural...branes. Conformal mapping has also been used Applcaton f th coforal appig tchnque recently to study the vibration characteristics of is straightforward
NASA Astrophysics Data System (ADS)
Carmona, P.; Molina, M.; Lasagabaster, A.
1995-05-01
The conformational structure of fragment 1-29 of human growth hormone releasing factor, hGHRF (1-29), in aqueous solution and in the solid state is investigated by infrared and Raman spectroscopy. The polypeptide backbone is found to be unordered in the solid state. However, the spectra of the peptide prepared as 5% (w/w) aqueous solutions show that approximately 28% of the peptide is involved in intermolecular β-sheet aggregation. The remainder of the peptide exists largely as disordered and β-sheet conformations with a small portion of α-helices. Tyrosine residues are found to be exposed to the solvent. The secondary structures are quantitatively examined through infrared spectroscopy, the conformational percentages being near those obtained by HONDAet al. [ Biopolymers31, 869 (1991)] using circular dichroism. The fast hydrogen/deuterium exchange in peptide groups and the absence of any NMR sign indicative of ordered structure [ G. M. CLOREet al., J. Molec. Biol.191, 553 (1986)] support that the solution conformations of the non-aggregated peptide interconvert in dynamic equilibrium. Some physiological advantages that may derive from this conformational flexibility are also discussed
Li, Yan; Li, Xiang; Ma, Weiya; Dong, Zigang
2014-08-12
The epidermal growth factor receptor (EGFR) is aberrantly activated in various cancer cells and an important target for cancer treatment. Deep understanding of EGFR conformational changes between the active and inactive states is of pharmaceutical interest. Here we present a strategy combining multiply targeted molecular dynamics simulations, unbiased molecular dynamics simulations, and Bayesian clustering to investigate transition pathways during the activation/inactivation process of EGFR kinase domain. Two distinct pathways between the active and inactive forms are designed, explored, and compared. Based on Bayesian clustering and rough two-dimensional free energy surfaces, the energy-favorable pathway is recognized, though DFG-flip happens in both pathways. In addition, another pathway with different intermediate states appears in our simulations. Comparison of distinct pathways also indicates that disruption of the Lys745-Glu762 interaction is critically important in DFG-flip while movement of the A-loop significantly facilitates the conformational change. Our simulations yield new insights into EGFR conformational transitions. Moreover, our results verify that this approach is valid and efficient in sampling of protein conformational changes and comparison of distinct pathways.
Static models with conformal symmetry
NASA Astrophysics Data System (ADS)
Manjonjo, A. M.; Maharaj, S. D.; Moopanar, S.
2018-02-01
We study static spherically symmetric spacetimes with a spherical conformal symmetry and a nonstatic conformal factor associated with the conformal Killing field. With these assumptions we find an explicit relationship relating two metric components of the metric tensor field. This leads to the general solution of the Einstein field equations with a conformal symmetry in a static spherically symmetric spacetime. For perfect fluids we can find all metrics explicitly and show that the models always admit a barotropic equation of state. Contained within this class of spacetimes are the well known metrics of (interior) Schwarzschild, Tolman, Kuchowicz, Korkina and Orlyanskii, Patwardhan and Vaidya, and Buchdahl and Land. The isothermal metric of Saslaw et al also admits a conformal symmetry. For imperfect fluids an infinite family of exact solutions to the field equations can be generated.
Molyneux, David H; Ward, Steve A
2015-12-01
The award of the Nobel Prize to Dr Bill Campbell and Professor Satoshi Ōmura for their role in the discovery of avermectin and Professor Youyou Tu for her work on the development of artemisinin has been universally welcomed by the International Health community for what the Nobel Committee described as 'The discoveries of Avermectin and Artemisinin have revolutionized therapy for patients suffering from devastating parasitic diseases. Campbell, Ōmura and Tu have transformed the treatment of parasitic diseases. The global impact of their discoveries and the resulting benefit to mankind are immeasurable'. Copyright © 2015 Elsevier Ltd. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Cao, Q; Hu, Q; Khan, S
2007-03-05
The toxicity effect of two deleterious elements of arsenic (As) and cadmium (Cd) (individually or in combination) on root elongation of wheat seedlings (Triticum aestivum, L.) were investigated both in hydroponics and in soils freshly spiked with the toxic elements. Median effective concentration (EC{sub 50}) and non-observed effect concentration (NOEC) were used to investigate the toxic thresholds and potencies of the two elements. The EC{sub 50} for As was 0.97 {mu}M in hydroponics and 196 mg {center_dot} kg{sup -1} in soil, and 4.32 {mu}M and 449 mg {center_dot} kg{sup -1} for Cd, respectively. Toxic unit (TU) and additive index (AI)more » concepts were introduced to determine the combined outcomes, and different behaviors were obtained: synergism in solution culture (EC{sub 50mix} = 0.36 TU{sub mix} and AI: 1.76) and antagonism in soil experiments (EC{sub 50mix} = 1.49 TU{sub mix} and AI: -0.33). Furthermore, the data of soil bioavailable As and Cd can not explain the discrepancy between the results derived from soil and hydroponics experiments.« less
Alvarez, Florencia; Schilardi, Patricia L; de Mele, Monica Fernández Lorenzo
2012-01-01
The copper intrauterine device is a contraceptive method that is based on the release of copper ions from a copper wire. Immediately after insertion, the dissolution of copper in the uterine fluid is markedly higher ("burst release") than that necessary for contraception action, leading to a variety of harmful effects. Pretreatments with organic compounds [thiourea (TU) and purine (PU), 10(-4)-10(-2) M concentration range, 1- and 3-h immersion times] were tested. The dissolution of copper with and without pretreatments in TU and PU solutions was analyzed by conventional electrochemical techniques and surface analysis. Pretreatments in PU solutions reduced the initial corrosion rate of copper in simulated uterine solutions, with inhibitory efficiencies that depend on the PU concentration and on the immersion time assayed. Inhibitory efficiency values higher than 98% for pretreatments with ≥10(-3) M PU were found. Conversely, after TU pretreatments, a high copper release was measured. It was concluded that 10(-3) M PU pretreatment is a promising strategy able to reduce the "burst release" of copper and to ensure contraceptive action. Copyright © 2012 Elsevier Inc. All rights reserved.
Flight Test Measurements From The Tu-144LL Structure/Cabin Noise Follow-On Experiment
NASA Technical Reports Server (NTRS)
Rizzi, Stephen A.; Rackl, Robert G.; Andrianov, Eduard V.
2000-01-01
This follow-on flight experiment on the TU-144LL Supersonic Flying Laboratory, conducted during the period September 1998 to April 1999, was a continuation of previous Structure/Cabin Noise Experiment 2.1. Data was obtained over a wide range of altitudes and Mach numbers. Measured were: turbulent boundary layer pressure fluctuations on the fuselage over its length; structural response on skin panels using accelerometers; and flow direction over three windows using 'flow cones'. The effect of steps in the flow was also measured using two window blank pairs; each pair bridged by a plate which created small sharp forward and aft facing steps. The effect of transducer flushness with the exterior surface was also measured during flight. Height test points were chosen to cover much of the TU-144's flight envelope, as well as to obtain as large a unit Reynolds number range as possible at various Mach numbers: takeoff, subsonic, transonic, and supersonic cruise conditions up to Mach 2. Data on engine runups and background noise were acquired on the ground. The data in the form of time histories of the acoustic signals, together with auxiliary data and basic MATLAB processing modules, are available on CD-R disks.
NASA Technical Reports Server (NTRS)
Curry, Timothy J.; Batterson, James G. (Technical Monitor)
2000-01-01
Low order equivalent system (LOES) models for the Tu-144 supersonic transport aircraft were identified from flight test data. The mathematical models were given in terms of transfer functions with a time delay by the military standard MIL-STD-1797A, "Flying Qualities of Piloted Aircraft," and the handling qualities were predicted from the estimated transfer function coefficients. The coefficients and the time delay in the transfer functions were estimated using a nonlinear equation error formulation in the frequency domain. Flight test data from pitch, roll, and yaw frequency sweeps at various flight conditions were used for parameter estimation. Flight test results are presented in terms of the estimated parameter values, their standard errors, and output fits in the time domain. Data from doublet maneuvers at the same flight conditions were used to assess the predictive capabilities of the identified models. The identified transfer function models fit the measured data well and demonstrated good prediction capabilities. The Tu-144 was predicted to be between level 2 and 3 for all longitudinal maneuvers and level I for all lateral maneuvers. High estimates of the equivalent time delay in the transfer function model caused the poor longitudinal rating.
Li, Bojun; Lin, Zhe; Mitsi, Maria; Zhang, Yang; Vogel, Viola
2015-01-01
An increasing body of evidence suggests important roles of extracellular matrix (ECM) in regulating stem cell fate. This knowledge can be exploited in tissue engineering applications for the design of ECM scaffolds appropriate to direct stem cell differentiation. By probing the conformation of fibronectin (Fn) using fluorescence resonance energy transfer (FRET), we show here that heparin treatment of the fibroblast-derived ECM scaffolds resulted in more extended conformations of fibrillar Fn in ECM. Since heparin is a highly negatively charged molecule while fibronectin contains segments of positively charged modules, including FnIII13, electrostatic interactions between Fn and heparin might interfere with residual quaternary structure in relaxed fibronectin fibers thereby opening up buried sites. The conformation of modules FnIII12-14 in particular, which contain one of the heparin binding sites as well as binding sites for many growth factors, may be activated by heparin, resulting in alterations in growth factor binding to Fn. Indeed, upregulated osteogenic differentiation was observed when hMSCs were seeded on ECM scaffolds that had been treated with heparin and were subsequently chemically fixed. In contrast, either rigidifying relaxed fibers by fixation alone, or heparin treatment without fixation had no effect. We hypothesize that fibronectin's conformations within the ECM are activated by heparin such as to coordinate with other factors to upregulate hMSC osteogenic differentiation. Thus, the conformational changes of fibronectin within the ECM could serve as a 'converter' to tune hMSC differentiation in extracellular matrices. This knowledge could also be exploited to promote osteogenic stem cell differentiation on biomedical surfaces.
A DFT and structural investigation of the conformations of Fischer carbene complexes
NASA Astrophysics Data System (ADS)
Landman, Marilé
2015-09-01
A set of different Fischer carbene complexes of group VI and VII metals, with varied heteroatom and heteroaromatic substituents on the carbene carbon atom, was studied. Density functional theory as well as single crystal diffraction techniques were employed to investigated the most stable conformation of these complexes. The complexes studied, [M(CO)4L{C(X)Z}], with L = PPh3 or CO, X = ethoxy (-OCH2CH3) or amino (-NH2 or NHCy) substituents as the heteroatom carbene substituents, Z = 2-furyl (-C4H3O), 2-thienyl (-C4H3S), 2-(N-methyl)pyrrolyl (-C4H3NCH3) as the second carbene substituent had their substituents varied systematically to give all the possible conformations of these complexes. The conformations of the complexes, in particular the relative orientations of the heteroatoms in the molecule (syn vs. anti), E/Z isomerism in the aminocarbene complexes and cis/trans isomerism in the ligand substituted complexes as well as various combinations of these aspects, were studied. In general, it was found that the most stable conformation theoretically as well as in the solid state for most of the complexes preferred the syn conformation. The Z-isomer is generally preferred over the E isomer while the cis is more predominant than the trans isomer. Using DFT and NBO calculations, explanations for the preferred conformations were explored. It was concluded that both steric and electronic factors influence the conformations of the carbene complexes, with the extent of contribution of these two factors varying for each of the different carbene substituents.
NASA Astrophysics Data System (ADS)
Sarver, Ronald W.; Friedman, Alan R.; Thamann, Thomas J.
1997-10-01
The secondary structure of the bovine growth hormone releasing factor analog, [Ile 2, Ser 8,28, Ala 15, Leu 27, Hse 30] bGRF(1-30)-NH-Ethyl, acetate salt (U-90699F) was studied in solution by Fourier transform infrared and Raman spectroscopies. Spectroscopic studies revealed that concentrated aqueous solutions of U-90699F (100 mg ml -1) undergo a secondary structure transition from disordered coil/α-helix to intermolecular β-sheet. Disordered coil and α-helical structure were grouped together in the infrared and Raman studies since the amide I vibrations are close in frequency and overlap in assignments was possible. Before the conformational transition, the facile exchange of the peptide's amide hydrogens for deuterium indicated that the majority of amide hydrogens were readily accessible to solvent. The kinetics of the conformational transition coincided with an increase in solution viscosity and turbidity. An initiation phase preceded the conformational transition during which only minor spectral changes were observed by infrared spectroscopy. The initiation phase and reaction kinetics were consistent with a highly cooperative nucleation ultimately leading to a network of intermolecular β-sheet structure and gel formation. Increased temperature accelerated the conformational transition. The conformational transition was thermally irreversible but the β-sheet structure of aggregated or gelled peptide could be disrupted by dilution and agitation.
Accelerating the Conformational Sampling of Intrinsically Disordered Proteins.
Do, Trang Nhu; Choy, Wing-Yiu; Karttunen, Mikko
2014-11-11
Intrinsically disordered proteins (IDPs) are a class of proteins lacking a well-defined secondary structure. Instead, they are able to attain multiple conformations, bind to multiple targets, and respond to changes in their surroundings. Functionally, IDPs have been associated with molecular recognition, cell regulation, and signal transduction. The dynamic conformational ensemble of IDPs is highly environmental and binding partner dependent, rendering the characterization of IDPs extremely challenging. Here, we compare the sampling efficiencies of conventional molecular dynamics (MD), well-tempered metadynamics (WT-META), and bias-exchange metadynamics (BE-META). The total simulation time was over 10 μs, and a 20-mer peptide derived from the Neh2 domain of the Nuclear factor erythroid 2-related factor 2 (Nrf2) protein was simulated. BE-META, with a neutral replica and seven biased replicas employing a set of seven relevant collective variables (CVs), provided the most reliable and efficient sampling. Finally, we propose a free-energy reconstruction method based on the probability distribution of the secondary structure contents. This postprocessing analysis confirms the presence of not only the β-hairpin conformation of the free Neh2 peptide but also its rare bound-state-like conformation, both of that have been experimentally observed. In addition, our simulations also predict other possible conformations to be verified with future experiments.
Park, Chang-Jin; Caddell, Daniel F.; Ronald, Pamela C.
2012-01-01
Plants are continuously challenged by pathogens including viruses, bacteria, and fungi. The plant immune system recognizes invading pathogens and responds by activating an immune response. These responses occur rapidly and often involve post-translational modifications (PTMs) within the proteome. Protein phosphorylation is a common and intensively studied form of these PTMs and regulates many plant processes including plant growth, development, and immunity. Most well-characterized pattern recognition receptors (PRRs), including Xanthomonas resistance 21, flagellin sensitive 2, and elongation factor-Tu receptor, possess intrinsic protein kinase activity and regulate downstream signaling through phosphorylation events. Here, we focus on the phosphorylation events of plant PRRs that play important roles in the immune response. We also discuss the role of phosphorylation in regulating mitogen-associated protein kinase cascades and transcription factors in plant immune signaling. PMID:22876255
Main atmospheric heavy metal sources in Portugal by biomonitor analysis
NASA Astrophysics Data System (ADS)
Reis, M. A.; Alves, L. C.; Wolterbeek, H. Th.; Verburg, T.; Freitas, M. C.; Gouveia, A.
1996-04-01
During the months of July and August of 1993 a lichen collection campaign was held in Portugal where about 250 samples were collected and analysed by thick target PIXE and INAA. Results for 43 different elements were obtained and a data base was built and subjected to Monte Carlo aided target transform factor analysis (MCATTFA), method developed at IRI TU Delft. 10 × 10 km coast and 50 × 50 km far from coast sampling grids were used for collection, concentration data as well as factor patterns were extrapolated to the whole country making use of an extinction rule of 1/r 3. In this work we present the results that were obtained based on a reduced data set of 22 elements measured by TTPIXE. The results for INAA data subset and the total data set are presented elsewhere.
TU-AB-201-07: Image Guided Endorectal HDR Brachytherapy Using a Compliant Balloon Applicator
DOE Office of Scientific and Technical Information (OSTI.GOV)
Cohen, G; Goodman, K
2015-06-15
Purpose: High dose rate endorectal brachytherapy is an option to deliver a focal, high-dose radiotherapy to rectal tumors for patients undergoing non-operative management. We investigate a new multichannel, MR compatible applicator with a novel balloon-based design to provide improved treatment geometry. We report on the initial clinical experience using this applicator. Methods: Patients were enrolled on an IRB-approved, dose-escalation protocol evaluating the use of the anorectal (AR-1) applicator (Ancer Medical, Hialeah, FL), a multichannel applicator with two concentric balloons. The inner balloon supports 8 source lumens; the compliant outer balloon expands to separate the normal rectal wall and the sourcemore » lumens, yet deforms around a firm, exophytic rectal mass, leading to dose escalation to tumor while sparing normal rectum. Under general anesthesia, gold fiducial markers were inserted above and below the tumor, and the AR applicator was placed in the rectum. MRI-based treatment plans were prepared to deliver 15 Gy in 3 weekly fractions to the target volume while sparing healthy rectal tissue, bladder, bowel and anal muscles. Prior to each treatment, CBCT/Fluoroscopy were used to place the applicator in the treatment position and confirm the treatment geometry using rigid registration of the CBCT and planning MRI. After registration of the applicator images, positioning was evaluated based on the match of the gold markers. Results: Highly conformal treatment plans were achieved. MR compatibility of the applicator enabled good tumor visualization. In spite of the non-rigid nature of the applicators and the fact that a new applicator was used at each treatment session, treatment geometry was reproducible to within 2.5 mm. Conclusions: This is the first report on using the AR applicator in patients. Highly conformal plans, confidence in MRI target delineation, in combination with reproducible treatment geometry provide encouraging feedback for continuation with dose escalation in these patients.« less
Complement Factor H and Simian Virus 40 bind the GM1 ganglioside in distinct conformations.
Blaum, Bärbel S; Frank, Martin; Walker, Ross C; Neu, Ursula; Stehle, Thilo
2016-05-01
Mammalian cell surfaces are decorated with a variety of glycan chains that orchestrate development and defense and are exploited by pathogens for cellular attachment and entry. While glycosidic linkages are, in principle, flexible, the conformational space that a given glycan can sample is subject to spatial and electrostatic restrictions imposed by its overall chemical structure. Here, we show how the glycan moiety of the GM1 ganglioside, a branched, monosialylated pentasaccharide that serves as a ligand for various proteins, undergoes differential conformational selection in its interactions with different lectins. Using STD NMR and X-ray crystallography, we found that the innate immune regulator complement Factor H (FH) binds a previously not reported GM1 conformation that is not compatible with the GM1-binding sites of other structurally characterized GM1-binding lectins such as the Simian Virus 40 (SV40) capsid. Molecular dynamics simulations of the free glycan in explicit solvent on the 10 μs timescale reveal that the FH-bound conformation nevertheless corresponds to a minimum in the Gibbs free energy plot. In contrast to the GM1 conformation recognized by SV40, the FH-bound GM1 conformation is associated with poor NOE restraints, explaining how it escaped(1)H-(1)H NOE-restrained modeling in the past and highlighting the necessity for ensemble representations of glycan structures. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Reexamination of Ball-Race Conformity Effects on Ball Bearing Life
NASA Technical Reports Server (NTRS)
Zaretsky, Erwin V.; Poplawski, Joseph V.; Root, Lawrence E.
2007-01-01
The analysis in this report considers the life of the ball set as well as the respective lives of the races to reassess the effect of ball-race conformity on ball bearing life. The related changes in ball bearing life are incorporated in life factors that can be used to modify the bearing predicted life using the Lundberg-Palmgren equations and the ANSI/ABMA and ISO Standards. Two simple algebraic relationships were established to calculate life factors LF(sub c) to determine the effect of inner- and outer-race conformity combinations on bearing L(sub 10) life for deepgroove and angular-contact ball bearings, respectively. Depending on the bearing type and series as well as conformity combinations, the calculated life for deep-groove ball bearings can be over 40 percent less than that calculated by the Lundberg-Palmgren equations. For angular-contact ball bearings, the life can vary between +16 and -39 percent from that calculated by the Lundberg-Palmgren equations. Comparing the two ball bearing types, the life factors LF(sub c) for the deep-groove bearings can be as much as 40 percent lower than that for angular-contact ball bearings.
Padula, Daniele; Pescitelli, Gennaro
2018-01-09
Chiroptical spectra such as electronic circular dichroism (ECD) are said to be much more sensitive to conformation than their non-chiroptical counterparts, however, it is difficult to demonstrate such a common notion in a clear-cut way. We run DFT and TDDFT calculations on two closely related 1,1-diarylmethanols which show mirror-image ECD spectra for the same absolute configuration. We demonstrate that the main reason for the different chiroptical response of the two compounds lies in different conformational ensembles, caused by a single hydrogen-to-methyl substitution. We conclude that two compounds, having the same configuration but different conformation, may exhibit mirror-image ECD signals, stressing the importance and impact of conformational factors on ECD spectra.
Peer pressure and alcohol use in young men: a mediation analysis of drinking motives.
Studer, Joseph; Baggio, Stéphanie; Deline, Stéphane; N'Goran, Alexandra A; Henchoz, Yves; Mohler-Kuo, Meichun; Daeppen, Jean-Bernard; Gmel, Gerhard
2014-07-01
Peer pressure (PP) has been shown to play a major role in the development and continuation of alcohol use and misuse. To date, almost all the studies investigating the association of PP with alcohol use only considered the PP for misconduct but largely ignored other aspects of PP, such as pressure for peer involvement and peer conformity. Moreover, it is not clear whether the association of PP with alcohol use is direct or mediated by other factors. The aim of the present study was to investigate the association of different aspects of peer pressure (PP) with drinking volume (DV) and risky single-occasion drinking (RSOD), and to explore whether these associations were mediated by drinking motives (DM). A representative sample of 5521 young Swiss men, aged around 20 years old, completed a questionnaire assessing their usual weekly DV, the frequency of RSOD, DM (i.e. enhancement, social, coping, and conformity motives), and 3 aspects of PP (i.e. misconduct, peer involvement, and peer conformity). Associations between PP and alcohol outcomes (DV and RSOD) as well as the mediation of DM were tested using structural equation models. Peer pressure to misconduct was associated with more alcohol use, whereas peer involvement and peer conformity were associated with less alcohol use. Associations of drinking outcomes with PP to misconduct and peer involvement were partially mediated by enhancement and coping motives, while the association with peer conformity was partially mediated by enhancement and conformity motives. Results suggest that PP to misconduct constitutes a risk factor, while peer conformity and peer involvement reflect protective factors with regard to alcohol use. Moreover, results from the mediation analyses suggest that part of the association of PP with alcohol use came indirectly through DM: PP was associated with DM, which in turn were associated with alcohol use. Copyright © 2014 Elsevier B.V. All rights reserved.
Molecular characterization of two genotypes of a new polerovirus infecting brassicas in China.
Xiang, Hai-Ying; Dong, Shu-Wei; Shang, Qiao-Xia; Zhou, Cui-Ji; Li, Da-Wei; Yu, Jia-Lin; Han, Cheng-Gui
2011-12-01
The genomic RNA sequences of two genotypes of a brassica-infecting polerovirus from China were determined. Sequence analysis revealed that the virus was closely related to but significantly different from turnip yellows virus (TuYV). This virus and other poleroviruses, including TuYV, had less than 90% amino acid sequence identity in all gene products except the coat protein. Based on the molecular criterion (>10% amino acid sequence difference) for species demarcation in the genus Polerovirus, the virus represents a distinct species for which the name Brassica yellows virus (BrYV) is proposed. Interestingly, there were two genotypes of BrYV, which mainly differed in the 5'-terminal half of the genome.
