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Sample records for activity strongly suggesting

  1. Molecular multiproxy analysis of ancient root systems suggests strong alteration of deep subsoil organic matter by rhizomicrobial activity

    NASA Astrophysics Data System (ADS)

    Gocke, Martina; Huguet, Arnaud; Derenne, Sylvie; Kolb, Steffen; Wiesenberg, Guido L. B.

    2013-04-01

    decreasing contents of archeal GDGTs from rhizolith via rhizosphere towards root-free loess. Furthermore, the bacterial fingerprint revealed - similar to modern root systems - higher taxonomic diversity in rhizosphere compared to rhizoliths and reference loess. This argues for microorganisms benefiting from root deposits and exudates. Highest concentrations of branched GDGTs in rhizoliths suggest that their source organisms feed on root remains. Incorporation of rhizomicrobial remains as represented by RNA and GDGTs usually affected the sediment at maximum to a distance of 2-3 cm from the former root. FA contents in rhizosphere showed strong scatter and were in part depleted compared to reference loess or, especially in deeper transects, enriched. This indicates the presence of degradation products originating from former rhizosphere processes. Especially at larger depth not affected by modern pedogenic processes, portions of mainly microbial derived C16 homologues were higher in rhizosphere loess up to distances of 10 cm, revealing that the possible extension of the rhizosphere was underestimated so far. In Corg poor subsoil, the occurence of diverse rhizosphere microorganisms and degradation processes even in several centimeters distant from roots point to a strong alteration of OM, possibly contributing to carbon mineralisation.

  2. Studies and Suggestions on Prewriting Activities

    ERIC Educational Resources Information Center

    Zheng, Shigao; Dai, Weiping

    2012-01-01

    This paper studies and suggests the need for writing instruction by which students can experience writing as a creative process in exploring and communicating meaning. The prewriting activities generate ideas which can encourage a free flow of thoughts and help students discover both what they want to say and how to say it on paper. Through the…

  3. Burden analysis of rare microdeletions suggests a strong impact of neurodevelopmental genes in genetic generalised epilepsies.

    PubMed

    Lal, Dennis; Ruppert, Ann-Kathrin; Trucks, Holger; Schulz, Herbert; de Kovel, Carolien G; Kasteleijn-Nolst Trenité, Dorothée; Sonsma, Anja C M; Koeleman, Bobby P; Lindhout, Dick; Weber, Yvonne G; Lerche, Holger; Kapser, Claudia; Schankin, Christoph J; Kunz, Wolfram S; Surges, Rainer; Elger, Christian E; Gaus, Verena; Schmitz, Bettina; Helbig, Ingo; Muhle, Hiltrud; Stephani, Ulrich; Klein, Karl M; Rosenow, Felix; Neubauer, Bernd A; Reinthaler, Eva M; Zimprich, Fritz; Feucht, Martha; Møller, Rikke S; Hjalgrim, Helle; De Jonghe, Peter; Suls, Arvid; Lieb, Wolfgang; Franke, Andre; Strauch, Konstantin; Gieger, Christian; Schurmann, Claudia; Schminke, Ulf; Nürnberg, Peter; Sander, Thomas

    2015-05-01

    Genetic generalised epilepsy (GGE) is the most common form of genetic epilepsy, accounting for 20% of all epilepsies. Genomic copy number variations (CNVs) constitute important genetic risk factors of common GGE syndromes. In our present genome-wide burden analysis, large (≥ 400 kb) and rare (< 1%) autosomal microdeletions with high calling confidence (≥ 200 markers) were assessed by the Affymetrix SNP 6.0 array in European case-control cohorts of 1,366 GGE patients and 5,234 ancestry-matched controls. We aimed to: 1) assess the microdeletion burden in common GGE syndromes, 2) estimate the relative contribution of recurrent microdeletions at genomic rearrangement hotspots and non-recurrent microdeletions, and 3) identify potential candidate genes for GGE. We found a significant excess of microdeletions in 7.3% of GGE patients compared to 4.0% in controls (P = 1.8 x 10-7; OR = 1.9). Recurrent microdeletions at seven known genomic hotspots accounted for 36.9% of all microdeletions identified in the GGE cohort and showed a 7.5-fold increased burden (P = 2.6 x 10-17) relative to controls. Microdeletions affecting either a gene previously implicated in neurodevelopmental disorders (P = 8.0 x 10-18, OR = 4.6) or an evolutionarily conserved brain-expressed gene related to autism spectrum disorder (P = 1.3 x 10-12, OR = 4.1) were significantly enriched in the GGE patients. Microdeletions found only in GGE patients harboured a high proportion of genes previously associated with epilepsy and neuropsychiatric disorders (NRXN1, RBFOX1, PCDH7, KCNA2, EPM2A, RORB, PLCB1). Our results demonstrate that the significantly increased burden of large and rare microdeletions in GGE patients is largely confined to recurrent hotspot microdeletions and microdeletions affecting neurodevelopmental genes, suggesting a strong impact of fundamental neurodevelopmental processes in the pathogenesis of common GGE syndromes. PMID:25950944

  4. Burden Analysis of Rare Microdeletions Suggests a Strong Impact of Neurodevelopmental Genes in Genetic Generalised Epilepsies

    PubMed Central

    Trucks, Holger; Schulz, Herbert; de Kovel, Carolien G.; Kasteleijn-Nolst Trenité, Dorothée; Sonsma, Anja C. M.; Koeleman, Bobby P.; Lindhout, Dick; Weber, Yvonne G.; Lerche, Holger; Kapser, Claudia; Schankin, Christoph J.; Kunz, Wolfram S.; Surges, Rainer; Elger, Christian E.; Gaus, Verena; Schmitz, Bettina; Helbig, Ingo; Muhle, Hiltrud; Stephani, Ulrich; Klein, Karl M.; Rosenow, Felix; Neubauer, Bernd A.; Reinthaler, Eva M.; Zimprich, Fritz; Feucht, Martha; Møller, Rikke S.; Hjalgrim, Helle; De Jonghe, Peter; Suls, Arvid; Lieb, Wolfgang; Franke, Andre; Strauch, Konstantin; Gieger, Christian; Schurmann, Claudia; Schminke, Ulf; Nürnberg, Peter; Sander, Thomas

    2015-01-01

    Genetic generalised epilepsy (GGE) is the most common form of genetic epilepsy, accounting for 20% of all epilepsies. Genomic copy number variations (CNVs) constitute important genetic risk factors of common GGE syndromes. In our present genome-wide burden analysis, large (≥ 400 kb) and rare (< 1%) autosomal microdeletions with high calling confidence (≥ 200 markers) were assessed by the Affymetrix SNP 6.0 array in European case-control cohorts of 1,366 GGE patients and 5,234 ancestry-matched controls. We aimed to: 1) assess the microdeletion burden in common GGE syndromes, 2) estimate the relative contribution of recurrent microdeletions at genomic rearrangement hotspots and non-recurrent microdeletions, and 3) identify potential candidate genes for GGE. We found a significant excess of microdeletions in 7.3% of GGE patients compared to 4.0% in controls (P = 1.8 x 10-7; OR = 1.9). Recurrent microdeletions at seven known genomic hotspots accounted for 36.9% of all microdeletions identified in the GGE cohort and showed a 7.5-fold increased burden (P = 2.6 x 10-17) relative to controls. Microdeletions affecting either a gene previously implicated in neurodevelopmental disorders (P = 8.0 x 10-18, OR = 4.6) or an evolutionarily conserved brain-expressed gene related to autism spectrum disorder (P = 1.3 x 10-12, OR = 4.1) were significantly enriched in the GGE patients. Microdeletions found only in GGE patients harboured a high proportion of genes previously associated with epilepsy and neuropsychiatric disorders (NRXN1, RBFOX1, PCDH7, KCNA2, EPM2A, RORB, PLCB1). Our results demonstrate that the significantly increased burden of large and rare microdeletions in GGE patients is largely confined to recurrent hotspot microdeletions and microdeletions affecting neurodevelopmental genes, suggesting a strong impact of fundamental neurodevelopmental processes in the pathogenesis of common GGE syndromes. PMID:25950944

  5. Dynamo Activity in Strongly Magnetized Accretion Disks

    NASA Astrophysics Data System (ADS)

    Salvesen, Greg; Simon, Jacob B.; Armitage, Philip J.; Begelman, Mitchell C.

    2016-01-01

    Strongly magnetized accretion disks around black holes have many attractive features that may explain the enigmatic behavior observed from X-ray binaries. The physics and structure of these disks are governed by a dynamo-like mechanism, which channels the accretion power liberated by the magnetorotational instability into an ordered toroidal magnetic field. To study dynamo activity, we performed three-dimensional, stratified, isothermal, ideal magnetohydrodynamic shearing box simulations. In our simulations, the strength of this self-sustained toroidal magnetic field depends on the net vertical magnetic flux we impose, which allows us to study weak-to-strong magnetization regimes. We find that the entire disk develops into a magnetic pressure-dominated state for a sufficiently strong net vertical magnetic flux. Over the two orders of magnitude in net vertical magnetic flux that we consider, the effective α-viscosity parameter scales as a power-law. We quantify dynamo properties of toroidal magnetic flux production and its buoyant escape as a function of disk magnetization. Finally, we compare our simulations to an analytic model for the vertical structure of strongly magnetized disks applicable to the high/soft state of X-ray binaries.

  6. World War II Commemoration Committee: Fact Sheet and Suggested Activities.

    ERIC Educational Resources Information Center

    Department of Defense, Washington, DC.

    This packet suggests activities and events that school districts, schools, classes, and educational organizations can conduct to commemorate World War II. Suggestions are made to include local veterans, including those in veteran's and nursing homes and hospitals, and youth at every possible opportunity. Recognition can take the form of military…

  7. Net Fluorescein Flux Across Corneal Endothelium Strongly Suggests Fluid Transport is due to Electro-osmosis.

    PubMed

    Sanchez, J M; Cacace, V; Kusnier, C F; Nelson, R; Rubashkin, A A; Iserovich, P; Fischbarg, J

    2016-08-01

    We have presented prior evidence suggesting that fluid transport results from electro-osmosis at the intercellular junctions of the corneal endothelium. Such phenomenon ought to drag other extracellular solutes. We have investigated this using fluorescein-Na2 as an extracellular marker. We measured unidirectional fluxes across layers of cultured human corneal endothelial (HCE) cells. SV-40-transformed HCE layers were grown to confluence on permeable membrane inserts. The medium was DMEM with high glucose and no phenol red. Fluorescein-labeled medium was placed either on the basolateral or the apical side of the inserts; the other side carried unlabeled medium. The inserts were held in a CO2 incubator for 1 h (at 37 °C), after which the entire volume of the unlabeled side was collected. After that, label was placed on the opposite side, and the corresponding paired sample was collected after another hour. Fluorescein counts were determined with a (Photon Technology) DeltaScan fluorometer (excitation 380 nm; emission 550 nm; 2 nm bwth). Samples were read for 60 s. The cells utilized are known to transport fluid from the basolateral to the apical side, just as they do in vivo in several species. We used 4 inserts for influx and efflux (total: 20 1-h periods). We found a net flux of fluorescein from the basolateral to the apical side. The flux ratio was 1.104 ± 0.056. That difference was statistically significant (p = 0.00006, t test, paired samples). The endothelium has a definite restriction at the junctions. Hence, an asymmetry in unidirectional fluxes cannot arise from osmosis, and can only point instead to paracellular solvent drag. We suggest, once more, that such drag is due to electro-osmotic coupling at the paracellular junctions. PMID:26989056

  8. Vesicular stomatitis virus polymerase's strong affinity to its template suggests exotic transcription models.

    PubMed

    Tang, Xiaolin; Bendjennat, Mourad; Saffarian, Saveez

    2014-12-01

    Vesicular stomatitis virus (VSV) is the prototype for negative sense non segmented (NNS) RNA viruses which include potent human and animal pathogens such as Rabies, Ebola and measles. The polymerases of NNS RNA viruses only initiate transcription at or near the 3' end of their genome template. We measured the dissociation constant of VSV polymerases from their whole genome template to be 20 pM. Given this low dissociation constant, initiation and sustainability of transcription becomes nontrivial. To explore possible mechanisms, we simulated the first hour of transcription using Monte Carlo methods and show that a one-time initial dissociation of all polymerases during entry is not sufficient to sustain transcription. We further show that efficient transcription requires a sliding mechanism for non-transcribing polymerases and can be realized with different polymerase-polymerase interactions and distinct template topologies. In conclusion, we highlight a model in which collisions between transcribing and sliding non-transcribing polymerases result in release of the non-transcribing polymerases allowing for redistribution of polymerases between separate templates during transcription and suggest specific experiments to further test these mechanisms. PMID:25501005

  9. Microbiota studies in the bile duct strongly suggest a role for Helicobacter pylori in extrahepatic cholangiocarcinoma.

    PubMed

    Avilés-Jiménez, F; Guitron, A; Segura-López, F; Méndez-Tenorio, A; Iwai, S; Hernández-Guerrero, A; Torres, J

    2016-02-01

    Biliary tract cancer or extrahepatic cholangiocarcinoma (ECCA) represents the sixth commonest cause of cancer in the gastrointestinal tract in western countries. We aimed to characterize the microbiota and its predicted associated functions in the biliary tract of ECCA and benign biliary pathology (BBP). Samples were taken from 100 patients with ECCA and 100 patients with BBP by endoscopic cholangio-pancreatography for DNA extraction. Ten patients with ECCA and ten with BBP were selected for microbiota studies using the V4-16S rRNA gene and sequenced in Illumina platform. Microbiota analyses included sample-to-sample distance metrics, ordination/clustering and prediction of functions. Presence of Nesterenkonia sp. and Helicobacter pylori cagA and vacA genes were tested in the 100 ECCA and 100 BBP samples. Phylum Proteobacteria dominated all samples (60.4% average). Ordination multicomponent analyses showed significant microbiota separation between ECCA and BBP (p 0.010). Analyses of 4002 operational taxonomic units with presence variation in at least one category probed a separation of ECCA from BBP. Among these, Nesterenkonia decreased, whereas Methylophilaceae, Fusobacterium, Prevotella, Actinomyces, Novosphingobium and H. pylori increased in ECCA. Predicted associated functions showed increased abundance of H. pylori virulence genes in ECCA. cagA and vacA genes were confirmed by PCR in ECCA and BBP samples. This is the first microbiota report in ECCA and BBP to show significant changes in microbial composition. Bacterial species unusual for human flora were found: Methylophilaceae and Nesterenkonia are reported in hypersaline soils, and Mesorhizobium is a nitrogen-fixing bacterium. Enrichment of virulence genes confirms previous studies suggesting that H. pylori might be associated with ECCA. PMID:26493848

  10. An Inventory of Underwater Landslides in Lake Baikal Suggests a Strong Link with Gas Hydrates

    NASA Astrophysics Data System (ADS)

    De Batist, M. A. O.; Naudts, L.; Casier, R.; Khlystov, O.; Khabuev, A.; Minami, H.; Grachev, M.; Shoji, H.

    2014-12-01

    Multibeam bathymetry data from Lake Baikal were analyzed for the identification of morphologies that could indicate the presence of underwater landslides. The data were collected in 2009 by a Belgian-Russian-Japanese consortium, using a 50 kHz Seabeam 1050 echosounder, operated from RV Titov. The data cover the entire lake floor -in water depths between 200 m and 1637 m- of the Southern and Central Basins, i.e. a total surface of 15,000 km2. Our analysis revealed the presence of 26 possible underwater landslides. At least 11 of these are characterized by distinctive headwalls, scars and overall morphology, and were confirmed to be mass-wasting features by high-resolution reflection seismic data. Most of the identified underwater landslides scar the slopes of the Selenga river delta, and the sediment-charged slopes of the shoaling eastern margin of the half-graben basins. Most of the underwater landslides have a headwall occurring at water depths between 300 and 450 m; only a few occur at larger water depths. All underwater landslides occur in areas in which gas hydrates have been inferred (i.e. based on the observation of bottom-simulating reflections on seismic data) or confirmed (i.e. by deep drilling or shallow coring). The clustering of many headwalls at a water depth that is not characterized by any distinct change in slope gradient or stratigraphy, but that is close to the stability limit of gas hydrates (i.e. ca. 380 m, for pure methane hydrates, under Lake Baikal conditions), suggests that the presence of the hydrates may be one of the most important controlling factors in conditioning the underwater slopes of Lake Baikal and rendering them unstable and prone to failure. The exact conditioning process remains, however, unclear as the hydrate reservoir in Lake Baikal is considered to have remained stable, even over relatively long time scales, in the absence of any important fluctuations in lake-level and in bottom-water temperature.

  11. Geoethical suggestions for reducing risk of next (not only strong) earthquakes

    NASA Astrophysics Data System (ADS)

    Nemec, Vaclav

    2013-04-01

    Three relatively recent examples of earthquakes can be used as a background for suggesting geoethical views into any prediction accompanied by a risk analysis. ĹAquila earthquake (Italy - 2009): ĹAquila was largely destroyed by earthquakes in 1315, 1319, 1452, 1461, 1501, 1646, 1703 (until that time altogether about 3000 victims) and 1786 (about 6000 victims of this event only). The city was rebuilt and remained stable until October 2008, when tremors began again. From January 1 through April 5, 2009, additional 304 tremors were reported. When after measuring increased levels of radon emitted from the ground a local citizen (for many years working for the Italian National Institute of Astrophysics) predicted a major earthquake on Italian television, he was accused of being alarmist. Italy's National Commission for Prediction and Prevention of Major Risks met in L'Aquila for one hour on March 31, 2009, without really evaluating and characterising the risks that were present. On April 6 a 6.3 magnitude earthquake struck Aquila and nearby towns, killing 309 people and injuring more than 1,500. The quake also destroyed roughly 20,000 buildings, temporarily displacing another 65,000 people. In July 2010, prosecutor Fabio Picuti charged the Commission members with manslaughter and negligence for failing to warn the public of the impending risk. Many international organizations joined the chorus of criticism wrongly interpreting the accusation and sentence at the first stage as a problem of impossibility to predict earthquakes. - The Eyjafjallajokull volcano eruption (Iceland - 2010) is a reminder that in our globalized, interconnected world because of the increased sensibility of the new technology even a relatively small natural disaster may cause unexpected range of problems. - Earthquake and tsunami (Japan - 2011) - the most powerful known earthquake ever to have hit Japan on March 11. Whereas the proper earthquake with the magnitude of 9.0 has caused minimum of

  12. Strong optical activity from twisted-cross photonic metamaterials.

    PubMed

    Decker, M; Ruther, M; Kriegler, C E; Zhou, J; Soukoulis, C M; Linden, S; Wegener, M

    2009-08-15

    Following a recent theoretical suggestion and microwave experiments, we fabricate photonic metamaterials composed of pairs of twisted gold crosses using two successive electron-beam-lithography steps and intermediate planarization via a spin-on dielectric. The resulting two effective resonances of the coupled system lie in the 1-2 microm wavelength regime and exhibit pronounced circular dichroism, while the circular polarization conversion is very small. In between the two resonances, we find a fairly broad spectral regime with strong optical activity, i.e., with a pure rotation of incident linear polarization. The measured optical transmittance spectra agree well with theory. PMID:19684829

  13. Think Texas! Suggested Activities to Help Celebrate Our Sesquicentennial.

    ERIC Educational Resources Information Center

    Texas Education Agency, Austin.

    A packet of teaching activities helps elementary and secondary teachers commemorate the sesquicentennial of Texas' independence. Activities include listening to stories about the mockingbird, bluebonnet, and pecan tree, drawing interpretations of these stories, and using a graphics tablet, light pen, or graphics software to illustrate a Texas folk…

  14. Extensive phenotypic plasticity of a Red Sea coral over a strong latitudinal temperature gradient suggests limited acclimatization potential to warming

    NASA Astrophysics Data System (ADS)

    Sawall, Yvonne; Al-Sofyani, Abdulmoshin; Hohn, Sönke; Banguera-Hinestroza, Eulalia; Voolstra, Christian R.; Wahl, Martin

    2015-03-01

    Global warming was reported to cause growth reductions in tropical shallow water corals in both, cooler and warmer, regions of the coral species range. This suggests regional adaptation with less heat-tolerant populations in cooler and more thermo-tolerant populations in warmer regions. Here, we investigated seasonal changes in the in situ metabolic performance of the widely distributed hermatypic coral Pocillopora verrucosa along 12° latitudes featuring a steep temperature gradient between the northern (28.5°N, 21-27°C) and southern (16.5°N, 28-33°C) reaches of the Red Sea. Surprisingly, we found little indication for regional adaptation, but strong indications for high phenotypic plasticity: Calcification rates in two seasons (winter, summer) were found to be highest at 28-29°C throughout all populations independent of their geographic location. Mucus release increased with temperature and nutrient supply, both being highest in the south. Genetic characterization of the coral host revealed low inter-regional variation and differences in the Symbiodinium clade composition only at the most northern and most southern region. This suggests variable acclimatization potential to ocean warming of coral populations across the Red Sea: high acclimatization potential in northern populations, but limited ability to cope with ocean warming in southern populations already existing at the upper thermal margin for corals.

  15. Extensive phenotypic plasticity of a Red Sea coral over a strong latitudinal temperature gradient suggests limited acclimatization potential to warming.

    PubMed

    Sawall, Yvonne; Al-Sofyani, Abdulmoshin; Hohn, Sönke; Banguera-Hinestroza, Eulalia; Voolstra, Christian R; Wahl, Martin

    2015-01-01

    Global warming was reported to cause growth reductions in tropical shallow water corals in both, cooler and warmer, regions of the coral species range. This suggests regional adaptation with less heat-tolerant populations in cooler and more thermo-tolerant populations in warmer regions. Here, we investigated seasonal changes in the in situ metabolic performance of the widely distributed hermatypic coral Pocillopora verrucosa along 12° latitudes featuring a steep temperature gradient between the northern (28.5°N, 21-27°C) and southern (16.5°N, 28-33°C) reaches of the Red Sea. Surprisingly, we found little indication for regional adaptation, but strong indications for high phenotypic plasticity: Calcification rates in two seasons (winter, summer) were found to be highest at 28-29°C throughout all populations independent of their geographic location. Mucus release increased with temperature and nutrient supply, both being highest in the south. Genetic characterization of the coral host revealed low inter-regional variation and differences in the Symbiodinium clade composition only at the most northern and most southern region. This suggests variable acclimatization potential to ocean warming of coral populations across the Red Sea: high acclimatization potential in northern populations, but limited ability to cope with ocean warming in southern populations already existing at the upper thermal margin for corals. PMID:25754672

  16. Strong population genetic structuring in an annual fish, Nothobranchius furzeri, suggests multiple savannah refugia in southern Mozambique

    PubMed Central

    2013-01-01

    Background Intraspecific genetic variation of African fauna has been significantly affected by pronounced climatic fluctuations in Plio-Pleistocene, but, with the exception of large mammals, very limited empirical data on diversity of natural populations are available for savanna-dwelling animals. Nothobranchius furzeri is an annual fish from south-eastern Africa, inhabiting discrete temporary savannah pools outside main river alluvia. Their dispersal is limited and population processes affecting its genetic structure are likely a combination of those affecting terrestrial and aquatic taxa. N. furzeri is a model taxon in ageing research and several populations of known geographical origin are used in laboratory studies. Here, we analysed the genetic structure, diversity, historical demography and temporal patterns of divergence in natural populations of N. furzeri across its entire distribution range. Results Genetic structure and historical demography of N. furzeri were analysed using a combination of mitochondrial (partial cytochrome b sequences, 687 bp) and nuclear (13 microsatellites) markers in 693 fish from 36 populations. Genetic markers consistently demonstrated strong population structuring and suggested two main genetic groups associated with river basins. The split was dated to the Pliocene (>2 Mya). The northern group inhabits savannah pools across the basin of the intermittent river Chefu in south-western Mozambique and eastern Zimbabwe. The southern group (from southernmost Mozambique) is subdivided, with the River Limpopo forming a barrier (maximum divergence time 1 Mya). A strong habitat fragmentation (isolated temporary pools) is reflected in significant genetic structuring even between adjacent pools, with a major influence of genetic drift and significant isolation-by-distance. Analysis of historical demography revealed that the expansion of both groups is ongoing, supported by frequent founder effects in marginal parts of the range and evidence

  17. Chemistry: Experiments, Demonstrations and Other Activities Suggested for Chemistry.

    ERIC Educational Resources Information Center

    New York State Education Dept., Albany. Bureau of Secondary Curriculum Development.

    This publication is a handbook used in conjunction with the course of study in chemistry developed through the New York State Education Department and The University of the State of New York. It contains experiments, demonstrations, and other activities for a chemistry course. Areas covered include the science of chemistry, the atomic structure of…

  18. Suggestions, Resources and Activities for Teaching about Japan.

    ERIC Educational Resources Information Center

    Thomas, Paul F.

    This teacher resource packet contains a total of 28 modules for teaching about Japan at the elementary and secondary level. Activities on the Japanese family appropriate for grade 1 focus on similarities and differences, family size, family needs, and family roles. Grade 2 lessons look at the school, neighborhood, roles of children in the…

  19. Low genetic diversity and strong but shallow population differentiation suggests genetic homogenization by metapopulation dynamics in a social spider.

    PubMed

    Settepani, V; Bechsgaard, J; Bilde, T

    2014-12-01

    Mating systems and population dynamics influence genetic diversity and structure. Species that experience inbreeding and limited gene flow are expected to evolve isolated, divergent genetic lineages. Metapopulation dynamics with frequent extinctions and colonizations may, on the other hand, deplete and homogenize genetic variation, if extinction rate is sufficiently high compared to the effect of drift in local demes. We investigated these theoretical predictions empirically in social spiders that are highly inbred. Social spiders show intranest mating, female-biased sex ratio, and frequent extinction and colonization events, factors that deplete genetic diversity within nests and populations and limit gene flow. We characterized population genetic structure in Stegodyphus sarasinorum, a social spider distributed across the Indian subcontinent. Species-wide genetic diversity was estimated over approximately 2800 km from Sri Lanka to Himalayas, by sequencing 16 protein-coding nuclear loci. We found 13 SNPs in 6592 bp (π = 0.00045) indicating low species-wide nucleotide diversity. Three genetic lineages were strongly differentiated; however, only one fixed difference among them suggests recent divergence. This is consistent with a scenario of metapopulation dynamics that homogenizes genetic diversity across the species' range. Ultimately, low standing genetic variation may hamper a species' ability to track environmental change and render social inbreeding spiders 'evolutionary dead-ends'. PMID:25348843

  20. Is Peroxiredoxin II's peroxidase activity strongly inhibited in human erythrocytes?

    PubMed

    Benfeitas, Rui; Selvaggio, Gianluca; Antunes, Fernando; Coelho, Pedro; Salvador, Armindo

    2014-10-01

    H2O2 elimination in human erythrocytes is mainly carried out by catalase (Cat), glutathione peroxidase (GPx1) and the more recently discovered peroxiredoxin 2 (Prx2). However, the contribution of Prx2 to H2O2 consumption is still unclear. Prx2's high reactivity with H2O2 (kPrx2=10×10(7) M(-1)s(-1), kCat =7×10(7) M(-1)s(-1), kGPx1 =4×10(7) M(-1)s(-1)) and high abundance ([Prx2]= 570µM, [Cat]= 32µM, [GPx1]= 1µM) suggest that under low H2O2 supply rates it should consume >99% of the H2O2. However, extensive evidence indicates that in intact erythrocytes Prx2 contributes no more than Cat to H2O2 consumption. In order for this to be attained, Prx2's effective rate constant with H2O2would have to be just ~10(5) M(-1)s(-1), much lower than that determined in multiple experiments with the purified proteins. Nevertheless, nearly all Prx2 is oxidized within 1min of exposing erythrocytes to a H2O2 bolus, which is inconsistent with an irreversible inhibition. A mathematical model of the H2O2 metabolism in human erythrocytes [Benfeitas et al. (2014) Free Radic. Biol. Med.] where Prx2 either has a low kPrx2 or is subject to a strong (>99%) but readily reversible inhibition achieves quantitative agreement with detailed experimental observations of the responses of the redox status of Prx2 in human erythrocytes and suggests functional advantages of this design (see companion abstract). By contrast, a variant where Prx2 is fully active with kPrx2=10(8) M(-1)s(-1) shows important qualitative discrepancies. Altogether, these results suggest that Prx2's peroxidase activity is strongly inhibited in human erythrocytes. We acknowledge fellowship SFRH/BD/51199/2010, grants PEst-C/SAU/LA0001/2013-2014, PEst-OE/QUI/UI0612/2013, PEst-OE/QUI/UI0313/2014, and FCOMP-01-0124-FEDER-020978 (PTDC/QUI-BIQ/119657/2010) co-financed by FEDER through the COMPETE program and by FCT. PMID:26461310

  1. Suggested improvements to the standard filter paper assay used to measure cellulase activity.

    PubMed

    Coward-Kelly, Guillermo; Aiello-Mazzari, Cateryna; Kim, Sehoon; Granda, Cesar; Holtzapple, Mark

    2003-06-20

    Two suggestions can be found in the literature to improve the reproducibility of the Mandels' filter paper assay: add supplemental cellobiase and increase the boiling time for color development. Here we provide data that strongly supports adding supplemental cellobiase. Adding supplemental cellobiase increased assay response by 56%. Cellulases from different sources have different cellobiase activities, which would cause significant variation in the assay response. There is no need for additional boiling time-5 minutes is sufficient. For maximum reproducibility, it is essential that the water bath vigorously boil so that temperature excursions are minimized. PMID:12673775

  2. Acceleration of Nucelophilic CH Activation by Strongly Basic Solvents

    SciTech Connect

    Hashiguchi, Brian G; Young, Kenneth J. H.; Yousufuddin, Muhammed; Goddard, William A; Periana, Roy A

    2010-09-15

    (IPI)Ru(II)(OH){sub n}(H{sub 2}O){sub m}, 2, where IPI is the NNN-pincer ligand, 2,6-diimidizoylpyridine, is shown to catalyze H/D exchange between hydrocarbons and strongly basic solvents at higher rates than in the case of the solvent alone. Significantly, catalysis by 2 is accelerated rather than inhibited by increasing solvent basicity. The evidence is consistent with the reaction proceeding by base modulated nucleophilic CH activation.

  3. Manual of Suggested Activities for the Development of Sound Localization Skills.

    ERIC Educational Resources Information Center

    Brothers, Roy J.; Huff, Roger A.

    The manual is intended to provide teachers of young blind children with activities to develop sound localization skills. Both group and individual activities are suggested for the following four categories: activities in which both child and sound are stationary, activities in which the child is stationary but the sound is moving, activities in…

  4. ISS Plasma Contactor Units Operations During Strong Geomagnetic Activity

    NASA Astrophysics Data System (ADS)

    Alred, J.; Mikatarian, R.; Barsamian, H.; Minow, J.; Koontz, S.

    2003-12-01

    The large structure and high voltage arrays of the ISS represent a complex system that interacts with the Earth's ionosphere. To mitigate spacecraft charging problems on the ISS, two Plasma Contactor Units discharge ionized xenon gas to "clamp" the potential of the ISS with respect to the low Earth orbit plasma. The Plasma Interaction Model, a model of ISS plasma interaction developed from the basic physics of the interaction phenomena, includes magnetic induction effects, plasma temperature and density effects, interaction of the high voltage solar arrays with ionospheric plasma, and accounts for other conductive areas on the ISS. To augment this model, the PCU discharge current has been monitored for the ISS in a variety of flight attitudes as well as during the annual seasons. A review of the PCU discharge currents shows a correlation to the geomagnetic activity. The variation in the PCU discharge current during strong geomagnetic activity will be presented. Also, the PCU discharge currents during periods of low geomagnetic activity will be discussed. The presentation will conclude with a comparison of satellite plasma measurements during different stages of geomagnetic activity.

  5. Strongly Accelerated Margination of Active Particles in Blood Flow.

    PubMed

    Gekle, Stephan

    2016-01-19

    Synthetic nanoparticles and other stiff objects injected into a blood vessel filled with red blood cells are known to marginate toward the vessel walls. By means of hydrodynamic lattice-Boltzmann simulations, we show that active particles can strongly accelerate their margination by moving against the flow direction: particles located initially in the channel center migrate much faster to their final position near the wall than in the nonactive case. We explain our findings by an enhanced rate of collisions between the stiff particles and the deformable red blood cells. Our results imply that a significantly faster margination can be achieved either technically by the application of an external magnetic field (if the particles are magnetic) or biologically by self-propulsion (if the particles are, e.g., swimming bacteria). PMID:26789773

  6. A novel nucleic acid analogue shows strong angiogenic activity

    SciTech Connect

    Tsukamoto, Ikuko; Sakakibara, Norikazu; Maruyama, Tokumi; Igarashi, Junsuke; Kosaka, Hiroaki; Kubota, Yasuo; Tokuda, Masaaki; Ashino, Hiromi; Hattori, Kenichi; Tanaka, Shinji; Kawata, Mitsuhiro; Konishi, Ryoji

    2010-09-03

    Research highlights: {yields} A novel nucleic acid analogue (2Cl-C.OXT-A, m.w. 284) showed angiogenic potency. {yields} It stimulated the tube formation, proliferation and migration of HUVEC in vitro. {yields} 2Cl-C.OXT-A induced the activation of ERK1/2 and MEK in HUVEC. {yields} Angiogenic potency in vivo was confirmed in CAM assay and rabbit cornea assay. {yields} A synthesized small angiogenic agent would have great clinical therapeutic value. -- Abstract: A novel nucleic acid analogue (2Cl-C.OXT-A) significantly stimulated tube formation of human umbilical endothelial cells (HUVEC). Its maximum potency at 100 {mu}M was stronger than that of vascular endothelial growth factor (VEGF), a positive control. At this concentration, 2Cl-C.OXT-A moderately stimulated proliferation as well as migration of HUVEC. To gain mechanistic insights how 2Cl-C.OXT-A promotes angiogenic responses in HUVEC, we performed immunoblot analyses using phospho-specific antibodies as probes. 2Cl-C.OXT-A induced robust phosphorylation/activation of MAP kinase ERK1/2 and an upstream MAP kinase kinase MEK. Conversely, a MEK inhibitor PD98059 abolished ERK1/2 activation and tube formation both enhanced by 2Cl-C.OXT-A. In contrast, MAP kinase responses elicited by 2Cl-C.OXT-A were not inhibited by SU5416, a specific inhibitor of VEGF receptor tyrosine kinase. Collectively these results suggest that 2Cl-C.OXT-A-induces angiogenic responses in HUVEC mediated by a MAP kinase cascade comprising MEK and ERK1/2, but independently of VEGF receptor tyrosine kinase. In vivo assay using chicken chorioallantoic membrane (CAM) and rabbit cornea also suggested the angiogenic potency of 2Cl-C.OXT-A.

  7. Silver nanoparticles synthesised using plant extracts show strong antibacterial activity.

    PubMed

    Kumari, Avnesh; Guliani, Anika; Singla, Rubbel; Yadav, Ramdhan; Yadav, Sudesh Kumar

    2015-06-01

    In this study, three plants Populus alba, Hibiscus arboreus and Lantana camara were explored for the synthesis of silver nanoparticles (SNPs). The effect of reaction temperature and leaf extract (LE) concentration of P. alba, H. arboreus and L. camara was evaluated on the synthesis and size of SNPs. The SNPs were characterised by ultra-violet-visible spectroscopy, scanning electron microscopy and atomic force microscopy. The synthesis rate of SNPs was highest with LE of L. camara followed by H. arboreus and P. alba under similar conditions. L. camara LE showed maximum potential of smaller size SNPs synthesis, whereas bigger particles were formed by H. arboreous LE. The size and shape of L. camara LE synthesised SNPs were analysed by transmission electron microscopy (TEM) and energy dispersive X-ray spectroscopy (EDX). TEM analysis revealed the formation of SNPs of average size 17±9.5 nm with 5% LE of L. camara. The SNPs synthesised by LE of L. camara showed strong antibacterial activity against Escherichia coli. The results document that desired size SNPs can be synthesised using these plant LEs at a particular temperature for applications in the biomedical field. PMID:26023158

  8. High physical activity in young children suggests positive effects by altering autoantigen-induced immune activity.

    PubMed

    Carlsson, E; Ludvigsson, J; Huus, K; Faresjö, M

    2016-04-01

    Physical activity in children is associated with several positive health outcomes such as decreased cardiovascular risk factors, improved lung function, enhanced motor skill development, healthier body composition, and also improved defense against inflammatory diseases. We examined how high physical activity vs a sedentary lifestyle in young children influences the immune response with focus on autoimmunity. Peripheral blood mononuclear cells, collected from 55 5-year-old children with either high physical activity (n = 14), average physical activity (n = 27), or low physical activity (n = 14), from the All Babies In Southeast Sweden (ABIS) cohort, were stimulated with antigens (tetanus toxoid and beta-lactoglobulin) and autoantigens (GAD65 , insulin, HSP60, and IA-2). Immune markers (cytokines and chemokines), C-peptide and proinsulin were analyzed. Children with high physical activity showed decreased immune activity toward the autoantigens GAD65 (IL-5, P < 0.05), HSP60 and IA-2 (IL-10, P < 0.05) and also low spontaneous pro-inflammatory immune activity (IL-6, IL-13, IFN-γ, TNF-α, and CCL2 (P < 0.05)) compared with children with an average or low physical activity. High physical activity in young children seems to have positive effects on the immune system by altering autoantigen-induced immune activity. PMID:25892449

  9. Acquisition of Mathematical Language: Suggestions and Activities for English Language Learners

    ERIC Educational Resources Information Center

    Cirillo, Michelle; Bruna, Katherine Richardson; Herbel-Eisenmann, Beth

    2010-01-01

    In this article, we describe aspects of mathematical language that could be problematic to English-language learners, provide recommendations for teaching English-language learners, and suggest activities intended to foster language development in mathematics. (Contains 1 figure.)

  10. Exome Sequencing Followed by Large-Scale Genotyping Suggests a Limited Role for Moderately Rare Risk Factors of Strong Effect in Schizophrenia

    PubMed Central

    Need, Anna C.; McEvoy, Joseph P.; Gennarelli, Massimo; Heinzen, Erin L.; Ge, Dongliang; Maia, Jessica M.; Shianna, Kevin V.; He, Min; Cirulli, Elizabeth T.; Gumbs, Curtis E.; Zhao, Qian; Campbell, C. Ryan; Hong, Linda; Rosenquist, Peter; Putkonen, Anu; Hallikainen, Tero; Repo-Tiihonen, Eila; Tiihonen, Jari; Levy, Deborah L.; Meltzer, Herbert Y.; Goldstein, David B.

    2012-01-01

    Schizophrenia is a severe psychiatric disorder with strong heritability and marked heterogeneity in symptoms, course, and treatment response. There is strong interest in identifying genetic risk factors that can help to elucidate the pathophysiology and that might result in the development of improved treatments. Linkage and genome-wide association studies (GWASs) suggest that the genetic basis of schizophrenia is heterogeneous. However, it remains unclear whether the underlying genetic variants are mostly moderately rare and can be identified by the genotyping of variants observed in sequenced cases in large follow-up cohorts or whether they will typically be much rarer and therefore more effectively identified by gene-based methods that seek to combine candidate variants. Here, we consider 166 persons who have schizophrenia or schizoaffective disorder and who have had either their genomes or their exomes sequenced to high coverage. From these data, we selected 5,155 variants that were further evaluated in an independent cohort of 2,617 cases and 1,800 controls. No single variant showed a study-wide significant association in the initial or follow-up cohorts. However, we identified a number of case-specific variants, some of which might be real risk factors for schizophrenia, and these can be readily interrogated in other data sets. Our results indicate that schizophrenia risk is unlikely to be predominantly influenced by variants just outside the range detectable by GWASs. Rather, multiple rarer genetic variants must contribute substantially to the predisposition to schizophrenia, suggesting that both very large sample sizes and gene-based association tests will be required for securely identifying genetic risk factors. PMID:22863191

  11. Suggestions for Designing Learning Activity Packets, Instructional Systems, and Other Self Instructional Strategies.

    ERIC Educational Resources Information Center

    Midgley, Thomas Keith

    These guidelines for writing a learning activity packet (LAP) include a rationale for self instruction; suggested format for writing a LAP; analysis of the LAP format item by item; general instructions for writing a LAP; examples of performance objectives; affective domain attitudinal objectives; and student/teacher contracts for learning;…

  12. Tractography Activation Patterns in Dorsolateral Prefrontal Cortex Suggest Better Clinical Responses in OCD DBS

    PubMed Central

    Hartmann, Christian J.; Lujan, J. Luis; Chaturvedi, Ashutosh; Goodman, Wayne K.; Okun, Michael S.; McIntyre, Cameron C.; Haq, Ihtsham U.

    2016-01-01

    Background: Medication resistant obsessive-compulsive disorder (OCD) patients can be successfully treated with Deep Brain Stimulation (DBS) which targets the anterior limb of the internal capsule (ALIC) and the nucleus accumbens (NA). Growing evidence suggests that in patients who respond to DBS, axonal fiber bundles surrounding the electrode are activated, but it is currently unknown which discrete pathways are critical for optimal benefit. Our aim was to identify axonal pathways mediating clinical effects of ALIC-NA DBS. Methods: We created computational models of ALIC-NA DBS to simulate the activation of fiber tracts and to identify connected cerebral regions. The pattern of activated axons and their cortical targets was investigated in six OCD patients who underwent ALIC-NA DBS. Results: Modulation of the right anterior middle frontal gyrus (dorsolateral prefrontal cortex) was associated with an excellent response. In contrast, non-responders showed high activation in the orbital part of the right inferior frontal gyrus (lateral orbitofrontal cortex/anterior ventrolateral prefrontal cortex). Factor analysis followed by step-wise linear regression indicated that YBOCS improvement was inversely associated with factors that were predominantly determined by gray matter activation results. Discussion: Our findings support the hypothesis that optimal therapeutic results are associated with the activation of distinct fiber pathways. This suggests that in DBS for OCD, focused stimulation of specific fiber pathways, which would allow for stimulation with lower amplitudes, may be superior to activation of a wide array of pathways, typically associated with higher stimulation amplitudes. PMID:26834544

  13. The Changing Surface of Saturn's Titan: Cassini Observations Suggest Active Cryovolcanism

    NASA Astrophysics Data System (ADS)

    Nelson, R. M.

    2008-12-01

    conclude that the VIMS instrument has found two instances in which selected regions on Titan's surface became unusually reflective and remained reflective on time scales of days to months. In both cases the area of reflectance variability is large (~100000 sq km), larger than either Loki or the Big Island of Hawaii. This is a strong evidence for currently active surface processes on Titan. Pre-Cassini, Titan was thought of as a pre-biotic earth that was frozen in time. Cassini VIMS and SAR observations combined suggest that Titan is the present day is not frozen solid, and is instead an episodically changing or evolving world. References: [1] Nelson R. M. et al, LPSC 2007 , Europlanets 2007, AGU 2007, EGU 2008, Accepted in Icarus 2008. [2] Lopes et al (this meeting), Stofan et al. Icarus 185, 443-456, 2007. Lopes et al. Icarus 186, 395- 412, 2007. Kirk et al., DPS 2007. Acknowledgement: This work done at JPL under contract with NASA

  14. The Activation of Free Dipeptides Promoted by Strong Activating Agents in Water Does not Yield Diketopiperazines

    NASA Astrophysics Data System (ADS)

    Beaufils, Damien; Jepaul, Sandra; Liu, Ziwei; Boiteau, Laurent; Pascal, Robert

    2016-03-01

    The activation of dipeptides was studied in the perspective of the abiotic formation of oligopeptides of significant length as a requirement for secondary structure formation. The formation of piperazin-2,5-diones (DKP), previously considered as a dead end when activating free dipeptides, was shown in this work to be efficiently suppressed when using strong activating agents (e.g., carbodiimides). This behaviour was explained by the fast formation of a 5(4 H)-oxazolone intermediate at a rate that exceeds the time scale of the rotation of the peptide bond from the predominant trans-conformation into the cis-isomer required for DKP formation. No DKP was observed when using strong activating agents whereas phosphate mixed anhydrides or moderately activated esters were observed to predominantly yield DKP. The DKP side-reaction no longer constitutes a drawback for the C-terminus elongation of peptides. These results are considered as additional evidence that pathways involving strong activation are required to drive the emergence of living entities rather than close to equilibrium processes.

  15. Familial clustering strongly suggests that the phenotypic variation of the 8344 A>G lys mitochondrial tRNA mutation is encoded in cis.

    PubMed

    Kazakos, Kyriakos; Kotsa, Kalliopi; Yavropoulou, Maria; Dionyssopoulos, Alexander; Grabs, Rosemary; Yovos, John; Polychronakos, Constantin

    2012-07-01

    The maternally inherited 8344 A>G mutation in the mitochondrial Lys tRNA is classically associated with the myoclonic epilepsy, ragged-red muscle fiber (MERRF) syndrome. Multiple lipomatosis (Madelung's disease) is occasionally described. Here we report a large kindred with a statistically significant clustering of very unusual clinical manifestations. We have studied a Greek family that includes seven symptomatic cases of 8344 A>G. Clinical features, glucose tolerance and heteroplasmy in fat, muscle and blood were analyzed. The patients, aged 34-76 at the time of assessment, all suffer from progressive proximal limb-girdle myopathy and extensive lipomatosis. Four of the seven have either impaired glucose tolerance or diabetes but none has had epilepsy, a cardinal feature of MERRF. Heteroplasmy was not higher in adipose tissue than that found in the literature. Compared to literature reports, the familial clustering of this unusual combination of manifestations (lipomatosis in all, epilepsy in none) is statistically significant. The clustering of unusual manifestations in this large kindred strongly suggests that much of the phenotypic variability of 8344 A>G is determined by mitochondrially encoded modifiers in cis. PMID:22681518

  16. Aftershock activity of the 2015 Gorkha, Nepal, earthquake determined using the Kathmandu strong motion seismographic array

    NASA Astrophysics Data System (ADS)

    Ichiyanagi, Masayoshi; Takai, Nobuo; Shigefuji, Michiko; Bijukchhen, Subeg; Sasatani, Tsutomu; Rajaure, Sudhir; Dhital, Megh Raj; Takahashi, Hiroaki

    2016-02-01

    The characteristics of aftershock activity of the 2015 Gorkha, Nepal, earthquake (Mw 7.8) were evaluated. The mainshock and aftershocks were recorded continuously by the international Kathmandu strong motion seismographic array operated by Hokkaido University and Tribhuvan University. Full waveform data without saturation for all events enabled us to clarify aftershock locations and decay characteristics. The aftershock distribution was determined using the estimated local velocity structure. The hypocenter distribution in the Kathmandu metropolitan region was well determined and indicated earthquakes located shallower than 12 km depth, suggesting that aftershocks occurred at depths shallower than the Himalayan main thrust fault. Although numerical investigation suggested less resolution for the depth component, the regional aftershock epicentral distribution of the entire focal region clearly indicated earthquakes concentrated in the eastern margin of the major slip region of the mainshock. The calculated modified Omori law's p value of 1.35 suggests rapid aftershock decay and a possible high temperature structure in the aftershock region.

  17. Metabolic brain activity suggestive of persistent pain in a rat model of neuropathic pain

    PubMed Central

    Thompson, Scott J; Millecamps, Magali; Aliaga, Antonio; Seminowicz, David A; Low, Lucie A; Bedell, Barry J; Stone, Laura S; Schweinhardt, Petra; Bushnell, M Catherine

    2014-01-01

    Persistent pain is a central characteristic of neuropathic pain conditions in humans. Knowing whether rodent models of neuropathic pain produce persistent pain is therefore crucial to their translational applicability. We investigated the Spared Nerve Injury (SNI) model of neuropathic pain and the formalin pain model in rats using Positron Emission Tomography (PET) with the metabolic tracer [18F]fluorodeoxyglucose (FDG) to determine if there is ongoing brain activity suggestive of persistent pain. For the formalin model, under brief anesthesia we injected one hindpaw with 5% formalin and the FDG tracer into a tail vein. We then allowed the animals to awaken and observed pain behavior for 30 min during the FDG uptake period. The rat was then anesthetized and placed in the scanner for static image acquisition, which took place between minutes 45 and 75 post-tracer injection. A single reference rat brain magnetic resonance image (MRI) was used to align the PET images with the Paxinos and Watson rat brain atlas. Increased glucose metabolism was observed in the somatosensory region associated with the injection site (S1 hindlimb contralateral), S1 jaw/upper lip and cingulate cortex. Decreases were observed in the prelimbic cortex and hippocampus. Second, SNI rats were scanned 3 weeks post-surgery using the same scanning paradigm, and region-of-interest analyses revealed increased metabolic activity in the contralateral S1 hindlimb. Finally, a second cohort of SNI rats were scanned while anesthetized during the tracer uptake period, and the S1 hindlimb increase was not observed. Increased brain activity in the somatosensory cortex of SNI rats resembled the activity produced with the injection of formalin, suggesting that the SNI model may produce persistent pain. The lack of increased activity in S1 hindlimb with general anesthetic demonstrates that this effect can be blocked, as well as highlights the importance of investigating brain activity in awake and behaving

  18. Spatial Structure of Seagrass Suggests That Size-Dependent Plant Traits Have a Strong Influence on the Distribution and Maintenance of Tropical Multispecies Meadows

    PubMed Central

    Ooi, Jillian L. S.; Van Niel, Kimberly P.; Kendrick, Gary A.; Holmes, Karen W.

    2014-01-01

    Background Seagrass species in the tropics occur in multispecies meadows. How these meadows are maintained through species co-existence and what their ecological drivers may be has been an overarching question in seagrass biogeography. In this study, we quantify the spatial structure of four co-existing species and infer potential ecological processes from these structures. Methods and Results Species presence/absence data were collected using underwater towed and dropped video cameras in Pulau Tinggi, Malaysia. The geostatistical method, utilizing semivariograms, was used to describe the spatial structure of Halophila spp, Halodule uninervis, Syringodium isoetifolium and Cymodocea serrulata. Species had spatial patterns that were oriented in the along-shore and across-shore directions, nested with larger species in meadow interiors, and consisted of multiple structures that indicate the influence of 2–3 underlying processes. The Linear Model of Coregionalization (LMC) was used to estimate the amount of variance contributing to the presence of a species at specific spatial scales. These distances were <2.5 m (micro-scale), 2.5–50 m (fine-scale) and >50 m (broad-scale) in the along-shore; and <2.5 m (micro-scale), 2.5–140 m (fine-scale) and >140 m (broad-scale) in the across-shore. The LMC suggests that smaller species (Halophila spp and H. uninervis) were most influenced by broad-scale processes such as hydrodynamics and water depth whereas large, localised species (S. isoetifolium and C. serrulata) were more influenced by finer-scale processes such as sediment burial, seagrass colonization and growth, and physical disturbance. Conclusion In this study, we provide evidence that spatial structure is distinct even when species occur in well-mixed multispecies meadows, and we suggest that size-dependent plant traits have a strong influence on the distribution and maintenance of tropical marine plant communities. This study offers a contrast from previous spatial

  19. Computational Investigations of Trichoderma Reesei Cel7A Suggest New Routes for Enzyme Activity Improvements

    SciTech Connect

    Beckham, G. T.; Payne, C. M.; Bu, L.; Taylor, C. B.; McCabe, C.; Chu, J. W.; Himmel, M. E.; Crowley, M. F.

    2012-01-01

    The Trichoderma reesei Family 7 cellulase (Cel7A) is a key industrial enzyme in the production of biofuels from lignocellulosic biomass. It is a multi-modular enzyme with a Family 1 carbohydrate-binding module, a flexible O-glycosylated linker, and a large catalytic domain. We have used simulation to elucidate new functions for the 3 sub-domains, which suggests new routes to increase the activity of this central enzyme. These findings include new roles for glycosylation, which we have shown can be used to tune the binding affinity. We have also examined the structures of the catalytically-active complex of Cel7A and its non-processive counterpart, Cel7B, engaged on cellulose, which suggests allosteric mechanisms involved in chain binding when these cellulases are complexed on cellulose. Our computational results also suggest that product inhibition varies significantly between Cel7A and Cel7B, and we offer a molecular-level explanation for this observation. Finally, we discuss simulations of the absolute and relative binding free energy of cellulose ligands and various mutations along the CD tunnel, which will affect processivity and the ability of Cel7A (and related enzymes) to digest cellulose. These results highlight new considerations in protein engineering for processive and non-processive cellulases for production of lignocellulosic biofuels.

  20. The structure of the PERK kinase domain suggests the mechanism for its activation

    SciTech Connect

    Cui, Wenjun; Li, Jingzhi; Ron, David; Sha, Bingdong

    2011-05-01

    The endoplasmic reticulum-localized transmembrane kinase PERK is one of three major ER stress transducers. The crystal structure of PERK’s kinase domain has been determined to 2.8 Å resolution. The endoplasmic reticulum (ER) unfolded protein response (UPR) is comprised of several intracellular signaling pathways that alleviate ER stress. The ER-localized transmembrane kinase PERK is one of three major ER stress transducers. Oligomerization of PERK’s N-terminal ER luminal domain by ER stress promotes PERK trans-autophosphorylation of the C-terminal cytoplasmic kinase domain at multiple residues including Thr980 on the kinase activation loop. Activated PERK phosphorylates Ser51 of the α-subunit of translation initiation factor 2 (eIF2α), which inhibits initiation of protein synthesis and reduces the load of unfolded proteins entering the ER. The crystal structure of PERK’s kinase domain has been determined to 2.8 Å resolution. The structure resembles the back-to-back dimer observed in the related eIF2α kinase PKR. Phosphorylation of Thr980 stabilizes both the activation loop and helix αG in the C-terminal lobe, preparing the latter for eIF2α binding. The structure suggests conservation in the mode of activation of eIF2α kinases and is consistent with a ‘line-up’ model for PERK activation triggered by oligomerization of its luminal domain.

  1. The structure of the PERK kinase domain suggests the mechanism for its activation

    SciTech Connect

    Cui, Wenjun; Li, Jingzhi; Ron, David; Sha, Bingdong

    2012-08-31

    The endoplasmic reticulum (ER) unfolded protein response (UPR) is comprised of several intracellular signaling pathways that alleviate ER stress. The ER-localized transmembrane kinase PERK is one of three major ER stress transducers. Oligomerization of PERK's N-terminal ER luminal domain by ER stress promotes PERK trans-autophosphorylation of the C-terminal cytoplasmic kinase domain at multiple residues including Thr980 on the kinase activation loop. Activated PERK phosphorylates Ser51 of the {alpha}-subunit of translation initiation factor 2 (eIF2{alpha}), which inhibits initiation of protein synthesis and reduces the load of unfolded proteins entering the ER. The crystal structure of PERK's kinase domain has been determined to 2.8 {angstrom} resolution. The structure resembles the back-to-back dimer observed in the related eIF2{alpha} kinase PKR. Phosphorylation of Thr980 stabilizes both the activation loop and helix {alpha}G in the C-terminal lobe, preparing the latter for eIF2{alpha} binding. The structure suggests conservation in the mode of activation of eIF2{alpha} kinases and is consistent with a 'line-up' model for PERK activation triggered by oligomerization of its luminal domain.

  2. The structure of the PERK kinase domain suggests the mechanism for its activation

    PubMed Central

    Cui, Wenjun; Li, Jingzhi; Ron, David; Sha, Bingdong

    2011-01-01

    The endoplasmic reticulum (ER) unfolded protein response (UPR) is comprised of several intracellular signaling pathways that alleviate ER stress. The ER-localized transmembrane kinase PERK is one of three major ER stress transducers. Oligomerization of PERK’s N-terminal ER luminal domain by ER stress promotes PERK trans-autophosphorylation of the C-terminal cytoplasmic kinase domain at multiple residues including Thr980 on the kinase activation loop. Activated PERK phosphorylates Ser51 of the α-subunit of translation initiation factor 2 (eIF2α), which inhibits initiation of protein synthesis and reduces the load of unfolded proteins entering the ER. The crystal structure of PERK’s kinase domain has been determined to 2.8 Å resolution. The structure resembles the back-to-back dimer observed in the related eIF2α kinase PKR. Phosphorylation of Thr980 stabilizes both the activation loop and helix αG in the C-terminal lobe, preparing the latter for eIF2α binding. The structure suggests conservation in the mode of activation of eIF2α kinases and is consistent with a ‘line-up’ model for PERK activation triggered by oligomerization of its luminal domain. PMID:21543844

  3. Individual differences in FFA activity suggest independent processing at different spatial scales.

    PubMed

    Gauthier, Isabel; Curby, Kim M; Skudlarski, Pawel; Epstein, Russell A

    2005-06-01

    The brain processes images at different spatial scales, but it is unclear how far into the visual stream different scales remain segregated. Using functional magnetic resonance imaging, we found evidence that BOLD activity in the fusiform face area (FFA) reflects computations based on separate spatial frequency inputs. When subjects perform different tasks (attend location vs. identity; attend whole vs. parts) or the same task with different stimuli (upright or inverted) with high- and low-pass images of cars and faces, individual differences in the FFA in one condition are correlated with those in the other condition. However, FFA activity in response to low-pass stimuli is independent of its response to high-pass stimuli. These results suggest that spatial scales are not integrated before the FFA and that processing in this area could support the flexible use of different sources of information present in broad-pass images. PMID:16180628

  4. Shipwreck rates and tree rings suggest reduced North Atlantic tropical cyclone activity during the Maunder Minimum.

    NASA Astrophysics Data System (ADS)

    Harley, G. L.; Trouet, V.; Dominguez Delmas, M.

    2014-12-01

    The observational record of North Atlantic TCs is too short to inform our understanding of decadal-scale climatic controls on TC regimes. We combined two new annual-resolution proxies of Atlantic storm activity to extend the observational TC record back to the 16th Century. A tree-growth suppression chronology (1707-2010 CE) from the Florida Keys, U.S.A. captures 91% of observed North Atlantic TCs (1850-2010 CE) and shares significant peak events with a documentary time series of Spanish shipwrecks in the Caribbean (1495-1820). Decadal-scale shipwreck rates were lowest during the Maunder Minimum (ca. 1645-1715), indicating that cooler Atlantic sea surface temperatures (SSTs) during this period reduced Caribbean TC activity. Our results support global-scale climate proxy data and suggest that cooler tropical Atlantic SSTs and a generally negative mode of the North Atlantic Oscillation during the Little Ice Age reduced TC frequency.

  5. Fractal analysis reveals subclasses of neurons and suggests an explanation of their spontaneous activity.

    PubMed

    Favela, Luis H; Coey, Charles A; Griff, Edwin R; Richardson, Michael J

    2016-07-28

    The present work used fractal time series analysis (detrended fluctuation analysis; DFA) to examine the spontaneous activity of single neurons in an anesthetized animal model, specifically, the mitral cells in the rat main olfactory bulb. DFA bolstered previous research in suggesting two subclasses of mitral cells. Although there was no difference in the fractal scaling of the interspike interval series at the shorter timescales, there was a significant difference at longer timescales. Neurons in Group B exhibited fractal, power-law scaled interspike intervals, whereas neurons in Group A exhibited random variation. These results raise questions about the role of these different cells within the olfactory bulb and potential explanations of their dynamics. Specifically, self-organized criticality has been proposed as an explanation of fractal scaling in many natural systems, including neural systems. However, this theory is based on certain assumptions that do not clearly hold in the case of spontaneous neural activity, which likely reflects intrinsic cell dynamics rather than activity driven by external stimulation. Moreover, it is unclear how self-organized criticality might account for the random dynamics observed in Group A, and how these random dynamics might serve some functional role when embedded in the typical activity of the olfactory bulb. These theoretical considerations provide direction for additional experimental work. PMID:27189719

  6. Antifungal activity in thrips soldiers suggests a dual role for this caste.

    PubMed

    Turnbull, Christine; Caravan, Holly; Chapman, Thomas; Nipperess, David; Dennison, Siobhan; Schwarz, Michael; Beattie, Andrew

    2012-08-23

    The social insect soldier is perhaps the most widely known caste, because it often exhibits spectacular weapons, such as highly enlarged jaws or reinforced appendages, which are used to defend the colony against enemies ranging in size from wasps to anteaters. We examined the function of the enlarged forelimbs of soldiers (both male and female) of the eusocial, gall-inhabiting insect Kladothrips intermedius, and discovered that they have little impact on their ability to repel the specialized invading thrips Koptothrips species. While the efficacy of the enlarged forelimb appears equivocal, we show that soldiers secrete strong antifungal compounds capable of controlling the specialized insect fungal pathogen, Cordyceps bassiana. Our data suggest that these thrips soldiers have evolved in response to selection by both macro- and micro-organisms. While it is unknown whether specialized fungal pathogens have been major selective agents in the evolution of the soldier caste in general, they were probably present when sociality first evolved and may have been the primordial enemies of social insects. PMID:22496077

  7. An active loudness model suggesting tinnitus as increased central noise and hyperacusis as increased nonlinear gain

    PubMed Central

    Zeng, Fan-Gang

    2012-01-01

    The present study uses a systems engineering approach to delineate the relationship between tinnitus and hyperacusis as a result of either hearing loss in the ear or an imbalanced state in the brain. Specifically examined is the input–output function, or loudness growth as a function of intensity in both normal and pathological conditions. Tinnitus reduces the output dynamic range by raising the floor, while hyperacusis reduces the input dynamic range by lowering the ceiling or sound tolerance level. Tinnitus does not necessarily steepen the loudness growth function but hyperacusis always does. An active loudness model that consists of an expansion stage following a compression stage can account for these key properties in tinnitus and hyperacusis loudness functions. The active loudness model suggests that tinnitus is a result of increased central noise, while hyperacusis is due to increased nonlinear gain. The active loudness model also generates specific predictions on loudness growth in tinnitus, hyperacusis, hearing loss or any combinations of the three conditions. These predictions need to be verified by experimental data and have explicit implications for treatment of tinnitus and hyperacusis. PMID:22641191

  8. Modelling and analysis of bacterial tracks suggest an active reorientation mechanism in Rhodobacter sphaeroides

    PubMed Central

    Rosser, Gabriel; Baker, Ruth E.; Armitage, Judith P.; Fletcher, Alexander G.

    2014-01-01

    Most free-swimming bacteria move in approximately straight lines, interspersed with random reorientation phases. A key open question concerns varying mechanisms by which reorientation occurs. We combine mathematical modelling with analysis of a large tracking dataset to study the poorly understood reorientation mechanism in the monoflagellate species Rhodobacter sphaeroides. The flagellum on this species rotates counterclockwise to propel the bacterium, periodically ceasing rotation to enable reorientation. When rotation restarts the cell body usually points in a new direction. It has been assumed that the new direction is simply the result of Brownian rotation. We consider three variants of a self-propelled particle model of bacterial motility. The first considers rotational diffusion only, corresponding to a non-chemotactic mutant strain. Two further models incorporate stochastic reorientations, describing ‘run-and-tumble’ motility. We derive expressions for key summary statistics and simulate each model using a stochastic computational algorithm. We also discuss the effect of cell geometry on rotational diffusion. Working with a previously published tracking dataset, we compare predictions of the models with data on individual stopping events in R. sphaeroides. This provides strong evidence that this species undergoes some form of active reorientation rather than simple reorientation by Brownian rotation. PMID:24872500

  9. McIntosh active-region class similarities and suggestions for mergers

    NASA Technical Reports Server (NTRS)

    Bornmann, P. L.; Kalmbach, D.; Kulhanek, D.

    1994-01-01

    McIntosh active-region classifications reported during a five-year period were examined to determine similarities among the classes. Two methods were used extensively to determine these similarities. The number of transitions among classes were used to determine the most frequent transitions out of each class, and the alternative classes reported for the same region by different sites were used to establish which classes were neighboring classes. These transition frequencies and neighboring classes were used to identify classes that could be eliminated or merged with other classes. Class similarities were used to investigate the relative importance of several pairs of decisions that occur within a single McIntosh parameter. In particular, the redundancy of parameters in some classes was examined, and the class similarities were used to identify which of these parameters could be eliminated. Infrequently reported classes were also considered, and suggestions for mergers were made when similarities between classes could be identified.