Zhu, Shijun; Moore, Terry W.; Lin, Xiaoqian; Morii, Nao; Mancini, Alessandra; Howard, Randy B.; Culver, Deborah; Arrendale, Richard F.; Reddy, Prabhakar; Evers, Taylor J.; Zhang, Hongzheng; Sica, Gabriel; Chen, Zhuo G.; Sun, Aiming; Fu, Haian; Khuri, Fadlo R.; Shin, Dong M.; Snyder, James P.; Shoji, Mamoru
2013-01-01
Objectives are to examine the efficacy of new synthetic curcumin analogs EF31 in head and neck squamous cell carcinoma in vitro and in vivo, and study their pharmacokinetic and toxicologic effects in vivo. The synthesis of EF31 was described for the first time. Solubility of EF24, EF31 was compared using nephelometric analysis. Human head and neck squamous cell carcinoma Tu212 xenograft tumors were established in athymic nude mice and treated with EF31 i.p. once daily five days a week for about 5 – 6 weeks. The long term effect of EF31 on the NF-κB signaling system in the tumors was examined by Western blot analysis. EF31 at 25 mg/kg, i.p. inhibited tumor growth almost completely. Solubility of EF24 and EF31 are <10, 13 μg/mL or <32, 47 μM, respectively. The serum chemistry profiles of treated mice were within the limits of normal, it revealed a linear increase of Cmax. EF31 decreased the level of phosphorylation of NF-κB p65. In conclusion, the novel synthetic curcumin analogs EF31 is efficacious in inhibiting the growth of Tu212 xenograft tumors and may be useful for treating head and neck squamous cell carcinoma. The long term EF31 treatment inhibited NF-kB p65 phosphorylation in xenografts, implicating downregulation of cancer promoting transcription factors such as angiogenesis and metastasis. PMID:22532032
Zhu, Shijun; Moore, Terry W; Lin, Xiaoqian; Morii, Nao; Mancini, Alessandra; Howard, Randy B; Culver, Deborah; Arrendale, Richard F; Reddy, Prabhakar; Evers, Taylor J; Zhang, Hongzheng; Sica, Gabriel; Chen, Zhuo G; Sun, Aiming; Fu, Haian; Khuri, Fadlo R; Shin, Dong M; Snyder, James P; Shoji, Mamoru
2012-06-01
Objectives are to examine the efficacy, pharmacokinetics, and toxicology of a synthetic curcumin analog EF31 in head and neck squamous cell carcinoma. The synthesis of EF31 was described for the first time. Solubility of EF24 and EF31 was compared using nephelometric analysis. Human head and neck squamous cell carcinoma Tu212 xenograft tumors were established in athymic nude mice and treated with EF31 i.p. once daily five days a week for about 5-6 weeks. The long term effect of EF31 on the NF-κB signaling system in the tumors was examined by Western blot analysis. EF31 at 25 mg kg(-1), i.p. inhibited tumor growth almost completely. Solubilities of EF24 and EF31 are <10 and 13 μg mL(-1) or <32 and 47 μM, respectively. The serum chemistry profiles of treated mice were within the limits of normal, they revealed a linear increase of C(max). EF31 decreased the level of phosphorylation of NF-κB p65. In conclusion, the novel synthetic curcumin analog EF31 is efficacious in inhibiting the growth of Tu212 xenograft tumors and may be useful for treating head and neck squamous cell carcinoma. The long term EF31 treatment inhibited NF-κB p65 phosphorylation in xenografts, implicating downregulation of cancer promoting transcription factors such as angiogenesis and metastasis.
Kuttel, Michelle M; Timol, Zaheer; Ravenscroft, Neil
2017-06-29
The capsular polysaccharide is the main virulence factor in meningococcus. The capsular polysaccharides for meningococcal serogroups Y and W are almost identical polymers of hexose-sialic acid, suggesting the possibility of cross-protection between group Y and W vaccines. However, early studies indicated that they elicit different levels of cross-protection. Here we explore the conformations of the meningococcal Y and W polysaccharides with molecular dynamics simulations of three repeating unit oligosaccharide strands. We find differences in Y and W antigen conformation: the Y polysaccharide has a single dominant conformation, whereas W exhibits a family of conformations including the Y conformation. This result is supported by our NMR NOESY analysis, which indicates key close contacts for W that are not present in Y. These conformational differences provide an explanation for the different levels of cross-protection measured for the Y and W monovalent vaccines and the high group W responses observed in HibMenCY-TT vaccinees. Copyright © 2017 Elsevier Ltd. All rights reserved.
Structural Landscape of the Proline-Rich Domain of Sos1 Nucleotide Exchange Factor
McDonald, Caleb B.; Bhat, Vikas; Kurouski, Dmitry; Mikles, David C.; Deegan, Brian J.; Seldeen, Kenneth L.; Lednev, Igor K.; Farooq, Amjad
2013-01-01
Despite its key role in mediating a plethora of cellular signaling cascades pertinent to health and disease, little is known about the structural landscape of the proline-rich (PR) domain of Sos1 guanine nucleotide exchange factor. Herein, using a battery of biophysical tools, we provide evidence that the PR domain of Sos1 is structurally disordered and adopts an extended random coil-like conformation in solution. Of particular interest is the observation that while chemical denaturation of PR domain results in the formation of a significant amount of polyproline II (PPII) helices, it has little or negligible effect on its overall size as measured by its hydrodynamic radius. Our data also show that the PR domain displays a highly dynamic conformational basin in agreement with the knowledge that the intrinsically unstructured proteins rapidly interconvert between an ensemble of conformations. Collectively, our study provides new insights into the conformational equilibrium of a key signaling molecule with important consequences on its physiological function. PMID:23528987
Waßmuth, Ralf
2015-01-01
Certification of conformity in health care should provide assurance of compliance with quality standards. This also includes risk management and patient safety. Based on a comprehensive definition of quality, beneficial effects on the management of risks and the enhancement of patient safety can be expected from certification of conformity. While these effects have strong face validity, they are currently not sufficiently supported by evidence from health care research. Whether this relates to a lack of evidence or a lack of investigation remains open. Advancing safety culture and "climate", as well as learning from adverse events rely in part on quality management and are at least in part reflected in the certification of healthcare quality. However, again, evidence of the effectiveness of such measures is limited. Moreover, additional factors related to personality, attitude and proactive action of healthcare professionals are crucial factors in advancing risk management and patient safety which are currently not adequately reflected in certification of conformity programs.
Nakahashi, Wataru
2007-08-01
Conformity is often observed in human social learning. Social learners preferentially imitate the majority or most common behavior in many situations, though the strength of conformity varies with the situation. Why has such a psychological tendency evolved? I investigate this problem by extending a standard model of social learning evolution with infinite environmental states (Feldman, M.W., Aoki, K., Kumm, J., 1996. Individual versus social learning: evolutionary analysis in a fluctuating environment. Anthropol. Sci. 104, 209-231) to include conformity bias. I mainly focus on the relationship between the strength of conformity bias that evolves and environmental stability, which is one of the most important factors in the evolution of social learning. Using the evolutionarily stable strategy (ESS) approach, I show that conformity always evolves when environmental stability and the cost of adopting a wrong behavior are small, though environmental stability and the cost of individual learning both negatively affect the strength of conformity.
Chen, Rubing; Vasilakis, Nikos
2011-01-01
Dengue viruses (DENV) are by far the most important arboviral pathogens in the tropics around the world, putting at risk of infection nearly a third of the global human population. DENV are members of the genus Flavivirus in the Family Flaviviridae and comprise four antigenically distinct serotypes (DENV-1-4). Although they share almost identical epidemiological features, they are genetically distinct. Phylogenetic analyses have revealed valuable insights into the origins, epidemiology and the forces that shape DENV evolution in nature. In this review, we examine the current status of DENV evolution, including but not limited to rates of evolution, selection pressures, population sizes and evolutionary constraints, and we discuss how these factors influence transmission, pathogenesis and emergence. PMID:21994796
Rodríguez Ortega, P G; Montejo, M; Márquez, F; López González, J J
2015-07-01
A thorough DFT and MM study of the conformational landscape, molecular and electronic structures of (-)-S-anabasine is reported aimed to reveal the mechanism controlling its conformational preference. Although the conformational flexibility and diversity of this system is quite extensive, only two structures are populated both in gas-phase and solution (CCl4 and DMSO). NBO-aided electronic structure analyses performed for the eight conformers representing minima in the potential energy surface of (-)-S-anabasine indicate that both steric and electrostatic factors are determinant in the conformational distribution of the sample in gas phase. Nonetheless, hyperconjugative effects are the key force tipping the balance in the conformational equilibrium between the two main rotamers. Increasing the polarity of the medium (using the IEF-PCM formalism) barely affect the conformational energy profile, although a slight increase in the theoretical population of those structures more affected by electrostatic interactions is predicted. The validity of the theoretical models and calculated conformers populations are endorsed by the accurate reproduction of the IR and VCD spectra (recorded in pure liquid and in CCl4 solution) of the sample (that have been firstly recorded and assigned in the present work) which are consistent with the occurrence of a 2:1 conformational ratio. Copyright © 2015 Elsevier Inc. All rights reserved.
Novel phosphorylation states of the yeast spindle pole body.
Fong, Kimberly K; Zelter, Alex; Graczyk, Beth; Hoyt, Jill M; Riffle, Michael; Johnson, Richard; MacCoss, Michael J; Davis, Trisha N
2018-06-14
Phosphorylation regulates yeast spindle pole body (SPB) duplication and separation and likely regulates microtubule nucleation. We report a phosphoproteomic analysis using tandem mass spectrometry of enriched Saccharomyces cerevisiae SPBs for two cell cycle arrests, G1/S and the mitotic checkpoint, expanding on previously reported phosphoproteomic data sets. We present a novel phosphoproteomic state of SPBs arrested in G1/S by a cdc4-1 temperature sensitive mutation, with particular focus on phosphorylation events on the γ-tubulin small complex (γ-TuSC). The cdc4-1 arrest is the earliest arrest at which microtubule nucleation has occurred at the newly duplicated SPB. Several novel phosphorylation sites were identified in G1/S and during mitosis on the microtubule nucleating γ-TuSC. These sites were analyzed in vivo by fluorescence microscopy and were shown to be required for proper regulation of spindle length. Additionally, in vivo analysis of two mitotic sites in Spc97 found that phosphorylation of at least one of these sites is required for progression through the cell cycle. This phosphoproteomic data set not only broadens the scope of the phosphoproteome of SPBs, it also identifies several γ-TuSC phosphorylation sites that influence microtubule formation. © 2018. Published by The Company of Biologists Ltd.
Mohamed, Rania G; Elantabli, Fatma M; Helal, Nadia H; El-Medani, Samir M
2015-04-15
Thermal reaction of M(CO)6 (M=Cr, Mo or W) with a Schiff base (DMPA) derived from the condensation of 4,5-dimethyl-1,2-phenylenediamine and pyridine-2-carboxaldehyde in THF in absence and presence of a secondary ligand; 2-aminobenzimidazole (Abz), thiourea (Tu) or 2-(2'-pyridyl)benzimidazole (pybz) were studied. The reaction of Cr(CO)6 gave the four complexes Cr2(CO)2(DMPA)2; 1, Cr(DMPA)2(Abz)2; 2, Cr2(CO)4(DMPA)2(Tu)2; 3 and Cr(DMPA)2(Pybz); 4, while the thermal reaction of Mo(CO)6 resulted in the formation of the two complexes Mo2(O)6(DMPA)2; 5, and Mo2(O)2(CO)2(DMPA)2(Tu)2; 6. Thermal reaction of W(CO)6 and the Schiff base DMPA gave the complex W(O)2(DMPA)2; 7. The ligand DMPA and its metal complexes have been reported and characterized based on elemental analyses, IR, (1)H NMR, magnetic measurements, and thermal analysis. Cyclic voltammetry and biological activity were also investigated. Copyright © 2015 Elsevier B.V. All rights reserved.
Predicting bioactive conformations and binding modes of macrocycles
NASA Astrophysics Data System (ADS)
Anighoro, Andrew; de la Vega de León, Antonio; Bajorath, Jürgen
2016-10-01
Macrocyclic compounds experience increasing interest in drug discovery. It is often thought that these large and chemically complex molecules provide promising candidates to address difficult targets and interfere with protein-protein interactions. From a computational viewpoint, these molecules are difficult to treat. For example, flexible docking of macrocyclic compounds is hindered by the limited ability of current docking approaches to optimize conformations of extended ring systems for pose prediction. Herein, we report predictions of bioactive conformations of macrocycles using conformational search and binding modes using docking. Conformational ensembles generated using specialized search technique of about 70 % of the tested macrocycles contained accurate bioactive conformations. However, these conformations were difficult to identify on the basis of conformational energies. Moreover, docking calculations with limited ligand flexibility starting from individual low energy conformations rarely yielded highly accurate binding modes. In about 40 % of the test cases, binding modes were approximated with reasonable accuracy. However, when conformational ensembles were subjected to rigid body docking, an increase in meaningful binding mode predictions to more than 50 % of the test cases was observed. Electrostatic effects did not contribute to these predictions in a positive or negative manner. Rather, achieving shape complementarity at macrocycle-target interfaces was a decisive factor. In summary, a combined computational protocol using pre-computed conformational ensembles of macrocycles as a starting point for docking shows promise in modeling binding modes of macrocyclic compounds.
Campa, Ana; Giraldez, Ramón; Ferreira, Juan José
2009-06-01
Resistance to nine races of the pathogenic fungus Colletotrichum lindemuthianum, causal agent of anthracnose, was evaluated in F(3) families derived from the cross between the anthracnose differential bean cultivars TU (resistant to races, 3, 6, 7, 31, 38, 39, 102, and 449) and MDRK (resistant to races, 449, and 1545). Molecular marker analyses were carried out in the F(2) individuals in order to map and characterize the anthracnose resistance genes or gene clusters present in these two differential cultivars. The results of the combined segregation indicate that at least three independent loci conferring resistance to anthracnose are present in TU. One of them, corresponding to the previously described anthracnose resistance locus Co-5, is located in linkage group B7, and is formed by a cluster of different genes conferring specific resistance to races, 3, 6, 7, 31, 38, 39, 102, and 449. Evidence of intra-cluster recombination between these specific resistance genes was found. The second locus present in TU confers specific resistance to races 31 and 102, and the third locus confers specific resistance to race 102, the location of these two loci remains unknown. The resistance to race 1545 present in MDRK is due to two independent dominant genes. The results of the combined segregation of two F(4) families showing monogenic segregation for resistance to race 1545 indicates that one of these two genes is linked to marker OF10(530), located in linkage group B1, and corresponds to the previously described anthracnose resistance locus Co-1. The second gene conferring resistance to race 1545 in MDRK is linked to marker Pv-ctt001, located in linkage group B4, and corresponds to the Co-3/Co-9 cluster. The resistance to race 449 present in MDRK is conferred by a single gene, located in linkage group B4, probably included in the same Co-3/Co-9 cluster.
Chang, Sunny Li-Yun; Chen, Shih-Yun; Huang, Huai-Huei; Ko, Hsin-An; Liu, Pei-Tsen; Liu, Ya-Chi; Chen, Ping-Hau; Liu, Fu-Chin
2013-01-01
Nolz-1, as a murine member of the NET zinc-finger protein family, is expressed in post-mitotic differentiating neurons of striatum during development. To explore the function of Nolz-1 in regulating the neurogenesis of forebrain, we studied the effects of ectopic expression of Nolz-1 in neural progenitors. We generated the Cre-loxP dependent conditional transgenic mice in which Nolz-1 was ectopically expressed in proliferative neural progenitors. Ectopic expression of Nolz-1 in neural progenitors by intercrossing the Nolz-1 conditional transgenic mice with the nestin-Cre mice resulted in hypoplasia of telencephalon in double transgenic mice. Decreased proliferation of neural progenitor cells were found in the telencephalon, as evidenced by the reduction of BrdU−, Ki67− and phospho-histone 3-positive cells in E11.5–12.5 germinal zone of telencephalon. Transgenic Nolz-1 also promoted cell cycle exit and as a consequence might facilitate premature differentiation of progenitors, because TuJ1-positive neurons were ectopically found in the ventricular zone and there was a general increase of TuJ1 immunoreactivity in the telencephalon. Moreover, clusters of strong TuJ1-expressing neurons were present in E12.5 germinal zone. Some of these strong TuJ1-positive clusters, however, contained apoptotic condensed DNA, suggesting that inappropriate premature differentiation may lead to abnormal apoptosis in some progenitor cells. Consistent with the transgenic mouse analysis in vivo, similar effects of Nozl-1 over-expression in induction of apoptosis, inhibition of cell proliferation and promotion of neuronal differentiation were also observed in three different N18, ST14A and N2A neural cell lines in vitro. Taken together, our study indicates that ectopic expression of Nolz-1 in neural progenitors promotes cell cycle exit/premature neuronal differentiation and induces abnormal apoptosis in the developing telencephalon. PMID:24073229
Chang, Sunny Li-Yun; Chen, Shih-Yun; Huang, Huai-Huei; Ko, Hsin-An; Liu, Pei-Tsen; Liu, Ya-Chi; Chen, Ping-Hau; Liu, Fu-Chin
2013-01-01
Nolz-1, as a murine member of the NET zinc-finger protein family, is expressed in post-mitotic differentiating neurons of striatum during development. To explore the function of Nolz-1 in regulating the neurogenesis of forebrain, we studied the effects of ectopic expression of Nolz-1 in neural progenitors. We generated the Cre-loxP dependent conditional transgenic mice in which Nolz-1 was ectopically expressed in proliferative neural progenitors. Ectopic expression of Nolz-1 in neural progenitors by intercrossing the Nolz-1 conditional transgenic mice with the nestin-Cre mice resulted in hypoplasia of telencephalon in double transgenic mice. Decreased proliferation of neural progenitor cells were found in the telencephalon, as evidenced by the reduction of BrdU-, Ki67- and phospho-histone 3-positive cells in E11.5-12.5 germinal zone of telencephalon. Transgenic Nolz-1 also promoted cell cycle exit and as a consequence might facilitate premature differentiation of progenitors, because TuJ1-positive neurons were ectopically found in the ventricular zone and there was a general increase of TuJ1 immunoreactivity in the telencephalon. Moreover, clusters of strong TuJ1-expressing neurons were present in E12.5 germinal zone. Some of these strong TuJ1-positive clusters, however, contained apoptotic condensed DNA, suggesting that inappropriate premature differentiation may lead to abnormal apoptosis in some progenitor cells. Consistent with the transgenic mouse analysis in vivo, similar effects of Nozl-1 over-expression in induction of apoptosis, inhibition of cell proliferation and promotion of neuronal differentiation were also observed in three different N18, ST14A and N2A neural cell lines in vitro. Taken together, our study indicates that ectopic expression of Nolz-1 in neural progenitors promotes cell cycle exit/premature neuronal differentiation and induces abnormal apoptosis in the developing telencephalon.
Pfaar, O; Hohlfeld, J M; Al-Kadah, B; Hauswald, B; Homey, B; Hunzelmann, N; Schliemann, S; Velling, P; Worm, M; Klimek, L
2017-11-01
Subcutaneous allergen immunotherapy with grass pollen allergoids has been proven to be effective and safe in the treatment of patients with allergic rhinoconjunctivitis. Based on the extensive cross-reactivity among Pooideae species, it has been suggested that grass pollen extracts could be prepared from a single species, rather than from a multiple species mixture. To find the optimal dose of a Phleum pratense (P. pratense) allergoid preparation and compare its efficacy and safety to a 6-grass pollen allergoid preparation. In this double-blind, placebo-controlled study (EudraCT: 2011-000674-58), three doses of P. pratense allergoid (1800 therapeutic units (TU), standard-dose 6000 TU and 18 000 TU) were compared with placebo and the marketed 6-grass pollen allergoid (6000 TU). In a pre-seasonal dosing regimen, 102 patients were randomized to five treatment groups and received nine subcutaneous injections. The primary efficacy endpoint was the change in weal size (late-phase reaction [LPR]) in response to the intracutaneous testing (ICT) before and after treatment, comparing the active allergoids to placebo. Secondary outcomes were the change in Total Nasal Symptom Score (TNSS) assessed in the allergen exposure chamber (AEC), the changes in P. pratense-serum-specific IgG 4 and the incidence of adverse events (AEs). All three doses of the P. pratense and the 6-grass pollen allergoid preparations were significantly superior to placebo for the primary outcome, whereas there were no significant differences in the change in TNSS. Compared to the standard-dose, the high-dose of P. pratense did not produce any additional significant benefit, but showed a slight increase in AEs. Yet this increase in AEs was lower than for the 6-grass pollen preparation. The standard-dose of the new P. pratense allergoid was comparable to the marketed 6-grass pollen preparation at equal dose for the parameters measured. © 2017 The Authors. Clinical & Experimental Allergy Published by John Wiley & Sons Ltd.
Zhang, Xiaoyan; Peng, Yanmei; Wang, Ying; Zhang, Zongying; Li, Dawei; Yu, Jialin; Han, Chenggui
2016-11-22
Brassica yellows virus (BrYV), proposed to be a new polerovirus species, three distinct genotypes (BrYV-A, BrYV-B and BrYV-C) have been described. This study was to develop a simple, rapid, sensitive, cost-effective method for simultaneous detection and differentiation of three genotypes of BrYV. In this study, a multiplex reverse transcription-polymerase chain reaction (mRT-PCR) was developed for simultaneous detection and differentiation of the three genotypes of BrYV. The three genotypes of BrYV and Tunip yellows virus (TuYV) could be differentiated simultaneously using six optimized specific oligonucleotide primers, including one universal primer for detecting BrYV, three BrYV genotype-specific primers, and a pair of primers for specific detection of TuYV. Primers were designed from conserved regions of each virus and their specificity was confirmed by sequencing PCR products. The mRT-PCR products were 278 bp for BrYV-A, 674 bp for BrYV-B, 505 bp for BrYV-C, and 205 bp for TuYV. Amplification of three target genotypes was optimized by increasing the PCR annealing temperatures to 62 °C. One to three fragments specific for the virus genotypes were simultaneously amplified from infected samples and identified by their specific molecular sizes in agarose gel electrophoresis. No specific products could be amplified from cDNAs of other viruses which could infect crucifer crops. Detection limits of the plasmids for multiplex PCR were 100 fg for BrYV-A and BrYV-B, 10 pg for BrYV-C, and 1 pg for TuYV, respectively. The mRT-PCR was applied successfully for detection of three BrYV genotypes from field samples collected in China. The simple, rapid, sensitive, and cost-effective mRT-PCR was developed successfully for detection and differentiation of the three genotypes of BrYV.
Wang, Xingliang; Puinean, Alin M; O Reilly, Andrias O; Williamson, Martin S; Smelt, Charles L C; Millar, Neil S; Wu, Yidong
2017-07-01
Abamectin is one of the most widely used avermectins for agricultural pests control, but the emergence of resistance around the world is proving a major threat to its sustained application. Abamectin acts by directly activating glutamate-gated chloride channels (GluCls) and modulating other Cys-loop ion channels. To date, three mutations occurring in the transmembrane domain of arthropod GluCls are associated with target-site resistance to abamectin: A309V in Plutella xylostella GluCl (PxGluCl), G323D in Tetranychus urticae GluCl1 (TuGluCl1) and G326E in TuGluCl3. To compare the effects of these mutations in a single system, A309V/I/G and G315E (corresponding to G323 in TuGluCl1 and G326 in TuGluCl3) substitutions were introduced individually into the PxGluCl channel. Functional analysis using Xenopus oocytes showed that the A309V and G315E mutations reduced the sensitivity to abamectin by 4.8- and 493-fold, respectively. In contrast, the substitutions A309I/G show no significant effects on the response to abamectin. Interestingly, the A309I substitution increased the channel sensitivity to glutamate by one order of magnitude (∼12-fold). Analysis of PxGluCl homology models indicates that the G315E mutation interferes with abamectin binding through a steric hindrance mechanism. In contrast, the structural consequences of the A309 mutations are not so clear and an allosteric modification of the binding site is the most likely mechanism. Overall the results show that both A309V and G315E mutations may contribute to target-site resistance to abamectin and may be important for the future prediction and monitoring of abamectin resistance in P. xylostella and other arthropod pests. Copyright © 2017 Elsevier Ltd. All rights reserved.
Jansen, E; Eccles, D; Chandler, G N
1994-01-01
Two factors characterize innovative organizational climates as perceived by nonmanagerial hospital employees. The first, innovation, comprises perceptions about the consequences or contingencies (e.g., punished, ignored, rewarded) of such proactive activities as implementing new ideas, questioning established methods, and communicating with other departments and the supervisor. The second, restrictive conformity, comprises perceptions about the consequences of risk-aversive, conflict-avoidant activities that suggest dysfunctional conformity (e.g., "sticking to the rules no matter what"). Positive personal outcomes--greater role clarity, organizational involvement, and satisfaction, and lower role conflict and willingness to leave the organization--are associated with innovation; negative personal outcomes are associated with restrictive conformity. The dialectical tension between conformity and innovation is discussed in terms of loose coupling and a reward systems perspective.
NASA Astrophysics Data System (ADS)
Pajewski, Lara; Solla, Mercedes; Fontul, Simona
2017-04-01
This work aims at presenting the main results achieved by Working Group (WG) 4 "Different applications of GPR and other NDT technologies in civil engineering" of the COST (European COoperation in Science and Technology) Action TU1208 "Civil Engineering Applications of Ground Penetrating Radar" (www.GPRadar.eu, www.cost.eu). The main objective of the Action TU1208, started in April 2013 and ending in October 2017, is to exchange and increase scientific-technical knowledge and experience of Ground Penetrating Radar (GPR) techniques in civil engineering, whilst promoting in Europe the effective use of this safe non-destructive technique. The Action involves more than 150 Institutions from 28 COST Countries, a Cooperating State, 6 Near Neighbour Countries and 6 International Partner Countries. WG4 deals with the use of GPR outside from the civil engineering area, namely in archaeological prospecting and cultural heritage diagnostics, agriculture and management of water resources, investigation of polluted industrial sites, non-destructive testing of living tree trunks, planetary exploration, demining, localization of people buried under avalanches and debris, and more. Furthermore, this WG studies the integration of GPR with other Non-Destructive Testing (NDT) methods. The most relevant achievements stemming from WG4 will be presented during the 2017 EGU GA. These are: (i) The collection of thorough information on the state-of-the-art, ongoing studies, problems and future research needs on the topics of interest for this WG; (ii) The performance of a plethora of interesting case studies in important sites all over Europe, including well-known historical places such as Stonehenge (United Kingdom), Carnuntum (Austria), the Wawel Cathedral (Cracow, Poland), the Tholos Tomb of Acharnon (Athens, Greece), the Łazienki Royal Palace (Warsaw, Poland), and more; (iii) WG4 contributed to the TU1208 Education Pack, an open educational package conceived to teach GPR in University courses. Additionally, WG4 was very active in offering training activities. In cooperation with the other WGs, the following courses were successfully organised: Training School (TS) "Civil engineering applications of Ground Penetrating Radar" (Pisa, Italy, September 2014), TS "Applications of Ground Penetrating Radar in urban areas: the sensitive case of historical cities" (Cracow, Poland, May 2015), TS "Applications of GPR to civil engineering and archaeology" (Valletta, Malta, January 2016), and TS "Non-destructive testing techniques for civil engineering" (Barcelona, Spain, March 2016). Finally, WG4 contributed to the organization of a series of national events devoted to fostering the interaction of Action Members with stakeholders, new potential GPR end-users, and interested citizens. During such events, participants could discover what is Ground Penetrating Radar (GPR) and how this technique can be effectively used in civil engineering works as well as in different fields ("TU1208 GPR Road Show"). Acknowledgement: The Authors are deeply grateful to COST (European Cooperation in Science and Technology, www.cost.eu), for funding and supporting the COST Action TU1208 "Civil engineering applications of Ground Penetrating Radar" (www.GPRadar.eu).
NASA Astrophysics Data System (ADS)
Masoumi, Rahim
2017-04-01
From a hydrogeochemical point of view the geothermal fluids in the study area can be divided into two categories, (1) Na-Cl and (2) Na-Ca-HCO3. In the study area, the hot water samples depict temperature and pH ranges of 22 °C to 77 °C and 6.4 to 7.3, respectively. The total dissolved solids vary from 456 mg/L to 7006 mg/L. The concentration of rare metallic and non-metallic elements such as Li, Rb, B, Ba, Sr, CS, Se, Al, As, Hg in cold and hot spring waters in the Bushdi area were also analyzed. The utmost concentration belongs to Se which ranges from 135 mg/L to 273 mg/L. Boron also shows notable concentration values, in most samples it exceeds 20 mg/L, and in certain samples it ranges from 28 mg/L to 33.5 mg/L. The concentration value of arsenic ranges from 3 mg/L to 4 mg/L. The maximum concentration value of mercury is 0.01 mg/L. The δ18O values of these samples vary from -12.4 ‰ to -7.5 ‰ and the δD values range from -78.6 ‰ to -70.6 ‰. Plotting δ18O versus δD demonstrates that the data points are clustered close to both, the global meteoric water line (GMWL) with the equation δD = 8 δ18O + 10 and, the national meteoric water line (NMWL) with the equation δD = 6.89 δ18O + 6.57. As can be observed, the geothermal fluids in the Bushdi area show relatively slight increase in δ18O values that may be caused by interaction of hot fluids with host volcanic rocks. In fact, this relatively slight increment in δ18O values may indicate the low to moderate temperature of the geothermal system. The δD values, in general, do not show notable variation because of very low hydrogen content of the host rocks. The slight increase in δD, however, may be in conjunction with vaporization and isotopic interaction with the host rocks. The 3H content of the cold and hot waters in the Bushdi area is relatively high and varies from 0.65 TU to 41.4 TU. This may be caused either by mixing with meteoric sources or rapid fluid flow within the system in a shorter time than the β- disintegration of the isotope 3H. The δ18O versus δD diagram demonstrates that the data for the Bushdi area is plotted in three distinct domains, a, b, c. In a, the 3H content is > 10 TU indicating these waters being modern waters. Domain b belongs to samples whose 3H values are within the range of 1 TU to 10 TU being temporally categorized as sub-modern waters. The water samples in c possess 3H values < 1 TU indicating the oldest waters within the geothermal system in the study area. Key words: Geothermal fluids, Stable isotopes, Tracemetals, Sabalan volcano.
Shinar, D; Valero-Mora, P; van Strijp-Houtenbos, M; Haworth, N; Schramm, A; De Bruyne, Guido; Cavallo, V; Chliaoutakis, J; Dias, J; Ferraro, O E; Fyhri, A; Sajatovic, A Hursa; Kuklane, K; Ledesma, R; Mascarell, O; Morandi, A; Muser, M; Otte, D; Papadakaki, M; Sanmartín, J; Dulf, D; Saplioglu, M; Tzamalouka, G
2018-01-01
Police crash reports are often the main source for official data in many countries. However, with the exception of fatal crashes, crashes are often underreported in a biased manner. Consequently, the countermeasures adopted according to them may be inefficient. In the case of bicycle crashes, this bias is most acute and it probably varies across countries, with some of them being more prone to reporting accidents to police than others. Assessing if this bias occurs and the size of it can be of great importance for evaluating the risks associated with bicycling. This study utilized data collected in the COST TU1101 action "Towards safer bicycling through optimization of bicycle helmets and usage". The data came from an online survey that included questions related to bicyclists' attitudes, behaviour, cycling habits, accidents, and patterns of use of helmets. The survey was filled by 8655 bicyclists from 30 different countries. After applying various exclusion factors, 7015 questionnaires filled by adult cyclists from 17 countries, each with at least 100 valid responses, remained in our sample. The results showed that across all countries, an average of only 10% of all crashes were reported to the police, with a wide range among countries: from a minimum of 0.0% (Israel) and 2.6% (Croatia) to a maximum of a 35.0% (Germany). Some factors associated with the reporting levels were type of crash, type of vehicle involved, and injury severity. No relation was found between the likelihood of reporting and the cyclist's gender, age, educational level, marital status, being a parent, use of helmet, and type of bicycle. The significant under-reporting - including injury crashes that do not lead to hospitalization - justifies the use of self-report survey data for assessment of bicycling crash patterns as they relate to (1) crash risk issues such as location, infrastructure, cyclists' characteristics, and use of helmet and (2) strategic approaches to bicycle crash prevention and injury reduction. Copyright © 2017 Elsevier Ltd. All rights reserved.
Research Pilot C. Gordon Fullerton in Cockpit of TU-144LL SST Flying Laboratory
NASA Technical Reports Server (NTRS)
1998-01-01
NASA Research pilot C. Gordon Fullerton sits in cockpit of TU-144LL SST Flying Laboratory. Fullerton was one of two NASA pilots who flew the aircraft as part of a joint high speed research program. NASA teamed with American and Russian aerospace industries for an extended period in a joint international research program featuring the Russian-built Tu-144LL supersonic aircraft. The object of the program was to develop technologies for a proposed future second-generation supersonic airliner to be developed in the 21st Century. The aircraft's initial flight phase began in June 1996 and concluded in February 1998 after 19 research flights. A shorter follow-on program involving seven flights began in September 1998 and concluded in April 1999. All flights were conducted in Russia from Tupolev's facility at the Zhukovsky Air Development Center near Moscow. The centerpiece of the research program was the Tu 144LL, a first-generation Russian supersonic jetliner that was modified by its developer/builder, Tupolev ANTK (aviatsionnyy nauchno-tekhnicheskiy kompleks-roughly, aviation technical complex), into a flying laboratory for supersonic research. Using the Tu-144LL to conduct flight research experiments, researchers compared full-scale supersonic aircraft flight data with results from models in wind tunnels, computer-aided techniques, and other flight tests. The experiments provided unique aerodynamic, structures, acoustics, and operating environment data on supersonic passenger aircraft. Data collected from the research program was being used to develop the technology base for a proposed future American-built supersonic jetliner. Although actual development of such an advanced supersonic transport (SST) is currently on hold, commercial aviation experts estimate that a market for up to 500 such aircraft could develop by the third decade of the 21st Century. The Tu-144LL used in the NASA-sponsored research program was a 'D' model with different engines than were used in production-model aircraft. Fifty experiments were proposed for the program and eight were selected, including six flight and two ground (engine) tests. The flight experiments included studies of the aircraft's exterior surface, internal structure, engine temperatures, boundary-layer airflow, the wing's ground-effect characteristics, interior and exterior noise, handling qualities in various flight profiles, and in-flight structural flexibility. The ground tests studied the effect of air inlet structures on airflow entering the engine and the effect on engine performance when supersonic shock waves rapidly change position in the engine air inlet. A second phase of testing further studied the original six in-flight experiments with additional instrumentation installed to assist in data acquisition and analysis. A new experiment aimed at measuring the in-flight deflections of the wing and fuselage was also conducted. American-supplied transducers and sensors were installed to measure nose boom pressures, angle of attack, and sideslip angles with increased accuracy. Two NASA pilots, Robert Rivers of Langley Research Center, Hampton, Virginia, and Gordon Fullerton from Dryden Flight Research Center, Edwards, California, assessed the aircraft's handling at subsonic and supersonic speeds during three flight tests in September 1998. The program concluded after four more data-collection flights in the spring of 1999. The Tu-144LL model had new Kuznetsov NK-321 turbofan engines rated at more than 55,000 pounds of thrust in full afterburner. The aircraft is 215 feet, 6 inches long and 42 feet, 2 inches high with a wingspan of 94 feet, 6 inches. The aircraft is constructed mostly of light aluminum alloy with titanium and stainless steel on the leading edges, elevons, rudder, and the under-surface of the rear fuselage.
Russian Tu-144LL SST Roll-Out for Joint NASA Research Program
NASA Technical Reports Server (NTRS)
1996-01-01
The modified Tu-144LL supersonic flying laboratory is rolled out of its hangar at the Zhukovsky Air Development Center near Moscow, Russia in March 1996 at the beginning of a joint U.S. - Russian high-speed flight research program. The 'LL' stands for Letayuschaya Laboratoriya, which means Flying Laboratory. NASA teamed with American and Russian aerospace industries for an extended period in a joint international research program featuring the Russian-built Tu-144LL supersonic aircraft. The object of the program was to develop technologies for a proposed future second-generation supersonic airliner to be developed in the 21st Century. The aircraft's initial flight phase began in June 1996 and concluded in February 1998 after 19 research flights. A shorter follow-on program involving seven flights began in September 1998 and concluded in April 1999. All flights were conducted in Russia from Tupolev's facility at the Zhukovsky Air Development Center near Moscow. The centerpiece of the research program was the Tu 144LL, a first-generation Russian supersonic jetliner that was modified by its developer/builder, Tupolev ANTK (aviatsionnyy nauchno-tekhnicheskiy kompleks-roughly, aviation technical complex), into a flying laboratory for supersonic research. Using the Tu-144LL to conduct flight research experiments, researchers compared full-scale supersonic aircraft flight data with results from models in wind tunnels, computer-aided techniques, and other flight tests. The experiments provided unique aerodynamic, structures, acoustics, and operating environment data on supersonic passenger aircraft. Data collected from the research program was being used to develop the technology base for a proposed future American-built supersonic jetliner. Although actual development of such an advanced supersonic transport (SST) is currently on hold, commercial aviation experts estimate that a market for up to 500 such aircraft could develop by the third decade of the 21st Century. The Tu-144LL used in the NASA-sponsored research program was a 'D' model with different engines than were used in production-model aircraft. Fifty experiments were proposed for the program and eight were selected, including six flight and two ground (engine) tests. The flight experiments included studies of the aircraft's exterior surface, internal structure, engine temperatures, boundary-layer airflow, the wing's ground-effect characteristics, interior and exterior noise, handling qualities in various flight profiles, and in-flight structural flexibility. The ground tests studied the effect of air inlet structures on airflow entering the engine and the effect on engine performance when supersonic shock waves rapidly change position in the engine air inlet. A second phase of testing further studied the original six in-flight experiments with additional instrumentation installed to assist in data acquisition and analysis. A new experiment aimed at measuring the in-flight deflections of the wing and fuselage was also conducted. American-supplied transducers and sensors were installed to measure nose boom pressures, angle of attack, and sideslip angles with increased accuracy. Two NASA pilots, Robert Rivers of Langley Research Center, Hampton, Virginia, and Gordon Fullerton from Dryden Flight Research Center, Edwards, California, assessed the aircraft's handling at subsonic and supersonic speeds during three flight tests in September 1998. The program concluded after four more data-collection flights in the spring of 1999. The Tu-144LL model had new Kuznetsov NK-321 turbofan engines rated at more than 55,000 pounds of thrust in full afterburner. The aircraft is 215 feet, 6 inches long and 42 feet, 2 inches high with a wingspan of 94 feet, 6 inches. The aircraft is constructed mostly of light aluminum alloy with titanium and stainless steel on the leading edges, elevons, rudder, and the under-surface of the rear fuselage.
Russian Tu-144LL SST Roll-out for Joint NASA Research Program
NASA Technical Reports Server (NTRS)
1996-01-01
U.S. Ambassador Pickering addresses Russian and American dignitaries, industry representatives and members of the press during a roll-out ceremony for the modified Tu-144LL supersonic flying laboratory. The ceremony was held at the Zhukovsky Air Development Center near Moscow, Russia, on March 17, 1996. The 'LL' designation for the aircraft stands for Letayuschaya Laboratoriya, which means Flying Laboratory in Russian. NASA teamed with American and Russian aerospace industries for an extended period in a joint international research program featuring the Russian-built Tu-144LL supersonic aircraft. The object of the program was to develop technologies for a proposed future second-generation supersonic airliner to be developed in the 21st Century. The aircraft's initial flight phase began in June 1996 and concluded in February 1998 after 19 research flights. A shorter follow-on program involving seven flights began in September 1998 and concluded in April 1999. All flights were conducted in Russia from Tupolev's facility at the Zhukovsky Air Development Center near Moscow. The centerpiece of the research program was the Tu 144LL, a first-generation Russian supersonic jetliner that was modified by its developer/builder, Tupolev ANTK (aviatsionnyy nauchno-tekhnicheskiy kompleks-roughly, aviation technical complex), into a flying laboratory for supersonic research. Using the Tu-144LL to conduct flight research experiments, researchers compared full-scale supersonic aircraft flight data with results from models in wind tunnels, computer-aided techniques, and other flight tests. The experiments provided unique aerodynamic, structures, acoustics, and operating environment data on supersonic passenger aircraft. Data collected from the research program was being used to develop the technology base for a proposed future American-built supersonic jetliner. Although actual development of such an advanced supersonic transport (SST) is currently on hold, commercial aviation experts estimate that a market for up to 500 such aircraft could develop by the third decade of the 21st Century. The Tu-144LL used in the NASA-sponsored research program was a 'D' model with different engines than were used in production-model aircraft. Fifty experiments were proposed for the program and eight were selected, including six flight and two ground (engine) tests. The flight experiments included studies of the aircraft's exterior surface, internal structure, engine temperatures, boundary-layer airflow, the wing's ground-effect characteristics, interior and exterior noise, handling qualities in various flight profiles, and in-flight structural flexibility. The ground tests studied the effect of air inlet structures on airflow entering the engine and the effect on engine performance when supersonic shock waves rapidly change position in the engine air inlet. A second phase of testing further studied the original six in-flight experiments with additional instrumentation installed to assist in data acquisition and analysis. A new experiment aimed at measuring the in-flight deflections of the wing and fuselage was also conducted. American-supplied transducers and sensors were installed to measure nose boom pressures, angle of attack, and sideslip angles with increased accuracy. Two NASA pilots, Robert Rivers of Langley Research Center, Hampton, Virginia, and Gordon Fullerton from Dryden Flight Research Center, Edwards, California, assessed the aircraft's handling at subsonic and supersonic speeds during three flight tests in September 1998. The program concluded after four more data-collection flights in the spring of 1999. The Tu-144LL model had new Kuznetsov NK-321 turbofan engines rated at more than 55,000 pounds of thrust in full afterburner. The aircraft is 215 feet, 6 inches long and 42 feet, 2 inches high with a wingspan of 94 feet, 6 inches. The aircraft is constructed mostly of light aluminum alloy with titanium and stainless steel on the leading edges, elevons, rudder, and the under-surface of the rear fuselage.
Feng, Yan Wen; Ooishi, Ayako; Honda, Shinya
2012-01-05
A simple systematic approach using Fourier transform infrared (FTIR) spectroscopy, size exclusion chromatography (SEC) and design of experiments (DOE) techniques was applied to the analysis of aggregation factors for protein formulations in stress and accelerated testings. FTIR and SEC were used to evaluate protein conformational and storage stabilities, respectively. DOE was used to determine the suitable formulation and to analyze both the main effect of single factors and the interaction effect of combined factors on aggregation. Our results indicated that (i) analysis at a low protein concentration is not always applicable to high concentration formulations; (ii) an investigation of interaction effects of combined factors as well as main effects of single factors is effective for improving conformational stability of proteins; (iii) with the exception of pH, the results of stress testing with regard to aggregation factors would be available for suitable formulation instead of performing time-consuming accelerated testing; (iv) a suitable pH condition should not be determined in stress testing but in accelerated testing, because of inconsistent effects of pH on conformational and storage stabilities. In summary, we propose a three-step strategy, using FTIR, SEC and DOE techniques, to effectively analyze the aggregation factors and perform a rapid screening for suitable conditions of protein formulation. Copyright © 2011 Elsevier B.V. All rights reserved.
Stereotype Threat, Gender-Role Conformity, and New Zealand Adolescent Males in Choirs
ERIC Educational Resources Information Center
Watson, Penelope; Rubie-Davies, Christine Margaret; Hattie, John Allan
2017-01-01
Choirs have been stereotypically gendered feminine in many national contexts. When gender-role conformity has been expected in such settings, male choral participation and performance has often been rendered gender incongruent and consequently threatening. Gender stereotype threat was explored as a factor which might instigate a potentially…
Tan, Cheng; Li, Wenfei; Wang, Wei
2013-12-19
Protein TFIIIA is composed of nine tandemly arranged Cys2His2 zinc fingers. It can bind either to the 5S RNA gene as a transcription factor or to the 5S RNA transcript as a chaperone. Although structural and biochemical data provided valuable information on the recognition between the TFIIIIA and the 5S DNA/RNA, the involved conformational motions and energetic factors contributing to the binding affinity and specificity remain unclear. In this work, we conducted MD simulations and MM/GBSA calculations to investigate the binding-induced conformational changes in the recognition of the 5S RNA by the central three zinc fingers of TFIIIA and the energetic factors that influence the binding affinity and specificity at an atomistic level. Our results revealed drastic interdomain conformational changes between these three zinc fingers, involving the exposure/burial of several crucial DNA/RNA binding residues, which can be related to the competition between DNA and RNA for the binding of TFIIIA. We also showed that the specific recognition between finger 4/finger 6 and the 5S RNA introduces frustrations to the nonspecific interactions between finger 5 and the 5S RNA, which may be important to achieve optimal binding affinity and specificity.
NASA Technical Reports Server (NTRS)
1985-01-01
Topics include: NASA TU Services; New Product Ideas; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials; Life Sciences; Mechanics; Machinery; Fabrication Technology; Mathematics and Information Sciences.
NASA Technical Reports Server (NTRS)
1985-01-01
Topic include: NASA TU Services; New Product Ideas; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials; Life Sciences; Mechanics; Machinery; Fabrication Technology; Mathematics and Information Sciences.
Effect of intradermal tuberculin tests on BCG-induced allergy
Magnus, Knut
1957-01-01
Trials are going forward to determine whether intradermal tuberculin testing with 10 TU at yearly intervals after BCG vaccination may prevent waning of BCG-induced allergy in schoolchildren. Meanwhile, two experiments to the same purpose, carried out in guinea-pigs, are described. They show that waning allergy in guinea-pigs can be sustantially enhanced by intradermal injection of either purified tuberculin or Old Tuberculin, the effect lasting for at least 8 weeks, even with so small a dose as 5 TU. It is pointed out that this enhancing effect has been demonstrated only in BCG-vaccinated guinea-pigs and that it is not known whether the same phenomenon would occur in guinea-pigs infected with living human tubercle bacilli. PMID:13489466
Xu, T; Peng, H S
2016-03-01
Ben cao tu jing (Illustrated Classic of Materia Medica) is the earliest extant atlas book of materia medica in China, with 933 attached drawings. Among them, the largest portion, amounting to 670, are herbaceous plants, mostly commonly used, with definite marks of the origin producing areas, distributed across 149 administrative divisions(prefectures and counties) of the Song Dynasty, most of them in Northern area which were distributed denser than those in Southern area. The densest ones were located in Southern Shanxi, Eastern Sichuan and Eastern Anhui. In the attached drawings, the frequency of highest occurrence appeared in this Classic are three prefectures, Chuzhou, Shizhou and Guangzhou.