  10. The structures of the kinase domain and UBA domain of MPK38 suggest the activation mechanism for kinase activity.

    PubMed

    Cho, Yong-Soon; Yoo, Jiho; Park, Soomin; Cho, Hyun-Soo

    2014-02-01

    Murine protein serine/threonine kinase 38 (MPK38) is the murine orthologue of human maternal embryonic leucine-zipper kinase (MELK), which belongs to the SNF1/AMPK family. MELK is considered to be a promising drug target for anticancer therapy because overexpression and hyperactivation of MELK is correlated with several human cancers. Activation of MPK38 requires the extended sequence (ExS) containing the ubiquitin-associated (UBA) linker and UBA domain and phosphorylation of the activation loop. However, the activation mechanism of MPK38 is unknown. This paper reports the crystal structure of MPK38 (T167E), which mimics a phosphorylated state of the activation loop, in complex with AMP-PNP. In the MPK38 structure, the UBA linker forces an inward movement of the αC helix. Phosphorylation of the activation loop then induces movement of the activation loop towards the C-lobe and results in interlobar cleft closure. These processes generate a fully active state of MPK38. This structure suggests that MPK38 has a similar molecular mechanism regulating activation as in other kinases of the SNF1/AMPK family. PMID:24531485

  11. Three-dimensional Reconstruction of Tarantula Myosin Filaments Suggests How Phosphorylation May Regulate Myosin Activity

    PubMed Central

    Alamo, Lorenzo; Wriggers, Willy; Pinto, Antonio; Bártoli, Fulvia; Salazar, Leiría; Zhao, Fa-Qing; Craig, Roger; Padrón, Raúl

    2008-01-01

    Summary Muscle contraction involves the interaction of the myosin heads of the thick filaments with actin subunits of the thin filaments. Relaxation occurs when this interaction is blocked by molecular switches on these filaments. In many muscles, myosin-linked regulation involves phosphorylation of the myosin regulatory light chains (RLC). Electron microscopy of vertebrate smooth muscle myosin molecules (regulated by phosphorylation) has provided insight into the relaxed structure, revealing that myosin is switched off by intramolecular interactions between its two heads, the free-head and the blocked head. Three-dimensional reconstruction of frozen-hydrated specimens reveals that this asymmetric head interaction is also present in native thick filaments of tarantula striated muscle. Our goal here has been to elucidate the structural features of the tarantula filament involved in phosphorylation-based regulation. A new reconstruction reveals intra- and intermolecular myosin interactions in addition to those seen previously. To help interpret the interactions, we sequenced the tarantula RLC, and fitted to the reconstruction an atomic model of the myosin head that included the predicted RLC atomic structure and an S2 crystal structure. The fitting suggests an intramolecular interaction between the cardiomyopathy loop of the free-head and its own S2 and two intermolecular interactions—between the cardio-loop of the free head and the ELC of the blocked head, and between the Leu-305 - Gln-327 “interaction loop” (loop I) of the free-head and the N-terminal fragment of the RLC of the blocked-head. These interactions, added to those previously described, would help to switch off the thick filament. Molecular dynamics simulations suggest how phosphorylation could increase the helical content of the RLC N-terminus, weakening these interactions, thus releasing both heads and activating the thick filament. PMID:18951904

  12. Activation of HER3 Interferes with Antitumor Effects of Axl Receptor Tyrosine Kinase Inhibitors: Suggestion of Combination Therapy1

    PubMed Central

    Torka, Robert; Pénzes, Kinga; Gusenbauer, Simone; Baumann, Christine; Szabadkai, István; Őrfi, Lászlȯ; Kéri, György; Ullrich, Axel

    2014-01-01

    The Axl receptor tyrosine kinase (RTK) has been established as a strong candidate for targeted therapy of cancer. However, the benefits of targeted therapies are limited due to acquired resistance and activation of alternative RTKs. Therefore, we asked if cancer cells are able to overcome targeted Axl therapies. Here, we demonstrate that inhibition of Axl by short interfering RNA or the tyrosine kinase inhibitor (TKI) BMS777607 induces the expression of human epidermal growth factor receptor 3 (HER3) and the neuregulin 1(NRG1)–dependent phosphorylation of HER3 in MDA-MB231 and Ovcar8 cells. Moreover, analysis of 20 Axl-expressing cancer cell lines of different tissue origin indicates a low basal phosphorylation of RAC-α serine/threonine-protein kinase (AKT) as a general requirement for HER3 activation on Axl inhibition. Consequently, phosphorylation of AKT arises as an independent biomarker for Axl treatment. Additionally, we introduce phosphorylation of HER3 as an independent pharmacodynamic biomarker for monitoring of anti-Axl therapy response. Inhibition of cell viability by BMS777607 could be rescued by NRG1-dependent activation of HER3, suggesting an escape mechanism by tumor microenvironment. The Axl-TKI MPCD84111 simultaneously blocked Axl and HER2/3 signaling and thereby prohibited HER3 feedback activation. Furthermore, dual inhibition of Axl and HER2/3 using BMS777607 and lapatinib led to a significant inhibition of cell viability in Axl-expressing MDA-MB231 and Ovcar8 cells. Therefore, we conclude that, in patient cohorts with expression of Axl and low basal activity of AKT, a combined inhibition of Axl and HER2/3 kinase would be beneficial to overcome acquired resistance to Axl-targeted therapies. PMID:24862757

  13. Head movements suggest canal and otolith projections are activated during galvanic vestibular stimulation.

    PubMed

    Kim, J

    2013-12-01

    Three-dimensional changes in the angular orientation of the head were monitored during galvanic vestibular stimulation (GVS) delivered through electrodes implanted bilaterally in the tensor tympani muscle of the guinea-pig middle ear. Bilateral GVS was delivered by passing current between both ears with the anode situated in one ear and the cathode in the other ear. Unilateral GVS was also delivered between one ear and an indifferent electrode on the skull. Constant-current stimulation caused the head to tilt predominantly within the roll and yaw planes toward an ear stimulated with anodal current and away from an ear stimulated with cathodal current. No significant head tilt in the pitch plane was observed with either bilateral or unilateral GVS. Bilateral GVS was found to induce significantly greater roll head tilt (RHT) and yaw head tilt (YHT) than the same intensity of unilateral anodal or cathodal GVS, but not the sum of responses induced by the two polarities of unilateral GVS. Significant asymmetries were observed in the responses of YHT and RHT for unilateral anodal and cathodal GVS; unilateral cathodal stimulation generated greater head deviation compared with the same intensity of unilateral anodal stimulation. These asymmetric responses are consistent with activation of irregularly discharging afferents, which have been shown previously to exhibit asymmetric responses for anodal and cathodal GVS (Kim and Curthoys, 2004). Together with the observations of previous guinea-pig studies, the results suggest that head movements induced by GVS may be mediated by irregularly discharging afferents innervating the otoliths, and possibly the horizontal semicircular canals. PMID:24021920

  14. Suggested Activities on Sociological Health Problems: Drugs, Alcoholism, Smoking for Student Teachers.

    ERIC Educational Resources Information Center

    Samalonis, Bernice

    This is a list of recommendations for a neophyte teacher for discussions with students on drugs, alcoholism, and smoking. Included are suggested readings, suggested questions for the school's drug education coordinator, recommended readings, and New York sources of information. (Related document is SP 006 468.) (JA)

  15. Vv-AMP1, a ripening induced peptide from Vitis vinifera shows strong antifungal activity

    PubMed Central

    de Beer, Abré; Vivier, Melané A

    2008-01-01

    Background Latest research shows that small antimicrobial peptides play a role in the innate defense system of plants. These peptides typically contribute to preformed defense by developing protective barriers around germinating seeds or between different tissue layers within plant organs. The encoding genes could also be upregulated by abiotic and biotic stimuli during active defense processes. The peptides display a broad spectrum of antimicrobial activities. Their potent anti-pathogenic characteristics have ensured that they are promising targets in the medical and agricultural biotechnology sectors. Results A berry specific cDNA sequence designated Vv-AMP1, Vitis vinifera antimicrobial peptide 1, was isolated from Vitis vinifera. Vv-AMP1 encodes for a 77 amino acid peptide that shows sequence homology to the family of plant defensins. Vv-AMP1 is expressed in a tissue specific, developmentally regulated manner, being only expressed in berry tissue at the onset of berry ripening and onwards. Treatment of leaf and berry tissue with biotic or abiotic factors did not lead to increased expression of Vv-AMP1 under the conditions tested. The predicted signal peptide of Vv-AMP1, fused to the green fluorescent protein (GFP), showed that the signal peptide allowed accumulation of its product in the apoplast. Vv-AMP1 peptide, produced in Escherichia coli, had a molecular mass of 5.495 kDa as determined by mass spectrometry. Recombinant Vv-AMP1 was extremely heat-stable and showed strong antifungal activity against a broad spectrum of plant pathogenic fungi, with very high levels of activity against the wilting disease causing pathogens Fusarium oxysporum and Verticillium dahliae. The Vv-AMP1 peptide did not induce morphological changes on the treated fungal hyphae, but instead strongly inhibited hyphal elongation. A propidium iodide uptake assay suggested that the inhibitory activity of Vv-AMP1 might be associated with altering the membrane permeability of the fungal

  16. Towards Responsive Teaching and Learning of the "Odyssey": Suggested Lesson Plans and Activities.

    ERIC Educational Resources Information Center

    Seranis, Panos

    This booklet presents lesson plans and activities that were used in a study exploring the reader response patterns produced by Year 12 students from three different schools to the teaching of classical literature in translation. The emphasis is placed on their reading and reacting to the Homeric "Odyssey." Lesson plans and activities using reader…

  17. Adapting Physical Activities to Promote Overall Health and Development: Suggestions for Interventionists and Families

    ERIC Educational Resources Information Center

    Menear, Kristi Sayers; Davis, Laura

    2007-01-01

    Early movement successes for young children are related to performing activities of daily living without assistance or with minimum assistance, recreational opportunities, and overall health wellness, growth, and development. As children are provided with frequent opportunities to participate in everyday fun and engaging physical activities, they…

  18. Greater Intermanual Transfer in the Elderly Suggests Age-Related Bilateral Motor Cortex Activation Is Compensatory

    PubMed Central

    Graziadio, Sara; Nazarpour, Kianoush; Gretenkord, Sabine; Jackson, Andrew; Eyre, Janet A.

    2015-01-01

    ABSTRACT. Hemispheric lateralization of movement control diminishes with age; whether this is compensatory or maladaptive is debated. The authors hypothesized that if compensatory, bilateral activation would lead to greater intermanual transfer in older subjects learning tasks that activate the cortex unilaterally in young adults. They studied 10 young and 14 older subjects, learning a unimanual visuomotor task comprising a feedforward phase, where there is unilateral cortical activation in young adults, and a feedback phase, which activates the cortex bilaterally in both age groups. Increased intermanual transfer was demonstrated in older subjects during feedforward learning, with no difference between groups during feedback learning. This finding is consistent with bilateral cortical activation being compensatory to maintain performance despite declining computational efficiency in neural networks. PMID:25575222

  19. Genetic analysis of response regulator activation in bacterial chemotaxis suggests an intermolecular mechanism

    PubMed Central

    Re, Sandra Da; Tolstykh, Tatiana; Wolanin, Peter M.; Stock, Jeffry B.

    2002-01-01

    Response regulator proteins of two-component systems are usually activated by phosphorylation. The phosphorylated response regulator protein CheY∼P mediates the chemotaxis response in Escherichia coli. We performed random mutagenesis and selected CheY mutants that are constitutively active in the absence of phosphorylation. Although a single amino acid substitution can lead to constitutive activation, no single DNA base change can effect such a transition. Numerous different sets of mutations that activate in synergy were selected in several different combinations. These mutations were all located on the side of CheY defined by α4, β5, α5, and α1. Our findings argue against the two-state hypothesis for response regulator activation. We propose an alternative intermolecular mechanism that involves a dynamic interplay between response regulators and their effector targets. PMID:12381847

  20. Strong variable linear polarization in the cool active star II Peg

    NASA Astrophysics Data System (ADS)

    Rosén, Lisa; Kochukhov, Oleg; Wade, Gregg A.

    2014-08-01

    Magnetic fields of cool active stars are currently studied polarimetrically using only circular polarization observations. This provides limited information about the magnetic field geometry since circular polarization is only sensitive to the line-of-sight component of the magnetic field. Reconstructions of the magnetic field topology will therefore not be completely trustworthy when only circular polarization is used. On the other hand, linear polarization is sensitive to the transverse component of the magnetic field. By including linear polarization in the reconstruction the quality of the reconstructed magnetic map is dramatically improved. For that reason, we wanted to identify cool stars for which linear polarization could be detected at a level sufficient for magnetic imaging. Four active RS CVn binaries, II Peg, HR 1099, IM Peg, and σ Gem were observed with the ESPaDOnS spectropolarimeter at the Canada-France-Hawaii Telescope. Mean polarization profiles in all four Stokes parameters were derived using the multi-line technique of least-squares deconvolution (LSD). Not only was linear polarization successfully detected in all four stars in at least one observation, but also, II Peg showed an extraordinarily strong linear polarization signature throughout all observations. This qualifies II Peg as the first promising target for magnetic Doppler imaging in all four Stokes parameters and, at the same time, suggests that other such targets can possibly be identified.

  1. Emergent Literacy in Kindergarten: A Review of the Research and Related Suggested Activities and Learning Strategies.

    ERIC Educational Resources Information Center

    Robinson, Violet B.; Ross, Gretchen; Neal, Harriet C.

    Educators are placing increasing emphasis on developing literacy requirements for young children. This book reviews research on emergent literacy among preschool and kindergarten children and provides suggestions for kindergarten teachers to create instructional programs that enhance children's literacy learning and to avoid developmentally…

  2. Comment on Birgegard and Sohlberg's (1999) suggestions for research in subliminal psychodynamic activation.

    PubMed

    Fudin, R

    2000-06-01

    Methodological changes in subliminal psychodynamic activation experiments based on the assumption that multiletter messages can be encoded automatically (Birgegard & Sohlberg, 1999) are questioned. Their contention that partial experimental messages and appropriate nonsense anagram controls (Fudin, 1986) need not be presented in every experiment is supported, with a reservation. If the difference between responses to the complete message and its control is significant in the predicted direction, then Fudin's procedure should be used. A nonsignificant difference between the response to each partial message and its control is needed to support the assumption of proponents of subliminal psychodynamic activation that successful outcomes are effected by the encoding of the meaning of a complete message. Experiments in subliminal psychodynamic activation can be improved if their methodologies take into account variables that may operate when subliminal stimuli are presented and encoded. PMID:10883752

  3. Treasury Dept. Suggests Plan to Limit Colleges' Tax Exemption for Business Activities.

    ERIC Educational Resources Information Center

    Jaschik, Scott

    1987-01-01

    Revisions of federal tax law governing the business operations of nonprofit institutions would no longer define a business activity as "related" to the organization's primary mission, and thus tax exempt, solely because it is operated for the convenience of members or students. (MSE)

  4. Hazardous Waste Environmental Education Resource Kit for Manitoba Teachers: Suggested Activities K-12.

    ERIC Educational Resources Information Center

    Downey-Franchuk, Andrea J.

    Society has become increasingly aware of the harmful effects that the disposal of chemical waste products have on the environment and human health. Public information is central to the development of a responsible waste management plan. The activities contained in this guide are organized in sequence from kindergarten to grade 12, and provide…

  5. Cosmological Studies with Galaxy Clusters, Active Galactic Nuclei, and Strongly Lensed Quasars

    NASA Astrophysics Data System (ADS)

    Rumbaugh, Nicholas Andrew

    The large-scale structure (LSS) of the universe provides scientists with one of the best laboratories for studying Lambda Cold Dark Matter (LambdaCDM) cosmology. Especially at high redshift, we see increased rates of galaxy cluster and galaxy merging in LSS relative to the field, which is useful for studying the hierarchical merging predicted by LambdaCDM. The largest identified bound structures, superclusters, have not yet virialized. Despite the wide range of dynamical states of their constituent galaxies, groups, and clusters, they are all still actively evolving, providing an ideal laboratory in which to study cluster and galaxy evolution. In this dissertation, I present original research on several aspects of LSS and LambdaCDM cosmology. Three separate studies are included, each one focusing on a different aspect. In the first study, we use X-ray and optical observations from nine galaxy clusters at high redshift, some embedded in larger structures and some isolated, to study their evolutionary states. We extract X-ray gas temperatures and luminosities as well as optical velocity dispersions. These cluster properties are compared using low-redshift scaling relations. In addition, we employ several tests of substructure, using velocity histograms, Dressler-Shectman tests, and centroiding offsets. We conclude that two clusters out of our sample are most likely unrelaxed, and find support for deviations from self-similarity in the redshift evolution of the Lx-T relation. Our numerous complementary tests of the evolutionary state of clusters suggest potential under-estimations of systematic error in studies employing only a single such test. In the second study, we use multi-band imaging and spectroscopy to study active galactic nuclei (AGN) in high-redshift LSS. The AGN were identified using X-ray imaging and matched to optical catalogs that contained spectroscopic redshifts to identify members of the structures. AGN host galaxies tended to be associated with the

  6. Stochastic Fusion Simulations and Experiments Suggest Passive and Active Roles of Hemagglutinin during Membrane Fusion

    PubMed Central

    Lee, Donald W.; Thapar, Vikram; Clancy, Paulette; Daniel, Susan

    2014-01-01

    Influenza enters the host cell cytoplasm by fusing the viral and host membrane together. Fusion is mediated by hemagglutinin (HA) trimers that undergo conformational change when acidified in the endosome. It is currently debated how many HA trimers, w, and how many conformationally changed HA trimers, q, are minimally required for fusion. Conclusions vary because there are three common approaches for determining w and q from fusion data. One approach correlates the fusion rate with the fraction of fusogenic HA trimers and leads to the conclusion that one HA trimer is required for fusion. A second approach correlates the fusion rate with the total concentration of fusogenic HA trimers and indicates that more than one HA trimer is required. A third approach applies statistical models to fusion rate data obtained at a single HA density to establish w or q and suggests that more than one HA trimer is required. In this work, all three approaches are investigated through stochastic fusion simulations and experiments to elucidate the roles of HA and its ability to bend the target membrane during fusion. We find that the apparent discrepancies among the results from the various approaches may be resolved if nonfusogenic HA participates in fusion through interactions with a fusogenic HA. Our results, based on H3 and H1 serotypes, suggest that three adjacent HA trimers and one conformationally changed HA trimer are minimally required to induce membrane fusion (w = 3 and q = 1). PMID:24559987

  7. INCLINATION-DEPENDENT ACTIVE GALACTIC NUCLEUS FLUX PROFILES FROM STRONG LENSING OF THE KERR SPACETIME

    SciTech Connect

    Chen, Bin; Dai, Xinyu; Baron, E.

    2013-01-10

    Recent quasar microlensing observations have constrained the X-ray emission sizes of quasars to be about 10 gravitational radii, one order of magnitude smaller than the optical emission sizes. Using a new ray-tracing code for the Kerr spacetime, we find that the observed X-ray flux is strongly influenced by the gravity field of the central black hole, even for observers at moderate inclination angles. We calculate inclination-dependent flux profiles of active galactic nuclei in the optical and X-ray bands by combining the Kerr lensing and projection effects for future reference. We further study the dependence of the X-ray-to-optical flux ratio on the inclination angle caused by differential lensing distortion of the X-ray and optical emission, assuming several corona geometries. The strong lensing X-ray-to-optical magnification ratio can change by a factor of {approx}10 for normal quasars in some cases, and a further factor of {approx}10 for broad absorption line (BAL) quasars and obscured quasars. Comparing our results with the observed distributions in normal and BAL quasars, we find that the inclination angle dependence of the magnification ratios can significantly change the X-ray-to-optical flux ratio distributions. In particular, the mean value of the spectrum slope parameter {alpha}{sub ox}, 0.3838log F {sub 2keV}/F {sub 2500A}, can differ by {approx}0.1-0.2 between normal and BAL quasars, depending on corona geometries, suggesting larger intrinsic absorptions in BAL quasars.

  8. Structures of human Bruton's tyrosine kinase in active and inactive conformations suggest a mechanism of activation for TEC family kinases

    SciTech Connect

    Marcotte, Douglas J.; Liu, Yu-Ting; Arduini, Robert M.; Hession, Catherine A.; Miatkowski, Konrad; Wildes, Craig P.; Cullen, Patrick F.; Hong, Victor; Hopkins, Brian T.; Mertsching, Elisabeth; Jenkins, Tracy J.; Romanowski, Michael J.; Baker, Darren P.; Silvian, Laura F.

    2010-11-15

    Bruton's tyrosine kinase (BTK), a member of the TEC family of kinases, plays a crucial role in B-cell maturation and mast cell activation. Although the structures of the unphosphorylated mouse BTK kinase domain and the unphosphorylated and phosphorylated kinase domains of human ITK are known, understanding the kinase selectivity profiles of BTK inhibitors has been hampered by the lack of availability of a high resolution, ligand-bound BTK structure. Here, we report the crystal structures of the human BTK kinase domain bound to either Dasatinib (BMS-354825) at 1.9 {angstrom} resolution or to 4-amino-5-(4-phenoxyphenyl)-7H-pyrrolospyrimidin- 7-yl-cyclopentane at 1.6 {angstrom} resolution. This data provides information relevant to the development of small molecule inhibitors targeting BTK and the TEC family of nonreceptor tyrosine kinases. Analysis of the structural differences between the TEC and Src families of kinases near the Trp-Glu-Ile motif in the N-terminal region of the kinase domain suggests a mechanism of regulation of the TEC family members.

  9. Characterization of cell death inducing Phytophthora capsici CRN effectors suggests diverse activities in the host nucleus

    PubMed Central

    Stam, Remco; Howden, Andrew J. M.; Delgado-Cerezo, Magdalena; M. M. Amaro, Tiago M.; Motion, Graham B.; Pham, Jasmine; Huitema, Edgar

    2013-01-01

    Plant-Microbe interactions are complex associations that feature recognition of Pathogen Associated Molecular Patterns by the plant immune system and dampening of subsequent responses by pathogen encoded secreted effectors. With large effector repertoires now identified in a range of sequenced microbial genomes, much attention centers on understanding their roles in immunity or disease. These studies not only allow identification of pathogen virulence factors and strategies, they also provide an important molecular toolset suited for studying immunity in plants. The Phytophthora intracellular effector repertoire encodes a large class of proteins that translocate into host cells and exclusively target the host nucleus. Recent functional studies have implicated the CRN protein family as an important class of diverse effectors that target distinct subnuclear compartments and modify host cell signaling. Here, we characterized three necrosis inducing CRNs and show that there are differences in the levels of cell death. We show that only expression of CRN20_624 has an additive effect on PAMP induced cell death but not AVR3a induced ETI. Given their distinctive phenotypes, we assessed localization of each CRN with a set of nuclear markers and found clear differences in CRN subnuclear distribution patterns. These assays also revealed that expression of CRN83_152 leads to a distinct change in nuclear chromatin organization, suggesting a distinct series of events that leads to cell death upon over-expression. Taken together, our results suggest diverse functions carried by CRN C-termini, which can be exploited to identify novel processes that take place in the host nucleus and are required for immunity or susceptibility. PMID:24155749

  10. Active galaxies. A strong magnetic field in the jet base of a supermassive black hole.

    PubMed

    Martí-Vidal, Ivan; Muller, Sébastien; Vlemmings, Wouter; Horellou, Cathy; Aalto, Susanne

    2015-04-17

    Active galactic nuclei (AGN) host some of the most energetic phenomena in the universe. AGN are thought to be powered by accretion of matter onto a rotating disk that surrounds a supermassive black hole. Jet streams can be boosted in energy near the event horizon of the black hole and then flow outward along the rotation axis of the disk. The mechanism that forms such a jet and guides it over scales from a few light-days up to millions of light-years remains uncertain, but magnetic fields are thought to play a critical role. Using the Atacama Large Millimeter/submillimeter Array (ALMA), we have detected a polarization signal (Faraday rotation) related to the strong magnetic field at the jet base of a distant AGN, PKS 1830-211. The amount of Faraday rotation (rotation measure) is proportional to the integral of the magnetic field strength along the line of sight times the density of electrons. The high rotation measures derived suggest magnetic fields of at least tens of Gauss (and possibly considerably higher) on scales of the order of light-days (0.01 parsec) from the black hole. PMID:25883352

  11. Kinetic energy budget during strong jet stream activity over the eastern United States

    NASA Technical Reports Server (NTRS)

    Fuelberg, H. E.; Scoggins, J. R.

    1980-01-01

    Kinetic energy budgets are computed during a cold air outbreak in association with strong jet stream activity over the eastern United States. The period is characterized by large generation of kinetic energy due to cross-contour flow. Horizontal export and dissipation of energy to subgrid scales of motion constitute the important energy sinks. Rawinsonde data at 3 and 6 h intervals during a 36 h period are used in the analysis and reveal that energy fluctuations on a time scale of less than 12 h are generally small even though the overall energy balance does change considerably during the period in conjunction with an upper level trough which moves through the region. An error analysis of the energy budget terms suggests that this major change in the budget is not due to random errors in the input data but is caused by the changing synoptic situation. The study illustrates the need to consider the time and space scales of associated weather phenomena in interpreting energy budgets obtained through use of higher frequency data.

  12. Cerebral activation focusing on strong tasting food: a functional magnetic resonance imaging study.

    PubMed

    Kikuchi, Senichiro; Kubota, Fumio; Nisijima, Koichi; Washiya, Sumio; Kato, Satoshi

    2005-02-28

    Very little research has been conducted on taste imagery because of the difficulty of doing so. We conducted a functional magnetic resonance imaging study to observe cerebral activation patterns produced in volunteers concentrating on pickled plums (umeboshi), a traditional Japanese food with a strong and sour taste. Activation was observed in the right insula, the bilateral opercula, the bilateral orbitofrontal cortices and the left Broca's area. Activation in the insula (primary gustatory area) was very weak and limited to one side. The activation pattern was similar to that of taste perception. Our results showed that it is possible for humans to imagine tastes. PMID:15706236

  13. Polarographic assay based on hydrogen peroxide scavenging in determination of antioxidant activity of strong alcohol beverages.

    PubMed

    Gorjanović, Stanislava Z; Novaković, Miroslav M; Vukosavljević, Predrag V; Pastor, Ferenc T; Tesević, Vele V; Suznjević, Desanka Z

    2010-07-28

    Total antioxidant (AO) activity of strong alcohol beverages such as wine and plum brandies, whiskeys, herbal and sweet fruit liqueurs have been assessed using a polarographic assay based on hydrogen peroxide scavenging (HPS). Rank of order of total AO activity, expressed as percentage of decrease of anodic oxidation current of hydrogen peroxide, was found analogous with total phenolic content estimated by Folin-Ciocalteau (FC) assay and radical scavenging capacity against the stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH). Application of the assay for surveying of a quarter century long maturation of plum brandy in oak barrel was demonstrated. In addition, influence of different storage conditions on preservation of AO activity of some herbal liqueurs was surveyed. Wide area of application of this simple, fast, low cost and reliable assay in analysis and quality monitoring of various strong alcohol beverages was confirmed. PMID:20604507

  14. Modeling of the atmospheric response to a strong decrease of the solar activity

    NASA Astrophysics Data System (ADS)

    Rozanov, Eugene V.; Egorova, Tatiana A.; Shapiro, Alexander I.; Schmutz, Werner K.

    2012-07-01

    We estimate the consequences of a potential strong decrease of the solar activity using the model simulations of the future driven by pure anthropogenic forcing as well as its combination with different solar activity related factors: total solar irradiance, spectral solar irradiance, energetic electron precipitation, solar protons and galactic cosmic rays. The comparison of the model simulations shows that introduced strong decrease of solar activity can lead to some delay of the ozone recovery and partially compensate greenhouse warming acting in the direction opposite to anthropogenic effects. The model results also show that all considered solar forcings are important in different atmospheric layers and geographical regions. However, in the global scale the solar irradiance variability can be considered as the most important solar forcing. The obtained results constitute probably the upper limit of the possible solar influence. Development of the better constrained set of future solar forcings is necessary to address the problem of future climate and ozone layer with more confidence.

  15. Complementary chiral metasurface with strong broadband optical activity and enhanced transmission

    SciTech Connect

    Jia, Yan-Peng; Zhang, Yong-Liang; Dong, Xian-Zi E-mail: xmduan@mail.ipc.ac.cn; Zheng, Mei-Ling; Li, Jing; Liu, Jie; Zhao, Zhen-Sheng; Duan, Xuan-Ming E-mail: xmduan@mail.ipc.ac.cn

    2014-01-06

    We present the design and realization of ultra-thin chiral metasurfaces with giant broadband optical activity in the infrared wavelength. The chiral metasurfaces consisting of periodic hole arrays of complementary asymmetric split ring resonators are fabricated by femtosecond laser two-photon polymerization. Enhanced transmission with strong polarization conversion up to 97% is observed owing to the chiral surface plasmons resulting from mirror symmetry broken. The dependence of optical activity on the degree of structural asymmetry is investigated. This simple planar metasurface is expected to be useful for designing ultra-thin active devices and tailoring the polarization behavior of complex metallic nanostructures.

  16. N2 activation by an iron complex with a strong electron-donating iminophosphorane ligand.

    PubMed

    Suzuki, Tatsuya; Wasada-Tsutsui, Yuko; Ogawa, Takahiko; Inomata, Tomohiko; Ozawa, Tomohiro; Sakai, Yoichi; Fryzuk, Michael D; Masuda, Hideki

    2015-10-01

    A new tridentate cyclopentane-bridged iminophosphorane ligand, N-(2-diisopropylphosphinophenyl)-P,P-diisopropyl-P-(2-(2,6-diisopropylphenylamido)cyclopent-1-enyl)phosphoranimine (NpNPiPr), was synthesized and used in the preparation of a diiron dinitrogen complex. The reaction of the iron complex FeBr(NpNPiPr) with KC8 under dinitrogen yielded the dinuclear dinitrogen Fe complex [Fe(NpNPiPr)]2(μ-N2), which was characterized by X-ray analysis and resonance Raman and NMR spectroscopies. The X-ray analysis revealed a diiron complex bridged by the dinitrogen molecule, with each metal center coordinated by an NpNPiPr ligand and dinitrogen in a trigonal-monopyramidal geometry. The N–N bond length is 1.184(6) Å, and resonance Raman spectra indicate that the N–N stretching mode ν(14N2/15N2) is 1755/1700 cm–1. The magnetic moment of [Fe(NpNPiPr)]2(μ-N2) in benzene-d6 solution, as measured by 1H NMR spectroscopy by the Evans method, is 6.91μB (S = 3). The Mössbauer spectrum at 78 K showed δ = 0.73 mm/s and ΔEQ = 1.83 mm/s. These findings suggest that the iron ions are divalent with a high-spin configuration and that the N2 molecule has (N═N)2– character. Density functional theory calculations performed on [Fe(NpNPiPr)]2(μ-N2) also suggested that the iron is in a high-spin divalent state and that the coordinated dinitrogen molecule is effectively activated by π back-donation from the two iron ions (dπ) to the dinitrogen molecule (πx* and πy*). This is supported by cooperation between a large negative charge on the iminophosphorane ligand and strong electron donation and effective orbital overlap between the iron dπ orbitals and N2 π* orbitals supplied by the phosphine ligand. PMID:26135343

  17. Sixth-Grade Boys' Perceived Benefits of and Barriers to Physical Activity and Suggestions for Increasing Physical Activity

    ERIC Educational Resources Information Center

    Robbins, Lorraine B.; Talley, Henry C.; Wu, Tsu-Yin; Wilbur, JoEllen

    2010-01-01

    Interventions are needed to reduce the high overweight prevalence noted among boys in early high school. Because decreased physical activity (PA) is a factor for weight gain and a decline in boys' PA occurs across the middle school years, a need exists to intervene, as soon as boys reach middle school, to help them get adequate PA. The purpose of…

  18. N-methyl-D-aspartate receptors strongly regulate postsynaptic activity levels during optic nerve regeneration.

    PubMed

    Kolls, Brad J; Meyer, Ronald L

    2013-10-01

    During development, neuronal activity is used as a cue to guide synaptic rearrangements to refine connections. Many studies, especially in the visual system, have shown that the N-methyl-D-aspartate receptor (NMDAr) plays a key role in mediating activity-dependent refinement through long-term potentiation (LTP)-like processes. Adult goldfish can regenerate their optic nerve and utilize neuronal activity to generate precise topography in their projection onto tectum. Although the NMDAr has been implicated in this process, its precise role in regeneration has not been extensively studied. In examining NMDAr function during regeneration, we found salient differences compared with development. By using field excitatory postsynaptic potential (fEPSP) recordings, the contribution of the NMDAr at the primary optic synapse was measured. In contrast to development, no increase in NMDAr function was detectable during synaptic refinement. Unlike development, LTP could not be reliably elicited during regeneration. Unexpectedly, we found that NMDAr exerted a major effect on regulating ongoing tectal (postsynaptic) activity levels during regeneration. Blocking NMDAr strongly suppressed spontaneous activity during regeneration but had no significant effect in the normal projection. This difference could be attributed to an occlusion effect of strong optic drive in the normal projection, which dominated ongoing tectal activity. During regeneration, this optic drive is largely absent. Optic nerve stimulation further indicated that the NMDAr had little effect on the ability of optic fibers to evoke early postsynaptic impulse activity but was important for late network activity. These results indicate that, during regeneration, the NMDAr may play a critical role in the homeostatic regulation of ongoing activity and network excitability. PMID:23873725

  19. Silver nanoparticles strongly enhance and restore bactericidal activity of inactive antibiotics against multiresistant Enterobacteriaceae.

    PubMed

    Panáček, Aleš; Smékalová, Monika; Večeřová, Renata; Bogdanová, Kateřina; Röderová, Magdaléna; Kolář, Milan; Kilianová, Martina; Hradilová, Šárka; Froning, Jens P; Havrdová, Markéta; Prucek, Robert; Zbořil, Radek; Kvítek, Libor

    2016-06-01

    Bacterial resistance to conventional antibiotics is currently one of the most important healthcare issues, and has serious negative impacts on medical practice. This study presents a potential solution to this problem, using the strong synergistic effects of antibiotics combined with silver nanoparticles (NPs). Silver NPs inhibit bacterial growth via a multilevel mode of antibacterial action at concentrations ranging from a few ppm to tens of ppm. Silver NPs strongly enhanced antibacterial activity against multiresistant, β-lactamase and carbapenemase-producing Enterobacteriaceae when combined with the following antibiotics: cefotaxime, ceftazidime, meropenem, ciprofloxacin and gentamicin. All the antibiotics, when combined with silver NPs, showed enhanced antibacterial activity at concentrations far below the minimum inhibitory concentrations (tenths to hundredths of one ppm) of individual antibiotics and silver NPs. The enhanced activity of antibiotics combined with silver NPs, especially meropenem, was weaker against non-resistant bacteria than against resistant bacteria. The double disk synergy test showed that bacteria produced no β-lactamase when treated with antibiotics combined with silver NPs. Low silver concentrations were required for effective enhancement of antibacterial activity against multiresistant bacteria. These low silver concentrations showed no cytotoxic effect towards mammalian cells, an important feature for potential medical applications. PMID:26970828

  20. Activation of Vago by interferon regulatory factor (IRF) suggests an interferon system-like antiviral mechanism in shrimp

    PubMed Central

    Li, Chaozheng; Li, Haoyang; Chen, Yixiao; Chen, Yonggui; Wang, Sheng; Weng, Shao-Ping; Xu, Xiaopeng; He, Jianguo

    2015-01-01

    There is a debate on whether invertebrates possess an antiviral immunity similar to the interferon (IFN) system of vertebrates. The Vago gene from arthropods encodes a viral-activated secreted peptide that restricts virus infection through activating the JAK-STAT pathway and is considered to be a cytokine functionally similar to IFN. In this study, the first crustacean IFN regulatory factor (IRF)-like gene was identified in Pacific white shrimp, Litopenaeus vannamei. The L. vannamei IRF showed similar protein nature to mammalian IRFs and could be activated during virus infection. As a transcriptional regulatory factor, L. vannamei IRF could activate the IFN-stimulated response element (ISRE)-containing promoter to regulate the expression of mammalian type I IFNs and initiate an antiviral state in mammalian cells. More importantly, IRF could bind the 5′-untranslated region of L. vannamei Vago4 gene and activate its transcription, suggesting that shrimp Vago may be induced in a similar manner to that of IFNs and supporting the opinion that Vago might function as an IFN-like molecule in invertebrates. These suggested that shrimp might possess an IRF-Vago-JAK/STAT regulatory axis, which is similar to the IRF-IFN-JAK/STAT axis of vertebrates, indicating that invertebrates might possess an IFN system-like antiviral mechanism. PMID:26459861

  1. How a Small Change in Retinal Leads to G-Protein Activation: Initial Events Suggested by Molecular Dynamics Calculations

    PubMed Central

    Crozier, Paul S.; Stevens, Mark J.; Woolf, Thomas B.

    2010-01-01

    Rhodopsin is the prototypical G-protein coupled receptor, coupling light activation with high efficiency to signaling molecules. The dark-state X-ray structures of the protein provide a starting point for consideration of the relaxation from initial light activation to conformational changes that may lead to signaling. In this study we create an energetically unstable retinal in the light activated state and then use molecular dynamics simulations to examine the types of compensation, relaxation, and conformational changes that occur following the cis–trans light activation. The results suggest that changes occur throughout the protein, with changes in the orientation of Helices 5 and 6, a closer interaction between Ala 169 on Helix 4 and retinal, and a shift in the Schiff base counterion that also reflects changes in sidechain interactions with the retinal. Taken together, the simulation is suggestive of the types of changes that lead from local conformational change to light-activated signaling in this prototypical system. PMID:17109408

  2. Antenna gain of actively compensated free-space optical communication systems under strong turbulence conditions.

    PubMed

    Juarez, Juan C; Brown, David M; Young, David W

    2014-05-19

    Current Strehl ratio models for actively compensated free-space optical communications terminals do not accurately predict system performance under strong turbulence conditions as they are based on weak turbulence theory. For evaluation of compensated systems, we present an approach for simulating the Strehl ratio with both low-order (tip/tilt) and higher-order (adaptive optics) correction. Our simulation results are then compared to the published models and their range of turbulence validity is assessed. Finally, we propose a new Strehl ratio model and antenna gain equation that are valid for general turbulence conditions independent of the degree of compensation. PMID:24921373

  3. Comparative Analysis of the Flax Immune Receptors L6 and L7 Suggests an Equilibrium-Based Switch Activation Model.

    PubMed

    Bernoux, Maud; Burdett, Hayden; Williams, Simon J; Zhang, Xiaoxiao; Chen, Chunhong; Newell, Kim; Lawrence, Gregory J; Kobe, Bostjan; Ellis, Jeffrey G; Anderson, Peter A; Dodds, Peter N

    2016-01-01

    NOD-like receptors (NLRs) are central components of the plant immune system. L6 is a Toll/interleukin-1 receptor (TIR) domain-containing NLR from flax (Linum usitatissimum) conferring immunity to the flax rust fungus. Comparison of L6 to the weaker allele L7 identified two polymorphic regions in the TIR and the nucleotide binding (NB) domains that regulate both effector ligand-dependent and -independent cell death signaling as well as nucleotide binding to the receptor. This suggests that a negative functional interaction between the TIR and NB domains holds L7 in an inactive/ADP-bound state more tightly than L6, hence decreasing its capacity to adopt the active/ATP-bound state and explaining its weaker activity in planta. L6 and L7 variants with a more stable ADP-bound state failed to bind to AvrL567 in yeast two-hybrid assays, while binding was detected to the signaling active variants. This contrasts with current models predicting that effectors bind to inactive receptors to trigger activation. Based on the correlation between nucleotide binding, effector interaction, and immune signaling properties of L6/L7 variants, we propose that NLRs exist in an equilibrium between ON and OFF states and that effector binding to the ON state stabilizes this conformation, thereby shifting the equilibrium toward the active form of the receptor to trigger defense signaling. PMID:26744216

  4. Exceptionally strong sorption of infochemicals to activated carbon reduces their bioavailability to fish.

    PubMed

    Jonker, Michiel T O; van Mourik, Louise

    2014-03-01

    The addition of activated carbon (AC) to sediments is a relatively new approach to remediate contaminated sites. Activated carbon strongly sorbs hydrophobic organic contaminants, thereby reducing their bioavailability and uptake in organisms. Because of its high sorption capacity, AC might, however, also sorb other chemicals that are not contaminants but instead have ecological functions. Examples of such compounds are infochemicals or pheromones (i.e., compounds serving as chemical inter- and intraspecies information vectors). The present study investigated the sorption of 2 known infochemicals, hypoxanthine-3-N-oxide (H3NO) and pyridine-N-oxide (PNO), to 5 different powdered ACs. Sorption isotherms of these low-molecular-weight, polar fish kairomone substances appeared highly nonlinear, with logarithmic Freundlich sorption coefficients of up to 7.6. At physiologically relevant concentrations, sorption was up to 7 to 9 orders of magnitude stronger than expected on the basis of hydrophobic forces only (i.e., the compounds' log octanol-water partition coefficient, being approximately -1), indicating exceptionally strong binding to specific sites. This binding effectively reduced the bioavailability of H3NO to Sarasa goldfish, as was shown in a behavioral assay. The present study demonstrates the previously unrecognized potential of AC to sorb ecologically relevant chemicals. Whether this potential may lead to subtle, unwanted ecological effects in the field will have to be investigated in more detail during future research. PMID:24272993

  5. Characterization of a novel β-glucosidase from a compost microbial metagenome with strong transglycosylation activity.

    PubMed

    Uchiyama, Taku; Miyazaki, Kentaro; Yaoi, Katsuro

    2013-06-21

    The β-glucosidase encoded by the td2f2 gene was isolated from a compost microbial metagenomic library by functional screening. The protein was identified to be a member of the glycoside hydrolase family 1 and was overexpressed in Escherichia coli, purified, and biochemically characterized. The recombinant β-glucosidase, Td2F2, exhibited enzymatic activity with β-glycosidic substrates, with preferences for glucose, fucose, and galactose. Hydrolysis occurred at the nonreducing end and in an exo manner. The order of catalytic efficiency for glucodisaccharides and cellooligosaccharides was sophorose > cellotetraose > cellotriose > laminaribiose > cellobiose > cellopentaose > gentiobiose, respectively. Intriguingly, the p-nitrophenyl-β-D-glucopyranoside hydrolysis activity of Td2F2 was activated by various monosaccharides and sugar alcohols. At a D-glucose concentration of 1000 mM, enzyme activity was 6.7-fold higher than that observed in the absence of D-glucose. With 31.3 mM D-glucose, Td2F2 catalyzed transglycosylation to generate sophorose, laminaribiose, cellobiose, and gentiobiose. Transglycosylation products were detected under all activated conditions, suggesting that the activity enhancement induced by monosaccharides and sugar alcohols may be due to the transglycosylation activity of the enzyme. These results show that Td2F2 obtained from a compost microbial metagenome may be a potent candidate for industrial applications. PMID:23661705

  6. Characterization of a Novel β-Glucosidase from a Compost Microbial Metagenome with Strong Transglycosylation Activity*

    PubMed Central

    Uchiyama, Taku; Miyazaki, Kentaro; Yaoi, Katsuro

    2013-01-01

    The β-glucosidase encoded by the td2f2 gene was isolated from a compost microbial metagenomic library by functional screening. The protein was identified to be a member of the glycoside hydrolase family 1 and was overexpressed in Escherichia coli, purified, and biochemically characterized. The recombinant β-glucosidase, Td2F2, exhibited enzymatic activity with β-glycosidic substrates, with preferences for glucose, fucose, and galactose. Hydrolysis occurred at the nonreducing end and in an exo manner. The order of catalytic efficiency for glucodisaccharides and cellooligosaccharides was sophorose > cellotetraose > cellotriose > laminaribiose > cellobiose > cellopentaose > gentiobiose, respectively. Intriguingly, the p-nitrophenyl-β-d-glucopyranoside hydrolysis activity of Td2F2 was activated by various monosaccharides and sugar alcohols. At a d-glucose concentration of 1000 mm, enzyme activity was 6.7-fold higher than that observed in the absence of d-glucose. With 31.3 mm d-glucose, Td2F2 catalyzed transglycosylation to generate sophorose, laminaribiose, cellobiose, and gentiobiose. Transglycosylation products were detected under all activated conditions, suggesting that the activity enhancement induced by monosaccharides and sugar alcohols may be due to the transglycosylation activity of the enzyme. These results show that Td2F2 obtained from a compost microbial metagenome may be a potent candidate for industrial applications. PMID:23661705

  7. Expression of essential B cell genes and immunoglobulin isotypes suggests active development and gene recombination during equine gestation.

    PubMed

    Tallmadge, Rebecca L; McLaughlin, Kristin; Secor, Erica; Ruano, Diana; Matychak, Mary Beth; Flaminio, M Julia B F

    2009-09-01

    Many features of the equine immune system develop during fetal life, yet the naïve or immature immune state of the neonate renders the foal uniquely susceptible to particular pathogens. RT-PCR and immunohistochemical experiments investigated the progressive expression of developmental B cell markers and immunoglobulins in lymphoid tissues from equine fetus, pre-suckle neonate, foal, and adult horses. Serum IgM, IgG isotype, and IgA concentrations were also quantified in pre-suckle foals and adult horses. The expression of essential B cell genes suggests active development and gene recombination during equine gestation, including immunoglobulin isotype switching. The corresponding production of IgM and IgG proteins is detectable in a limited scale at birth. Although the equine neonate humoral response seems competent, B cell activation factors derived from antigen presenting cells and T cells may control critical developmental regulation and immunoglobulin production during the initial months of life. PMID:19442687

  8. High adenylyl cyclase activity and in vivo cAMP fluctuations in corals suggest central physiological role.

    PubMed

    Barott, K L; Helman, Y; Haramaty, L; Barron, M E; Hess, K C; Buck, J; Levin, L R; Tresguerres, M

    2013-01-01

    Corals are an ecologically and evolutionarily significant group, providing the framework for coral reef biodiversity while representing one of the most basal of metazoan phyla. However, little is known about fundamental signaling pathways in corals. Here we investigate the dynamics of cAMP, a conserved signaling molecule that can regulate virtually every physiological process. Bioinformatics revealed corals have both transmembrane and soluble adenylyl cyclases (AC). Endogenous cAMP levels in live corals followed a potential diel cycle, as they were higher during the day compared to the middle of the night. Coral homogenates exhibited some of the highest cAMP production rates ever to be recorded in any organism; this activity was inhibited by calcium ions and stimulated by bicarbonate. In contrast, zooxanthellae or mucus had >1000-fold lower AC activity. These results suggest that cAMP is an important regulator of coral physiology, especially in response to light, acid/base disturbances and inorganic carbon levels. PMID:23459251

  9. The Novel Antitubulin Agent TR-764 Strongly Reduces Tumor Vasculature and Inhibits HIF-1α Activation.

    PubMed

    Porcù, Elena; Persano, Luca; Ronca, Roberto; Mitola, Stefania; Bortolozzi, Roberta; Romagnoli, Romeo; Oliva, Paola; Basso, Giuseppe; Viola, Giampietro

    2016-01-01

    Tubulin binding agents (TBAs) are commonly used in cancer therapy as antimitotics. It has been described that TBAs, like combretastatin A-4 (CA-4), present also antivascular activity and among its derivatives we identified TR-764 as a new inhibitor of tubulin polymerization, based on the 2-(alkoxycarbonyl)-3-(3',4',5'-trimethoxyanilino)benzo[b]thiophene molecular skeleton. The antiangiogenic activity of TR-764 (1-10 nM) was tested in vitro on human umbilical endothelial cells (HUVECs), and in vivo, on the chick embryo chorioallantoic membrane (CAM) and two murine tumor models. TR-764 binding to tubulin triggers cytoskeleton rearrangement without affecting cell cycle and viability. It leads to capillary tube disruption, increased cell permeability, and cell motility reduction. Moreover it disrupts adherens junctions and focal adhesions, through mechanisms involving VE-cadherin/β-catenin and FAK/Src. Importantly, TR-764 is active in hypoxic conditions significantly reducing HIF-1α. In vivo TR-764 (1-100 pmol/egg) remarkably blocks the bFGF proangiogenic activity on CAM and shows a stronger reduction of tumor mass and microvascular density both in murine syngeneic and xenograft tumor models, compared to the lead compound CA-4P. Altogether, our results indicate that TR-764 is a novel TBA with strong potential as both antivascular and antitumor molecule that could improve the common anticancer therapies, by overcoming hypoxia-induced resistance mechanisms. PMID:27292568

  10. Elk3 from hamster--a ternary complex factor with strong transcriptional repressor activity.

    PubMed

    Hjortoe, Gertrud Malene; Weilguny, Dietmar; Willumsen, Berthe Marie

    2005-01-01

    Elk3 belongs to the Ets family of transcription factors, which are regulated by the Ras/mitogen-activated protein kinase-signaling pathway. In the absence of Ras, this protein is a strong inhibitor of transcription and may be directly involved in regulation of growth by downregulating the transcription of genes that are activated during entry into G1. We have isolated the Cricetulus griseus Elk3 gene from the Chinese hamster ovary (CHO) cell line and investigated the transcriptional potential of this factor. Transient transfections revealed that, in addition to its regulation of the c-fos promoter, Elk3 from CHO cells seems to inhibit other promoters controlling expression of proteins involved in G1/S phase progression; Cyclin D1 and DHFR. As has been described for the Elk3 homologs Net (Mouse) and Sap-2 (Human), the results of the present study further indicate that hamster Elk3 is a target of the Ras-Raf-MAPK pathway, and cotransfections with constitutively active H-ras relieves its negative transcriptional activity. No cells stably expressing exogenous Elk3 could be obtained, possibly due to an unspecified toxic or growth retarding effect. These findings support a possible role for Elk3 in growth regulation and reveal a high degree of homology for this protein across species. PMID:15684718

  11. The Novel Antitubulin Agent TR-764 Strongly Reduces Tumor Vasculature and Inhibits HIF-1α Activation

    PubMed Central

    Porcù, Elena; Persano, Luca; Ronca, Roberto; Mitola, Stefania; Bortolozzi, Roberta; Romagnoli, Romeo; Oliva, Paola; Basso, Giuseppe; Viola, Giampietro

    2016-01-01

    Tubulin binding agents (TBAs) are commonly used in cancer therapy as antimitotics. It has been described that TBAs, like combretastatin A-4 (CA-4), present also antivascular activity and among its derivatives we identified TR-764 as a new inhibitor of tubulin polymerization, based on the 2-(alkoxycarbonyl)-3-(3′,4′,5′-trimethoxyanilino)benzo[b]thiophene molecular skeleton. The antiangiogenic activity of TR-764 (1–10 nM) was tested in vitro on human umbilical endothelial cells (HUVECs), and in vivo, on the chick embryo chorioallantoic membrane (CAM) and two murine tumor models. TR-764 binding to tubulin triggers cytoskeleton rearrangement without affecting cell cycle and viability. It leads to capillary tube disruption, increased cell permeability, and cell motility reduction. Moreover it disrupts adherens junctions and focal adhesions, through mechanisms involving VE-cadherin/β-catenin and FAK/Src. Importantly, TR-764 is active in hypoxic conditions significantly reducing HIF-1α. In vivo TR-764 (1–100 pmol/egg) remarkably blocks the bFGF proangiogenic activity on CAM and shows a stronger reduction of tumor mass and microvascular density both in murine syngeneic and xenograft tumor models, compared to the lead compound CA-4P. Altogether, our results indicate that TR-764 is a novel TBA with strong potential as both antivascular and antitumor molecule that could improve the common anticancer therapies, by overcoming hypoxia-induced resistance mechanisms. PMID:27292568

  12. Characterization of human paraoxonase 1 variants suggest that His residues at 115 and 134 positions are not always needed for the lactonase/arylesterase activities of the enzyme

    PubMed Central

    Bajaj, Priyanka; Tripathy, Rajan K; Aggarwal, Geetika; Pande, Abhay H

    2013-01-01

    Human paraoxonase 1 (h-PON1) hydrolyzes variety of substrates and the hydrolytic activities of enzyme can be broadly grouped into three categories; arylesterase, phosphotriesterase, and lactonase. Current models of the catalytic mechanism of h-PON1 suggest that catalytic residues H115 and H134 mediate the lactonase and arylesterase activities of the enzyme. H-PON1 is a strong candidate for the development of catalytic bioscavenger for organophosphate poisoning in humans. Recently, Gupta et al. (Nat. Chem. Biol. 2011. 7, 120) identified amino acid substitutions that significantly increased the activity of chimeric-PON1 variant (4E9) against some organophosphate nerve agents. In this study we have examined the effect of these (L69G/S111T/H115W/H134R/R192K/F222S/T332S) and other substitutions (H115W/H134R and H115W/H134R/R192K) on the hydrolytic activities of recombinant h-PON1 (rh-PON1) variants. Our results show that the substitutions resulted in a significant increase in the organophosphatase activity of all the three variants of rh-PON1 enzyme while had a variable effect on the lactonase/arylesterase activities. The results suggest that H residues at positions 115 and 134 are not always needed for the lactonase/arylesterase activities of h-PON1 and force a reconsideration of the current model(s) of the catalytic mechanism of h-PON1. PMID:24123308

  13. Functional conservation of Drosophila FTZ-F1 and its mammalian homologs suggests ligand-independent regulation of NR5A family transcriptional activity.

    PubMed

    Lu, Yong; Anderson, W Ray; Zhang, Hua; Feng, Siqian; Pick, Leslie

    2013-05-01

    Drosophila Ftz-F1 is an orphan nuclear receptor required for segmentation and metamorphosis. Its mammalian orthologs, SF-1 and LRH-1, function in sexual development and homeostasis, and have been implicated in stem cell pluripotency maintenance and tumorigenesis. These NR5A family members bind DNA as monomers and strongly activate transcription. However, controversy exists as to whether their activity is regulated by ligand-binding. Structural evidence suggested that SF-1 and human LRH-1 bind regulatory ligands, but mouse LRH-1 and Drosophila FTZ-F1 are active in the absence of ligand. We found that Dm-Ftz-F1 and mLRH-1, thought not to bind ligand, or mSF-1 and hLRH-1, predicted to bind ligand, each efficiently rescued the defects of Drosophila ftz-f1 mutants. Further, each correctly activated expression of a Dm-Ftz-F1 target gene in Drosophila embryos. The functional equivalence of ftz-f1 orthologs in these sensitive in vivo assays argues against specific activating ligands for NR5A family members. PMID:23340581

  14. Preparation of graphite-like carbon nitride nanoflake film with strong fluorescent and electrochemiluminescent activity

    NASA Astrophysics Data System (ADS)

    Chen, Lichan; Huang, Danjun; Ren, Shuyan; Dong, Tongqing; Chi, Yuwu; Chen, Guonan

    2012-12-01

    The preparation, characterization, fluorescence (FL) and electrochemiluminescence (ECL) of graphite-like carbon nitride nanoflake particles (g-C3N4 NFPs) and nanoflake films (g-C3N4 NFFs) have been reported. Highly water-dispersible g-C3N4 NFPs with a height of ~5 to 35 nm and a lateral dimension of ~40 to 220 nm have been extracted from bulk g-C3N4 materials by chemical oxidation. New, stable and defined g-C3N4 NFFs can be easily obtained by drying NFPs on certain hydrophilic substrates such as glass or electrode surfaces. Both g-C3N4 NFPs and g-C3N4 NFFs have good FL activities, i.e. they can give strong blue light (435 nm) emission under UV light (365 nm) excitation. The as-prepared g-C3N4 NFFs on a glassy carbon electrode exhibit strong non-surface state ECL activity in the presence of reductive-oxidative coreactants, including dissolved oxygen (O2), hydrogen peroxide (H2O2) and peroxydisulfate (S2O82-) and give rise to blue light emission (435 nm), which is the same as the wavelength of FL. The non-surface state ECL mechanisms of the g-C3N4 NFF-coreactant systems have been studied and discussed in detail.The preparation, characterization, fluorescence (FL) and electrochemiluminescence (ECL) of graphite-like carbon nitride nanoflake particles (g-C3N4 NFPs) and nanoflake films (g-C3N4 NFFs) have been reported. Highly water-dispersible g-C3N4 NFPs with a height of ~5 to 35 nm and a lateral dimension of ~40 to 220 nm have been extracted from bulk g-C3N4 materials by chemical oxidation. New, stable and defined g-C3N4 NFFs can be easily obtained by drying NFPs on certain hydrophilic substrates such as glass or electrode surfaces. Both g-C3N4 NFPs and g-C3N4 NFFs have good FL activities, i.e. they can give strong blue light (435 nm) emission under UV light (365 nm) excitation. The as-prepared g-C3N4 NFFs on a glassy carbon electrode exhibit strong non-surface state ECL activity in the presence of reductive-oxidative coreactants, including dissolved oxygen (O2

  15. A novel fMRI paradigm suggests that pedaling-related brain activation is altered after stroke

    PubMed Central

    Promjunyakul, Nutta-on; Schmit, Brian D.; Schindler-Ivens, Sheila M.

    2015-01-01

    regions were examined separately, reduced brain activation volume reached statistical significance in BA6 [p = 0.04; 4,350 (2,347) μL stroke; 6,938 (3,134) μL control] and cerebellum [p = 0.001; 4,591 (1,757) μL stroke; 8,381 (2,835) μL control]. Regardless of whether activated regions were examined together or separately, there were no significant between-group differences in brain activation intensity [p = 0.17; 1.30 (0.25)% stroke; 1.16 (0.20)% control]. Reduced volume in the stroke group was not observed during lower limb tapping and could not be fully attributed to differences in head motion or movement rate. There was a tendency for pedaling-related brain activation volume to increase with increasing work performed by the paretic limb during pedaling (p = 0.08, r = 0.525). Hence, the results of this study provide two original and important contributions. First, we demonstrated that pedaling can be used with fMRI to examine brain activation associated with lower limb movement in people with stroke. Unlike previous lower limb movements examined with fMRI, pedaling involves continuous, reciprocal, multijoint movement of both limbs. In this respect, pedaling has many characteristics of functional lower limb movements, such as walking. Thus, the importance of our contribution lies in the establishment of a novel paradigm that can be used to understand how the brain adapts to stroke to produce functional lower limb movements. Second, preliminary observations suggest that brain activation volume is reduced during pedaling post-stroke. Reduced brain activation volume may be due to anatomic, physiology, and/or behavioral differences between groups, but methodological issues cannot be excluded. Importantly, brain action volume post-stroke was both task-dependent and mutable, which suggests that it could be modified through rehabilitation. Future work will explore these possibilities. PMID:26089789

  16. Dual crosslinked iminoboronate-chitosan hydrogels with strong antifungal activity against Candida planktonic yeasts and biofilms.

    PubMed

    Ailincai, Daniela; Marin, Luminita; Morariu, Simona; Mares, Mihai; Bostanaru, Andra-Cristina; Pinteala, Mariana; Simionescu, Bogdan C; Barboiu, Mihai

    2016-11-01

    Chitosan based hydrogels are a class of cross-linked materials intensely studied for their biomedical, industrial and environmental application, but their biomedical use is limited because of the toxicity of different organic crosslinkers. To overcome this disadvantage, a new strategy to produce supramolecular chitosan hydrogels using low molecular weight compounds able to form covalent linkages and H-bonds to give a dual crosslinking is proposed. For this purpose we used 2-formylphenylboronic acid, which brings the advantage of imine stabilization via iminoboronate formation and potential antifungal activity due to the presence of boric acid residue. FTIR and NMR spectroscopy indicated that the gelling process took place by chemo-physical crosslinking forming a dual iminoboronate-chitosan network. Further, X-ray diffraction demonstrated a three-dimensional nanostructuring of the iminoboronate network with consequences on the micrometer-scale morphology and on the improvement of mechanical properties, as demonstrated by SEM and rheological investigation. The hydrogels proved strong antifungal activity against Candida planktonic yeasts and biofilms, promising to be a friendly treatment of the recurrent vulvovaginitis infections. PMID:27516277

  17. Strong Blue Asymmetry in H α Line as a Preflare Activity

    NASA Astrophysics Data System (ADS)

    Cho, Kyuhyoun; Lee, Jeongwoo; Chae, Jongchul; Wang, Haimin; Ahn, Kwangsu; Yang, Heesu; Lim, Eun-kyung; Maurya, Ram Ajor

    2016-08-01

    Chromospheric activities before solar flares provide important clues to the mechanisms that initiate solar flares, but are as yet poorly understood. We report a significant and rapid H α line broadening before the solar flare SOL2011-09-29T18:08 that was detected using the unprecedented high-resolution H α imaging spectroscopy with the Fast Imaging Solar Spectrograph (FISS) installed on the 1.6 m New Solar Telescope (NST) at Big Bear Solar Observatory. The strong H α broadening extends as a blue excursion up to -4.5 Å and as a red excursion up to 2.0 Å, which implies a mixture of velocities in the range of -130 km s^{-1} to 38 km s-1 derived by applying the cloud model, comparable to the highest chromospheric motions reported before. The H α blueshifted broadening lasts for about six minutes and is temporally and spatially correlated with the start of a rising filament, which is later associated with the main phase of the flare as detected by the Atmosphere Imaging Assembly (AIA) onboard the Solar Dynamics Observatory (SDO). The potential importance of this H α blueshifted broadening as a preflare chromospheric activity is briefly discussed within the context of the two-step eruption model.

  18. Peculiarities of ULF electromagnetic disturbances before strong earthquakes in seismic active zone of Kamchatka peninsula

    NASA Astrophysics Data System (ADS)

    Kopytenko, Y. A.; Ismagilov, V. S.; Schekotov, A.; Molchanov, O.; Chebrov, V.; Raspopov, O. M.

    2006-12-01

    Regular observations of ULF electromagnetic disturbances and acoustic emissions at st. Karymshino in seismic active zone of Kamchatka peninsula were carried out during 2001-2003 years. Five seismic active periods with strong earthquakes (M>5) were displayed during this period. These EQs occurred at the Pacific at 20-60 km depth at 100-140 km distances to the East from the st. Karymshino. Analysis of normalized dynamic power spectra of data of high-sensitive (0.2 pT/sqrt(Hz)) three-component induction magnetometer achieved a significant disorder of daily variation and increasing of the magnetic disturbance intensities (from 0.2 to ~1 pT) in the whole investigated frequency range (0.2-5 Hz). The anomaly intensity increasing was observed during the 12-18 hours before main seismic shocks. Maximum of the increasing occurred during 4-6 hours before the EQs. An increasing of acoustic emissions (F=30 Hz) was observed during the same period. A sharp decreasing of the magnetic disturbance intensities was observed 2-4 hours before the EQs. We suppose that physical processes in a hearth of forthcoming EQ lead to an irreversible avalanche-like formation of cracks and stimulation of the acoustic and ULF electromagnetic disturbances.

  19. Radiotherapy combined with TLR7/8 activation induces strong immune responses against gastrointestinal tumors.

    PubMed

    Schölch, Sebastian; Rauber, Conrad; Tietz, Alexandra; Rahbari, Nuh N; Bork, Ulrich; Schmidt, Thomas; Kahlert, Christoph; Haberkorn, Uwe; Tomai, Mark A; Lipson, Kenneth E; Carretero, Rafael; Weitz, Jürgen; Koch, Moritz; Huber, Peter E

    2015-03-10

    In addition to local cytotoxic activity, radiotherapy may also elicit local and systemic antitumor immunity, which may be augmented by immunotherapeutic agents including Toll-like receptor (TLR) 7/8 agonists. Here, we investigated the ability of 3M-011 (854A), a TLR7/8 agonist, to boost the antigen-presenting activity of dendritic cells (DC) as an adjuvant to radiotherapy. The combined treatment induced marked local and systemic responses in subcutaneous and orthotopic mouse models of colorectal and pancreatic cancer. In vitro cytotoxicity assays as well as in vivo depletion experiments with monoclonal antibodies identified NK and CD8 T cells as the cell populations mediating the cytotoxic effects of the treatment, while in vivo depletion of CD11c+ dendritic cells (DC) in CD11c-DTR transgenic mice revealed DC as the pivotal immune hub in this setting. The specificity of the immune reaction was confirmed by ELISPOT assays. TLR7/8 agonists therefore seem to be potent adjuvants to radiotherapy, inducing strong local and profound systemic immune responses to tumor antigens released by conventional therapy. PMID:25609199

  20. Radiotherapy combined with TLR7/8 activation induces strong immune responses against gastrointestinal tumors

    PubMed Central

    Tietz, Alexandra; Rahbari, Nuh N.; Bork, Ulrich; Schmidt, Thomas; Kahlert, Christoph; Haberkorn, Uwe; Tomai, Mark A.; Lipson, Kenneth E.; Carretero, Rafael; Weitz, Jürgen; Koch, Moritz; Huber, Peter E.

    2015-01-01

    In addition to local cytotoxic activity, radiotherapy may also elicit local and systemic antitumor immunity, which may be augmented by immunotherapeutic agents including Toll-like receptor (TLR) 7/8 agonists. Here, we investigated the ability of 3M-011 (854A), a TLR7/8 agonist, to boost the antigen-presenting activity of dendritic cells (DC) as an adjuvant to radiotherapy. The combined treatment induced marked local and systemic responses in subcutaneous and orthotopic mouse models of colorectal and pancreatic cancer. In vitro cytotoxicity assays as well as in vivo depletion experiments with monoclonal antibodies identified NK and CD8 T cells as the cell populations mediating the cytotoxic effects of the treatment, while in vivo depletion of CD11c+ dendritic cells (DC) in CD11c-DTR transgenic mice revealed DC as the pivotal immune hub in this setting. The specificity of the immune reaction was confirmed by ELISPOT assays. TLR7/8 agonists therefore seem to be potent adjuvants to radiotherapy, inducing strong local and profound systemic immune responses to tumor antigens released by conventional therapy. PMID:25609199

  1. Comparison of the White-Nose Syndrome Agent Pseudogymnoascus destructans to Cave-Dwelling Relatives Suggests Reduced Saprotrophic Enzyme Activity

    PubMed Central

    Reynolds, Hannah T.; Barton, Hazel A.

    2014-01-01

    White-nose Syndrome (WNS) is an emerging infectious mycosis that has impacted multiple species of North American bats since its initial discovery in 2006, yet the physiology of the causal agent, the psychrophilic fungus Pseudogymnoascus destructans ( = Geomyces destructans), is not well understood. We investigated the ability of P. destructans to secrete enzymes that could permit environmental growth or affect pathogenesis and compared enzyme activity across several Pseudogymnoascus species isolated from both hibernating bats and cave sediments. We found that P. destructans produced enzymes that could be beneficial in either a pathogenic or saprotrophic context, such as lipases, hemolysins, and urease, as well as chitinase and cellulases, which could aid in saprotrophic growth. The WNS pathogen showed significantly lower activity for urease and endoglucanase compared to con-generic species (Pseudogymnoascus), which may indicate a shift in selective pressure to the detriment of P. destructans’ saprotrophic ability. Based on the positive function of multiple saprotrophic enzymes, the causal agent of White-nose Syndrome shows potential for environmental growth on a variety of substrates found in caves, albeit at a reduced level compared to environmental strains. Our data suggest that if P. destructans emerged as an opportunistic infection from an environmental source, co-evolution with its host may have led to a reduced capacity for saprotrophic growth. PMID:24466096

  2. Comparison of the white-nose syndrome agent Pseudogymnoascus destructans to cave-dwelling relatives suggests reduced saprotrophic enzyme activity.

    PubMed

    Reynolds, Hannah T; Barton, Hazel A

    2014-01-01

    White-nose Syndrome (WNS) is an emerging infectious mycosis that has impacted multiple species of North American bats since its initial discovery in 2006, yet the physiology of the causal agent, the psychrophilic fungus Pseudogymnoascus destructans ( = Geomyces destructans), is not well understood. We investigated the ability of P. destructans to secrete enzymes that could permit environmental growth or affect pathogenesis and compared enzyme activity across several Pseudogymnoascus species isolated from both hibernating bats and cave sediments. We found that P. destructans produced enzymes that could be beneficial in either a pathogenic or saprotrophic context, such as lipases, hemolysins, and urease, as well as chitinase and cellulases, which could aid in saprotrophic growth. The WNS pathogen showed significantly lower activity for urease and endoglucanase compared to con-generic species (Pseudogymnoascus), which may indicate a shift in selective pressure to the detriment of P. destructans' saprotrophic ability. Based on the positive function of multiple saprotrophic enzymes, the causal agent of White-nose Syndrome shows potential for environmental growth on a variety of substrates found in caves, albeit at a reduced level compared to environmental strains. Our data suggest that if P. destructans emerged as an opportunistic infection from an environmental source, co-evolution with its host may have led to a reduced capacity for saprotrophic growth. PMID:24466096

  3. Case report: a prototypical experience of 'poltergeist' activity, conspicuous quantitative electroencephalographic patterns, and sLORETA profiles - suggestions for intervention.

    PubMed

    Roll, William G; Saroka, Kevin S; Mulligan, Bryce P; Hunter, Mathew D; Dotta, Blake T; Gang, Noa; Scott, Mandy A; St-Pierre, Linda S; Persinger, Michael A

    2012-01-01

    People who report objects moving in their presence, unusual sounds, glows around other people, and multiple sensed presences but do not meet the criteria for psychiatric disorders have been shown to exhibit electrical anomalies over the right temporal lobes. This article reports the striking quantitative electroencephalography, sLORETA results, and experimental elicitation of similar subjective experiences in a middle-aged woman who has been distressed by these classic phenomena that began after a head injury. She exhibited a chronic electrical anomaly over the right temporoinsular region. The rotation of a small pinwheel near her while she 'concentrated' upon it was associated with increased coherence between the left and right temporal lobes and concurrent activation of the left prefrontal region. The occurrence of the unusual phenomena and marked 'sadness' was associated with increased geomagnetic activity; she reported a similar mood when these variations were simulated experimentally. Our quantitative measurements suggest people displaying these experiences and possible anomalous energies can be viewed clinically and potentially treated. PMID:22229671

  4. Large plasmaspheric electric fields at L approximately 2 measured by the S3-3 satellite during strong geomagnetic activity

    NASA Technical Reports Server (NTRS)

    Gonzalez, W. D.; Pinto, O., Jr.; Mendes, O., Jr.; Mozer, F. S.