Tritium in Australian Precipitation: a 40 Year Record
NASA Astrophysics Data System (ADS)
Tadros, C. V.; Stone, D. J.; Hill, D. M.; Henderson-Sellers, A.
2004-12-01
Tritium, the radioisotope of hydrogen, directly incorporated into water molecules in the global hydrological system, is the most commonly used radioisotope indicator of groundwater recharge. Tritium in precipitation has been measured in Australia over the past 40 years, as an essential research tool in hydro-climate studies and to contribute to the Global Network for Isotopes in Precipitation (GNIP). Tritium, which as tritiated water (3H 1H O) is very mobile in the environment, delivers the benefit of tracing groundwater systems in a 10 - 20 year timeframe as a result of last century's atmospheric thermonuclear testing. The concentration of tritium in Australian precipitation reached a maximum level of 160 TU in 1963, during one of the most intense periods of nuclear testing. Our data reveal Australia experienced a `minor' bomb pulse compared to the Northern Hemisphere eg. in Ottawa, Canada a value of 6000 TU was recorded in 1963 for tritium in precipitation. From 1963 to 1980 we observe a rapid drop in the concentration of tritium, more than expected from natural decay, mainly due to the wash out of tritium into the oceans and groundwater. Since 1990 the levels of tritium have stabilised globally and regionally. Currently the levels of tritium in Australia have stabilised to 2 to 3 TU latitudinally across the continent, a factor of 10 lower than values observed at stations in the Northern Hemisphere. At present, levels of tritium in Australia appear to have ceased declining and our analyses suggest that today the tritium in precipitation is predominantly natural. We believe that it may be possible that the increased levels observed in the Northern Hemisphere, due to nuclear power generation [1] could `leak' into the Southern Hemisphere. This is important for research in Australia because it could hinder the exploitation of tritium in providing information on the origin and mechanism of recharge of shallow groundwaters and rivers [2]. 1. J.D. Happell, et al. A history of atmospheric tritium gas (HT) 1950-2002. Tellus(2004) 56B, 183-193. 2. D.J.M. Stone, et al. Investigation of Groundwater-Streamflow interactions in the Bega alluvial aquifer using tritium and stable isotopic ratios. ANA 2001, 4th Conference on Nuclear Science and Engineering in Australasia, pp 191-197, Sydney, NSW.
Makarova, Olga; Contaldo, Nicoletta; Paltrinieri, Samanta; Kawube, Geofrey; Bertaccini, Assunta; Nicolaisen, Mogens
2012-01-01
Background Phytoplasmas are bacterial phytopathogens responsible for significant losses in agricultural production worldwide. Several molecular markers are available for identification of groups or strains of phytoplasmas. However, they often cannot be used for identification of phytoplasmas from different groups simultaneously or are too long for routine diagnostics. DNA barcoding recently emerged as a convenient tool for species identification. Here, the development of a universal DNA barcode based on the elongation factor Tu (tuf) gene for phytoplasma identification is reported. Methodology/Principal Findings We designed a new set of primers and amplified a 420–444 bp fragment of tuf from all 91 phytoplasmas strains tested (16S rRNA groups -I through -VII, -IX through -XII, -XV, and -XX). Comparison of NJ trees constructed from the tuf barcode and a 1.2 kbp fragment of the 16S ribosomal gene revealed that the tuf tree is highly congruent with the 16S rRNA tree and had higher inter- and intra- group sequence divergence. Mean K2P inter−/intra- group divergences of the tuf barcode did not overlap and had approximately one order of magnitude difference for most groups, suggesting the presence of a DNA barcoding gap. The use of the tuf barcode allowed separation of main ribosomal groups and most of their subgroups. Phytoplasma tuf barcodes were deposited in the NCBI GenBank and Q-bank databases. Conclusions/Significance This study demonstrates that DNA barcoding principles can be applied for identification of phytoplasmas. Our findings suggest that the tuf barcode performs as well or better than a 1.2 kbp fragment of the 16S rRNA gene and thus provides an easy procedure for phytoplasma identification. The obtained sequences were used to create a publicly available reference database that can be used by plant health services and researchers for online phytoplasma identification. PMID:23272216
Evidence for Horizontal Gene Transfer in Evolution of Elongation Factor Tu in Enterococci
Ke, Danbing; Boissinot, Maurice; Huletsky, Ann; Picard, François J.; Frenette, Johanne; Ouellette, Marc; Roy, Paul H.; Bergeron, Michel G.
2000-01-01
The elongation factor Tu, encoded by tuf genes, is a GTP binding protein that plays a central role in protein synthesis. One to three tuf genes per genome are present, depending on the bacterial species. Most low-G+C-content gram-positive bacteria carry only one tuf gene. We have designed degenerate PCR primers derived from consensus sequences of the tuf gene to amplify partial tuf sequences from 17 enterococcal species and other phylogenetically related species. The amplified DNA fragments were sequenced either by direct sequencing or by sequencing cloned inserts containing putative amplicons. Two different tuf genes (tufA and tufB) were found in 11 enterococcal species, including Enterococcus avium, Enterococcus casseliflavus, Enterococcus dispar, Enterococcus durans, Enterococcus faecium, Enterococcus gallinarum, Enterococcus hirae, Enterococcus malodoratus, Enterococcus mundtii, Enterococcus pseudoavium, and Enterococcus raffinosus. For the other six enterococcal species (Enterococcus cecorum, Enterococcus columbae, Enterococcus faecalis, Enterococcus sulfureus, Enterococcus saccharolyticus, and Enterococcus solitarius), only the tufA gene was present. Based on 16S rRNA gene sequence analysis, the 11 species having two tuf genes all have a common ancestor, while the six species having only one copy diverged from the enterococcal lineage before that common ancestor. The presence of one or two copies of the tuf gene in enterococci was confirmed by Southern hybridization. Phylogenetic analysis of tuf sequences demonstrated that the enterococcal tufA gene branches with the Bacillus, Listeria, and Staphylococcus genera, while the enterococcal tufB gene clusters with the genera Streptococcus and Lactococcus. Primary structure analysis showed that four amino acid residues encoded within the sequenced regions are conserved and unique to the enterococcal tufB genes and the tuf genes of streptococci and Lactococcus lactis. The data suggest that an ancestral streptococcus or a streptococcus-related species may have horizontally transferred a tuf gene to the common ancestor of the 11 enterococcal species which now carry two tuf genes. PMID:11092850
Tunca, Evren; Aydın, Mehmet; Şahin, Ülkü Alver
2018-03-01
The aim of this study is an assessment of metal pollution levels in Aegean Sea sediment. Sediment samples collected from 7 different locations (Yeniköy, Edremit, Ayvalık, Dikili, Aliağa, Hekimadası, and Ildır) along the northern Mediterranean region of Turkey were investigated for 11 elements (Cu, Fe, Zn, V, Cd, Ni, As, Pb, Mn, Co, and Cr). Graphite furnace atomic absorption spectrophotometry (GFAAS) and flame atomic absorption spectrophotometry (FAAS) were used for elemental analysis. The findings were evaluated with sediment assessment methods by taking two different values as a reference and then investigating the adverse biological effects of elemental profiles on living organisms. Pb, Mn, As, Cd, and Cr concentrations were within a moderate to significant range in terms of contamination factor [Formula: see text]), albeit varying according to reference and location. The most problematic region and elements regarding the enrichment factor (EF) was Ayvalık and As, Ni, Cu, Pb, Co, and Cd. However, according to the EF, the anthropogenic effect was not at an alarming level. This was further supported by the results of the geoaccumulation index (Igeo). The findings of the modified degree of contamination (mC d ) and the pollution load index (PLI) suggested that the accumulation was greatest in Ayvalık, and the least in Hekimadası and Ildır. The location with the highest elemental total toxic unit (ΣTU) was Edremit. The effect of the existing element profile on organisms was 21% in this location when the mean effect range-median quotient (m-ERM-q) was considered. As and Ni concentrations in all stations were found to be higher than threshold effect level (TEL) and Effect Range Low (ERL). Ni levels in Edremit exceeded the probable effect level (PEL) and Effect Range Median (ERM). Toxic unit (TU) values of these two elements in all stations ranged from 59.30 to 80.43%.
Structural basis for signal recognition and transduction by platelet-activating-factor receptor.
Cao, Can; Tan, Qiuxiang; Xu, Chanjuan; He, Lingli; Yang, Linlin; Zhou, Ye; Zhou, Yiwei; Qiao, Anna; Lu, Minmin; Yi, Cuiying; Han, Gye Won; Wang, Xianping; Li, Xuemei; Yang, Huaiyu; Rao, Zihe; Jiang, Hualiang; Zhao, Yongfang; Liu, Jianfeng; Stevens, Raymond C; Zhao, Qiang; Zhang, Xuejun C; Wu, Beili
2018-06-01
Platelet-activating-factor receptor (PAFR) responds to platelet-activating factor (PAF), a phospholipid mediator of cell-to-cell communication that exhibits diverse physiological effects. PAFR is considered an important drug target for treating asthma, inflammation and cardiovascular diseases. Here we report crystal structures of human PAFR in complex with the antagonist SR 27417 and the inverse agonist ABT-491 at 2.8-Å and 2.9-Å resolution, respectively. The structures, supported by molecular docking of PAF, provide insights into the signal-recognition mechanisms of PAFR. The PAFR-SR 27417 structure reveals an unusual conformation showing that the intracellular tips of helices II and IV shift outward by 13 Å and 4 Å, respectively, and helix VIII adopts an inward conformation. The PAFR structures, combined with single-molecule FRET and cell-based functional assays, suggest that the conformational change in the helical bundle is ligand dependent and plays a critical role in PAFR activation, thus greatly extending knowledge about signaling by G-protein-coupled receptors.
Effects of oncogenic mutations on the conformational free-energy landscape of EGFR kinase
Sutto, Ludovico; Gervasio, Francesco Luigi
2013-01-01
Activating mutations in the epidermal growth factor receptor (EGFR) tyrosine kinase are frequently found in many cancers. It has been suggested that changes in the equilibrium between its active and inactive conformations are linked to its oncogenic potential. Here, we quantify the effects of some of the most common single (L858R and T790M) and double (T790M-L858R) oncogenic mutations on the conformational free-energy landscape of the EGFR kinase domain by using massive molecular dynamics simulations together with parallel tempering, metadynamics, and one of the best force-fields available. Whereas the wild-type EGFR catalytic domain monomer is mostly found in an inactive conformation, our results show a clear shift toward the active conformation for all of the mutants. The L858R mutation stabilizes the active conformation at the expense of the inactive conformation and rigidifies the αC-helix. The T790M gatekeeper mutant favors activation by stabilizing a hydrophobic cluster. Finally, T790M with L858R shows a significant positive epistasis effect. This combination not only stabilizes the active conformation, but in nontrivial ways changes the free-energy landscape lowering the transition barriers. PMID:23754386
NASA Astrophysics Data System (ADS)
Melo, Ulisses Zonta de; Yamazaki, Diego Alberto dos Santos; Cândido, Augusto de Araújo; Basso, Ernani Abicht; Gauze, Gisele de Freitas
2018-07-01
The three-dimensional structure of a potential drug molecule is of critical importance. Factors that determine its conformational stability and, consequently, corresponding biological/physicochemical properties of interest must therefore be carefully analyzed. Conformational properties and molecular structures of cis and trans-3-phenylaminocyclohexyl N,N-dimethylcarbamates were studied by low temperature 1H and 13C NMR spectroscopy and electronic structure calculations. B3LYP and M06-2X methods associated with the 6-311++G(2df,2p) basis set, and the integral-equation-formalism polarizable continuum model were used to study the conformational preferences in dichloromethane, acetone and methanol. NMR measurements indicated that for the cis isomer, the conformer with both substituents in equatorial position is the most stable, while for the trans isomer, the conformer with the carbamate group in the axial position and the arylamine in the equatorial position is favored in all solvents. B3LYP/6-311++G(2df,2p) theory level associated with IEF-PCM described properly the conformational preference in solution. NBO analyses were applied to determine the importance of hyperconjugative interactions in the conformational equilibrium.
Effects of oncogenic mutations on the conformational free-energy landscape of EGFR kinase.
Sutto, Ludovico; Gervasio, Francesco Luigi
2013-06-25
Activating mutations in the epidermal growth factor receptor (EGFR) tyrosine kinase are frequently found in many cancers. It has been suggested that changes in the equilibrium between its active and inactive conformations are linked to its oncogenic potential. Here, we quantify the effects of some of the most common single (L858R and T790M) and double (T790M-L858R) oncogenic mutations on the conformational free-energy landscape of the EGFR kinase domain by using massive molecular dynamics simulations together with parallel tempering, metadynamics, and one of the best force-fields available. Whereas the wild-type EGFR catalytic domain monomer is mostly found in an inactive conformation, our results show a clear shift toward the active conformation for all of the mutants. The L858R mutation stabilizes the active conformation at the expense of the inactive conformation and rigidifies the αC-helix. The T790M gatekeeper mutant favors activation by stabilizing a hydrophobic cluster. Finally, T790M with L858R shows a significant positive epistasis effect. This combination not only stabilizes the active conformation, but in nontrivial ways changes the free-energy landscape lowering the transition barriers.
Pan, Yufang; Li, Qiaofeng; Wang, Zhizheng; Wang, Yang; Ma, Rui; Zhu, Lili; He, Guangcun; Chen, Rongzhi
2014-12-16
Thermosensitive genic male sterile (TGMS) lines and photoperiod-sensitive genic male sterile (PGMS) lines have been successfully used in hybridization to improve rice yields. However, the molecular mechanisms underlying male sterility transitions in most PGMS/TGMS rice lines are unclear. In the recently developed TGMS-Co27 line, the male sterility is based on co-suppression of a UDP-glucose pyrophosphorylase gene (Ugp1), but further study is needed to fully elucidate the molecular mechanisms involved. Microarray-based transcriptome profiling of TGMS-Co27 and wild-type Hejiang 19 (H1493) plants grown at high and low temperatures revealed that 15462 probe sets representing 8303 genes were differentially expressed in the two lines, under the two conditions, or both. Environmental factors strongly affected global gene expression. Some genes important for pollen development were strongly repressed in TGMS-Co27 at high temperature. More significantly, series-cluster analysis of differentially expressed genes (DEGs) between TGMS-Co27 plants grown under the two conditions showed that low temperature induced the expression of a gene cluster. This cluster was found to be essential for sterility transition. It includes many meiosis stage-related genes that are probably important for thermosensitive male sterility in TGMS-Co27, inter alia: Arg/Ser-rich domain (RS)-containing zinc finger proteins, polypyrimidine tract-binding proteins (PTBs), DEAD/DEAH box RNA helicases, ZOS (C2H2 zinc finger proteins of Oryza sativa), at least one polyadenylate-binding protein and some other RNA recognition motif (RRM) domain-containing proteins involved in post-transcriptional processes, eukaryotic initiation factor 5B (eIF5B), ribosomal proteins (L37, L1p/L10e, L27 and L24), aminoacyl-tRNA synthetases (ARSs), eukaryotic elongation factor Tu (eEF-Tu) and a peptide chain release factor protein involved in translation. The differential expression of 12 DEGs that are important for pollen development, low temperature responses or TGMS was validated by quantitative RT-PCR (qRT-PCR). Temperature strongly affects global gene expression and may be the common regulator of fertility in PGMS/TGMS rice lines. The identified expression changes reflect perturbations in the transcriptomic regulation of pollen development networks in TGMS-Co27. Findings from this and previous studies indicate that sets of genes involved in post-transcriptional and translation processes are involved in thermosensitive male sterility transitions in TGMS-Co27.
Marco, Esther; Martín-Santamaría, Sonsoles; Cuevas, Carmen; Gago, Federico
2004-08-26
Didemnins and tamandarins are closely related marine natural products with potent inhibitory effects on protein synthesis and cell viability. On the basis of available biochemical and structural evidence and results from molecular dynamics simulations, a model is proposed that accounts for the strong and selective binding of these compounds to human elongation factor eEF1A in the presence of GTP. We suggest that the p-methoxyphenyl ring of these cyclic depsipeptides is inserted into the same pocket in eEF1A that normally lodges either the 3' terminal adenine of aminoacylated tRNA, as inferred from two prokaryotic EF-Tu.GTP.tRNA complexes, or the aromatic side chain of Phe/Tyr-163 from the nucleotide exchange factor eEF1Balpha, as observed in several X-ray crystal structures of a yeast eEF1A:eEF1Balpha complex. This pocket, which has a strong hydrophobic character, is formed by two protruding loops on the surface of eEF1A domain 2. Further stabilization of the bound depsipeptide is brought about by additional crucial interactions involving eEF1A domain 1 in such a way that the molecule fits snugly at the interface between these two domains. In the GDP-bound form of eEF1A, this binding site exists only as two separate halves, which accounts for the much greater affinity of didemnins for the GTP-bound form of this elongation factor. This binding mode is entirely different from those seen in the complexes of the homologous prokaryotic EF-Tu with kirromycin-type antibiotics or the cyclic thiazolyl peptide antibiotic GE2270A. Interestingly, the set of interactions used by didemnins to bind to eEF1A is also distinct from that used by eEF1Balpha or eEF1Bbeta, thus establishing a competition for binding to a common site that goes beyond simple molecular mimicry. The model presented here is consistent with both available biochemical evidence and known structure-activity relationships for these two classes of natural compounds and synthetic analogues and provides fertile ground for future research.
Influence of conformity on the wear of total knee replacement: An experimental study
Brockett, Claire L; Carbone, Silvia; Fisher, John; Jennings, Louise M
2017-01-01
Wear of total knee replacement continues to be a significant factor influencing the clinical longevity of implants. Historically, failure due to delamination and fatigue directed design towards more conforming inserts to reduce contact stress. As new generations of more oxidatively stable polyethylene have been developed, more flexibility in bearing design has been introduced. The aim of this study was to investigate the effect of insert conformity on the wear performance of a fixed bearing total knee replacement through experimental simulation. Two geometries of insert were studied under standard gait conditions. There was a significant reduction in wear with reducing implant conformity. This study has demonstrated that bearing conformity has a significant impact on the wear performance of a fixed bearing total knee replacement, providing opportunities to improve clinical performance through enhanced material and design selection. PMID:29251167
Anti-de Sitter-space/conformal-field-theory Casimir energy for rotating black holes.
Gibbons, G W; Perry, M J; Pope, C N
2005-12-02
We show that, if one chooses the Einstein static universe as the metric on the conformal boundary of Kerr-anti-de Sitter spacetime, then the Casimir energy of the boundary conformal field theory can easily be determined. The result is independent of the rotation parameters, and the total boundary energy then straightforwardly obeys the first law of thermodynamics. Other choices for the metric on the conformal boundary will give different, more complicated, results. As an application, we calculate the Casimir energy for free self-dual tensor multiplets in six dimensions and compare it with that of the seven-dimensional supergravity dual. They differ by a factor of 5/4.
The Secondary Structure of Human Hageman Factor (Factor XII) and its Alteration by Activating Agents
McMillin, Carl R.; Saito, Hidehiko; Ratnoff, Oscar D.; Walton, Alan G.
1974-01-01
Hageman factor (factor XII) is activated by exposure to surfaces such as glass or by solutions of certain compounds, notably ellagic acid. Changes in the structure of Hageman factor accompanying activation have been examined in this study by circular dichroism spectroscopy. The spectrum of unactivated Hageman factor in aqueous solutions suggests that its conformation is mainly aperiodic. Various perturbants altered the conformation of Hageman factor in differing ways, demonstrating the sensitivity of Hageman factor to its environment. After activation of Hageman factor with solutions of ellagic acid, a negative trough appeared in the region of the circular dichroism spectrum commonly assigned to tyrosine residues, along with other minor changes in the peptide spectral region. Some of these changes are similar to changes that occurred upon partial neutralization of the basic residues at alkali pH. Activation of Hageman factor by adsorption to quartz surfaces (in an aqueous environment) also produced changes similar to those in the ellagic acid-activated Hageman factor, including the negative ellipticity in the tyrosine region. These observations suggest that the activation process may be related to a change in status of some of the basic amino acid residues, coupled with a specific change in the environment of some tyrosine residues. The importance of these changes during the activation process remains to be determined. The sensitivity of Hageman factor to its environment is consistent with the view that the initiation of clotting by exposure of plasma to appropriate agents is brought about by alterations in the conformation of Hageman factor that occur in the apparent absence of Fletcher factor or other recognized clotting factors. Images PMID:4373492
Owen, Jesse
2011-03-01
The current study examined the psychometric properties of the abbreviated versions, 55- and 22-items, of the Conformity to Masculine Norms Inventory (CMNI). The authors tested the factor structure for the 11 subscales of the CMNI-55 and the global masculinity factor for the CMNI-55 and the CMNI-22. In a clinical sample of men and women (n=522), the results supported the 11-factor model. Furthermore, the factor structure was invariant for men and women. The higher order model, which tested the utility of the global masculine score, demonstrated marginal fit. The factor structures for the global masculinity score for the CMNI-22 demonstrated poor fit. Collectively, the results suggest that the CMNI-55 is better represented in a multidimensional construct. The subscales' alpha levels and factor loadings were, generally, within acceptable limits. Gender and ethnic mean level differences are also reported. © The Author(s) 2011
Structural landscape of the proline-rich domain of Sos1 nucleotide exchange factor.
McDonald, Caleb B; Bhat, Vikas; Kurouski, Dmitry; Mikles, David C; Deegan, Brian J; Seldeen, Kenneth L; Lednev, Igor K; Farooq, Amjad
2013-01-01
Despite its key role in mediating a plethora of cellular signaling cascades pertinent to health and disease, little is known about the structural landscape of the proline-rich (PR) domain of Sos1 guanine nucleotide exchange factor. Herein, using a battery of biophysical tools, we provide evidence that the PR domain of Sos1 is structurally disordered and adopts an extended random coil-like conformation in solution. Of particular interest is the observation that while chemical denaturation of PR domain results in the formation of a significant amount of polyproline II (PPII) helices, it has little or negligible effect on its overall size as measured by its hydrodynamic radius. Our data also show that the PR domain displays a highly dynamic conformational basin in agreement with the knowledge that the intrinsically unstructured proteins rapidly interconvert between an ensemble of conformations. Collectively, our study provides new insights into the conformational equilibrium of a key signaling molecule with important consequences on its physiological function. Copyright © 2013 Elsevier B.V. All rights reserved.
NASA Astrophysics Data System (ADS)
Banchelli, Martina; Guardiani, Carlo; Sandberg, Robert B.; Menichetti, Stefano; Procacci, Piero; Caminati, Gabriella
2015-07-01
Small-molecule inhibitors of Tumor Necrosis Factor α Converting Enzyme (TACE) are a promising therapeutic tool for Rheumatoid Arthritis, Multiple Sclerosis and other autoimmune diseases. Here we report on an extensive chemical-physical analysis of the media effects in modulating the conformational landscape of MBET306, the common scaffold and a synthetic precursor of a family of recently discovered tartrate-based TACE inhibitors. The structural features of this molecule with potential pharmaceutical applications have been disclosed by interpreting extensive photophysical measurements in various solvents with the aid of enhanced sampling molecular dynamics simulations and time dependent density functional calculations. Using a combination of experimental and computational techniques, the paper provides a general protocol for studying the structure in solution of molecular systems characterized by the existence of conformational metastable states.
Zheng, Huanquan
2015-01-01
Plant viruses move systemically in plants through the phloem. They move as virions or as ribonucleic protein complexes, although it is not clear what these complexes are made of. The approximately 10-kb RNA genome of Turnip mosaic virus (TuMV) encodes a membrane protein, known as 6K2, that induces endomembrane rearrangements for the formation of viral replication factories. These factories take the form of vesicles that contain viral RNA (vRNA) and viral replication proteins. In this study, we report the presence of 6K2-tagged vesicles containing vRNA and the vRNA-dependent RNA polymerase in phloem sieve elements and in xylem vessels. Transmission electron microscopy observations showed the presence in the xylem vessels of vRNA-containing vesicles that were associated with viral particles. Stem-girdling experiments, which leave xylem vessels intact but destroy the surrounding tissues, confirmed that TuMV could establish a systemic infection of the plant by going through xylem vessels. Phloem sieve elements and xylem vessels from Potato virus X-infected plants also contained lipid-associated nonencapsidated vRNA, indicating that the presence of membrane-associated ribonucleic protein complexes in the phloem and xylem may not be limited to TuMV. Collectively, these studies indicate that viral replication factories could end up in the phloem and the xylem. PMID:25717035
NASA Astrophysics Data System (ADS)
Horton, Peter; Moore, Peter
This year marks the twentieth anniversary of the introduction of Concorde into commercial airline service. The first commercial flights were on 21 January 1976 - British Airways from Heathrow to Bahrain and Air France from Paris to Rio via Dakar. Later in that year commercial flights to Washington/Dulles began on 24 May. Services to New York were delayed until 22 November 1977. The first flight of Concorde was some seven years earlier. The prototype took off out of Toulouse on 2 March 1969 and this was followed by 002 from Filton to Fairford on 9 April. At the time it was anticipated that this was the beginning of an era when supersonic flight would be the normal way to travel long distances. Now, in 1996, Concorde is still the world's only supersonic commercial passenger airliner in airline service. This is an extraordinary achievement. The Boeing SST proved to be too ambitious and the programme was halted in 1971 after the United States Government withdrew support, while the Russian TU 144 was beset with problems. One TU 144 crashed at the Paris Air Show in 1973. The aircraft entered internal airline service in December 1975, flying supersonically between Moscow and Alma-Ata, capital of Kazakhstan, carrying mail and freight, but it did not have the range to operate viable intercontinental passenger serives. Certainly by 1985, if not many years before, the TU 144 was out of service.
On the hydration and conformation of cocaine in solution
NASA Astrophysics Data System (ADS)
Gillams, Richard J.; Lorenz, Christian D.; McLain, Sylvia E.
2017-05-01
In order to develop theories relating to the mechanism through which cocaine can diffuse across the blood-brain barrier, it is important to understand the interplay between the hydration of the molecule and the adopted conformation. Here key differences in the hydration of cocaine hydrochloride (CHC) and freebase cocaine (CFB) are highlighted on the atomic scale in solution, through the use of molecular dynamics simulations. By adopting different conformations, CHC and CFB experience differing hydration environments. The interplay between these two factors may account for the vast difference in solubility of these two molecules.
Ryu, HyungChul; Lim, Ju-Ok; Kang, Dong Wook; Pearce, Larry V.; Tran, Richard; Toth, Attila; Lee, Jeewoo; Blumberg, Peter M.
2012-01-01
A series of bicyclic analogues having indan and tetrahydronaphthalene templates in the A-region were designed as conformationally constrained analogues of our previously reported potent TRPV1 antagonists (1, 3). The activities for rat TRPV1 of the conformationally restricted analogues were moderately or markedly diminished, particularly in the case of the tetrahydronaphthalene analogues. The analysis indicated that steric constraints at the benzylic position in the bicyclic analogues were an important factor for their unfavorable interaction with the receptor. PMID:18406014
Symmetric factorization of the conformation tensor in viscoelastic fluid models
NASA Astrophysics Data System (ADS)
Thomases, Becca; Balci, Nusret; Renardy, Michael; Doering, Charles
2010-11-01
The positive definite symmetric polymer conformation tensor possesses a unique symmetric square root that satisfies a closed evolution equation in the Oldroyd-B and FENE-P models of viscoelastic fluid flow. When expressed in terms of the velocity field and the symmetric square root of the conformation tensor, these models' equations of motion formally constitute an evolution in a Hilbert space with a total energy functional that defines a norm. Moreover, this formulation is easily implemented in direct numerical simulations resulting in significant practical advantages in terms of both accuracy and stability.
La Sala, Giuseppina; Riccardi, Laura; Gaspari, Roberto; Cavalli, Andrea; Hantschel, Oliver; De Vivo, Marco
2016-11-08
A number of structural factors modulate the activity of Abelson (Abl) tyrosine kinase, whose deregulation is often related to oncogenic processes. First, only the open conformation of the Abl kinase domain's activation loop (A-loop) favors ATP binding to the catalytic cleft. In this regard, the trans-autophosphorylation of the Y412 residue, which is located along the A-loop, favors the stability of the open conformation, in turn enhancing Abl activity. Another key factor for full Abl activity is the formation of active conformations of the catalytic DFG motif in the Abl kinase domain. Furthermore, binding of the SH2 domain to the N-lobe of the Abl kinase was recently demonstrated to have a long-range allosteric effect on the stabilization of the A-loop open state. Intriguingly, these distinct structural factors imply a complex signal transmission network for controlling the A-loop's flexibility and conformational preference for optimal Abl function. However, the exact dynamical features of this signal transmission network structure remain unclear. Here, we report on microsecond-long molecular dynamics coupled with enhanced sampling simulations of multiple Abl model systems, in the presence or absence of the SH2 domain and with the DFG motif flipped in two ways (in or out conformation). Through comparative analysis, our simulations augment the interpretation of the existing Abl experimental data, revealing a dynamical network of interactions that interconnect SH2 domain binding with A-loop plasticity and Y412 autophosphorylation in Abl. This signaling network engages the DFG motif and, importantly, other conserved structural elements of the kinase domain, namely, the EPK-ELK H-bond network and the HRD motif. Our results show that the signal propagation for modulating the A-loop spatial localization is highly dependent on the HRD motif conformation, which thus acts as the central hub of this (allosteric) signaling network controlling Abl activation and function.
NASA Tech Briefs, May 1988. Volume 12, No. 5
NASA Technical Reports Server (NTRS)
1988-01-01
Topics : New Product Ideas; NASA TU Services; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials; Computer Programs; Mechanics ; Machinery; Fabrication Technology; Mathematics and Information Sciences.
NASA Tech Briefs, November 1990. Volume 14, No. 11
NASA Technical Reports Server (NTRS)
1990-01-01
Topics: New Product Ideas; NASA TU Services; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials; Computer Programs; Mechanics; Machinery; Fabrication Technology; Mathematics and Information Sciences.
NASA Tech Briefs, April 1990. Volume 14, No. 4
NASA Technical Reports Server (NTRS)
1990-01-01
Topics: New Product Ideas; NASA TU Services; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials; Computer Programs; Mechanics; Machinery; Fabrication Technology; Mathematics and Information Sciences.
DOE Office of Scientific and Technical Information (OSTI.GOV)
LaMarche, Matthew J.; Leeds, Jennifer A.; Amaral, Kerri
4-Aminothiazolyl analogues of the antibiotic natural product GE2270 A (1) were designed, synthesized, and optimized for their activity against Gram positive bacterial infections. Optimization efforts focused on improving the physicochemical properties (e.g., aqueous solubility and chemical stability) of the 4-aminothiazolyl natural product template while improving the in vitro and in vivo antibacterial activity. Structure-activity relationships were defined, and the solubility and efficacy profiles were improved over those of previous analogues and 1. These studies identified novel, potent, soluble, and efficacious elongation factor-Tu inhibitors, which bear cycloalkylcarboxylic acid side chains, and culminated in the selection of development candidates amide 48 andmore » urethane 58.« less
Molaee, Neda; Abtahi, Hamid; Ghannadzadeh, Mohammad Javad; Karimi, Masoude; Ghaznavi-Rad, Ehsanollah
2015-01-01
Polymerase chain reaction (PCR) is preferred to other methods for detecting Escherichia coli (E. coli) in water in terms of speed, accuracy and efficiency. False positive result is considered as the major disadvantages of PCR. For this reason, reverse transcriptase-polymerase chain reaction (RT-PCR) can be used to solve this problem. The aim of present study was to determine the efficiency of RT-PCR for rapid detection of viable Escherichia coli in drinking water samples and enhance its sensitivity through application of different filter membranes. Specific primers were designed for 16S rRNA and elongation Factor II genes. Different concentrations of bacteria were passed through FHLP and HAWP filters. Then, RT-PCR was performed using 16srRNA and EF -Tu primers. Contamination of 10 wells was determined by RT-PCR in Arak city. To evaluate RT-PCR efficiency, the results were compared with most probable number (MPN) method. RT-PCR is able to detect bacteria in different concentrations. Application of EF II primers reduced false positive results compared to 16S rRNA primers. The FHLP hydrophobic filters have higher ability to absorb bacteria compared with HAWB hydrophilic filters. So the use of hydrophobic filters will increase the sensitivity of RT-PCR. RT-PCR shows a higher sensitivity compared to conventional water contamination detection method. Unlike PCR, RT-PCR does not lead to false positive results. The use of EF-Tu primers can reduce the incidence of false positive results. Furthermore, hydrophobic filters have a higher ability to absorb bacteria compared to hydrophilic filters.
Experimentally observed conformation-dependent geometry and hidden strain in proteins.
Karplus, P. A.
1996-01-01
A database has been compiled documenting the peptide conformations and geometries from 70 diverse proteins refined at 1.75 A or better. Analysis of the well-ordered residues within the database shows phi, psi-distributions that have more fine structure than is generally observed. Also, clear evidence is presented that the peptide covalent geometry depends on conformation, with the interpeptide N-C alpha-C bond angle varying by nearly +/-5 degrees from its standard value. The observed deviations from standard peptide geometry are greatest near the edges of well-populated regions, consistent with strain occurring in these conformations. Minimization of such hidden strain could be an important factor in thermostability of proteins. These empirical data describing how equilibrium peptide geometry varies as a function of conformation confirm and extend quantum mechanics calculations, and have predictive value that will aid both theoretical and experimental analyses of protein structure. PMID:8819173
NASA Tech Briefs, June 1988. Volume 12, No. 6
NASA Technical Reports Server (NTRS)
1988-01-01
Topics covered: New Product Ideas; NASA TU Services; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials; Computer Programs; Mechanics; Machinery; Fabrication Technology; Mathematics and Information Sciences.
NASA Tech Briefs, Fall 1985. Volume 9, No. 3
NASA Technical Reports Server (NTRS)
1985-01-01
Topics include: NASA TU Services; New Product Ideas; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials; Life Sciences Mechanics; Machinery; Fabrication Technology; Mathematics and Information Sciences.
NASA Tech Briefs, April 1988. Volume 12, No. 4
NASA Technical Reports Server (NTRS)
1988-01-01
Topics include: New Product Ideas; NASA TU Services; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials; Computer Programs; Mechanics; Machinery; Fabrication Technology; Mathematics and Information Sciences.
NASA Tech Briefs, July 1989. Volume 13, No. 7
NASA Technical Reports Server (NTRS)
1989-01-01
Topics include New Product Ideas; NASA TU Services; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials;;Computer Programs; Mechanics; Machinery; Fabrication Technology; Mathematics and Information Sciences.
Incirlik Air Base, Turkey. Revised Uniform Summary of Surface Weather Observations. Parts A-F
1987-10-01
REPORTING STATIONS WORLD wICE. S" h * 0 suMMot ANTI V4 "W AM.. 17 173500 INCIRLIK AB TURKEY/ADANA N 37 00 t 0)s s 238 LTAG 17350 STATION LOCATION...TU PERIOD OF QECORD: 77-83,85-87 14ONTH: WAR HOL;RS(LST|: 03CO--05O I aINO ,PEE’U IN KNOTS DIRECTION I 1-3 4-6 7-1i 11-16 17-21 2Z-2,7 i’s-33 34-40 41...EAT,-ER ,ERv1CE/M&C STATION NUMPPER. 1735CO S TATICN NAME: . CIRLIN AB TU PERIQO CF RECOR•: 77-83,8S-87 MON’H: WAR HtoURSLST)J: 06CO-CtiCO
NASA Astrophysics Data System (ADS)
Pajewski, Lara; Giannopoulos, Antonis; van der Kruk, Jan
2015-04-01
This work aims at presenting the ongoing research activities carried out in Working Group 3 (WG3) 'EM methods for near-field scattering problems by buried structures; data processing techniques' of the COST (European COoperation in Science and Technology) Action TU1208 'Civil Engineering Applications of Ground Penetrating Radar' (www.GPRadar.eu). The principal goal of the COST Action TU1208 is to exchange and increase scientific-technical knowledge and experience of GPR techniques in civil engineering, simultaneously promoting throughout Europe the effective use of this safe and non-destructive technique in the monitoring of infrastructures and structures. WG3 is structured in four Projects. Project 3.1 deals with 'Electromagnetic modelling for GPR applications.' Project 3.2 is concerned with 'Inversion and imaging techniques for GPR applications.' The topic of Project 3.3 is the 'Development of intrinsic models for describing near-field antenna effects, including antenna-medium coupling, for improved radar data processing using full-wave inversion.' Project 3.4 focuses on 'Advanced GPR data-processing algorithms.' Electromagnetic modeling tools that are being developed and improved include the Finite-Difference Time-Domain (FDTD) technique and the spectral domain Cylindrical-Wave Approach (CWA). One of the well-known freeware and versatile FDTD simulators is GprMax that enables an improved realistic representation of the soil/material hosting the sought structures and of the GPR antennas. Here, input/output tools are being developed to ease the definition of scenarios and the visualisation of numerical results. The CWA expresses the field scattered by subsurface two-dimensional targets with arbitrary cross-section as a sum of cylindrical waves. In this way, the interaction is taken into account of multiple scattered fields within the medium hosting the sought targets. Recently, the method has been extended to deal with through-the-wall scenarios. One of the inversion techniques currently being improved is Full-Waveform Inversion (FWI) for on-ground, off-ground, and crosshole GPR configurations. In contrast to conventional inversion tools which are often based on approximations and use only part of the available data, FWI uses the complete measured data and detailed modeling tools to obtain an improved estimation of medium properties. During the first year of the Action, information was collected and shared about state-of-the-art of the available modelling, imaging, inversion, and data-processing methods. Advancements achieved by WG3 Members were presented during the TU1208 Second General Meeting (April 30 - May 2, 2014, Vienna, Austria) and the 15th International Conference on Ground Penetrating Radar (June 30 - July 4, 2014, Brussels, Belgium). Currently, a database of numerical and experimental GPR responses from natural and manmade structures is being designed. A geometrical and physical description of the scenarios, together with the available synthetic and experimental data, will be at the disposal of the scientific community. Researchers will thus have a further opportunity of testing and validating, against reliable data, their electromagnetic forward- and inverse-scattering techniques, imaging methods and data-processing algorithms. The motivation to start this database came out during TU1208 meetings and takes inspiration by successful past initiatives carried out in different areas, as the Ipswich and Fresnel databases in the field of free-space electromagnetic scattering, and the Marmousi database in seismic science. Acknowledgement The Authors thank COST, for funding the Action TU1208 'Civil Engineering Applications of Ground Penetrating Radar.'
Troconis, Eileen L.; Kalmar, Lajos; Price, David J.; Wright, Hattie E.; Adams, Vicki J.
2017-01-01
Extremely brachycephalic, or short-muzzled, dog breeds such as pugs, French bulldogs, and bulldogs are prone to the conformation-related respiratory disorder—brachycephalic obstructive airway syndrome (BOAS). Affected dogs present with a wide range of clinical signs from snoring and exercise intolerance, to life-threatening events such as syncope. In this study, conformational risk factors for BOAS that could potentially aid in breeding away from BOAS were sought. Six hundred and four pugs, French bulldogs, and bulldogs were included in the study. Soft tape measurements of the head and body were used and the inter-observer reproducibility was evaluated. Breed-specific models were developed to assess the associations between the conformational factors and BOAS status based on functional grading. The models were further validated by means of a BOAS index, which is an objective measurement of respiratory function using whole-body barometric plethysmography. The final models have good predictive power for discriminating BOAS (-) and BOAS (+) phenotypes indicated by the area under the curve values of >80% on the receiver operating curves. When other factors were controlled, stenotic nostrils were associated with BOAS in all three breeds; pugs and bulldogs with higher body condition scores (BCS) had a higher risk of developing BOAS. Among the standardized conformational measurements (i.e. craniofacial ratio (CFR), eye width ratio (EWR), skull index (SI), neck girth ratio (NGR), and neck length ratio (NLR)), for pugs EWR and SI, for French bulldogs NGR and NLR, and for bulldogs SI and NGR showed significant associations with BOAS status. However, the NGR in bulldogs was the only significant predictor that also had satisfactory inter-observer reproducibility. A NGR higher than 0.71 in male bulldogs was predictive of BOAS with approximately 70% sensitivity and specificity. In conclusion, stenotic nostrils, BCS, and NGR were found to be valid, easily applicable predictors for BOAS (+). PMID:28763490
Nature vs. nurture in human sociality: multi-level genomic analyses of social conformity.
Chen, Biqing; Zhu, Zijian; Wang, Yingying; Ding, Xiaohu; Guo, Xiaobo; He, Mingguang; Fang, Wan; Zhou, Qin; Zhou, Shanbi; Lei, Han; Huang, Ailong; Chen, Tingmei; Ni, Dongsheng; Gu, Yuping; Liu, Jianing; Rao, Yi
2018-05-01
Social conformity is fundamental to human societies and has been studied for more than six decades, but our understanding of its mechanisms remains limited. Individual differences in conformity have been attributed to social and cultural environmental influences, but not to genes. Here we demonstrate a genetic contribution to conformity after analyzing 1,140 twins and single-nucleotide polymorphism (SNP)-based studies of 2,130 young adults. A two-step genome-wide association study (GWAS) revealed replicable associations in 9 genomic loci, and a meta-analysis of three GWAS with a sample size of ~2,600 further confirmed one locus, corresponding to the NAV3 (Neuron Navigator 3) gene which encodes a protein important for axon outgrowth and guidance. Further multi-level (haplotype, gene, pathway) GWAS strongly associated genes including NAV3, PTPRD (protein tyrosine phosphatase receptor type D), ARL10 (ADP ribosylation factor-like GTPase 10), and CTNND2 (catenin delta 2), with conformity. Magnetic resonance imaging of 64 subjects shows correlation of activation or structural features of brain regions with the SNPs of these genes, supporting their functional significance. Our results suggest potential moderate genetic influence on conformity, implicate several specific genetic elements in conformity and will facilitate further research on cellular and molecular mechanisms underlying human conformity.
NASA Astrophysics Data System (ADS)
Campbell, Diarmad; de Beer, Johannes; Lawrence, David; van der Meulen, Michiel; Mielby, Susie; Hay, David; Scanlon, Ray; Campenhout, Ignace; Taugs, Renate; Eriksson, Ingelov
2014-05-01
Sustainable urbanisation is the focus of SUB-URBAN, a European Cooperation in Science and Technology (COST) Action TU1206 - A European network to improve understanding and use of the ground beneath our cities. This aims to transform relationships between experts who develop urban subsurface geoscience knowledge - principally national Geological Survey Organisations (GSOs), and those who can most benefit from it - urban decision makers, planners, practitioners and the wider research community. Under COST's Transport and Urban Development Domain, SUB-URBAN has established a network of GSOs and other researchers in over 20 countries, to draw together and evaluate collective urban geoscience research in 3D/4D characterisation, prediction and visualisation. Knowledge exchange between researchers and City-partners within 'SUB-URBAN' is already facilitating new city-scale subsurface projects, and is developing a tool-box of good-practice guidance, decision-support tools, and cost-effective methodologies that are appropriate to local needs and circumstances. These are intended to act as catalysts in the transformation of relationships between geoscientists and urban decision-makers more generally. As a result, the importance of the urban sub-surface in the sustainable development of our cities will be better appreciated, and the conflicting demands currently placed on it will be acknowledged, and resolved appropriately. Existing city-scale 3D/4D model exemplars are being developed by partners in the UK (Glasgow, London), Germany (Hamburg) and France (Paris). These draw on extensive ground investigation (10s-100s of thousands of boreholes) and other data. Model linkage enables prediction of groundwater, heat, SuDS, and engineering properties. Combined subsurface and above-ground (CityGML, BIMs) models are in preparation. These models will provide valuable tools for more holistic urban planning; identifying subsurface opportunities and saving costs by reducing uncertainty in ground conditions. A key area of interest, and one of potential collaboration with COST Action TU1208, is in characterising and parameterising the very near urban subsurface, and especially the anthropogenic deposits, to assist decision-making by civil engineers, and others. Anthropogenic deposits may be many metres thick, are typically very heterogeneous, have complex histories of accumulation, and may including important archaeological assets. They display complex stratigraphies which are difficult to resolve using traditional methodologies, even with extensive invasive ground investigation. Ground Penetrating Radar, and other non-destructive methods of ground investigation hold considerable promise in greatly improving the resolution, understanding, and modelling, of these and other near-surface deposits in particular. This work is a contribution both to COST Action TU1208 "Civil Engineering Applications of Ground Penetrating Radar" and to COST Action TU1206 "SUB-URBAN - A European network to improve understanding and use of the ground beneath our cities"
NASA Tech Briefs, May 1991. Volume 15, No. 5
NASA Technical Reports Server (NTRS)
1991-01-01
Topics: New Product Ideas; NASA TU Services; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials; Computer Programs; Mechanics; Machinery; Fabrication Technology; Mathematics and Information Sciences; Life Sciences.
NASA Tech Briefs, January 1991. Volume 15, No. 1
NASA Technical Reports Server (NTRS)
1991-01-01
Topics: New Product Ideas; NASA TU Services; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials; Computer Programs; Mechanics; Machinery; Fabrication Technology; Mathematics and Information Sciences;Life Sciences.
NASA Tech Briefs, September 1991. Volume 15, No. 9
NASA Technical Reports Server (NTRS)
1991-01-01
Topics: New Product Ideas; NASA TU Services; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials; Computer Programs; Mechanics; Machinery; Fabrication Technology; Mathematics and Information Sciences; Life Sciences.
NASA Tech Briefs, June 1990. Volume 14, No. 6
NASA Technical Reports Server (NTRS)
1990-01-01
Topics: New Product Ideas; NASA TU Services; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials; Computer Programs; Mechanics; Machinery; Fabrication Technology; Mathematics and Information Sciences; Life Sciences.
NASA Tech Briefs, August 1991. Volume 15, No. 8
NASA Technical Reports Server (NTRS)
1991-01-01
Topics: New Product Ideas; NASA TU Services; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials; Computer Programs; Mechanics; Machinery; Fabrication Technology; Mathematics and Information Sciences; Life Sciences.
NASA Tech Briefs, February 1991. Volume 15, No. 2
NASA Technical Reports Server (NTRS)
1991-01-01
Topics: New Product Ideas; NASA TU Services; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials; Computer Programs; Mechanics; Machinery; Fabrication Technology; Mathematics and Information Sciences; Life Sciences.
NASA Tech Briefs, March 1991. Volume 15, No. 3
NASA Technical Reports Server (NTRS)
1991-01-01
Topics: New Product Ideas; NASA TU Services; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials; Computer Programs; Mechanics; Machinery; Fabrication Technology; Mathematics and Information Sciences; Life Sciences.
NASA Tech Briefs, December 1990. Volume 14, No. 12
NASA Technical Reports Server (NTRS)
1990-01-01
Topics: New Product Ideas; NASA TU Services; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials; Computer Programs; Mechanics; Machinery; Fabrication Technology; Mathematics and Information Sciences; Life Sciences.