    1986-01-01

    Large plasmaspheric electric fields at L is approximately 2 measured by the S3-3 satellite during strong geomagnetic activity are reported. Since these measurements have amplitudes comparable to those of the local corotation electric field, during such events the plasmasphere is expected to get strongly altered event at such low L-values. Furthermore, those measurements could contribute to the understanding of the physics of the convection/electric field penetration to the low latitude plasmaphere as well as the disturbed dynamo, during strong geomagnetic activity. For this purpose, critical parameters related to geomagnetic activity are also presented for the reported electric field events.

  5. Increased expression and activity of nuclear cathepsin L in cancer cells suggests a novel mechanism of cell transformation.

    PubMed

    Goulet, Brigitte; Sansregret, Laurent; Leduy, Lam; Bogyo, Matthew; Weber, Ekkehard; Chauhan, Shyam S; Nepveu, Alain

    2007-09-01

    It is generally accepted that the role of cathepsin L in cancer involves its activities outside the cells once it has been secreted. However, cathepsin L isoforms that are devoid of a signal peptide were recently shown to be present in the nucleus where they proteolytically process the CCAAT-displacement protein/cut homeobox (CDP/Cux) transcription factor. A role for nuclear cathepsin L in cell proliferation could be inferred from the observation that the CDP/Cux processed isoform can accelerate entry into S phase. Here, we report that in many transformed cells the proteolytic processing of CDP/Cux is augmented and correlates with increased cysteine protease expression and activity in the nucleus. Taking advantage of an antibody that recognizes the prodomain of human cathepsin L, we showed that human cells express short cathepsin L species that do not contain a signal peptide, do not transit through the endoplasmic reticulum, are not glycosylated, and localize to the nucleus. We also showed that transformation by the ras oncogene causes rapid increases both in the production of short nuclear cathepsin L isoforms and in the processing of CDP/Cux. Using a cell-based assay, we showed that a cell-permeable inhibitor of cysteine proteases is able to delay the progression into S phase and the proliferation in soft agar of ras-transformed cells, whereas the non-cell-permeable inhibitor had no effect. Taken together, these results suggest that the role of cathepsin L in cancer might not be limited to its extracellular activities but may also involve its processing function in the nucleus. PMID:17855659

  6. Strong Nonadditivity as a Key Structure–Activity Relationship Feature: Distinguishing Structural Changes from Assay Artifacts

    PubMed Central

    2015-01-01

    Nonadditivity in protein–ligand affinity data represents highly instructive structure–activity relationship (SAR) features that indicate structural changes and have the potential to guide rational drug design. At the same time, nonadditivity is a challenge for both basic SAR analysis as well as many ligand-based data analysis techniques such as Free-Wilson Analysis and Matched Molecular Pair analysis, since linear substituent contribution models inherently assume additivity and thus do not work in such cases. While structural causes for nonadditivity have been analyzed anecdotally, no systematic approaches to interpret and use nonadditivity prospectively have been developed yet. In this contribution, we lay the statistical framework for systematic analysis of nonadditivity in a SAR series. First, we develop a general metric to quantify nonadditivity. Then, we demonstrate the non-negligible impact of experimental uncertainty that creates apparent nonadditivity, and we introduce techniques to handle experimental uncertainty. Finally, we analyze public SAR data sets for strong nonadditivity and use recourse to the original publications and available X-ray structures to find structural explanations for the nonadditivity observed. We find that all cases of strong nonadditivity (ΔΔpKi and ΔΔpIC50 > 2.0 log units) with sufficient structural information to generate reasonable hypothesis involve changes in binding mode. With the appropriate statistical basis, nonadditivity analysis offers a variety of new attempts for various areas in computer-aided drug design, including the validation of scoring functions and free energy perturbation approaches, binding pocket classification, and novel features in SAR analysis tools. PMID:25760829

  7. Benzo[b]quinolizinium Derivatives Have a Strong Antimalarial Activity and Inhibit Indoleamine Dioxygenase

    PubMed Central

    Jortzik, Esther; Zocher, Kathleen; Isernhagen, Antje; Mailu, Boniface M.; Rahlfs, Stefan; Viola, Giampietro; Wittlin, Sergio; Hunt, Nicholas H.; Ihmels, Heiko

    2015-01-01

    The heme-containing enzymes indoleamine 2,3-dioxygenase-1 (IDO-1) and IDO-2 catalyze the conversion of the essential amino acid tryptophan into kynurenine. Metabolites of the kynurenine pathway and IDO itself are involved in immunity and the pathology of several diseases, having either immunoregulatory or antimicrobial effects. IDO-1 plays a central role in the pathogenesis of cerebral malaria, which is the most severe and often fatal neurological complication of infection with Plasmodium falciparum. Mouse models are usually used to study the underlying pathophysiology. In this study, we screened a natural compound library against mouse IDO-1 and identified 8-aminobenzo[b]quinolizinium (compound 2c) to be an inhibitor of IDO-1 with potency at nanomolar concentrations (50% inhibitory concentration, 164 nM). Twenty-one structurally modified derivatives of compound 2c were synthesized for structure-activity relationship analyses. The compounds were found to be selective for IDO-1 over IDO-2. We therefore compared the roles of prominent amino acids in the catalytic mechanisms of the two isoenzymes via homology modeling, site-directed mutagenesis, and kinetic analyses. Notably, methionine 385 of IDO-2 was identified to interfere with the entrance of l-tryptophan to the active site of the enzyme, which explains the selectivity of the inhibitors. Most interestingly, several benzo[b]quinolizinium derivatives (6 compounds with 50% effective concentration values between 2.1 and 6.7 nM) were found to be highly effective against P. falciparum 3D7 blood stages in cell culture with a mechanism independent of IDO-1 inhibition. We believe that the class of compounds presented here has unique characteristics; it combines the inhibition of mammalian IDO-1 with strong antiparasitic activity, two features that offer potential for drug development. PMID:26459907

  8. The StrongWomen Change Clubs: Engaging Residents to Catalyze Positive Change in Food and Physical Activity Environments

    PubMed Central

    Seguin, Rebecca A.; Folta, Sara C.; Nelson, Miriam E.; Heidkamp-Young, Eleanor; Fenton, Mark; Junot, Bridgid

    2014-01-01

    Introduction. The epidemic of obesity is a multifaceted public health issue. Positive policy and environmental changes are needed to support healthier eating and increased physical activity. Methods. StrongWomen Change Clubs (SWCCs) were developed through an academic-community research partnership between researchers at Cornell University and Tufts University and community partners (cooperative extension educators) in rural towns in seven U.S. states. Extension educators served as the local leader and each recruited 10–15 residents to undertake a project to improve some aspect of the nutrition or physical activity environment. Most residents had limited (or no) experience in civic engagement. At 6 and 12 months after implementation, the research team conducted key informant interviews with SWCC leaders to capture their perceptions of program process, benchmark achievement, and self-efficacy. Results. At 12 months, each SWCC had accomplished one benchmark; the majority had completed three or more benchmarks. They described common processes for achieving benchmarks such as building relationships and leveraging stakeholder partnerships. Barriers to benchmark achievement included busy schedules and resistance to and slow pace of change. Conclusion. Findings suggest that community change initiatives that involve stakeholders, build upon existing activities and organizational resources, and establish feasible timelines and goals can successfully catalyze environmental change. PMID:25525441

  9. Multiple sclerosis: a role for astroglia in active demyelination suggested by class II MHC expression and ultrastructural study.

    PubMed

    Lee, S C; Moore, G R; Golenwsky, G; Raine, C S

    1990-03-01

    Central nervous system (CNS) tissue was studied by immunocytochemistry and electron microscopy from three cases of multiple sclerosis (MS) in which evidence of ongoing myelin breakdown could be documented. The study focussed upon the role of glial cells in the pathogenesis of demyelination. In acute MS, demyelination involved the vesicular dissolution of myelin from intact axons and a paucity of fibrillary astrogliosis. Foamy macrophages, many of them probably derived from transformed and recently proliferated microglia, contained recognizable myelin debris and lipid droplets and were abundant throughout the lesions. These cells formed the major phagocytic population and stained positively for class II major histocompatibility complex antigens (HLA-DR; Ia). In acute MS lesions, rounded astrocytes were encountered which possessed membrane-bound compartments enclosing phagocytosed fragments of myelin basic protein-positive debris. Despite the superficial resemblance of these cells to foamy macrophages, the presence of intermediate filaments, glycogen granules and diffuse glial fibrillary acidic protein positivity supported an astroglial identity. Astrocyte processes were involved in myelin removal and invested recently demyelinated axons. Hypertrophic fibrous astrocytes were common in chronic active lesions, were capable of myelin degradation and on occasion, contained myelin debris attached to clathrin-coated pits. These astrocytes were sometimes Ia+. Oligodendrocytes were depleted from the center of active lesions but were numerous at the lesion margin, suggesting survival and proliferation. They stained positively for myelin-associated glycoprotein, a marker for immature oligodendrocytes. However, they were invariably Ia-. The findings confirm and further support a role for the astrocyte as both an antigen presenting cell and a phagocyte in the CNS during MS. PMID:2307980

  10. Subcaste differences in neural activation suggest a prosocial role for oxytocin in eusocial naked mole-rats.

    PubMed

    Hathaway, Georgia A; Faykoo-Martinez, Mariela; Peragine, Deane E; Mooney, Skyler J; Holmes, Melissa M

    2016-03-01

    The neuropeptide oxytocin (OT) influences prosocial behavior(s), aggression, and stress responsiveness, and these diverse effects are regulated in a species- and context-specific manner. The naked mole-rat (Heterocephalus glaber) is a unique species with which to study context-dependent effects of OT, exhibiting a strict social hierarchy with behavioral specialization within the subordinate caste: soldiers are aggressive and defend colonies against unfamiliar conspecifics while workers are prosocial and contribute to in-colony behaviors such as pup care. To determine if OT is involved in subcaste-specific behaviors, we compared behavioral responses between workers and soldiers of both sexes during a modified resident/intruder paradigm, and quantified activation of OT neurons in the hypothalamic paraventricular nucleus (PVN) and supraoptic nucleus (SON) using the immediate-early-gene marker c-fos co-localized with OT neurons. Resident workers and soldiers were age-matched with unfamiliar worker stimulus animals as intruders, and encounters were videorecorded and scored for aggressive behaviors. Colony-matched controls were left in their home colony for the duration of the encounters. Brains were extracted and cell counts were conducted for OT immunoreactive (ir), c-fos-ir, and percentage of OT-c-fos double-labeled cells. Results indicate that resident workers were less aggressive but showed greater OT neural activity than soldiers. Furthermore, a linear model including social treatment, cortisol, and subcaste revealed that subcaste was the only significant predictor of OT-c-fos double-labeled cells in the PVN. These data suggest that in naked mole-rats OT promotes prosocial behaviors rather than aggression and that even within subordinates status exerts robust effects on brain and behavior. PMID:26718226

  11. IODP Expedition 331: Strong and Expansive Subseafloor Hydrothermal Activities in the Okinawa Trough

    NASA Astrophysics Data System (ADS)

    Takai, K.; Mottl, M. J.; Nielsen, S. H. H.; IODP Expedition 331 Scientists, the

    2012-04-01

    Integrated Ocean Drilling Program (IODP) Expedition 331 drilled into the Iheya North hydrothermal system in the middle Okinawa Trough in order to investigate active subseafloor microbial ecosystems and their physical and chemical settings. We drilled five sites during Expedition 331 using special guide bases at three holes for reentry, casing, and capping, including installation of a steel mesh platform with valve controls for postcruise sampling of fluids. At Site C0016, drilling at the base of the North Big Chimney (NBC) mound yielded low recovery, but core included the first Kuroko-type black ore ever recovered from the modern subseafloor. The other four sites yielded interbedded hemipelagic and strongly pumiceous volcaniclastic sediment, along with volcanogenic breccias that are variably hydrothermally altered and mineralized. At most sites, analyses of interstitial water and headspace gas yielded complex patterns with depth and lateral distance of only a few meters. Documented processes included formation of brines and vapor-rich fluids by phase separation and segregation, uptake of Mg and Na by alteration minerals in exchange for Ca, leaching of K at high temperature and uptake at low temperature, anhydrite precipitation, potential microbial oxidation of organic matter and anaerobic oxidation of methane utilizing sulfate, and methanogenesis. Shipboard analyses have found evidence for microbial activity in sediments within the upper 10-30 m below seafloor (mbsf) where temperatures were relatively low, but little evidence in the deeper hydrothermally altered zones and hydrothermal fluid regime. doi:10.2204/iodp.sd.13.03.2011

  12. Association of Strong Immune Responses to PPE Protein Rv1168c with Active Tuberculosis ▿

    PubMed Central

    Khan, Nooruddin; Alam, Kaiser; Nair, Shiny; Valluri, Vijaya Lakshmi; Murthy, Kolluri J. R.; Mukhopadhyay, Sangita

    2008-01-01

    Accurate diagnosis of tuberculosis (TB) infection is critical for the treatment, prevention, and control of TB. Conventional diagnostic tests based on purified protein derivative (PPD) do not achieve the required diagnostic sensitivity. Therefore, in this study, we have evaluated the immunogenic properties of Rv1168c, a member of the PPE family, in comparison with PPD, which is routinely used in the tuberculin test, and Hsp60 and ESAT-6, well-known immunodominant antigens of Mycobacterium tuberculosis. In a conventional enzyme immunoassay, the recombinant Rv1168c protein displayed stronger immunoreactivity against the sera obtained from patients with clinically active TB than did PPD, Hsp60, or ESAT-6 and could distinguish TB patients from Mycobacterium bovis BCG-vaccinated controls. Interestingly, Rv1168c antigen permits diagnosis of smear-negative pulmonary TB as well as extrapulmonary TB cases, which are often difficult to diagnose by conventional tests. The immunodominant nature of Rv1168c makes it a promising candidate to use in serodiagnosis of TB. In addition, our studies also show that Rv1168c is a potent T-cell antigen which elicits a strong gamma interferon response in sensitized peripheral blood mononuclear cells obtained from TB patients. PMID:18400969

  13. Generalized Laplacian for magnetograms of solar active region as possible predictor of strong flare.

    NASA Astrophysics Data System (ADS)

    Volobuev, D. M.; Makarenko, N. G.; Knyazeva, I. S.

    2016-02-01

    Search for predictors of strong flare produced in solar active region (AR) is important application of solar physics. Here we consider the sequence of magnetogram (LOS SDO/HMI instrument) for AR 2034, 2035 and 2036 (April 2014). All three AR were observed on the Sun at about the same time, characterized by low probability of flare events according to official forecasts of NOAA, but 2036 still produced X1-flare near the center of solar disc (April 18). We propose that Generalized Laplacian is a descriptor which could help predict this and similar events. The Laplacian is associated with the flow of Ricci curvature and with topological invariants of the observed field - Betti numbers for compact manifolds. Using discrete version of Morse theory, we consider each pixel of energy flux (B2) image as a simplex and calculate its combinatorial Bochner Laplacian. It was found that maximum of Laplacian is located near AR polarity inversion line. Evolution of total spatial variation of the Laplacian has a number of maxima in time for each of examined AR. However, the maxima in AR 2035 and AR 2034 have relatively low amplitude, while the highest maximum prefaced X1 flare in AR 2036 by about 29 hours.

  14. Simulation suggests that rapid activation of social distancing can arrest epidemic development due to a novel strain of influenza

    PubMed Central

    Kelso, Joel K; Milne, George J; Kelly, Heath

    2009-01-01

    Background Social distancing interventions such as school closure and prohibition of public gatherings are present in pandemic influenza preparedness plans. Predicting the effectiveness of intervention strategies in a pandemic is difficult. In the absence of other evidence, computer simulation can be used to help policy makers plan for a potential future influenza pandemic. We conducted simulations of a small community to determine the magnitude and timing of activation that would be necessary for social distancing interventions to arrest a future pandemic. Methods We used a detailed, individual-based model of a real community with a population of approximately 30,000. We simulated the effect of four social distancing interventions: school closure, increased isolation of symptomatic individuals in their household, workplace nonattendance, and reduction of contact in the wider community. We simulated each of the intervention measures in isolation and in several combinations; and examined the effect of delays in the activation of interventions on the final and daily attack rates. Results For an epidemic with an R0 value of 1.5, a combination of all four social distancing measures could reduce the final attack rate from 33% to below 10% if introduced within 6 weeks from the introduction of the first case. In contrast, for an R0 of 2.5 these measures must be introduced within 2 weeks of the first case to achieve a similar reduction; delays of 2, 3 and 4 weeks resulted in final attack rates of 7%, 21% and 45% respectively. For an R0 of 3.5 the combination of all four measures could reduce the final attack rate from 73% to 16%, but only if introduced without delay; delays of 1, 2 or 3 weeks resulted in final attack rates of 19%, 35% or 63% respectively. For the higher R0 values no single measure has a significant impact on attack rates. Conclusion Our results suggest a critical role of social distancing in the potential control of a future pandemic and indicate that such

  15. The evolution from weak to strong geomagnetic activity - An interpretation in terms of deterministic chaos

    NASA Technical Reports Server (NTRS)

    Baker, D. N.; Klimas, A. J.; Mcpherron, R. L.; Buechner, J.

    1990-01-01

    An analogue of the magnetosphere developed on the basis of Shaw's (1984) dripping faucet model was used to model the mechanisms of the magnetospheric response to energy transfer from the solar wind. It is demonstrated that geomagnetic activity results from nonlinearly coupled physical processes and that the strength and the nature of the coupling changes dramatically as the magnetosphere is driven harder and harder by increasing energy input. Based on initial results obtained from the model, is is suggested that a chaotic transition takes place in the analogue system as the loading rate is increased beyond a critical value. This model is able to explain many of the features in the results of linear prediction filtering techniques.

  16. One-Dimensional Chirality: Strong Optical Activity in Epsilon-Near-Zero Metamaterials.

    PubMed

    Rizza, Carlo; Di Falco, Andrea; Scalora, Michael; Ciattoni, Alessandro

    2015-07-31

    We suggest that electromagnetic chirality, generally displayed by 3D or 2D complex chiral structures, can occur in 1D patterned composites whose components are achiral. This feature is highly unexpected in a 1D system which is geometrically achiral since its mirror image can always be superposed onto it by a 180 deg rotation. We analytically evaluate from first principles the bianisotropic response of multilayered metamaterials and we show that the chiral tensor is not vanishing if the system is geometrically one-dimensional chiral; i.e., its mirror image cannot be superposed onto it by using translations without resorting to rotations. As a signature of 1D chirality, we show that 1D chiral metamaterials support optical activity and we prove that this phenomenon undergoes a dramatic nonresonant enhancement in the epsilon-near-zero regime where the magnetoelectric coupling can become dominant in the constitutive relations. PMID:26274441

  17. Crystal Structures of the Response Regulator DosR From Mycobacterium Tuberculosis Suggest a Helix Rearrangement Mechanism for Phosphorylation Activation

    SciTech Connect

    Wisedchaisri, G.; Wu, M.; Sherman, D.R.; Hol, W.G.J.

    2009-05-26

    The response regulator DosR is essential for promoting long-term survival of Mycobacterium tuberculosis under low oxygen conditions in a dormant state and may be responsible for latent tuberculosis in one-third of the world's population. Here, we report crystal structures of full-length unphosphorylated DosR at 2.2 {angstrom} resolution and its C-terminal DNA-binding domain at 1.7 {angstrom} resolution. The full-length DosR structure reveals several features never seen before in other response regulators. The N-terminal domain of the full-length DosR structure has an unexpected ({beta}{alpha}){sub 4} topology instead of the canonical ({beta}{alpha}){sub 5} fold observed in other response regulators. The linker region adopts a unique conformation that contains two helices forming a four-helix bundle with two helices from another subunit, resulting in dimer formation. The C-terminal domain in the full-length DosR structure displays a novel location of helix {alpha}10, which allows Gln199 to interact with the catalytic Asp54 residue of the N-terminal domain. In contrast, the structure of the DosR C-terminal domain alone displays a remarkable unstructured conformation for helix {alpha}10 residues, different from the well-defined helical conformations in all other known structures, indicating considerable flexibility within the C-terminal domain. Our structures suggest a mode of DosR activation by phosphorylation via a helix rearrangement mechanism.

  18. Anti-Inflammation Activities of Mycosporine-Like Amino Acids (MAAs) in Response to UV Radiation Suggest Potential Anti-Skin Aging Activity

    PubMed Central

    Suh, Sung-Suk; Hwang, Jinik; Park, Mirye; Seo, Hyo Hyun; Kim, Hyoung-Shik; Lee, Jeong Hun; Moh, Sang Hyun; Lee, Taek-Kyun

    2014-01-01

    Certain photosynthetic marine organisms have evolved mechanisms to counteract UV-radiation by synthesizing UV-absorbing compounds, such as mycosporine-like amino acids (MAAs). In this study, MAAs were separated from the extracts of marine green alga Chlamydomonas hedleyi using HPLC and were identified as porphyra-334, shinorine, and mycosporine-glycine (mycosporine-Gly), based on their retention times and maximum absorption wavelengths. Furthermore, their structures were confirmed by triple quadrupole MS/MS. Their roles as UV-absorbing compounds were investigated in the human fibroblast cell line HaCaT by analyzing the expression levels of genes associated with antioxidant activity, inflammation, and skin aging in response to UV irradiation. The mycosporine-Gly extract, but not the other MAAs, had strong antioxidant activity in the 2,2-diphenyl-1-picryhydrazyl (DPPH) assay. Furthermore, treatment with mycosporine-Gly resulted in a significant decrease in COX-2 mRNA levels, which are typically increased in response to inflammation in the skin, in a concentration-dependent manner. Additionally, in the presence of MAAs, the UV-suppressed genes, procollagen C proteinase enhancer (PCOLCE) and elastin, which are related to skin aging, had increased expression levels equal to those in UV-mock treated cells. Interestingly, the increased expression of involucrin after UV exposure was suppressed by treatment with the MAAs mycosporine-Gly and shinorine, but not porphyra-334. This is the first report investigating the biological activities of microalgae-derived MAAs in human cells. PMID:25317535

  19. Effect of a strong, DC-induced magnetic field on circadian singing activity of the house cricket (orthoptera:gryllidae)

    SciTech Connect

    Shaw, K.C.; Bitzer, R.J.; Galliart, L.

    1995-05-01

    We investigated the effect of a strong, DC-induced electromagnetic field (EMF) on the circadian singing activity of the house cricket, Acheta domesticus (L.). Groups of 10 crickets were exposed to strong, DC-induced EMFs under two light regimes, 12:12 (L:D) h and 0:24 (L:D) h. Exposure to the strong EMF resulted in an increase in mean time per hour during which one or more crickets were singing and in number of crickets singing per hour. Correcting for phase shift during O:24 (L:D) h, the daily pattern of singing was apparently unaffected by any treatment. The greatest percentage of singing and number of crickets singing per hour occurred during actual or expected scotophase. This is the first report of an increase in insect activity during exposure to a strong DC-induced EMF.

  20. Strongly coupled Pd nanotetrahedron/tungsten oxide nanosheet hybrids with enhanced catalytic activity and stability as oxygen reduction electrocatalysts.

    PubMed

    Lu, Yizhong; Jiang, Yuanyuan; Gao, Xiaohui; Wang, Xiaodan; Chen, Wei

    2014-08-20

    The design and synthesis of highly active oxygen reduction reaction (ORR) catalysts with strong durability at low cost is extremely desirable but still remains a significant challenge. Here we develop an efficient strategy that utilizes organopalladium(I) complexes containing palladium-palladium bonds as precursors for the synthesis of strongly coupled Pd tetrahedron-tungsten oxide nanosheet hybrids (Pd/W18O49) to improve the electrocatalytic activity and stability of Pd nanocrystals. The hybrid materials are synthesized by direct nucleation, growth, and anchoring of Pd tetrahedral nanocrystals on the in situ-synthesized W18O49 nanosheets. Compared to supportless Pd nanocrystals and W18O49, their hybrids exhibited not only surprisingly high activity but also superior stability to Pt for the ORR in alkaline solutions. X-ray photoelectron spectroscopy, high-resolution transmission electron microscopy, and electrochemical analyses indicated that the enhanced electrocatalytic activity and durability are associated with the increased number and improved catalytic activity of active sites, which is induced by the strong interaction between the Pd tetrahedrons and W18O49 nanosheet supports. The present study provides a novel strategy for synthesizing hybrid catalysts with strong chemical attachment and electrical coupling between nanocatalysts and supports. The strategy is expected to open up exciting opportunities for developing a novel class of metal-support hybrid nanoelectrocatalysts with improved ORR activity and durability for both fuel cells and metal-air batteries. PMID:25054583

  1. Optical Activity Enhanced by Strong Inter-molecular Coupling in Planar Chiral Metamaterials

    PubMed Central

    Kim, Teun-Teun; Oh, Sang Soon; Park, Hyun-Sung; Zhao, Rongkuo; Kim, Seong-Han; Choi, Wonjune; Min, Bumki; Hess, Ortwin

    2014-01-01

    The polarization of light can be rotated in materials with an absence of molecular or structural mirror symmetry. While this rotating ability is normally rather weak in naturally occurring chiral materials, artificial chiral metamaterials have demonstrated extraordinary rotational ability by engineering intra-molecular couplings. However, while in general, chiral metamaterials can exhibit strong rotatory power at or around resonances, they convert linearly polarized waves into elliptically polarized ones. Here, we demonstrate that strong inter-molecular coupling through a small gap between adjacent chiral metamolecules can lead to a broadband enhanced rotating ability with pure rotation of linearly polarized electromagnetic waves. Strong inter-molecular coupling leads to nearly identical behaviour in magnitude, but engenders substantial difference in phase between transmitted left and right-handed waves. PMID:25209452

  2. Redox-active tetraruthenium metallacycles: reversible release of up to eight electrons resulting in strong electrochromism.

    PubMed

    Fink, Daniel; Weibert, Bernhard; Winter, Rainer F

    2016-05-01

    Tetraruthenium macrocycles with 1,4-divinylphenylene and diarylamine-substituted isophthalic acids as the sides display up to eight one-electron redox steps and rich electrochromic behaviour with strong absorptions of the dications in the near infrared and of the tetra- and hexacations at low energies in the visible. PMID:27067796

  3. Nicotinic Activity of Arecoline, the Psychoactive Element of "Betel Nuts", Suggests a Basis for Habitual Use and Anti-Inflammatory Activity

    PubMed Central

    Papke, Roger L.; Horenstein, Nicole A.; Stokes, Clare

    2015-01-01

    Habitual chewing of "betel nut" preparations constitutes the fourth most common human self-administration of a psychoactive substance after alcohol, caffeine, and nicotine. The primary active ingredient in these preparations is arecoline, which comes from the areca nut, the key component of all such preparations. Arecoline is known to be a relatively non-selective muscarinic partial agonist, accounting for many of the overt peripheral and central nervous system effects, but not likely to account for the addictive properties of the drug. We report that arecoline has activity on select nicotinic acetylcholine receptor (nAChR) subtypes, including the two classes of nAChR most related to the addictive properties of nicotine: receptors containing α4 and β2 subunits and those which also contain α6 and β3 subunits. Arecoline is a partial agonist with about 6–10% efficacy for the α4* and α6* receptors expressed in Xenopus oocytes. Additionally, arecoline is a silent agonist of α7 nAChR; while it does not activate α7 receptors when applied alone, it produces substantial activation when co-applied with the positive allosteric modulator PNU-120696. Some α7 silent agonists are effective inhibitors of inflammation, which might account for anti-inflammatory effects of arecoline. Arecoline's activity on nAChR associated with addiction may account for the habitual use of areca nut preparations in spite of the well-documented risk to personal health associated with oral diseases and cancer. The common link between betel and tobacco suggests that partial agonist therapies with cytisine or the related compound varenicline may also be used to aid betel cessation attempts. PMID:26488401

  4. Barriers to and Suggestions for a Healthful, Active Lifestyle as Perceived by Rural and Urban Costa Rican Adolescents

    ERIC Educational Resources Information Center

    Monge-Rojas, Rafael; Garita-Arce, Carlos; Sanchez-Lopez, Marta; Colon-Ramos, Uriyoan

    2009-01-01

    Objective: To assess the perceptions of rural and urban Costa Rican adolescents regarding which barriers and motivators affect their adoption of an active lifestyle. Design: Data were collected in focus group discussions. Participants: 108 male and female adolescents aged 12 to 18 from the 7th to 11th grades. Setting: Two urban and 1 rural high…

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

    PubMed

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

    2002-10-01

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

  6. Isolation of a strong promoter fragment from endophytic Enterobacter cloacae and verification of its promoter activity when its host strain colonizes banana plants.

    PubMed

    Wang, Yu Guang; Xia, Qi Yu; Gu, Wen Liang; Sun, Jian Bo; Zhang, He; Lu, Xue Hua; Lu, Juan; Peng, Ming; Zhang, Xin

    2012-02-01

    To engineer endophytic Enterobacter cloacae as a biocontrol agent against banana fusarium wilt, a promoter-probe plasmid pUCK was constructed to identify a strong promoter to express disease resistance genes. Using a kanamycin resistance gene for selection, 10 fragments with strong promoter activity were identified from the genome of the E. cloacae KKWB-10 strain. The regions of these 10 fragments that were the primary contributors to the promoter function were identified, and their promoter activities were further evaluated using green fluorescent protein (GFP) as a reporter gene. Fragment 132a″ drove the highest level of GFP activity when the bacteria bearing the fragments were cultured in Luria-Bertani and banana stem extract media. The GFP-expressing strain harboring fragment 132a″ (K-pUCK7-132a″-GT) was then inoculated into banana plantlets (about 1 × 10(7) CFU per plant) to verify the activity of fragment 132a″ in planta. Ten days after inoculation, tissue sections of these banana plantlets were observed by laser confocal scanning microscope. Green fluorescence was observed in the tissues of banana plantlets inoculated with K-pUCK7-132a″-GT but not in uninoculated controls. These results suggest that fragment 132a″ possesses strong promoter activity when its host strain colonizes the banana plants and can be used to engineer endophytic E. cloacae KKWB-10 for biocontrol. PMID:22080347

  7. A strong pelvic floor is associated with higher rates of sexual activity in women with pelvic floor disorders

    PubMed Central

    Kanter, Gregg; Rogers, Rebecca G; Pauls, Rachel N; Kammerer-Doak, Dorothy; Thakar, Ranee

    2015-01-01

    Introduction and Hypothesis We evaluated the associations between pelvic floor muscle strength and tone with sexual activity and sexual function in women with pelvic floor disorders. Methods This was a secondary analysis of a multicenter study of women with pelvic floor disorders from the US and UK performed to validate the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire, IUGA-Revised (PISQ-IR). Participants were surveyed about whether they were sexually active and completed the PISQ-IR and Female Sexual Function Index (FSFI) questionnaires to assess sexual function. Physical exams included assessment of pelvic floor strength by the Oxford Grading Scale, and assessment of pelvic floor tone per ICS guidelines. Results The cohort of 585 women was middle aged (mean age 54.9 +/−12.1) with 395 (67.5%) reporting sexual activity. Women with a strong pelvic floor (n=275) were more likely to report sexual activity than women with weak strength (n=280) (75.3 vs. 61.8%, p<0.001), but normal or hypoactive pelvic floor tone was not associated with sexual activity (68.8 vs. 60.2%, normal vs. hypoactive, p=0.08). After multivariable analysis, a strong pelvic floor remained predictive of sexual activity (OR 1.89, CI 1.18–3.03, p<0.01). Among sexually active women (n=370), a strong pelvic floor was associated with higher scores on the PISQ-IR domain of condition impact (Parameter Estimate 0.20+/−0.09, P=0.04), and FSFI orgasm domain (PE 0.51+/−0.17, P=0.004). Conclusion A strong pelvic floor is associated with higher rates of sexual activity as well as higher sexual function scores on the condition impact domain of the PISQ-IR and orgasm domain of the FSFI. PMID:25994625

  8. Cleavage of Chordin by Xolloid Metalloprotease Suggests a Role for Proteolytic Processing in the Regulation of Spemann Organizer Activity

    PubMed Central

    Piccolo, Stefano; Agius, Eric; Lu, Bin; Goodman, Shelley; Dale, Leslie

    2011-01-01

    Summary The Xolloid secreted metalloprotease, a tolloid-related protein, was found to cleave Chordin and Chordin/BMP-4 complexes at two specific sites in biochemical experiments. Xolloid mRNA blocks secondary axes caused by chordin, but not by noggin, follistatin, or dominant-negative BMP receptor, mRNA injection. Xolloid-treated Chordin protein was unable to antagonize BMP activity. Furthermore, Xolloid digestion released biologically active BMPs from Chordin/BMP inactive complexes. Injection of dominant-negative Xolloid mRNA indicated that the in vivo function of Xolloid is to limit the extent of Spemann’s organizer field. We propose that Xolloid regulates organizer function by a novel proteolytic mechanism involving a double inhibition pathway required to pattern the dorsoventral axis: XOLL⊣CHD⊣BMPs→BMPR PMID:9363949

  9. Strong nonlinear focusing of light in nonlinearly controlled electromagnetic active metamaterial field concentrators

    NASA Astrophysics Data System (ADS)

    Rapoport, Yu G.; Boardman, A. D.; Grimalsky, V. V.; Ivchenko, V. M.; Kalinich, N.

    2014-05-01

    The idea of nonlinear ‘transformation optics-inspired’ [1-6] electromagnetic cylindrical field concentrators has been taken up in a preliminary manner in a number of conference reports [7-9]. Such a concentrator includes both external linear region with a dielectric constant increased towards the centre and internal region with nonlinearity characterized by constant coefficients. Then, in the process of farther investigations we realized the following factors considered neither in [7-9] nor in the recent paper [10]: saturation of nonlinearity, nonlinear losses, linear gain, numerical convergence, when nonlinear effect becomes very strong and formation of ‘hotspots’ starts. It is clearly demonstrated here that such a strongly nonlinear process starts when the nonlinear amplitude of any incident beam(s) exceeds some ‘threshold’ value. Moreover, it is shown that the formation of hotspots may start as the result of any of the following processes: an increase of the input amplitude, increasing the linear amplification in the central nonlinear region, decreasing the nonlinear losses, a decrease in the saturation of the nonlinearity. Therefore, a tendency to a formation of ‘hotspots’ is a rather universal feature of the strongly nonlinear behaviour of the ‘nonlinear resonator’ system, while at the same time the system is not sensitive to the ‘prehistory’ of approaching nonlinear threshold intensity (amplitude). The new proposed method includes a full-wave nonlinear solution analysis (in the nonlinear region), a new form of complex geometric optics (in the linear inhomogeneous external cylinder), and new boundary conditions, matching both solutions. The observed nonlinear phenomena will have a positive impact upon socially and environmentally important devices of the future. Although a graded-index concentrator is used here, it is a direct outcome of transformation optics. Numerical evaluations show that for known materials these nonlinear effects

  10. The complex structures of isocitrate dehydrogenase from Clostridium thermocellum and Desulfotalea psychrophila suggest a new active site locking mechanism

    PubMed Central

    Leiros, Hanna-Kirsti S.; Fedøy, Anita-Elin; Leiros, Ingar; Steen, Ida Helene

    2012-01-01

    Isocitrate dehydrogenase (IDH) catalyzes the oxidative NAD(P)+-dependent decarboxylation of isocitrate into α-ketoglutarate and CO2 and is present in organisms spanning the biological range of temperature. We have solved two crystal structures of the thermophilic Clostridium thermocellum IDH (CtIDH), a native open apo CtIDH to 2.35 Å and a quaternary complex of CtIDH with NADP+, isocitrate and Mg2+ to 2.5 Å. To compare to these a quaternary complex structure of the psychrophilic Desulfotalea psychrophila IDH (DpIDH) was also resolved to 1.93 Å. CtIDH and DpIDH showed similar global thermal stabilities with melting temperatures of 67.9 and 66.9 °C, respectively. CtIDH represents a typical thermophilic enzyme, with a large number of ionic interactions and hydrogen bonds per residue combined with stabilization of the N and C termini. CtIDH had a higher activity temperature optimum, and showed greater affinity for the substrates with an active site that was less thermolabile compared to DpIDH. The uncompensated negative surface charge and the enlarged methionine cluster in the hinge region both of which are important for cold activity in DpIDH, were absent in CtIDH. These structural comparisons revealed that prokaryotic IDHs in subfamily II have a unique locking mechanism involving Arg310, Asp251′ and Arg255 (CtIDH). These interactions lock the large domain to the small domain and direct NADP+ into the correct orientation, which together are important for NADP+ selectivity. PMID:23650595

  11. Toward understanding the mechanism underlying the strong adjuvant activity of aluminum salt nanoparticles.

    PubMed

    Ruwona, Tinashe B; Xu, Haiyue; Li, Xu; Taylor, Amber N; Shi, Yan-Chun; Cui, Zhengrong

    2016-06-01

    Aluminum salts such as aluminum oxyhydroxide and aluminum hydroxyphosphate are commonly used human vaccine adjuvants. In an effort to improve the adjuvant activity of aluminum salts, we previously showed that the adjuvant activity of aluminum oxyhydroxide nanoparticles is significantly more potent than that of aluminum oxyhydroxide microparticles. The present study was designed to (i) understand the mechanism underlying the potent adjuvant activity of aluminum oxyhydroxide nanoparticles, relative to microparticles, and (ii) to test whether aluminum hydroxyphosphate nanoparticles have a more potent adjuvant activity than aluminum hydroxyphosphate microparticles as well. In human THP-1 myeloid cells, wild-type and NLRP3-deficient, both aluminum oxyhydroxide nanoparticles and microparticles stimulate the secretion of proinflammatory cytokine IL-1β by activating NLRP3 inflammasome, although aluminum oxyhydroxide nanoparticles are more potent than microparticles, likely related to the higher uptake of the nanoparticles by the THP-1 cells than the microparticles. Aluminum hydroxyphosphate nanoparticles also have a more potent adjuvant activity than microparticles in helping a model antigen lysozyme to stimulate specific antibody response, again likely related to their stronger ability to activate the NLRP3 inflammasome. PMID:27155490

  12. A Drosophila model of GSS syndrome suggests defects in active zones are responsible for pathogenesis of GSS syndrome

    PubMed Central

    Choi, Jin-Kyu; Jeon, Yong-Chul; Lee, Dae-Weon; Oh, Jae-Min; Lee, Hyun-Pil; Jeong, Byung-Hoon; Carp, Richard I.; Koh, Young Ho; Kim, Yong-Sun

    2010-01-01

    We have established a Drosophila model of Gerstmann–Sträussler–Scheinker (GSS) syndrome by expressing mouse prion protein (PrP) having leucine substitution at residue 101 (MoPrPP101L). Flies expressing MoPrPP101L, but not wild-type MoPrP (MoPrP3F4), showed severe defects in climbing ability and early death. Expressed MoPrPP101L in Drosophila was differentially glycosylated, localized at the synaptic terminals and mainly present as deposits in adult brains. We found that behavioral defects and early death of MoPrPP101L flies were not due to Caspase 3-dependent programmed cell death signaling. In addition, we found that Type 1 glutamatergic synaptic boutons in larval neuromuscular junctions of MoPrPP101L flies showed significantly increased numbers of satellite synaptic boutons. Furthermore, the amount of Bruchpilot and Discs large in MoPrPP101L flies was significantly reduced. Brains from scrapie-infected mice showed significantly decreased ELKS, an active zone matrix marker compared with those of age-matched control mice. Thus, altered active zone structures at the molecular level may be involved in the pathogenesis of GSS syndrome in Drosophila and scrapie-infected mice. PMID:20829230

  13. Bivalent Regions of Cytosine Methylation and H3K27 Acetylation Suggest an Active Role for DNA Methylation at Enhancers.

    PubMed

    Charlet, Jessica; Duymich, Christopher E; Lay, Fides D; Mundbjerg, Kamilla; Dalsgaard Sørensen, Karina; Liang, Gangning; Jones, Peter A

    2016-05-01

    The role of cytosine methylation in the structure and function of enhancers is not well understood. In this study, we investigate the role of DNA methylation at enhancers by comparing the epigenomes of the HCT116 cell line and its highly demethylated derivative, DKO1. Unlike promoters, a portion of regular and super- or stretch enhancers show active H3K27ac marks co-existing with extensive DNA methylation, demonstrating the unexpected presence of bivalent chromatin in both cultured and uncultured cells. Furthermore, our findings also show that bivalent regions have fewer nucleosome-depleted regions and transcription factor-binding sites than monovalent regions. Reduction of DNA methylation genetically or pharmacologically leads to a decrease of the H3K27ac mark. Thus, DNA methylation plays an unexpected dual role at enhancer regions, being anti-correlated focally at transcription factor-binding sites but positively correlated globally with the active H3K27ac mark to ensure structural enhancer integrity. PMID:27153539

  14. An interactive activation and competition model of person knowledge, suggested by proactive interference by traits spontaneously inferred from behaviours.

    PubMed

    Wang, Yuanbo E; Higgins, Nancy C; Uleman, James S; Michaux, Aaron; Vipond, Douglas

    2016-03-01

    People unconsciously and unintentionally make inferences about others' personality traits based on their behaviours. In this study, a classic memory phenomenon - proactive interference (PI) - is for the first time used to detect spontaneous trait inferences. PI should occur when lists of behaviour descriptions, all implying the same trait, are to be remembered. Switching to a new trait should produce 'release' from proactive interference (or RPI). Results from two experiments supported these predictions. PI and RPI effects are consistent with an interactive activation and competition model of person perception (e.g., McNeill & Burton, 2002, J. Exp. Psychol., 55A, 1141), which predicts categorical organization of social behaviours based on personality traits. Advantages of this model are discussed. PMID:26096621

  15. Early-light embryonic stimulation suggests a second route, via gene activation, to cerebral lateralization in vertebrates

    PubMed Central

    Chiandetti, Cinzia; Galliussi, Jessica; Andrew, Richard J.; Vallortigara, Giorgio

    2013-01-01

    Genetic factors determine the asymmetrical position of vertebrate embryos allowing asymmetric environmental stimulation to shape cerebral lateralization. In birds, late-light stimulation, just before hatching, on the right optic nerve triggers anatomical and functional cerebral asymmetries. However, some brain asymmetries develop in absence of embryonic light stimulation. Furthermore, early-light action affects lateralization in the transparent zebrafish embryos before their visual system is functional. Here we investigated whether another pathway intervenes in establishing brain specialization. We exposed chicks' embryos to light before their visual system was formed. We observed that such early stimulation modulates cerebral lateralization in a comparable vein of late-light stimulation on active retinal cells. Our results show that, in a higher vertebrate brain, a second route, likely affecting the genetic expression of photosensitive regions, acts before the development of a functional visual system. More than one sensitive period seems thus available to light stimulation to trigger brain lateralization. PMID:24048072

  16. Comparative modeling and molecular dynamics suggest high carboxylase activity of the Cyanobium sp. CACIAM14 RbcL protein.

    PubMed

    Siqueira, Andrei Santos; Lima, Alex Ranieri Jerônimo; Dall'Agnol, Leonardo Teixeira; de Azevedo, Juliana Simão Nina; da Silva Gonçalves Vianez, João Lídio; Gonçalves, Evonnildo Costa

    2016-03-01

    Rubisco catalyzes the first step reaction in the carbon fixation pathway, bonding atmospheric CO2/O2 to ribulose 1,5-bisphosphate; it is therefore considered one of the most important enzymes in the biosphere. Genetic modifications to increase the carboxylase activity of rubisco are a subject of great interest to agronomy and biotechnology, since this could increase the productivity of biomass in plants, algae and cyanobacteria and give better yields in crops and biofuel production. Thus, the aim of this study was to characterize in silico the catalytic domain of the rubisco large subunit (rbcL gene) of Cyanobium sp. CACIAM14, and identify target sites to improve enzyme affinity for ribulose 1,5-bisphosphate. A three-dimensional model was built using MODELLER 9.14, molecular dynamics was used to generate a 100 ns trajectory by AMBER12, and the binding free energy was calculated using MM-PBSA, MM-GBSA and SIE methods with alanine scanning. The model obtained showed characteristics of form-I rubisco, with 15 beta sheets and 19 alpha helices, and maintained the highly conserved catalytic site encompassing residues Lys175, Lys177, Lys201, Asp203, and Glu204. The binding free energy of the enzyme-substrate complexation of Cyanobium sp. CACIAM14 showed values around -10 kcal mol(-1) using the SIE method. The most important residues for the interaction with ribulose 1,5-bisphosphate were Arg295 followed by Lys334. The generated model was successfully validated, remaining stable during the whole simulation, and demonstrated characteristics of enzymes with high carboxylase activity. The binding analysis revealed candidates for directed mutagenesis sites to improve rubisco's affinity. PMID:26936271

  17. Structure of Epstein-Barr Virus Glycoprotein 42 Suggests a Mechanism for Triggering Receptor-Activated Virus Entry

    SciTech Connect

    Kirschner, Austin N.; Sorem, Jessica; Longnecker, Richard; Jardetzky, Theodore S.

    2009-05-26

    Epstein-Barr virus requires glycoproteins gH/gL, gB, and gp42 to fuse its lipid envelope with B cells. Gp42 is a type II membrane protein consisting of a flexible N-terminal region, which binds gH/gL, and a C-terminal lectin-like domain that binds to the B-cell entry receptor human leukocyte antigen (HLA) class II. Gp42 triggers membrane fusion after HLA binding, a process that requires simultaneous binding to gH/gL and a functional hydrophobic pocket in the lectin domain adjacent to the HLA binding site. Here we present the structure of gp42 in its unbound form. Comparisons to the previously determined structure of a gp42:HLA complex reveals additional N-terminal residues forming part of the gH/gL binding site and structural changes in the receptor binding domain. Although the core of the lectin domain remains similar, significant shifts in two loops and an {alpha} helix bordering the essential hydrophobic pocket suggest a structural mechanism for triggering fusion.

  18. Anthropogenic and temporal components in a complex trigger of type 1 diabetes suggest the active participation of antipyretics.

    PubMed

    Veteikis, Darijus

    2016-08-01

    Tremendous efforts in research without a conclusion on the cause of type 1 diabetes allow the presumption that there is still a blind spot in the development of T1D that is not covered by current hypotheses. The review of geographical knowledge suggests that there is a well-expressed anthropogenic element within the complex environmental trigger of T1D. On the other hand, the initiation of T1D's directed autoimmunity is temporally related to the organism's immune response, induced by entero-viruses, most expectedly. Consequently, the searched for anthropogenic environmental factor is a player temporally linked to enteroviral infections. This paper discusses the participation of antipyretic medicines, and especially paracetamol, with a whole century's history of growing sales and popularity, including indirect influence through phenacetin during the first half of the 20th century. As proposed by several independent studies, the use of pharmaceuticals to reduce fever may counteract with the protective features of the immune system and create favourable conditions for a virus to spread within the organism and damage specific tissue. A preliminary comparison of paracetamol sales with the incidence of T1D data in Lithuania and the other countries in the North-eastern Baltic region supports this hypothesis. PMID:27372871

  19. Insight into the strong inhibitory action of salt on activity of neocarzinostatin.

    PubMed

    Chin, Der-Hang; Li, Huang-Hsien; Sudhahar, Christopher G; Tsai, Pei-Yin

    2010-03-01

    Enediyne anticancer drugs belong to one of the most potent category in inducing DNA damage. We report 85+/-5% inhibition on activity of neocarzinostatin by salt. As high sodium ion concentration is a known tumor cell feature, we explored the dynamic mechanism of inhibition. Using various analytical tools, we examined parameters involved in the four consecutive steps of the drug action, namely, drug releasing from carrier protein, drug-DNA binding, drug activating, and DNA damaging. Neither protein stability, nor drug release rate, was altered by salt. The salt inhibition level was similar in between the protein-bound and unbound enediyne chromophore. Salt did not quench the thiol-induced drug activation. The inhibition was independent of DNA lesion types and irrelevant with thiol structures. Collectively, no salt interaction was found in the releasing, activating, and DNA damaging step of the drug action. However, binding with DNA decreased linearly with salt and corresponded well with the salt-induced inhibition on the drug activity. Salt interference on the affinity of DNA binding was the main and sole cause of the severe salt inhibition. The inhibition factor should be carefully considered for all agents with similar DNA binding mode. PMID:20137955

  20. Bacterial diversity is strongly associated with historical penguin activity in an Antarctic lake sediment profile.

    PubMed

    Zhu, Renbin; Shi, Yu; Ma, Dawei; Wang, Can; Xu, Hua; Chu, Haiyan

    2015-01-01

    Current penguin activity in Antarctica affects the geochemistry of sediments and their microbial communities; the effects of historical penguin activity are less well understood. Here, bacterial diversity in ornithogenic sediment was investigated using high-throughput pyrosequencing. The relative abundances of dominant phyla were controlled by the amount of historical penguin guano deposition. Significant positive correlations were found between both the bacterial richness and diversity, and the relative penguin number (p < 0.01); this indicated that historical penguin activity drove the vertical distribution of the bacterial communities. The lowest relative abundances of individual phyla corresponded to lowest number of penguin population at 1,800-2,300 yr BP during a drier and colder period; the opposite was observed during a moister and warmer climate (1,400-1,800 yr BP). This study shows that changes in the climate over millennia affected penguin populations and the outcomes of these changes affect the sediment bacterial community today. PMID:26601753

  1. Suggested management guidelines for participation in collision activities with congenital, developmental, or postinjury lesions involving the cervical spine.

    PubMed

    Torg, J S; Ramsey-Emrhein, J A

    1997-07-01

    Many conditions involving the cervical spine in the athlete require a management decision. The purpose of this paper is to present appropriate guidelines for return to collision activities in those with congenital, developmental, or post-injury lesions. Information compiled from over 1200 cervical spine lesions documented by the National Football Head & Neck Injury Registry, an extensive literature review, as well as an understanding of injury mechanisms have resulted in reasonable management guidelines. Each of the congenital, developmental, and post-traumatic conditions presented are determined to present either no contraindication, relative contraindication, or an absolute contraindication on the basis of a variety of parameters. Conditions included in the discussion are: odontoid anomalies; spina bifida occulta; atlanto-occipital fusion; Klipple-Feil anomalies; cervical canal stenosis; spear tackler's spine; and traumatic conditions of the upper, middle, and lower cervical spine, including ligamentous injuries and fractures, intervertebral disc injuries, and post-cervical spine fusion. Emphasized is the fact that the proposed guidelines should be used in the decision-making process in conjuction with other factors such as the age, experience, ability of the individual, level of participation, position played, as well as the attitude and desires of the athlete and his parents after an informed discussion of the problem with particular regard to potential risk. PMID:9247923

  2. Tissue distribution and activity testing suggest a similar but not identical function of fetuin-B and fetuin-A.

    PubMed Central

    Denecke, Bernd; Gräber, Steffen; Schäfer, Cora; Heiss, Alexander; Wöltje, Michael; Jahnen-Dechent, Willi

    2003-01-01

    Fetuins are serum proteins with diverse functions including the regulation of osteogenesis and inhibition of unwanted mineralization. Besides the alpha2-Heremans and Schmid glycoprotein/fetuin-A, the recently identified fetuin-B is a second member of the fetuin family [Olivier, Soury, Risler, Smih, Schneider, Lochner, Jouzeau, Fey and Salier (1999) Genomics 57, 352-364; Olivier, Soury, Ruminy, Husson, Parmentier, Daveau and Salier (2000) Biochem. J. 350, 589-597], which belongs to the cystatin superfamily. We compared the expressions of fetuin-B and fetuin-A at the RNA level and established that both genes are most highly expressed in liver tissue. Like fetuin-A, fetuin-B mRNA is also highly expressed in tongue and placenta tissues. We demonstrated for the first time that fetuin-B is also expressed at the protein level in sera and several organs of mouse, rat and human. We isolated contiguous genomic clones containing both fetuin-B and fetuin-A genes, indicating that these genes are closely linked at the genome level. The close proximity of both these genes may explain our observation that fetuin-B expression was decreased in fetuin-A-deficient mice. Unlike fetuin-A, the amount of fetuin-B protein in human serum varied with gender and was higher in females than in males. Functional analysis revealed that fetuin-B, similarly to fetuin-A, is an inhibitor of basic calcium phosphate precipitation, albeit less active when compared with fetuin-A. Therefore fetuin-B may have a function that is partly overlapping, if not identical, with the function of fetuin-A. PMID:12943536

  3. Overweight, Obesity and Strong Attitudes: Predicting Participation in Physical Activity in a Predominantly Hispanic College Population

    ERIC Educational Resources Information Center

    Magoc, Dejan; Tomaka, Joe; Thompson, Sharon

    2010-01-01

    Background: Obesity is the leading cause of preventable death and conveys risk for diabetes, hypertension, heart disease and stroke. Overweight and obesity are common among college students, with surveys showing 35 per cent of college students to be overweight. Unhealthy diets and low physical activity are the major causes. Objective: To examine…

  4. 10Be surface exposure dating reveals strong active deformation in the central Andean backarc interior

    NASA Astrophysics Data System (ADS)

    García Morabito, Ezequiel; Terrizzano, Carla; Zech, Roland; Willett, Sean; Yamin, Marcela; Haghipour, Negar; Wuethrich, Lorenz; Christl, Marcus; María Cortes, José; Ramos, Victor

    2016-04-01

    Understanding the deformation associated with active thrust wedges is essential to evaluate seismic hazard. How is active faulting distributed throughout the wedge, and how much deformation is taken up by individual structures? We address these questions for our study region, the central Andean backarc of Argentina. We combined a structural and geomorphological approach with surface exposure dating (10Be) of alluvial fans and strath terraces in two key localities at ~32° S: the Cerro Salinas, located in the active orogenic front of the Precordillera, and the Barreal block in the interior of the Andean mountain range. We analysed 22 surface samples and 6 depth profiles. At the thrust front, the oldest terrace (T1) yields an age of 100-130 ka, the intermediate terrace (T2) between 40-95 ka, and the youngest terrace (T3) an age of ~20 ka. In the Andean interior, T1´ dates to 117-146 ka, T2´ to ~70 ka, and T3´ to ~20 ka, all calculations assuming negligible erosion and using the scaling scheme for spallation based on Lal 1991, Stone 2000. Vertical slip rates of fault offsets are 0.3-0.5 mm/yr and of 0.6-1.2 mm/yr at the thrust front and in the Andean interior, respectively. Our results highlight: i) fault activity related to the growth of the Andean orogenic wedge is not only limited to a narrow thrust front zone. Internal structures have been active during the last 150 ka, ii) deformation rates in the Andean interior are comparable or even higher that those estimated and reported along the emerging thrust front, iii) distribution of active faulting seems to account for unsteady state conditions, and iv) seismic hazards may be more relevant in the internal parts of the Andean orogen than assumed so far. References Lal, D., 1991: Cosmic ray labeling of erosion surfaces: In situ nuclide production rates and erosion models. Earth and Planetary Science Letters 104: 424-439. Stone, J.O., 2000: Air pressure and cosmogenic isotope production. Journal of Geophysical

  5. Bacterial diversity is strongly associated with historical penguin activity in an Antarctic lake sediment profile

    PubMed Central

    Zhu, Renbin; Shi, Yu; Ma, Dawei; Wang, Can; Xu, Hua; Chu, Haiyan

    2015-01-01

    Current penguin activity in Antarctica affects the geochemistry of sediments and their microbial communities; the effects of historical penguin activity are less well understood. Here, bacterial diversity in ornithogenic sediment was investigated using high-throughput pyrosequencing. The relative abundances of dominant phyla were controlled by the amount of historical penguin guano deposition. Significant positive correlations were found between both the bacterial richness and diversity, and the relative penguin number (p < 0.01); this indicated that historical penguin activity drove the vertical distribution of the bacterial communities. The lowest relative abundances of individual phyla corresponded to lowest number of penguin population at 1,800–2,300 yr BP during a drier and colder period; the opposite was observed during a moister and warmer climate (1,400–1,800 yr BP). This study shows that changes in the climate over millennia affected penguin populations and the outcomes of these changes affect the sediment bacterial community today. PMID:26601753

  6. PEGylated ofloxacin nanoparticles render strong antibacterial activity against many clinically important human pathogens.

    PubMed

    Marslin, Gregory; Revina, Ann Mary; Khandelwal, Vinoth Kumar Megraj; Balakumar, Krishnamoorthy; Sheeba, Caroline J; Franklin, Gregory

    2015-08-01

    The rise of bacterial resistance against important drugs threatens their clinical utility. Fluoroquinones, one of the most important classes of contemporary antibiotics has also reported to suffer bacterial resistance. Since the general mechanism of bacterial resistance against fluoroquinone antibiotics (e.g. ofloxacin) consists of target mutations resulting in reduced membrane permeability and increased efflux by the bacteria, strategies that could increase bacterial uptake and reduce efflux of the drug would provide effective treatment. In the present study, we have compared the efficiencies of ofloxacin delivered in the form of free drug (OFX) and as nanoparticles on bacterial uptake and antibacterial activity. Although both poly(lactic-co-glycolic acid) (OFX-PLGA) and methoxy poly(ethylene glycol)-b-poly(lactic-co-glycolic acid) (OFX-mPEG-PLGA) nanoformulations presented improved bacterial uptake and antibacterial activity against all the tested human bacterial pathogens, namely, Escherichia coli, Proteus vulgaris, Salmonella typhimurium, Pseudomonas aeruginosa, Klebsiella pneumoniae and Staphylococcus aureus, OFX-mPEG-PLGA showed significantly higher bacterial uptake and antibacterial activity compared to OFX-PLGA. We have also found that mPEG-PLGA nanoencapsulation could significantly inhibit Bacillus subtilis resistance development against OFX. PMID:26005932

  7. Fermi-LAT detection of strong flaring activity from the FSRQ CTA 102

    NASA Astrophysics Data System (ADS)

    Becerra, J.; Carpenter, Bryce; Cutini, Sara

    2016-02-01

    The Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope has observed increasing gamma-ray activity from a source positionally consistent with the flat spectrum radio quasar CTA 102 (also known as 3FGL J2232.5+1143, Acero et al. 2015, ApJS, 218, 23) with radio coordinates R.A.: 338.1517038 deg, Dec: 11.7308067 deg (J2000, Johnston et al. 1995, AJ, 110, 880) at redshift z=1.037 (Schmidt 1965, ApJ, 141, 1295).

  8. CpG oligodeoxynucleotides with double stem-loops show strong immunostimulatory activity.

    PubMed

    Yang, Liang; Wu, Xiuli; Wan, Min; Yu, Yue; Yu, Yongli; Wang, Liying

    2013-01-01

    Based on the current understanding of TLR9 recognition of CpG ODN, we have tried to design a series of CpG ODNs that display double stem-loops when being analyzed for their secondary structures using 'mfold web server'. Proliferation of human PBMC and bioassay for IFN production were used as technical platforms in primary screening. Interestingly, two of them, designated as DSL01 and D-SL03, belonging to B class CpG ODN and C class CpG ODN respectively, showed vigorous immunostimulatory activity and were chosen for further tests. Flow cytometry analysis showed that both of them could activate human B cells, NK cells, mononuclear cells and T cells and up-regulate expression of CD80, CD86 and HLA-DR on the surface of subsets in human PBMCs. Furthermore, we demonstrated that those two ODNs potently stimulated proliferation of PBMC/splenocytes obtained from diverse vertebrate species. Noticeably, both of them displayed anti-breast cancer effect in mice when administered by peritumoral injection. PMID:23142503

  9. Controlled green synthesis of silver nanoparticles by Allium cepa and Musa acuminata with strong antimicrobial activity

    NASA Astrophysics Data System (ADS)

    Sahni, Geetika; Panwar, Amit; Kaur, Balpreet

    2015-02-01

    A controlled "green synthesis" approach to synthesize silver nanoparticles by Allium cepa and Musa acuminata plant extract has been reported. The effect of different process parameters, such as pH, temperature and time, on synthesis of Ag nanoparticles from plant extracts has been highlighted. The work reports an easy approach to control the kinetics of interaction of metal ions with reducing agents, stabilized by ammonia to achieve sub-10 nm particles with narrow size distribution. The nanoparticles have been characterized by UV-Visible spectra and TEM analysis. Excellent antimicrobial activity at extremely low concentration of the nanoparticles was observed against Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis and Fusarium oxysporum which may allow their exploitation as a new generation nanoproduct in biomedical and agricultural applications.

  10. Design, synthesis, and structure-activity relationship studies of novel thienopyrrolidone derivatives with strong antifungal activity against Aspergillus fumigates.

    PubMed

    Cao, Xufeng; Xu, Yuanyuan; Cao, Yongbing; Wang, Ruilian; Zhou, Ran; Chu, Wenjing; Yang, Yushe

    2015-09-18

    In order to further enhance the anti-Aspergillus efficacy of our previously discovered antifungal lead compounds (I), two series of novel azoles featuring thieno[2,3-c]pyrrolidone and thieno[3,2-c]pyrrolidone nuclei were designed and evaluated for their in vitro activity on the basis of the binding mode of albaconazole using molecular docking, along with SARs of antifungal triazoles. Most of target compounds exhibited excellent activity against Candida and Cryptococcus spp., with MIC values in the range of 0.0625 μg/ml to 0.0156 μg/ml. The thieno[3,2-c]pyrrolidone unit was more suited for improving activity against Aspergillus spp. The most potent compound, 18a, was selected for further development due to its significant in vitro activity against Aspergillus spp. (MIC = 0.25 μg/ml), as well as its high metabolic stability in human liver microsomes. PMID:26310892

  11. High-titer production and strong antimicrobial activity of sophorolipids from Rhodotorula bogoriensis.

    PubMed

    Solaiman, Daniel K Y; Ashby, Richard D; Crocker, Nicole V

    2015-01-01

    Rhodotorula bogoriensis produces sophorolipids (SLs) that contain 13-hydroxydocosanoic acid (OH-C22 ) as the lipid moiety. A systematic study was conducted to further understand the fermentative production of SLs containing OH-C22 (C22 -SL) by R. bogoriensis. Shake-flask studies showed that R. bogoriensis consumed glucose at a slow pace. HPLC analysis of the C22 -SL products from shake-flask fermentations at different glucose concentrations showed a correlation between glucose depletion and the extent of C22 -SL deacetylation. A large-scale bioreactor fermentation resulted in the isolation of C22 -SL at a volumetric product yield of 51 g/L. HPLC analysis of C22 -SL product from the bioreactor fermentation corroborated the finding that glucose depletion correlated with extensive deacetylation of C22 -SL. The antimicrobial activity of C22 -SL was established for the first time to be stronger than the C18 -SL from Candida bombicola against Propionibacterium acnes in a plate assay. PMID:25960338

  12. Nontoxic hydrophilic polymeric nanocomposites containing silver nanoparticles with strong antimicrobial activity

    PubMed Central

    Pozdnyakov, Alexander S; Emel’yanov, Artem I; Kuznetsova, Nadezhda P; Ermakova, Tamara G; Fadeeva, Tat’yana V; Sosedova, Larisa M; Prozorova, Galina F

    2016-01-01

    New nontoxic hydrophilic nanocomposites containing metallic silver nanoparticles (AgNPs) in a polymer matrix were synthesized by the chemical reduction of silver ions in an aqueous medium. A new nontoxic water soluble copolymer of 1-vinyl-1,2,4-triazole and N-vinylpyrrolidone synthesized by free radical-initiated polymerization was used as a stabilizing agent. Transmission electron microscopy, scanning electron microscopy, ultraviolet–visible spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, atomic absorption, and thermogravimetric analysis were used to characterize polymeric AgNPs nanocomposites. The results showed that the diameter of the synthesized AgNPs ranged from 2 to 6 nm. The toxicity of the initial copolymer of 1-vinyl-1,2,4-triazole and N-vinylpyrrolidone and its nanocomposite with AgNPs was found to be more than 5,000 mg/kg. The synthesized AgNP polymeric nanocomposite showed significant antimicrobial activity against different strains of Gram-negative and -positive bacteria. The minimum inhibitory concentrations suppressing the growth of the microorganisms ranged from 0.5 to 8 µg/mL and the minimum bactericidal concentrations ranged from 0.5 to 16 µg/mL. The fabricated AgNP nanocomposites are promising materials for the design of novel nontoxic hydrophilic antiseptics and antimicrobial components for medical purposes. PMID:27099492

  13. Alkyl Galactofuranosides Strongly Interact with Leishmania donovani Membrane and Provide Antileishmanial Activity

    PubMed Central

    Suleman, Muhammad; Gangneux, Jean-Pierre; Legentil, Laurent; Belaz, Sorya; Cabezas, Yari; Manuel, Christelle; Dureau, Rémy; Sergent, Odile; Burel, Agnès; Daligault, Franck; Ferrières, Vincent

    2014-01-01

    We investigated the in vitro effects of four alkyl-galactofuranoside derivatives, i.e., octyl-β-d-galactofuranoside (compound 1), 6-amino-β-d-galactofuranoside (compound 2), 6-N-acetamido-β-d-galactofuranoside (compound 3), and 6-azido-β-d-galactofuranoside (compound 4), on Leishmania donovani. Their mechanism of action was explored using electron paramagnetic resonance spectroscopy (EPR) and nuclear magnetic resonance (NMR), and ultrastructural alterations were analyzed by transmission electron microscopy (TEM). Compound 1 showed the most promising effects by inhibiting promastigote growth at a 50% inhibitory concentration (IC50) of 8.96 ± 2.5 μM. All compounds exhibit low toxicity toward human macrophages. Compound 1 had a higher selectivity index than the molecule used for comparison, i.e., miltefosine (159.7 versus 37.9, respectively). EPR showed that compound 1 significantly reduced membrane fluidity compared to control promastigotes and to compound 3. The furanose ring was shown to support this effect, since the isomer galactopyranose had no effect on parasite membrane fluidity or growth. NMR showed a direct interaction of all compounds (greatest with compound 1, followed by compounds 2, 3, and 4, in descending order) with the promastigote membrane and with octyl-galactopyranose and octanol, providing evidence that the n-octyl chain was primarily involved in anchoring with the parasite membrane, followed by the putative crucial role of the furanose ring in the antileishmanial activity. A morphological analysis of compound 1-treated promastigotes by TEM revealed profound alterations in the parasite membrane and organelles, but this was not the case with compound 3. Quantification of annexin V binding by flow cytometry confirmed that compound 1 induced apoptosis in >90% of promastigotes. The effect of compound 1 was also assessed on intramacrophagic amastigotes and showed a reduction in amastigote growth associated with an increase of reactive oxygen

  14. Dynamics of self-sustained asynchronous-irregular activity in random networks of spiking neurons with strong synapses

    PubMed Central

    Kriener, Birgit; Enger, Håkon; Tetzlaff, Tom; Plesser, Hans E.; Gewaltig, Marc-Oliver; Einevoll, Gaute T.