NASA Tech Briefs, June 1991. Volume 15, No. 6
NASA Technical Reports Server (NTRS)
1991-01-01
Topics: New Product Ideas; NASA TU Services; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials; Computer Programs; Mechanics; Machinery; Fabrication Technology; Mathematics and Information Sciences; Life Sciences.
NASA Tech Briefs, May 1990. Volume 14, No. 5
NASA Technical Reports Server (NTRS)
1990-01-01
Topics: New Product Ideas; NASA TU Services; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials; Computer Programs; Mechanics; Machinery; Fabrication Technology; Mathematics and Information Sciences; Life Sciences.
NASA Tech Briefs, Winter 1985. Volume 9, No. 4
NASA Technical Reports Server (NTRS)
1985-01-01
Topics covered include: NASA TU Services; New Product Ideas; Electronic Components and Circuits;Electronic Systems; Physical Sciences; Materials; Life Sciences; Mechanics; Machinery; Fabrication Technology; Mathematics and Information Sciences.
NASA Tech Briefs, April 1991. Volume 15, No. 4
NASA Technical Reports Server (NTRS)
1991-01-01
Topics: New Product Ideas; NASA TU Services; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials; Computer Programs; Mechanics; Machinery; Fabrication Technology; Mathematics and Information Sciences; Life Sciences.
NASA Tech Briefs, October 1990. Volume 14, No. 10
NASA Technical Reports Server (NTRS)
1990-01-01
Topics: New Product Ideas; NASA TU Services; Electronic Components and Circuits; Electronic Systems; Physical' Sciences; Materials; Computer Programs; Mechanics; Machinery; Fabrication Technology; Mathematics and Information Sciences; Life Sciences.
NASA Tech Briefs, January/February 1986. Volume 10, No. 1
NASA Technical Reports Server (NTRS)
1986-01-01
Topics include: NASA TU Services; New Product Ideas; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials; Life Sciences; Mechanics; Machinery; Fabrication Technology; Mathematics and Information Sciences.
NASA Tech Briefs, October 1991. Volume 15, No. 10
NASA Technical Reports Server (NTRS)
1991-01-01
Topics: New Product Ideas; NASA TU Services; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials; Computer Programs; Mechanics; Machinery; Fabrication Technology; Mathematics and Information Sciences; Life Sciences.
NASA Astrophysics Data System (ADS)
Pajewski, Lara; Benedetto, Andrea; Loizos, Andreas; Slob, Evert; Tosti, Fabio
2014-05-01
This work aims at presenting the first-year activities and results of COST (European COoperation in Science and Technology) Action TU1208 "Civil Engineering Applications of Ground Penetrating Radar". This Action was launched in April 2013 and will last four years. The principal aim of COST Action TU1208 is to exchange and increase scientific-technical knowledge and experience of GPR techniques in civil engineering, whilst simultaneously promoting throughout Europe the effective use of this safe and non-destructive technique in the monitoring of infrastructures and structures. Moreover, the Action is oriented to the following specific objectives and expected deliverables: (i) coordinating European scientists to highlight problems, merits and limits of current GPR systems; (ii) developing innovative protocols and guidelines, which will be published in a handbook and constitute a basis for European standards, for an effective GPR application in civil- engineering tasks; safety, economic and financial criteria will be integrated within the protocols; (iii) integrating competences for the improvement and merging of electromagnetic scattering techniques and of data- processing techniques; this will lead to a novel freeware tool for the localization of buried objects, shape-reconstruction and estimation of geophysical parameters useful for civil engineering needs; (iv) networking for the design, realization and optimization of innovative GPR equipment; (v) comparing GPR with different NDT techniques, such as ultrasonic, radiographic, liquid-penetrant, magnetic-particle, acoustic-emission and eddy-current testing; (vi) comparing GPR technology and methodology used in civil engineering with those used in other fields; (vii) promotion of a more widespread, advanced and efficient use of GPR in civil engineering; and (viii) organization of a high-level modular training program for GPR European users. Four Working Groups (WGs) carry out the research activities. The first WG focuses on the design of innovative GPR equipment, on the building of prototypes and on the testing and optimisation of new systems. The second WG focuses on the GPR surveying of pavement, bridges, tunnels and buildings, as well as on the sensing of underground utilities and voids. The third WG deals with the development of electromagnetic forward and inverse scattering methods, for the characterization of GPR scenarios, as well as with data- processing algorithms for the elaboration of the data collected during GPR surveys. The fourth WG works on the use of GPR in fields different from the civil engineering, as well as on the integration of GPR with other non-destructive testing techniques. Each WG includes several Projects. COST Action TU1208 is active through a range of networking tools: meetings, workshops, conferences, training schools, short-term scientific missions, dissemination activities. During the first year of activities, a First General Meeting was organized in Rome, in July 2013, a second meeting took place in Nantes, in February 2014, and the Second General Meeting is being held jointly with the 2014 EGU General Assembly. A training school on "Microwave Imaging and Diagnostics: Theory, Techniques, and Applications", held in March 2014, was co-organised with the European School of Antennas. Four Short-Term Scientific Missions were funded, allowing young researchers to spend a period of time in an institution abroad, in order to carry out a research project contributing to the scientific objectives of the Action. The Action's activities were disseminated in international conferences [1]-[4], as well as in further workshops and meetings. Two volumes were published [5]-[6], and several scientific papers on peer-reviewed journals. A Springer book presenting the state of the art on civil engineering applications of Ground Penetrating Radar is being prepared and is going to be published in summer 2014. A COST Action is a wide bottom-up interdisciplinary science and technology network, open to researchers from universities, public and private research institutions, as well as to NGOs, industry and SMEs. At present, About 100 Institutions from 24 COST Member Countries (Austria, Belgium, Croatia, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Italy, Latvia, Malta, Macedonia, The Netherlands, Norway, Poland, Portugal, Slovakia, Slovenia, Spain, Switzerland, Turkey, United Kingdom) have already joined the Action, together with an Institution from Armenia (Near Neighbour Country, NNC). Beyond European borders, six Institutions from U.S.A., one from Rwanda and one from Australia have joined the Action. Further applications from two NNCs (Egypt and Ukraine) and International Partner Countries (Hong Kong and Japan) are under examination. COST Action TU1208 is still open to the participation of new parties and it is possible to include, in the scientific work plan, new perspectives and activities. Scientists and scientific institutions willing to join COST Action TU1208 are encouraged to contact the Chair of the Action and to follow the procedure described at http://www.cost.eu/participate/join_action. For more information on COST Action TU1208, please visit www.GPRadar.eu. ----------------------------- Acknowledgement The Authors thanks COST for funding COST Action TU1208. References [1] L. Pajewski, A. Benedetto, A. Loizos, E. Slob, F. Tosti, "Civil Engineering Applications of Ground Penetrating Radar: Research Perspectives in COST Action TU1208," Geophysical Research Abstracts, European Geosciences Union (EGU) General Assembly 2013, 7-12 April 2013, Vienna, Austria, article ID EGU2013-13941. [2] L. Pajewski, A. Benedetto, G. Schettini, F. Soldovieri, "Applications of GPR in archaeological prospecting and cultural heritage diagnostics: Research Perspectives in COST Action TU1208," Geophysical Research Abstracts, European Geosciences Union (EGU) General Assembly 2013, 7-12 April 2013, Vienna, Austria, article ID EGU2013-14010. [3] L. Pajewski, A. Benedetto, X. Dérobert, A. Giannopoulos, A. Loizos, G. Manacorda, M. Marciniak, C. Plati, G. Schettini, I. Trinks, "Applications of Ground Penetrating Radar in Civil Engineering - COST Action TU1208," Proc. 7th International Workshop on Advanced Ground Penetrating Radar (IWAGPR), 2-5 July 2013, Nantes, France, pp. 1-6 (INVITED). ISBN 978-1-4799-0937-7, doi:10.1109/ IWAGPR.2013.6601528). [4] L. Pajewski, A. Benedetto, "Advanced Ground Penetrating Radar: open issues and new research opportunities in Europe," Proc. 10th European Radar Conference (EuRad), 2013 European Microwave Week (EuMW), 6-11 October 2013, Nuremberg, Germany, pp. 1847-1850. [5] Proceedings of the First Action's General Meeting (Editors: L. Pajewski and A. Benedetto; Publishing House: Aracne; Rome, July 2013; 194 pp.; ISBN 978-88-548-6191-6; o.o. 978-88-548-6190-9) - available as free download on www.GPRadar.eu [6] Booklet of Participants and Institutions (Editors: L. Pajewski and A. Benedetto; Publishing House: Aracne; Rome, July 2013; 127 pp.; ISBN 978-88-548-6192-3; o.o. 978-88-548-6190-9) - available as free download on www.GPRadar.eu
2015-01-01
Dehaloperoxidase hemoglobin A (DHP A) is a multifunctional hemoglobin that appears to have evolved oxidative pathways for the degradation of xenobiotics as a protective function that complements the oxygen transport function. DHP A possesses at least two internal binding sites, one for substrates and one for inhibitors, which include various halogenated phenols and indoles. Herein, we report the X-ray crystallographic structure of the carbonmonoxy complex (DHPCO). Unlike other DHP structures with 6-coordinated heme, the conformation of the distal histidine (H55) in DHPCO is primarily external or solvent exposed, despite the fact that the heme Fe is 6-coordinated. As observed generally in globins, DHP exhibits two distal histidine conformations (one internal and one external). In previous structural studies, we have shown that the distribution of H55 conformations is weighted strongly toward the external position when the DHP heme Fe is 5-coordinated. The large population of the external conformation of the distal histidine observed in DHPCO crystals at pH 6.0 indicates that some structural factor in DHP must account for the difference from other globins, which exhibit a significant external conformation only when pH < 4.5. While the original hypothesis suggested that interaction with a heme-Fe-bound ligand was the determinant of H55 conformation, the current study forces a refinement of that hypothesis. The external or open conformation of H55 is observed to have interactions with two propionate groups in heme, at distances of 3.82 and 2.73 Å, respectively. A relatively weak hydrogen bonding interaction between H55 and CO, combined with strong interactions with heme propionate (position 6), is hypothesized to strengthen the external conformation of H55. Density function theory (DFT) calculations were conducted to test whether there is a weaker hydrogen bond interaction between H55 and heme bonded CO or O2. Molecular dynamics simulations were conducted to examine how the tautomeric forms of H55 affect the dynamic motions of the distal histidine that govern the switching between open and closed conformations. The calculations support the modified hypothesis suggesting a competition between the strength of interactions with heme ligand and the heme propionates as the factors that determine the conformation of the distal histidine. PMID:24670063
Zeng, Danyun; Shen, Qingliang; Cho, Jae-Hyun
2017-02-26
Biological functions of intrinsically disordered proteins (IDPs), and proteins containing intrinsically disordered regions (IDRs) are often mediated by short linear motifs, like proline-rich motifs (PRMs). Upon binding to their target proteins, IDPs undergo a disorder-to-order transition which is accompanied by a large conformational entropy penalty. Hence, the molecular mechanisms underlying control of conformational entropy are critical for understanding the binding affinity and selectivity of IDPs-mediated protein-protein interactions (PPIs). Here, we investigated the backbone conformational entropy change accompanied by binding of the N-terminal SH3 domain (nSH3) of CrkII and PRM derived from guanine nucleotide exchange factor 1 (C3G). In particular, we focused on the estimation of conformational entropy change of disordered PRM upon binding to the nSH3 domain. Quantitative characterization of conformational dynamics of disordered peptides like PRMs is limited. Hence, we combined various methods, including NMR model-free analysis, δ2D, DynaMine, and structure-based calculation of entropy loss. This study demonstrates that the contribution of backbone conformational entropy change is significant in the PPIs mediated by IDPs/IDRs. Copyright © 2017 Elsevier Inc. All rights reserved.
Yang, Rong; Lee, Matthew C; Yan, Honggao; Duan, Yong
2005-07-01
Comparison of the crystallographic and NMR structures of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) suggests that the enzyme may undergo significant conformational change upon binding to its first substrate, ATP. Two of the three surface loops (loop 2 and loop 3) accounting for most of the conformational differences appear to be confined by crystal contacts, raising questions about the putative large-scale induced-fit conformational change of HPPK and the functional roles of the conserved side-chain residues on the loops. To investigate the loop dynamics in crystal-free environment, we carried out molecular dynamics and locally enhanced sampling simulations of the apo-enzyme and the HPPK.MgATP complex. Our simulations showed that the crystallographic B-factors underestimated the loop dynamics considerably. We found that the open-conformation of loop 3 in the binary complex is accessible to the apo-enzyme and is the favored conformation in solution phase. These results revise our previous view of HPPK-substrate interactions and the associated functional mechanism of conformational change. The lessons learned here offer valuable structural insights into the workings of HPPK and should be useful for structure-based drug design.
Banyasz, Akos; Esposito, Luciana; Douki, Thierry; Perron, Marion; Lepori, Clément; Improta, Roberto; Markovitsi, Dimitra
2016-05-12
C5-methylation of cytosines is strongly correlated with UV-induced mutations detected in skin cancers. Mutational hot-spots appearing at TCG sites are due to the formation of pyrimidine cyclobutane dimers (CPDs). The present study, performed for the model DNA duplex (TCGTA)3·(TACGA)3 and the constitutive single strands, examines the factors underlying the effect of C5-methylation on pyrimidine dimerization at TCG sites. This effect is quantified for the first time by quantum yields ϕ. They were determined following irradiation at 255, 267, and 282 nm and subsequent photoproduct analysis using HPLC coupled to mass spectrometry. C5-methylation leads to an increase of the CPD quantum yield up to 80% with concomitant decrease of that of pyrimidine(6-4) pyrimidone adducts (64PPs) by at least a factor of 3. The obtained ϕ values cannot be explained only by the change of the cytosine absorption spectrum upon C5-methylation. The conformational and electronic factors that may affect the dimerization reaction are discussed in light of results obtained by fluorescence spectroscopy, molecular dynamics simulations, and quantum mechanical calculations. Thus, it appears that the presence of an extra methyl on cytosine affects the sugar puckering, thereby enhancing conformations of the TC step that are prone to CPD formation but less favorable to 64PPs. In addition, C5-methylation diminishes the amplitude of conformational motions in duplexes; in the resulting stiffer structure, ππ* excitations may be transferred from initially populated exciton states to reactive pyrimidines giving rise to CPDs.
NASA Tech Briefs, September 1988. Volume 12, No. 8
NASA Technical Reports Server (NTRS)
1988-01-01
Topics include: New Product Ideas; NASA TU Services; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials; Computer Programs; Mechanics; Machinery; Fabrication Technology; Mathematics and Information Sciences; Life Sciences.
NASA Tech Briefs, July/August 1988. Volume 12, No. 7
NASA Technical Reports Server (NTRS)
1988-01-01
Topics: New Product Ideas; NASA TU Services; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials; Computer Programs; Mechanics; Machinery; Fabrication Technology; Mathematics and Information Sciences; Life Sciences.
NASA Tech Briefs, October 1988. Volume 12, No. 9
NASA Technical Reports Server (NTRS)
1988-01-01
Topics include: New Product Ideas; NASA TU Services; Electronic Components and Circuits; Electronic Systems; Physical Sciences Materials; Computer Programs; Mechanics; Machinery; Fabrication Technology; Mathematics and Information Sciences; Life Sciences.
NASA Tech Briefs, July 1991. Volume 15, No. 7
NASA Technical Reports Server (NTRS)
1991-01-01
Topics include: New Product Ideas; NASA TU Services; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials; Computer Programs; Mechanics; Machinery; Fabrication Technology; Mathematics and Information Sciences; Life Sciences.
NASA Tech Briefs, March 1987. Volume 11, No. 3
NASA Technical Reports Server (NTRS)
1987-01-01
Topics include: NASA TU Services; New Product Ideas; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials; Computer Programs; Mechanics; Fabrication Technology; Machinery; Mathematics and Information Sciences; Life Sciences.
NASA Tech Briefs, May 1987. Volume 11, No. 5
NASA Technical Reports Server (NTRS)
1987-01-01
Topics include: NASA TU Services; New Product Ideas; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials; Computer Programs; Mechanics; Fabrication Technology; Machinery; Mathematics and Information Sciences; Life Sciences.
NASA Tech Briefs, October 1987. Volume 11, No. 9
NASA Technical Reports Server (NTRS)
1987-01-01
Topics include: NASA TU Services; New Product Ideas; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials; Computer Programs; Mechanics; Fabrication Technology; Machinery; Mathematics and Information Sciences; Life Sciences.
NASA Tech Briefs, June 1989. Volume 13, No. 6
NASA Technical Reports Server (NTRS)
1989-01-01
Topics include: New Product Ideas; NASA TU Services; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials; Computer Programs; Mechanics; Machinery; Fabrication Technology; Mathematics and Information Sciences; Life Sciences.
NASA Tech Briefs, February 1987. Volume 11, No. 2
NASA Technical Reports Server (NTRS)
1987-01-01
Topics include: NASA TU Services; New Product Ideas; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials; Computer Programs; Mechanics; Fabrication Technology; Machinery; Mathematics and Information Sciences; Life Sciences.
NASA Tech Briefs, January 1987. Volume 11, No. 2
NASA Technical Reports Server (NTRS)
1987-01-01
Topics include: NASA TU Services; New Product Ideas; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials; Computer Programs; Mechanics; Fabrication Technology; Machinery; Mathematics and Information Sciences; Life Sciences.
NASA Tech Briefs, July 1990. Volume 14, No. 7
NASA Technical Reports Server (NTRS)
1990-01-01
Topics include: New Product Ideas; NASA TU Services; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials; Computer Programs; Mechanics; Machinery; Fabrication Technology; Mathematics and Information Sciences; Life Sciences.
NASA Tech Briefs, August 1990. Volume 14, No. 8
NASA Technical Reports Server (NTRS)
1990-01-01
Topics covered: New Product Ideas; NASA TU Services; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials; Computer Programs; Mechanics; Machinery; Fabrication Technology; Mathematics and Information Sciences; Life Sciences.
Bladder Cancer Advocacy Network
... Event No Repeat Daily Weekly Monthly Yearly Repeat gap Repeat by day SU MO TU WE TH ... is Bladder Cancer? Newly Diagnosed Treatments Clinical Trials Research Research Grants Think Tank Research Network Genomics Consortium ...
NASA Tech Briefs, April 1987. Volume 11, No. 4
NASA Technical Reports Server (NTRS)
1987-01-01
Topics include: NASA TU Services; New Product Ideas; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials; Computer Programs; Mechanics; Fabrication Technology; Machinery; Mathematics and Information Sciences; Life Sciences.
NASA Tech Briefs, September 1987. Volume 11, No. 8
NASA Technical Reports Server (NTRS)
1987-01-01
Topics include: NASA TU Services; New Product Ideas; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials; Computer Programs; Mechanics; Fabrication Technology; Machinery; Mathematics and Information Sciences; Life Sciences.
NASA Tech Briefs, June 1987. Volume 11, No. 6
NASA Technical Reports Server (NTRS)
1987-01-01
Topics include: NASA TU Services; New Product Ideas; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials; Computer Programs; Mechanics; Fabrication Technology; Machinery; Mathematics and Information Sciences; Life Sciences.
NASA Tech Briefs, August 1989. Volume 13, No. 8
NASA Technical Reports Server (NTRS)
1989-01-01
Topics covered: New Product Ideas; NASA TU Services; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials; Computer Programs; Mechanics; Machinery; Fabrication Technology; Mathematics and Information Sciences; Life Sciences.
NASA Astrophysics Data System (ADS)
Fenton, O.; Vero, S.; Ibrahim, T. G.; Murphy, P. N. C.; Sherriff, S. C.; Ó hUallacháin, D.
2015-11-01
Elucidation of when the loss of pollutants, below the rooting zone in agricultural landscapes, affects water quality is important when assessing the efficacy of mitigation measures. Investigation of this inherent time lag (tT) is divided into unsaturated (tu) and saturated (ts) components. The duration of these components relative to each other differs depending on soil characteristics and the landscape position. The present field study focuses on tu estimation in a scenario where the saturated zone is likely to constitute a higher proportion of tT. In such instances, or where only initial breakthrough (IBT) or centre of mass (COM) is of interest, utilisation of site and depth specific "simple" textural class or actual sand-silt-clay percentages to generate soil water characteristic curves with associated soil hydraulic parameters is acceptable. With the same data it is also possible to estimate a soil physical quality (S) parameter for each soil layer which can be used to infer many other physical, chemical and biological quality indicators. In this study, hand texturing in the field was used to determine textural classes of a soil profile. Laboratory methods, including hydrometer, pipette and laser diffraction methods were used to determine actual sand-silt-clay percentages of sections of the same soil profile. Results showed that in terms of S, hand texturing resulted in a lower index value (inferring a degraded soil) than that of pipette, hydrometer and laser equivalents. There was no difference between S index values determined using the pipette, hydrometer and laser diffraction methods. The difference between the three laboratory methods on both the IBT and COM stages of tu were negligible, and in this instance were unlikely to affect either groundwater monitoring decisions, or to be of consequence from a policy perspective. When tu estimates are made over the full depth of the vadose zone, which may extend to several metres, errors resulting from the use of hydraulic parameters generated from hand texture data will be resultantly greater, and may lead to flawed predictions regarding the achievability of water policy targets. For this reason laboratory analysis, regardless of method, should be preferred to simple field assessments.
A guidelines handbook for GPR surveys in tunnels: a COST Action TU1208 contribution
NASA Astrophysics Data System (ADS)
Bianchini Ciampoli, Luca; Alani, Amir M.; Pajewski, Lara; Benedetto, Andrea; Loizos, Andreas; Tosti, Fabio
2016-04-01
A significant open issue concerning the reliability of geophysical methods and in particular of ground penetrating radar (GPR), both in research and professional context, is a general lack of international standards. This is a major problem to be faced, in order to gain scientific strictness for the GPR practices, and to easily extend to the international community the results achieved within the area of single virtuous countries. Producing international guidelines can represent an important step forward, in this sense. In the memorandum of understanding of the COST Action TU1208 is clearly stated that one of the main purposes of the Action is the "development of innovative protocols and guidelines which will be published in a handbook and constitute a basis for European Standards, for an effective GPR application in CE tasks; safety, economic and financial criteria will be integrated within the protocols". Of course this is not a simple task to be accomplished. Firstly, survey procedures are highly dependent on the objective of the survey itself. On the basis of the objective of each geophysical test, the GPR system, the antenna configuration, and even the processing procedures may change. Besides, these procedures are also influenced by the environmental conditions in which the tests are performed. This affects several aspects spanning from hardware to software, but including, for instance, also safety issues. Due to these reasons, one of the main goal of the COST Action TU1208 is the development of several guidelines related to the main applications of GPR in the field of civil engineering. In this work, the structure of a guidelines handbook for GPR activities in tunnels is outlined. In the first sections, the principal references in the field are provided, and the most common GPR equipment and complementary technologies are described. Subsequently, the survey methodologies are explained. Particular attention is paid to the preliminary activities to be carried out prior to the GPR surveys, which can cover an important role in such a complex environment. Lastly, the main applications of GPR technology in tunnels are discussed. Acknowledgement The Authors thank COST, for funding the Action TU1208 "Civil Engineering Applications of Ground Penetrating Radar."