    2014-01-01

    Random networks of integrate-and-fire neurons with strong current-based synapses can, unlike previously believed, assume stable states of sustained asynchronous and irregular firing, even without external random background or pacemaker neurons. We analyze the mechanisms underlying the emergence, lifetime and irregularity of such self-sustained activity states. We first demonstrate how the competition between the mean and the variance of the synaptic input leads to a non-monotonic firing-rate transfer in the network. Thus, by increasing the synaptic coupling strength, the system can become bistable: In addition to the quiescent state, a second stable fixed-point at moderate firing rates can emerge by a saddle-node bifurcation. Inherently generated fluctuations of the population firing rate around this non-trivial fixed-point can trigger transitions into the quiescent state. Hence, the trade-off between the magnitude of the population-rate fluctuations and the size of the basin of attraction of the non-trivial rate fixed-point determines the onset and the lifetime of self-sustained activity states. During self-sustained activity, individual neuronal activity is moreover highly irregular, switching between long periods of low firing rate to short burst-like states. We show that this is an effect of the strong synaptic weights and the finite time constant of synaptic and neuronal integration, and can actually serve to stabilize the self-sustained state. PMID:25400575

  15. Regional Biases in Droplet Activation Parameterizations: Strong Influence on Aerosol Second Indirect Effect in the Community Atmosphere Model v5.

    NASA Astrophysics Data System (ADS)

    Morales, R.; Nenes, A.

    2014-12-01

    Aerosol-cloud interactions constitute one of the most uncertain aspects of anthropogenic climate change estimates. The magnitude of these interactions as represented in climate models strongly depends on the process of aerosol activation. This process is the most direct physical link between aerosols and cloud microphysical properties. Calculation of droplet number in GCMs requires the computation of new droplet formation (i.e., droplet activation), through physically based activation parameterizations. Considerable effort has been placed in ensuring that droplet activation parameterizations have a physically consistent response to changes in aerosol number concentration. However, recent analyses using an adjoint sensitivity approach showed that parameterizations can exhibit considerable biases in their response to other aerosol properties, such as aerosol modal diameter or to the aerosol chemical composition. This is a potentially important factor in estimating aerosol indirect effects since changes in aerosol properties from pre-industrial times to present day exhibit a very strong regional signature. In this work we use the Community Atmosphere Model (CAM5) to show that the regional imprint of the changes in aerosol properties during the last century interacts with the droplet activation parameterization in a way that these biases are amplified over climatically relevant regions. Two commonly used activation routines, the CAM5 default, Abdul-Razzak and Ghan parameterization, as well as the Fountoukis and Nenes parameterization are used in this study. We further explored the impacts of Nd parameterization biases in the first and second aerosol indirect effects separately, by performing simulations were droplet number was not allowed to intervene in the precipitation initiation process. The simulations performed show that an unphysical response to changes in the diameter of accumulation mode aerosol translates into extremely high Nd concentrations over South

  16. Copper ions strongly activate the phosphoinositide-3-kinase/Akt pathway independent of the generation of reactive oxygen species.

    PubMed

    Ostrakhovitch, Elena A; Lordnejad, Mohammad Reza; Schliess, Freimut; Sies, Helmut; Klotz, Lars-Oliver

    2002-01-15

    Copper is implicated in metabolic disorders, such as Wilson's disease or Alzheimer's disease. Analysis of signaling pathways regulating cellular survival and function in response to a copper stress is crucial for understanding the pathogenesis of such diseases. Exposure of human skin fibroblasts or HeLa cells to Cu(2+) resulted in a dose- and time-dependent activation of the antiapoptotic kinase Akt/protein kinase B, starting at concentrations as low as 3 microM. Only Cu(II), but not Cu(I), had this effect. Activation of Akt was accompanied by phosphorylation of a downstream target of Akt, glycogen synthase kinase-3. Inhibitors of phosphoinositide-3-kinase (PI3K) completely blocked activation of Akt by Cu(2+), indicating a requirement of PI3K for Cu(2+)-induced activation of Akt. Indeed, cellular PI3K activity was strongly enhanced after exposure to Cu(2+). Copper ions may lead to the formation of reactive oxygen species, such as hydrogen peroxide. Activation of Akt by hydrogen peroxide or growth factors is known to proceed via the activation growth factor receptors. In line with this, pretreatment with inhibitors of growth factor receptor tyrosine kinases blocked activation of Akt by hydrogen peroxide and growth factors, as did a src-family tyrosine kinase inhibitor or the broad-spectrum tyrosine kinase inhibitor genistein. Activation of Akt by Cu(2+), however, remained unimpaired, implying (i) that tyrosine kinase activation is not involved in Cu(2+) activation of Akt and (ii) that activation of the PI3K/Akt pathway by Cu(2+) is initiated independently of that induced by reactive oxygen species. Comparison of the time course of the oxidation of 2',7'-dichlorodihydrofluorescein in copper-treated cells with that of Akt activation led to the conclusion that production of hydroperoxides cannot be an upstream event in copper-induced Akt activation. Rather, both activation of Akt and generation of ROS are proposed to occur in parallel, regulating cell survival after a

  17. Career Education: Learning with a Purpose. Secondary Guide-Vol. 5. Mathematics and Career Clusters, Mathematics Related Activity Suggestions, Field Trip Sites and Guest Speakers.

    ERIC Educational Resources Information Center

    Atkinson, Marilyn; And Others

    The guide offers a compilation of teacher-developed career education materials which may be integrated with secondary level curriculum in mathematics. Suggested activities and ideas present the following units based on career clusters as they relate to mathematics: construction, communications and media, hospitality and recreation, public service,…

  18. Complete genome sequence of Bacillus amyloliquefaciens B15 isolated from grape skin, a strain of strong inhibitory activity against fungi.

    PubMed

    Yan, Yinzhuo; Liu, Shiyu; Wang, Deliang; Xue, Jie; Guo, Danyang; Song, Xulei; Zhang, Fengjie; Huang, Shihai; Luan, Chunguang

    2016-06-20

    Bacillus amyloliquefaciens B15 is a Gram-positive, plant-associated bacterium which shows strong antifungal activity, isolated from grape skin in Xinjiang, China. The genome of B. amyloliquefaciens B15 comprises a 4,006,754bp long circular chromosome containing 3991 protein coding genes and 109 RNA genes. Based on genomic analysis, we identified the giant gene clusters, nonribosomal peptidesynthetases (NRPS), and polyketide synthases (PKS), responsible for the biosynthesis of numerous bioactive metabolites. In addition, several functionally related genes, such as TasA, were also been identified for the antagonistic effect on pathogenic fungi but has no effect on the growth of itself. PMID:27114322

  19. Structure-Activity Relationship of Oligomeric Flavan-3-ols: Importance of the Upper-Unit B-ring Hydroxyl Groups in the Dimeric Structure for Strong Activities.

    PubMed

    Hamada, Yoshitomo; Takano, Syota; Ayano, Yoshihiro; Tokunaga, Masahiro; Koashi, Takahiro; Okamoto, Syuhei; Doi, Syoma; Ishida, Masahiko; Kawasaki, Takashi; Hamada, Masahiro; Nakajima, Noriyuki; Saito, Akiko

    2015-01-01

    Proanthocyanidins, which are composed of oligomeric flavan-3-ol units, are contained in various foodstuffs (e.g., fruits, vegetables, and drinks) and are strongly biologically active compounds. We investigated which element of the proanthocyanidin structure is primarily responsible for this functionality. In this study, we elucidate the importance of the upper-unit of 4-8 condensed dimeric flavan-3-ols for antimicrobial activity against Saccharomyces cerevisiae (S. cerevisiae) and cervical epithelioid carcinoma cell line HeLa S3 proliferation inhibitory activity. To clarify the important constituent unit of proanthocyanidin, we synthesized four dimeric compounds, (-)-epigallocatechin-[4,8]-(+)-catechin, (-)-epigallocatechin-[4,8]-(-)-epigallocatechin, (-)-epigallocatechin-[4,8]-(-)-epigallocatechin-3-O-gallate, and (+)-catechin-[4,8]-(-)-epigallocatechin and performed structure-activity relationship (SAR) studies. In addition to antimicrobial activity against S. cerevisiae and proliferation inhibitory activity on HeLa S3 cells, the correlation of 2,2-diphenyl-l-picrylhydrazyl radical scavenging activity with the number of phenolic hydroxyl groups was low. On the basis of the results of our SAR studies, we concluded that B-ring hydroxyl groups of the upper-unit of the dimer are crucially important for strong and effective activity. PMID:26501251

  20. Mechanism of Activation for Transcription Factor PhoB Suggested by Different Modes of Dimerization in the Inactive and Active States

    PubMed Central

    Bachhawat, Priti; Swapna, GVT; Stock, Ann M

    2013-01-01

    Summary Response regulators (RRs), which undergo phosphorylation/dephosphorylation at aspartate residues, are highly prevalent in bacterial signal transduction. RRs typically contain an N-terminal receiver domain that regulates the activities of a C-terminal DNA-binding domain in a phosphorylation-dependent manner. We present crystallography and solution NMR data for the receiver domain of Escherichia coli PhoB, which show distinct two-fold symmetric dimers in the inactive and active states, providing the first such pair within the OmpR/PhoB subfamily, the largest group of RRs. These structures together with the previously determined structure of the C-terminal domain of PhoB bound to DNA, define the conformation of the active transcription factor, and provide a model for the mechanism of activation in this subfamily. In the active state, the receiver domains dimerize with two-fold rotational symmetry using their α4-β5-α5 faces, while the effector domains bind to DNA direct repeats with tandem symmetry, implying a loss of intramolecular interactions. PMID:16154092

  1. Efficient Amide Bond Formation through a Rapid and Strong Activation of Carboxylic Acids in a Microflow Reactor**

    PubMed Central

    Fuse, Shinichiro; Mifune, Yuto; Takahashi, Takashi

    2014-01-01

    The development of highly efficient amide bond forming methods which are devoid of side reactions, including epimerization, is important, and such a method is described herein and is based on the concept of rapid and strong activation of carboxylic acids. Various carboxylic acids are rapidly (0.5 s) converted into highly active species, derived from the inexpensive and less-toxic solid triphosgene, and then rapidly (4.3 s) reacted with various amines to afford the desired peptides in high yields (74 %–quant.) without significant epimerization (≤3 %). Our process can be carried out at ambient temperature, and only CO2 and HCl salts of diisopropylethyl amine are generated. In the long history of peptide synthesis, a significant number of active coupling reagents have been abandoned because the highly active electrophilic species generated are usually susceptible to side reactions such as epimerization. The concept presented herein should renew interest in the use of these reagents. PMID:24402801

  2. Structural Insights into the Unusually Strong ATPase Activity of the AAA Domain of the Caenorhabditis elegans Fidgetin-like 1 (FIGL-1) Protein*

    PubMed Central

    Peng, Wentao; Lin, Zhijie; Li, Weirong; Lu, Jing; Shen, Yuequan; Wang, Chunguang

    2013-01-01

    The FIGL-1 (fidgetin like-1) protein is a homolog of fidgetin, a protein whose mutation leads to multiple developmental defects. The FIGL-1 protein contains an AAA (ATPase associated with various activities) domain and belongs to the AAA superfamily. However, the biological functions and developmental implications of this protein remain unknown. Here, we show that the AAA domain of the Caenorhabditis elegans FIGL-1 protein (CeFIGL-1-AAA), in clear contrast to homologous AAA domains, has an unusually high ATPase activity and forms a hexamer in solution. By determining the crystal structure of CeFIGL-1-AAA, we found that the loop linking helices α9 and α10 folds into the short helix α9a, which has an acidic surface and interacts with a positively charged surface of the neighboring subunit. Disruption of this charge interaction by mutagenesis diminishes both the ATPase activity and oligomerization capacity of the protein. Interestingly, the acidic residues in helix α9a of CeFIGL-1-AAA are not conserved in other homologous AAA domains that have relatively low ATPase activities. These results demonstrate that the sequence of CeFIGL-1-AAA has adapted to establish an intersubunit charge interaction, which contributes to its strong oligomerization and ATPase activity. These unique properties of CeFIGL-1-AAA distinguish it from other homologous proteins, suggesting that CeFIGL-1 may have a distinct biological function. PMID:23979136

  3. The response of short-scale density fluctuations to the activity of beta-induced Alfvén eigenmodes during strong tearing modes on EAST tokamak

    NASA Astrophysics Data System (ADS)

    Cao, G. M.; Li, Y. D.; Li, Q.; Sun, P. J.; Wu, G. J.; Hu, L. Q.; the EAST Team

    2015-08-01

    Beta-induced Alfvén eigenmodes (BAEs) during strong tearing modes (TMs) have been frequently observed in fast-electron plasmas of EAST tokamak. The dynamics of the short-scale ({k}\\perp {ρ }s~{1.5-4.3}) density fluctuations during the activity of BAEs with strong TMs has been preliminarily investigated by a tangential CO2 laser collective scattering system. The results suggest the active, but different, response of short-scale density fluctuations to the TMs and BAEs. In the low-frequency (0-10 kHz) part of density fluctuations, there are harmonic oscillations totally corresponding to those of TMs. In the medium-high frequency (10-250 kHz) part of density fluctuations, with the appearance of the BAEs, the medium-high frequency density fluctuations begin to be dominated by several quasi-coherent (QC) modes, and the frequencies of the QC modes seem to be related to the changes of both TMs and BAEs. These results would shed some light on the understanding of the multi-scale interaction physics.

  4. The Shewanella algae strain YM8 produces volatiles with strong inhibition activity against Aspergillus pathogens and aflatoxins

    PubMed Central

    Gong, An-Dong; Li, He-Ping; Shen, Lu; Zhang, Jing-Bo; Wu, Ai-Bo; He, Wei-Jie; Yuan, Qing-Song; He, Jing-De; Liao, Yu-Cai

    2015-01-01

    Aflatoxigenic Aspergillus fungi and associated aflatoxins are ubiquitous in the production and storage of food/feed commodities. Controlling these microbes is a challenge. In this study, the Shewanella algae strain YM8 was found to produce volatiles that have strong antifungal activity against Aspergillus pathogens. Gas chromatography-mass spectrometry profiling revealed 15 volatile organic compounds (VOCs) emitted from YM8, of which dimethyl trisulfide was the most abundant. We obtained authentic reference standards for six of the VOCs; these all significantly reduced mycelial growth and conidial germination in Aspergillus; dimethyl trisulfide and 2,4-bis(1,1-dimethylethyl)-phenol showed the strongest inhibitory activity. YM8 completely inhibited Aspergillus growth and aflatoxin biosynthesis in maize and peanut samples stored at different water activity levels, and scanning electron microscopy revealed severely damaged conidia and a complete lack of mycelium development and conidiogenesis. YM8 also completely inhibited the growth of eight other agronomically important species of phytopathogenic fungi: A. parasiticus, A. niger, Alternaria alternate, Botrytis cinerea, Fusarium graminearum, Fusarium oxysporum, Monilinia fructicola, and Sclerotinia sclerotiorum. This study demonstrates the susceptibility of Aspergillus and other fungi to VOCs from marine bacteria and indicates a new strategy for effectively controlling these pathogens and the associated mycotoxin production during storage and possibly in the field. PMID:26500631

  5. The Shewanella algae strain YM8 produces volatiles with strong inhibition activity against Aspergillus pathogens and aflatoxins.

    PubMed

    Gong, An-Dong; Li, He-Ping; Shen, Lu; Zhang, Jing-Bo; Wu, Ai-Bo; He, Wei-Jie; Yuan, Qing-Song; He, Jing-De; Liao, Yu-Cai

    2015-01-01

    Aflatoxigenic Aspergillus fungi and associated aflatoxins are ubiquitous in the production and storage of food/feed commodities. Controlling these microbes is a challenge. In this study, the Shewanella algae strain YM8 was found to produce volatiles that have strong antifungal activity against Aspergillus pathogens. Gas chromatography-mass spectrometry profiling revealed 15 volatile organic compounds (VOCs) emitted from YM8, of which dimethyl trisulfide was the most abundant. We obtained authentic reference standards for six of the VOCs; these all significantly reduced mycelial growth and conidial germination in Aspergillus; dimethyl trisulfide and 2,4-bis(1,1-dimethylethyl)-phenol showed the strongest inhibitory activity. YM8 completely inhibited Aspergillus growth and aflatoxin biosynthesis in maize and peanut samples stored at different water activity levels, and scanning electron microscopy revealed severely damaged conidia and a complete lack of mycelium development and conidiogenesis. YM8 also completely inhibited the growth of eight other agronomically important species of phytopathogenic fungi: A. parasiticus, A. niger, Alternaria alternate, Botrytis cinerea, Fusarium graminearum, Fusarium oxysporum, Monilinia fructicola, and Sclerotinia sclerotiorum. This study demonstrates the susceptibility of Aspergillus and other fungi to VOCs from marine bacteria and indicates a new strategy for effectively controlling these pathogens and the associated mycotoxin production during storage and possibly in the field. PMID:26500631

  6. Fragmentation patterns of novel dispirocyclopiperazinium dibromides with strong analgesic activity under electrospray ionization tandem mass spectrometry conditions

    NASA Astrophysics Data System (ADS)

    Wang, Xin; Sha, Yaowu; Li, Runtao

    2004-07-01

    The fragmentation patterns of a series of dispirocyclopiperazinium dibromides with strong analgesic activity were analyzed by positive ion electrospray ionization mass spectrometry in conjunction with tandem mass spectrometry (ESI-MSn). The [C2+Br-]+ ions showed the characteristic isotopic peaks with high intensity. In each of their MS2 spectra, only the [C2+Br----HBr]+ ion peak was observable. Further analysis indicated that a selective rearrangement occurred in the unsaturated spirocyclopiperazine ring to achieve dihydropyrrole moiety. Meanwhile, the [C]2+ ions were unique and always the base peaks. The ions [C2+Br-]+ and [C]2+ were formed from the equilibrium of precursor molecules 1 in solution, and the latter ions could not be observed in the MS2 spectra of ions [C2+Br-]+. The related fragmentation mechanisms were proposed.

  7. Installation of a digital, wireless, strong-motion network for monitoring seismic activity in a western Colorado coal mining region

    SciTech Connect

    Peter Swanson; Collin Stewart; Wendell Koontz

    2007-01-15

    A seismic monitoring network has recently been installed in the North Fork Valley coal mining region of western Colorado as part of a NIOSH mine safety technology transfer project with two longwall coal mine operators. Data recorded with this network will be used to characterize mining related and natural seismic activity in the vicinity of the mines and examine potential hazards due to ground shaking near critical structures such as impoundment dams, reservoirs, and steep slopes. Ten triaxial strong-motion accelerometers have been installed on the surface to form the core of a network that covers approximately 250 square kilometers (100 sq. miles) of rugged canyon-mesa terrain. Spread-spectrum radio networks are used to telemeter continuous streams of seismic waveform data to a central location where they are converted to IP data streams and ported to the Internet for processing, archiving, and analysis. 4 refs.

  8. Structure of Membrane-active Toxin from Crab Spider Heriaeus melloteei Suggests Parallel Evolution of Sodium Channel Gating Modifiers in Araneomorphae and Mygalomorphae*

    PubMed Central

    Berkut, Antonina A.; Peigneur, Steve; Myshkin, Mikhail Yu.; Paramonov, Alexander S.; Lyukmanova, Ekaterina N.; Arseniev, Alexander S.; Grishin, Eugene V.; Tytgat, Jan; Shenkarev, Zakhar O.; Vassilevski, Alexander A.

    2015-01-01

    We present a structural and functional study of a sodium channel activation inhibitor from crab spider venom. Hm-3 is an insecticidal peptide toxin consisting of 35 amino acid residues from the spider Heriaeus melloteei (Thomisidae). We produced Hm-3 recombinantly in Escherichia coli and determined its structure by NMR spectroscopy. Typical for spider toxins, Hm-3 was found to adopt the so-called “inhibitor cystine knot” or “knottin” fold stabilized by three disulfide bonds. Its molecule is amphiphilic with a hydrophobic ridge on the surface enriched in aromatic residues and surrounded by positive charges. Correspondingly, Hm-3 binds to both neutral and negatively charged lipid vesicles. Electrophysiological studies showed that at a concentration of 1 μm Hm-3 effectively inhibited a number of mammalian and insect sodium channels. Importantly, Hm-3 shifted the dependence of channel activation to more positive voltages. Moreover, the inhibition was voltage-dependent, and strong depolarizing prepulses attenuated Hm-3 activity. The toxin is therefore concluded to represent the first sodium channel gating modifier from an araneomorph spider and features a “membrane access” mechanism of action. Its amino acid sequence and position of the hydrophobic cluster are notably different from other known gating modifiers from spider venom, all of which are described from mygalomorph species. We hypothesize parallel evolution of inhibitor cystine knot toxins from Araneomorphae and Mygalomorphae suborders. PMID:25352595

  9. Secretion of Antonospora (Paranosema) locustae Proteins into Infected Cells Suggests an Active Role of Microsporidia in the Control of Host Programs and Metabolic Processes

    PubMed Central

    Senderskiy, Igor V.; Timofeev, Sergey A.; Seliverstova, Elena V.; Pavlova, Olga A.; Dolgikh, Viacheslav V.

    2014-01-01

    Molecular tools of the intracellular protozoan pathogens Apicomplexa and Kinetoplastida for manipulation of host cell machinery have been the focus of investigation for approximately two decades. Microsporidia, fungi-related microorganisms forming another large group of obligate intracellular parasites, are characterized by development in direct contact with host cytoplasm (the majority of species), strong minimization of cell machinery, and acquisition of unique transporters to exploit host metabolic system. All the aforementioned features are suggestive of the ability of microsporidia to modify host metabolic and regulatory pathways. Seven proteins of the microsporidium Antonospora (Paranosema) locustae with predicted signal peptides but without transmembrane domains were overexpressed in Escherichia coli. Western-blot analysis with antibodies against recombinant products showed secretion of parasite proteins from different functional categories into the infected host cell. Secretion of parasite hexokinase and α/β-hydrolase was confirmed by immunofluorescence microscopy. In addition, this method showed specific accumulation of A. locustae hexokinase in host nuclei. Expression of hexokinase, trehalase, and two leucine-rich repeat proteins without any exogenous signal peptide led to their secretion in the yeast Pichia pastoris. In contrast, α/β-hydrolase was not found in the culture medium, though a significant amount of this enzyme accumulated in the yeast membrane fraction. These results suggest that microsporidia possess a broad set of enzymes and regulatory proteins secreted into infected cells to control host metabolic processes and molecular programs. PMID:24705470

  10. Secretion of Antonospora (Paranosema) locustae proteins into infected cells suggests an active role of microsporidia in the control of host programs and metabolic processes.

    PubMed

    Senderskiy, Igor V; Timofeev, Sergey A; Seliverstova, Elena V; Pavlova, Olga A; Dolgikh, Viacheslav V

    2014-01-01

    Molecular tools of the intracellular protozoan pathogens Apicomplexa and Kinetoplastida for manipulation of host cell machinery have been the focus of investigation for approximately two decades. Microsporidia, fungi-related microorganisms forming another large group of obligate intracellular parasites, are characterized by development in direct contact with host cytoplasm (the majority of species), strong minimization of cell machinery, and acquisition of unique transporters to exploit host metabolic system. All the aforementioned features are suggestive of the ability of microsporidia to modify host metabolic and regulatory pathways. Seven proteins of the microsporidium Antonospora (Paranosema) locustae with predicted signal peptides but without transmembrane domains were overexpressed in Escherichia coli. Western-blot analysis with antibodies against recombinant products showed secretion of parasite proteins from different functional categories into the infected host cell. Secretion of parasite hexokinase and α/β-hydrolase was confirmed by immunofluorescence microscopy. In addition, this method showed specific accumulation of A. locustae hexokinase in host nuclei. Expression of hexokinase, trehalase, and two leucine-rich repeat proteins without any exogenous signal peptide led to their secretion in the yeast Pichia pastoris. In contrast, α/β-hydrolase was not found in the culture medium, though a significant amount of this enzyme accumulated in the yeast membrane fraction. These results suggest that microsporidia possess a broad set of enzymes and regulatory proteins secreted into infected cells to control host metabolic processes and molecular programs. PMID:24705470

  11. An RNA polymerase II transcription factor has an associated DNA-dependent ATPase (dATPase) activity strongly stimulated by the TATA region of promoters.

    PubMed Central

    Conaway, R C; Conaway, J W

    1989-01-01

    A transcription factor required for synthesis of accurately initiated run-off transcripts by RNA polymerase II has been purified and shown to have an associated DNA-dependent ATPase (dATPase) activity that is strongly stimulated by the TATA region of promoters. This transcription factor, designated delta, was purified more than 3000-fold from extracts of crude rat liver nuclei and has a native molecular mass of approximately 230 kDa. DNA-dependent ATPase (dATPase) and transcription activities copurify when delta is analyzed by hydrophobic interaction and ion-exchange HPLC, arguing that transcription factor delta possesses an ATPase (dATPase) activity. ATPase (dATPase) is specific for adenine nucleotides; ATP and dATP, but not CTP, UTP, or GTP, are hydrolyzed. ATPase (dATPase) is stimulated by both double-stranded and single-stranded DNAs, including pUC18, ssM13, and poly(dT); however, DNA fragments containing the TATA region of either the adenovirus 2 major late or mouse interleukin 3 promoters stimulate ATPase as much as 10-fold more effectively than DNA fragments containing nonpromoter sequences. These data suggest the intriguing possibility that delta plays a critical role in the ATP (dATP)-dependent activation of run-off transcription through a direct interaction with the TATA region of promoters. Images PMID:2552440

  12. PTS-Mediated Regulation of the Transcription Activator MtlR from Different Species: Surprising Differences despite Strong Sequence Conservation.

    PubMed

    Joyet, Philippe; Derkaoui, Meriem; Bouraoui, Houda; Deutscher, Josef

    2015-01-01

    The hexitol D-mannitol is transported by many bacteria via a phosphoenolpyruvate (PEP):carbohydrate phosphotransferase system (PTS). In most Firmicutes, the transcription activator MtlR controls the expression of the genes encoding the D-mannitol-specific PTS components and D-mannitol-1-P dehydrogenase. MtlR contains an N-terminal helix-turn-helix motif followed by an Mga-like domain, two PTS regulation domains (PRDs), an EIIB(Gat)- and an EIIA(Mtl)-like domain. The four regulatory domains are the target of phosphorylation by PTS components. Despite strong sequence conservation, the mechanisms controlling the activity of MtlR from Lactobacillus casei, Bacillus subtilis and Geobacillus stearothermophilus are quite different. Owing to the presence of a tyrosine in place of the second conserved histidine (His) in PRD2, L. casei MtlR is not phosphorylated by Enzyme I (EI) and HPr. When the corresponding His in PRD2 of MtlR from B. subtilis and G. stearothermophilus was replaced with alanine, the transcription regulator was no longer phosphorylated and remained inactive. Surprisingly, L. casei MtlR functions without phosphorylation in PRD2 because in a ptsI (EI) mutant MtlR is constitutively active. EI inactivation prevents not only phosphorylation of HPr, but also of the PTS(Mtl) components, which inactivate MtlR by phosphorylating its EIIB(Gat)- or EIIA(Mtl)-like domain. This explains the constitutive phenotype of the ptsI mutant. The absence of EIIB(Mtl)-mediated phosphorylation leads to induction of the L. caseimtl operon. This mechanism resembles mtlARFD induction in G. stearothermophilus, but differs from EIIA(Mtl)-mediated induction in B. subtilis. In contrast to B. subtilis MtlR, L. casei MtlR activation does not require sequestration to the membrane via the unphosphorylated EIIB(Mtl) domain. PMID:26159071

  13. Strong Interaction

    SciTech Connect

    Karsch, F.; Vogelsang, V.

    2009-09-29

    We will give here an overview of our theory of the strong interactions, Quantum Chromo Dynamics (QCD) and its properties. We will also briefly review the history of the study of the strong interactions, and the discoveries that ultimately led to the formulation of QCD. The strong force is one of the four known fundamental forces in nature, the others being the electromagnetic, the weak and the gravitational force. The strong force, usually referred to by scientists as the 'strong interaction', is relevant at the subatomic level, where it is responsible for the binding of protons and neutrons to atomic nuclei. To do this, it must overcome the electric repulsion between the protons in an atomic nucleus and be the most powerful force over distances of a few fm (1fm=1 femtometer=1 fermi=10{sup -15}m), the typical size of a nucleus. This property gave the strong force its name.

  14. Var Gene promoter activation in clonal Plasmodium falciparum isolates follows a hierarchy and suggests a conserved switching program that is independent of genetic background.

    PubMed

    Enderes, Corinna; Kombila, Davy; Dal-Bianco, Matthias; Dzikowski, Ron; Kremsner, Peter; Frank, Matthias

    2011-11-15

    Antigenic variation of Plasmodium falciparum is mediated by a mutually exclusive expression mechanism that limits expression to an individual member of the multicopy var gene family. This process determines the antigenic and adhesive phenotype of the infected red blood cell. Previously, we showed that var gene switching is influenced by chromosomal position. Here, we address whether var gene transcription follows a general conserved pattern in long-term laboratory parasites and in recently culture-adapted field parasites. Activation of the var gene family was monitored in biological replicates in each parasite isolate every 3-5 generations for up to 3 months. We used transgenic parasites carrying a drug-selectable marker at a defined var locus to characterize var gene activation after the exclusive expression of the transgene. Transgenic parasites exhibited a repeatable hierarchy of var gene activation and a fluctuating transcriptional activity of the transgenic var locus. Transcriptional profiling of wild-type laboratory and field parasites showed a universal bias toward transcription of UpsC var genes and a fluctuating transcriptional activity of the dominant var promoter. The data suggest the existence of an intrinsic var gene transcription program that is independent of genetic background. PMID:21926380

  15. Active-to-absorbing-state phase transition in the presence of fluctuating environments: weak and strong dynamic scaling.

    PubMed

    Sarkar, Niladri; Basu, Abhik

    2012-08-01

    We investigate the scaling properties of phase transitions between survival and extinction (active-to-absorbing-state phase transition, AAPT) in a model that by itself belongs to the directed percolation (DP) universality class, interacting with a spatiotemporally fluctuating environment having its own nontrivial dynamics. We model the environment by (i) a randomly stirred fluid, governed by the Navier-Stokes (NS) equation, and (ii) a fluctuating surface, described either by the Kardar-Parisi-Zhang (KPZ) or the Edward-Wilkinson (EW) equations. We show, by using a one-loop perturbative field theoretic setup that, depending upon the spatial scaling of the variance of the external forces that drive the environment (i.e., the NS, KPZ, or EW equations), the system may show weak or strong dynamic scaling at the critical point of active-to-absorbing-state phase transitions. In the former case AAPT displays scaling belonging to the DP universality class, whereas in the latter case the universal behavior is different. PMID:23005737

  16. The impact of solar wind ULF Bz fluctuations on geomagnetic activity for viscous timescales during strongly northward and southward IMF

    NASA Astrophysics Data System (ADS)

    Osmane, A.; Dimmock, A. P.; Naderpour, R.; Pulkkinen, T. I.; Nykyri, K.

    2015-11-01

    We analyze more than 17 years of OMNI data to statistically quantify the impact of IMF Bz fluctuations on AL by using higher-order moments in the AL-distribution as a proxy. For strongly southward interplanetary magnetic field (IMF), the AL distribution function is characterized by a decrease of the skewness, a shift of its peak from -30 nT to -200 nT, and a broadening of the distribution core. During northward IMF, the distribution of AL is characterized by a significant reduction of the standard deviation and weight in the tail. Following this characterization of AL for southward and northward IMF, we show that IMF fluctuations enhance the driving on timescales smaller than those of substorms by shifting the peak of the probability distribution function by more than 150 nT during southward IMF, and by narrowing the distribution function by a factor of 2 during northward IMF. For both southward and northward IMF, we demonstrate that high power fluctuations in Bz systematically result in a greater level of activity on timescales consistent with viscous processes. Our results provide additional quantitative evidence of the role of the solar wind fluctuations in geomagnetic activity. The methodology presented also provides a framework to characterize short timescale magnetospheric dynamics taking place on the order of viscous timescales τ ≪ 1 hour.

  17. 20(S)-protopanaxadiol, an active ginseng metabolite, exhibits strong antidepressant-like effects in animal tests.

    PubMed

    Xu, Changjiang; Teng, Jijun; Chen, Weidong; Ge, Qiang; Yang, Zhiqi; Yu, Chunying; Yang, Zirong; Jia, William

    2010-12-01

    Ginseng has been used for mood adjustment in traditional Chinese medicine for thousands of years. Our previous study has shown that, total ginsenosides, the major pharmacologically functional ingredients of ginseng, possess antidepressant activity. In the present study, we hypothesized that an intestinal metabolite of ginseng, 20(S)-protopanaxadiol (code name S111), as a post metabolism compound (PMC) of ingested ginsenosides, may be responsible for the antidepressant activity of ginseng. To test this hypothesis, antidepressant-like activity of orally given S111 was measured in animal tests including tail suspension test, forced swimming test and rat olfactory bulbectomy depression model. In all those tests, S111 demonstrated antidepressant-like activity as potent as fluoxetine. S111 treated bulbectomy animals had higher levels of monoamine neurotransmitters in the brain and in vitro reuptake assay showed that S111 had a mild inhibitory effect. Furthermore, S111 but not fluoxetine significantly reduced brain oxidative stress and down-regulated serum corticosterone concentration in bulbectomy animals. No disturbance to central nervous system (CNS) normal functions were found in S111 treated animals. These results suggest that the ginseng active metabolite S111 is a potential antidepressant. Since the monoamine reuptake activity of this compound is rather weak, it remains to be investigated whether its antidepressant-like effect is by mechanisms that are different from current antidepressants. Furthermore, this study has demonstrated that post metabolism compounds (PMCs) of herb medicines such as S111 may be a novel source for drug discovery from medicinal herbs. PMID:20647027

  18. Crystal structure of type I 3-dehydroquinate dehydratase of Aquifex aeolicus suggests closing of active site flap is not essential for enzyme action.

    PubMed

    Devi, Aribam Swarmistha; Ebihara, Akio; Kuramitsu, Seiki; Yokoyama, Shigeyuki; Kumarevel, Thirumananseri; Ponnuraj, Karthe

    2013-03-01

    Structural analyses of enzymes involved in biosynthetic pathways that are present in micro-organisms, but absent from mammals (for example Shikimate pathway) are important in developing anti-microbial drugs. Crystal structure of the Shikimate pathway enzyme, type I 3-dehydroquinate dehydratase (3-DHQase) from the hyperthermophilic bacterium Aquifex aeolicus was solved both as an apo form and in complex with a ligand. The complex structure revealed an interesting structural difference when compared to other ligand-bound type I 3-DHQases suggesting that closure of the active site loop is not essential for catalysis. This provides new insights into the catalytic mechanism of type I 3-DHQases. PMID:23396056

  19. Genes Upregulated in Winter Wheat (Triticum aestivum L.) during Mild Freezing and Subsequent Thawing Suggest Sequential Activation of Multiple Response Mechanisms

    PubMed Central

    Skinner, Daniel Z.

    2015-01-01

    Exposing fully cold-acclimated wheat plants to a mild freeze-thaw cycle of −3°C for 24h followed by +3°C for 24 or 48h results in dramatically improved tolerance of subsequent exposure to sub-freezing temperatures. Gene enrichment analysis of crown tissue from plants collected before or after the −3°C freeze or after thawing at +3°C for 24 or 48h revealed that many biological processes and molecular functions were activated during the freeze-thaw cycle in an increasing cascade of responses such that over 150 processes or functions were significantly enhanced by the end of the 48 h, post-freeze thaw. Nearly 2,000 individual genes were upregulated more than 2-fold over the 72 h course of freezing and thawing, but more than 70% of these genes were upregulated during only one of the time periods examined, suggesting a series of genes and gene functions were involved in activation of the processes that led to enhanced freezing tolerance. This series of functions appeared to include extensive cell signaling, activation of stress response mechanisms and the phenylpropanoid biosynthetic pathway, extensive modification of secondary metabolites, and physical restructuring of cell membranes. By identifying plant lines that are especially able to activate these multiple mechanisms it may be possible to develop lines with enhanced winterhardiness. PMID:26173115

  20. Activation of anthocyanin biosynthesis in Gerbera hybrida (Asteraceae) suggests conserved protein-protein and protein-promoter interactions between the anciently diverged monocots and eudicots.

    PubMed

    Elomaa, Paula; Uimari, Anne; Mehto, Merja; Albert, Victor A; Laitinen, Roosa A E; Teeri, Teemu H

    2003-12-01

    We have identified an R2R3-type MYB factor, GMYB10, from Gerbera hybrida (Asteraceae) that shares high sequence homology to and is phylogenetically grouped together with the previously characterized regulators of anthocyanin pigmentation in petunia (Petunia hybrida) and Arabidopsis. GMYB10 is able to induce anthocyanin pigmentation in transgenic tobacco (Nicotiana tabacum), especially in vegetative parts and anthers. In G. hybrida, GMYB10 is involved in activation of anthocyanin biosynthesis in leaves, floral stems, and flowers. In flowers, its expression is restricted to petal epidermal cell layers in correlation with the anthocyanin accumulation pattern. We have shown, using yeast (Saccharomyces cerevisiae) two-hybrid assay, that GMYB10 interacts with the previously isolated bHLH factor GMYC1. Particle bombardment analysis was used to show that GMYB10 is required for activation of a late anthocyanin biosynthetic gene promoter, PGDFR2. cis-Analysis of the target PGDFR2 revealed a sequence element with a key role in activation by GMYB10/GMYC1. This element shares high homology with the anthocyanin regulatory elements characterized in maize (Zea mays) anthocyanin promoters, suggesting that the regulatory mechanisms involved in activation of anthocyanin biosynthesis have been conserved for over 125 million years not only at the level of transcriptional regulators but also at the level of the biosynthetic gene promoters. PMID:14605235

  1. Activation of Anthocyanin Biosynthesis in Gerbera hybrida (Asteraceae) Suggests Conserved Protein-Protein and Protein-Promoter Interactions between the Anciently Diverged Monocots and Eudicots1

    PubMed Central

    Elomaa, Paula; Uimari, Anne; Mehto, Merja; Albert, Victor A.; Laitinen, Roosa A.E.; Teeri, Teemu H.

    2003-01-01

    We have identified an R2R3-type MYB factor, GMYB10, from Gerbera hybrida (Asteraceae) that shares high sequence homology to and is phylogenetically grouped together with the previously characterized regulators of anthocyanin pigmentation in petunia (Petunia hybrida) and Arabidopsis. GMYB10 is able to induce anthocyanin pigmentation in transgenic tobacco (Nicotiana tabacum), especially in vegetative parts and anthers. In G. hybrida, GMYB10 is involved in activation of anthocyanin biosynthesis in leaves, floral stems, and flowers. In flowers, its expression is restricted to petal epidermal cell layers in correlation with the anthocyanin accumulation pattern. We have shown, using yeast (Saccharomyces cerevisiae) two-hybrid assay, that GMYB10 interacts with the previously isolated bHLH factor GMYC1. Particle bombardment analysis was used to show that GMYB10 is required for activation of a late anthocyanin biosynthetic gene promoter, PGDFR2. cis-Analysis of the target PGDFR2 revealed a sequence element with a key role in activation by GMYB10/GMYC1. This element shares high homology with the anthocyanin regulatory elements characterized in maize (Zea mays) anthocyanin promoters, suggesting that the regulatory mechanisms involved in activation of anthocyanin biosynthesis have been conserved for over 125 million years not only at the level of transcriptional regulators but also at the level of the biosynthetic gene promoters. PMID:14605235

  2. Hypnosis, suggestion, and suggestibility: an integrative model.

    PubMed

    Lynn, Steven Jay; Laurence, Jean-Roch; Kirsch, Irving

    2015-01-01

    This article elucidates an integrative model of hypnosis that integrates social, cultural, cognitive, and neurophysiological variables at play both in and out of hypnosis and considers their dynamic interaction as determinants of the multifaceted experience of hypnosis. The roles of these variables are examined in the induction and suggestion stages of hypnosis, including how they are related to the experience of involuntariness, one of the hallmarks of hypnosis. It is suggested that studies of the modification of hypnotic suggestibility; cognitive flexibility; response sets and expectancies; the default-mode network; and the search for the neurophysiological correlates of hypnosis, more broadly, in conjunction with research on social psychological variables, hold much promise to further understanding of hypnosis. PMID:25928681

  3. The level of glucose-6-phosphate dehydrogenase activity strongly influences xylose fermentation and inhibitor sensitivity in recombinant Saccharomyces cerevisiae strains.

    PubMed

    Jeppsson, Marie; Johansson, Björn; Jensen, Peter Ruhdal; Hahn-Hägerdal, Bärbel; Gorwa-Grauslund, Marie F

    2003-11-01

    Disruption of the ZWF1 gene encoding glucose-6-phosphate dehydrogenase (G6PDH) has been shown to reduce the xylitol yield and the xylose consumption in the xylose-utilizing recombinant Saccharomyces cerevisiae strain TMB3255. In the present investigation we have studied the influence of different production levels of G6PDH on xylose fermentation. We used a synthetic promoter library and the copper-regulated CUP1 promoter to generate G6PDH-activities between 0% and 179% of the wild-type level. G6PDH-activities of 1% and 6% of the wild-type level resulted in 2.8- and 5.1-fold increase in specific xylose consumption, respectively, compared with the ZWF1-disrupted strain. Both strains exhibited decreased xylitol yields (0.13 and 0.19 g/g xylose) and enhanced ethanol yields (0.36 and 0.34 g/g xylose) compared with the control strain TMB3001 (0.29 g xylitol/g xylose, 0.31 g ethanol/g xylose). Cytoplasmic transhydrogenase (TH) from Azotobacter vinelandii has previously been shown to transfer NADPH and NAD(+) into NADP(+) and NADH, and TH-overproduction resulted in lower xylitol yield and enhanced glycerol yield during xylose utilization. Strains with low G6PDH-activity grew slower in a lignocellulose hydrolysate than the strain with wild-type G6PDH-activity, which suggested that the availability of intracellular NADPH correlated with tolerance towards lignocellulose-derived inhibitors. Low G6PDH-activity strains were also more sensitive to H(2)O(2) than the control strain TMB3001. PMID:14618564

  4. Suggested Involvement of PP1/PP2A Activity and De Novo Gene Expression in Anhydrobiotic Survival in a Tardigrade, Hypsibius dujardini, by Chemical Genetic Approach

    PubMed Central

    Kondo, Koyuki; Kubo, Takeo; Kunieda, Takekazu

    2015-01-01

    Upon desiccation, some tardigrades enter an ametabolic dehydrated state called anhydrobiosis and can survive a desiccated environment in this state. For successful transition to anhydrobiosis, some anhydrobiotic tardigrades require pre-incubation under high humidity conditions, a process called preconditioning, prior to exposure to severe desiccation. Although tardigrades are thought to prepare for transition to anhydrobiosis during preconditioning, the molecular mechanisms governing such processes remain unknown. In this study, we used chemical genetic approaches to elucidate the regulatory mechanisms of anhydrobiosis in the anhydrobiotic tardigrade, Hypsibius dujardini. We first demonstrated that inhibition of transcription or translation drastically impaired anhydrobiotic survival, suggesting that de novo gene expression is required for successful transition to anhydrobiosis in this tardigrade. We then screened 81 chemicals and identified 5 chemicals that significantly impaired anhydrobiotic survival after severe desiccation, in contrast to little or no effect on survival after high humidity exposure only. In particular, cantharidic acid, a selective inhibitor of protein phosphatase (PP) 1 and PP2A, exhibited the most profound inhibitory effects. Another PP1/PP2A inhibitor, okadaic acid, also significantly and specifically impaired anhydrobiotic survival, suggesting that PP1/PP2A activity plays an important role for anhydrobiosis in this species. This is, to our knowledge, the first report of the required activities of signaling molecules for desiccation tolerance in tardigrades. The identified inhibitory chemicals could provide novel clues to elucidate the regulatory mechanisms underlying anhydrobiosis in tardigrades. PMID:26690982

  5. Receptor activating NF-κB ligand (RANKL) is a constitutive intracellular protein in resting human basophils and is strongly induced on their surface by interleukin 3.

    PubMed

    Poli, Caroline; Martin, Jérôme C; Braudeau, Cécile; Bériou, Gaelle; Hémont, Caroline; Charrier, Céline; Guérin, Sarah; Heslan, Michèle; Josien, Régis

    2015-05-01

    Receptor activating NF-κB ligand (RANKL) is a member of the TNF superfamily that plays a pivotal role in bone homeostasis as being the major osteoclastogenesis factor. RANKL also has pleiotropic effects in the immune system in which it is expressed by activated T and B cells and some innate lymphoid cells. RANKL-RANK interactions mediate lymph node organogenesis and immunoregulatory functions in autoimmune disease and carcinogenesis as well as cross talk between the immune system and bone. In this study, we show that basophils were the strongest RANKL mRNA-expressing cells amongst major leukocyte subsets in human blood. RANKL was preformed as an intracellular protein in resting basophils and was rapidly and strongly expressed on their surface upon stimulation with IL-3, but not other stimuli. This expression was stable for at least 6 days. Activated basophils could also release soluble RANKL in small quantities upon interaction with DCs or monocytes. In the blood, basophils were the sole cells to express membrane RANKL in response to IL-3. This study indicates that basophils should be considered as new players in the pleiotropic and complex RANKL-RANK interaction system and suggests a role for RANKL in the interaction between basophils and immune cells in inflammatory allergic tissues and secondary lymphoid organs. PMID:25433635

  6. Iron- and Cobalt-Catalyzed Alkene Hydrogenation: Catalysis with Both Redox-Active and Strong Field Ligands.

    PubMed

    Chirik, Paul J

    2015-06-16

    The hydrogenation of alkenes is one of the most impactful reactions catalyzed by homogeneous transition metal complexes finding application in the pharmaceutical, agrochemical, and commodity chemical industries. For decades, catalyst technology has relied on precious metal catalysts supported by strong field ligands to enable highly predictable two-electron redox chemistry that constitutes key bond breaking and forming steps during turnover. Alternative catalysts based on earth abundant transition metals such as iron and cobalt not only offer potential environmental and economic advantages but also provide an opportunity to explore catalysis in a new chemical space. The kinetically and thermodynamically accessible oxidation and spin states may enable new mechanistic pathways, unique substrate scope, or altogether new reactivity. This Account describes my group's efforts over the past decade to develop iron and cobalt catalysts for alkene hydrogenation. Particular emphasis is devoted to the interplay of the electronic structure of the base metal compounds and their catalytic performance. First generation, aryl-substituted pyridine(diimine) iron dinitrogen catalysts exhibited high turnover frequencies at low catalyst loadings and hydrogen pressures for the hydrogenation of unactivated terminal and disubstituted alkenes. Exploration of structure-reactivity relationships established smaller aryl substituents and more electron donating ligands resulted in improved performance. Second generation iron and cobalt catalysts where the imine donors were replaced by N-heterocyclic carbenes resulted in dramatically improved activity and enabled hydrogenation of more challenging unactivated, tri- and tetrasubstituted alkenes. Optimized cobalt catalysts have been discovered that are among the most active homogeneous hydrogenation catalysts known. Synthesis of enantiopure, C1 symmetric pyridine(diimine) cobalt complexes have enabled rare examples of highly enantioselective

  7. Accretion disc dynamo activity in local simulations spanning weak-to-strong net vertical magnetic flux regimes

    NASA Astrophysics Data System (ADS)

    Salvesen, Greg; Simon, Jacob B.; Armitage, Philip J.; Begelman, Mitchell C.

    2016-03-01

    Strongly magnetized accretion discs around black holes have attractive features that may explain enigmatic aspects of X-ray binary behaviour. The structure and evolution of these discs are governed by a dynamo-like mechanism, which channels part of the accretion power liberated by the magnetorotational instability (MRI) into an ordered toroidal magnetic field. To study dynamo activity, we performed three-dimensional, stratified, isothermal, ideal magnetohydrodynamic shearing box simulations. The strength of the self-sustained toroidal magnetic field depends on the net vertical magnetic flux, which we vary across almost the entire range over which the MRI is linearly unstable. We quantify disc structure and dynamo properties as a function of the initial ratio of mid-plane gas pressure to vertical magnetic field pressure, β _0^mid = p_gas / p_B. For 10^5 ≥ β _0^mid ≥ 10 the effective α-viscosity parameter scales as a power law. Dynamo activity persists up to and including β _0^mid = 10^2, at which point the entire vertical column of the disc is magnetic pressure dominated. Still stronger fields result in a highly inhomogeneous disc structure, with large density fluctuations. We show that the turbulent steady state βmid in our simulations is well matched by the analytic model of Begelman et al. describing the creation and buoyant escape of toroidal field, while the vertical structure of the disc can be broadly reproduced using this model. Finally, we discuss the implications of our results for observed properties of X-ray binaries.

  8. Clonality Analysis of Immunoglobulin Gene Rearrangement by Next-Generation Sequencing in Endemic Burkitt Lymphoma Suggests Antigen Drive Activation of BCR as Opposed to Sporadic Burkitt Lymphoma

    PubMed Central

    Amato, Teresa; Abate, Francesco; Piccaluga, Pierpaolo; Iacono, Michele; Fallerini, Chiara; Renieri, Alessandra; De Falco, Giulia; Ambrosio, Maria Raffaella; Mourmouras, Vaselious; Ogwang, Martin; Calbi, Valeria; Rabadan, Roul; Hummel, Michael; Pileri, Stefano; Bellan, Cristiana

    2016-01-01

    Objectives: Recent studies using next-generation sequencing (NGS) analysis disclosed the importance of the intrinsic activation of the B-cell receptor (BCR) pathway in the pathogenesis of sporadic Burkitt lymphoma (sBL) due to mutations of TCF3/ID3 genes. Since no definitive data are available on the genetic landscape of endemic Burkitt (eBL), we first assessed the mutation frequency of TCF3/ID3 in eBL compared with sBL and subsequently the somatic hypermutation status of the BCR to answer whether an extrinsic activation of BCR signaling could also be demonstrated in Burkitt lymphoma. Methods: We assessed the mutations of TCF3/ID3 by RNAseq and the BCR status by NGS analysis of the immunoglobulin genes (IGs). Results: We detected mutations of TCF3/ID3 in about 30% of the eBL cases. This rate is significantly lower than that detected in sBL (64%). The NGS analysis of IGs revealed intraclonal diversity, suggesting an active targeted somatic hypermutation process in eBL compared with sBL. Conclusions: These findings support the view that the antigenic pressure plays a key role in the pathogenetic pathways of eBL, which may be partially distinct from those driving sBL development. PMID:26712879

  9. STRONG VARIABLE ULTRAVIOLET EMISSION FROM Y GEM: ACCRETION ACTIVITY IN AN ASYMPTOTIC GIANT BRANCH STAR WITH A BINARY COMPANION?

    SciTech Connect

    Sahai, Raghvendra; Neill, James D.; Gil de Paz, Armando; Sanchez Contreras, Carmen

    2011-10-20

    Binarity is believed to dramatically affect the history and geometry of mass loss in asymptotic giant branch (AGB) and post-AGB stars, but observational evidence of binarity is sorely lacking. As part of a project to look for hot binary companions to cool AGB stars using the Galaxy Evolution Explorer archive, we have discovered a late-M star, Y Gem, to be a source of strong and variable UV emission. Y Gem is a prime example of the success of our technique of UV imaging of AGB stars in order to search for binary companions. Y Gem's large and variable UV flux makes it one of the most prominent examples of a late-AGB star with a mass accreting binary companion. The UV emission is most likely due to emission associated with accretion activity and a disk around a main-sequence companion star. The physical mechanism generating the UV emission is extremely energetic, with an integrated luminosity of a few x L{sub sun} at its peak. We also find weak CO J = 2-1 emission from Y Gem with a very narrow line profile (FWHM of 3.4 km s{sup -1}). Such a narrow line is unlikely to arise in an outflow and is consistent with emission from an orbiting, molecular reservoir of radius 300 AU. Y Gem may be the progenitor of the class of post-AGB stars which are binaries and possess disks but no outflows.

  10. Structure-Based Design of Potent Bcl-2/Bcl-xL Inhibitors with Strong in Vivo Antitumor Activity

    SciTech Connect

    Zhou, Haibin; Aguilar, Angelo; Chen, Jianfang; Bai, Longchuan; Liu, Liu; Meagher, Jennifer L.; Yang, Chao-Yie; McEachern, Donna; Cong, Xin; Stuckey, Jeanne A.; Wang, Shaomeng

    2012-08-21

    Bcl-2 and Bcl-xL are key apoptosis regulators and attractive cancer therapeutic targets. We have designed and optimized a class of small-molecule inhibitors of Bcl-2 and Bcl-xL containing a 4,5-diphenyl-1H-pyrrole-3-carboxylic acid core structure. A 1.4 {angstrom} resolution crystal structure of a lead compound, 12, complexed with Bcl-xL has provided a basis for our optimization. The most potent compounds, 14 and 15, bind to Bcl-2 and Bcl-xL with subnanomolar K{sub i} values and are potent antagonists of Bcl-2 and Bcl-xL in functional assays. Compounds 14 and 15 inhibit cell growth with low nanomolar IC{sub 50} values in multiple small-cell lung cancer cell lines and induce robust apoptosis in cancer cells at concentrations as low as 10 nM. Compound 14 also achieves strong antitumor activity in an animal model of human cancer.

  11. Synthesis of N-acyl homoserine lactone analogues reveals strong activators of SdiA, the Salmonella enterica serovar Typhimurium LuxR homologue.

    PubMed

    Janssens, Joost C A; Metzger, Kristine; Daniels, Ruth; Ptacek, Dave; Verhoeven, Tine; Habel, Lothar W; Vanderleyden, Jos; De Vos, Dirk E; De Keersmaecker, Sigrid C J

    2007-01-01

    N-Acyl homoserine lactones (AHLs) are molecules that are synthesized and detected by many gram-negative bacteria to monitor the population density, a phenomenon known as quorum sensing. Salmonella enterica serovar Typhimurium is an exceptional species since it does not synthesize its own AHLs, while it does encode a LuxR homologue, SdiA, which enables this bacterium to detect AHLs that are produced by other species. To obtain more information about the specificity of the ligand binding by SdiA, we synthesized and screened a limited library of AHL analogues. We identified two classes of analogues that are strong activators of SdiA: the N-(3-oxo-acyl)-homocysteine thiolactones (3O-AHTLs) and the N-(3-oxo-acyl)-trans-2-aminocyclohexanols. To our knowledge, this is the first report of compounds (the 3O-AHTLs) that are able to activate a LuxR homologue at concentrations that are lower than the concentrations of the most active AHLs. SdiA responds with greatest sensitivity to AHTLs that have a keto modification at the third carbon atom and an acyl chain that is seven or eight carbon atoms long. The N-(3-oxo-acyl)-trans-2-aminocyclohexanols were found to be less sensitive to deactivation by lactonase and alkaline pH than the 3O-AHTLs and the AHLs are. We also examined the activity of our library with LuxR of Vibrio fischeri and identified three new inhibitors of LuxR. Finally, we performed preliminary binding experiments which suggested that SdiA binds its activators reversibly. These results increase our understanding of the specificity of the SdiA-ligand interaction, which could have uses in the development of anti-quorum-sensing-based antimicrobials. PMID:17085703

  12. Living Bones, Strong Bones

    NASA Video Gallery

    In this classroom activity, engineering, nutrition, and physical activity collide when students design and build a healthy bone model of a space explorer which is strong enough to withstand increas...

  13. Inhibition of Beta Interferon Induction by Severe Acute Respiratory Syndrome Coronavirus Suggests a Two-Step Model for Activation of Interferon Regulatory Factor 3

    PubMed Central

    Spiegel, Martin; Pichlmair, Andreas; Martínez-Sobrido, Luis; Cros, Jerome; García-Sastre, Adolfo; Haller, Otto; Weber, Friedemann

    2005-01-01

    Severe acute respiratory syndrome (SARS) is caused by a novel coronavirus termed SARS-CoV. We and others have previously shown that the replication of SARS-CoV can be suppressed by exogenously added interferon (IFN), a cytokine which is normally synthesized by cells as a reaction to virus infection. Here, we demonstrate that SARS-CoV escapes IFN-mediated growth inhibition by preventing the induction of IFN-β. In SARS-CoV-infected cells, no endogenous IFN-β transcripts and no IFN-β promoter activity were detected. Nevertheless, the transcription factor interferon regulatory factor 3 (IRF-3), which is essential for IFN-β promoter activity, was transported from the cytoplasm to the nucleus early after infection with SARS-CoV. However, at a later time point in infection, IRF-3 was again localized in the cytoplasm. By contrast, IRF-3 remained in the nucleus of cells infected with the IFN-inducing control virus Bunyamwera delNSs. Other signs of IRF-3 activation such as hyperphosphorylation, homodimer formation, and recruitment of the coactivator CREB-binding protein (CBP) were found late after infection with the control virus but not with SARS-CoV. Our data suggest that nuclear transport of IRF-3 is an immediate-early reaction to virus infection and may precede its hyperphosphorylation, homodimer formation, and binding to CBP. In order to escape activation of the IFN system, SARS-CoV appears to block a step after the early nuclear transport of IRF-3. PMID:15681410

  14. A Comparison of Vanadate to a 2'-5' Linkage at the Active Site of a Small Ribozyme Suggests a Role for Water in Transition-State Stabilization

    SciTech Connect

    Torelli, A.T.; Krucinska, J.; Wedekind, J.E.

    2009-06-04

    The potential for water to participate in RNA catalyzed reactions has been the topic of several recent studies. Here, we report crystals of a minimal, hinged hairpin ribozyme in complex with the transition-state analog vanadate at 2.05 A resolution. Waters are present in the active site and are discussed in light of existing views of catalytic strategies employed by the hairpin ribozyme. A second structure harboring a 2',5'-phosphodiester linkage at the site of cleavage was also solved at 2.35 A resolution and corroborates the assignment of active site waters in the structure containing vanadate. A comparison of the two structures reveals that the 2',5' structure adopts a conformation that resembles the reaction intermediate in terms of (1) the positioning of its nonbridging oxygens and (2) the covalent attachment of the 2'-O nucleophile with the scissile G+1 phosphorus. The 2',5'-linked structure was then overlaid with scissile bonds of other small ribozymes including the glmS metabolite-sensing riboswitch and the hammerhead ribozyme, and suggests the potential of the 2',5' linkage to elicit a reaction-intermediate conformation without the need to form metalloenzyme complexes. The hairpin ribozyme structures presented here also suggest how water molecules bound at each of the nonbridging oxygens of G+1 may electrostatically stabilize the transition state in a manner that supplements nucleobase functional groups. Such coordination has not been reported for small ribozymes, but is consistent with the structures of protein enzymes. Overall, this work establishes significant parallels between the RNA and protein enzyme worlds.

  15. A recent strong X-ray flaring activity of 1ES 1959+650 with possibly less efficient stochastic acceleration

    NASA Astrophysics Data System (ADS)

    Kapanadze, B.; Dorner, D.; Vercellone, S.; Romano, P.; Kapanadze, S.; Mdzinarishvili, T.

    2016-09-01

    We present an X-ray flaring activity of 1ES 1959+650 in 2015 August-2016 January, which was the most powerful and prolonged during the 10.75 yr period since the start of its monitoring with X-ray Telescope onboard Swift. A new highest historical 0.3-10 keV count rate was recorded three times that makes this object the third BL Lacertae source exceeding the level of 20 counts s-1. Along with the overall variability by a factor of 5.7, this epoch was characterized by fast X-ray flares by a factor of 2.0-3.1, accompanied with an extreme spectral variability. The source also shows a simultaneous flaring activity in the optical - UV and 0.3-100 GeV bands, although a fast γ-ray flare without significant optical - X-ray counterparts is also found. In contrast to the X-ray flares in the previous years, the stochastic acceleration seems be less important for the electrons responsible for producing X-ray emission during this flare that challenges the earlier suggestion that the electrons in the jets of TeV-detected BL Lacertae objects should undergo an efficient stochastic acceleration resulting in a lower X-ray spectral curvature.

  16. A recent strong X-ray flaring activity of 1ES 1959+650 with possibly less efficient stochastic acceleration

    NASA Astrophysics Data System (ADS)

    Kapanadze, B.; Dorner, D.; Vercellone, S.; Romano, P.; Kapanadze, S.; Mdzinarishvili, T.

    2016-03-01

    We present an X-ray flaring activity of 1ES 1959+650 in 2015 August - 2016 January, which was the most powerful and prolonged during the 10.75 yr period since the start of its monitoring with X-ray Telescope onboard Swift. A new highest historical 0.3 - 10 keV count rate was recorded three times that makes this object the third BL Lacertae source exceeding the level of 20 cts s-1. Along with the overall variability by a factor of 5.7, this epoch was characterized by fast X-ray flares by a factor of 2.0 - 3.1, accompanied with an extreme spectral variability. The source also shows a simultaneous flaring activity in the optical - UV and 0.3 - 100 GeV bands, although a fast γ-ray flare without significant optical - X-ray counterparts is also found. In contrast to the X-ray flares in the previous years, the stochastic acceleration seems be less important for the electrons responsible for producing X-ray emission during this flare that challenges the earlier suggestion that the electrons in the jets of TeV-detected BL Lacertae objects should undergo an efficient stochastic acceleration resulting in a lower X-ray spectral curvature.

  17. Active and passive biomonitoring suggest metabolic adaptation in blue mussels (Mytilus spp.) chronically exposed to a moderate contamination in Brest harbor (France).

    PubMed

    Lacroix, Camille; Richard, Gaëlle; Seguineau, Catherine; Guyomarch, Julien; Moraga, Dario; Auffret, Michel

    2015-05-01

    Brest harbor (Bay of Brest, Brittany, France) has a severe past of anthropogenic chemical contamination, but inputs tended to decrease, indicating a reassessment of its ecotoxicological status should be carried out. Here, native and caged mussels (Mytilus spp.) were used in combination to evaluate biological effects of chronic chemical contamination in Brest harbor. Polycyclic aromatic hydrocarbon (PAH) contamination was measured in mussel tissues as a proxy of harbor and urban pollution. Biochemical biomarkers of xenobiotic biotransformation, antioxidant defenses, generation of reducing equivalents, energy metabolism and oxidative damage were studied in both gills and digestive glands of native and caged mussels. In particular, activities of glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), NADP-dependent isocitrate dehydrogenase (IDP), pyruvate kinase (PK) and phosphoenolpyruvate carboxykinase (PEPCK) were measured and lipid peroxidation was assessed by malondialdehyde (MDA) quantification. In addition, a condition index was calculated to assess the overall health of the mussels. Moderate PAH contamination was detected in digestive glands of both native and caged individuals from the exposed site. Modulations of biomarkers were detected in digestive glands of native harbor mussels indicating the presence of a chemical pressure. In particular, results suggested increased biotransformation (GST), antioxidant defenses (CAT), NADPH generation (IDP) and gluconeogenesis (PEPCK), which could represent a coordinated response against chemically-induced cellular stress. Lipid peroxidation assessment and condition index indicated an absence of acute stress in the same mussels suggesting metabolic changes could, at least partially, offset the negative effects of contamination. In caged mussels, only GR was found modulated compared to non-exposed mussels but significant differences in

  18. Metal-induced conformational changes in ZneB suggest an active role of membrane fusion proteins in efflux resistance systems.

    PubMed

    De Angelis, Fabien; Lee, John K; O'Connell, Joseph D; Miercke, Larry J W; Verschueren, Koen H; Srinivasan, Vasundara; Bauvois, Cédric; Govaerts, Cédric; Robbins, Rebecca A; Ruysschaert, Jean-Marie; Stroud, Robert M; Vandenbussche, Guy

    2010-06-15

    Resistance nodulation cell division (RND)-based efflux complexes mediate multidrug and heavy-metal resistance in many Gram-negative bacteria. Efflux of toxic compounds is driven by membrane proton/substrate antiporters (RND protein) in the plasma membrane, linked by a membrane fusion protein (MFP) to an outer-membrane protein. The three-component complex forms an efflux system that spans the entire cell envelope. The MFP is required for the assembly of this complex and is proposed to play an important active role in substrate efflux. To better understand the role of MFPs in RND-driven efflux systems, we chose ZneB, the MFP component of the ZneCAB heavy-metal efflux system from Cupriavidus metallidurans CH34. ZneB is shown to be highly specific for Zn(2+) alone. The crystal structure of ZneB to 2.8 A resolution defines the basis for metal ion binding in the coordination site at a flexible interface between the beta-barrel and membrane proximal domains. The conformational differences observed between the crystal structures of metal-bound and apo forms are monitored in solution by spectroscopy and chromatography. The structural rearrangements between the two states suggest an active role in substrate efflux through metal binding and release. PMID:20534468

  19. Lanthanide-Assisted Deposition of Strongly Electro-optic PZT Thin Films on Silicon: Toward Integrated Active Nanophotonic Devices.

    PubMed

    George, J P; Smet, P F; Botterman, J; Bliznuk, V; Woestenborghs, W; Van Thourhout, D; Neyts, K; Beeckman, J

    2015-06-24

    The electro-optical properties of lead zirconate titanate (PZT) thin films depend strongly on the quality and crystallographic orientation of the thin films. We demonstrate a novel method to grow highly textured PZT thin films on silicon using the chemical solution deposition (CSD) process. We report the use of ultrathin (5-15 nm) lanthanide (La, Pr, Nd, Sm) based intermediate layers for obtaining preferentially (100) oriented PZT thin films. X-ray diffraction measurements indicate preferentially oriented intermediate Ln2O2CO3 layers providing an excellent lattice match with the PZT thin films grown on top. The XRD and scanning electron microscopy measurements reveal that the annealed layers are dense, uniform, crack-free and highly oriented (>99.8%) without apparent defects or secondary phases. The EDX and HRTEM characterization confirm that the template layers act as an efficient diffusion barrier and form a sharp interface between the substrate and the PZT. The electrical measurements indicate a dielectric constant of ∼650, low dielectric loss of ∼0.02, coercive field of 70 kV/cm, remnant polarization of 25 μC/cm(2), and large breakdown electric field of 1000 kV/cm. Finally, the effective electro-optic coefficients of the films are estimated with a spectroscopic ellipsometer measurement, considering the electric field induced variations in the phase reflectance ratio. The electro-optic measurements reveal excellent linear effective pockels coefficients of 110 to 240 pm/V, which makes the CSD deposited PZT thin film an ideal candidate for Si-based active integrated nanophotonic devices. PMID:26043103

  20. Genome-wide identification and expression analysis of the mitogen-activated protein kinase gene family from banana suggest involvement of specific members in different stages of fruit ripening.

    PubMed

    Asif, Mehar Hasan; Lakhwani, Deepika; Pathak, Sumya; Bhambhani, Sweta; Bag, Sumit K; Trivedi, Prabodh Kumar

    2014-03-01

    Mitogen-activated protein kinases (MAPKs) are important components of the tripartite mitogen-activated protein kinase signaling cascade and play an important role in plant growth and development. Although members of the MAPK gene family have been identified in model plants, little information is available regarding this gene family in fruit crops. In this study, we carried out a computational analysis using the Musa Genome database to identify members of the MAPK gene family in banana, an economically important crop and the most popular fruit worldwide. Our analysis identified 25 members of the MAP kinase (MAPK or MPK) gene family. Phylogenetic analyses of MPKs in Arabidopsis, Oryza, and Populus have classified these MPKs into four subgroups. The presence of conserved domains in the deduced amino acid sequences, phylogeny, and genomic organization strongly support their identity as members of the MPK gene family. Expression analysis during ethylene-induced banana fruit ripening suggests the involvement of several MPKs in the ethylene signal transduction pathway that are necessary for banana fruit ripening. Analysis of the cis-regulatory elements in the promoter regions and the involvement of the identified MPKs in various cellular processes, as analyzed using Pathway Studio, suggest a role for the banana MPK gene family in diverse functions related to growth, development, and the stress response. This report is the first concerning the identification of members of a gene family and the elucidation of their role in various processes using the Musa Genome database. PMID:24275941

  1. Open to Suggestion.

    ERIC Educational Resources Information Center

    Journal of Reading, 1987

    1987-01-01

    Offers (1) suggestions for improving college students' study skills; (2) a system for keeping track of parent, teacher, and community contacts; (3) suggestions for motivating students using tic tac toe; (4) suggestions for using etymology to improve word retention; (5) a word search grid; and (6) suggestions for using postcards in remedial reading…

  2. Ground Motion Simulation for a Large Active Fault System using Empirical Green's Function Method and the Strong Motion Prediction Recipe - a Case Study of the Noubi Fault Zone -

    NASA Astrophysics Data System (ADS)

    Kuriyama, M.; Kumamoto, T.; Fujita, M.

    2005-12-01

    propagation. Moreover, it was clarified that the horizontal velocities by assuming the cascade model was underestimated more than one standard deviation of empirical relation by Si and Midorikawa (1999). The scaling and cascade models showed an approximately 6.4-fold difference for the case, in which the rupture started along the southeastern edge of the Umehara Fault at observation point GIF020. This difference is significantly large in comparison with the effect of different rupture starting points, and shows that it is important to base scenario earthquake assumptions on active fault datasets before establishing the source characterization model. The distribution map of seismic intensity for the 1891 Noubi Earthquake also suggests that the synthetic waveforms in the southeastern Noubi Fault zone may be underestimated. Our results indicate that outer fault parameters (e.g., earthquake moment) related to the construction of scenario earthquakes influence strong motion prediction, rather than inner fault parameters such as the rupture starting point. Based on these methods, we will predict strong motion for approximately 140 to 150 km of the Itoigawa-Shizuoka Tectonic Line.

  3. Microtremor Array Measurement Survey and Strong Ground Motion Observation Activities of The MarDiM (SATREPS) Project

    NASA Astrophysics Data System (ADS)

    Ozgur Citak, Seckin; Karagoz, Ozlem; Chimoto, Kosuke; Ozel, Oguz; Yamanaka, Hiroaki; Aksahin, Bengi; Arslan, Safa; Hatayama, Ken; Ohori, Michihiro; Hori, Muneo

    2015-04-01

    Since 1939, devastating earthquakes with magnitude greater than seven ruptured North Anatolian Fault (NAF) westward, starting from 1939 Erzincan (Ms=7.9) at the eastern Turkey and including the latest 1999 Izmit-Golcuk (Ms=7.4) and the Duzce (Ms=7.2) earthquakes in the eastern Marmara region, Turkey. On the other hand, the west of the Sea of Marmara an Mw7.4 earthquake ruptured the NAF' s Ganos segment in 1912. The only un-ruptured segments of the NAF in the last century are within the Sea of Marmara, and are identified as a "seismic gap" zone that its rupture may cause a devastating earthquake. In order to unravel the seismic risks of the Marmara region a comprehensive multidisciplinary research project The MarDiM project "Earthquake And Tsunami Disaster Mitigation in The Marmara Region and Disaster Education in Turkey", has already been started since 2003. The project is conducted in the framework of "Science and Technology Research Partnership for Sustainable Development (SATREPS)" sponsored by Japan Science and Technology Agency (JST) and Japan International Cooperation Agency (JICA). One of the main research field of the project is "Seismic characterization and damage prediction" which aims to improve the prediction accuracy of the estimation of the damages induced by strong ground motions and tsunamis based on reliable source parameters, detailed deep and shallow velocity structure and building data. As for detailed deep and shallow velocity structure microtremor array measurement surveys were conducted in Zeytinburnu district of Istanbul and Tekirdag province at about 81 sites on October 2013 and September 2014. Also in September 2014, 11 accelerometer units were installed mainly in public buildings in both Zeytinburnu and Tekirdag area and are currently in operation. Each accelerometer unit compose of a Network Sensor (CV-374A2) by Tokyo Sokushin, post processing PC for data storage and power supply unit. The Network Sensor (CV-374A2) consist of three servo

  4. Hybrid germanium iodide perovskite semiconductors: active lone pairs, structural distortions, direct and indirect energy gaps, and strong nonlinear optical properties.

    PubMed

    Stoumpos, Constantinos C; Frazer, Laszlo; Clark, Daniel J; Kim, Yong Soo; Rhim, Sonny H; Freeman, Arthur J; Ketterson, John B; Jang, Joon I; Kanatzidis, Mercouri G

    2015-06-01

    The synthesis and properties of the hybrid organic/inorganic germanium perovskite compounds, AGeI3, are reported (A = Cs, organic cation). The systematic study of this reaction system led to the isolation of 6 new hybrid semiconductors. Using CsGeI3 (1) as the prototype compound, we have prepared methylammonium, CH3NH3GeI3 (2), formamidinium, HC(NH2)2GeI3 (3), acetamidinium, CH3C(NH2)2GeI3 (4), guanidinium, C(NH2)3GeI3 (5), trimethylammonium, (CH3)3NHGeI3 (6), and isopropylammonium, (CH3)2C(H)NH3GeI3 (7) analogues. The crystal structures of the compounds are classified based on their dimensionality with 1–4 forming 3D perovskite frameworks and 5–7 1D infinite chains. Compounds 1–7, with the exception of compounds 5 (centrosymmetric) and 7 (nonpolar acentric), crystallize in polar space groups. The 3D compounds have direct band gaps of 1.6 eV (1), 1.9 eV (2), 2.2 eV (3), and 2.5 eV (4), while the 1D compounds have indirect band gaps of 2.7 eV (5), 2.5 eV (6), and 2.8 eV (7). Herein, we report on the second harmonic generation (SHG) properties of the compounds, which display remarkably strong, type I phase-matchable SHG response with high laser-induced damage thresholds (up to ∼3 GW/cm(2)). The second-order nonlinear susceptibility, χS(2), was determined to be 125.3 ± 10.5 pm/V (1), (161.0 ± 14.5) pm/V (2), 143.0 ± 13.5 pm/V (3), and 57.2 ± 5.5 pm/V (4). First-principles density functional theory electronic structure calculations indicate that the large SHG response is attributed to the high density of states in the valence band due to sp-hybridization of the Ge and I orbitals, a consequence of the lone pair activation. PMID:25950197

  5. Microtremor Array Measurement Survey and Strong Ground Motion observation activities of The SATREPS, MarDiM project -Part 2-

    NASA Astrophysics Data System (ADS)

    Citak, Seckin; Karagoz, Ozlem; Chimoto, Kosuke; Ozel, Oguz; Yamanaka, Hiroaki; Arslan, Safa; Aksahin, Bengi; Hatayama, Ken; Ohori, Michihiro; Hori, Muneo

    2016-04-01

    Since 1939, devastating earthquakes with magnitude greater than seven ruptured North Anatolian Fault (NAF) westward, starting from 1939 Erzincan (Ms=7.9) at the eastern Turkey and including the latest 1999 Izmit-Golcuk (Ms=7.4) and the Duzce (Ms=7.2) earthquakes in the eastern Marmara region, Turkey. On the other hand, the west of the Sea of Marmara an Mw7.4 earthquake ruptured the NAF' s Ganos segment in 1912. The only un-ruptured segments of the NAF in the last century are within the Sea of Marmara, and are identified as a "seismic gap" zone that its rupture may cause a devastating earthquake. In order to unravel the seismic risks of the Marmara region a comprehensive multidisciplinary research project The MarDiM project "Earthquake And Tsunami Disaster Mitigation in The Marmara Region and Disaster Education in Turkey", has already been started since 2003. The project is conducted in the framework of "Science and Technology Research Partnership for Sustainable Development (SATREPS)" sponsored by Japan Science and Technology Agency (JST) and Japan International Cooperation Agency (JICA). One of the main research field of the project is "Seismic characterization and damage prediction" which aims to improve the prediction accuracy of the estimation of the damages induced by strong ground motions and tsunamis based on reliable source parameters, detailed deep and shallow velocity structure and building data. As for detailed deep and shallow velocity structure microtremor array measurement surveys were conducted in Zeytinburnu district of Istanbul, Tekirdag, Canakkale and Edirne provinces at about 109 sites on October 2013, September 2014 and 2015. Also in September 2014, 11 accelerometer units were installed mainly in public buildings in both Zeytinburnu and Tekirdag area and are currently in operation. Each accelerometer unit compose of a Network Sensor (CV-374A) by Tokyo Sokushin, post processing PC for data storage and power supply unit. The Network Sensor (CV-374

  6. The Life of Suggestions

    ERIC Educational Resources Information Center

    Pearce, Cathie

    2010-01-01

    Using the notion of a suggestion, or rather charting the life of suggestions, this article considers the happenings of chance and embodiment as the "problems that got away." The life of suggestions helps us to ask how connectivities are made, how desire functions, and how "immanence" rather than "transcendence" can open up the politics and ethics…

  7. Analysis of multi-domain hypothetical proteins containing iron-sulphur clusters and fad ligands reveal rieske dioxygenase activity suggesting their plausible roles in bioremediation

    PubMed Central

    Sathyanarayanan, Nitish; Nagendra, Holenarasipur Gundurao

    2012-01-01

    ‘Conserved hypothetical’ proteins pose a challenge not just for functional genomics, but also to biology in general. As long as there are hundreds of conserved proteins with unknown function in model organisms such as Escherichia coli, Bacillus subtilis or Saccharomyces cerevisiae, any discussion towards a ‘complete’ understanding of these biological systems will remain a wishful thinking. Insilico approaches exhibit great promise towards attempts that enable appreciating the plausible roles of these hypothetical proteins. Among the majority of genomic proteins, two-thirds in unicellular organisms and more than 80% in metazoa, are multi-domain proteins, created as a result of gene duplication events. Aromatic ring-hydroxylating dioxygenases, also called Rieske dioxygenases (RDOs), are class of multi-domain proteins that catalyze the initial step in microbial aerobic degradation of many aromatic compounds. Investigations here address the computational characterization of hypothetical proteins containing Ferredoxin and Flavodoxin signatures. Consensus sequence of each class of oxidoreductase was obtained by a phylogenetic analysis, involving clustering methods based on evolutionary relationship. A synthetic sequence was developed by combining the consensus, which was used as the basis to search for their homologs via BLAST. The exercise yielded 129 multidomain hypothetical proteins containing both 2Fe-2S (Ferredoxin) and FNR (Flavodoxin) domains. In the current study, 40 proteins with N-terminus 2Fe-2S domain and C-terminus FNR domain are characterized, through homology modelling and docking exercises which suggest dioxygenase activity indicating their plausible roles in degradation of aromatic moieties. PMID:23275712

  8. Suggestion and psychoanalytic technique.

    PubMed

    Levy, S T; Inderbitzin, L B

    2000-01-01

    The role of the analyst's suggestive influence on the course and outcome of psychoanalytic treatment is explored, and traditional and newer perspectives on analytic technique are contrasted. The intersubjective critique of the neutral, objective analyst in relation to suggestion is examined. The inevitable presence and need for suggestive factors in analysis, and the relationship of suggestion to transference susceptibility, are emphasized. The manner in which the analysis of suggestive factors is subsumed in transference analysis as part of traditional technique is highlighted. PMID:11059395

  9. Sodium Lidar-observed Strong Inertia-gravity Wave Activities in the Mesopause Region over Fort Collins, Colorado (41 deg N, 105 deg W)

    NASA Technical Reports Server (NTRS)

    Li, Tao; She, C. -Y.; Liu, Han-Li; Leblanc, Thierry; McDermid, I. Stuart

    2007-01-01

    In December 2004, the Colorado State University sodium lidar system at Fort Collins, Colorado (41 deg N, 105 deg W), conducted an approximately 80-hour continuous campaign for the simultaneous observations of mesopause region sodium density, temperature, and zonal and meridional winds. This data set reveals the significant inertia-gravity wave activities with a period of approximately 18 hours, which are strong in both wind components since UT day 338 (second day of the campaign), and weak in temperature and sodium density. The considerable variability of wave activities was observed with both wind amplitudes growing up to approximately 40 m/s at 95-100 km in day 339 and then decreasing dramatically in day 340. We also found that the sodium density wave perturbation is correlated in phase with temperature perturbation below 90 km, and approximately 180 deg out of phase above. Applying the linear wave theory, we estimated the wave horizontal propagation direction, horizontal wavelength, and apparent horizontal phase speed to be approximately 25 deg south of west, approximately 1800 +/- 150 km, and approximately 28 +/- 2 m/s, respectively of wave intrinsic period, intrinsic phase speed, and vertical wavelength were also estimated. While the onset of enhanced inertia-gravity wave amplitude in the night of 338 was observed to be in coincidence with short-period gravity wave breaking via convective instability, the decrease of inertia-gravity wave amplitude after noon of day 339 was also observed to coincide with the development of atmospheric dynamical instability layers with downward phase progression clearly correlated with the 18-hour inertia-gravity wave, suggesting likely breaking of this inertia-gravity wave via dynamical (shear) instability.

  10. Analysis of Immune Response Markers in Jorge Lobo's Disease Lesions Suggests the Occurrence of Mixed T Helper Responses with the Dominance of Regulatory T Cell Activity.

    PubMed

    Azevedo, Michelle de C S; Rosa, Patricia S; Soares, Cleverson T; Fachin, Luciana R V; Baptista, Ida Maria F D; Woods, William J; Garlet, Gustavo P; Trombone, Ana Paula F; Belone, Andrea de F F

    2015-01-01

    Jorge Lobo's disease (JLD) is a chronic infection that affects the skin and subcutaneous tissues. Its etiologic agent is the fungus Lacazia loboi. Lesions are classified as localized, multifocal, or disseminated, depending on their location. Early diagnosis and the surgical removal of lesions are the best therapeutic options currently available for JLD. The few studies that evaluate the immunological response of JLD patients show a predominance of Th2 response, as well as a high frequency of TGF-β and IL-10 positive cells in the lesions; however, the overall immunological status of the lesions in terms of their T cell phenotype has yet to be determined. Therefore, the objective of this study was to evaluate the pattern of Th1, Th2, Th17 and regulatory T cell (Treg) markers mRNA in JLD patients by means of real-time PCR. Biopsies of JLD lesions (N = 102) were classified according to their clinical and histopathological features and then analyzed using real-time PCR in order to determine the expression levels of TGF-β1, FoxP3, CTLA4, IKZF2, IL-10, T-bet, IFN-γ, GATA3, IL-4, IL-5, IL-13, IL-33, RORC, IL-17A, IL-17F, and IL-22 and to compare these levels to those of healthy control skin (N = 12). The results showed an increased expression of FoxP3, CTLA4, TGF-β1, IL-10, T-bet, IL-17F, and IL-17A in lesions, while GATA3 and IL-4 levels were found to be lower in diseased skin than in the control group. When the clinical forms were compared, TGF-β1 was found to be highly expressed in patients with a single localized lesion while IL-5 and IL-17A levels were higher in patients with multiple/disseminated lesions. These results demonstrate the occurrence of mixed T helper responses and suggest the dominance of regulatory T cell activity, which could inhibit Th-dependent protective responses to intracellular fungi such as L. loboi. Therefore, Tregs may play a key role in JLD pathogenesis. PMID:26700881

  11. Analysis of Immune Response Markers in Jorge Lobo's Disease Lesions Suggests the Occurrence of Mixed T Helper Responses with the Dominance of Regulatory T Cell Activity

    PubMed Central

    Azevedo, Michelle de C. S.; Rosa, Patricia S.; Soares, Cleverson T.; Fachin, Luciana R. V.; Baptista, Ida Maria F. D.; Woods, William J.; Garlet, Gustavo P.

    2015-01-01

    Jorge Lobo’s disease (JLD) is a chronic infection that affects the skin and subcutaneous tissues. Its etiologic agent is the fungus Lacazia loboi. Lesions are classified as localized, multifocal, or disseminated, depending on their location. Early diagnosis and the surgical removal of lesions are the best therapeutic options currently available for JLD. The few studies that evaluate the immunological response of JLD patients show a predominance of Th2 response, as well as a high frequency of TGF-β and IL-10 positive cells in the lesions; however, the overall immunological status of the lesions in terms of their T cell phenotype has yet to be determined. Therefore, the objective of this study was to evaluate the pattern of Th1, Th2, Th17 and regulatory T cell (Treg) markers mRNA in JLD patients by means of real-time PCR. Biopsies of JLD lesions (N = 102) were classified according to their clinical and histopathological features and then analyzed using real-time PCR in order to determine the expression levels of TGF-β1, FoxP3, CTLA4, IKZF2, IL-10, T-bet, IFN-γ, GATA3, IL-4, IL-5, IL-13, IL-33, RORC, IL-17A, IL-17F, and IL-22 and to compare these levels to those of healthy control skin (N = 12). The results showed an increased expression of FoxP3, CTLA4, TGF-β1, IL-10, T-bet, IL-17F, and IL-17A in lesions, while GATA3 and IL-4 levels were found to be lower in diseased skin than in the control group. When the clinical forms were compared, TGF-β1 was found to be highly expressed in patients with a single localized lesion while IL-5 and IL-17A levels were higher in patients with multiple/disseminated lesions. These results demonstrate the occurrence of mixed T helper responses and suggest the dominance of regulatory T cell activity, which could inhibit Th-dependent protective responses to intracellular fungi such as L. loboi. Therefore, Tregs may play a key role in JLD pathogenesis. PMID:26700881

  12. [Therapy and suggestion].

    PubMed

    Barrucand, D; Paille, F

    1986-12-01

    Therapy and suggestion are closely related. That is clear for the ancient time: primitive medicine gives a good place to the Word. In plant, animal or mineral remedies, the suggestion is clearly preponderant. Towards the end of the 19th century, the "Ecole de Nancy" sets up a real theory of the suggestion, and Bernheim, its leader, bases hypnosis, then psychotherapy on this concept. Thereafter Coué will bring up the "conscious autosuggestion". Today, despite the progress of scientific medicine, the part of suggestion is still very important in medical therapy (with or without drugs), or in chirurgical therapy; this part is also very important in psychotherapies, whatever has been said in this field. This has to be known and used consciously in the doctor-patient relation, which is always essential in the therapeutic effectiveness. PMID:3555209

  13. Lewis base activation of borane-dimethylsulfide into strongly reducing ion pairs for the transformation of carbon dioxide to methoxyboranes.

    PubMed

    Légaré, Marc-André; Courtemanche, Marc-André; Fontaine, Frédéric-Georges

    2014-10-01

    The hydroboration of carbon dioxide into methoxyboranes by borane-dimethylsulfide using different base catalysts is described. A non-nucleophilic proton sponge is found to be the most active catalyst, with TOF reaching 64 h(-1) at 80 °C, and is acting via the activation of BH3·SMe2 into a boronium-borohydride ion pair. PMID:25164269

  14. SiRNAs conjugated with aromatic compounds induce RISC-mediated antisense strand selection and strong gene-silencing activity

    SciTech Connect

    Kubo, Takanori; Yanagihara, Kazuyoshi; Takei, Yoshifumi; Mihara, Keichiro; Sato, Yuichiro; Seyama, Toshio

    2012-10-05

    Highlights: Black-Right-Pointing-Pointer SiRNAs conjugated with aromatic compounds (Ar-siRNAs) at 5 Prime -sense strand were synthesized. Black-Right-Pointing-Pointer Ar-siRNAs increased resistance against nuclease degradation. Black-Right-Pointing-Pointer Ar-siRNAs were thermodynamically stable compared with the unmodified siRNA. Black-Right-Pointing-Pointer High levels of cellular uptake and cytoplasmic localization were found. Black-Right-Pointing-Pointer Strong gene-silencing efficacy was exhibited in the Ar-siRNAs. -- Abstract: Short interference RNA (siRNA) is a powerful tool for suppressing gene expression in mammalian cells. In this study, we focused on the development of siRNAs conjugated with aromatic compounds in order to improve the potency of RNAi and thus to overcome several problems with siRNAs, such as cellular delivery and nuclease stability. The siRNAs conjugated with phenyl, hydroxyphenyl, naphthyl, and pyrenyl derivatives showed strong resistance to nuclease degradation, and were thermodynamically stable compared with unmodified siRNA. A high level of membrane permeability in HeLa cells was also observed. Moreover, these siRNAs exhibited enhanced RNAi efficacy, which exceeded that of locked nucleic acid (LNA)-modified siRNAs, against exogenous Renilla luciferase in HeLa cells. In particular, abundant cytoplasmic localization and strong gene-silencing efficacy were found in the siRNAs conjugated with phenyl and hydroxyphenyl derivatives. The novel siRNAs conjugated with aromatic compounds are promising candidates for a new generation of modified siRNAs that can solve many of the problems associated with RNAi technology.

  15. Observations of a gradual transition between Ps 6 activity with auroral torches and surgelike pulsations during strong geomagnetic disturbances

    NASA Technical Reports Server (NTRS)

    Steen, A.; Collis, P. N.; Evans, D.; Kremser, G.; Capelle, S.; Rees, D.; Tsurutani, B. T.

    1988-01-01

    This paper describes a long-lasting large-amplitude pulsation event, which occurred on January 10, 1983 in the ionosphere and magnetosphere and was characterized by Steen and Rees (1983). Over the 4-h period (0200-0600 UT), the characteristics of the pulsations in the ionosphere changed from being Ps 6 auroral torches toward substorms and back to Ps 6. At GEO, the corresponding characteristics were a modulation of the high-energy particle intensity and plasma dropouts. Based on the ideas presented by Rostoker and Samson (1984), an interpretation of the event is offered, according to which the pulsations are caused by the Kelvin-Helmholtz instability during an interval of strong magnetospheric convection. On the basis of this explanation, a new interpretation of the substorm time sequence is proposed.

  16. Suggestion in Oral Performance: A Shadow of an Image.

    ERIC Educational Resources Information Center

    Pearse, James A.

    Oral performance of literature can be compared with film viewing, in that both are strongly based on suggestion, which forces the spectator to participate actively in the creation of images. Film is actually a series of still pictures, but persistence of vision produces the idea of motion in the mind. Likewise, literature in performance involves…

  17. Highly activated RNA silencing via strong induction of dicer by one virus can interfere with the replication of an unrelated virus

    PubMed Central

    Chiba, Sotaro; Suzuki, Nobuhiro

    2015-01-01

    Viruses often coinfect single host organisms in nature. Depending on the combination of viruses in such coinfections, the interplay between them may be synergistic, apparently neutral with no effect on each other, or antagonistic. RNA silencing is responsible for many cases of interference or cross-protection between viruses, but such antagonistic interactions are usually restricted to closely related strains of the same viral species. In this study, we present an unprecedented example of RNA silencing-mediated one-way interference between unrelated viruses in a filamentous model fungus, Cryphonectria parasitica. The replication of Rosellinia necatrix victorivirus 1 (RnVV1; Totiviridae) was strongly impaired by coinfection with the prototypic member of the genus Mycoreovirus (MyRV1) or a mutant of the prototype hypovirus (Cryphonectria hypovirus 1, CHV1) lacking the RNA silencing suppressor (CHV1-Δp69). This interference was associated with marked transcriptional induction of key genes in antiviral RNA silencing, dicer-like 2 (dcl2) and argonaute-like 2 (agl2), following MyRV1 or CHV1-Δp69 infection. Interestingly, the inhibition of RnVV1 replication was reproduced when the levels of dcl2 and agl2 transcripts were elevated by transgenic expression of a hairpin construct of an endogenous C. parasitica gene. Disruption of dcl2 completely abolished the interference, whereas that of agl2 did not always lead to its abolishment, suggesting more crucial roles of dcl2 in antiviral defense. Taken altogether, these results demonstrated the susceptible nature of RnVV1 to the antiviral silencing in C. parasitica activated by distinct viruses or transgene-derived double-stranded RNAs and provide insight into the potential for broad-spectrum virus control mediated by RNA silencing. PMID:26283371

  18. A novel cysteine-free venom peptide with strong antimicrobial activity against antibiotics-resistant pathogens from the scorpion Opistophthalmus glabrifrons.

    PubMed

    Bao, Aorigele; Zhong, Jie; Zeng, Xian-Chun; Nie, Yao; Zhang, Lei; Peng, Zhao Feng

    2015-10-01

    Antibiotic-resistant bacteria, such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus, pose serious threat to human health. The outbreak of antibiotic-resistant pathogens in recent years emphasizes once again the urgent need for the development of new antimicrobial agents. Here, we discovered a novel antimicrobial peptide from the scorpion Opistophthalmus glabrifrons, which was referred to as Opisin. Opisin consists of 19 amino acid residues without disulfide bridges. It is a cationic, amphipathic, and α-helical molecule. Protein sequence homology search revealed that Opisin shares 42.1-5.3% sequence identities to the 17/18-mer antimicrobial peptides from scorpions. Antimicrobial assay showed that Opisin is able to potently inhibit the growth of the tested Gram-positive bacteria with the minimal inhibitory concentration (MIC) values of 4.0-10.0 μM; in contrast, it possesses much lower activity against the tested Gram-negative bacteria and a fungus. It is interesting to see that Opisin is able to strongly inhibit the growth of methicillin- and vancomycin-resistant pathogens with the MICs ranging from 2.0 to 4.0 μM and from 4.0 to 6.0 μM, respectively. We found that at a concentration of 5 × MIC, Opisin completely killed all the cultured methicillin-resistant Staphylococcus aureus. These results suggest that Opisin is a promising therapeutic candidate for the treatment of the antibiotic-resistant bacterial infections. PMID:26251012

  19. Highly activated RNA silencing via strong induction of dicer by one virus can interfere with the replication of an unrelated virus.

    PubMed

    Chiba, Sotaro; Suzuki, Nobuhiro

    2015-09-01

    Viruses often coinfect single host organisms in nature. Depending on the combination of viruses in such coinfections, the interplay between them may be synergistic, apparently neutral with no effect on each other, or antagonistic. RNA silencing is responsible for many cases of interference or cross-protection between viruses, but such antagonistic interactions are usually restricted to closely related strains of the same viral species. In this study, we present an unprecedented example of RNA silencing-mediated one-way interference between unrelated viruses in a filamentous model fungus, Cryphonectria parasitica. The replication of Rosellinia necatrix victorivirus 1 (RnVV1; Totiviridae) was strongly impaired by coinfection with the prototypic member of the genus Mycoreovirus (MyRV1) or a mutant of the prototype hypovirus (Cryphonectria hypovirus 1, CHV1) lacking the RNA silencing suppressor (CHV1-Δp69). This interference was associated with marked transcriptional induction of key genes in antiviral RNA silencing, dicer-like 2 (dcl2) and argonaute-like 2 (agl2), following MyRV1 or CHV1-Δp69 infection. Interestingly, the inhibition of RnVV1 replication was reproduced when the levels of dcl2 and agl2 transcripts were elevated by transgenic expression of a hairpin construct of an endogenous C. parasitica gene. Disruption of dcl2 completely abolished the interference, whereas that of agl2 did not always lead to its abolishment, suggesting more crucial roles of dcl2 in antiviral defense. Taken altogether, these results demonstrated the susceptible nature of RnVV1 to the antiviral silencing in C. parasitica activated by distinct viruses or transgene-derived double-stranded RNAs and provide insight into the potential for broad-spectrum virus control mediated by RNA silencing. PMID:26283371

  20. Turkish EFL Academicians' Problems Concerning Translation Activities and Practices, Attitudes towards the Use of Online and Printed Translation Tools, and Suggestions for Quality Translation Practice

    ERIC Educational Resources Information Center

    Zengin, Bugra; Kacar, Isil Gunseli

    2011-01-01

    This mixed method research study aimed to highlight the problems of EFL academicians concerning their current translation practices, their attitudes towards the use of various translation tools, and offer suggestions for more quality translation practices. Seventy-three EFL academicians from three Turkish universities participated in the study.…

  1. Open to Suggestion.

    ERIC Educational Resources Information Center

    Journal of Reading, 1987

    1987-01-01

    Recounts the use of: (1) a game of reading trivia to review a unit in reading, (2) a reading-related art activity that emphasized the importance of following directions, and (3) the assignment of a research paper in a remedial curriculum. (NKA)

  2. A Bacterial Flagellin, Vibrio vulnificus FlaB, Has a Strong Mucosal Adjuvant Activity To Induce Protective Immunity

    PubMed Central

    Lee, Shee Eun; Kim, Soo Young; Jeong, Byung Chul; Kim, Young Ran; Bae, Soo Jang; Ahn, Ouk Seon; Lee, Je-Jung; Song, Ho-Chun; Kim, Jung Mogg; Choy, Hyon E.; Chung, Sun Sik; Kweon, Mi-Na; Rhee, Joon Haeng

    2006-01-01

    Flagellin, the structural component of flagellar filament in various locomotive bacteria, is the ligand for Toll-like receptor 5 (TLR5) of host cells. TLR stimulation by various pathogen-associated molecular patterns leads to activation of innate and subsequent adaptive immune responses. Therefore, TLR ligands are considered attractive adjuvant candidates in vaccine development. In this study, we show the highly potent mucosal adjuvant activity of a Vibrio vulnificus major flagellin (FlaB). Using an intranasal immunization mouse model, we observed that coadministration of the flagellin with tetanus toxoid (TT) induced significantly enhanced TT-specific immunoglobulin A (IgA) responses in both mucosal and systemic compartments and IgG responses in the systemic compartment. The mice immunized with TT plus FlaB were completely protected from systemic challenge with a 200× minimum lethal dose of tetanus toxin. Radiolabeled FlaB administered into the nasal cavity readily reached the cervical lymph nodes and systemic circulation. FlaB bound directly to human TLR5 expressed on cultured epithelial cells and consequently induced NF-κB and interleukin-8 activation. Intranasally administered FlaB colocalized with CD11c as patches in putative dendritic cells and caused an increase in the number of TLR5-expressing cells in cervical lymph nodes. These results indicate that flagellin would serve as an efficacious mucosal adjuvant inducing protective immune responses through TLR5 activation. PMID:16369026

  3. Diminished hERG K+ channel activity facilitates strong human labour contractions but is dysregulated in obese women.

    PubMed

    Parkington, Helena C; Stevenson, Janet; Tonta, Mary A; Paul, Jonathan; Butler, Trent; Maiti, Kaushik; Chan, Eng-Cheng; Sheehan, Penelope M; Brennecke, Shaun P; Coleman, Harold A; Smith, Roger

    2014-01-01

    Human ether-a-go-go-related gene (hERG) potassium channels determine cardiac action potential and contraction duration. Human uterine contractions are underpinned by an action potential that also possesses an initial spike followed by prolonged depolarization. Here we show that hERG channel proteins (α-conducting and β-inhibitory subunits) and hERG currents exist in isolated patch-clamped human myometrial cells. We show that hERG channel activity suppresses contraction amplitude and duration before labour, thereby facilitating quiescence. During established labour, expression of β-inhibitory protein is markedly enhanced, resulting in reduced hERG activity that is associated with an increased duration of uterine action potentials and contractions. Thus, changes in hERG channel activity contribute to electrophysiological mechanisms that produce contractions during labour. We also demonstrate that this system fails in women with elevated BMI, who have enhanced hERG activity as a result of low β-inhibitory protein expression, which likely contributes to the weak contractions and poor labour outcomes observed in many obese women necessitating caesarean delivery. PMID:24937480

  4. Observations of a gradual transition between Ps 6 activity with auroral torches and surgelike pulsations during strong geomagnetic disturbances

    SciTech Connect

    Steen, A.; Collis, P.N.; Evans, D.; Kremser, G.; Capelle, S.; Rees, D.; Tsurutani, B.T.

    1988-08-01

    A long-lasting large-amplitude pulsation event was observed on January 10, 1983, 0200--0600 UT (0411--0745 MLT) in the ionosphere and in the magnetosphere. In the ionosphere the characteristics of the pulsations changed from being Ps 6/auroral torches toward substorms and back to Ps 6 over the 4-hour period. At the geostationary orbit (6.6 Re) the corresponding characteristics were a modulation of the high-energy (greater than or equal to20 keV) particle intensity and plasma dropouts. Following the work by Rostoker and Samson (1984), we propose an interpretation of the event in which the pulsations are caused by the Kelvin-Helmholtz instability, during an interval of strong magnetospheric convection. The gradual transition between Ps 6 pulsations and substorm structures is interpreted as being different results of the Kelvin-Helmholtz instability, caused by different states of the magnetospheric convection. The proposed explanation forms the basis for a discussion on a simplified scheme of the substorm sequence. copyright American Geophysical Union 1988

  5. The Crystal Structure of a Quercetin 2,3-Dioxygenase from Bacillus subtilis Suggests Modulation of Enzyme Activity by a Change in the Metal Ion at the Active Site(s)

    SciTech Connect

    Gopal, B.; Madan, Lalima L.; Betz, Stephen F.; Kossiakoff, Anthony A.

    2010-11-10

    Common structural motifs, such as the cupin domains, are found in enzymes performing different biochemical functions while retaining a similar active site configuration and structural scaffold. The soil bacterium Bacillus subtilis has 20 cupin genes (0.5% of the total genome) with up to 14% of its genes in the form of doublets, thus making it an attractive system for studying the effects of gene duplication. There are four bicupins in B. subtilis encoded by the genes yvrK, yoaN, yxaG, and ywfC. The gene products of yvrK and yoaN function as oxalate decarboxylases with a manganese ion at the active site(s), whereas YwfC is a bacitracin synthetase. Here we present the crystal structure of YxaG, a novel iron-containing quercetin 2,3-dioxygenase with one active site in each cupin domain. Yxag is a dimer, both in solution and in the crystal. The crystal structure shows that the coordination geometry of the Fe ion is different in the two active sites of YxaG. Replacement of the iron at the active site with other metal ions suggests modulation of enzymatic activity in accordance with the Irving-Williams observation on the stability of metal ion complexes. This observation, along with a comparison with the crystal structure of YvrK determined recently, has allowed for a detailed structure-function analysis of the active site, providing clues to the diversification of function in the bicupin family of proteins.

  6. Pattern Triggered Immunity (PTI) in Tobacco: Isolation of Activated Genes Suggests Role of the Phenylpropanoid Pathway in Inhibition of Bacterial Pathogens

    PubMed Central

    Szatmári, Ágnes; Zvara, Ágnes; Móricz, Ágnes M.; Besenyei, Eszter; Szabó, Erika; Ott, Péter G.; Puskás, László G.; Bozsó, Zoltán

    2014-01-01

    Background Pattern Triggered Immunity (PTI) or Basal Resistance (BR) is a potent, symptomless form of plant resistance. Upon inoculation of a plant with non-pathogens or pathogenicity-mutant bacteria, the induced PTI will prevent bacterial proliferation. Developed PTI is also able to protect the plant from disease or HR (Hypersensitive Response) after a challenging infection with pathogenic bacteria. Our aim was to reveal those PTI-related genes of tobacco (Nicotiana tabacum) that could possibly play a role in the protection of the plant from disease. Methodology/Principal Findings Leaves were infiltrated with Pseudomonas syringae pv. syringae hrcC- mutant bacteria to induce PTI, and samples were taken 6 and 48 hours later. Subtraction Suppressive Hybridization (SSH) resulted in 156 PTI-activated genes. A cDNA microarray was generated from the SSH clone library. Analysis of hybridization data showed that in the early (6 hpi) phase of PTI, among others, genes of peroxidases, signalling elements, heat shock proteins and secondary metabolites were upregulated, while at the late phase (48 hpi) the group of proteolysis genes was newly activated. Microarray data were verified by real time RT-PCR analysis. Almost all members of the phenyl-propanoid pathway (PPP) possibly leading to lignin biosynthesis were activated. Specific inhibition of cinnamic-acid-4-hydroxylase (C4H), rate limiting enzyme of the PPP, decreased the strength of PTI - as shown by the HR-inhibition and electrolyte leakage tests. Quantification of cinnamate and p-coumarate by thin-layer chromatography (TLC)-densitometry supported specific changes in the levels of these metabolites upon elicitation of PTI. Conclusions/Significance We believe to provide first report on PTI-related changes in the levels of these PPP metabolites. Results implicated an actual role of the upregulation of the phenylpropanoid pathway in the inhibition of bacterial pathogenic activity during PTI. PMID:25101956

  7. A strongly greenish-blue-emitting Cu4Cl4 cluster with an efficient spin-orbit coupling (SOC): fast phosphorescence versus thermally activated delayed fluorescence.

    PubMed

    Chen, Xu-Lin; Yu, Rongmin; Wu, Xiao-Yuan; Liang, Dong; Jia, Ji-Hui; Lu, Can-Zhong

    2016-05-01

    In this communication, we report a new greenish-blue-emitting Cu(i) complex, Cu4Cl4(NP)2, a with high photoluminescence quantum yield of 90% and a short decay time of 9.9 μs. Due to the strong SOC combined with the small activation energy ΔEST, the emission at room temperature consists of approximately equivalent fast phosphorescence and TADF. PMID:27086679

  8. Reduced mitochondrial malate dehydrogenase activity has a strong effect on photorespiratory metabolism as revealed by 13C labelling.

    PubMed

    Lindén, Pernilla; Keech, Olivier; Stenlund, Hans; Gardeström, Per; Moritz, Thomas

    2016-05-01

    Mitochondrial malate dehydrogenase (mMDH) catalyses the interconversion of malate and oxaloacetate (OAA) in the tricarboxylic acid (TCA) cycle. Its activity is important for redox control of the mitochondrial matrix, through which it may participate in regulation of TCA cycle turnover. In Arabidopsis, there are two isoforms of mMDH. Here, we investigated to which extent the lack of the major isoform, mMDH1 accounting for about 60% of the activity, affected leaf metabolism. In air, rosettes of mmdh1 plants were only slightly smaller than wild type plants although the fresh weight was decreased by about 50%. In low CO2 the difference was much bigger, with mutant plants accumulating only 14% of fresh weight as compared to wild type. To investigate the metabolic background to the differences in growth, we developed a (13)CO2 labelling method, using a custom-built chamber that enabled simultaneous treatment of sets of plants under controlled conditions. The metabolic profiles were analysed by gas- and liquid- chromatography coupled to mass spectrometry to investigate the metabolic adjustments between wild type and mmdh1 The genotypes responded similarly to high CO2 treatment both with respect to metabolite pools and (13)C incorporation during a 2-h treatment. However, under low CO2 several metabolites differed between the two genotypes and, interestingly most of these were closely associated with photorespiration. We found that while the glycine/serine ratio increased, a concomitant altered glutamine/glutamate/α-ketoglutarate relation occurred. Taken together, our results indicate that adequate mMDH activity is essential to shuttle reductants out from the mitochondria to support the photorespiratory flux, and strengthen the idea that photorespiration is tightly intertwined with peripheral metabolic reactions. PMID:26889011

  9. Reduced mitochondrial malate dehydrogenase activity has a strong effect on photorespiratory metabolism as revealed by 13C labelling

    PubMed Central

    Lindén, Pernilla; Keech, Olivier; Stenlund, Hans; Gardeström, Per; Moritz, Thomas

    2016-01-01

    Mitochondrial malate dehydrogenase (mMDH) catalyses the interconversion of malate and oxaloacetate (OAA) in the tricarboxylic acid (TCA) cycle. Its activity is important for redox control of the mitochondrial matrix, through which it may participate in regulation of TCA cycle turnover. In Arabidopsis, there are two isoforms of mMDH. Here, we investigated to which extent the lack of the major isoform, mMDH1 accounting for about 60% of the activity, affected leaf metabolism. In air, rosettes of mmdh1 plants were only slightly smaller than wild type plants although the fresh weight was decreased by about 50%. In low CO2 the difference was much bigger, with mutant plants accumulating only 14% of fresh weight as compared to wild type. To investigate the metabolic background to the differences in growth, we developed a 13CO2 labelling method, using a custom-built chamber that enabled simultaneous treatment of sets of plants under controlled conditions. The metabolic profiles were analysed by gas- and liquid- chromatography coupled to mass spectrometry to investigate the metabolic adjustments between wild type and mmdh1. The genotypes responded similarly to high CO2 treatment both with respect to metabolite pools and 13C incorporation during a 2-h treatment. However, under low CO2 several metabolites differed between the two genotypes and, interestingly most of these were closely associated with photorespiration. We found that while the glycine/serine ratio increased, a concomitant altered glutamine/glutamate/α-ketoglutarate relation occurred. Taken together, our results indicate that adequate mMDH activity is essential to shuttle reductants out from the mitochondria to support the photorespiratory flux, and strengthen the idea that photorespiration is tightly intertwined with peripheral metabolic reactions. PMID:26889011

  10. Monothiocarbamates Strongly Inhibit Carbonic Anhydrases in Vitro and Possess Intraocular Pressure Lowering Activity in an Animal Model of Glaucoma.

    PubMed

    Vullo, Daniela; Durante, Mariaconcetta; Di Leva, Francesco Saverio; Cosconati, Sandro; Masini, Emanuela; Scozzafava, Andrea; Novellino, Ettore; Supuran, Claudiu T; Carta, Fabrizio

    2016-06-23

    A series of monothiocarbamates (MTCs) were prepared from primary/secondary amines and COS as potential carbonic anhydrase (CA, EC 4.2.1.1) inhibitors, using the dithiocarbamates, the xanthates, and the trithiocarbonates as lead compounds. The MTCs effectively inhibited the pharmacologically relevant human (h) hCAs isoforms I, II, IX, and XII in vitro and showed KIs spanning between the low and medium nanomolar range. By means of a computational study, the MTC moiety binding mode on the CAs was explained. Furthermore, a selection of MTCs were evaluated in a normotensive glaucoma rabbit model for their intraocular pressure (IOP) lowering effects and showed interesting activity. PMID:27253845

  11. Strong In Vitro Activities of Two New Rifabutin Analogs against Multidrug-Resistant Mycobacterium tuberculosis ▿ †

    PubMed Central

    García, Ana-Belén; Palacios, Juan J.; Ruiz, María-Jesús; Barluenga, José; Aznar, Fernando; Cabal, María-Paz; García, José María; Díaz, Natalia

    2010-01-01

    Two new rifabutin analogs, RFA-1 and RFA-2, show high in vitro antimycobacterial activities against Mycobacterium tuberculosis. MIC values of RFA-1 and RFA-2 were ≤0.02 μg/ml against rifamycin-susceptible strains and 0.5 μg/ml against a wide selection of multidrug-resistant strains, compared to ≥50 μg/ml for rifampin and 10 μg/ml for rifabutin. Molecular dynamic studies indicate that the compounds may exert tighter binding to mutants of RNA polymerase that have adapted to the rifamycins. PMID:20855731

  12. Analysis of biosurfactants from industrially viable Pseudomonas strain isolated from crude oil suggests how rhamnolipids congeners affect emulsification property and antimicrobial activity

    PubMed Central

    Das, Palashpriya; Yang, Xin-Ping; Ma, Luyan Z.

    2014-01-01

    Rhamnolipid biosurfactants produced mainly by Pseudomonas sp. had been reported to possess a wide range of potential industrial application. These biosurfactants are produced as monorhamnolipid (MRL) and di-rhamnolipid (DRL) congeners. The present study deals with rhamnolipid biosurfactants produced by three bacterial isolates from crude oil. Biosurfactants produced by one of the strains (named as IMP67) was found to be very efficacious based on its critical micelle concentration value and hydrocarbon emulsification property. Strikingly, antimicrobial, and anti-biofilm potential of this biosurfactant were higher than biosurfactants produced by other two strains. Thin layer chromatography analysis and rhamnose quantification showed that the rhamnolipids of IMP67 had more MRL congeners than biosurfactants of the other two strains. Emulsification and antimicrobial actions were affected by manual change of MRL and DRL congener proportions. Increase of MRL proportion enhanced emulsification index and antimicrobial property to Gram negative bacteria. This result indicated that the ratio of MRL and DRL affected the emulsification potentials of rhamnolipids, and suggested that high emulsification potentials might enhance rhamnolipids to penetrate the cell wall of Gram negative bacteria. In line with this finding, rhamnolipids of IMP67 also reduced the MIC of some antibiotics against bacteria, suggesting their synergistic role with the antibiotics. PMID:25566212

  13. Learning Semantic Query Suggestions

    NASA Astrophysics Data System (ADS)

    Meij, Edgar; Bron, Marc; Hollink, Laura; Huurnink, Bouke; de Rijke, Maarten

    An important application of semantic web technology is recognizing human-defined concepts in text. Query transformation is a strategy often used in search engines to derive queries that are able to return more useful search results than the original query and most popular search engines provide facilities that let users complete, specify, or reformulate their queries. We study the problem of semantic query suggestion, a special type of query transformation based on identifying semantic concepts contained in user queries. We use a feature-based approach in conjunction with supervised machine learning, augmenting term-based features with search history-based and concept-specific features. We apply our method to the task of linking queries from real-world query logs (the transaction logs of the Netherlands Institute for Sound and Vision) to the DBpedia knowledge base. We evaluate the utility of different machine learning algorithms, features, and feature types in identifying semantic concepts using a manually developed test bed and show significant improvements over an already high baseline. The resources developed for this paper, i.e., queries, human assessments, and extracted features, are available for download.

  14. Strong metal-support interaction between mononuclear and polynuclear transition metal complexes and oxide supports which dramatically affects catalytic activity

    SciTech Connect

    Hucul, D.A.; Brenner, A.

    1981-03-05

    The interaction of carbonyl complexes with catalyst supports, primarily ..gamma..-alumina, has been studied by temperature-programmed decomposition. In all cases, including cluster complexes and complexes of noble metals, after heating to 600/sup 0/C in flowing He the catalysts are significantly oxidized due to a redox reaction between surface hydroxyl groups and the initially zero-valent metal. Contrary reports are probably incorrect and likely reflect the insensitivity of the experimental techniques used. For all but the most thermally unstable complexes, the oxidation occurs during the latter stages of decarbonylation indicating that there is no significant accumulation of bare zero-valent metal. Hence, decomposition does not in general provide a direct route to supported metals and, contrary to some claims, molecular cluster complexes cannot necessarily be used as precursors to supported metal clusters. Further, knowledge of this redox reaction is critical for understanding patterns of activity and for the development of improved catalysts.

  15. A Highly Reactive Mononuclear Non-Heme Manganese(IV)-Oxo Complex That Can Activate the Strong C-H Bonds of Alkanes

    SciTech Connect

    Wu, Xiujuan; Seo, Mi Sook; Davis, Katherine M; Lee, Yong-Min; Chen, Junying; Cho, Kyung-Bin; Pushkar, Yulia N; Nam, Wonwoo

    2012-03-15

    A mononuclear non-heme manganese(IV)-oxo complex has been synthesized and characterized using various spectroscopic methods. The Mn(IV)-oxo complex shows high reactivity in oxidation reactions, such as C-H bond activation, oxidations of olefins, alcohols, sulfides, and aromatic compounds, and N-dealkylation. In C-H bond activation, the Mn(IV)-oxo complex can activate C-H bonds as strong as those in cyclohexane. It is proposed that C-H bond activation by the non-heme Mn(IV)-oxo complex does not occur via an oxygen-rebound mechanism. The electrophilic character of the non-heme Mn(IV)-oxo complex is demonstrated by a large negative ρ value of ~4.4 in the oxidation of para-substituted thioanisoles.

  16. An Assessment of Magnetic Conditions for Strong Coronal Heating in Solar Active Regions by Comparing Observed Loops with Computed Potential Field Lines

    NASA Technical Reports Server (NTRS)

    Gary, G. A.; Moore, R. L.; Porter, J. G.; Falconer, D. A.

    1999-01-01

    We report further results on the magnetic origins of coronal heating found from registering coronal images with photospheric vector magnetograms. For two complementary active regions, we use computed potential field lines to examine the global non-potentiality of bright extended coronal loops and the three-dimensional structure of the magnetic field at their feet, and assess the role of these magnetic conditions in the strong coronal heating in these loops. The two active regions are complementary, in that one is globally potential and the other is globally nonpotential, while each is predominantly bipolar, and each has an island of included polarity in its trailing polarity domain. We find the following: (1) The brightest main-arch loops of the globally potential active region are brighter than the brightest main- arch loops of the globally strongly nonpotential active region. (2) In each active region, only a few of the mainarch magnetic loops are strongly heated, and these are all rooted near the island. (3) The end of each main-arch bright loop apparently bifurcates above the island, so that it embraces the island and the magnetic null above the island. (4) At any one time, there are other main-arch magnetic loops that embrace the island in the same manner as do the bright loops but that are not selected for strong coronal heating. (5) There is continual microflaring in sheared core fields around the island, but the main-arch bright loops show little response to these microflares. From these observational and modeling results we draw the following conclusions: (1) The heating of the main-arch bright loops arises mainly from conditions at the island end of these loops and not from their global non-potentiality. (2) There is, at most, only a loose coupling between the coronal heating in the bright loops of the main arch and the coronal heating in the sheared core fields at their feet, although in both the heating is driven by conditions/events in and around the

  17. An Assessment of Magnetic Conditions for Strong Coronal Heating in Solar Active Regions by Comparing Observed Loops with Computed Potential Field Lines

    NASA Astrophysics Data System (ADS)

    Falconer, D. A.; Gary, G. A.; Moore, R. L.; Porter, J. G.

    2000-01-01

    We report further results on the magnetic origins of coronal heating found from registering coronal images with photospheric vector magnetograms. For two complementary active regions, we use computed potential field lines to examine the global nonpotentiality of bright extended coronal loops and the three-dimensional structure of the magnetic field at their feet, and assess the role of these magnetic conditions in the strong coronal heating in these loops. The two active regions are complementary, in that one is globally potential and the other is globally nonpotential, while each is predominantly bipolar, and each has an island of included polarity in its trailing polarity domain. We find the following: (1) The brightest main-arch loops of the globally potential active region are brighter than the brightest main-arch loops of the globally strongly nonpotential active region. (2) In each active region, only a few of the mainarch magnetic loops are strongly heated, and these are all rooted near the island. (3) The end of each main-arch bright loop apparently bifurcates above the island, so that it embraces the island and the magnetic null above the island. (4) At any one time, there are other main-arch magnetic loops that embrace the island in the same manner as do the bright loops but that are not selected for strong coronal heating. (5) There is continual microflaring in sheared core fields around the island, but the main-arch bright loops show little response to these microflares. From these observational and modeling results we draw the following conclusions: (1) The heating of the main-arch bright loops arises mainly from conditions at the island end of these loops and not from their global nonpotentiality. (2) There is, at most, only a loose coupling between the coronal heating in the bright loops of the main arch and the coronal heating in the sheared core fields at their feet, although in both the heating is driven by conditions/events in and around the

  18. Processing, localization and binding activity of zonadhesin suggest a function in sperm adhesion to the zona pellucida during exocytosis of the acrosome.

    PubMed Central

    Bi, Ming; Hickox, John R; Winfrey, Virginia P; Olson, Gary E; Hardy, Daniel M

    2003-01-01

    Zonadhesin is a sperm protein that binds in a species-specific manner to the extracellular matrix ZP (zona pellucida) of the mammalian oocyte. The pig zonadhesin precursor is a 267000-Da mosaic protein with a Type I membrane topology and a large extracellular region comprising meprin/A5 antigen/mu receptor tyrosine phosphatase, mucin and five tandem von Willebrand D (VWD) domains. Multiple mature forms of zonadhesin in the sperm head differ in their avidities for the ZP. To determine the potential functions of zonadhesin forms in gamete adhesion, we characterized the processing, activation and localization of protein in pig spermatozoa. The predominant polypeptides of processed zonadhesin were M(r) 300000 (p300), 105000 (p105) and 45000 (p45). p45 and p105, comprised primarily the D1, D2-D3 domains respectively, and were N-glycosylated. p300 was heavily O-glycosylated, and spanned the meprin/A5 antigen/mu receptor tyrosine phosphatase, mucin and D0 domains. Hydrolysis of the precursor polypeptide occurred in the testis, and N-terminal sequencing of p45 and p105 identified Asp806-Pro and Asp1191-Pro in the D1 and D2 domains respectively as bonds cleaved in the protein's functional maturation. Testicular zonadhesin was extractable with non-ionic detergents, and localized to the developing outer acrosomal membrane of round and elongating spermatids. As spermatozoa transited the epididymis, most of the protein became incorporated into an extraction-resistant fraction, and the proportions of active and of multimeric zonadhesins in the cells increased. Zonadhesin localized to the perimeter of the acrosome in intact ejaculated spermatozoa and to the leading edge of acrosomal matrix overlying cells with disrupted acrosomal membranes. We conclude that the zonadhesin precursor is specifically proteolysed, glycosylated and assembled into particulate structures in the distal parts of the acrosome where it may mediate specific adhesion to the ZP during the initial stages of

  19. Symmetry-breaking magnetic fields create a vortex fluid that exhibits a negative viscosity, active wetting, and strong mixing.

    PubMed

    Martin, James E; Solis, Kyle J

    2014-06-14

    There are many areas of science and technology where being able to generate vigorous, noncontact flow would be desirable. We have discovered that three dimensional, time-dependent electric or magnetic fields having key symmetries can be used to generate controlled fluid motion by the continuous injection of energy. Unlike natural convection, this approach does not require a thermal gradient as an energy source, nor does it require gravity, so space applications are feasible. The result is a highly active material we call a vortex fluid. The homogeneous torque density of this fluid enables it to climb walls, induce ballistic droplet motion, and mix vigorously, even in such complex geometries as porous media. This vortex fluid can also exhibit a negative viscosity, which can immeasurably extend the control range of the "smart fluids" used in electro- and magnetorheological devices and can thus significantly increase their performance. Because the applied fields are uniform and modest in strength, vortex fluids of any scale can be created, making applications of any size, from directing microdroplet motion to controlling damping in magnetorheological dampers that protect bridges and buildings from earthquakes, feasible. PMID:24733404

  20. Active galactic nucleus feedback in an isolated elliptical galaxy: The effect of strong radiative feedback in the kinetic mode

    SciTech Connect

    Gan, Zhaoming; Yuan, Feng; Ostriker, Jeremiah P.; Ciotti, Luca; Novak, Gregory S.

    2014-07-10

    Based on two-dimensional high-resolution hydrodynamic numerical simulation, we study the mechanical and radiative feedback effects from the central active galactic nucleus (AGN) on the cosmological evolution of an isolated elliptical galaxy. The inner boundary of the simulation domain is carefully chosen so that the fiducial Bondi radius is resolved and the accretion rate of the black hole is determined self-consistently. It is well known that when the accretion rates are high and low, the central AGNs will be in cold and hot accretion modes, which correspond to the radiative and kinetic feedback modes, respectively. The emitted spectrum from the hot accretion flows is harder than that from the cold accretion flows, which could result in a higher Compton temperature accompanied by a more efficient radiative heating, according to previous theoretical works. Such a difference of the Compton temperature between the two feedback modes, the focus of this study, has been neglected in previous works. Significant differences in the kinetic feedback mode are found as a result of the stronger Compton heating. More importantly, if we constrain models to correctly predict black hole growth and AGN duty cycle after cosmological evolution, we find that the favored model parameters are constrained: mechanical feedback efficiency diminishes with decreasing luminosity (the maximum efficiency being ≅ 10{sup –3.5}), and X-ray Compton temperature increases with decreasing luminosity, although models with fixed mechanical efficiency and Compton temperature can be found that are satisfactory as well. We conclude that radiative feedback in the kinetic mode is much more important than previously thought.

  1. The active stem cell specific expression of sponge Musashi homolog EflMsiA suggests its involvement in maintaining the stem cell state.

    PubMed

    Okamoto, Kazuko; Nakatsukasa, Mikiko; Alié, Alexandre; Masuda, Yoshiki; Agata, Kiyokazu; Funayama, Noriko

    2012-01-01

    A hallmark of stem cells is the ability to sustainably generate stem cells themselves (self-renew) as well as differentiated cells. Although a full understanding of this ability will require clarifying underlying the primordial molecular and cellular mechanisms, how stem cells maintain their stem state and their population in the evolutionarily oldest extant multicellular organisms, sponges, is poorly understood. Here, we report the identification of the first stem cell-specific gene in demosponges, a homolog of Musashi (an evolutionarily conserved RNA binding protein that regulates the stem cell state in various organisms). EflMsiA, a Musashi paralog, is specifically expressed in stem cells (archeocytes) in the freshwater sponge Ephydatia fluviatilis. EflMsiA protein is localized predominantly in the nucleus, with a small fraction in the cytoplasm, in archeocytes. When archeocytes enter M-phase, EflMsiA protein diffuses into the cytoplasm, probably because of the breakdown of the nuclear membrane. In the present study, the existence of two types of M-phase archeocytes [(M)-archeocytes] was revealed by a precise analysis of the expression levels of EflMsiA mRNA and protein. In Type I (M)-archeocytes, presumably archeocytes undergoing self-renewal, the expression levels of EflMsiA mRNA and protein were high. In Type II (M)-archeocytes, presumably archeocytes committed to differentiate (committed archeocytes), the expression levels of EflMsiA mRNA and protein were about 60% and 30% lower than those in Type I (M)-archeocytes. From these results, archeocytes can be molecularly defined for the first time as EflMsiA-mRNA-expressing cells. Furthermore, these findings shed light on the mode of cell division of archeocytes and suggest that archeocytes divide symmetrically for both self-renewal and differentiation. PMID:22464976

  2. Strong immunostimulatory activity of AT-oligodeoxynucleotide requires a six-base loop with a self-stabilized 5'-C...G-3' stem structure.

    PubMed

    Shimosato, Takeshi; Kimura, Toshiro; Tohno, Masanori; Iliev, Iliyan Dimitrov; Katoh, Shinichiro; Ito, Yoshiyuki; Kawai, Yasushi; Sasaki, Takashi; Saito, Tadao; Kitazawa, Haruki

    2006-03-01

    Lactobacillus gasseri OLL2716 has recently been discovered as a probiotic that suppresses the growth of Helicobacter pylori and reduces gastric mucosal inflammation in humans. This has resulted in the development of a new type of probiotic yoghurt 'LG21' in Japan. In our previous study, we found an immunostimulatory AT5ACL oligodeoxynucleotide (AT-ODN) containing a unique core sequence (5'-ATTTTTAC-3') in L. gasseri JCM1131(T). Interestingly, although the AT-ODN does not contain any CpG sequences, it exerts mitogenic activity in B cells and augments Th-1-type immune responses via Toll-like receptor 9. These findings prompted us to identify strong immunostimulatory non-CpG AT-ODNs that contain the 5'-ATTTTTAC-3' motif in the genomic sequence of L. gasseri OLL2716. We identified 280 kinds of AT-ODNs in the L. gasseri OLL2716 genome. Mitogenicity and NF-kappaB gene reporting assays showed that 13 of the 280 AT-ODNs were strongly immunostimulatory when in the TLR9 transfectant. Of these, AT-ODNs LGAT-145 and LGAT-243 were the most potent. With respect to the induction of Th-1-type cytokines, LGAT-243 had the greatest activity and was more potent than the swine prototype, ODN D25. We further found that a six-base secondary loop structure containing a self-stabilized 5'-C...G-3' stem sequence is important for potent immunostimulatory activity. These results show for the first time that AT-ODNs with a specific loop and stem structure are important factors for immunostimulatory activity. Finally, we found that novel strong immunostimulatory non-CpG AT-ODNs exist in the genome of probiotic lactic acid bacteria. PMID:16469059

  3. Autophagy Defects Suggested by Low Levels of Autophagy Activator MAP1S and High Levels of Autophagy Inhibitor LRPPRC Predict Poor Prognosis of Prostate Cancer Patients

    PubMed Central

    Jiang, Xianhan; Zhong, Weide; Huang, Hai; He, Huichan; Jiang, Funeng; Chen, Yanru; Yue, Fei; Zou, Jing; Li, Xun; He, Yongzhong; You, Pan; Yang, Weiqiang; Lai, Yiming; Wang, Fen; Liu, Leyuan

    2016-01-01

    MAP1S (originally named C19ORF5) is a widely distributed homolog of neuronal-specific MAP1A and MAP1B, and bridges autophagic components with microtubules and mitochondria to affect autophagosomal biogenesis and degradation. Mitochondrion-associated protein LRPPRC functions as an inhibitor for autophagy initiation to protect mitochondria from autophagy degradation. MAP1S and LRPPRC interact with each other and may collaboratively regulate autophagy although the underlying mechanism is yet unknown. Previously, we have reported that LRPPRC levels serve as a prognosis marker of patients with prostate adenocarcinomas (PCA), and that patients with high LRPPRC levels survive a shorter period after surgery than those with low levels of LRPPRC. MAP1S levels are elevated in diethylnitrosamine-induced hepatocelular carcinomas in wildtype mice and the exposed MAP1S-deficient mice develop more malignant hepatocellular carcinomas. We performed immunochemical analysis to evaluate the co-relationship among the levels of MAP1S, LRPPRC, P62, and γ-H2AX. Samples were collected from wildtype and prostate-specific PTEN-deficient mice, 111 patients with PCA who had been followed up for 10 years and 38 patients with benign prostate hyperplasia enrolled in hospitals in Guangzhou, China. The levels of MAP1S were generally elevated so the MAP1S-mediated autophagy was activated in PCA developed in either PTEN-deficient mice or patients than their respective benign tumors. The MAP1S levels among patients with PCA vary dramatically, and patients with low MAP1S levels survive a shorter period than those with high MAP1S levels. Levels of MAP1S in collaboration with levels of LRPPRC can serve as markers for prognosis of prostate cancer patients. PMID:25043940

  4. LUR models for particulate matters in the Taipei metropolis with high densities of roads and strong activities of industry, commerce and construction.

    PubMed

    Lee, Jui-Huna; Wu, Chang-Fu; Hoek, Gerard; de Hoogh, Kees; Beelen, Rob; Brunekreef, Bert; Chan, Chang-Chuan

    2015-05-01

    Traffic intensity, length of road, and proximity to roads are the most common traffic indicators in the land use regression (LUR) models for particulate matter in ESCAPE study areas in Europe. This study explored what local variables can improve the performance of LUR models in an Asian metropolis with high densities of roads and strong activities of industry, commerce and construction. By following the ESCAPE procedure, we derived LUR models of PM₂.₅, PM₂.₅ absorbance, PM₁₀, and PMcoarse (PM₂.₅-₁₀) in Taipei. The overall annual average concentrations of PM₂.₅, PM₁₀, and PMcoarse were 26.0 ± 5.6, 48.6 ± 5.9, and 23.3 ± 3.1 μg/m(3), respectively, and the absorption coefficient of PM₂.₅ was 2.0 ± 0.4 × 10(-5)m(-1). Our LUR models yielded R(2) values of 95%, 96%, 87%, and 65% for PM₂.₅, PM₂.₅ absorbance, PM₁₀, and PMcoarse, respectively. PM₂.₅ levels were increased by local traffic variables, industrial, construction, and residential land-use variables and decreased by rivers; while PM₂.₅ absorbance levels were increased by local traffic variables, industrial, and commercial land-use variables in the models. PMcoarse levels were increased by elevated highways. Road area explained more variance than road length by increasing the incremental value of 27% and 6% adjusted R(2) for PM₂.₅ and PM₁₀ models, respectively. In the PM₂.₅ absorbance model, road area and transportation facility explain 29% more variance than road length. In the PMcoarse model, industrial and new local variables instead of road length improved the incremental value of adjusted R(2) from 39% to 60%. We concluded that road area can better explain the spatial distribution of PM₂.₅ and PM₂.₅ absorbance concentrations than road length. By incorporating road area and other new local variables, the performance of each PM LUR model was improved. The results suggest that road area is a better indicator of traffic intensity rather

  5. Strong effect of copper(II) coordination on antiproliferative activity of thiosemicarbazone-piperazine and thiosemicarbazone-morpholine hybrids.

    PubMed

    Bacher, Felix; Dömötör, Orsolya; Chugunova, Anastasia; Nagy, Nóra V; Filipović, Lana; Radulović, Siniša; Enyedy, Éva A; Arion, Vladimir B

    2015-05-21

    In this study, 2-formylpyridine thiosemicarbazones and three different heterocyclic pharmacophores were combined to prepare thiosemicarbazone–piperazine mPip-FTSC (HL1) and mPip-dm-FTSC (HL2), thiosemicarbazone–morpholine Morph-FTSC (HL3) and Morph-dm-FTSC (HL4), thiosemicarbazone–methylpyrrole-2-carboxylate hybrids mPyrr-FTSC (HL5) and mPyrr-dm-FTSC (HL6) as well as their copper(II) complexes [CuCl(mPipH-FTSC-H)]Cl (1 + H)Cl, [CuCl(mPipH-dm-FTSC-H)]Cl (2 + H)Cl, [CuCl(Morph-FTSC-H)] (3), [CuCl(Morph-dm-FTSC-H)] (4), [CuCl(mPyrr-FTSC-H)(H2O)] (5) and [CuCl(mPyrr-dm-FTSC-H)(H2O)] (6). The substances were characterized by elemental analysis, one- and two-dimensional NMR spectroscopy (HL1–HL6), ESI mass spectrometry, IR and UV–vis spectroscopy and single crystal X-ray diffraction (1–5). All compounds were prepared in an effort to generate potential antitumor agents with an improved therapeutic index. In addition, the effect of structural alterations with organic hybrids on aqueous solubility and copper(II) coordination ability was investigated. Complexation of ligands HL2 and HL4 with copper(II) was studied in aqueous solution by pH-potentiometry, UV–vis spectrophotometry and EPR spectroscopy. Proton dissociation processes of HL2 and HL4 were also characterized in detail and microscopic constants for the Z/E isomers were determined. While the hybrids HL5, HL6 and their copper(II) complexes 5 and 6 proved to be insoluble in aqueous solution, precluding antiproliferative activity studies, the thiosemicarbazone–piperazine and thiosemicarbazone–morpholine hybrids HL1–HL4, as well as copper(II) complexes 1–4 were soluble in water enabling cytotoxicity assays. Interestingly, the metal-free hybrids showed very low or even a lack of cytotoxicity (IC50 values > 300 μM) in two human cancer cell lines HeLa (cervical carcinoma) and A549 (alveolar basal adenocarcinoma), whereas their copper(II) complexes were cytotoxic showing IC50 values from 25.5 to 65.1

  6. Recombinant targeted toxin based on HER2-specific DARPin possesses a strong selective cytotoxic effect in vitro and a potent antitumor activity in vivo.