Mendoza-Pérez, Julia; Gu, Jian; Herrera, Luis A; Tannir, Nizar M; Zhang, Shanyu; Matin, Surena; Karam, Jose A; Wood, Christopher G; Wu, Xifeng
2017-09-15
Greater than 40% of renal cell carcinoma (RCC) cases in the United States are attributed to excessive body weight. Moreover, obesity also may be linked to RCC prognosis. However, the molecular mechanisms underlying these associations are unclear. In the current study, the authors evaluated the role of promoter methylation in obesity-related genes in RCC tumorigenesis and disease recurrence. Paired tumors (TU) and normal adjacent (N-Adj) tissues from 240 newly diagnosed and previously untreated white patients with RCC were examined. For the discovery phase, 63 RCC pairs were analyzed. An additional 177 RCC pairs were evaluated for validation. Pyrosequencing was used to determine CpG methylation in 20 candidate obesity-related genes. An independent data set from The Cancer Genome Atlas also was analyzed for functional validation. The association between methylation and disease recurrence was analyzed using multivariate Cox proportional hazards models and Kaplan-Meier survival analysis. Methylation in neuropeptide Y (NPY), leptin (LEP), and leptin receptor (LEPR) was significantly higher in TU compared with N-Adj tissues (P<.0001) in both the discovery and validation groups. High methylation in LEPR was associated with an increased risk of disease recurrence (hazard ratio, 3.15; 95% confidence interval, 1.23-8.07 [P = .02]). Patients with high methylation in LEPR had a shorter recurrence-free survival compared with patients in the low-methylation group (log-rank P = 2.25 × 10 -3 ). In addition, high LEPR methylation in TU was associated with more advanced features (P≤.05). Consistent with the findings of the current study, lower LEPR expression in TU compared with N-Adj tissues (P = 1.00 × 10 -3 ) was found in data from The Cancer Genome Atlas. Somatic alterations of promoter methylation in the NPY, LEP, and LEPR genes are involved in RCC tumorigenesis. Furthermore, LEPR methylation appears to be associated with RCC recurrence. Future research to elucidate the biology underlying this association is warranted. Cancer 2017;123:3617-27. © 2017 American Cancer Society. © 2017 American Cancer Society.
Mukhina, T M; Nikolaienko, T Yu
2015-01-01
Recent studies on Escherichia coli bacteria cultivation, in which DNA thymine was replaced with 5-chlorouracil have refreshed the problem of understanding the changes to physical properties of DNA monomers resultant from chemical modifications. These studies have shown that the replacement did not affect the normal activities and division of the bacteria, but has significantly reduced its life span. In this paper a comparative analysis was carried out by the methods of computational experiment of a set of 687 possible conformers of natural monomeric DNA unit (2'-deoxyribonucleotide thymidine monophosphate) and 660 conformers of 5-chloro-2'-deoxyuridine monophosphate - a similar molecules in which the natural nitrogenous base thymine is substituted with 5-chlorouracil. Structures of stable conformers of the modified deoxyribonucleotide have been obtained and physical factors, which determine their variation from the conformers of the unmodified molecule have been analyzed. A comparative analysis of the elastic properties of conformers of investigated molecules and non-covalent interactions present in them was conducted. The results can be usedfor planning experiments on synthesis of artficial DNA suitable for incorporation into living organisms.
Dielectric Properties of Poly(ethylene oxide) from Molecular Dynamics Simulations
NASA Technical Reports Server (NTRS)
Smith, Grant D.
1994-01-01
The order, conformations and dynamics of poly(oxyethylene) (POE) melts have been investigated through molecular dynamics simulations. The potential energy functions were determined from detailed ab initio electronic structure calculations of the conformational energies of the model molecules 1,2-dimethoxyethane (DME) and diethylether. The x-ray structure factor for POE from simulation will be compared to experiment. In terms of conformation, simulations reveal that chains are extended in the melt relative to isolated chains due to the presence of strong intermolecular O...H interactions, which occur at the expense of intramolecular O...H interactions. Conformational dynamics about the C-C bond were found to be significantly faster than in polymethylene, while conformational dynamics about the C-O bond even faster than the C-C dynamics. The faster local dynamics in POE relative to polymethylene is consistent with C-13 NMR spin-lattice relaxation experiments. Conformational transitions showed significant second-neighbor correlation, as was found for polymethylene. This correlation of transitions with C-C neighbors was found to be reduced relative to C-O neighbors. Dielectric relaxation from simulation will also be compared with experiment.
Interconversion of two GDP-bound conformations and their selection in an Arf-family small G protein.
Okamura, Hideyasu; Nishikiori, Masaki; Xiang, Hongyu; Ishikawa, Masayuki; Katoh, Etsuko
2011-07-13
ADP-ribosylation factor (Arf) and other Arf-family small G proteins participate in many cellular functions via their characteristic GTP/GDP conformational cycles, during which a nucleotide(∗)Mg(2+)-binding site communicates with a remote N-terminal helix. However, the conformational interplay between the nucleotides, the helix, the protein core, and Mg(2+) has not been fully delineated. Herein, we report a study of the dynamics of an Arf-family protein, Arl8, under various conditions by means of NMR relaxation spectroscopy. The data indicated that, when GDP is bound, the protein core, which does not include the N-terminal helix, reversibly transition between an Arf-family GDP form and another conformation that resembles the Arf-family GTP form. Additionally, we found that the N-terminal helix and Mg(2+), respectively, stabilize the aforementioned former and latter conformations in a population-shift manner. Given the dynamics of the conformational changes, we can describe the Arl8 GTP/GDP cycle in terms of an energy diagram. Copyright © 2011 Elsevier Ltd. All rights reserved.
NASA Tech Briefs, November 1988. Volume 12, No. 10
NASA Technical Reports Server (NTRS)
1988-01-01
Topics covered include: New Product Ideas; NASA TU Services; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials; Computer Programs; Mechanics; Machinery; Fabrication Technology; Mathematics and Information Sciences; Life Sciences.
NASA Tech Briefs, September/October 1986. Volume 10, No. 5
NASA Technical Reports Server (NTRS)
1986-01-01
Topics include: NASA TU Services; New Product Ideas; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials; Computer Programs; Mechanics; Fabrication Technology; Machinery; Mathematics and Information Sciences; Life Sciences.
NASA Tech Briefs, November/December 1986. Volume 10, No. 6
NASA Technical Reports Server (NTRS)
1986-01-01
Topics include: NASA TU Services; New Product Ideas; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials; Computer Programs; Mechanics; Fabrication Technology; Machinery; Mathematics and Information Sciences; Life Sciences.
NASA Tech Briefs, May/June 1986. Volume 10, No. 3
NASA Technical Reports Server (NTRS)
1986-01-01
Topics discussed include: NASA TU Services; New Product Ideas; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials; Computer Programs; Machinery; Fabrication Technology; Mathematics and Information Sciences; Life Sciences.
NASA Tech Briefs, September 1990. Volume 14, No. 9
NASA Technical Reports Server (NTRS)
1990-01-01
Topics covered include: New Product Ideas; NASA TU Services; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials; Computer Programs; Mechanics; Machinery; Fabrication Technology; Mathematics and Information Sciences; Life Sciences.
NASA Tech Briefs, November/December 1987. Volume 11, No. 10
NASA Technical Reports Server (NTRS)
1987-01-01
Topics include: NASA TU Services; New Product Ideas; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials; Computer Programs; Mechanics; Fabrication Technology; Machinery; Mathematics and Information Sciences; Life Sciences.
NASA Tech Briefs, March 1988. Volume 12, No. 3
NASA Technical Reports Server (NTRS)
1988-01-01
Topics include: New Product Ideas; NASA TU Services; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials; Computer Programs; Mechanics; Machinery; Fabrication Technology; Mathematics and Information Sciences; and Life Sciences.
NASA Tech Briefs, July/August 1987. Volume 11, No. 7
NASA Technical Reports Server (NTRS)
1987-01-01
Topics include: NASA TU Services; New Product Ideas; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials; Computer Programs; Mechanics; Fabrication Technology; Machinery; Mathematics and Information Sciences; Life Sciences.
Tracing the conformational changes in BSA using FRET with environmentally-sensitive squaraine probes
NASA Astrophysics Data System (ADS)
Govor, Iryna V.; Tatarets, Anatoliy L.; Obukhova, Olena M.; Terpetschnig, Ewald A.; Gellerman, Gary; Patsenker, Leonid D.
2016-06-01
A new potential method of detecting the conformational changes in hydrophobic proteins such as bovine serum albumin (BSA) is introduced. The method is based on the change in the Förster resonance energy transfer (FRET) efficiency between protein-sensitive fluorescent probes. As compared to conventional FRET based methods, in this new approach the donor and acceptor dyes are not covalently linked to protein molecules. Performance of the new method is demonstrated using the protein-sensitive squaraine probes Square-634 (donor) and Square-685 (acceptor) to detect the urea-induced conformational changes of BSA. The FRET efficiency between these probes can be considered a more sensitive parameter to trace protein unfolding as compared to the changes in fluorescence intensity of each of these probes. Addition of urea followed by BSA unfolding causes a noticeable decrease in the emission intensities of these probes (factor of 5.6 for Square-634 and 3.0 for Square-685), and the FRET efficiency changes by a factor of up to 17. Compared to the conventional method the new approach therefore demonstrates to be a more sensitive way to detect the conformational changes in BSA.
Improved light output of plastic scintillator by a modified self-assembled photonic crystal
NASA Astrophysics Data System (ADS)
Chen, Liang; Zhu, Zhichao; Liu, Bo; Cheng, Chuanwei; Liu, Jinliang; Ruan, Jinlu; Zhang, Zhongbin; Ouyang, Xiaoping; Gu, Mu; Chen, Hong
2017-11-01
In this investigation, we have demonstrated that a modified self-assembled photonic crystal with conformal high refractive index material TiO2 can achieve a great enhancement of light extraction efficiency. A 2.26 fold wavelength- and angle-integrated enhancement ratio can be achieved. The conformal layer increases the number of leaky modes and thus improve the extraction efficiency. The enhancement is attributed to the leaky modes based on the individual microspheres with conformal layer. Their low quality factors with a broadband characteristic are advantageous to the broadband enhancement for the emission spectra of plastic scintillator. Furthermore, the dense conformal layers have excellent combination with the self-assembled microspheres and the whole preparation process cannot destroy the plastic scintillator, which is beneficial to the practical application.
Molecular dynamics studies of the protein-protein interactions in inhibitor of κB kinase-β.
Jones, Michael R; Liu, Cong; Wilson, Angela K
2014-02-24
Activation of the inhibitor of κB kinase subunit β (IKKβ) oligomer initiates a cascade that results in the translocation of transcription factors involved in mediating immune responses. Dimerization of IKKβ is required for its activation. Coarse-grained and atomistic molecular dynamics simulations were used to investigate the conformation-activity and structure-activity relationships within the oligomer assembly of IKKβ that are impacted upon activation, mutation, and binding of ATP. Intermolecular interactions, free energies, and conformational changes were compared among several conformations, including a monomer, two different dimers, and the tetramer. Modifications to the activation segment induce conformational changes that disrupt dimerization and suggest that the multimeric assembly mediates a global stability for the enzyme that influences the activity of IKKβ.
Quantum chemical calculations in the structural analysis of phloretin
NASA Astrophysics Data System (ADS)
Gómez-Zavaglia, Andrea
2009-07-01
In this work, a conformational search on the molecule of phloretin [2',4',6'-Trihydroxy-3-(4-hydroxyphenyl)-propiophenone] has been performed. The molecule of phloretin has eight dihedral angles, four of them taking part in the carbon backbone and the other four, related with the orientation of the hydroxyl groups. A systematic search involving a random variation of the dihedral angles has been used to generate input structures for the quantum chemical calculations. Calculations at the DFT(B3LYP)/6-311++G(d,p) level of theory permitted the identification of 58 local minima belonging to the C 1 symmetry point group. The molecular structures of the conformers have been analyzed using hierarchical cluster analysis. This method allowed us to group conformers according to their similarities, and thus, to correlate the conformers' stability with structural parameters. The dendrogram obtained from the hierarchical cluster analysis depicted two main clusters. Cluster I included all the conformers with relative energies lower than 25 kJ mol -1 and cluster II, the remaining conformers. The possibility of forming intramolecular hydrogen bonds resulted the main factor contributing for the stability. Accordingly, all conformers depicting intramolecular H-bonds belong to cluster I. These conformations are clearly favored when the carbon backbone is as planar as possible. The values of the νC dbnd O and νOH vibrational modes were compared among all the conformers of phloretin. The redshifts associated with intramolecular H-bonds were correlated with the H-bonds distances and energies.
Maintaining and Enhancing Diversity of Sampled Protein Conformations in Robotics-Inspired Methods.
Abella, Jayvee R; Moll, Mark; Kavraki, Lydia E
2018-01-01
The ability to efficiently sample structurally diverse protein conformations allows one to gain a high-level view of a protein's energy landscape. Algorithms from robot motion planning have been used for conformational sampling, and several of these algorithms promote diversity by keeping track of "coverage" in conformational space based on the local sampling density. However, large proteins present special challenges. In particular, larger systems require running many concurrent instances of these algorithms, but these algorithms can quickly become memory intensive because they typically keep previously sampled conformations in memory to maintain coverage estimates. In addition, robotics-inspired algorithms depend on defining useful perturbation strategies for exploring the conformational space, which is a difficult task for large proteins because such systems are typically more constrained and exhibit complex motions. In this article, we introduce two methodologies for maintaining and enhancing diversity in robotics-inspired conformational sampling. The first method addresses algorithms based on coverage estimates and leverages the use of a low-dimensional projection to define a global coverage grid that maintains coverage across concurrent runs of sampling. The second method is an automatic definition of a perturbation strategy through readily available flexibility information derived from B-factors, secondary structure, and rigidity analysis. Our results show a significant increase in the diversity of the conformations sampled for proteins consisting of up to 500 residues when applied to a specific robotics-inspired algorithm for conformational sampling. The methodologies presented in this article may be vital components for the scalability of robotics-inspired approaches.
NASA Tech Briefs, March/April 1986. Volume 10, No. 2
NASA Technical Reports Server (NTRS)
1986-01-01
Topics covered include: NASA TU Services; New Product Ideas; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials; Computer Programs; Mechanics; Machinery; Fabrication Technology; Mathematics and Information Sciences; Life Sciences.
NASA Tech Briefs, February 1988. Volume 12, No. 2
NASA Technical Reports Server (NTRS)
1988-01-01
Topics covered include: New Product Ideas; NASA TU Services; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials; Computer Programs; Mechanics; Machinery; Fabrication Technology; Mathematics and Information Systems; and Life Sciences.
NASA Tech Briefs, January 1988. Volume 12, No. 1
NASA Technical Reports Server (NTRS)
1988-01-01
Topics covered include: New Product Ideas; NASA TU Services; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials; Computer Programs; Mechanics; Machinery; Fabrication Technology; Mathematics and Information Sciences; and Life Sciences.
The Study of Pre-sight for the Air Transportation Systems
NASA Astrophysics Data System (ADS)
Zhao, Wenzhi; Guo, Zhi
The internal reasons of the deceptive air crashes were studied for the purpose of explanation its nature to reduce the accidents and the injuries. An approach of synthetic comparison is deployed. The Concorde aircraft accident was analyzed detailed to recognize what the real human error is. All the passengers were killed in the crash. Other similar accidents relating aircraft DC-10, Tu-154 and Tu-144 were discussed about the risk perception of the pilots and system. Certain higher survival rate was reached in these cases. Then the conclusion is obtained that the real problem is the lack of pre-sight for the risk in operation and system management relating to the pilots and the organizations. The conclusion suggests some changes be made in complex system management regulations and in thinking mode for the general applications to safety.
Uppada, Dharma Rao; Selvam, Sumithra; Jesuraj, Nelson; Bennett, Sean; Verver, Suzanne; Grewal, Harleen M S; Vaz, Mario
2014-11-18
India has generally used 1 TU purified protein derivative (PPD) as opposed to 2 TU PPD globally, limiting comparisons. It is important to assess latent TB infection in adolescents given that they may be a target group for new post-exposure TB vaccines. The aim of this study is to describe the pattern and associations of tuberculin skin test (TST) responses (0.1 ml 2 TU) in adolescents in South India. 6643 school-going adolescents (11 to <18 years) underwent TST. Trained tuberculin reader made the reading visit between 48 and 96 hours after the skin test Of 6608 available TST results, 9% had 0 mm, and 12% ≥10 mm responses. The proportion of TST positive (≥10 mm) was higher among older children, boys, those with a history of TB contact and reported BCG immunization Those with no TST response (0 mm) included younger participants (<14 years), those whose mothers were illiterate and those with a recent history of weight loss. Those of a higher socio-economic status (houses with brick walls, LPG gas as cooking fuel) and those with a visible BCG scar were less likely to be non-responders. Proportion of non-responders was lower than elsewhere in the world. Proportion of TST positivity was higher in those already exposed to TB and in children who had been BCG immunized, with a zero response more likely in younger adolescents and those with recent weight loss.
Pérez-Fernández, Virginia; Marchese, Stefano; Gentili, Alessandra; García, María Ángeles; Curini, Roberta; Caretti, Fulvia; Perret, Daniela
2014-11-07
This paper describes development and validation of a new method for the simultaneous determination of six antithyroid drugs (ATDs) in surface waters by using liquid chromatography-triple quadrupole mass spectrometry (LC-MS/MS). Target compounds include two ATD classes: thiouracil derivatives (thiouracil (TU), methyl-thiouracil (MTU), propyl-thiouracil (PTU), phenyl-thiouracil (PhTU)) and imidazole derivatives (tapazole (TAP), and mercaptobenzimidazole (MBI)). Sensitivity and selectivity of the LC-multiple reaction monitoring (MRM) analysis allowed applying a simple pre-concentration procedure and "shooting" the concentrated sample into the LC-MS/MS system without any other treatment. Recoveries were higher than 75% for all analytes. Intra-day precision and inter-day precision, calculated as relative standard deviation (RSD), were below 19 and 22%, respectively. Limits of detection (LODs) ranged from 0.05 to 0.25 μg/L; limits of quantitation (LOQs) varied between 0.15 and 0.75 μg/L. The validated method was successfully applied to the analysis of ATD residues in surface water samples collected from the Tiber River basin and three lakes of Lazio (central Italy). The analytes were quantified based on matrix-matched calibration curves with mercaptobenzimidazole-d4 (MBI-d4) as the internal standard (IS). The most widespread compound was TAP, one of the most common ATDs used in human medicine, but also TU and MBI were often detected in the analysed samples. Copyright © 2014 Elsevier B.V. All rights reserved.
Held, Martina; Berz, Annuska; Hensgen, Ronja; Muenz, Thomas S; Scholl, Christina; Rössler, Wolfgang; Homberg, Uwe; Pfeiffer, Keram
2016-01-01
While the ability of honeybees to navigate relying on sky-compass information has been investigated in a large number of behavioral studies, the underlying neuronal system has so far received less attention. The sky-compass pathway has recently been described from its input region, the dorsal rim area (DRA) of the compound eye, to the anterior optic tubercle (AOTU). The aim of this study is to reveal the connection from the AOTU to the central complex (CX). For this purpose, we investigated the anatomy of large microglomerular synaptic complexes in the medial and lateral bulbs (MBUs/LBUs) of the lateral complex (LX). The synaptic complexes are formed by tubercle-lateral accessory lobe neuron 1 (TuLAL1) neurons of the AOTU and GABAergic tangential neurons of the central body's (CB) lower division (TL neurons). Both TuLAL1 and TL neurons strongly resemble neurons forming these complexes in other insect species. We further investigated the ultrastructure of these synaptic complexes using transmission electron microscopy. We found that single large presynaptic terminals of TuLAL1 neurons enclose many small profiles (SPs) of TL neurons. The synaptic connections between these neurons are established by two types of synapses: divergent dyads and divergent tetrads. Our data support the assumption that these complexes are a highly conserved feature in the insect brain and play an important role in reliable signal transmission within the sky-compass pathway.
Short-time dynamics of 2-thiouracil in the light absorbing S{sub 2}(ππ{sup ∗}) state
DOE Office of Scientific and Technical Information (OSTI.GOV)
Jiang, Jie; Zhang, Teng-shuo; Xue, Jia-dan
2015-11-07
Ultrahigh quantum yields of intersystem crossing to the lowest triplet state T{sub 1} are observed for 2-thiouracils (2TU), which is in contrast to the natural uracils that predominantly exhibit ultrafast internal conversion to the ground state upon excitation to the singlet excited state. The intersystem crossing mechanism of 2TU has recently been investigated using second-order perturbation methods with a high-level complete-active space self-consistent field. Three competitive nonadiabatic pathways to the lowest triplet state T{sub 1} from the initially populated singlet excited state S{sub 2} were proposed. We investigate the initial decay dynamics of 2TU from the light absorbing excited statesmore » using resonance Raman spectroscopy, time-dependent wave-packet theory in the simple model, and complete-active space self-consistent field (CASSCF) and time dependent-Becke’s three-parameter exchange and correlation functional with the Lee-Yang-Parr correlation functional (TD-B3LYP) calculations. The obtained short-time structural dynamics in easy-to-visualize internal coordinates were compared with the CASSCF(16,11) predicted key nonadiabatic decay routes. Our results indicate that the predominant decay pathway initiated at the Franck-Condon region is toward the S{sub 2}/S{sub 1} conical intersection point and S{sub 2}T{sub 3} intersystem crossing point, but not toward the S{sub 2}T{sub 2} intersystem crossing point.« less
Bringing alcohol on campus to raise money: impact on student drinking and drinking problems
Voas, Robert B.; Johnson, Mark; Turrisi, Robert J.; Taylor, Dexter; Honts, Charles Robert; Nelsen, Lisa
2010-01-01
Aims Universities are striving to raise funds, often attracting spectators by selling alcohol at campus events. This study evaluates the effect of a policy change on student drinking at a large western university that had historically banned alcohol on campus but transitioned to permitting the sale of alcohol in some of its facilities. Methods Surveys of student drinking and perceptions of other students' drinking were conducted before, during and after the policy change at the transition university (TU) and compared to similar data from a control university (CU). Surveys of student drinking at on-campus and off-campus venues and observations of alcohol service practices were also conducted. Results The policy change at the TU was introduced cautiously, and sales to underage drinkers were relatively well controlled. Despite this, student drinking rose initially, then declined after 1 year. Perceptions of the amount of drinking by other students increased slightly, but there was no overall measurable increase in student drinking during the first 3 years of the new policy. Conclusions The conservative TU policy—to sell alcohol only at select events and to control sales to minors—may have limited the impact of on-campus alcohol sales on student consumption. Although the study results did not find a stable increase in student drinking, they do not necessarily support the liberalization of campus alcohol policy, because the transition is still ‘in progress’ and the final outcome has not been evaluated. PMID:18482416
Bringing alcohol on campus to raise money: impact on student drinking and drinking problems.
Voas, Robert B; Johnson, Mark; Turrisi, Robert J; Taylor, Dexter; Honts, Charles Robert; Nelsen, Lisa
2008-06-01
Universities are striving to raise funds, often attracting spectators by selling alcohol at campus events. This study evaluates the effect of a policy change on student drinking at a large western university that had historically banned alcohol on campus but transitioned to permitting the sale of alcohol in some of its facilities. Surveys of student drinking and perceptions of other students' drinking were conducted before, during and after the policy change at the transition university (TU) and compared to similar data from a control university (CU). Surveys of student drinking at on-campus and off-campus venues and observations of alcohol service practices were also conducted. The policy change at the TU was introduced cautiously, and sales to underage drinkers were relatively well controlled. Despite this, student drinking rose initially, then declined after 1 year. Perceptions of the amount of drinking by other students increased slightly, but there was no overall measurable increase in student drinking during the first 3 years of the new policy. The conservative TU policy-to sell alcohol only at select events and to control sales to minors-may have limited the impact of on-campus alcohol sales on student consumption. Although the study results did not find a stable increase in student drinking, they do not necessarily support the liberalization of campus alcohol policy, because the transition is still 'in progress' and the final outcome has not been evaluated.