    PubMed

    Sokolova, Evgeniya; Proshkina, Galina; Kutova, Olga; Shilova, Olga; Ryabova, Anastasiya; Schulga, Alexey; Stremovskiy, Oleg; Zdobnova, Tatiana; Balalaeva, Irina; Deyev, Sergey

    2016-07-10

    DARPins fused with other proteins are promising non-immunoglobulin scaffolds for specific binding to target cells. In this study HER2-specific DARPin (DARPin_9-29) was used as a tumor-targeting moiety for the delivery of a cytotoxic agent - the fragment of Pseudomonas aeruginosa exotoxin A. It was determined that DARPin-PE40 possesses a considerable cytotoxic activity and induces apoptosis in HER2-positive cells. Cytotoxic effect of DARPin-PE40 strongly correlates with the HER2 expression level. The effect of intravenous administration of DARPin-PE40 was tested in the xenograft model of breast cancer. It was shown that treatment of animals with DARPin-PE40 caused strong and prolonged suppression of xenograft tumor growth. PMID:27178808

  7. A suggested emergency medicine boot camp curriculum for medical students based on the mapping of Core Entrustable Professional Activities to Emergency Medicine Level 1 milestones

    PubMed Central

    Lamba, Sangeeta; Wilson, Bryan; Natal, Brenda; Nagurka, Roxanne; Anana, Michael; Sule, Harsh

    2016-01-01

    Background An increasing number of students rank Emergency Medicine (EM) as a top specialty choice, requiring medical schools to provide adequate exposure to EM. The Core Entrustable Professional Activities (EPAs) for Entering Residency by the Association of American Medical Colleges combined with the Milestone Project for EM residency training has attempted to standardize the undergraduate and graduate medical education goals. However, it remains unclear as to how the EPAs correlate to the milestones, and who owns the process of ensuring that an entering EM resident has competency at a certain minimum level. Recent trends establishing specialty-specific boot camps prepare students for residency and address the variability of skills of students coming from different medical schools. Objective Our project’s goal was therefore to perform a needs assessment to inform the design of an EM boot camp curriculum. Toward this goal, we 1) mapped the core EPAs for graduating medical students to the EM residency Level 1 milestones in order to identify the possible gaps/needs and 2) conducted a pilot procedure workshop that was designed to address some of the identified gaps/needs in procedural skills. Methods In order to inform the curriculum of an EM boot camp, we used a systematic approach to 1) identify gaps between the EPAs and EM milestones (Level 1) and 2) determine what essential and supplemental competencies/skills an incoming EM resident should ideally possess. We then piloted a 1-day, three-station advanced ABCs procedure workshop based on the identified needs. A pre-workshop test and survey assessed knowledge, preparedness, confidence, and perceived competence. A post-workshop survey evaluated the program, and a posttest combined with psychomotor skills test using three simulation cases assessed students’ skills. Results Students (n=9) reported increased confidence in the following procedures: intubation (1.5–2.1), thoracostomy (1.1–1.9), and central venous

  8. A strong comeback

    SciTech Connect

    Marier, D.

    1992-03-01

    This article presents the results of a financial rankings survey which show a strong economic activity in the independent energy industry. The topics of the article include advisor turnover, overseas banks, and the increase in public offerings. The article identifies the top project finance investors for new projects and restructurings and rankings for lenders.

  9. Magnetic susceptibility of strongly interacting matter across the deconfinement transition.

    PubMed

    Bonati, Claudio; D'Elia, Massimo; Mariti, Marco; Negro, Francesco; Sanfilippo, Francesco

    2013-11-01

    We propose a method to determine the total magnetic susceptibility of strongly interacting matter by lattice QCD simulations and present numerical results for the theory with two light flavors, which suggest a weak magnetic activity in the confined phase and the emergence of strong paramagnetism in the deconfined, quark-gluon plasma phase. PMID:24237508

  10. Temporal Dynamics of the Cecal Gut Microbiota of Juvenile Arctic Ground Squirrels: a Strong Litter Effect across the First Active Season

    PubMed Central

    Stevenson, Timothy J.; Buck, C. Loren

    2014-01-01

    Arctic ground squirrels (Urocitellus parryii) are active for a scant 3 to 5 months of the year. During the active season, adult squirrels compete for mates, reproduce, and fatten in preparation for hibernation, while juvenile squirrels, weaned in early July, must grow and acquire sufficient fat to survive their first hibernation season. During hibernation, the gut microbial community is altered in diversity, abundance, and activity. To date, no studies have examined the gut microbiota of hibernators across the truncated active season. We characterized trends in diversity (454 pyrosequencing), density (flow cytometry), viability (flow cytometry), and metabolism (short-chain fatty acid analysis) of the gut microbial community of juvenile arctic ground squirrels across their first active season at weaning and at 4, 6, 8, and 10 weeks postweaning. At 8 weeks postweaning, the mean bacterial density was significantly higher than that at weaning, and the mean percentage of live bacteria was significantly higher than that at either weaning or 4 weeks postweaning. No significant differences in microbial diversity, total short-chain fatty acid concentrations, or molar proportions of individual short-chain fatty acids were observed among sample periods. The level of variability in gut microbial diversity among squirrels was high across the active season but was most similar among littermates, except at weaning, indicating strong maternal or genetic influences across development. Our results indicate that genetic or maternal influences exert profound effects on the gut microbial community of juvenile arctic ground squirrels. We did not find a correlation between host adiposity and gut microbial diversity during prehibernation fattening, likely due to a high level of variability among squirrels. PMID:24795380

  11. Temporal dynamics of the cecal gut microbiota of juvenile arctic ground squirrels: a strong litter effect across the first active season.

    PubMed

    Stevenson, Timothy J; Buck, C Loren; Duddleston, Khrystyne N

    2014-07-01

    Arctic ground squirrels (Urocitellus parryii) are active for a scant 3 to 5 months of the year. During the active season, adult squirrels compete for mates, reproduce, and fatten in preparation for hibernation, while juvenile squirrels, weaned in early July, must grow and acquire sufficient fat to survive their first hibernation season. During hibernation, the gut microbial community is altered in diversity, abundance, and activity. To date, no studies have examined the gut microbiota of hibernators across the truncated active season. We characterized trends in diversity (454 pyrosequencing), density (flow cytometry), viability (flow cytometry), and metabolism (short-chain fatty acid analysis) of the gut microbial community of juvenile arctic ground squirrels across their first active season at weaning and at 4, 6, 8, and 10 weeks postweaning. At 8 weeks postweaning, the mean bacterial density was significantly higher than that at weaning, and the mean percentage of live bacteria was significantly higher than that at either weaning or 4 weeks postweaning. No significant differences in microbial diversity, total short-chain fatty acid concentrations, or molar proportions of individual short-chain fatty acids were observed among sample periods. The level of variability in gut microbial diversity among squirrels was high across the active season but was most similar among littermates, except at weaning, indicating strong maternal or genetic influences across development. Our results indicate that genetic or maternal influences exert profound effects on the gut microbial community of juvenile arctic ground squirrels. We did not find a correlation between host adiposity and gut microbial diversity during prehibernation fattening, likely due to a high level of variability among squirrels. PMID:24795380

  12. Strong correlation in acene sheets from the active-space variational two-electron reduced density matrix method: effects of symmetry and size.

    PubMed

    Pelzer, Kenley; Greenman, Loren; Gidofalvi, Gergely; Mazziotti, David A

    2011-06-01

    Polyaromatic hydrocarbons (PAHs) are a class of organic molecules with importance in several branches of science, including medicine, combustion chemistry, and materials science. The delocalized π-orbital systems in PAHs require highly accurate electronic structure methods to capture strong electron correlation. Treating correlation in PAHs has been challenging because (i) traditional wave function methods for strong correlation have not been applicable since they scale exponentially in the number of strongly correlated orbitals, and (ii) alternative methods such as the density-matrix renormalization group and variational two-electron reduced density matrix (2-RDM) methods have not been applied beyond linear acene chains. In this paper we extend the earlier results from active-space variational 2-RDM theory [Gidofalvi, G.; Mazziotti, D. A. J. Chem. Phys. 2008, 129, 134108] to the more general two-dimensional arrangement of rings--acene sheets--to study the relationship between geometry and electron correlation in PAHs. The acene-sheet calculations, if performed with conventional wave function methods, would require wave function expansions with as many as 1.5 × 10(17) configuration state functions. To measure electron correlation, we employ several RDM-based metrics: (i) natural-orbital occupation numbers, (ii) the 1-RDM von Neumann entropy, (iii) the correlation energy per carbon atom, and (iv) the squared Frobenius norm of the cumulant 2-RDM. The results confirm a trend of increasing polyradical character with increasing molecular size previously observed in linear PAHs and reveal a corresponding trend in two-dimensional (arch-shaped) PAHs. Furthermore, in PAHs of similar size they show significant variations in correlation with geometry. PAHs with the strictly linear geometry (chains) exhibit more electron correlation than PAHs with nonlinear geometries (sheets). PMID:21563790

  13. The Blockade of NF-κB Activation by a Specific Inhibitory Peptide Has a Strong Neuroprotective Role in a Sprague-Dawley Rat Kernicterus Model.

    PubMed

    Li, Mengwen; Song, Sijie; Li, Shengjun; Feng, Jie; Hua, Ziyu

    2015-12-11

    Kernicterus, the permanent nerve damage occurring as a result of bilirubin precipitation, still occurs worldwide and may lead to death or permanent neurological impairments. However, the underlying mechanisms remain unclear, and effective therapeutic strategies are lacking. The present study aims to investigate the activation of NF-κB and to identify the effect of NF-κB inhibition on the newborn rat kernicterus model. The NF-κB essential modifier-binding domain peptide (NBD), coupled with the HIV trans-activator of transcription peptide (TAT) was used to inhibit NF-κB. NF-κB was significantly activated in the cerebrum at 1 and 3 h (p < 0.05) after the model was established, as measured by EMSA. NF-κB activation was inhibited by intraperitoneal administration of TAT-NBD. The general conditions of the TAT-NBD-treated rats were improved; meanwhile, these rats performed much better on the neurological evaluation, the rotarod test, and the Morris water maze test (p < 0.05) than the vehicle-treated rats at 28 days. Furthermore, the morphology of the nerve cells was better preserved in the TAT-NBD group, and these cells displayed less neurodegeneration and astrocytosis. Simultaneously, apoptosis in the brain was attenuated, and the levels of the TNF-α and IL-1β proteins were decreased (p < 0.01). These results suggested that NF-κB was activated, and inhibition of NF-κB activation by TAT-NBD not only attenuated the acute neurotoxicity, apoptosis, and inflammation, but also improved the long term neurobehavioral impairments in the kernicterus model rats in vivo. Thus, inhibiting NF-κB activation might be a potential therapeutic approach for kernicterus. PMID:26499797

  14. A Staphylococcus aureus ypfP mutant with strongly reduced lipoteichoic acid (LTA) content: LTA governs bacterial surface properties and autolysin activity

    PubMed Central

    Fedtke, Iris; Mader, Diana; Kohler, Thomas; Moll, Hermann; Nicholson, Graeme; Biswas, Raja; Henseler, Katja; Götz, Friedrich; Zähringer, Ulrich; Peschel, Andreas

    2007-01-01

    Many Gram-positive bacteria produce lipoteichoic acid (LTA) polymers whose physiological roles have remained a matter of debate because of the lack of LTA-deficient mutants. The ypfP gene responsible for biosynthesis of a glycolipid found in LTA was deleted in Staphylococcus aureus SA113, causing 87% reduction of the LTA content. Mass spectrometry and nuclear magnetic resonance spectroscopy revealed that the mutant LTA contained a diacylglycerol anchor instead of the glycolipid, whereas the remaining part was similar to the wild-type polymer except that it was shorter. The LTA mutant strain revealed no major changes in patterns of cell wall proteins or autolytic enzymes compared with the parental strain indicating that LTA may be less important in S. aureus protein attachment than previously thought. However, the autolytic activity of the mutant was strongly reduced demonstrating a role of LTA in controlling autolysin activity. Moreover, the hydrophobicity of the LTA mutant was altered and its ability to form biofilms on plastic was completely abrogated indicating a profound impact of LTA on physicochemical properties of bacterial surfaces. We propose to consider LTA and its biosynthetic enzymes as targets for new antibiofilm strategies. PMID:17640274

  15. An actinomycete isolate from solitary wasp mud nest having strong antibacterial activity and kills the Candida cells due to the shrinkage and the cytosolic loss

    PubMed Central

    Kumar, Vijay; Naik, Bindu; Gusain, Omprakash; Bisht, Gajraj S.

    2014-01-01

    An actinomycetes strain designated as MN 2(6) was isolated from the solitary wasp mud nest. The isolate was identified using polyphasic taxonomy. It produced the extensive branched brown substrate and white aerial hyphae that changed into grayish black. The aerial mycelia produced the spiral spore chains with rugose spore surface. The growth was observed between temperature range of 27–37°C, pH 8–10 and below salt concentration of 6% (w/v). The comparative analysis of 16S rRNA gene sequence and phylogenetic relationship showed that strain MN 2(6) lies in clade with Streptomyces hygroscopicus subsp. hygroscopicus NRRL 2387T, Streptomyces sporocinereus NBRC 100766T and Streptomyces demainii NRRL B-1478T with which it shares a 16S rRNA gene sequence similarity of 99.3%. The strain MN 2(6) can be differentiated from type strains based on phenotypic characteristics. The strain MN 2(6) showed most promising activity against Gram-positive, Gram-negative bacteria, acid-fast bacilli and Candida species suggesting broad-spectrum characteristics of the active metabolite. Evaluation of anti-candidal activity of the metabolite of strain MN 2(6) by scanning electron microscopy (SEM) revealed changed external morphology of yeast. It kills the Candida cells due to the shrinkage and the cytosolic loss. However, further studies are required to elucidate the structure of the active metabolite produced by the isolate MN 2(6). PMID:25191320

  16. A strong loss-of-function mutation in RAN1 results in constitutive activation of the ethylene response pathway as well as a rosette-lethal phenotype

    NASA Technical Reports Server (NTRS)

    Woeste, K. E.; Kieber, J. J.; Evans, M. L. (Principal Investigator)

    2000-01-01

    A recessive mutation was identified that constitutively activated the ethylene response pathway in Arabidopsis and resulted in a rosette-lethal phenotype. Positional cloning of the gene corresponding to this mutation revealed that it was allelic to responsive to antagonist1 (ran1), a mutation that causes seedlings to respond in a positive manner to what is normally a competitive inhibitor of ethylene binding. In contrast to the previously identified ran1-1 and ran1-2 alleles that are morphologically indistinguishable from wild-type plants, this ran1-3 allele results in a rosette-lethal phenotype. The predicted protein encoded by the RAN1 gene is similar to the Wilson and Menkes disease proteins and yeast Ccc2 protein, which are integral membrane cation-transporting P-type ATPases involved in copper trafficking. Genetic epistasis analysis indicated that RAN1 acts upstream of mutations in the ethylene receptor gene family. However, the rosette-lethal phenotype of ran1-3 was not suppressed by ethylene-insensitive mutants, suggesting that this mutation also affects a non-ethylene-dependent pathway regulating cell expansion. The phenotype of ran1-3 mutants is similar to loss-of-function ethylene receptor mutants, suggesting that RAN1 may be required to form functional ethylene receptors. Furthermore, these results suggest that copper is required not only for ethylene binding but also for the signaling function of the ethylene receptors.

  17. A Porphyromonas gingivalis Mutant Defective in a Putative Glycosyltransferase Exhibits Defective Biosynthesis of the Polysaccharide Portions of Lipopolysaccharide, Decreased Gingipain Activities, Strong Autoaggregation, and Increased Biofilm Formation▿ †

    PubMed Central

    Yamaguchi, Mikiyo; Sato, Keiko; Yukitake, Hideharu; Noiri, Yuichiro; Ebisu, Shigeyuki; Nakayama, Koji

    2010-01-01

    The Gram-negative anaerobic bacterium Porphyromonas gingivalis is a major pathogen in periodontal disease, one of the biofilm-caused infectious diseases. The bacterium possesses potential virulence factors, including fimbriae, proteinases, hemagglutinin, lipopolysaccharide (LPS), and outer membrane vesicles, and some of these factors are associated with biofilm formation; however, the precise mechanism of biofilm formation is still unknown. Colonial pigmentation of the bacterium on blood agar plates is related to its virulence. In this study, we isolated a nonpigmented mutant that had an insertion mutation within the new gene PGN_1251 (gtfB) by screening a transposon insertion library. The gene shares homology with genes encoding glycosyltransferase 1 of several bacteria. The gtfB mutant was defective in biosynthesis of both LPSs containing O side chain polysaccharide (O-LPS) and anionic polysaccharide (A-LPS). The defect in the gene resulted in a complete loss of surface-associated gingipain proteinases, strong autoaggregation, and a marked increase in biofilm formation, suggesting that polysaccharide portions of LPSs influence attachment of gingipain proteinases to the cell surface, autoaggregation, and biofilm formation of P. gingivalis. PMID:20624909

  18. Novel derivatives of 1,3,4-oxadiazoles are potent mitostatic agents featuring strong microtubule depolymerizing activity in the sea urchin embryo and cell culture assays.

    PubMed

    Kiselyov, Alex S; Semenova, Marina N; Chernyshova, Natalya B; Leitao, Andrei; Samet, Alexandr V; Kislyi, Konstantine A; Raihstat, Mikhail M; Oprea, Tudor; Lemcke, Heiko; Lantow, Margaréta; Weiss, Dieter G; Ikizalp, Nazli N; Kuznetsov, Sergei A; Semenov, Victor V

    2010-05-01

    A series of novel 1,3,4-oxadiazole derivatives based on structural and electronic overlap with combretastatins have been designed and synthesized. Initially, we tested all new compounds in vivo using the phenotypic sea urchin embryo assay to yield a number of agents with anti-proliferative, anti-mitotic, and microtubule destabilizing activities. The experimental data led to identification of 1,3,4-oxadiazole derivatives with isothiazole (5-8) and phenyl (9-12) pharmacophores featuring activity profiles comparable to that of combretastatins, podophyllotoxin and nocodazole. Cytotoxic effects of the two lead molecules, namely 6 and 12, were further confirmed and evaluated by conventional assays with the A549 human cancer cell line including cell proliferation, cell cycle arrest at the G2/M phase, cellular microtubule distribution, and finally in vitro microtubule assembly with purified tubulin. The modeling results using 3D similarity (ROCS) and docking (FRED) correlated well with the observed activity of the molecules. Docking data suggested that the most potent molecules are likely to target the colchicine binding site. PMID:20110137

  19. Menopause Hastens Aging, Studies Suggest

    MedlinePlus

    ... gov/news/fullstory_160079.html Menopause Hastens Aging, Studies Suggest Researchers found it boosted cellular aging by ... it, can speed aging in women, two new studies suggest. "For decades, scientists have disagreed over whether ...

  20. Expression and/or activity of the SVCT2 ascorbate transporter may be decreased in many aggressive cancers, suggesting potential utility for sodium bicarbonate and dehydroascorbic acid in cancer therapy.

    PubMed

    McCarty, Mark F

    2013-10-01

    Hypoxia-inducible factor-1 (HIF-1) is a heterodimer transcription factor whose elevated activity in many cancers helps them to survive under hypoxic conditions and enhances their capacity to grow invasively, establish metastases, and survive chemo- or radiotherapy. Optimal intracellular levels of ascorbate suppress the level and transcriptional activity of HIF-1under normoxic or mildly hypoxic conditions by supporting the activity of proly and asparagyl hydroxylases that target HIF-1alpha. High intracellular ascorbate can also work in various ways to down-regulate activation of NF-kappaB which, like HIF-1 is constitutively active in many cancers and promotes aggressive behavior - in part by promoting transcription of HIF-1alpha. Yet recent evidence suggests that, even in the context of adequate ascorbate nutrition, the intracellular ascorbate content of many aggressive cancers may be supoptimal for effective HIF-1 control. This likely reflects low expression or activity of the SVCT2 ascorbate transporter. The expression of SVCT2 in cancers has so far received little study; but the extracellular acidity characteristic of many tumors would be expected to reduce the activity of this transporter, which has a mildly alkaline pH optimum. Unfortunately, since SVCT2 has a high affinity for ascorbate, and its activity is nearly saturated at normal healthy serum levels of this vitamin, increased oral administration of ascorbate would be unlikely to have much impact on the intracellular ascorbate content of tumors. However, cancers in which HIF-1 is active express high levels of glucose transporters such as GLUT-1, and these transporters can promote influx of dehydroascorbic acid (DHA) via facilitated diffusion; once inside the cell, DHA is rapidly reduced to ascorbate, which effectively is "trapped" within the cell. Hence, episodic intravenous infusions of modest doses of DHA may have potential for optimizing the intracellular ascorbate content of cancers, potentially

  1. Quenched Assembly of NIR-Active Gold Nanoclusters Capped with Strongly Bound Ligands by Tuning Particle Charge via pH and Salinity

    PubMed Central

    2015-01-01

    Gold nanospheres coated with a binary monolayer of bound citrate and cysteine ligands were assembled into nanoclusters, in which the size and near-infrared (NIR) extinction were tuned by varying the pH and concentration of added NaCl. During full evaporation of an aqueous dispersion of 4.5 ± 1.8 nm Au primary particles, the nanoclusters were formed and quenched by the triblock copolymer polylactic acid (PLA)(1K)-b-poly(ethylene glycol) (PEG)(10K)-b-PLA(1K), which also provided steric stabilization. The short-ranged depletion and van der Waals attractive forces were balanced against longer ranged electrostatic repulsion to tune the nanocluster diameter and NIR extinction. Upon lowering the pH from 7 to 5 at a given salinity, the magnitude of the charge on the primary particles decreased, such that the weaker electrostatic repulsion increased the hydrodynamic diameter and, consequently, NIR extinction of the clusters. At a given pH, as the concentration of NaCl was increased, the NIR extinction decreased monotonically. Furthermore, the greater screening of the charges on the nanoclusters weakened the interactions with PLA(1K)-b-PEG(10K)-b-PLA(1K) and thus lowered the amount of adsorbed polymer on the nanocluster surface. The generalization of the concept of self-assembly of small NIR-active nanoclusters to include a strongly bound thiol and the manipulation of the morphologies and NIR extinction by variation of pH and salinity not only is of fundamental interest but also is important for optical biomedical imaging and therapy. PMID:25061496

  2. Combined treatment with cotylenin A and phenethyl isothiocyanate induces strong antitumor activity mainly through the induction of ferroptotic cell death in human pancreatic cancer cells.

    PubMed

    Kasukabe, Takashi; Honma, Yoshio; Okabe-Kado, Junko; Higuchi, Yusuke; Kato, Nobuo; Kumakura, Shunichi

    2016-08-01

    The treatment of pancreatic cancer, one of the most aggressive gastrointestinal tract malignancies, with current chemotherapeutic drugs has had limited success due to its chemoresistance and poor prognosis. Therefore, the development of new drugs or effective combination therapies is urgently needed. Cotylenin A (CN-A) (a plant growth regulator) is a potent inducer of differentiation in myeloid leukemia cells and exhibits potent antitumor activities in several cancer cell lines. In the present study, we demonstrated that CN-A and phenethyl isothiocyanate (PEITC), an inducer of reactive oxygen species (ROS) and a dietary anticarcinogenic compound, synergistically inhibited the proliferation of MIAPaCa-2, PANC-1 and gemcitabine-resistant PANC-1 cells. A combined treatment with CN-A and PEITC also effectively inhibited the anchorage-independent growth of these cancer cells. The combined treatment with CN-A and PEITC strongly induced cell death within 1 day at concentrations at which CN-A or PEITC alone did not affect cell viability. A combined treatment with synthetic CN-A derivatives (ISIR-005 and ISIR-042) or fusicoccin J (CN-A-related natural product) and PEITC did not have synergistic effects on cell death. The combined treatment with CN-A and PEITC synergistically induced the generation of ROS. Antioxidants (N-acetylcysteine and trolox), ferroptosis inhibitors (ferrostatin-1 and liproxstatin), and the lysosomal iron chelator deferoxamine canceled the synergistic cell death. Apoptosis inhibitors (Z-VAD-FMK and Q-VD-OPH) and the necrosis inhibitor necrostatin-1s did not inhibit synergistic cell death. Autophagy inhibitors (3-metyladenine and chloroquine) partially prevented cell death. These results show that synergistic cell death induced by the combined treatment with CN-A and PEITC is mainly due to the induction of ferroptosis. Therefore, the combination of CN-A and PEITC has potential as a novel therapeutic strategy against pancreatic cancer. PMID:27375275

  3. Quenched Assembly of NIR-Active Gold Nanoclusters Capped with Strongly Bound Ligands by Tuning Particle Charge via pH and Salinity.

    PubMed

    Stover, Robert J; Murthy, Avinash K; Nie, Golay D; Gourisankar, Sai; Dear, Barton J; Truskett, Thomas M; Sokolov, Konstantin V; Johnston, Keith P

    2014-07-01

    Gold nanospheres coated with a binary monolayer of bound citrate and cysteine ligands were assembled into nanoclusters, in which the size and near-infrared (NIR) extinction were tuned by varying the pH and concentration of added NaCl. During full evaporation of an aqueous dispersion of 4.5 ± 1.8 nm Au primary particles, the nanoclusters were formed and quenched by the triblock copolymer polylactic acid (PLA)(1K)-b-poly(ethylene glycol) (PEG)(10K)-b-PLA(1K), which also provided steric stabilization. The short-ranged depletion and van der Waals attractive forces were balanced against longer ranged electrostatic repulsion to tune the nanocluster diameter and NIR extinction. Upon lowering the pH from 7 to 5 at a given salinity, the magnitude of the charge on the primary particles decreased, such that the weaker electrostatic repulsion increased the hydrodynamic diameter and, consequently, NIR extinction of the clusters. At a given pH, as the concentration of NaCl was increased, the NIR extinction decreased monotonically. Furthermore, the greater screening of the charges on the nanoclusters weakened the interactions with PLA(1K)-b-PEG(10K)-b-PLA(1K) and thus lowered the amount of adsorbed polymer on the nanocluster surface. The generalization of the concept of self-assembly of small NIR-active nanoclusters to include a strongly bound thiol and the manipulation of the morphologies and NIR extinction by variation of pH and salinity not only is of fundamental interest but also is important for optical biomedical imaging and therapy. PMID:25061496

  4. Personalized and not general suggestion produces false autobiographical memories and suggestion-consistent behavior.

    PubMed

    Scoboria, Alan; Mazzoni, Giuliana; Jarry, Josée L; Bernstein, Daniel M

    2012-01-01

    Suggesting false childhood events produces false autobiographical beliefs, memories and suggestion-consistent behavior. The mechanisms by which suggestion affects behavior are not understood, and whether false beliefs and memories are necessary for suggestions to impact behavior remains unexplored. We examined the relative effects of providing a personalized suggestion (suggesting that an event occurred to the person in the past), and/or a general suggestion (suggesting that an event happened to others in the past). Participants (N=122) received a personalized suggestion, a general suggestion, both or neither, about childhood illness due to spoiled peach yogurt. The personalized suggestion resulted in false beliefs, false memories, and suggestion-consistent behavioral intentions immediately after the suggestion. One week or one month later participants completed a taste test that involved eating varieties of crackers and yogurts. The personalized suggestion led to reduced consumption of only peach yogurt, and those who reported a false memory showed the most eating suppression. This effect on behavior was equally strong after one week and one month, showing a long lived influence of the personalized suggestion. The general suggestion showed no effects. Suggestions that convey personal information about a past event produce false autobiographical memories, which in turn impact behavior. PMID:22112639

  5. Foreshocks of strong earthquakes

    NASA Astrophysics Data System (ADS)

    Guglielmi, A. V.; Sobisevich, L. E.; Sobisevich, A. L.; Lavrov, I. P.

    2014-07-01

    The specific enhancement of ultra-low-frequency (ULF) electromagnetic oscillations a few hours prior to the strong earthquakes, which was previously mentioned in the literature, motivated us to search for the distinctive features of the mechanical (foreshock) activity of the Earth's crust in the epicentral zones of the future earthquakes. Activation of the foreshocks three hours before the main shock is revealed, which is roughly similar to the enhancement of the specific electromagnetic ULF emission. It is hypothesized that the round-the-world seismic echo signals from the earthquakes, which form the peak of energy release 2 h 50 min before the main events, act as the triggers of the main shocks due to the cumulative action of the surface waves converging to the epicenter. It is established that the frequency of the fluctuations in the foreshock activity decreases at the final stages of the preparation of the main shocks, which probably testifies to the so-called mode softening at the approach of the failure point according to the catastrophe theory.

  6. Uridine adenosine tetraphosphate (Up{sub 4}A) is a strong inductor of smooth muscle cell migration via activation of the P2Y{sub 2} receptor and cross-communication to the PDGF receptor

    SciTech Connect

    Wiedon, Annette; Toelle, Markus; Bastine, Joschika; Schuchardt, Mirjam; Huang, Tao; Jankowski, Vera; Jankowski, Joachim; Zidek, Walter; Giet, Markus van der

    2012-01-20

    Highlights: Black-Right-Pointing-Pointer Up{sub 4}A induces VSMC migration. Black-Right-Pointing-Pointer VSMC migration towards Up{sub 4}A involves P2Y{sub 2} activation. Black-Right-Pointing-Pointer Up{sub 4}A-induced VSMC migration is OPN-dependent. Black-Right-Pointing-Pointer Activation of ERK1/2 pathway is necessary for VSMC migration towards Up{sub 4}A. Black-Right-Pointing-Pointer Up{sub 4}A-directed VSMC migration cross-communicates with the PDGFR. -- Abstract: The recently discovered dinucleotide uridine adenosine tetraphosphate (Up{sub 4}A) was found in human plasma and characterized as endothelium-derived vasoconstrictive factor (EDCF). A further study revealed a positive correlation between Up{sub 4}A and vascular smooth muscle cell (VSMC) proliferation. Due to the dominant role of migration in the formation of atherosclerotic lesions our aim was to investigate the migration stimulating potential of Up{sub 4}A. Indeed, we found a strong chemoattractant effect of Up{sub 4}A on VSMC by using a modified Boyden chamber. This migration dramatically depends on osteopontin secretion (OPN) revealed by the reduction of the migration signal down to 23% during simultaneous incubation with an OPN-blocking antibody. Due to inhibitory patterns using specific and unspecific purinoreceptor inhibitors, Up{sub 4}A mediates it's migratory signal mainly via the P2Y{sub 2}. The signaling behind the receptor was investigated with luminex technique and revealed an activation of the extracellular signal-regulated kinases 1 and 2 (ERK1/2) pathway. By use of the specific PDGF receptor (PDGFR) inhibitor AG1296 and siRNA technique against PDGFR-{beta} we found a strongly reduced migration signal after Up{sub 4}A stimulation in the PDGFR-{beta} knockdown cells compared to control cells. In this study, we present substantiate data that Up{sub 4}A exhibits migration stimulating potential probably involving the signaling cascade of MEK1 and ERK1/2 as well as the matrix protein OPN. We

  7. A novel human BTB-kelch protein KLHL31, strongly expressed in muscle and heart, inhibits transcriptional activities of TRE and SRE.

    PubMed

    Yu, Weishi; Li, Yongqing; Zhou, Xijin; Deng, Yun; Wang, Zequn; Yuan, Wuzhou; Li, Dali; Zhu, Chuanbing; Zhao, Xueying; Mo, Xiaoyang; Huang, Wen; Luo, Na; Yan, Yan; Ocorr, Karen; Bodmer, Rolf; Wang, Yuequn; Wu, Xiushan

    2008-11-30

    The Bric-a-brac, Tramtrack, Broad-complex (BTB) domain is a protein-protein interaction domain that is found in many zinc finger transcription factors. BTB containing proteins play important roles in a variety of cellular functions including regulation of transcription, regulation of the cytoskeleton, protein ubiquitination, angiogenesis, and apoptosis. Here, we report the cloning and characterization of a novel human gene, KLHL31, from a human embryonic heart cDNA library. The cDNA of KLHL31 is 5743 bp long, encoding a protein product of 634 amino acids containing a BTB domain. The protein is highly conserved across different species. Western blot analysis indicates that the KLHL31 protein is abundantly expressed in both embryonic skeletal and heart tissue. In COS-7 cells, KLHL31 proteins are localized to both the nucleus and the cytoplasm. In primary cultures of nascent mouse cardiomyocytes, the majority of endogenous KLHL31 proteins are localized to the cytoplasm. KLHL31 acts as a transcription repressor when fused to GAL4 DNA-binding domain and deletion analysis indicates that the BTB domain is the main region responsible for this repression. Overexpression of KLHL31 in COS-7 cells inhibits the transcriptional activities of both the TPA-response element (TRE) and serum response element (SRE). KLHL31 also significantly reduces JNK activation leading to decreased phosphorylation and protein levels of the JNK target c-Jun in both COS-7 and Hela cells. These results suggest that KLHL31 protein may act as a new transcriptional repressor in MAPK/JNK signaling pathway to regulate cellular functions. PMID:18719355

  8. ZmGns, a maize class I β-1,3-glucanase, is induced by biotic stresses and possesses strong antimicrobial activity.

    PubMed

    Xie, Yu-Rong; Raruang, Yenjit; Chen, Zhi-Yuan; Brown, Robert L; Cleveland, Thomas E

    2015-03-01

    Plant β-1,3-glucanases are members of the pathogenesis-related protein 2 (PR-2) family, which is one of the 17 PR protein families and plays important roles in biotic and abiotic stress responses. One of the differentially expressed proteins (spot 842) identified in a recent proteomic comparison between five pairs of closely related maize (Zea mays L.) lines differing in aflatoxin resistance was further investigated in the present study. Here, the corresponding cDNA was cloned from maize and designated as ZmGns. ZmGns encodes a protein of 338 amino acids containing a potential signal peptide. The expression of ZmGns was detectible in all tissues studied with the highest level in silks. ZmGns was significantly induced by biotic stresses including three bacteria and the fungus Aspergillus flavus. ZmGns was also induced by most abiotic stresses tested and growth hormones including salicylic acid. In vivo, ZmGns showed a significant inhibitory activity against the bacterial pathogen Pseudomonas syringae pv. tomato DC3000 and fungal pathogen Botrytis cinerea when it overexpressed in Arabidopsis. Its high level of expression in the silk tissue and its induced expression by phytohormone treatment, as well as by bacterial and fungal infections, suggest it plays a complex role in maize growth, development, and defense. PMID:25251325

  9. The Active Tamoxifen Metabolite Endoxifen (4OHNDtam) Strongly Down-Regulates Cytokeratin 6 (CK6) in MCF-7 Breast Cancer Cells

    PubMed Central

    Dankel, Simon; Fenne, Ingvild S.; Skartveit, Linn; Drangevåg, Andreas; Bozickovic, Olivera; Flågeng, Marianne Hauglid; Søiland, Håvard; Mellgren, Gunnar; Lien, Ernst A.

    2015-01-01

    Introduction Tamoxifen is an anti-estrogen drug used in treatment of Estrogen Receptor (ER) positive breast cancer. Effects and side effects of tamoxifen is the sum of tamoxifen and all its metabolites. 4-Hydroxytamoxifen (4OHtam) and 4-hydroxy-N-demethyltamoxifen (4OHNDtam, endoxifen) both have ER affinity exceeding that of the parent drug tamoxifen. 4OHNDtam is considered the main active metabolite of tamoxifen. Ndesmethyltamoxifen (NDtam) is the major tamoxifen metabolite. It has low affinity to the ER and is not believed to influence tumor growth. However, NDtam might mediate adverse effects of tamoxifen treatment. In this study we investigated the gene regulatory effects of the three metabolites of tamoxifen in MCF-7 breast cancer cells. Material and Methods Using concentrations that mimic the clinical situation we examined effects of 4OHtam, 4OHNDtam and NDtam on global gene expression in 17β-estradiol (E2) treated MCF-7 cells. Transcriptomic responses were assessed by correspondence analysis, differential expression, gene ontology analysis and quantitative real time PCR (Q-rt-PCR). E2 deprivation and knockdown of Steroid Receptor Coactivator-3 (SRC-3)/Amplified in Breast Cancer 1 (AIB1) mRNA in MCF-7 cells were performed to further characterize specific effects on gene expression. Results 4OHNDtam and 4OHtam caused major changes in gene expression compared to treatment with E2 alone, with a stronger effect of 4OHNDtam. NDtam had nearly no effect on the global gene expression profile. Treatment of MCF-7 cells with 4OHNDtam led to a strong down-regulation of the CytoKeratin 6 isoforms (KRT6A, KRT6B and KRT6C). The CytoKeratin 6 mRNAs were also down-regulated in MCF-7 cells after E2 deprivation and after SRC-3/AIB1 knockdown. Conclusion Using concentrations that mimic the clinical situation we report global gene expression changes that were most pronounced with 4OHNDtam and minimal with NDtam. Genes encoding CytoKeratin 6, were highly down-regulated by 4

  10. Chemically synthesized dicarba H2 relaxin analogues retain strong RXFP1 receptor activity but show an unexpected loss of in vitro serum stability.

    PubMed

    Hossain, Mohammed Akhter; Haugaard-Kedström, Linda M; Rosengren, K Johan; Bathgate, Ross A D; Wade, John D

    2015-11-28

    Peptides and proteins are now acknowledged as viable alternatives to small molecules as potential therapeutic agents. A primary limitation to their more widespread acceptance is their generally short in vivo half-lives due to serum enzyme susceptibility and rapid renal clearance. Numerous chemical approaches to address this concern have been undertaken in recent years. The replacement of disulfide bonds with non-reducible elements has been demonstrated to be one effective means by eliminating the deleterious effect of serum reductases. In particular, substitution with dicarba bonds via ring closure metathesis has been increasingly applied to many bioactive cystine-rich peptides. We used this approach for the replacement of the A-chain intramolecular disulfide bond of human relaxin 2 (H2 relaxin), an insulin-like peptide that has important regulatory roles in cardiovascular and connective tissue homeostasis that has led to successful Phase IIIa clinical trials for the treatment of acute heart failure. Use of efficient solid phase synthesis of the two peptide chains was followed by on-resin ring closure metathesis and formation of the dicarba bond within the A-chain and then by off-resin combination with the B-chain via sequential directed inter-chain disulfide bond formation. After purification and comprehensive chemical characterization, the two isomeric synthetic H2 relaxin analogues were shown to retain near-equipotent RXFP1 receptor binding and activation propensity. Unexpectedly, the in vitro serum stability of the analogues was greatly reduced compared with the native peptide. Circular dichroism spectroscopy studies showed subtle differences in the secondary structures between dicarba analogues and H2 relaxin suggesting that, although the overall fold is retained, it may be destabilized which could account for rapid degradation of dicarba analogues in serum. Caution is therefore recommended when using ring closure metathesis as a general approach to enhance

  11. 10 Suggestions for Enhancing Lecturing

    ERIC Educational Resources Information Center

    Heitzmann, Ray

    2010-01-01

    Criticism of the lecture method remains a staple of discussion and writing in academia--and most of the time it's deserved! Those interested in improving this aspect of their teaching might wish to consider some or all of the following suggestions for enhancing lectures. These include: (1) Lectures must start with a "grabber"; (2) Lectures must be…

  12. TAL effectors and activation of predicted host targets distinguish Asian from African strains of the rice pathogen Xanthomonas oryzae pv. oryzicola while strict conservation suggests universal importance of five TAL effectors

    PubMed Central

    Wilkins, Katherine E.; Booher, Nicholas J.; Wang, Li; Bogdanove, Adam J.

    2015-01-01

    Xanthomonas oryzae pv. oryzicola (Xoc) causes the increasingly important disease bacterial leaf streak of rice (BLS) in part by type III delivery of repeat-rich transcription activator-like (TAL) effectors to upregulate host susceptibility genes. By pathogen whole genome, single molecule, real-time sequencing and host RNA sequencing, we compared TAL effector content and rice transcriptional responses across 10 geographically diverse Xoc strains. TAL effector content is surprisingly conserved overall, yet distinguishes Asian from African isolates. Five TAL effectors are conserved across all strains. In a prior laboratory assay in rice cv. Nipponbare, only two contributed to virulence in strain BLS256 but the strict conservation indicates all five may be important, in different rice genotypes or in the field. Concatenated and aligned, TAL effector content across strains largely reflects relationships based on housekeeping genes, suggesting predominantly vertical transmission. Rice transcriptional responses did not reflect these relationships, and on average, only 28% of genes upregulated and 22% of genes downregulated by a strain are up- and down- regulated (respectively) by all strains. However, when only known TAL effector targets were considered, the relationships resembled those of the TAL effectors. Toward identifying new targets, we used the TAL effector-DNA recognition code to predict effector binding elements in promoters of genes upregulated by each strain, but found that for every strain, all upregulated genes had at least one. Filtering with a classifier we developed previously decreases the number of predicted binding elements across the genome, suggesting that it may reduce false positives among upregulated genes. Applying this filter and eliminating genes for which upregulation did not strictly correlate with presence of the corresponding TAL effector, we generated testable numbers of candidate targets for four of the five strictly conserved TAL

  13. Patterns of Gene Conversion in Duplicated Yeast Histones Suggest Strong Selection on a Coadapted Macromolecular Complex

    PubMed Central

    Scienski, Kathy; Fay, Justin C.; Conant, Gavin C.

    2015-01-01

    We find evidence for interlocus gene conversion in five duplicated histone genes from six yeast species. The sequences of these duplicated genes, surviving from the ancient genome duplication, show phylogenetic patterns inconsistent with the well-resolved orthology relationships inferred from a likelihood model of gene loss after the genome duplication. Instead, these paralogous genes are more closely related to each other than any is to its nearest ortholog. In addition to simulations supporting gene conversion, we also present evidence for elevated rates of radical amino acid substitutions along the branches implicated in the conversion events. As these patterns are similar to those seen in ribosomal proteins that have undergone gene conversion, we speculate that in cases where duplicated genes code for proteins that are a part of tightly interacting complexes, selection may favor the fixation of gene conversion events in order to maintain high protein identities between duplicated copies. PMID:26560339

  14. Suggestions for Popularizing Civil Aviation

    NASA Technical Reports Server (NTRS)

    1926-01-01

    The public generally is taking very little interest in the progress of Civil Aviation, and the time has come to educate the public in aeronautics and to make them realize the far-reaching importance of air transport. Briefly, the whole problem resolves itself into discovering and applying means for bringing some of the many aspects and effects of civil aviation into the everyday lives of the public. The report suggests three principal groups of methods: (1) Bring aviation into daily contact with the public. (2) Bring the public into daily contact with aviation. (3) General publicity.

  15. Alkylator-Induced and Patient-Derived Xenograft Mouse Models of Therapy-Related Myeloid Neoplasms Model Clinical Disease and Suggest the Presence of Multiple Cell Subpopulations with Leukemia Stem Cell Activity

    PubMed Central

    Johnson, Carl; Gratzinger, Dita; Majeti, Ravindra

    2016-01-01

    Acute myeloid leukemia (AML) is a heterogeneous group of aggressive bone marrow cancers arising from transformed hematopoietic stem and progenitor cells (HSPC). Therapy-related AML and MDS (t-AML/MDS) comprise a subset of AML cases occurring after exposure to alkylating chemotherapy and/or radiation and are associated with a very poor prognosis. Less is known about the pathogenesis and disease-initiating/leukemia stem cell (LSC) subpopulations of t-AML/MDS compared to their de novo counterparts. Here, we report the development of mouse models of t-AML/MDS. First, we modeled alkylator-induced t-AML/MDS by exposing wild type adult mice to N-ethyl-N-nitrosurea (ENU), resulting in several models of AML and MDS that have clinical and pathologic characteristics consistent with human t-AML/MDS including cytopenia, myelodysplasia, and shortened overall survival. These models were limited by their inability to transplant clinically aggressive disease. Second, we established three patient-derived xenograft models of human t-AML. These models led to rapidly fatal disease in recipient immunodeficient xenografted mice. LSC activity was identified in multiple HSPC subpopulations suggesting there is no canonical LSC immunophenotype in human t-AML. Overall, we report several new t-AML/MDS mouse models that could potentially be used to further define disease pathogenesis and test novel therapeutics. PMID:27428079

  16. Alkylator-Induced and Patient-Derived Xenograft Mouse Models of Therapy-Related Myeloid Neoplasms Model Clinical Disease and Suggest the Presence of Multiple Cell Subpopulations with Leukemia Stem Cell Activity.

    PubMed

    Jonas, Brian A; Johnson, Carl; Gratzinger, Dita; Majeti, Ravindra

    2016-01-01

    Acute myeloid leukemia (AML) is a heterogeneous group of aggressive bone marrow cancers arising from transformed hematopoietic stem and progenitor cells (HSPC). Therapy-related AML and MDS (t-AML/MDS) comprise a subset of AML cases occurring after exposure to alkylating chemotherapy and/or radiation and are associated with a very poor prognosis. Less is known about the pathogenesis and disease-initiating/leukemia stem cell (LSC) subpopulations of t-AML/MDS compared to their de novo counterparts. Here, we report the development of mouse models of t-AML/MDS. First, we modeled alkylator-induced t-AML/MDS by exposing wild type adult mice to N-ethyl-N-nitrosurea (ENU), resulting in several models of AML and MDS that have clinical and pathologic characteristics consistent with human t-AML/MDS including cytopenia, myelodysplasia, and shortened overall survival. These models were limited by their inability to transplant clinically aggressive disease. Second, we established three patient-derived xenograft models of human t-AML. These models led to rapidly fatal disease in recipient immunodeficient xenografted mice. LSC activity was identified in multiple HSPC subpopulations suggesting there is no canonical LSC immunophenotype in human t-AML. Overall, we report several new t-AML/MDS mouse models that could potentially be used to further define disease pathogenesis and test novel therapeutics. PMID:27428079

  17. Revision of Suggested State Regulations.

    PubMed

    Winston, John P

    2016-02-01

    It is the mission of the Conference of Radiation Control Program Directors (CRCPD) to promote radiological health in all aspects and phases of implementation and to create a seamless and coherent regulatory structure across the United States. CRCPD currently has 25 committees charged with the development of Suggested State Regulations (SSRs) for everything from transportation and waste disposal to tanning and medical therapy. The SR-F Committee is responsible for the suggested regulations of the equipment and processes used in medical diagnostic and interventional x-ray procedures. Several states are required by law to adopt the SSR verbatim, making it vital that they are kept current. The current revision of SR-F brought together representatives from the state radiation control programs, the Food and Drug Administration, the American Association of Physicists in Medicine, American College of Radiology, and industry. Through the course of two meetings and multiple conference calls, the Committee finalized an updated draft. The CRCPD process for the development of SSR is well established and includes internal and external peer review, review by the state Director Members, approval by the Board of Directors, and concurrence from relevant federal agencies. Once final, an SSR allows a state radiation control program to proceed through the state's own regulatory process with a vetted set of regulations, making this difficult process more efficient and effective. PMID:26717174

  18. What Is Strong Correlation?

    ERIC Educational Resources Information Center

    Kozak, Marcin

    2009-01-01

    Interpretation of correlation is often based on rules of thumb in which some boundary values are given to help decide whether correlation is non-important, weak, strong or very strong. This article shows that such rules of thumb may do more harm than good, and instead of supporting interpretation of correlation--which is their aim--they teach a…

  19. Strong Navajo Marriages

    ERIC Educational Resources Information Center

    Skogrand, Linda; Mueller, Mary Lou; Arrington, Rachel; LeBlanc, Heidi; Spotted Elk, Davina; Dayzie, Irene; Rosenbrand, Reva

    2008-01-01

    The purpose of this qualitative study, conducted in two Navajo Nation chapters, was to learn what makes Navajo marriages strong because no research has been done on this topic. Twenty-one Navajo couples (42 individuals) who felt they had strong marriages volunteered to participate in the study. Couples identified the following marital strengths:…

  20. Physics Courses--Some Suggested Case Studies

    ERIC Educational Resources Information Center

    Swetman, T. P.

    1972-01-01

    To communicate the relevance and excitement of science activity to students, the use of more imaginative, and even openly speculative, case studies in physics courses is suggested. Some useful examples are Magnetic Monopoles, Constants, Black Holes, Antimatter, Zero Mass Particles, Tachyons, and the Bootstrap Hypothesis. (DF)

  1. Youth Physical Fitness. Suggestions for School Programs.

    ERIC Educational Resources Information Center

    President's Council on Physical Fitness and Sports, Washington, DC.

    This book, divided into three main parts--basic, advanced, and comprehensive programs--suggests (a) basic physical education programs designed to assist classroom teachers inexperienced in physical education to develop activities that will make a contribution to the physical fitness of the children in their charge and (b) advanced activities…

  2. Discovery of anti-cancer activity for benzo[1,2,4]triazin-7-ones: Very strong correlation to pleurotin and thioredoxin reductase inhibition.

    PubMed

    Sweeney, Martin; Coyle, Robert; Kavanagh, Paul; Berezin, Andrey A; Lo Re, Daniele; Zissimou, Georgia A; Koutentis, Panayiotis A; Carty, Michael P; Aldabbagh, Fawaz

    2016-08-15

    The thioredoxin (Trx)-thioredoxin reductase (TrxR) system plays a key role in maintaining the cellular redox balance with Trx being over-expressed in a number of cancers. Inhibition of TrxR is an important strategy for anti-cancer drug discovery. The natural product pleurotin is a well-known irreversible inhibitor of TrxR. The cytotoxicity data for benzo[1,2,4]triazin-7-ones showed very strong correlation (Pearson correlation coefficients ∼0.8) to pleurotin using National Cancer Institute COMPARE analysis. A new 3-CF3 substituted benzo[1,2,4]triazin-7-one gave submicromolar inhibition of TrxR, although the parent compound 1,3-diphenylbenzo[1,2,4]triazin-7-one was more cytotoxic against cancer cell lines. Benzo[1,2,4]triazin-7-ones exhibited different types of reversible inhibition of TrxR, and cyclic voltammetry showed characteristic quasi-reversible redox processes. Cell viability studies indicated strong dependence of cytotoxicity on substitution at the 6-position of the 1,3-diphenylbenzo[1,2,4]triazin-7-one ring. PMID:27290691

  3. Strong morphological effect of Mn3O4 nanocrystallites on the catalytic activity of Mn3O4 and Au/Mn3O4 in benzene combustion.

    PubMed

    Fei, Zhao-Yang; Sun, Bo; Zhao, Liang; Ji, Wei-Jie; Au, Chak-Tong

    2013-05-10

    Gold nanoparticles (3-4 nm) were deposited on Mn3O4 nanocrystallites with three distinct morphologies (cubic, hexagonal, and octahedral). The resulting structures were characterized, and their activities for benzene combustion were evaluated. The dominant exposed facets for the three kinds of Mn3O4 polyhedrons show the activity order: (103)≈(200)>(101). A similar activity order was derived for the interfaces between the Au and the Mn3O4 facet: Au/(200)≈Au/(103)>Au/(101). The metal-support interactions between the Au nanoclusters and specific facets of the Mn3O4 polyhedrons lead to a unique interfacial synergism in which the electronic modification of the Au nanoparticles and the morphology of the Mn3O4 substrate have a joint effect that is responsible for a significant enhancement in the catalytic activity of the Au/Mn3O4 system. PMID:23526641

  4. Building false memories without suggestions.

    PubMed

    Foster, Jeffrey L; Garry, Maryanne

    2012-01-01

    People can come to remember doing things they have never done. The question we asked in this study is whether people can systematically come to remember performing actions they never really did, in the absence of any suggestion from the experimenter. People built LEGO vehicles, performing some steps but not others. For half the people, all the pieces needed to assemble each vehicle were laid out in order in front of them while they did the building; for the other half, the pieces were hidden from view. The next day, everyone returned for a surprise recognition test. People falsely and confidently remembered having carried out steps they did not; those who saw all the pieces while they built each vehicle were more likely to correctly remember performing steps they did perform but equally likely to falsely remember performing steps they did not. We explain our results using the source monitoring framework: People used the relationships between actions to internally generate the missing, related actions, later mistaking that information for genuine experience. PMID:22774684

  5. Polyalkoxybenzenes from plants. 5. Parsley seed extract in synthesis of azapodophyllotoxins featuring strong tubulin destabilizing activity in the sea urchin embryo and cell culture assays.

    PubMed

    Semenova, Marina N; Kiselyov, Alex S; Tsyganov, Dmitry V; Konyushkin, Leonid D; Firgang, Sergei I; Semenov, Roman V; Malyshev, Oleg R; Raihstat, Mikhail M; Fuchs, Fabian; Stielow, Anne; Lantow, Margareta; Philchenkov, Alex A; Zavelevich, Michael P; Zefirov, Nikolay S; Kuznetsov, Sergei A; Semenov, Victor V

    2011-10-27

    A series of 4-azapodophyllotoxin derivatives with modified rings B and E have been synthesized using allylpolyalkoxybenzenes from parsley seed oil. The targeted molecules were evaluated in vivo in a phenotypic sea urchin embryo assay for antimitotic and tubulin destabilizing activity. The most active compounds identified by the in vivo sea urchin embryo assay featured myristicin-derived ring E. These molecules were determined to be more potent than podophyllotoxin. Cytotoxic effects of selected molecules were further confirmed and evaluated by conventional assays with A549 and Jurkat human leukemic T-cell lines including cell growth inhibition, cell cycle arrest, cellular microtubule disruption, and induction of apoptosis. The ring B modification yielded 6-OMe substituted molecule as the most active compound. Finally, in Jurkat cells, compound induced caspase-dependent apoptosis mediated by the apical caspases-2 and -9 and not caspase-8, implying the involvement of the intrinsic caspase-9-dependent apoptotic pathway. PMID:21916509

  6. Pretreatment HIV-1 drug resistance is strongly associated with virologic failure in HIV-infected patients receiving partly active antiretroviral regimens

    PubMed Central

    Parikh, Urvi M; Mellors, John W

    2016-01-01

    The scale-up of antiretroviral therapy in sub-Saharan Africa has significantly reduced mortality from AIDS. Hamers et al. explores the impact of pretreatment HIV-1 drug resistance on virologic failure, immunologic response, and acquisition of drug resistance after 1 year of first-line antiretroviral therapy by longitudinally evaluating 2579 participants with pretreatment drug resistance results from the PharmAccess African Studies to Evaluate Resistance Monitoring (PASER-M) cohort. Participants with pretreatment drug resistance who were given a treatment regimen with reduced activity to at least one prescribed drug had a significantly greater risk of virologic failure and acquired drug resistance compared with both participants without pretreatment drug resistance, and participants with pretreatment drug resistance who were prescribed fully active regimens. This paper by Hamers et al. validates the need for at least three fully active antiretroviral drugs to prevent the acquisition of drug resistance and to optimize treatment success in resource limited settings. PMID:22913352

  7. Functional and evolutionary analyses of Helicobacter pylori HP0231 (DsbK) protein with strong oxidative and chaperone activity characterized by a highly diverged dimerization domain

    PubMed Central

    Bocian-Ostrzycka, Katarzyna M.; Łasica, Anna M.; Dunin-Horkawicz, Stanisław; Grzeszczuk, Magdalena J.; Drabik, Karolina; Dobosz, Aneta M.; Godlewska, Renata; Nowak, Elżbieta; Collet, Jean-Francois; Jagusztyn-Krynicka, Elżbieta K.

    2015-01-01

    Helicobacter pylori does not encode the classical DsbA/DsbB oxidoreductases that are crucial for oxidative folding of extracytoplasmic proteins. Instead, this microorganism encodes an untypical two proteins playing a role in disulfide bond formation – periplasmic HP0231, which structure resembles that of EcDsbC/DsbG, and its redox partner, a membrane protein HpDsbI (HP0595) with a β-propeller structure. The aim of presented work was to assess relations between HP0231 structure and function. We showed that HP0231 is most closely related evolutionarily to the catalytic domain of DsbG, even though it possesses a catalytic motif typical for canonical DsbA proteins. Similarly, the highly diverged N-terminal dimerization domain is homologous to the dimerization domain of DsbG. To better understand the functioning of this atypical oxidoreductase, we examined its activity using in vivo and in vitro experiments. We found that HP0231 exhibits oxidizing and chaperone activities but no isomerizing activity, even though H. pylori does not contain a classical DsbC. We also show that HP0231 is not involved in the introduction of disulfide bonds into HcpC (Helicobacter cysteine-rich protein C), a protein involved in the modulation of the H. pylori interaction with its host. Additionally, we also constructed a truncated version of HP0231 lacking the dimerization domain, denoted HP0231m, and showed that it acts in Escherichia coli cells in a DsbB-dependent manner. In contrast, HP0231m and classical monomeric EcDsbA (E. coli DsbA protein) were both unable to complement the lack of HP0231 in H. pylori cells, though they exist in oxidized forms. HP0231m is inactive in the insulin reduction assay and possesses high chaperone activity, in contrast to EcDsbA. In conclusion, HP0231 combines oxidative functions characteristic of DsbA proteins and chaperone activity characteristic of DsbC/DsbG, and it lacks isomerization activity. PMID:26500620

  8. Purvalanol A is a strong apoptotic inducer via activating polyamine catabolic pathway in MCF-7 estrogen receptor positive breast cancer cells.

    PubMed

    Obakan, Pınar; Arısan, Elif Damla; Özfiliz, Pelin; Çoker-Gürkan, Ajda; Palavan-Ünsal, Narçin

    2014-01-01

    Purvalanol A is a specific CDK inhibitor which triggers apoptosis by causing cell cycle arrest in cancer cells. Although it has strong apoptotic potential, the mechanistic action of Purvalanol A on significant cell signaling targets has not been clarified yet. Polyamines are crucial metabolic regulators affected by CDK inhibition because of their role in cell cycle progress as well. In addition, malignant cells possess impaired polyamine homeostasis with high level of intracellular polyamines. Especially induction of polyamine catabolic enzymes spermidine/spermine N1-acetyltransferase (SSAT), polyamine oxidase (PAO) and spermine oxidase (SMO) induced toxic by-products in correlation with the induction of apoptosis in cancer cells. In this study, we showed that Purvalanol A induced apoptosis in caspase- dependent manner in MCF-7 ER(+) cells, while MDA-MB-231 (ER-) cells were less sensitive against drug. In addition Bcl-2 is a critical target for Purvalanol A, since Bcl-2 overexpressed cells are more resistant to Purvalanol A-mediated apoptosis. Furthermore, exposure of MCF-7 cells to Purvalanol A triggered SSAT and PAO upregulation and the presence of PAO/SMO inhibitor, MDL 72,527 prevented Purvalanol A-induced apoptosis. PMID:24190492

  9. ZnO Nanoparticles Impose a Panmetabolic Toxic Effect Along with Strong Necrosis, Inducing Activation of the Envelope Stress Response in Salmonella enterica Serovar Enteritidis

    PubMed Central

    Vidovic, Sinisa; Elder, Jeff; Medihala, Prabhakara; Lawrence, John R.; Predicala, Bernardo; Zhang, Haixia

    2015-01-01

    In this study, we tested the antimicrobial activity of three metal nanoparticles (NPs), ZnO, MgO, and CaO NPs, against Salmonella enterica serovar Enteritidis in liquid medium and on solid surfaces. Out of the three tested metal NPs, ZnO NPs exhibited the most significant antimicrobial effect both in liquid medium and when embedded on solid surfaces. Therefore, we focused on revealing the mechanisms of surface-associated ZnO biocidal activity. Using the global proteome approach, we report that a great majority (79%) of the altered proteins in biofilms formed by Salmonella enterica serovar Enteritidis were downregulated, whereas a much smaller fraction (21%) of proteins were upregulated. Intriguingly, all downregulated proteins were enzymes involved in a wide range of the central metabolic pathways, including translation; amino acid biosynthetic pathways; nucleobase, nucleoside, and nucleotide biosynthetic processes; ATP synthesis-coupled proton transport; the pentose phosphate shunt; and carboxylic acid metabolic processes, indicating that ZnO NPs exert a panmetabolic toxic effect on this prokaryotic organism. In addition to their panmetabolic toxicity, ZnO NPs induced profound changes in cell envelope morphology, imposing additional necrotic effects and triggering the envelope stress response of Salmonella serovar Enteritidis. The envelope stress response effect activated periplasmic chaperones and proteases, transenvelope complexes, and regulators, thereby facilitating protection of this prokaryotic organism against ZnO NPs. PMID:25801570

  10. ZnO nanoparticles impose a panmetabolic toxic effect along with strong necrosis, inducing activation of the envelope stress response in Salmonella enterica serovar Enteritidis.

    PubMed

    Vidovic, Sinisa; Elder, Jeff; Medihala, Prabhakara; Lawrence, John R; Predicala, Bernardo; Zhang, Haixia; Korber, Darren R

    2015-01-01

    In this study, we tested the antimicrobial activity of three metal nanoparticles (NPs), ZnO, MgO, and CaO NPs, against Salmonella enterica serovar Enteritidis in liquid medium and on solid surfaces. Out of the three tested metal NPs, ZnO NPs exhibited the most significant antimicrobial effect both in liquid medium and when embedded on solid surfaces. Therefore, we focused on revealing the mechanisms of surface-associated ZnO biocidal activity. Using the global proteome approach, we report that a great majority (79%) of the altered proteins in biofilms formed by Salmonella enterica serovar Enteritidis were downregulated, whereas a much smaller fraction (21%) of proteins were upregulated. Intriguingly, all downregulated proteins were enzymes involved in a wide range of the central metabolic pathways, including translation; amino acid biosynthetic pathways; nucleobase, nucleoside, and nucleotide biosynthetic processes; ATP synthesis-coupled proton transport; the pentose phosphate shunt; and carboxylic acid metabolic processes, indicating that ZnO NPs exert a panmetabolic toxic effect on this prokaryotic organism. In addition to their panmetabolic toxicity, ZnO NPs induced profound changes in cell envelope morphology, imposing additional necrotic effects and triggering the envelope stress response of Salmonella serovar Enteritidis. The envelope stress response effect activated periplasmic chaperones and proteases, transenvelope complexes, and regulators, thereby facilitating protection of this prokaryotic organism against ZnO NPs. PMID:25801570

  11. Emerging ST121/agr4 community-associated methicillin-resistant Staphylococcus aureus (MRSA) with strong adhesin and cytolytic activities: trigger for MRSA pneumonia and fatal aspiration pneumonia in an influenza-infected elderly.

    PubMed

    Wan, T-W; Tomita, Y; Saita, N; Konno, K; Iwao, Y; Hung, W-C; Teng, L-J; Yamamoto, T

    2016-09-01

    The pathogenesis of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) pneumonia in influenza-infected elderly individuals has not yet been elucidated in detail. In the present study, a 92-year-old man infected with influenza developed CA-MRSA pneumonia. His CA-MRSA was an emerging type, originated in ST121/agr4 S. aureus, with diversities of Panton-Valentine leucocidin (PVL)(-)/spat5110/SCCmecV(+) versus PVL(+)/spat159((etc.))/SCCmec (-), but with common virulence potentials of strong adhesin and cytolytic activities. Resistance to erythromycin/clindamycin (inducible-type) and gentamicin was detected. Pneumonia improved with the administration of levofloxacin, but with the subsequent development of fatal aspiration pneumonia. Hence, characteristic CA-MRSA with strong adhesin and cytolytic activities triggered influenza-related sequential complications. PMID:27358743

  12. On Strong Anticipation

    PubMed Central

    Stepp, N.; Turvey, M. T.

    2009-01-01

    We examine Dubois's (2003) distinction between weak anticipation and strong anticipation. Anticipation is weak if it arises from a model of the system via internal simulations. Anticipation is strong if it arises from the system itself via lawful regularities embedded in the system's ordinary mode of functioning. The assumption of weak anticipation dominates cognitive science and neuroscience and in particular the study of perception and action. The assumption of strong anticipation, however, seems to be required by anticipation's ubiquity. It is, for example, characteristic of homeostatic processes at the level of the organism, organs, and cells. We develop the formal distinction between strong and weak anticipation by elaboration of anticipating synchronization, a phenomenon arising from time delays in appropriately coupled dynamical systems. The elaboration is conducted in respect to (a) strictly physical systems, (b) the defining features of circadian rhythms, often viewed as paradigmatic of biological behavior based in internal models, (c) Pavlovian learning, and (d) forward models in motor control. We identify the common thread of strongly anticipatory systems and argue for its significance in furthering understanding of notions such as “internal”, “model” and “prediction”. PMID:20191086

  13. PROBING THE INNER JET OF THE QUASAR PKS 1510-089 WITH MULTI-WAVEBAND MONITORING DURING STRONG GAMMA-RAY ACTIVITY

    SciTech Connect

    Marscher, Alan P.; Jorstad, Svetlana G.; Larionov, Valeri M.; Hagen-Thorn, Vladimir A.; Konstantinova, Tatiana S.; Larionova, Elena G.; Larionova, Liudmila V.; Melnichuk, Daria A.; Blinov, Dmitry A.; Kopatskaya, Evgenia N.; Troitsky, Ivan S.; Aller, Margo F.; Aller, Hugh D.; Laehteenmaeki, Anne; Tornikoski, Merja; Hovatta, Talvikki; Agudo, Ivan; Smith, Paul S.; Schmidt, Gary D.; Gurwell, Mark

    2010-02-20

    We present results from monitoring the multi-waveband flux, linear polarization, and parsec-scale structure of the quasar PKS 1510 - 089, concentrating on eight major {gamma}-ray flares that occurred during the interval 2009.0-2009.5. The {gamma}-ray peaks were essentially simultaneous with maxima at optical wavelengths, although the flux ratio of the two wave bands varied by an order of magnitude. The optical polarization vector rotated by 720 deg. during a five-day period encompassing six of these flares. This culminated in a very bright, {approx}1 day, optical and {gamma}-ray flare as a bright knot of emission passed through the highest-intensity, stationary feature (the 'core') seen in 43 GHz Very Long Baseline Array images. The knot continued to propagate down the jet at an apparent speed of 22c and emit strongly at {gamma}-ray energies as a months-long X-ray/radio outburst intensified. We interpret these events as the result of the knot following a spiral path through a mainly toroidal magnetic field pattern in the acceleration and collimation zone of the jet, after which it passes through a standing shock in the 43 GHz core and then continues downstream. In this picture, the rapid {gamma}-ray flares result from scattering of infrared seed photons from a relatively slow sheath of the jet as well as from optical synchrotron radiation in the faster spine. The 2006-2009.7 radio and X-ray flux variations are correlated at very high significance; we conclude that the X-rays are mainly from inverse Compton scattering of infrared seed photons by 20-40 MeV electrons.

  14. High Pre-β1 HDL Concentrations and Low Lecithin: Cholesterol Acyltransferase Activities Are Strong Positive Risk Markers for Ischemic Heart Disease and Independent of HDL-Cholesterol

    PubMed Central

    Sethi, Amar A.; Sampson, Maureen; Warnick, Russell; Muniz, Nehemias; Vaisman, Boris; Nordestgaard, Børge G.; Tybjærg-Hansen, Anne; Remaley, Alan T.

    2016-01-01

    BACKGROUND We hypothesized that patients with high HDL-cholesterol (HDL-C) and ischemic heart disease (IHD) may have dysfunctional HDL or unrecognized nonconventional risk factors. METHODS Individuals with IHD (Copenhagen University Hospital) and either high HDL-C (n = 53; women ≥735 mg/L; men ≥619 mg/L) or low HDL-C (n = 42; women ≤387 mg/L; men ≤341 mg/L) were compared with individuals without IHD (Copenhagen City Heart Study) matched by age, sex, and HDL-C concentrations (n = 110). All participants had concentrations within reference intervals for LDL-C (<1600 mg/L) and triglyceride (<1500 mg/L), and none were treated with lipid-lowering medications. Pre-β1 HDL and phospholipid transfer protein concentrations were measured by using commercial kits and lecithin:cholesterol acyltransferase (LCAT) activity by using a proteoliposome cholesterol esterification assay. RESULTS Pre-β1 HDL concentrations were 2-fold higher in individuals with IHD vs no IHD in both the high [63 (5.7) vs 35 (2.3) mg/L; P < 0.0001] and low HDL-C [49 (5.0) vs 27 (1.5) mg/L; P = 0.001] groups. Low LCAT activity was also associated with IHD in the high [95.2 (6.7) vs 123.0 (5.3) μmol · L−1 · h−1; P = 0.002] and low [93.4 (8.3) vs 113.5 (4.9) μmol · L−1 · h−1; P = 0.03] HDL-C groups. ROC curves for pre-β1 HDL in the high–HDL-C groups yielded an area under the curve of 0.71 (95% CI: 0.61–0.81) for predicting IHD, which increased to 0.92 (0.87–0.97) when LCAT was included. Similar results were obtained for low HDL-C groups. An inverse correlation between LCAT activity and pre-β1 HDL was observed (r2 = 0.30; P < 0.0001) in IHD participants, which was stronger in the low HDL-C group (r2 = 0.56; P < 0.0001). CONCLUSIONS IHD was associated with high pre-β1 HDL concentrations and low LCAT levels, yielding correct classification in more than 90% of the IHD cases for which both were measured, thus making pre-β1 HDL concentration and LCAT activity level potentially

  15. Strong acoustic wave action

    NASA Astrophysics Data System (ADS)

    Gokhberg, M. B.

    1983-07-01

    Experiments devoted to acoustic action on the atmosphere-magnetosphere-ionosphere system using ground based strong explosions are reviewed. The propagation of acoustic waves was observed by ground observations over 2000 km in horizontal direction and to an altitude of 200 km. Magnetic variations up to 100 nT were detected by ARIEL-3 satellite near the epicenter of the explosion connected with the formation of strong field aligned currents in the magnetosphere. The enhancement of VLF emission at 800 km altitude is observed.

  16. Differences in the mannose oligomer specificities of the closely related lectins from Galanthus nivalis and Zea mays strongly determine their eventual anti-HIV activity

    PubMed Central

    2011-01-01

    Background In a recent report, the carbohydrate-binding specificities of the plant lectins Galanthus nivalis (GNA) and the closely related lectin from Zea mays (GNAmaize) were determined by glycan array analysis and indicated that GNAmaize recognizes complex-type N-glycans whereas GNA has specificity towards high-mannose-type glycans. Both lectins are tetrameric proteins sharing 64% sequence similarity. Results GNAmaize appeared to be ~20- to 100-fold less inhibitory than GNA against HIV infection, syncytia formation between persistently HIV-1-infected HuT-78 cells and uninfected CD4+ T-lymphocyte SupT1 cells, HIV-1 capture by DC-SIGN and subsequent transmission of DC-SIGN-captured virions to uninfected CD4+ T-lymphocyte cells. In contrast to GNA, which preferentially selects for virus strains with deleted high-mannose-type glycans on gp120, prolonged exposure of HIV-1 to dose-escalating concentrations of GNAmaize selected for mutant virus strains in which one complex-type glycan of gp120 was deleted. Surface Plasmon Resonance (SPR) analysis revealed that GNA and GNAmaize interact with HIV IIIB gp120 with affinity constants (KD) of 0.33 nM and 34 nM, respectively. Whereas immobilized GNA specifically binds mannose oligomers, GNAmaize selectively binds complex-type GlcNAcβ1,2Man oligomers. Also, epitope mapping experiments revealed that GNA and the mannose-specific mAb 2G12 can independently bind from GNAmaize to gp120, whereas GNAmaize cannot efficiently bind to gp120 that contained prebound PHA-E (GlcNAcβ1,2man specific) or SNA (NeuAcα2,6X specific). Conclusion The markedly reduced anti-HIV activity of GNAmaize compared to GNA can be explained by the profound shift in glycan recognition and the disappearance of carbohydrate-binding sites in GNAmaize that have high affinity for mannose oligomers. These findings underscore the need for mannose oligomer recognition of therapeutics to be endowed with anti-HIV activity and that mannose, but not complex-type glycan

  17. An amorphous CoSe film behaves as an active and stable full water-splitting electrocatalyst under strongly alkaline conditions.

    PubMed

    Liu, Tingting; Liu, Qian; Asiri, Abdullah M; Luo, Yonglan; Sun, Xuping

    2015-12-01

    It is attractive but still remains a big challenge to develop non-noble metal bifunctional electrocatalysts efficient for both oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) under alkaline conditions. Herein, an amorphous CoSe film electrodeposited on a Ti mesh (a-CoSe/Ti) is demonstrated to exhibit high electrocatalytic activity and stability for both reactions in 1.0 M KOH. It needs overpotentials of 292 and 121 mV to drive 10 mA cm(-2) for OER and HER, respectively. The two-electrode alkaline water electrolyzer affords a water-splitting current of 10 mA cm(-2) at a cell voltage of 1.65 V. This work offers an attractive cost-effective catalytic material toward full water splitting applications. PMID:26431349

  18. HER2 signaling pathway activation and response of breast cancer cells to HER2-targeting agents is dependent strongly on the 3D microenvironment

    SciTech Connect

    Weigelt, Britta; Lo, Alvin T; Park, Catherine C; Gray, Joe W; Bissell, Mina J

    2009-07-27

    Development of effective and durable breast cancer treatment strategies requires a mechanistic understanding of the influence of the microenvironment on response. Previous work has shown that cellular signaling pathways and cell morphology are dramatically influenced by three-dimensional (3D) cultures as opposed to traditional two-dimensional (2D) monolayers. Here, we compared 2D and 3D culture models to determine the impact of 3D architecture and extracellular matrix (ECM) on HER2 signaling and on the response of HER2-amplified breast cancer cell lines to the HER2-targeting agents Trastuzumab, Pertuzumab and Lapatinib. We show that the response of the HER2-amplified AU565, SKBR3 and HCC1569 cells to these anti-HER2 agents was highly dependent on whether the cells were cultured in 2D monolayer or 3D laminin-rich ECM gels. Inhibition of {beta}1 integrin, a major cell-ECM receptor subunit, significantly increased the sensitivity of the HER2-amplified breast cancer cell lines to the humanized monoclonal antibodies Trastuzumab and Pertuzumab when grown in a 3D environment. Finally, in the absence of inhibitors, 3D cultures had substantial impact on HER2 downstream signaling and induced a switch between PI3K-AKT- and RAS-MAPKpathway activation in all cell lines studied, including cells lacking HER2 amplification and overexpression. Our data provide direct evidence that breast cancer cells are able to rapidly adapt to different environments and signaling cues by activating alternative pathways that regulate proliferation and cell survival, events that may play a significant role in the acquisition of resistance to targeted therapies.

  19. Strong Little Magnets

    ERIC Educational Resources Information Center

    Moloney, Michael J.

    2007-01-01

    Did you know that some strong little cylindrical magnets available in local hardware stores can have an effective circumferential current of 2500 A? This intriguing information can be obtained by hanging a pair of magnets at the center of a coil, as shown in Fig. 1, and measuring the oscillation frequency as a function of coil current.

  20. DHCR24 associates strongly with the endoplasmic reticulum beyond predicted membrane domains: implications for the activities of this multi-functional enzyme

    PubMed Central

    Zerenturk, Eser J.; Sharpe, Laura J.; Brown, Andrew J.

    2014-01-01

    Cholesterol synthesis occurs in the ER (endoplasmic reticulum), where most of the cholesterogenic machinery resides. As membrane-bound proteins, their topology is difficult to determine, and thus their structures are largely unknown. To help resolve this, we focused on the final enzyme in cholesterol synthesis, DHCR24 (3β-hydroxysterol Δ24-reductase). Prediction programmes and previous studies have shown conflicting results regarding which regions of DHCR24 are associated with the membrane, although there was general agreement that this was limited to only the N-terminal portion. Here, we present biochemical evidence that in fact the majority of the enzyme is associated with the ER membrane. This has important consequences for the many functions attributed to DHCR24. In particular, those that suggest DHCR24 alters its localization within the cell should be reassessed in light of this new information. Moreover, we propose that the expanding database of post-translational modifications will be a valuable resource for mapping the topology of membrane-associated proteins, such as DHCR24, that is, flagging cytosolic residues accessible to modifying enzymes such as kinases and ubiquitin ligases. PMID:24502685

  1. The influence of strong connections on dynamics of neuron population with long-tailed synaptic weight distribution

    NASA Astrophysics Data System (ADS)

    Chizhkova, E. A.; Chizhov, A. V.

    2015-12-01

    This work is devoted to exploring the influence of long-tailed synaptic weights distribution on neural population dynamics. We show numerically that both strong sparse and very weak connections pay crucial role for spontaneous activity whereas they almost do not influence on driven population activity. Moreover, according to obtained results, we suggest that neurons with strong connections form multiple chains, which are the core of spontaneous activity, whereas neurons with weak connections pay little role of partially enhancing of population activity.

  2. Strong Saharan Dust Event Detected at Lalinet LOA-UNAL Station, over Medellín, Colombia by Active and Passive Remote Sensing

    NASA Astrophysics Data System (ADS)

    Bedoya, Andrés; Nisperuza, Daniel; Alegría, Dairo; Múnera, Mauricio; Guerrero-Rascado, Juan Luis; Zapata, Carmen E.; Jiménez, Jose F.; Landulfo, Eduardo; Bastidas, Álvaro

    2016-06-01

    Passive and active remote sensing techniques are well used for understanding optical and microphysical characteristics of aerosol layers. Lidar has the ability to resolve stratifications of the complex vertical structures in the atmosphere and determine the existence of aerosols which has been transported for long-ranges through the evaluation of the optical properties such as particle backscatter and extinction coefficients, among others. CIMEL sunphotometer data (AERONET network) give information about optical properties such as Aerosol Optical Depth (AOD), Single Scattering Albedo (SSA), and Angström Exponent (AE) and microphysical properties such as size distribution. The LOA-UNAL lidar station as part of the LALINET (Latin American LIdar NETwork) [1], involves an elastic coaxial system operating in zenith mode used for monitoring the atmosphere at Medellín-Colombia (6.26°N, 75.58°W, 1470 m asl). This work presents a Saharan dust even over Medellín, Colombia, 27th June, 2014, observed simultaneously with lidar, sun-photometer and complementary global mass transport model HYSPLIT.

  3. Composite strongly interacting dark matter

    NASA Astrophysics Data System (ADS)

    Cline, James M.; Liu, Zuowei; Moore, Guy D.; Xue, Wei

    2014-07-01

    It has been suggested that cold dark matter (CDM) has difficulties in explaining tentative evidence for noncuspy halo profiles in small galaxies, and the low velocity dispersions observed in the largest Milky Way satellites ("too-big-to-fail" problem). Strongly self-interacting dark matter has been noted as a robust solution to these problems. The elastic cross sections required are much larger than predicted by generic CDM models, but could naturally be of the right size if dark matter is composite. We explore in a general way the constraints on models where strongly interacting CDM is in the form of dark "atoms" or "molecules," or bound states of a confining gauge interaction ("hadrons"). These constraints include considerations of relic density, direct detection, big bang nucleosynthesis, the cosmic microwave background, and LHC data.

  4. Raising Strong Daughters.

    ERIC Educational Resources Information Center

    Gadeberg, Jeanette

    In response to an alarming drop in girls' self-esteem in early adolescence, this parents' guide provides suggestions for raising daughters to become confident, healthy, and independent. Chapter 1, "Yesterday's Daughters," examines how cultural messages inhibit girls' development. Chapter 2, "Raising an Opinionated Daughter," suggests how to help…

  5. Decrease of U(VI) immobilization capability of the facultative anaerobic strain Paenibacillus sp. JG-TB8 under anoxic conditions due to strongly reduced phosphatase activity.

    PubMed

    Reitz, Thomas; Rossberg, Andre; Barkleit, Astrid; Selenska-Pobell, Sonja; Merroun, Mohamed L

    2014-01-01

    Interactions of a facultative anaerobic bacterial isolate named Paenibacillus sp. JG-TB8 with U(VI) were studied under oxic and anoxic conditions in order to assess the influence of the oxygen-dependent cell metabolism on microbial uranium mobilization and immobilization. We demonstrated that aerobically and anaerobically grown cells of Paenibacillus sp. JG-TB8 accumulate uranium from aqueous solutions under acidic conditions (pH 2 to 6), under oxic and anoxic conditions. A combination of spectroscopic and microscopic methods revealed that the speciation of U(VI) associated with the cells of the strain depend on the pH as well as on the aeration conditions. At pH 2 and pH 3, uranium was exclusively bound by organic phosphate groups provided by cellular components, independently on the aeration conditions. At higher pH values, a part (pH 4.5) or the total amount (pH 6) of the dissolved uranium was precipitated under oxic conditions in a meta-autunite-like uranyl phosphate mineral phase without supplying an additional organic phosphate substrate. In contrast to that, under anoxic conditions no mineral formation was observed at pH 4.5 and pH 6, which was clearly assigned to decreased orthophosphate release by the cells. This in turn was caused by a suppression of the indigenous phosphatase activity of the strain. The results demonstrate that changes in the metabolism of facultative anaerobic microorganisms caused by the presence or absence of oxygen can decisively influence U(VI) biomineralization. PMID:25157416

  6. Decrease of U(VI) Immobilization Capability of the Facultative Anaerobic Strain Paenibacillus sp. JG-TB8 under Anoxic Conditions Due to Strongly Reduced Phosphatase Activity

    PubMed Central

    Reitz, Thomas; Rossberg, Andre; Barkleit, Astrid; Selenska-Pobell, Sonja; Merroun, Mohamed L.

    2014-01-01

    Interactions of a facultative anaerobic bacterial isolate named Paenibacillus sp. JG-TB8 with U(VI) were studied under oxic and anoxic conditions in order to assess the influence of the oxygen-dependent cell metabolism on microbial uranium mobilization and immobilization. We demonstrated that aerobically and anaerobically grown cells of Paenibacillus sp. JG-TB8 accumulate uranium from aqueous solutions under acidic conditions (pH 2 to 6), under oxic and anoxic conditions. A combination of spectroscopic and microscopic methods revealed that the speciation of U(VI) associated with the cells of the strain depend on the pH as well as on the aeration conditions. At pH 2 and pH 3, uranium was exclusively bound by organic phosphate groups provided by cellular components, independently on the aeration conditions. At higher pH values, a part (pH 4.5) or the total amount (pH 6) of the dissolved uranium was precipitated under oxic conditions in a meta-autunite-like uranyl phosphate mineral phase without supplying an additional organic phosphate substrate. In contrast to that, under anoxic conditions no mineral formation was observed at pH 4.5 and pH 6, which was clearly assigned to decreased orthophosphate release by the cells. This in turn was caused by a suppression of the indigenous phosphatase activity of the strain. The results demonstrate that changes in the metabolism of facultative anaerobic microorganisms caused by the presence or absence of oxygen can decisively influence U(VI) biomineralization. PMID:25157416

  7. Spectral energy distributions of QSOs at z > 5: Common active galactic nucleus-heated dust and occasionally strong star-formation

    SciTech Connect

    Leipski, C.; Meisenheimer, K.; Walter, F.; Klaas, U.; Krause, O.; Rix, H.-W.; Dannerbauer, H.; De Rosa, G.; Fan, X.; Haas, M.

    2014-04-20

    We present spectral energy distributions (SEDs) of 69 QSOs at z > 5, covering a rest frame wavelength range of 0.1 μm to ∼80 μm, and centered on new Spitzer and Herschel observations. The detection rate of the QSOs with Spitzer is very high (97% at λ{sub rest} ≲ 4 μm), but drops toward the Herschel bands with 30% detected in PACS (rest frame mid-infrared) and 15% additionally in the SPIRE (rest frame far-infrared; FIR). We perform multi-component SED fits for Herschel-detected objects and confirm that to match the observed SEDs, a clumpy torus model needs to be complemented by a hot (∼1300 K) component and, in cases with prominent FIR emission, also by a cold (∼50 K) component. In the FIR-detected cases the luminosity of the cold component is of the order of 10{sup 13} L {sub ☉} which is likely heated by star formation. From the SED fits we also determine that the active galactic nucleus (AGN) dust-to-accretion disk luminosity ratio declines with UV/optical luminosity. Emission from hot (∼1300 K) dust is common in our sample, showing that nuclear dust is ubiquitous in luminous QSOs out to redshift 6. However, about 15% of the objects appear under-luminous in the near infrared compared to their optical emission and seem to be deficient in (but not devoid of) hot dust. Within our full sample, the QSOs detected with Herschel are found at the high luminosity end in L {sub UV/opt} and L {sub NIR} and show low equivalent widths (EWs) in Hα and in Lyα. In the distribution of Hα EWs, as determined from the Spitzer photometry, the high-redshift QSOs show little difference to low-redshift AGN.

  8. Tetra-O-Methyl Nordihydroguaiaretic Acid Broadly Suppresses Cancer Metabolism and Synergistically Induces Strong Anticancer Activity in Combination with Etoposide, Rapamycin and UCN-01

    PubMed Central

    Kimura, Kotohiko; Huang, Ru Chih C.

    2016-01-01

    The ability of Tetra-O-methyl nordihydroguaiaretic acid (M4N) to induce rapid cell death in combination with Etoposide, Rapamycin, or UCN-01 was examined in LNCaP cells, both in cell culture and animal experiments. Mice treated with M4N drug combinations with either Etoposide or Rapamycin showed no evidence of tumor and had a 100% survival rate 100 days after tumor implantation. By comparison all other vehicles or single drug treated mice failed to survive longer than 30 days after implantation. This synergistic improvement of anticancer effect was also confirmed in more than 20 cancer cell lines. In LNCaP cells, M4N was found to reduce cellular ATP content, and suppress NDUFS1 expression while inducing hyperpolarization of mitochondrial membrane potential. M4N-treated cells lacked autophagy with reduced expression of BNIP3 and ATG5. To understand the mechanisms of this anticancer activity of M4N, the effect of this drug on three cancer cell lines (LNCaP, AsPC-1, and L428 cells) was further examined via transcriptome and metabolomics analyses. Metabolomic results showed that there were reductions of 26 metabolites essential for energy generation and/or production of cellular components in common with these three cell lines following 8 hours of M4N treatment. Deep RNA sequencing analysis demonstrated that there were sixteen genes whose expressions were found to be modulated following 6 hours of M4N treatment similarly in these three cell lines. Six out of these 16 genes were functionally related to the 26 metabolites described above. One of these up-regulated genes encodes for CHAC1, a key enzyme affecting the stress pathways through its degradation of glutathione. In fact M4N was found to suppress glutathione content and induce reactive oxygen species production. The data overall indicate that M4N has profound specific negative impacts on a wide range of cancer metabolisms supporting the use of M4N combination for cancer treatments. PMID:26886430

  9. Tetra-O-Methyl Nordihydroguaiaretic Acid Broadly Suppresses Cancer Metabolism and Synergistically Induces Strong Anticancer Activity in Combination with Etoposide, Rapamycin and UCN-01.

    PubMed

    Kimura, Kotohiko; Huang, Ru Chih C

    2016-01-01

    The ability of Tetra-O-methyl nordihydroguaiaretic acid (M4N) to induce rapid cell death in combination with Etoposide, Rapamycin, or UCN-01 was examined in LNCaP cells, both in cell culture and animal experiments. Mice treated with M4N drug combinations with either Etoposide or Rapamycin showed no evidence of tumor and had a 100% survival rate 100 days after tumor implantation. By comparison all other vehicles or single drug treated mice failed to survive longer than 30 days after implantation. This synergistic improvement of anticancer effect was also confirmed in more than 20 cancer cell lines. In LNCaP cells, M4N was found to reduce cellular ATP content, and suppress NDUFS1 expression while inducing hyperpolarization of mitochondrial membrane potential. M4N-treated cells lacked autophagy with reduced expression of BNIP3 and ATG5. To understand the mechanisms of this anticancer activity of M4N, the effect of this drug on three cancer cell lines (LNCaP, AsPC-1, and L428 cells) was further examined via transcriptome and metabolomics analyses. Metabolomic results showed that there were reductions of 26 metabolites essential for energy generation and/or production of cellular components in common with these three cell lines following 8 hours of M4N treatment. Deep RNA sequencing analysis demonstrated that there were sixteen genes whose expressions were found to be modulated following 6 hours of M4N treatment similarly in these three cell lines. Six out of these 16 genes were functionally related to the 26 metabolites described above. One of these up-regulated genes encodes for CHAC1, a key enzyme affecting the stress pathways through its degradation of glutathione. In fact M4N was found to suppress glutathione content and induce reactive oxygen species production. The data overall indicate that M4N has profound specific negative impacts on a wide range of cancer metabolisms supporting the use of M4N combination for cancer treatments. PMID:26886430

  10. Strong subadditivity and holography

    NASA Astrophysics Data System (ADS)

    Prudenziati, Andrea

    2016-05-01

    We study in detail the relationship between strong subadditivity for a boundary field theory and energy conditions for its bulk dual in 2 +1 dimensions. We provide a discussion of known facts and new results organized from the simplest case of a static system with collinear intervals to a time-dependent one in a generic configuration, with particular focus on the holographic geometric description.

  11. Plasmons in strong superconductors

    SciTech Connect

    Baldo, M.; Ducoin, C.

    2011-10-15

    We present a study of the possible plasmon excitations that can occur in systems where strong superconductivity is present. In these systems the plasmon energy is comparable to or smaller than the pairing gap. As a prototype of these systems we consider the proton component of Neutron Star matter just below the crust when electron screening is not taken into account. For the realistic case we consider in detail the different aspects of the elementary excitations when the proton, electron components are considered within the Random-Phase Approximation generalized to the superfluid case, while the influence of the neutron component is considered only at qualitative level. Electron screening plays a major role in modifying the proton spectrum and spectral function. At the same time the electron plasmon is strongly modified and damped by the indirect coupling with the superfluid proton component, even at moderately low values of the gap. The excitation spectrum shows the interplay of the different components and their relevance for each excitation modes. The results are relevant for neutrino physics and thermodynamical processes in neutron stars. If electron screening is neglected, the spectral properties of the proton component show some resemblance with the physical situation in high-T{sub c} superconductors, and we briefly discuss similarities and differences in this connection. In a general prospect, the results of the study emphasize the role of Coulomb interaction in strong superconductors.

  12. Seasonal survival probabilities suggest low migration mortality in migrating bats.

    PubMed

    Giavi, Simone; Moretti, Marco; Bontadina, Fabio; Zambelli, Nicola; Schaub, Michael

    2014-01-01

    Migration is adaptive if survival benefits are larger than costs of residency. Many aspects of bat migration ecology such as migratory costs, stopover site use and fidelity are largely unknown. Since many migrating bats are endangered, such information is urgently needed to promote conservation. We selected the migrating Leisler's bat (Nyctalus leisleri) as model species and collected capture-recapture data in southern Switzerland year round during 6 years. We estimated seasonal survival and site fidelity with Cormack-Jolly-Seber models that accounted for the presence of transients fitted with Bayesian methods and assessed differences between sexes and seasons. Activity peaked in autumn and spring, whereas very few individuals were caught during summer. We hypothesize that the study site is a migratory stopover site used during fall and spring migration for most individuals, but there is also evidence for wintering. Additionally, we found strong clues for mating during fall. Summer survival that included two major migratory journeys was identical to winter survival in males and slightly higher in females, suggesting that the migratory journeys did not bear significant costs in terms of survival. Transience probability was in both seasons higher in males than in females. Our results suggest that, similarly to birds, Leisler's bat also use stopover sites during migration with high site fidelity. In contrast to most birds, the stopover site was also used for mating and migratory costs in terms of survival seemed to be low. Transients' analyses highlighted strong individual variation in site use which makes particularly challenging the study and modelling of their populations as well as their conservation. PMID:24454906

  13. Seasonal Survival Probabilities Suggest Low Migration Mortality in Migrating Bats

    PubMed Central

    Giavi, Simone; Moretti, Marco; Bontadina, Fabio; Zambelli, Nicola; Schaub, Michael

    2014-01-01

    Migration is adaptive if survival benefits are larger than costs of residency. Many aspects of bat migration ecology such as migratory costs, stopover site use and fidelity are largely unknown. Since many migrating bats are endangered, such information is urgently needed to promote conservation. We selected the migrating Leisler's bat (Nyctalus leisleri) as model species and collected capture-recapture data in southern Switzerland year round during 6 years. We estimated seasonal survival and site fidelity with Cormack-Jolly-Seber models that accounted for the presence of transients fitted with Bayesian methods and assessed differences between sexes and seasons. Activity peaked in autumn and spring, whereas very few individuals were caught during summer. We hypothesize that the study site is a migratory stopover site used during fall and spring migration for most individuals, but there is also evidence for wintering. Additionally, we found strong clues for mating during fall. Summer survival that included two major migratory journeys was identical to winter survival in males and slightly higher in females, suggesting that the migratory journeys did not bear significant costs in terms of survival. Transience probability was in both seasons higher in males than in females. Our results suggest that, similarly to birds, Leisler's bat also use stopover sites during migration with high site fidelity. In contrast to most birds, the stopover site was also used for mating and migratory costs in terms of survival seemed to be low. Transients' analyses highlighted strong individual variation in site use which makes particularly challenging the study and modelling of their populations as well as their conservation. PMID:24454906

  14. High in vitro activity of the novel spiropyrimidinetrione AZD0914, a DNA gyrase inhibitor, against multidrug-resistant Neisseria gonorrhoeae isolates suggests a new effective option for oral treatment of gonorrhea.

    PubMed

    Jacobsson, Susanne; Golparian, Daniel; Alm, Richard A; Huband, Michael; Mueller, John; Jensen, Jorgen Skov; Ohnishi, Makoto; Unemo, Magnus

    2014-09-01

    We evaluated the activity of the novel spiropyrimidinetrione AZD0914 (DNA gyrase inhibitor) against clinical gonococcal isolates and international reference strains (n=250), including strains with diverse multidrug resistance and extensive drug resistance. The AZD0914 MICs were substantially lower than those of most other currently or previously recommended antimicrobials. AZD0914 should be further evaluated, including in vitro selection, in vivo emergence and mechanisms of resistance, pharmacokinetics/pharmacodynamics in humans, optimal dosing, and performance, in appropriate randomized and controlled clinical trials. PMID:24982070

  15. PREFACE: Strongly Coupled Coulomb Systems Strongly Coupled Coulomb Systems

    NASA Astrophysics Data System (ADS)

    Neilson, David; Senatore, Gaetano

    2009-05-01

    , condensed matter and ultra-cold plasmas. One hundred and thirty participants came from twenty countries and four continents to participate in the conference. Those giving presentations were asked to contribute to this special issue to make a representative record of an interesting conference. We thank the International Advisory Board and the Programme Committee for their support and suggestions. We thank the Local Organizing Committee (Stefania De Palo, Vittorio Pellegrini, Andrea Perali and Pierbiagio Pieri) for all their efforts. We highlight for special mention the dedication displayed by Andrea Perali, by Rocco di Marco for computer support, and by our tireless conference secretary Fiorella Paino. The knowledgeable guided tour of the historic centre of Camerino given by Fiorella Paino was appreciated by many participants. It is no exaggeration to say that without the extraordinary efforts put in by these three, the conference could not have been the success that it was. For their sustained interest and support we thank Fulvio Esposito, Rector of the University of Camerino, Fabio Beltram, Director of NEST, Scuola Normale Superiore, Pisa, and Daniel Cox, Co-Director of ICAM, University of California at Davis. We thank the Institute of Complex and Adaptive Matter ICAM-I2CAM, USA for providing a video record of the conference on the web (found at http://sccs2008.df.unicam.it/). Finally we thank the conference sponsors for their very generous support: the University of Camerino, the Institute of Complex and Adaptive Matter ICAM-I2CAM, USA, the International Centre for Theoretical Physics ICTP Trieste, and CNR-INFM DEMOCRITOS Modeling Center for Research in Atomistic Simulation, Trieste. Participants at the International Conference on Strongly Coupled Coulomb Systems (SCCS) (University of Camerino, Italy, 29 July-2 August 2008).

  16. Entrainment in solution of an oscillating NADH oxidase activity from the bovine milk fat globule membrane with a temperature-compensated period length suggestive of an ultradian time-keeping (clock) function

    NASA Technical Reports Server (NTRS)

    Morre, D. James; Lawler, Juliana; Wang, Sui; Keenan, Thomas W.; Morre, Dorothy M.

    2002-01-01

    Entrainment in solution of an oscillating activity with a temperature compensated period of 24 min is described for a NADH oxidase (NOX) activity of the bovine milk fat globule membrane, a derivative of the mammary epithelial cell plasma membrane. The period of 24 min remained unchanged at 17 degrees C, 27 degrees C and 37 degrees C whereas the amplitude approximately doubled with each 10 degree C rise in temperature (Q(10)congruent with 2). The periodicity was observed with both intact milk fat globule membranes and with detergent-solubilized membranes, demonstrating that the oscillations did not require an association with membranes. The periodicity was not the result of instrument variation or of chemical interactions among reactants in solution. Preparations with different periodicities entrained (autosynchronized) when mixed. Upon mixing, the preparations exhibited two oscillatory patterns but eventually a single pattern representing the mean of the farthest separated maxima of the two preparations analyzed separately emerged. The cell surface NOX protein is the first reported example of an entrainable biochemical entity with a temperature-compensated periodicity potentially capable of functioning as an ultradian or circadian clock driver.

  17. Strongly correlated electronic materials

    SciTech Connect

    Bedell, K.; Albers, R.; Balatsky, A.; Bishop, A.; Bonca, J.; Gubernatis, J.; Gulasci, M.; Silver, R.; Trugman, S.

    1996-04-01

    This is the final report of a 3-year project. Novel electronic materials characterized by strong electronic correlations display a number of unexpected, often extraordinary, properties. These are likely to play a major role in purpose-specific high-technology electronic materials of the future developed for electronic, magnetic, and optical applications. This project sought to develop predictive control of the novel properties by formulating, solving and applying many-body models for the underlying microscopic physics. This predictive control required the development of new analytical and numerical many-body techniques and strategies for materials of varying strengths of interactions, dimensionality and geometry. Results are compared with experiment on classes of novel materials, and the robust techniques are used to predict additional properties and motivate key additional experiments.

  18. Strongly-correlated heterostructures

    SciTech Connect

    Okamoto, Satoshi

    2012-01-01

    Electronic phase behavior in correlated-electron systems is a fundamental problem of condensed matter physics. The change in the phase behavior near surfaces and interfaces, i.e., {\\em electronic reconstruction}, is therefore the fundamental issue of the correlated-electron surface or interface science. In addition to basic science, understanding of such a phase behavior is of crucial importance for potential devices exploiting the novel properties of the correlated systems. In this article, we present a general overview of the field, and then discuss the recent theoretical progress mainly focusing on the correlation effects. We illustrate the general concept of {\\em electronic reconstruction} by studying model heterostructures consisting of strongly-correlated systems. Future directions for research are also discussed.

  19. Strong, Lightweight, Porous Materials

    NASA Technical Reports Server (NTRS)

    Leventis, Nicholas; Meador, Mary Ann B.; Johnston, James C.; Fabrizio, Eve F.; Ilhan, Ulvi

    2007-01-01

    A new class of strong, lightweight, porous materials has been invented as an outgrowth of an effort to develop reinforced silica aerogels. The new material, called X-Aerogel is less hygroscopic, but no less porous and of similar density to the corresponding unmodified aerogels. However, the property that sets X-Aerogels apart is their mechanical strength, which can be as much as two and a half orders of magnitude stronger that the unmodified aerogels. X-Aerogels are envisioned to be useful for making extremely lightweight, thermally insulating, structural components, but they may also have applications as electrical insulators, components of laminates, catalyst supports, templates for electrode materials, fuel-cell components, and filter membranes.

  20. Strongly correlated surface states

    NASA Astrophysics Data System (ADS)

    Alexandrov, Victor A.

    Everything has an edge. However trivial, this phrase has dominated theoretical condensed matter in the past half a decade. Prior to that, questions involving the edge considered to be more of an engineering problem rather than a one of fundamental science: it seemed self-evident that every edge is different. However, recent advances proved that many surface properties enjoy a certain universality, and moreover, are 'topologically' protected. In this thesis I discuss a selected range of problems that bring together topological properties of surface states and strong interactions. Strong interactions alone can lead to a wide spectrum of emergent phenomena: from high temperature superconductivity to unconventional magnetic ordering; interactions can change the properties of particles, from heavy electrons to fractional charges. It is a unique challenge to bring these two topics together. The thesis begins by describing a family of methods and models with interactions so high that electrons effectively disappear as particles and new bound states arise. By invoking the AdS/CFT correspondence we can mimic the physical systems of interest as living on the surface of a higher dimensional universe with a black hole. In a specific example we investigate the properties of the surface states and find helical spin structure of emerged particles. The thesis proceeds from helical particles on the surface of black hole to a surface of samarium hexaboride: an f-electron material with localized magnetic moments at every site. Interactions between electrons in the bulk lead to insulating behavior, but the surfaces found to be conducting. This observation motivated an extensive research: weather the origin of conduction is of a topological nature. Among our main results, we confirm theoretically the topological properties of SmB6; introduce a new framework to address similar questions for this type of insulators, called Kondo insulators. Most notably we introduce the idea of Kondo

  1. Kinematics of Strong Discontinuities

    NASA Technical Reports Server (NTRS)

    Peterson, K.; Nguyen, G.; Sulsky, D.

    2006-01-01

    Synthetic Aperture Radar (SAR) provides a detailed view of the Arctic ice cover. When processed with the RADARSAT Geophysical Processor System (RGPS), it provides estimates of sea ice motion and deformation over large regions of the Arctic for extended periods of time. The deformation is dominated by the appearance of linear kinematic features that have been associated with the presence of leads. The RGPS deformation products are based on the assumption that the displacement and velocity are smooth functions of the spatial coordinates. However, if the dominant deformation of multiyear ice results from the opening, closing and shearing of leads, then the displacement and velocity can be discontinuous. This presentation discusses the kinematics associated with strong discontinuities that describe possible jumps in displacement or velocity. Ice motion from SAR data are analyzed using this framework. It is assumed that RGPS cells deform due to the presence of a lead. The lead orientation is calculated to optimally account for the observed deformation. It is shown that almost all observed deformation can be represented by lead opening and shearing. The procedure used to reprocess motion data to account for leads will be described and applied to regions of the Beaufort Sea. The procedure not only provides a new view of ice deformation, it can be used to obtain information about the presence of leads for initialization and/or validation of numerical simulations.

  2. Strong-interaction nonuniversality

    SciTech Connect

    Volkas, R. R.; Foot, R.; He, X.; Joshi, G. C.

    1989-07-01

    The universal QCD color theory is extended to an SU(3)/sub 1//direct product/SU(3)/sub 2//direct product/SU(3)/sub 3/ gauge theory, where quarks of the /ital i/th generation transform as triplets under SU(3)/sub /ital i// and singlets under the other two factors. The usual color group is then identified with the diagonal subgroup, which remains exact after symmetry breaking. The gauge bosons associated with the 16 broken generators then form two massive octets under ordinary color. The interactions between quarks and these heavy gluonlike particles are explicitly nonuniversal and thus an exploration of their physical implications allows us to shed light on the fundamental issue of strong-interaction universality. Nonuniversality and weak flavor mixing are shown to generate heavy-gluon-induced flavor-changing neutral currents. The phenomenology of these processes is studied, as they provide the major experimental constraint on the extended theory. Three symmetry-breaking scenarios are presented. The first has color breaking occurring at the weak scale, while the second and third divorce the two scales. The third model has the interesting feature of radiatively induced off-diagonal Kobayashi-Maskawa matrix elements.

  3. Strong Poison Revisited

    SciTech Connect

    Prince, R.C.; Gailer, J.; Gunson, D.E.; Turner, R.J.; George, G.N.; Pickering, I.J.

    2009-06-04

    Selenium in the form of selenocysteine plays an essential role in a number of proteins, but its role in non-enzymatic biochemistry is also important. In this short review we discuss the interactions between inorganic selenium, arsenic and mercury under physiological conditions, especially in the presence of glutathione. This chemistry is obviously important in making the arsenic and mercury unavailable for more toxic interactions, but in the process it suggests that a side-effect of chronic arsenic and/or mercury exposure is likely to be functional selenium deficiency.

  4. Binding of estrogen receptors to switch sites and regulatory elements in the immunoglobulin heavy chain locus of activated B cells suggests a direct influence of estrogen on antibody expression.

    PubMed

    Jones, Bart G; Penkert, Rhiannon R; Xu, Beisi; Fan, Yiping; Neale, Geoff; Gearhart, Patricia J; Hurwitz, Julia L

    2016-09-01

    Females and males differ in antibody isotype expression patterns and in immune responses to foreign- and self-antigens. For example, systemic lupus erythematosus is a condition that associates with the production of isotype-skewed anti-self antibodies, and exhibits a 9:1 female:male disease ratio. To explain differences between B cell responses in males and females, we sought to identify direct interactions of the estrogen receptor (ER) with the immunoglobulin heavy chain locus. This effort was encouraged by our previous identification of estrogen response elements (ERE) in heavy chain switch (S) regions. We conducted a full-genome chromatin immunoprecipitation analysis (ChIP-seq) using DNA from LPS-activated B cells and an ERα-specific antibody. Results revealed ER binding to a wide region of DNA, spanning sequences from the JH cluster to Cδ, with peaks in Eμ and Sμ sites. Additional peaks of ERα binding were coincident with hs1,2 and hs4 sites in the 3' regulatory region (3'RR) of the heavy chain locus. This first demonstration of direct binding of ER to key regulatory elements in the immunoglobulin locus supports our hypothesis that estrogen and other nuclear hormone receptors and ligands may directly influence antibody expression and class switch recombination (CSR). Our hypothesis encourages the conduct of new experiments to evaluate the consequences of ER binding. A better understanding of ER:DNA interactions in the immunoglobulin heavy chain locus, and respective mechanisms, may ultimately translate to better control of antibody expression, better protection against pathogens, and prevention of pathologies caused by auto-immune disease. PMID:27494228

  5. b values and ω−γ seismic source models: Implications for tectonic stress variations along active crustal fault zones and the estimation of high-frequency strong ground motion

    USGS Publications Warehouse

    Hanks, Thomas C.

    1979-01-01

    In this study the tectonic stress along active crustal fault zones is taken to be of the form , where  is the average tectonic stress at depth y and Δσp(x, y) is a seismologically observable, essentially random function of both fault plane coordinates; the stress differences arising in the course of crustal faulting are derived from Δσp(x, y). Empirically known frequency of occurrence statistics, moment-magnitude relationships, and the constancy of earthquake stress drops may be used to infer that the number of earthquakes N of dimension ≥r is of the form N ∼ 1/r2 and that the spectral composition of Δσp(x, y) is of the form , where  is the two-dimensional Fourier transform of Δσp(x, y) expressed in radial wave number k. The γ = 2 model of the far-field shear wave displacement spectrum is consistent with the spectral composition , provided that the number of contributions to the spectral representation of the radiated field at frequency ƒ goes as (k/k0)2, consistent with the quasi-static frequency of occurrence relation N ∼ 1/r2;k0 is a reference wave number associated with the reciprocal source dimension. Separately, a variety of seismologic observations suggests that the γ = 2 model is the one generally, although certainly not always, applicable to the high-frequency spectral decay of the far-field radiation of earthquakes. In this framework, then, b values near 1, the general validity of the γ = 2 model, and the constancy of earthquake stress drops independent of size are all related to the average spectral composition of. Should one of these change as a result of premonitory effects leading to failure, as has been specifically proposed for b values, it seems likely that one or all of the other characteristics will change as well from their normative values. Irrespective of these associations, the far-field, high-frequency shear radiation for the γ = 2 model in the presence of anelastic attenuation may be interpreted as

  6. Strong volume, stable prices

    SciTech Connect

    1993-11-01

    This article is the September-October 1993 market report, providing trading volume and prices in the Uranium market. Activity was brisk, with 15 deals concluded. Six were in the spot concentrates market, with four of the six deals involving U.S. utilities and approximately 1.8M pounds of U3O8 equivalent. There were five conversion deals announced, with four of the five deals involving U.S. utilities. Four deals were concluded in the enrichment market, and the deals involving U.S. utilities were approximately 327k SWUs. On the horizon, there are deals for approximately 4.1M SWU.

  7. The Video Suggestibility Scale for Children: how generalizable is children's performance to other measures of suggestibility?

    PubMed

    McFarlane, Felicity; Powell, Martine B

    2002-01-01

    This study explored the generalizability of the Video Suggestibility Scale for Children (VSSC), which was developed by Scullin and colleagues (Scullin & Ceci, 2001; Scullin & Hembrooke, 1998) as a tool for discriminating among children (aged three to five years) who have different levels of suggestibility. The VSSC consists of two subscales; Yield (a measure of children's willingness to acquiesce to misleading questions) and Shift (a measure of children's tendency to change their responses after feedback from the interviewer). Children's (N = 77) performance on each of the subscales was compared with their performance using several other measures of suggestibility. These measures included children's willingness to assent to a false event as well as the number of false interviewer suggestions and false new details that the children provided when responding to cued-recall questions about an independent true-biased and an independent false (non-experienced) event. An independent samples t-test revealed that those children who assented to the false event generated higher scores on the Yield measure. Hierarchical regression analyses revealed that Yield was a significant predictor of the number of false details reported about the false activity, but not the true-biased activity. There was no significant relationship between the Shift subscale and any of the dependent variables. The potential contribution of the VSSC for forensic researchers and practitioners is discussed. PMID:12465135

  8. Strongly correlated quantum spin liquid in herbertsmithite

    SciTech Connect

    Shaginyan, V. R.; Popov, K. G.; Khodel, V. A.

    2013-05-15

    Strongly correlated Fermi systems are among the most intriguing and fundamental systems in physics. We show that the herbertsmithite ZnCu{sub 3}(OH){sub 6}Cl{sub 2} can be regarded as a new type of strongly correlated electrical insulator that possesses properties of heavy-fermion metals with one exception: it resists the flow of electric charge. We demonstrate that herbertsmithite's low-temperature properties are defined by a strongly correlated quantum spin liquid made with hypothetic particles such as fermionic spinons that carry spin 1/2 and no charge. Our calculations of its thermodynamic and relaxation properties are in good agreement with recent experimental facts and allow us to reveal their scaling behavior, which strongly resembles that observed in heavy-fermion metals. Analysis of the dynamic magnetic susceptibility of strongly correlated Fermi systems suggests that there exist at least two types of its scaling.

  9. 29 CFR 785.45 - Suggestion systems.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Suggestion systems. 785.45 Section 785.45 Labor Regulations..., Medical Attention, Civic and Charitable Work, and Suggestion Systems § 785.45 Suggestion systems... general suggestion system is not working time, but if employees are permitted to work on...

  10. Simulations suggest pharmacological methods for rescuing long-term potentiation.

    PubMed

    Smolen, Paul; Baxter, Douglas A; Byrne, John H

    2014-11-01

    Congenital cognitive dysfunctions are frequently due to deficits in molecular pathways that underlie the induction or maintenance of synaptic plasticity. For example, Rubinstein-Taybi syndrome (RTS) is due to a mutation in cbp, encoding the histone acetyltransferase CREB-binding protein (CBP). CBP is a transcriptional co-activator for CREB, and induction of CREB-dependent transcription plays a key role in long-term memory (LTM). In animal models of RTS, mutations of cbp impair LTM and late-phase long-term potentiation (LTP). As a step toward exploring plausible intervention strategies to rescue the deficits in LTP, we extended our previous model of LTP induction to describe histone acetylation and simulated LTP impairment due to cbp mutation. Plausible drug effects were simulated by model parameter changes, and many increased LTP. However no parameter variation consistent with a effect of a known drug class fully restored LTP. Thus we examined paired parameter variations consistent with effects of known drugs. A pair that simulated the effects of a phosphodiesterase inhibitor (slowing cAMP degradation) concurrent with a deacetylase inhibitor (prolonging histone acetylation) restored normal LTP. Importantly these paired parameter changes did not alter basal synaptic weight. A pair that simulated the effects of a phosphodiesterase inhibitor and an acetyltransferase activator was similarly effective. For both pairs strong additive synergism was present. The effect of the combination was greater than the summed effect of the separate parameter changes. These results suggest that promoting histone acetylation while simultaneously slowing the degradation of cAMP may constitute a promising strategy for restoring deficits in LTP that may be associated with learning deficits in RTS. More generally these results illustrate how the strategy of combining modeling and empirical studies may provide insights into the design of effective therapies for improving long-term synaptic

  11. Smoking Harms Black Americans' Kidneys, Study Suggests

    MedlinePlus

    ... medlineplus/news/fullstory_159032.html Smoking Harms Black Americans' Kidneys, Study Suggests Researchers say inflammation or cigarette ... a significant risk to kidney health for black Americans, new research suggests. The study included more than ...

  12. Strongly magnetized accretion discs require poloidal flux

    NASA Astrophysics Data System (ADS)

    Salvesen, Greg; Armitage, Philip J.; Simon, Jacob B.; Begelman, Mitchell C.

    2016-08-01

    Motivated by indirect observational evidence for strongly magnetized accretion discs around black holes, and the novel theoretical properties of such solutions, we investigate how a strong magnetization state can develop and persist. To this end, we perform local simulations of accretion discs with an initially purely toroidal magnetic field of equipartition strength. We demonstrate that discs with zero net vertical magnetic flux and realistic boundary conditions cannot sustain a strong toroidal field. However, a magnetic pressure-dominated disc can form from an initial configuration with a sufficient amount of net vertical flux and realistic boundary conditions. Our results suggest that poloidal flux is a necessary prerequisite for the sustainability of strongly magnetized accretion discs.

  13. Strongly magnetized accretion discs require poloidal flux

    NASA Astrophysics Data System (ADS)

    Salvesen, Greg; Armitage, Philip J.; Simon, Jacob B.; Begelman, Mitchell C.

    2016-05-01

    Motivated by indirect observational evidence for strongly magnetized accretion discs around black holes, and the novel theoretical properties of such solutions, we investigate how a strong magnetization state can develop and persist. To this end, we perform local simulations of accretion discs with an initially purely toroidal magnetic field of equipartition strength. We demonstrate that discs with zero net vertical magnetic flux and realistic boundary conditions cannot sustain a strong toroidal field. However, a magnetic pressure-dominated disc can form from an initial configuration with a sufficient amount of net vertical flux and realistic boundary conditions. Our results suggest that poloidal flux is a necessary prerequisite for the sustainability of strongly magnetized accretion discs.

  14. Effects of stereotypes and suggestion on memory.

    PubMed

    Shechory, Mally; Nachson, Israel; Glicksohn, Joseph

    2010-02-01

    In this study, the interactive effect of stereotype and suggestion on accuracy of memory was examined by presenting 645 participants (native Israelis and immigrants from the former Soviet Union and Ethiopia) with three versions of a story about a worker who is waiting in a manager's office for a meeting. All versions were identical except for the worker's name, which implied a Russian or an Ethiopian immigrant or a person of no ethnic origin. Each participant was presented with one version of the story. After an hour delay, the participants' memories were tested via two questionnaires that differed in terms of level of suggestion. Data analyses show that (a) when a suggestion matched the participant's stereotypical perception, the suggestion was incorporated into memory but (b) when the suggestion contradicted the stereotype, it did not influence memory. The conclusion was that recall is influenced by stereotypes but can be enhanced by compatible suggestions. PMID:18662974

  15. Hypnotizability, not suggestion, influences false memory development.

    PubMed

    Dasse, Michelle N; Elkins, Gary R; Weaver, Charles A

    2015-01-01

    Hypnotizability influences the development of false memories. In Experiment 1, participants heard a positive or negative suggestion regarding hypnosis and then listened to 8 Deese-Roediger-McDermott (DRM) false memory paradigm lists in a hypnotic state. Neither hypnosis nor prehypnotic suggestion affected memory. Highly hypnotizable participants were more accurate in recall and recognition. In Experiment 2, suggestions were delivered in the form of feedback. Participants heard a positive or negative suggestion about their performance prior to either the encoding or retrieval of 8 DRM lists. Neither accurate nor false memories were affected by the suggestion. Highly hypnotizable individuals recognized fewer critical lures if they received a negative suggestion about their performance. These results highlight the unusual role of hypnotizability in the creation of false memories. PMID:25365130

  16. Individual personality characteristics related to suggestibility.

    PubMed

    Van Hook, Cheryl W; Steele, Connie

    2002-12-01

    The current study investigated the relationship between suggestibility of memory, personality characteristics identified by the Millon Index of Personality Traits, and tolerance for ambiguity measured by MacDonald's Ambiguity Tolerance-20. 85 female and 16 male college students were assigned to either an experimental group receiving the suggestive information or a control group. Suggestibility was assessed using Lindberg's suggestibility measure consisting of a short video, followed by a questionnaire used to assess memory, and a second administration one week later. Logistical regression analyses were used to construct a model of the personality characteristics predictive of suggestibility and indicated that susceptibility to suggestive information may differ across personalities for variables such as sensing, innovating, agreeing, and low tolerance of ambiguity. PMID:12530759

  17. Electrophoresis in strong electric fields.

    PubMed

    Barany, Sandor

    2009-01-01

    Two kinds of non-linear electrophoresis (ef) that can be detected in strong electric fields (several hundred V/cm) are considered. The first ("classical" non-linear ef) is due to the interaction of the outer field with field-induced ionic charges in the electric double layer (EDL) under conditions, when field-induced variations of electrolyte concentration remain to be small comparatively to its equilibrium value. According to the Shilov theory, the non-linear component of the electrophoretic velocity for dielectric particles is proportional to the cubic power of the applied field strength (cubic electrophoresis) and to the second power of the particles radius; it is independent of the zeta-potential but is determined by the surface conductivity of particles. The second one, the so-called "superfast electrophoresis" is connected with the interaction of a strong outer field with a secondary diffuse layer of counterions (space charge) that is induced outside the primary (classical) diffuse EDL by the external field itself because of concentration polarization. The Dukhin-Mishchuk theory of "superfast electrophoresis" predicts quadratic dependence of the electrophoretic velocity of unipolar (ionically or electronically) conducting particles on the external field gradient and linear dependence on the particle's size in strong electric fields. These are in sharp contrast to the laws of classical electrophoresis (no dependence of V(ef) on the particle's size and linear dependence on the electric field gradient). A new method to measure the ef velocity of particles in strong electric fields is developed that is based on separation of the effects of sedimentation and electrophoresis using videoimaging and a new flowcell and use of short electric pulses. To test the "classical" non-linear electrophoresis, we have measured the ef velocity of non-conducting polystyrene, aluminium-oxide and (semiconductor) graphite particles as well as Saccharomice cerevisiae yeast cells as a

  18. Promoting Strong Written Communication Skills

    NASA Astrophysics Data System (ADS)

    Narayanan, M.

    2015-12-01

    The reason that an improvement in the quality of technical writing is still needed in the classroom is due to the fact that universities are facing challenging problems not only on the technological front but also on the socio-economic front. The universities are actively responding to the changes that are taking place in the global consumer marketplace. Obviously, there are numerous benefits of promoting strong written communication skills. They can be summarized into the following six categories. First, and perhaps the most important: The University achieves learner satisfaction. The learner has documented verbally, that the necessary knowledge has been successfully acquired. This results in learner loyalty that in turn will attract more qualified learners.Second, quality communication lowers the cost per pupil, consequently resulting in increased productivity backed by a stronger economic structure and forecast. Third, quality communications help to improve the cash flow and cash reserves of the university. Fourth, having high quality communication enables the university to justify the need for high costs of tuition and fees. Fifth, better quality in written communication skills result in attracting top-quality learners. This will lead to happier and satisfied learners, not to mention greater prosperity for the university as a whole. Sixth, quality written communication skills result in reduced complaints, thus meaning fewer hours spent on answering or correcting the situation. The University faculty and staff are thus able to devote more time on scholarly activities, meaningful research and productive community service. References Boyer, Ernest L. (1990). Scholarship reconsidered: Priorities of the Professorate.Princeton, NJ: Carnegie Foundation for the Advancement of Teaching. Hawkins, P., & Winter, J. (1997). Mastering change: Learning the lessons of the enterprise.London: Department for Education and Employment. Buzzel, Robert D., and Bradley T. Gale. (1987

  19. Strongly correlated perovskite fuel cells.

    PubMed

    Zhou, You; Guan, Xiaofei; Zhou, Hua; Ramadoss, Koushik; Adam, Suhare; Liu, Huajun; Lee, Sungsik; Shi, Jian; Tsuchiya, Masaru; Fong, Dillon D; Ramanathan, Shriram

    2016-06-01

    Fuel cells convert chemical energy directly into electrical energy with high efficiencies and environmental benefits, as compared with traditional heat engines. Yttria-stabilized zirconia is perhaps the material with the most potential as an electrolyte in solid oxide fuel cells (SOFCs), owing to its stability and near-unity ionic transference number. Although there exist materials with superior ionic conductivity, they are often limited by their ability to suppress electronic leakage when exposed to the reducing environment at the fuel interface. Such electronic leakage reduces fuel cell power output and the associated chemo-mechanical stresses can also lead to catastrophic fracture of electrolyte membranes. Here we depart from traditional electrolyte design that relies on cation substitution to sustain ionic conduction. Instead, we use a perovskite nickelate as an electrolyte with high initial ionic and electronic conductivity. Since many such oxides are also correlated electron systems, we can suppress the electronic conduction through a filling-controlled Mott transition induced by spontaneous hydrogen incorporation. Using such a nickelate as the electrolyte in free-standing membrane geometry, we demonstrate a low-temperature micro-fabricated SOFC with high performance. The ionic conductivity of the nickelate perovskite is comparable to the best-performing solid electrolytes in the same temperature range, with a very low activation energy. The results present a design strategy for high-performance materials exhibiting emergent properties arising from strong electron correlations. PMID:27279218

  20. Strongly correlated perovskite fuel cells

    NASA Astrophysics Data System (ADS)

    Zhou, You; Guan, Xiaofei; Zhou, Hua; Ramadoss, Koushik; Adam, Suhare; Liu, Huajun; Lee, Sungsik; Shi, Jian; Tsuchiya, Masaru; Fong, Dillon D.; Ramanathan, Shriram

    2016-06-01

    Fuel cells convert chemical energy directly into electrical energy with high efficiencies and environmental benefits, as compared with traditional heat engines. Yttria-stabilized zirconia is perhaps the material with the most potential as an electrolyte in solid oxide fuel cells (SOFCs), owing to its stability and near-unity ionic transference number. Although there exist materials with superior ionic conductivity, they are often limited by their ability to suppress electronic leakage when exposed to the reducing environment at the fuel interface. Such electronic leakage reduces fuel cell power output and the associated chemo-mechanical stresses can also lead to catastrophic fracture of electrolyte membranes. Here we depart from traditional electrolyte design that relies on cation substitution to sustain ionic conduction. Instead, we use a perovskite nickelate as an electrolyte with high initial ionic and electronic conductivity. Since many such oxides are also correlated electron systems, we can suppress the electronic conduction through a filling-controlled Mott transition induced by spontaneous hydrogen incorporation. Using such a nickelate as the electrolyte in free-standing membrane geometry, we demonstrate a low-temperature micro-fabricated SOFC with high performance. The ionic conductivity of the nickelate perovskite is comparable to the best-performing solid electrolytes in the same temperature range, with a very low activation energy. The results present a design strategy for high-performance materials exhibiting emergent properties arising from strong electron correlations.

  1. A Suggested Management System for Secondary Migrant Counselors.

    ERIC Educational Resources Information Center

    Vela, Jesus, Jr.

    A suggested management system for secondary migrant counselors is the second part of a guide to help migrant counselors meet the special needs of migrant students. It includes a list of counselors' competencies and suggested calendars of academic, vocational, and social activities. Competencies include organizing pre-registration and registration…

  2. Maltreated Children's Memory: Accuracy, Suggestibility, and Psychopathology

    ERIC Educational Resources Information Center

    Eisen, Mitchell L.; Goodman, Gail S.; Qin, Jianjian; Davis, Suzanne; Crayton, John

    2007-01-01

    Memory, suggestibility, stress arousal, and trauma-related psychopathology were examined in 328 3- to 16-year-olds involved in forensic investigations of abuse and neglect. Children's memory and suggestibility were assessed for a medical examination and venipuncture. Being older and scoring higher in cognitive functioning were related to fewer…

  3. Suggested Learnings: Consumer and Homemaking Education.

    ERIC Educational Resources Information Center

    Edmondson, Dorothy Jean; Swanson, Bettye B.

    The guide presents suggested learning concepts, experiences, and references for home economics educators in the planning and organization of secondary level consumer and homemaking programs. The suggestions are based on questionnaires and interviews with teachers and administrators involved in this program. The guide's main focus is on the process…

  4. The Conceptual Elements of Strong Interventions in School Settings.

    ERIC Educational Resources Information Center

    Lentz, Francis E., Jr.; And Others

    1996-01-01

    Presents a conceptual model of strong school-based interventions. Notes strong interventions are ecological in nature, naturalistic in scope, contain elements from the research base that are predictive for success, and incorporate the constructs of social validity in a practical manner. Provides suggestions and implications for strong school-based…

  5. Induction Technique: Beyond Simple Response to Suggestion.

    PubMed

    Barabasz, Arreed; Barabasz, Marianne

    2016-10-01

    The hypnotic induction is intended to induce hypnosis. This implies that what is sought is intended to go beyond what might be wrought by mere suggestion, expectancy, and social influence. The experimentally controlled research showing that the induction makes a difference and how small changes in wording of suggestions can produce orthogonal responses is briefly reviewed. This article explains the principles of induction and three critical phases of hypnotic induction in detail. An arm levitation scripted protocol demonstrating how to respond to the patient using the three phases to maximize responses to hypnotic suggestions is presented. PMID:27586048

  6. Suggested Minimum Cataloging Standards for Arizona.

    ERIC Educational Resources Information Center

    Scott, Sharon

    1979-01-01

    Notes problems with cataloging library materials in the small and medium sized public library and suggests interpretations of the Anglo-American cataloging rules, with recommendations for their adaptation to smaller libraries. (CWM)

  7. Social suggestibility to central and peripheral misinformation.

    PubMed

    Dalton, Andrea L; Daneman, Meredyth

    2006-05-01

    This study used a laboratory-based paradigm to investigate social influences on participants' susceptibility to misleading suggestions. Participants viewed a video clip of an action sequence with one or more peers, and then were required to discuss the event with the co-witness or with the group of co-witnesses. During the discussion a confederate, posing as a peer, presented misinformation about central and peripheral features of the co-witnessed event. Results indicated that participants were more susceptible to misleading suggestions during one-on-one discussions than during group discussions. In addition, participants were susceptible to misleading suggestions about central features of the witnessed event, although to a lesser extent than they were susceptible to misleading suggestions about peripheral features. PMID:16766450

  8. No Statins Before Heart Surgery, Study Suggests

    MedlinePlus

    ... harm, a new study suggests. In that setting, Crestor (rosuvastatin) did not prevent either the abnormal heart rhythm ... who were having elective heart surgery to take Crestor or a placebo before surgery. The researchers found ...

  9. Electronic Reference Services: Some Suggested Guidelines.

    ERIC Educational Resources Information Center

    Sloan, Bernie

    1998-01-01

    Suggests guidelines to help libraries formalize their electronic reference services. Covers the following issues: administration/management (library division/department, library administration, campus administration, academic departments); services; primary clientele; personnel; infrastructure/facilities; finances; and evaluation. (AEF)

  10. Credible suggestions affect false autobiographical beliefs.

    PubMed

    Scoboria, Alan; Wysman, Lauren; Otgaar, Henry

    2012-07-01

    False memory implantation studies are characterised by suggestions indicating that specific unremembered events occurred, attributing suggested events to a knowledgeable source (e.g., parents), and including true events that provide evidence that this source was consulted. These characteristics create a particular retrieval context that influences how individuals come to believe that false events occurred. Two studies used a variant of implantation methods to vary the proportion of events attributed to parents and the presence of true events within the suggestion. In Study 1 participants received six false events, and were told that all or some events came from parents. Participants told that all of the events came from parents formed more and stronger false beliefs. In Study 2 participants also received two true events, and a third group was told that half of the events came from their parents. Participants given the specific ratio ("half") endorsed more false beliefs, and beliefs between the other groups no longer differed. Across both studies participants told that some events came from parents reported stronger memory phenomenology. The effect of suggestions on false beliefs in implantation studies depends partly on the credibility of suggestions derived from providing information about the source of suggested events. PMID:22537029

  11. Strong-back safety latch

    SciTech Connect

    DeSantis, G.N.

    1995-03-06

    The calculation decides the integrity of the safety latch that will hold the strong-back to the pump during lifting. The safety latch will be welded to the strong-back and will latch to a 1.5-in. dia cantilever rod welded to the pump baseplate. The static and dynamic analysis shows that the safety latch will hold the strong-back to the pump if the friction clamps fail and the pump become free from the strong-back. Thus, the safety latch will meet the requirements of the Lifting and Rigging Manual for under the hook lifting for static loading; it can withstand shock loads from the strong-back falling 0.25 inch.

  12. Recent advances of strong-strong beam-beam simulation

    SciTech Connect

    Qiang, Ji; Furman, Miguel A.; Ryne, Robert D.; Fischer, Wolfram; Ohmi,Kazuhito

    2004-09-15

    In this paper, we report on recent advances in strong-strong beam-beam simulation. Numerical methods used in the calculation of the beam-beam forces are reviewed. A new computational method to solve the Poisson equation on nonuniform grid is presented. This method reduces the computational cost by a half compared with the standard FFT based method on uniform grid. It is also more accurate than the standard method for a colliding beam with low transverse aspect ratio. In applications, we present the study of coherent modes with multi-bunch, multi-collision beam-beam interactions at RHIC. We also present the strong-strong simulation of the luminosity evolution at KEKB with and without finite crossing angle.

  13. Measuring Children's Suggestibility in Forensic Interviews.

    PubMed

    Volpini, Laura; Melis, Manuela; Petralia, Stefania; Rosenberg, Melina D

    2016-01-01

    According to the scientific literature, childrens' cognitive development is not complete until adolescence. Therefore, the problems inherent in children serving as witnesses are crucial. In preschool-aged children, false memories may be identified because of misinformation and insight bias. Additionally, they are susceptible of suggestions. The aim of this study was to verify the levels of suggestibility in children between three and 5 years of age. Ninety-two children were examined (44 male, 48 female; M = 4.5 years, SD = 9.62). We used the correlation coefficient (Pearson's r) and the averages variance by SPSS statistical program. The results concluded that: younger children are almost always more susceptible to suggestibility. The dimension of immediate recall was negatively correlates with that of total suggestibility (r = -0.357 p < 0.001). Social compliance and source monitoring errors contribute to patterns of suggestibility, because older children shift their answers more often (r = 0.394 p < 0.001). Younger children change their answers more times (r = -0.395 p < 0.001). PMID:27404406

  14. Genetic Variations in the TP53 Pathway in Native Americans Strongly Suggest Adaptation to the High Altitudes of the Andes.

    PubMed

    Jacovas, Vanessa Cristina; Rovaris, Diego Luiz; Peréz, Orlando; de Azevedo, Soledad; Macedo, Gabriel Souza; Sandoval, José Raul; Salazar-Granara, Alberto; Villena, Mercedes; Dugoujon, Jean-Michel; Bisso-Machado, Rafael; Petzl-Erler, Maria Luiza; Salzano, Francisco Mauro; Ashton-Prolla, Patricia; Ramallo, Virginia; Bortolini, Maria Cátira

    2015-01-01

    The diversity of the five single nucleotide polymorphisms located in genes of the TP53 pathway (TP53, rs1042522; MDM2, rs2279744; MDM4, rs1563828; USP7, rs1529916; and LIF, rs929271) were studied in a total of 282 individuals belonging to Quechua, Aymara, Chivay, Cabanaconde, Yanke, Taquile, Amantani, Anapia, Uros, Guarani Ñandeva, and Guarani Kaiowá populations, characterized as Native American or as having a high level (> 90%) of Native American ancestry. In addition, published data pertaining to 100 persons from five other Native American populations (Surui, Karitiana, Maya, Pima, and Piapoco) were analyzed. The populations were classified as living in high altitude (≥ 2,500 m) or in lowlands (< 2,500 m). Our analyses revealed that alleles USP7-G, LIF-T, and MDM2-T showed significant evidence that they were selected for in relation to harsh environmental variables related to high altitudes. Our results show for the first time that alleles of classical TP53 network genes have been evolutionary co-opted for the successful human colonization of the Andes. PMID:26382048

  15. Genetic Variations in the TP53 Pathway in Native Americans Strongly Suggest Adaptation to the High Altitudes of the Andes

    PubMed Central

    Peréz, Orlando; de Azevedo, Soledad; Macedo, Gabriel Souza; Sandoval, José Raul; Salazar-Granara, Alberto; Villena, Mercedes; Dugoujon, Jean-Michel; Bisso-Machado, Rafael; Petzl-Erler, Maria Luiza; Salzano, Francisco Mauro; Ashton-Prolla, Patricia; Ramallo, Virginia; Bortolini, Maria Cátira

    2015-01-01

    The diversity of the five single nucleotide polymorphisms located in genes of the TP53 pathway (TP53, rs1042522; MDM2, rs2279744; MDM4, rs1563828; USP7, rs1529916; and LIF, rs929271) were studied in a total of 282 individuals belonging to Quechua, Aymara, Chivay, Cabanaconde, Yanke, Taquile, Amantani, Anapia, Uros, Guarani Ñandeva, and Guarani Kaiowá populations, characterized as Native American or as having a high level (> 90%) of Native American ancestry. In addition, published data pertaining to 100 persons from five other Native American populations (Surui, Karitiana, Maya, Pima, and Piapoco) were analyzed. The populations were classified as living in high altitude (≥ 2,500 m) or in lowlands (< 2,500 m). Our analyses revealed that alleles USP7-G, LIF-T, and MDM2-T showed significant evidence that they were selected for in relation to harsh environmental variables related to high altitudes. Our results show for the first time that alleles of classical TP53 network genes have been evolutionary co-opted for the successful human colonization of the Andes. PMID:26382048

  16. Titanium: light, strong, and white

    USGS Publications Warehouse

    Woodruff, Laurel; Bedinger, George

    2013-01-01

    Titanium (Ti) is a strong silver-gray metal that is highly resistant to corrosion and is chemically inert. It is as strong as steel but 45 percent lighter, and it is twice as strong as aluminum but only 60 percent heavier. Titanium dioxide (TiO2) has a very high refractive index, which means that it has high light-scattering ability. As a result, TiO2 imparts whiteness, opacity, and brightness to many products. ...Because of the unique physical properties of titanium metal and the whiteness provided by TiO2, titanium is now used widely in modern industrial societies.