Jacobeit, J W; Gooren, L J; Schulte, H M
2009-11-01
Testosterone treatment is essential for the induction and maintenance of virilization of female-to-male (FTM) transsexuals. Aim To test the safety of a novel testosterone preparation for this purpose. Parenteral long-acting testosterone undecanoate (TU) was administered to 17 FTM transsexuals over 36 months. Observations were made while subjects received treatment. Serum testosterone rose from 0.50+/-0.25 to 6.2+/-1.3 ng/ml at 6 months and remained stable thereafter. The testosterone profiles were largely identical with those in hypogonadal receiving TU. There were no side effects. Over the 36 months of the study, there was a small but significant decrease in plasma cholesterol (from 218+/-47 to 188+/-42 mg/dl) and low-density lipoprotein-cholesterol (from 139+/-48 to 139+/-48 mg/dl), while plasma levels of high-density lipoprotein-cholesterol and triglycerides did not change significantly. Liver enzymes did not change during treatment. There was an increase of both levels in hemoglobin (from 13.6+/-1.2 to 16.0+/-1.5 g/dl) and hematocrit (from 41+/-4 to 46+/-4) upon administration but they remained almost without exception within the physiological range. No special measures were needed. Breast and gonads/internal genitalia did not show pathological changes over the observation period. This study reports that TU is suited for induction of virilization in FTM transsexuals without significant side effects over a longer term.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Pogson, EM; University of Wollongong, Wollongong, NSW; Liverpool and Macarthur Cancer Therapy Centres, Liverpool, NSW
2016-06-15
Purpose: Breast cancers predominantly arise from Glandular Breast Tissue (GBT). If the GBT can be treated effectively post-operatively utilising radiotherapy this may be adequate volumetric coverage for adjuvant breast radiotherapy. Adequate imaging of the GBT is necessary and will be assessed between MRI and CT modalities. GBT visualisation is acknowledged to be qualitatively superior on Magnetic Resonance Image (MRI) compared to Computed Tomography (CT), the current radiotherapy imaging standard, however this has not been quantitatively assessed. For radiotherapy purposes it is important that any treatment volume can be consistently defined between observers. This study investigates the consistency of CT andmore » MRI GBT contours for potential radiotherapy planning. Methods: Ten experts (9 breast radiation oncologists and 1 radiologist) contoured the extent of the visible GBT for 33 patients on MRI and CT (both without contrast), which was performed according to a contouring guideline in supine and prone patient positions. The GBT volume was not a conventional whole breast radiotherapy planning volume, but rather the extent of GBT that was indicated from the CT or MR imaging. Volumes were compared utilizing the dice similarity coefficient (DSC), kappa statistic, and Hausdorff Distances (HDs) to ascertain the modality that was most consistently volumed. Results: The inter-observer concordance was of substantial agreement (kappa above 0.6) for the CT supine, CT prone, MRI supine and MRI prone datasets. The MRI GBT volumes were larger than the CT GBT volumes (p<0.001). Inter-observer conformity was higher for CT than MRI, although the magnitude of this difference was small (VOI<0.04). Conformity between modalities (CT and MRI) was in agreement for both prone and supine, DSC=0.75. Prone GBT volumes were larger than supine for both MRI and CT. Conclusion: MRI improves the extent of GBT delineation. The role of MRI guided, GBT-targeted radiotherapy requires investigation in a clinical trial. This work was supported by a grant number APP1033237 from Cancer Australia and the National Breast Cancer Foundation.« less
TU-H-BRC-01: A New Fabrication Method for Secondary Skin Collimation Using 3D Scanner and 3D Printer
DOE Office of Scientific and Technical Information (OSTI.GOV)
Jung, J; Potter, N; Suh, T
Purpose: Using secondary skin collimation (SSC) to protect the critical organ surrounding the tumors is always desirable for electron and/or ortho-voltage treatments. However, the time-consuming and labor-intensive fabrication processes of current method (manually fabricate the lead mask) restrict the general use of SSC. The aim of this study is to develop a new SSC fabrication method using 3D scanning and 3D printing technologies in order to largely decrease the human labor involvement and fabrication time, also improve the fabrication accuracy. Methods: First, the patient surface was scanned with a 3D scanner (Structure Sensor, Occipital, CO). The raw scan data wasmore » subsequently transferred to a 3D modeling software (Rhinoceros, Ver. 5.0, McNeel North America, Seattle, WA). The tumor contour was then digitized and shielding region was determined by clinicians in the same software. The corresponding SCC conformed to the skin surface was then automatically generated by the software with the proper shielding thickness. The shell of the SCC (with hollow inside) was consequently printed by a 3D printer (Lulzbot TAZ, Aleph Objects, CO) using plastic material. Finally, the hollow mold of SCC was filled up with a melted cerrobend alloy. Once the cerrobend alloy cooled down, the fabrication of SCC was accomplished. Results: The results indicated the proposed method can achieve a much shorter time on making a SCC compared with tradition fabrication method. The processes of making a skin contour model for patients have been eliminated with the new method. SCC created by the new method possessed better accuracy and better conformality to patient’s skin contours. Conclusion: In this study, we have demonstrated a new method for the SCC fabrication. It is anticipated that our method can be an alternative way to replace conventional manual-based methods for electron and/or ortho-voltage SCC fabrication. This research was supported by the Global Ph.D. Fellowship Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (Grant No. 2015H1A2A1034071), Republic of Korea.« less
NASA Technical Reports Server (NTRS)
Harrison, A. A.
1979-01-01
Group dynamics, sociological and psychological factors are examined. Crew composition and compatability are studied. Group dynamics analysis includes: leadership; cohesiveness; conformity; and conflict.
NASA Technical Reports Server (NTRS)
Harrison, A. A.
1978-01-01
Group dynamics, sociological and psychological factors are examined. Crew composition and compatibility are studied. Group dynamics analysis includes: leadership; cohesiveness; conformity; and conflict.
NASA Astrophysics Data System (ADS)
Hazwan, M. H. M.; Shayfull, Z.; Sharif, S.; Nasir, S. M.; Zainal, N.
2017-09-01
In injection moulding process, quality and productivity are notably important and must be controlled for each product type produced. Quality is measured as the extent of warpage of moulded parts while productivity is measured as a duration of moulding cycle time. To control the quality, many researchers have introduced various of optimisation approaches which have been proven enhanced the quality of the moulded part produced. In order to improve the productivity of injection moulding process, some of researches have proposed the application of conformal cooling channels which have been proven reduced the duration of moulding cycle time. Therefore, this paper presents an application of alternative optimisation approach which is Response Surface Methodology (RSM) with Glowworm Swarm Optimisation (GSO) on the moulded part with straight-drilled and conformal cooling channels mould. This study examined the warpage condition of the moulded parts before and after optimisation work applied for both cooling channels. A front panel housing have been selected as a specimen and the performance of proposed optimisation approach have been analysed on the conventional straight-drilled cooling channels compared to the Milled Groove Square Shape (MGSS) conformal cooling channels by simulation analysis using Autodesk Moldflow Insight (AMI) 2013. Based on the results, melt temperature is the most significant factor contribute to the warpage condition and warpage have optimised by 39.1% after optimisation for straight-drilled cooling channels and cooling time is the most significant factor contribute to the warpage condition and warpage have optimised by 38.7% after optimisation for MGSS conformal cooling channels. In addition, the finding shows that the application of optimisation work on the conformal cooling channels offers the better quality and productivity of the moulded part produced.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Simonetti, Angelita; Marzi, Stefano; Fabbretti, Attilio
2013-06-01
The crystal structures of the eubacterial translation initiation factor 2 in apo form and with bound GDP and GTP reveal conformational changes upon nucleotide binding and hydrolysis, notably of the catalytically important histidine in the switch II region. Translation initiation factor 2 (IF2) is involved in the early steps of bacterial protein synthesis. It promotes the stabilization of the initiator tRNA on the 30S initiation complex (IC) and triggers GTP hydrolysis upon ribosomal subunit joining. While the structure of an archaeal homologue (a/eIF5B) is known, there are significant sequence and functional differences in eubacterial IF2, while the trimeric eukaryotic IF2more » is completely unrelated. Here, the crystal structure of the apo IF2 protein core from Thermus thermophilus has been determined by MAD phasing and the structures of GTP and GDP complexes were also obtained. The IF2–GTP complex was trapped by soaking with GTP in the cryoprotectant. The structures revealed conformational changes of the protein upon nucleotide binding, in particular in the P-loop region, which extend to the functionally relevant switch II region. The latter carries a catalytically important and conserved histidine residue which is observed in different conformations in the GTP and GDP complexes. Overall, this work provides the first crystal structure of a eubacterial IF2 and suggests that activation of GTP hydrolysis may occur by a conformational repositioning of the histidine residue.« less
Comprehensive analysis of the dynamic structure of nuclear localization signals.
Yamagishi, Ryosuke; Okuyama, Takahide; Oba, Shuntaro; Shimada, Jiro; Chaen, Shigeru; Kaneko, Hiroki
2015-12-01
Most transcription and epigenetic factors in eukaryotic cells have nuclear localization signals (NLSs) and are transported to the nucleus by nuclear transport proteins. Understanding the features of NLSs and the mechanisms of nuclear transport might help understand gene expression regulation, somatic cell reprogramming, thus leading to the treatment of diseases associated with abnormal gene expression. Although many studies analyzed the amino acid sequence of NLSs, few studies investigated their three-dimensional structure. Therefore, we conducted a statistical investigation of the dynamic structure of NLSs by extracting the conformation of these sequences from proteins examined by X-ray crystallography and using a quantity defined as conformational determination rate (a ratio between the number of amino acids determining the conformation and the number of all amino acids included in a certain region). We found that determining the conformation of NLSs is more difficult than determining the conformation of other regions and that NLSs may tend to form more heteropolymers than monomers. Therefore, these findings strongly suggest that NLSs are intrinsically disordered regions.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wood, B.; Amyes, T; Fedorov, A
2010-01-01
The structural factors responsible for the extraordinary rate enhancement ({approx}10{sup 17}) of the reaction catalyzed by orotidine 5{prime}-monophosphate decarboxylase (OMPDC) have not been defined. Catalysis requires a conformational change that closes an active site loop and 'clamps' the orotate base proximal to hydrogen-bonded networks that destabilize the substrate and stabilize the intermediate. In the OMPDC from Methanobacter thermoautotrophicus, a 'remote' structurally conserved cluster of hydrophobic residues that includes Val 182 in the active site loop is assembled in the closed, catalytically active conformation. Substitution of these residues with Ala decreases k{sub cat}/K{sub m} with a minimal effect on k{sub cat},more » providing evidence that the cluster stabilizes the closed conformation. The intrinsic binding energies of the 5{prime}-phosphate group of orotidine 5{prime}-monophosphate for the mutant enzymes are similar to that for the wild type, supporting this conclusion.« less
Inherited defects in pedigree dogs. Part 1: disorders related to breed standards.
Asher, Lucy; Diesel, Gillian; Summers, Jennifer F; McGreevy, Paul D; Collins, Lisa M
2009-12-01
The United Kingdom pedigree-dog industry has faced criticism because certain aspects of dog conformation stipulated in the UK Kennel Club breed standards have a detrimental impact on dog welfare. A review of conformation-related disorders was carried out in the top 50 UK Kennel Club registered breeds using systematic searches of existing information. A novel index to score severity of disorders along a single scale was also developed and used to conduct statistical analyses to determine the factors affecting reported breed predisposition to defects. According to the literature searched, each of the top 50 breeds was found to have at least one aspect of its conformation predisposing it to a disorder; and 84 disorders were either directly or indirectly associated with conformation. The Miniature poodle, Bulldog, Pug and Basset hound had most associations with conformation-related disorders. Further research on prevalence and severity is required to assess the impact of different disorders on the welfare of affected breeds.
López-Martínez, C; Flores-Morales, P; Cruz, M; González, T; Feliz, M; Diez, A; Campanera, Josep M
2016-05-14
Cis and trans proline conformers are often associated with dramatic changes in the biological function of peptides. A slow equilibrium between cis and trans Ile-Pro amide bond conformers occurs in constrained derivatives of the native marine cyclic heptapeptide stylostatin 1 (cyclo-(NSLAIPF)), a potential anticancer agent. In this work, four cyclopeptides, cyclo-(NSTAIPF), cyclo-(KSTAIPF), cyclo-(RSTAIPF) and cyclo-(DSTAIPF), which are structurally related to stylostatin 1, are experimentally and computationally examined in order to assess the effect of residue mutations on the cis-trans conformational ratio and the apparent capacity to form dimeric aggregates. Primarily, cyclo-(KSTAIPF) and cyclo-(RSTAIPF) showed specific trends in circular dichroism, MALDI-TOF and HPLC purification experiments, which suggests the occurrence of peptide dimerization. Meanwhile, the NMR spectrum of cyclo-(KSTAIPF) indicates that this cyclopeptide exists in the two slow-exchange families of conformations mentioned above. Molecular dynamics simulations combined with quantum mechanical calculations have shed light on the factors governing the cis/trans conformational ratio. In particular, we have found that residue mutations affect the internal hydrogen bond pattern which ultimately tunes the cis/trans conformational ratio and that only trans conformers are capable of aggregating due to the shape complementarity of the two subunits.
NASA Tech Briefs, July/August 1986. Volume 10, No. 4
NASA Technical Reports Server (NTRS)
1986-01-01
Topic include: NASA TU Serv1ces; New Product Ideas; Electronic Components and Circuits; Electronic Systems; Materials; Computer Programs; Mechanics; Physical Sciences; Machinery; Fabrication Technology; Mathematics and Information Sciences; Life Sciences. 3
Kim, Jaewon; Lee, Jihun; Brych, Stephen R; Logan, Timothy M; Blaber, Michael
2005-02-01
The beta-turn is the most common type of nonrepetitive structure in globular proteins, comprising ~25% of all residues; however, a detailed understanding of effects of specific residues upon beta-turn stability and conformation is lacking. Human acidic fibroblast growth factor (FGF-1) is a member of the beta-trefoil superfold and contains a total of five beta-hairpin structures (antiparallel beta-sheets connected by a reverse turn). beta-Turns related by the characteristic threefold structural symmetry of this superfold exhibit different primary structures, and in some cases, different secondary structures. As such, they represent a useful system with which to study the role that turn sequences play in determining structure, stability, and folding of the protein. Two turns related by the threefold structural symmetry, the beta4/beta5 and beta8/beta9 turns, were subjected to both sequence-swapping and poly-glycine substitution mutations, and the effects upon stability, folding, and structure were investigated. In the wild-type protein these turns are of identical length, but exhibit different conformations. These conformations were observed to be retained during sequence-swapping and glycine substitution mutagenesis. The results indicate that the beta-turn structure at these positions is not determined by the turn sequence. Structural analysis suggests that residues flanking the turn are a primary structural determinant of the conformation within the turn.
Psychosocial Predictors and Correlates of Suicidality in Teenage Latino Males
ERIC Educational Resources Information Center
Locke, Thomas F.; Newcomb, Michael D.
2005-01-01
Multiple ecodevelopmental factors were tested as they influence suicidality in a community sample of Latino adolescent males. Risk factors tested included childhood maltreatment, parental alcohol-related problems, and polysubstance problems. Protective factors included general self-efficacy, social conformity, and family bonding. Male participants…
Topić Vučenović, Valentina; Rajkovača, Zvezdana; Jelić, Dijana; Stanimirović, Dragi; Vuleta, Goran; Miljković, Branislava; Vučićević, Katarina
2018-05-13
Radioiodine ( 131 I) therapy is the common treatment option for benign thyroid diseases. The objective of this study was to characterize 131 I biokinetics in patients with benign thyroid disease and to investigate and quantify the influence of patients' demographic and clinical characteristics on intra-thyroidal 131 I kinetics by developing a population model. Population pharmacokinetic analysis was performed using a nonlinear mixed effects approach. Data sets of 345 adult patients with benign thyroid disease, retrospectively collected from patients' medical records, were evaluated in the analysis. The two-compartment model of 131 I biokinetics representing the blood compartment and thyroid gland was used as the structural model. Results of the study indicate that the rate constant of the uptake of 131 I into the thyroid (k tu ) is significantly influenced by clinical diagnosis, age, functional thyroid volume, free thyroxine in plasma (fT 4 ), use of anti-thyroid drugs, and time of discontinuation of therapy before administration of the radioiodine (THDT), while the effective half-life of 131 I is affected by the age of the patients. Inclusion of the covariates in the base model resulted in a decrease of the between subject variability for k tu from 91 (3.9) to 53.9 (4.5)%. This is the first population model that accounts for the influence of fT 4 and THDT on radioiodine kinetics. The model could be used for further investigations into the correlation between thyroidal exposure to 131 I and the outcome of radioiodine therapy of benign thyroid disease as well as the development of dosing recommendations.
2015-01-01
The role of twist-boat conformers of cyclohexanones in hydride reductions was explored. The hydride reductions of a cis-2,6-disubstituted N-acylpiperidone, an N-acyltropinone, and tert-butylcyclohexanone by lithium aluminum hydride and by a bulky borohydride reagent were investigated computationally and compared to experiment. Our results indicate that in certain cases, factors such as substrate conformation, nucleophile bulkiness, and remote steric features can affect stereoselectivity in ways that are difficult to predict by the general Felkin–Anh model. In particular, we have calculated that a twist-boat conformation is relevant to the reactivity and facial selectivity of hydride reduction of cis-2,6-disubstituted N-acylpiperidones with a small hydride reagent (LiAlH4) but not with a bulky hydride (lithium triisopropylborohydride). PMID:25372509
Unattainable extended spacetime regions in conformal gravity
NASA Astrophysics Data System (ADS)
Chakrabarty, Hrishikesh; Benavides-Gallego, Carlos A.; Bambi, Cosimo; Modesto, Leonardo
2018-03-01
The Janis-Newman-Winicour metric is a solution of Einstein's gravity minimally coupled to a real massless scalar field. The γ-metric is instead a vacuum solution of Einstein's gravity. Both spacetimes have no horizon and possess a naked singularity at a finite value of the radial coordinate, where curvature invariants diverge and the spacetimes are geodetically incomplete. In this paper, we reconsider these solutions in the framework of conformal gravity and we show that it is possible to solve the spacetime singularities with a suitable choice of the conformal factor. Now curvature invariants remain finite over the whole spacetime. Massive particles never reach the previous singular surface and massless particles can never do it with a finite value of their affine parameter. Our results support the conjecture according to which conformal gravity can fix the singularity problem that plagues Einstein's gravity.
Sezen, Figen; Albayrak, Nurhan; Özkara, Şeref; Karagöz, Alper; Alp, Alpaslan; Duyar Ağca, Filiz; İnan Süer, Asiye; Müderris, Tuba; Ceyhan, İsmail; Durmaz, Rıza; Ertek, Mustafa
2015-04-01
The most effective method for monitoring country-level drug resistance frequency and to implement the necessary control measures is the establishment of a laboratory-based surveillance system. The aim of this study was to summarize the follow up trend of the drug-resistant tuberculosis (TB) cases, determine the load of resistance and evaluate the capacities of laboratories depending on laboratory quality assurance system for the installation work of National Tuberculosis Laboratory Surveillance Network (TuLSA) which has started in Ankara in 2011. TuLSA studies was carried out under the coordination of National Tuberculosis Reference Laboratory (NRL) with the participation of TB laboratories and dispensaries. Specimens of TB patients, reported from health institutions, were followed in TB laboratories, and the epidemiological information was collected from the dispensaries. One isolate per patient with the drug susceptibility test (DST) results were sent to NRL from TB laboratories and in NRL the isolates were rechecked with the genotypical (MTBDRplus, Hain Lifescience, Germany) and phenotypical (MGIT 960, BD, USA) DST methods. Molecular epidemiological analysis were also performed by spoligotyping and MIRU/VNTR. Second-line DST was applied to the isolates resistant to rifampin. A total of 1276 patients were reported between January 1st to December 31th 2011, and 335 cases were defined as "pulmonary TB from Ankara province". The mean age of those patients was 43.4 ± 20 years, and 67.5% were male. Three hundred seventeen (94.6%) patients were identified as new cases. The average sample number obtained from pulmonary TB cases was 3.26 ± 2.88, and 229 (68.3%) of them was culture positive. DST was applied to all culture positive isolates; 90.4% (207/229) of cases were susceptible to the five drugs tested (ethambutol, isoniazid, pyrazinamide, rifampicin, streptomycin). Eight (3.5%) of the isolates were multidrug-resistant (MDR-TB), while no extensively drug-resistant strains were detected. MDR-TB is likely to occur in 63.3 times more among previously treated cases, and 73.3 times more in legal aliens. The achievement of therapy among pulmonary TB cases was 91.9%. Spoligotyping performed for 221 M.tuberculosis complex isolates, showed that all strains were clustered in nine groups. SIT 41 (105/221; 47.5%) was the most frequent spoligotype detected, and clustering rate based on MIRU-VNTR results were found as 16.3%. All of the clustered strains were sensitive while all of MDR-TB isolates showed specific MIRU-VNTR profiles. In conclusion, TuLSA studies started in Ankara in 2011 and the system is still expanding in the country. Our data obtained with TuLSA have been published as a regional surveillance data in the WHO Global Tuberculosis Report 2011, and as a national surveillance data in Global Tuberculosis Report 2012.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Rashin, Alexander A., E-mail: alexander-rashin@hotmail.com; Iowa State University, 112 Office and Lab Bldg, Ames, IA 50011-3020; Domagalski, Marcin J.
Conformational differences between myoglobin structures are studied. Most structural differences in whale myoglobin beyond the uncertainty threshold can be correlated with a few specific structural factors. There are always exceptions and a search for additional factors is needed. The results might have serious implications for biological insights from conformational differences. Validation of general ideas about the origins of conformational differences in proteins is critical in order to arrive at meaningful functional insights. Here, principal component analysis (PCA) and distance difference matrices are used to validate some such ideas about the conformational differences between 291 myoglobin structures from sperm whale, horsemore » and pig. Almost all of the horse and pig structures form compact PCA clusters with only minor coordinate differences and outliers that are easily explained. The 222 whale structures form a few dense clusters with multiple outliers. A few whale outliers with a prominent distortion of the GH loop are very similar to the cluster of horse structures, which all have a similar GH-loop distortion apparently owing to intermolecular crystal lattice hydrogen bonds to the GH loop from residues near the distal histidine His64. The variations of the GH-loop coordinates in the whale structures are likely to be owing to the observed alternative intermolecular crystal lattice bond, with the change to the GH loop distorting bonds correlated with the binding of specific ‘unusual’ ligands. Such an alternative intermolecular bond is not observed in horse myoglobins, obliterating any correlation with the ligands. Intermolecular bonds do not usually cause significant coordinate differences and cannot be validated as their universal cause. Most of the native-like whale myoglobin structure outliers can be correlated with a few specific factors. However, these factors do not always lead to coordinate differences beyond the previously determined uncertainty thresholds. The binding of unusual ligands by myoglobin, leading to crystal-induced distortions, suggests that some of the conformational differences between the apo and holo structures might not be ‘functionally important’ but rather artifacts caused by the binding of ‘unusual’ substrate analogs. The causes of P6 symmetry in myoglobin crystals and the relationship between crystal and solution structures are also discussed.« less