  17. Autonomic responses to suggestions for cold and warmth in hypnosis.

    PubMed

    Kistler, A; Mariauzouls, C; Wyler, F; Bircher, A J; Wyler-Harper, J

    1999-02-01

    The goal of the present study was to investigate whether suggestions for cold or warmth during hypnosis affect fingertip skin temperature. Hypnosis without specific suggestions for cold or warmth ('neutral hypnosis') caused a drop in respiration frequency, however, pulse rate, fingertip skin temperature, and electrodermal activity were not affected. The cold and warmth suggestions decreased and increased fingertip skin temperature, respectively. Compared with the neutral trance phase, the other three autonomic variables measured were also affected by suggestions for cold. However, there was no association between the changes in autonomic variables induced by suggestions and hypnotizability scores measured by the 'Stanford Hypnotic Clinical Scale for Adults'. Fingertip skin temperature was mostly affected when the images used for the cold and warmth suggestions during hypnosis included experiences of physical temperature and psychological stress or relaxation, indicating that the psychological content of the imagery amplified the autonomic response. PMID:10213875

  18. Leadership Theories--Managing Practices, Challenges, Suggestions

    ERIC Educational Resources Information Center

    Hawkins, Cheryl

    2009-01-01

    A shortage of community college executives due to the number of retirements occurring among current leaders is predicted. An examination of three leadership theories--servant-leadership, business leadership and transformational leadership--suggests techniques for potential community college leaders. Servant-leaders focus on the needs of their…

  19. Suggestions for Career Exploration and Job Seeking.

    ERIC Educational Resources Information Center

    New York State Dept. of Labor, Albany.

    This booklet, which is intended for individuals seeking jobs in New York State, consists of suggestions for career exploration and job seeking. The booklet begins with a brief discussion of places to begin a job search: New York State Job Service and community service centers; schools and community organizations providing free advice; libraries;…

  20. Qualitative Research Articles: Guidelines, Suggestions and Needs

    ERIC Educational Resources Information Center

    Crescentini, Alberto; Mainardi, Giuditta

    2009-01-01

    Purpose: The purpose of this paper is to give ideas and suggestions to avoid some typical problems of qualitative articles. The aim is not to debate quality in qualitative research but to indicate some practical solutions. Design/methodology/approach: The paper discusses the design of qualitative research and the structure of a qualitative article…

  1. Accounting: Suggested Content for Postsecondary Tax Course

    ERIC Educational Resources Information Center

    King, Patricia H.; Morgan, Samuel D.

    1978-01-01

    Surveys of community college graduates and of certified public accountants were made to determine employment relevance of the accounting curriculum. The article suggests topics from the study data which should be included in taxation courses, e.g., income tax accounting, corporate taxation accounting, and tax law. (MF)

  2. Family Living: Suggestions for Effective Parenting.

    ERIC Educational Resources Information Center

    Katz, Lilian G.; And Others

    Suggestions for effective parenting of preschool children are provided in 33 brief articles on children's feelings concerning self-esteem; fear; adopted children; the birth of a sibling; death; depression; and coping with stress, trauma, and divorce. Children's behavior is discussed in articles on toddlers' eating habits, punishment and…

  3. Suggested Universals in the Ontogenesis of Grammar.

    ERIC Educational Resources Information Center

    Slobin, Dan I.

    This paper represents a preliminary attempt to determine universals of grammatical development in children. On the basis of language acquisition data, a limited number of findings are presented in the form of suggested developmental universals. These universals are grouped according to the psychological variables which may determine them, in the…

  4. Minimum Competency Program, Citizenship: Suggestions for Implementation.

    ERIC Educational Resources Information Center

    Virginia State Dept. of Education, Richmond.

    This monograph explains the need for graduating high school seniors to demonstrate minimum competence in citizenship and suggests performance-related assessment tasks to help school authorities determine whether these competency requirements have been met. Minimum citizenship competencies are interpreted to include essential skills and concepts…

  5. Current Research: 2013 Summer Reading Suggestions

    ERIC Educational Resources Information Center

    Journal of College Science Teaching, 2013

    2013-01-01

    To supplement the summer reading of National Science Teachers Association (NSTA) members, the NSTA Committee on Research in Science Education suggested a list of science education research articles that were published in the journals of NSTA's affiliates in 2012. These articles covered a variety of topics that include learning about…

  6. Technology Is Power: Suggestions for Beginning Teachers

    ERIC Educational Resources Information Center

    Shanklin, Nancy

    2010-01-01

    Shanklin knows it can be hard for new teachers to incorporate all they know about technology with the realities of a classroom. She suggests setting incremental, monthly technology goals; investing in equipment; assessing students' grasp of the technology at their disposal and their use of it in classroom projects; searching purposefully for…

  7. Suggestions for Structuring a Research Article

    ERIC Educational Resources Information Center

    Klein, James D.; Reiser, Robert A.

    2014-01-01

    Researchers often experience difficulty as they attempt to prepare journal articles that describe their work. The purpose of this article is to provide researchers in the field of education with a series of suggestions as to how to clearly structure each section of a research manuscript that they intend to submit for publication in a scholarly…

  8. Simulating strongly correlated electrons with a strongly interacting Fermi gas

    SciTech Connect

    Thomas, John E.

    2013-05-28

    The quantum many-body physics of strongly-correlated fermions is studied in a degenerate, strongly- interacting atomic Fermi gas, first realized by our group with DOE support in 2002. This system, which exhibits strong spin pairing, is now widely studied and provides an important paradigm for testing predictions based on state-of-the-art many-body theory in fields ranging from nuclear matter to high temperature superfluidity and superconductivity. As the system is strongly interacting, both the superfluid and the normal fluid are nontrivial and of great interest. A central part of our program on Fermi gases is the connection between the study of thermodynamics, supported by DOE and the study of hydrodynamic transport, supported by NSF. This connection is especially interesting in view of a recent conjecture from the string theory community on the concept of nearly perfect normal fluids, which exhibit a minimum ratio of shear viscosity to entropy density in strongly-interacting, scale-invariant systems.

  9. Strong Coupling between Nanoscale Metamaterials and Phonons

    SciTech Connect

    Shelton, David J.; Brener, Igal; Ginn, James C.; Sinclair, Michael B.; Peters, David W.; Coffey, Kevin R.; Boreman, Glenn D.

    2011-05-11

    We use split ring resonators (SRRs) at optical frequencies to study strong coupling between planar metamaterials and phonon vibrations in nanometer-scale dielectric layers. A series of SRR metamaterials were fabricated on a semiconductor wafer with a thin intervening SiO{sub 2} dielectric layer. The dimensions of the SRRs were varied to tune the fundamental metamaterial resonance across the infrared (IR) active phonon band of SiO{sub 2} at 130 meV (31 THz). Strong anticrossing of these resonances was observed, indicative of strong coupling between metamaterial and phonon excitations. This coupling is very general and can occur with any electrically polarizable resonance including phonon vibrations in other thin film materials and semiconductor band-to-band transitions in the near to far IR. These effects may be exploited to reduce loss and to create unique spectral features that are not possible with metamaterials alone.

  10. Vacuum birefringence in strong inhomogeneous electromagnetic fields

    NASA Astrophysics Data System (ADS)

    Karbstein, Felix; Gies, Holger; Reuter, Maria; Zepf, Matt

    2015-10-01

    Birefringence is one of the fascinating properties of the vacuum of quantum electrodynamics (QED) in strong electromagnetic fields. The scattering of linearly polarized incident probe photons into a perpendicularly polarized mode provides a distinct signature of the optical activity of the quantum vacuum and thus offers an excellent opportunity for a precision test of nonlinear QED. Precision tests require accurate predictions and thus a theoretical framework that is capable of taking the detailed experimental geometry into account. We derive analytical solutions for vacuum birefringence which include the spatio-temporal field structure of a strong optical pump laser field and an x-ray probe. We show that the angular distribution of the scattered photons depends strongly on the interaction geometry and find that scattering of the perpendicularly polarized scattered photons out of the cone of the incident probe x-ray beam is the key to making the phenomenon experimentally accessible with the current generation of FEL/high-field laser facilities.

  11. Cajal's brief experimentation with hypnotic suggestion.

    PubMed

    Stefanidou, Maria; Solà, Carme; Kouvelas, Elias; del Cerro, Manuel; Triarhou, Lazaros C

    2007-01-01

    Spanish histologist Santiago Ramón y Cajal, one of the most notable figures in Neuroscience, and winner, along with Camillo Golgi, of the 1906 Nobel Prize in Physiology or Medicine for his discoveries on the structure of the nervous system, did not escape experimenting with some of the psychiatric techniques available at the time, mainly hypnotic suggestion, albeit briefly. While a physician in his thirties, Cajal published a short article under the title, "Pains of labour considerably attenuated by hypnotic suggestion" in Gaceta Médica Catalana. That study may be Cajal's only documented case in the field of experimental psychology. We here provide an English translation of the original Spanish text, placing it historically within Cajal's involvement with some of the key scientific and philosophical issues at the time. PMID:17966053

  12. Simple nonlinear models suggest variable star universality

    NASA Astrophysics Data System (ADS)

    Lindner, John F.; Kohar, Vivek; Kia, Behnam; Hippke, Michael; Learned, John G.; Ditto, William L.

    2016-02-01

    Dramatically improved data from observatories like the CoRoT and Kepler spacecraft have recently facilitated nonlinear time series analysis and phenomenological modeling of variable stars, including the search for strange (aka fractal) or chaotic dynamics. We recently argued [Lindner et al., Phys. Rev. Lett. 114 (2015) 054101] that the Kepler data includes "golden" stars, whose luminosities vary quasiperiodically with two frequencies nearly in the golden ratio, and whose secondary frequencies exhibit power-law scaling with exponent near -1.5, suggesting strange nonchaotic dynamics and singular spectra. Here we use a series of phenomenological models to make plausible the connection between golden stars and fractal spectra. We thereby suggest that at least some features of variable star dynamics reflect universal nonlinear phenomena common to even simple systems.

  13. [Suggestions to improve dentist-endodontist collaboration].

    PubMed

    Zabalegui, B; Zabalegui, I; Flores, L

    1989-01-01

    Referrals from the general dentist to the endodontist are in some occasions complicated with lack of proper communication among dentist-patient-specialist, resulting in the loss of confidence or even the patient. Suggestions to improve this communication are discussed, which will provide the patient a higher confidence in the indicated endodontic treatment and a better dental service. It will also enhance the prestige of the general dentists' and specialists' practice. PMID:2640034

  14. SUGGESTED OPERATING PROCEDURES FOR AQUIFER PUMPING TESTS

    EPA Science Inventory

    There has been an increased interest in ground water resources throughout the United States. This interest has resulted from a combination of an increase in fund water development for public and domestic use; an increase in mining, agricultural, and industrial activities which mi...

  15. Strongly Secure Linear Network Coding

    NASA Astrophysics Data System (ADS)

    Harada, Kunihiko; Yamamoto, Hirosuke

    In a network with capacity h for multicast, information Xh=(X1, X2, …, Xh) can be transmitted from a source node to sink nodes without error by a linear network code. Furthermore, secret information Sr=(S1, S2, …, Sr) can be transmitted securely against wiretappers by k-secure network coding for k≤h-r. In this case, no information of the secret leaks out even if an adversary wiretaps k edges, i. e. channels. However, if an adversary wiretaps k+1 edges, some Si may leak out explicitly. In this paper, we propose strongly k-secure network coding based on strongly secure ramp secret sharing schemes. In this coding, no information leaks out for every (Si1, Si2, …,Sir-j) even if an adversary wiretaps k+j channels. We also give an algorithm to construct a strongly k-secure network code directly and a transform to convert a nonsecure network code to a strongly k-secure network code. Furthermore, some sufficient conditions of alphabet size to realize the strongly k-secure network coding are derived for the case of k

  16. Limits of quantitation - Yet another suggestion

    NASA Astrophysics Data System (ADS)

    Carlson, Jill; Wysoczanski, Artur; Voigtman, Edward

    2014-06-01

    The work presented herein suggests that the limit of quantitation concept may be rendered substantially less ambiguous and ultimately more useful as a figure of merit by basing it upon the significant figure and relative measurement error ideas due to Coleman, Auses and Gram, coupled with the correct instantiation of Currie's detection limit methodology. Simple theoretical results are presented for a linear, univariate chemical measurement system with homoscedastic Gaussian noise, and these are tested against both Monte Carlo computer simulations and laser-excited molecular fluorescence experimental results. Good agreement among experiment, theory and simulation is obtained and an easy extension to linearly heteroscedastic Gaussian noise is also outlined.

  17. Suggesting strategies improves creative visual synthesis.

    PubMed

    Antonietti, A; Martini, E

    2000-04-01

    An experiment assessed whether a figural or an interpretative strategy can enhance creative visual synthesis. 45 undergraduates were presented a set of simple figures and asked to imagine combining them to obtain a whole pattern corresponding to a creative product. In the figurative condition participants were instructed to combine figures in unusual ways; in the interpretative condition they were induced to look for unusual meanings embedded in the combinations; in the control condition no strategy was suggested. Results showed that certain strategies induced a more flexible visual synthesis. PMID:10833724

  18. Guidelines and Suggestions for Balloon Gondola Design

    NASA Technical Reports Server (NTRS)

    Franco, Hugo

    2016-01-01

    The Columbia Scientific Balloon Facility is responsible for ensuring that science payloads meet the appropriate design requirements. The ultimate goal is to ensure that payloads stay within the allowable launch limits as well as survive the termination event. The purpose of this presentation is to provide some general guidelines for Gondola Design. These include rules and reasons on why CSBF has a certain preference and location for certain components within the gondola as well as other suggestions. Additionally, some recommendations are given on how to avoid common pitfalls.

  19. Strong Bragg backscattering in reflectometry

    NASA Astrophysics Data System (ADS)

    Gusakov, E. Z.; Heuraux, S.; Popov, A. Yu

    2009-06-01

    The reflection of the probing microwave occurring in the vicinity of the backscattering Bragg resonance point (far from the cut-off) at a high enough density fluctuation level and leading to a large jump of the reflected wave phase and a corresponding time delay is described analytically using a 1D model. Explicit expressions for the reflection and transmission coefficients are derived and compared against results of numerical modelling. The criteria for transition to the nonlinear regime of strong Bragg backscattering (BBS) is obtained for both O-mode and X-mode reflectometry. It is shown that a strong nonlinear regime of BBS may occur in ITER at the 0.5-2% relative density perturbation level both for the ordinary and extraordinary mode probing. The possibility of probing wave trapping leading to strong enhancement of the electric field and associated high phase variation of the reflected wave due to BBS is demonstrated.

  20. Strongly interacting ultracold polar molecules

    NASA Astrophysics Data System (ADS)

    Gadway, Bryce; Yan, Bo

    2016-08-01

    This paper reviews recent advances in the study of strongly interacting systems of dipolar molecules. Heteronuclear molecules feature large and tunable electric dipole moments, which give rise to long-range and anisotropic dipole–dipole interactions. Ultracold samples of dipolar molecules with long-range interactions offer a unique platform for quantum simulations and the study of correlated many-body physics. We provide an introduction to the physics of dipolar quantum gases, both electric and magnetic, and summarize the multipronged efforts to bring dipolar molecules into the quantum regime. We discuss in detail the recent experimental progress in realizing and studying strongly interacting systems of polar molecules trapped in optical lattices, with particular emphasis on the study of interacting spin systems and non-equilibrium quantum magnetism. Finally, we conclude with a brief discussion of the future prospects for studies of strongly interacting dipolar molecules.

  1. The SNAP Strong Lens Survey

    SciTech Connect

    Marshall, P.

    2005-01-03

    Basic considerations of lens detection and identification indicate that a wide field survey of the types planned for weak lensing and Type Ia SNe with SNAP are close to optimal for the optical detection of strong lenses. Such a ''piggy-back'' survey might be expected even pessimistically to provide a catalogue of a few thousand new strong lenses, with the numbers dominated by systems of faint blue galaxies lensed by foreground ellipticals. After sketching out our strategy for detecting and measuring these galaxy lenses using the SNAP images, we discuss some of the scientific applications of such a large sample of gravitational lenses: in particular we comment on the partition of information between lens structure, the source population properties and cosmology. Understanding this partitioning is key to assessing strong lens cosmography's value as a cosmological probe.

  2. Dinosaur Peptides Suggest Mechanisms of Protein Survival

    PubMed Central

    San Antonio, James D.; Schweitzer, Mary H.; Jensen, Shane T.; Kalluri, Raghu; Buckley, Michael; Orgel, Joseph P. R. O.

    2011-01-01

    Eleven collagen peptide sequences recovered from chemical extracts of dinosaur bones were mapped onto molecular models of the vertebrate collagen fibril derived from extant taxa. The dinosaur peptides localized to fibril regions protected by the close packing of collagen molecules, and contained few acidic amino acids. Four peptides mapped to collagen regions crucial for cell-collagen interactions and tissue development. Dinosaur peptides were not represented in more exposed parts of the collagen fibril or regions mediating intermolecular cross-linking. Thus functionally significant regions of collagen fibrils that are physically shielded within the fibril may be preferentially preserved in fossils. These results show empirically that structure-function relationships at the molecular level could contribute to selective preservation in fossilized vertebrate remains across geological time, suggest a ‘preservation motif’, and bolster current concepts linking collagen structure to biological function. This non-random distribution supports the hypothesis that the peptides are produced by the extinct organisms and suggests a chemical mechanism for survival. PMID:21687667

  3. Dinosaur Peptides Suggest Mechanisms of Protein Survival

    SciTech Connect

    San Antonio, James D.; Schweitzer, Mary H.; Jensen, Shane T.; Kalluri, Raghu; Buckley, Michael; Orgel, Joseph P.R.O.

    2011-09-16

    Eleven collagen peptide sequences recovered from chemical extracts of dinosaur bones were mapped onto molecular models of the vertebrate collagen fibril derived from extant taxa. The dinosaur peptides localized to fibril regions protected by the close packing of collagen molecules, and contained few acidic amino acids. Four peptides mapped to collagen regions crucial for cell-collagen interactions and tissue development. Dinosaur peptides were not represented in more exposed parts of the collagen fibril or regions mediating intermolecular cross-linking. Thus functionally significant regions of collagen fibrils that are physically shielded within the fibril may be preferentially preserved in fossils. These results show empirically that structure-function relationships at the molecular level could contribute to selective preservation in fossilized vertebrate remains across geological time, suggest a 'preservation motif', and bolster current concepts linking collagen structure to biological function. This non-random distribution supports the hypothesis that the peptides are produced by the extinct organisms and suggests a chemical mechanism for survival.

  4. Strong Photoassociation in Ultracold Fermions

    NASA Astrophysics Data System (ADS)

    Jing, Li; Jamison, Alan; Rvachov, Timur; Ebadi, Sepher; Son, Hyungmok; Jiang, Yijun; Zwierlein, Martin; Ketterle, Wolfgang

    2016-05-01

    Despite many studies there are still open questions about strong photoassociation in ultracold gases. Photoassociation occurs only at short range and thus can be used as a tool to probe and control the two-body correlation function in an interacting many-body system and to engineer Hamiltonians using dissipation. We propose the possibility to slow down decoherence by photoassociation through the quantum Zeno effect. This can realized by shining strong photoassociation light on the superposition of the lowest two hyperfine states of Lithium 6. NSF, ARO-MURI, Samsung, NSERC.

  5. Semimetallization of dielectrics in strong optical fields

    DOE PAGESBeta

    Kwon, Ojoon; Paasch-Colberg, Tim; Apalkov, Vadym; Kim, Bum -Kyu; Kim, Ju -Jin; Stockman, Mark I.; Kim, D.

    2016-02-18

    At the heart of ever growing demands for faster signal processing is ultrafast charge transport and control by electromagnetic fields in semiconductors. Intense optical fields have opened fascinating avenues for new phenomena and applications in solids. Because the period of optical fields is on the order of a femtosecond, the current switching and its control by an optical field may pave a way to petahertz optoelectronic devices. Lately, a reversible semimetallization in fused silica on a femtosecond time scale by using a few-cycle strong field (~1 V/Å) is manifested. The strong Wannier-Stark localization and Zener-type tunneling were expected to drivemore » this ultrafast semimetallization. Wider spread of this technology demands better understanding of whether the strong field behavior is universally similar for different dielectrics. Here we employ a carrier-envelope-phase stabilized, few-cycle strong optical field to drive the semimetallization in sapphire, calcium fluoride and quartz and to compare this phenomenon and show its remarkable similarity between them. The similarity in response of these materials, despite the distinguishable differences in their physical properties, suggests the universality of the physical picture explained by the localization of Wannier-Stark states. Lastly, our results may blaze a trail to PHz-rate optoelectronics.« less

  6. Semimetallization of dielectrics in strong optical fields

    PubMed Central

    Kwon, Ojoon; Paasch-Colberg, Tim; Apalkov, Vadym; Kim, Bum-Kyu; Kim, Ju-Jin; Stockman, Mark I.; Kim, D.

    2016-01-01

    At the heart of ever growing demands for faster signal processing is ultrafast charge transport and control by electromagnetic fields in semiconductors. Intense optical fields have opened fascinating avenues for new phenomena and applications in solids. Because the period of optical fields is on the order of a femtosecond, the current switching and its control by an optical field may pave a way to petahertz optoelectronic devices. Lately, a reversible semimetallization in fused silica on a femtosecond time scale by using a few-cycle strong field (~1 V/Å) is manifested. The strong Wannier-Stark localization and Zener-type tunneling were expected to drive this ultrafast semimetallization. Wider spread of this technology demands better understanding of whether the strong field behavior is universally similar for different dielectrics. Here we employ a carrier-envelope-phase stabilized, few-cycle strong optical field to drive the semimetallization in sapphire, calcium fluoride and quartz and to compare this phenomenon and show its remarkable similarity between them. The similarity in response of these materials, despite the distinguishable differences in their physical properties, suggests the universality of the physical picture explained by the localization of Wannier-Stark states. Our results may blaze a trail to PHz-rate optoelectronics. PMID:26888147

  7. Semimetallization of dielectrics in strong optical fields.

    PubMed

    Kwon, Ojoon; Paasch-Colberg, Tim; Apalkov, Vadym; Kim, Bum-Kyu; Kim, Ju-Jin; Stockman, Mark I; Kim, D

    2016-01-01

    At the heart of ever growing demands for faster signal processing is ultrafast charge transport and control by electromagnetic fields in semiconductors. Intense optical fields have opened fascinating avenues for new phenomena and applications in solids. Because the period of optical fields is on the order of a femtosecond, the current switching and its control by an optical field may pave a way to petahertz optoelectronic devices. Lately, a reversible semimetallization in fused silica on a femtosecond time scale by using a few-cycle strong field (~1 V/Å) is manifested. The strong Wannier-Stark localization and Zener-type tunneling were expected to drive this ultrafast semimetallization. Wider spread of this technology demands better understanding of whether the strong field behavior is universally similar for different dielectrics. Here we employ a carrier-envelope-phase stabilized, few-cycle strong optical field to drive the semimetallization in sapphire, calcium fluoride and quartz and to compare this phenomenon and show its remarkable similarity between them. The similarity in response of these materials, despite the distinguishable differences in their physical properties, suggests the universality of the physical picture explained by the localization of Wannier-Stark states. Our results may blaze a trail to PHz-rate optoelectronics. PMID:26888147

  8. Semimetallization of dielectrics in strong optical fields

    NASA Astrophysics Data System (ADS)

    Kwon, Ojoon; Paasch-Colberg, Tim; Apalkov, Vadym; Kim, Bum-Kyu; Kim, Ju-Jin; Stockman, Mark I.; Kim, D.

    2016-02-01

    At the heart of ever growing demands for faster signal processing is ultrafast charge transport and control by electromagnetic fields in semiconductors. Intense optical fields have opened fascinating avenues for new phenomena and applications in solids. Because the period of optical fields is on the order of a femtosecond, the current switching and its control by an optical field may pave a way to petahertz optoelectronic devices. Lately, a reversible semimetallization in fused silica on a femtosecond time scale by using a few-cycle strong field (~1 V/Å) is manifested. The strong Wannier-Stark localization and Zener-type tunneling were expected to drive this ultrafast semimetallization. Wider spread of this technology demands better understanding of whether the strong field behavior is universally similar for different dielectrics. Here we employ a carrier-envelope-phase stabilized, few-cycle strong optical field to drive the semimetallization in sapphire, calcium fluoride and quartz and to compare this phenomenon and show its remarkable similarity between them. The similarity in response of these materials, despite the distinguishable differences in their physical properties, suggests the universality of the physical picture explained by the localization of Wannier-Stark states. Our results may blaze a trail to PHz-rate optoelectronics.

  9. Chest magnetic resonance imaging: a protocol suggestion*

    PubMed Central

    Hochhegger, Bruno; de Souza, Vinícius Valério Silveira; Marchiori, Edson; Irion, Klaus Loureiro; Souza Jr., Arthur Soares; Elias Junior, Jorge; Rodrigues, Rosana Souza; Barreto, Miriam Menna; Escuissato, Dante Luiz; Mançano, Alexandre Dias; Araujo Neto, César Augusto; Guimarães, Marcos Duarte; Nin, Carlos Schuler; Santos, Marcel Koenigkam; Silva, Jorge Luiz Pereira e

    2015-01-01

    In the recent years, with the development of ultrafast sequences, magnetic resonance imaging (MRI) has been established as a valuable diagnostic modality in body imaging. Because of improvements in speed and image quality, MRI is now ready for routine clinical use also in the study of pulmonary diseases. The main advantage of MRI of the lungs is its unique combination of morphological and functional assessment in a single imaging session. In this article, the authors review most technical aspects and suggest a protocol for performing chest MRI. The authors also describe the three major clinical indications for MRI of the lungs: staging of lung tumors; evaluation of pulmonary vascular diseases; and investigation of pulmonary abnormalities in patients who should not be exposed to radiation. PMID:26811555

  10. Extant mammal body masses suggest punctuated equilibrium.

    PubMed

    Mattila, Tiina M; Bokma, Folmer

    2008-10-01

    Is gradual microevolutionary change within species simultaneously the source of macroevolutionary differentiation between species? Since its first publication, Darwin's original idea that phenotypic differences between species develop gradually over time, as the accumulation of small selection-induced changes in successive generations has been challenged by palaeontologists claiming that, instead, new species quickly acquire their phenotypes to remain virtually unchanged until going extinct again. This controversy, widely known as the 'punctuated equilibrium' debate, remained unresolved, largely owing to the difficulty of distinguishing biological species from fossil remains. We analysed body masses of 2143 existing mammal species on a phylogeny comprising 4510 (i.e. nearly all) extant species to estimate rates of gradual (anagenetic) and speciational (cladogenetic) evolution. Our Bayesian estimates from mammals as well as separate sub-clades such as primates and carnivores suggest that gradual evolution is responsible for only a small part of body size variation between mammal species. PMID:18595835

  11. Proactive and retroactive effects of negative suggestion.

    PubMed

    Brown, Alan S; Brown, Christine M; Mosbacher, Joy L; Dryden, W Erich

    2006-11-01

    The negative effects of false information presented either prior to (proactive interference; PI) or following (retroactive interference; RI) true information was examined with word definitions (Experiment 1) and trivia facts (Experiment 2). Participants were explicitly aware of which information was true and false when shown, and true-false discrimination was evaluated via multiple-choice tests. Negative suggestion, defined as poorer performance on interference items than noninterference (control) items, consistently occurred when the wrong information followed the correct information (RI) but not when it preceded the correct information (PI). These effects did not change as a function of retention interval (immediate, 1 week, or 3 weeks) or number of incorrect alternatives (1 or 3). Implications of this outcome for experiencing incorrect information in both academic and nonacademic situations are considered. PMID:17087580

  12. Health Problems of the Navajo Area and Suggested Interventions.

    ERIC Educational Resources Information Center

    Kaltenbach, Charles

    Analysis of morbidity, mortality, and demographic data on Navajo people was undertaken to identify leading health problems in the Navajo area and to suggest intervention activities. Comparisons with total U.S. population were made to provide perspective. Data on Navajo mortality showed: a ratio of male to female deaths of 2:1, more than 50 percent…

  13. Strong coupling electroweak symmetry breaking

    SciTech Connect

    Barklow, T.L.; Burdman, G.; Chivukula, R.S.

    1997-04-01

    The authors review models of electroweak symmetry breaking due to new strong interactions at the TeV energy scale and discuss the prospects for their experimental tests. They emphasize the direct observation of the new interactions through high-energy scattering of vector bosons. They also discuss indirect probes of the new interactions and exotic particles predicted by specific theoretical models.

  14. A strongly coupled anyon material

    NASA Astrophysics Data System (ADS)

    Brattan, Daniel K.

    2015-11-01

    We use alternative quantisation of the D3-D5 system to explore properties of a strongly coupled anyon material at finite density and temperature. We study the transport properties of the material and find both diffusion and massive holographic zero sound modes. By studying the anyon number conductivity we also find evidence for the anyonic analogue of the metal-insulator transition.

  15. STRONG HEART STUDY DATA BOOK

    EPA Science Inventory

    Epidemiologic study of cardiovascular disease in American Indians. Examination on the prevalence of major risk factors of CVD in American Indian men and women ages 45-74 in the American Indian communities from the three centers that participate in the Strong Heart Study.

  16. Ergodicity convergence test suggests telomere motion obeys fractional dynamics.

    PubMed

    Kepten, E; Bronshtein, I; Garini, Y

    2011-04-01

    Anomalous diffusion, observed in many biological processes, is a generalized description of a wide variety of processes, all obeying the same law of mean-square displacement. Identifying the basic mechanisms of these observations is important for deducing the nature of the biophysical systems measured. We implement a previously suggested method for distinguishing between fractional Langevin dynamics, fractional Brownian motion, and continuous time random walk based on the ergodic nature of the data. We apply the method together with the recently suggested P-variation test and the displacement correlation to the lately measured dynamics of telomeres in the nucleus of mammalian cells and find strong evidence that the telomeres motion obeys fractional dynamics. The ergodic dynamics are observed experimentally to fit fractional Brownian or Langevin dynamics. PMID:21599212

  17. Ergodicity convergence test suggests telomere motion obeys fractional dynamics

    NASA Astrophysics Data System (ADS)

    Kepten, E.; Bronshtein, I.; Garini, Y.

    2011-04-01

    Anomalous diffusion, observed in many biological processes, is a generalized description of a wide variety of processes, all obeying the same law of mean-square displacement. Identifying the basic mechanisms of these observations is important for deducing the nature of the biophysical systems measured. We implement a previously suggested method for distinguishing between fractional Langevin dynamics, fractional Brownian motion, and continuous time random walk based on the ergodic nature of the data. We apply the method together with the recently suggested P-variation test and the displacement correlation to the lately measured dynamics of telomeres in the nucleus of mammalian cells and find strong evidence that the telomeres motion obeys fractional dynamics. The ergodic dynamics are observed experimentally to fit fractional Brownian or Langevin dynamics.

  18. Stone Morphology Suggestive of Randall's Plaque

    NASA Astrophysics Data System (ADS)

    Daudon, Michel; Traxer, Olivier; Jungers, Paul; Bazin, Dominique

    2007-04-01

    Randall's plaques are found in a number of calcium oxalate stone formers. Stones developed on a Randall's plaque typically present a small depressed zone ("umbilication") corresponding to the tip of the papilla and containing material detached from the plaque. By examining the morphology and infrared composition of 45,774 calculi referred to our laboratory over the past three decades, we identified 8,916 umbilicated calculi (19.5%). We have selected three periods of time corresponding to the first years of each decade. Over these periods, we analyzed 26,182 consecutive calculi. Among them, we identified 5,401 umbilicated calculi, of which 91.5% had an identifiable plaque. We analyzed the relative prevalence of umbilicated stones over time and the respective composition of Randall's plaque and stones. The proportion of umbilicated stones rose significantly from 10% in period 1 (1978-1984) to 21% in period 2 (1990-1993) and 22.2% in period 3 (2000-2006), with a parallel rise in the prevalence of stones with identifiable Randall's plaque. The main component of plaques was carbapatite in 90.8% of cases, whereas other components such as amorphous carbonated calcium phosphate, sodium hydrogen urate or uric acid were found in other cases. The morphology of plaques made of carbapatite was diverse, as was their carbonate content, thus suggesting variable pathophysiological mechanisms. Stones were made of whewellite as the main component in 51.4% of cases, or admixed with weddellite in 26.8%, predominant weddellite in 12.5% and other components (mainly uric acid) in 7.5% of cases. Our findings confirm that Randall's plaques are made of carbapatite in the great majority of cases, but with the stones more frequently composed of calcium oxalate monohydrate (which is associated with hyperoxaluria) than of calcium oxalate dihydrate (associated with hypercalciuria). In conclusion, in our country, stones developed on a carbapatite Randall's plaque are as frequently made of

  19. Quality control by <strong>HyperS>pectral <strong>I>maging (HSI) in solid waste recycling: logics, algorithms and procedures

    NASA Astrophysics Data System (ADS)

    Bonifazi, Giuseppe; Serranti, Silvia

    2014-03-01

    In secondary raw materials and recycling sectors, the products quality represents, more and more, the key issue to pursuit in order to be competitive in a more and more demanding market, where quality standards and products certification play a preheminent role. These goals assume particular importance when recycling actions are applied. Recovered products, resulting from waste materials, and/or dismissed products processing, are, in fact, always seen with a certain suspect. An adequate response of the industry to the market can only be given through the utilization of equipment and procedures ensuring pure, high-quality production, and efficient work and cost. All these goals can be reached adopting not only more efficient equipment and layouts, but also introducing new processing logics able to realize a full control of the handled material flow streams fulfilling, at the same time, i) an easy management of the procedures, ii) an efficient use of the energy, iii) the definition and set up of reliable and robust procedures, iv) the possibility to implement network connectivity capabilities finalized to a remote monitoring and control of the processes and v) a full data storage, analysis and retrieving. Furthermore the ongoing legislation and regulation require the implementation of recycling infrastructure characterised by high resources efficiency and low environmental impacts, both aspects being strongly linked to the waste materials and/or dismissed products original characteristics. For these reasons an optimal recycling infrastructure design primarily requires a full knowledge of the characteristics of the input waste. What previously outlined requires the introduction of a new important concept to apply in solid waste recycling, the recycling-oriented characterization, that is the set of actions addressed to strategically determine selected attributes, in order to get goaloriented data on waste for the development, implementation or improvement of recycling

  20. PREFACE: Strongly correlated electron systems Strongly correlated electron systems

    NASA Astrophysics Data System (ADS)

    Saxena, Siddharth S.; Littlewood, P. B.

    2012-07-01

    This special section is dedicated to the Strongly Correlated Electron Systems Conference (SCES) 2011, which was held from 29 August-3 September 2011, in Cambridge, UK. SCES'2011 is dedicated to 100 years of superconductivity and covers a range of topics in the area of strongly correlated systems. The correlated electronic and magnetic materials featured include f-electron based heavy fermion intermetallics and d-electron based transition metal compounds. The selected papers derived from invited presentations seek to deepen our understanding of the rich physical phenomena that arise from correlation effects. The focus is on quantum phase transitions, non-Fermi liquid phenomena, quantum magnetism, unconventional superconductivity and metal-insulator transitions. Both experimental and theoretical work is presented. Based on fundamental advances in the understanding of electronic materials, much of 20th century materials physics was driven by miniaturisation and integration in the electronics industry to the current generation of nanometre scale devices. The achievements of this industry have brought unprecedented advances to society and well-being, and no doubt there is much further to go—note that this progress is founded on investments and studies in the fundamentals of condensed matter physics from more than 50 years ago. Nevertheless, the defining challenges for the 21st century will lie in the discovery in science, and deployment through engineering, of technologies that can deliver the scale needed to have an impact on the sustainability agenda. Thus the big developments in nanotechnology may lie not in the pursuit of yet smaller transistors, but in the design of new structures that can revolutionise the performance of solar cells, batteries, fuel cells, light-weight structural materials, refrigeration, water purification, etc. The science presented in the papers of this special section also highlights the underlying interest in energy-dense materials, which

  1. EDITORIAL: Strongly correlated electron systems Strongly correlated electron systems

    NASA Astrophysics Data System (ADS)

    Ronning, Filip; Batista, Cristian

    2011-03-01

    Strongly correlated electrons is an exciting and diverse field in condensed matter physics. This special issue aims to capture some of that excitement and recent developments in the field. Given that this issue was inspired by the 2010 International Conference on Strongly Correlated Electron Systems (SCES 2010), we briefly give some history in order to place this issue in context. The 2010 International Conference on Strongly Correlated Electron Systems was held in Santa Fe, New Mexico, a reunion of sorts from the 1989 International Conference on the Physics of Highly Correlated Electron Systems that also convened in Santa Fe. SCES 2010—co-chaired by John Sarrao and Joe Thompson—followed the tradition of earlier conferences, in this century, hosted by Buzios (2008), Houston (2007), Vienna (2005), Karlsruhe (2004), Krakow (2002) and Ann Arbor (2001). Every three years since 1997, SCES has joined the International Conference on Magnetism (ICM), held in Recife (2000), Rome (2003), Kyoto (2006) and Karlsruhe (2009). Like its predecessors, SCES 2010 topics included strongly correlated f- and d-electron systems, heavy-fermion behaviors, quantum-phase transitions, non-Fermi liquid phenomena, unconventional superconductivity, and emergent states that arise from electronic correlations. Recent developments from studies of quantum magnetism and cold atoms complemented the traditional subjects and were included in SCES 2010. 2010 celebrated the 400th anniversary of Santa Fe as well as the birth of astronomy. So what's the connection to SCES? The Dutch invention of the first practical telescope and its use by Galileo in 1610 and subsequent years overturned dogma that the sun revolved about the earth. This revolutionary, and at the time heretical, conclusion required innovative combinations of new instrumentation, observation and mathematics. These same combinations are just as important 400 years later and are the foundation of scientific discoveries that were discussed

  2. Pattern Genes Suggest Functional Connectivity of Organs.

    PubMed

    Qin, Yangmei; Pan, Jianbo; Cai, Meichun; Yao, Lixia; Ji, Zhiliang

    2016-01-01

    Human organ, as the basic structural and functional unit in human body, is made of a large community of different cell types that organically bound together. Each organ usually exerts highly specified physiological function; while several related organs work smartly together to perform complicated body functions. In this study, we present a computational effort to understand the roles of genes in building functional connection between organs. More specifically, we mined multiple transcriptome datasets sampled from 36 human organs and tissues, and quantitatively identified 3,149 genes whose expressions showed consensus modularly patterns: specific to one organ/tissue, selectively expressed in several functionally related tissues and ubiquitously expressed. These pattern genes imply intrinsic connections between organs. According to the expression abundance of the 766 selective genes, we consistently cluster the 36 human organs/tissues into seven functional groups: adipose &gland, brain, muscle, immune, metabolism, mucoid and nerve conduction. The organs and tissues in each group either work together to form organ systems or coordinate to perform particular body functions. The particular roles of specific genes and selective genes suggest that they could not only be used to mechanistically explore organ functions, but also be designed for selective biomarkers and therapeutic targets. PMID:27225987

  3. Pattern Genes Suggest Functional Connectivity of Organs

    PubMed Central

    Qin, Yangmei; Pan, Jianbo; Cai, Meichun; Yao, Lixia; Ji, Zhiliang

    2016-01-01

    Human organ, as the basic structural and functional unit in human body, is made of a large community of different cell types that organically bound together. Each organ usually exerts highly specified physiological function; while several related organs work smartly together to perform complicated body functions. In this study, we present a computational effort to understand the roles of genes in building functional connection between organs. More specifically, we mined multiple transcriptome datasets sampled from 36 human organs and tissues, and quantitatively identified 3,149 genes whose expressions showed consensus modularly patterns: specific to one organ/tissue, selectively expressed in several functionally related tissues and ubiquitously expressed. These pattern genes imply intrinsic connections between organs. According to the expression abundance of the 766 selective genes, we consistently cluster the 36 human organs/tissues into seven functional groups: adipose & gland, brain, muscle, immune, metabolism, mucoid and nerve conduction. The organs and tissues in each group either work together to form organ systems or coordinate to perform particular body functions. The particular roles of specific genes and selective genes suggest that they could not only be used to mechanistically explore organ functions, but also be designed for selective biomarkers and therapeutic targets. PMID:27225987

  4. [Evidence that suggest the reality of reincarnation].

    PubMed

    Bonilla, Ernesto

    2015-06-01

    Worldwide, children can be found who reported that they have memories of a previous life. More than 2,500 cases have been studied and their specifications have been published and preserved in the archives of the Division of Perceptual Studies at the University of Virginia (United States). Many of those children come from countries where the majority of the inhabitants believe in reincarnation, but others come from countries with different cultures and religions that reject it. In many cases, the revelations of the children have been verified and have corresponded to a particular individual, already dead. A good number of these children have marks and birth defects corresponding to wounds on the body of his previous personality. Many have behaviors related to their claims to their former life: phobias, philias, and attachments. Others seem to recognize people and places of his supposed previous life, and some of their assertions have been made under controlled conditions. The hypothesis of reincarnation is controversial. We can never say that it does not occur, or will obtain conclusive evidence that it happens. The cases that have been described so far, isolated or combined, do not provide irrefutable proof of reincarnation, but they supply evidence that suggest its reality. PMID:26299061

  5. Pattern Genes Suggest Functional Connectivity of Organs

    NASA Astrophysics Data System (ADS)

    Qin, Yangmei; Pan, Jianbo; Cai, Meichun; Yao, Lixia; Ji, Zhiliang

    2016-05-01

    Human organ, as the basic structural and functional unit in human body, is made of a large community of different cell types that organically bound together. Each organ usually exerts highly specified physiological function; while several related organs work smartly together to perform complicated body functions. In this study, we present a computational effort to understand the roles of genes in building functional connection between organs. More specifically, we mined multiple transcriptome datasets sampled from 36 human organs and tissues, and quantitatively identified 3,149 genes whose expressions showed consensus modularly patterns: specific to one organ/tissue, selectively expressed in several functionally related tissues and ubiquitously expressed. These pattern genes imply intrinsic connections between organs. According to the expression abundance of the 766 selective genes, we consistently cluster the 36 human organs/tissues into seven functional groups: adipose & gland, brain, muscle, immune, metabolism, mucoid and nerve conduction. The organs and tissues in each group either work together to form organ systems or coordinate to perform particular body functions. The particular roles of specific genes and selective genes suggest that they could not only be used to mechanistically explore organ functions, but also be designed for selective biomarkers and therapeutic targets.

  6. Employee suggestion programs: the rewards of involvement.

    PubMed

    Mishra, J M; McKendall, M

    1993-09-01

    Successful ESPs are the products of a great deal of effort by managers, administrators, teams, individuals, and reviewers, who are all striving to achieve the goals of increased profitability and enhanced employee involvement. A review of the literature indicates that there are several prescriptions that will increase the likelihood of a successful ESP (see the box). Today's American business prophets sound ceaseless calls to arms in the name of "world class performance," "global competitiveness," "total quality management," and a variety of other buzz terms. A burgeoning industry has evolved that promises, through speeches, teleconferences, seminars, and consulting contracts, to teach American organizations how to achieve excellence. In the face of a sputtering economy and unrelenting competitive pressure, today's managers must translate these laudatory ideals into hands-on reality without sacrificing the firm's profit margin to experimentation. If any idea can help an organization achieve improvement through a workable program, then that idea and that program deserve real consideration. An ESP represents an opportunity to tap the intelligence and resourcefulness of an organization's employees, and by doing so, reap significant cost savings. Those companies and managers that have an ESP program uniformly list economic advantages first when describing the benefits of their employee suggestion programs. But there is another deeper and longer term benefit inherent in an ESP. These programs allow employees to become involved in their organization; they drive deaccession to lower levels, they give employees more responsibility, they foster creative approaches to work, and they encourage creativity in pursuit of company goals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:10127910

  7. Strongly interacting parton matter equilibration

    SciTech Connect

    Ozvenchuk, V.; Linnyk, O.; Bratkovskaya, E.; Gorenstein, M.; Cassing, W.

    2012-07-15

    We study the kinetic and chemical equilibration in 'infinite' parton matter within the Parton-Hadron-String Dynamics transport approach. The 'infinite' matter is simulated within a cubic box with periodic boundary conditions initialized at different energy densities. Particle abundances, kinetic energy distributions, and the detailed balance of the off-shell quarks and gluons in the strongly-interacting quarkgluon plasma are addressed and discussed.

  8. Strong CP and SUZ2

    NASA Astrophysics Data System (ADS)

    Albaid, Abdelhamid; Dine, Michael; Draper, Patrick

    2015-12-01

    Solutions to the strong CP problem typically introduce new scales associated with the spontaneous breaking of symmetries. Absent any anthropic argument for small overline{θ} , these scales require stabilization against ultraviolet corrections. Supersymmetry offers a tempting stabilization mechanism, since it can solve the "big" electroweak hierarchy problem at the same time. One family of solutions to strong CP, including generalized parity models, heavy axion models, and heavy η' models, introduces {Z}_2 copies of (part of) the Standard Model and an associated scale of {Z}_2 -breaking. We review why, without additional structure such as supersymmetry, the {Z}_2 -breaking scale is unacceptably tuned. We then study "SUZ2" models, supersymmetric theories with {Z}_2 copies of the MSSM. We find that the addition of SUSY typically destroys the {Z}_2 protection of overline{θ}=0 , even at tree level, once SUSY and {Z}_2 are broken. In theories like supersymmetric completions of the twin Higgs, where {Z}_2 addresses the little hierarchy problem but not strong CP, two axions can be used to relax overline{θ}.

  9. SENTINEL-1 Image Matching Using Strong Scatters

    NASA Astrophysics Data System (ADS)

    Ghannadi, M. A.; Saadatseresht, M.; Motagh, M.

    2015-12-01

    The availability of new radar spaceborne sensors offers new interesting potentialities for the geomatics application: spatial and temporal change detection, generation of Digital Elevation Model(DEM) using radargrametry and interferometry. Since the start of the sentinel-1 mission to take images from different regions all over the world, the ability to use these images in variety domains has been treasured. This paper suggests a method for image matching using strong scatters. all the experiments are done on sentinel-1 stereo images from Jam, Bushehr, Iran.

  10. Classical scattering in strongly attractive potentials

    NASA Astrophysics Data System (ADS)

    Khrapak, S. A.

    2014-03-01

    Scattering in central attractive potentials is investigated systematically, in the limit of strong interaction, when large-angle scattering dominates. In particular, three important model interactions (Lennard-Jones, Yukawa, and exponential), which are qualitatively different from each other, are studied in detail. It is shown that for each of these interactions the dependence of the scattering angle on the properly normalized impact parameter exhibits a quasiuniversal behavior. This implies simple scaling of the transport cross sections with energy in the considered limit. Accurate fits for the momentum transfer cross section are suggested. Applications of the obtained results are discussed.

  11. Classical scattering in strongly attractive potentials.

    PubMed

    Khrapak, S A

    2014-03-01

    Scattering in central attractive potentials is investigated systematically, in the limit of strong interaction, when large-angle scattering dominates. In particular, three important model interactions (Lennard-Jones, Yukawa, and exponential), which are qualitatively different from each other, are studied in detail. It is shown that for each of these interactions the dependence of the scattering angle on the properly normalized impact parameter exhibits a quasiuniversal behavior. This implies simple scaling of the transport cross sections with energy in the considered limit. Accurate fits for the momentum transfer cross section are suggested. Applications of the obtained results are discussed. PMID:24730827

  12. Testing increases suggestibility for narrative-based misinformation but reduces suggestibility for question-based misinformation.

    PubMed

    LaPaglia, Jessica A; Chan, Jason C K

    2013-01-01

    A number of recent studies have found that recalling details of an event following its occurrence can increase people's suggestibility to later presented misinformation. However, several other studies have reported the opposite result, whereby earlier retrieval can reduce subsequent eyewitness suggestibility. In the present study, we investigated whether differences in the way misinformation is presented can modulate the effects of testing on suggestibility. Participants watched a video of a robbery and some were questioned about the event immediately afterwards. Later, participants were exposed to misinformation in a narrative (Experiment 1) or in questions (Experiment 2). Consistent with previous studies, we found that testing increased suggestibility when misinformation was presented via a narrative. Remarkably, when misinformation was presented in questions, testing decreased suggestibility. PMID:24105926

  13. Strong interactive massive particles from a strong coupled theory

    SciTech Connect

    Khlopov, Maxim Yu.; Kouvaris, Chris

    2008-03-15

    Minimal walking technicolor models can provide a nontrivial solution for cosmological dark matter, if the lightest technibaryon is doubly charged. Technibaryon asymmetry generated in the early Universe is related to baryon asymmetry, and it is possible to create an excess of techniparticles with charge (-2). These excessive techniparticles are all captured by {sup 4}He, creating techni-O-helium tOHe atoms, as soon as {sup 4}He is formed in big bang nucleosynthesis. The interaction of techni-O-helium with nuclei opens new paths to the creation of heavy nuclei in big bang nucleosynthesis. Because of the large mass of technibaryons, the tOHe ''atomic'' gas decouples from the baryonic matter and plays the role of dark matter in large scale structure formation, while structures in small scales are suppressed. Nuclear interactions with matter slow down cosmic techni-O-helium in the Earth below the threshold of underground dark matter detectors, thus escaping severe cryogenic dark matter search constraints. On the other hand, these nuclear interactions are not sufficiently strong to exclude this form of strongly interactive massive particles by constraints from the XQC experiment. Experimental tests of this hypothesis are possible in the search for tOHe in balloon-borne experiments (or on the ground) and for its charged techniparticle constituents in cosmic rays and accelerators. The tOHe atoms can cause cold nuclear transformations in matter and might form anomalous isotopes, offering possible ways to exclude (or prove?) their existence.

  14. PREFACE: Strongly correlated electron systems Strongly correlated electron systems

    NASA Astrophysics Data System (ADS)

    Saxena, Siddharth S.; Littlewood, P. B.

    2012-07-01

    This special section is dedicated to the Strongly Correlated Electron Systems Conference (SCES) 2011, which was held from 29 August-3 September 2011, in Cambridge, UK. SCES'2011 is dedicated to 100 years of superconductivity and covers a range of topics in the area of strongly correlated systems. The correlated electronic and magnetic materials featured include f-electron based heavy fermion intermetallics and d-electron based transition metal compounds. The selected papers derived from invited presentations seek to deepen our understanding of the rich physical phenomena that arise from correlation effects. The focus is on quantum phase transitions, non-Fermi liquid phenomena, quantum magnetism, unconventional superconductivity and metal-insulator transitions. Both experimental and theoretical work is presented. Based on fundamental advances in the understanding of electronic materials, much of 20th century materials physics was driven by miniaturisation and integration in the electronics industry to the current generation of nanometre scale devices. The achievements of this industry have brought unprecedented advances to society and well-being, and no doubt there is much further to go—note that this progress is founded on investments and studies in the fundamentals of condensed matter physics from more than 50 years ago. Nevertheless, the defining challenges for the 21st century will lie in the discovery in science, and deployment through engineering, of technologies that can deliver the scale needed to have an impact on the sustainability agenda. Thus the big developments in nanotechnology may lie not in the pursuit of yet smaller transistors, but in the design of new structures that can revolutionise the performance of solar cells, batteries, fuel cells, light-weight structural materials, refrigeration, water purification, etc. The science presented in the papers of this special section also highlights the underlying interest in energy-dense materials, which

  15. Strong Vocational Interest Blank and Dogmatism

    ERIC Educational Resources Information Center

    Hansen, Jo-Ida C.; Johansson, Charles B.

    1974-01-01

    A Dogmatism scale was empirically constructed for the SVIB to differentiate high-and low- dogmatism criterion samples. High dogmatism included activities of a military, business, and managerial nature. Low dogmatism reflected artistic interests. Results suggest that the SVIB Dogmatism scale did identify dogmatic and nondogmatic patterns of…

  16. PREFACE: Strongly Coupled Coulomb Systems

    NASA Astrophysics Data System (ADS)

    Fortov, Vladimir E.; Golden, Kenneth I.; Norman, Genri E.

    2006-04-01

    This special issue contains papers presented at the International Conference on Strongly Coupled Coulomb Systems (SCCS) which was held during the week of 20 24 June 2005 in Moscow, Russia. The Moscow conference was the tenth in a series of conferences. The previous conferences were organized as follows. 1977: Orleans-la-Source, France, as a NATO Advanced Study Institute on Strongly Coupled Plasmas (organized by Marc Feix and Gabor J Kalman) 1982: Les Houches, France (organized by Marc Baus and Jean-Pierre Hansen) 1986: Santa Cruz, California, USA (hosted by Forrest J Rogers and Hugh E DeWitt) 1989: Tokyo, Japan (hosted by Setsuo Ichimaru) 1992: Rochester, NY, USA (hosted by Hugh M Van Horn and Setsuo Ichimaru) 1995: Binz, Germany (hosted by Wolf Dietrich Kraeft and Manfred Schlanges) 1997: Boston, Massachusetts, USA (hosted by Gabor J Kalman) 1999: St Malo, France (hosted by Claude Deutsch and Bernard Jancovici) 2002: Santa Fe, New Mexico, USA (hosted by John F Benage and Michael S Murillo) After 1995 the name of the series was changed from `Strongly Coupled Plasmas' to the present name in order to extend the topics of the conferences. The planned frequency for the future is once every three years. The purpose of these conferences is to provide an international forum for the presentation and discussion of research accomplishments and ideas relating to a variety of plasma liquid and condensed matter systems, dominated by strong Coulomb interactions between their constituents. Strongly coupled Coulomb systems encompass diverse many-body systems and physical conditions. Each meeting has seen an evolution of topics and emphasis as new discoveries and new methods appear. This year, sessions were organized for invited presentations and posters on dense plasmas and warm matter, astrophysics and dense hydrogen, non-neutral and ultracold plasmas, dusty plasmas, condensed matter 2D and layered charged-particle systems, Coulomb liquids, and statistical theory of SCCS. Within

  17. Strong turbulence of plasma waves

    NASA Technical Reports Server (NTRS)

    Goldman, M. V.

    1984-01-01

    This paper reviews recent work related to modulational instability and wave envelope self-focusing in dynamical and statistical systems. After introductory remarks pertinent to nonlinear optics realizations of these effects, the author summarizes the status of the subject in plasma physics, where it has come to be called 'strong Langmuir turbulence'. The paper treats the historical development of pertinent concepts, analytical theory, numerical simulations, laboratory experiments, and spacecraft observations. The role of self-similar self-focusing Langmuir envelope wave packets is emphasized, both in the Zakharov equation model for the wave dynamics and in a statistical theory based on this dynamical model.

  18. [DNA knots and strong triviality].

    PubMed

    Torisu, Ichiro

    2009-06-01

    A circle embedded in 3-space without self-intersection is called a knot. A knot is a mathematical object according to topology. Knot theory studies how complicated a given knot is, or whether it is trivial. Any knot can be represented by a diagram with above and below information at the crossings. Then a knot obtained by replacing the information at one crossing is generally another knot. This operation is called a crossing change. A crossing change is an important notion in knot theory. In this article, we survey the strong triviality of knots, which is one of the multi-crossing changes. PMID:19530562

  19. EDITORIAL: Strongly correlated electron systems Strongly correlated electron systems

    NASA Astrophysics Data System (ADS)

    Ronning, Filip; Batista, Cristian

    2011-03-01

    Strongly correlated electrons is an exciting and diverse field in condensed matter physics. This special issue aims to capture some of that excitement and recent developments in the field. Given that this issue was inspired by the 2010 International Conference on Strongly Correlated Electron Systems (SCES 2010), we briefly give some history in order to place this issue in context. The 2010 International Conference on Strongly Correlated Electron Systems was held in Santa Fe, New Mexico, a reunion of sorts from the 1989 International Conference on the Physics of Highly Correlated Electron Systems that also convened in Santa Fe. SCES 2010—co-chaired by John Sarrao and Joe Thompson—followed the tradition of earlier conferences, in this century, hosted by Buzios (2008), Houston (2007), Vienna (2005), Karlsruhe (2004), Krakow (2002) and Ann Arbor (2001). Every three years since 1997, SCES has joined the International Conference on Magnetism (ICM), held in Recife (2000), Rome (2003), Kyoto (2006) and Karlsruhe (2009). Like its predecessors, SCES 2010 topics included strongly correlated f- and d-electron systems, heavy-fermion behaviors, quantum-phase transitions, non-Fermi liquid phenomena, unconventional superconductivity, and emergent states that arise from electronic correlations. Recent developments from studies of quantum magnetism and cold atoms complemented the traditional subjects and were included in SCES 2010. 2010 celebrated the 400th anniversary of Santa Fe as well as the birth of astronomy. So what's the connection to SCES? The Dutch invention of the first practical telescope and its use by Galileo in 1610 and subsequent years overturned dogma that the sun revolved about the earth. This revolutionary, and at the time heretical, conclusion required innovative combinations of new instrumentation, observation and mathematics. These same combinations are just as important 400 years later and are the foundation of scientific discoveries that were discussed

  20. Research on determinants of breastfeeding duration: suggestions for biocultural studies.

    PubMed

    Allen, L H; Pelto, G H

    1985-01-01

    The main purpose of this paper is to suggest directions for future intra-cultural research on the factors that affect breastfeeding duration, especially policy-oriented research. A 2nd purpose is to call for a reexamination of the theoretical construct, biocultural determinants, with respect to infant feeding. The study compares determinants in 4 multivariate studies. One was carried out in Connecticut, 1 in a working class community in Scotland, another in England and the 4th in Sweden. Almost no biological factors are strongly associated with breastfeeding duration in any of the population studied. Of the external factors, those relating to social support and advice were the most consistent predictors. Socioeconomic status, income, and work outside the home were not good predictors. Maternal attitudes and experience are of great importance in predicting feeding duration. The general picture that emerged from all the studies is that if a mother wants to breastfeed, she can. Mothers breastfeed longer if they desire to breastfeed; they intend to do it for a longer period of time; they feel comfortable feeding in public; they are informed about breastfeeding; and they are not anxious about the process. There is also fairly strong evidence linking a number of biocultural factors to feeding duration. Whether the linkage is biological or behavioral has significant policy implications: if it is biological, successful intervention would require a change in hospital practices to earlier 1st feeding; if the linkage is behavioral, the problem might be resolved through improved maternal education. PMID:3836324

  1. Delusions of parasitosis; suggested dialogue between dermatologist and patient.

    PubMed

    Patel, Viraat; Koo, John Y M

    2015-10-01

    Delusions of parasitosis (DoP) is a psychocutaneous condition characterized by a fixed false belief that one is infested by skin parasites. Patients afflicted with DoP generally experience sensations of biting, stinging or crawling in the absence of any objective evidence of infestation. The most definitive treatment for DoP is antipsychotic agents. Though the diagnosis and treatment options are rather straightforward, the difficulty lies in the art of building a therapeutic rapport with the patient in order to encourage acceptance of antipsychotic treatment. This article is a practical guide that suggests verbatim how dermatologists might talk to a delusional patient in order to establish a strong therapeutic rapport. Strategies on how to optimize the initial encounter, build rapport and prescribe antipsychotic medications that are likely to be accepted by the patient are discussed. PMID:25490455

  2. Dynamics of strongly-coupled spiking neurons.

    PubMed

    Bressloff, P C; Coombes, S

    2000-01-01

    We present a dynamical theory of integrate-and-fire neurons with strong synaptic coupling. We show how phase-locked states that are stable in the weak coupling regime can destabilize as the coupling is increased, leading to states characterized by spatiotemporal variations in the interspike intervals (ISIs). The dynamics is compared with that of a corresponding network of analog neurons in which the outputs of the neurons are taken to be mean firing rates. A fundamental result is that for slow interactions, there is good agreement between the two models (on an appropriately defined timescale). Various examples of desynchronization in the strong coupling regime are presented. First, a globally coupled network of identical neurons with strong inhibitory coupling is shown to exhibit oscillator death in which some of the neurons suppress the activity of others. However, the stability of the synchronous state persists for very large networks and fast synapses. Second, an asymmetric network with a mixture of excitation and inhibition is shown to exhibit periodic bursting patterns. Finally, a one-dimensional network of neurons with long-range interactions is shown to desynchronize to a state with a spatially periodic pattern of mean firing rates across the network. This is modulated by deterministic fluctuations of the instantaneous firing rate whose size is an increasing function of the speed of synaptic response. PMID:10636934

  3. Probability densities in strong turbulence

    NASA Astrophysics Data System (ADS)

    Yakhot, Victor

    2006-03-01

    In this work we, using Mellin’s transform combined with the Gaussian large-scale boundary condition, calculate probability densities (PDFs) of velocity increments P(δu,r), velocity derivatives P(u,r) and the PDF of the fluctuating dissipation scales Q(η,Re), where Re is the large-scale Reynolds number. The resulting expressions strongly deviate from the Log-normal PDF P(δu,r) often quoted in the literature. It is shown that the probability density of the small-scale velocity fluctuations includes information about the large (integral) scale dynamics which is responsible for the deviation of P(δu,r) from P(δu,r). An expression for the function D(h) of the multifractal theory, free from spurious logarithms recently discussed in [U. Frisch, M. Martins Afonso, A. Mazzino, V. Yakhot, J. Fluid Mech. 542 (2005) 97] is also obtained.

  4. Strongly Interacting Homogeneous Fermi Gases

    NASA Astrophysics Data System (ADS)

    Mukherjee, Biswaroop; Patel, Parth; Yan, Zhenjie; Struck, Julian; Zwierlein, Martin

    2016-05-01

    We present a homogeneous box potential for strongly interacting Fermi gases. The local density approximation (LDA) allows measurements on traditional inhomogeneous traps to observe a continuous distribution of Fermi gases in a single shot, but also suffer from a broadened response due to line-of-sight averaging over varying densities. We trap ultracold Fermionic (6 Li) in an optical homogeneous potential and characterize its flatness through in-situ tomography. A hybrid approach combining a cylindrical optical potential with a harmonic magnetic trap allows us to exploit the LDA and measure local RF spectra without requiring significant image reconstruction. We extract various quantities from the RF spectra such as the Tan's contact, and discuss further measurements of homogeneous Fermi systems under spin imbalance and finite temperature.

  5. Strong shock implosion, approximate solution

    NASA Astrophysics Data System (ADS)

    Fujimoto, Y.; Mishkin, E. A.; Alejaldre, C.

    1983-01-01

    The self-similar, center-bound motion of a strong spherical, or cylindrical, shock wave moving through an ideal gas with a constant, γ= cp/ cv, is considered and a linearized, approximate solution is derived. An X, Y phase plane of the self-similar solution is defined and the representative curved of the system behind the shock front is replaced by a straight line connecting the mappings of the shock front with that of its tail. The reduced pressure P(ξ), density R(ξ) and velocity U1(ξ) are found in closed, quite accurate, form. Comparison with numerically obtained results, for γ= {5}/{3} and γ= {7}/{5}, is shown.

  6. Eikonal Scattering at Strong Coupling

    NASA Astrophysics Data System (ADS)

    Irizarry-Gelpi, Melvin Eloy

    The scattering of subatomic particles is a source of important physical phenomena. Decades of work have yielded many techniques for the computation of scattering amplitudes. Most of these techniques involve perturbative quantum field theory and thus apply only at weak coupling. Complementary to scattering is the formation of bound states, which are intrinsically nonperturbative. Regge theory arose in the late 1950s as an attempt to describe, with a single framework, both scattering and the formation of bound states. In Regge theory one obtains an amplitude with bound state poles after analytic continuation of a nonperturbative scattering amplitude, corresponding to a sum of an infinite number of Feynman diagrams at large energy and fixed momentum transfer (but with crossed kinematics). Thus, in order to obtain bound states at fixed energy, one computes an amplitude at large momentum transfer. In this dissertation we calculate amplitudes with bound states in the regime of fixed energy and small momentum transfer. We formulate the elastic scattering problem in terms of many-body path integrals, familiar from quantum mechanics. Then we invoke the semiclassical JWKB approximation, where the path integral is dominated by classical paths. The dynamics in the semiclassical regime are strongly coupled, as found by Halpern and Siegel. When the momentum transfer is small, the classical paths are simple straight lines and the resulting semiclassical amplitudes display a spectrum of bound states that agrees with the spectrum found by solving wave equations with potentials. In this work we study the bound states of matter particles with various types of interactions, including electromagnetic and gravitational interactions. Our work has many analogies with the work started by Alday and Maldacena, who computed scattering amplitudes of gluons at strong coupling with semiclassical quantum mechanics of strings in anti de-Sitter spacetime. We hope that in the future we can apply our

  7. Zinc inhibition of monomeric and dimeric proton channels suggests cooperative gating

    PubMed Central

    Musset, Boris; Smith, Susan M E; Rajan, Sindhu; Cherny, Vladimir V; Sujai, Sukrutha; Morgan, Deri; DeCoursey, Thomas E

    2010-01-01

    Voltage-gated proton channels are strongly inhibited by Zn2+, which binds to His residues. However, in a molecular model, the two externally accessible His are too far apart to coordinate Zn2+. We hypothesize that high-affinity Zn2+ binding occurs at the dimer interface between pairs of His residues from both monomers. Consistent with this idea, Zn2+ effects were weaker in monomeric channels. Mutation of His193 and His140 in various combinations and in tandem dimers revealed that channel opening was slowed by Zn2+ only when at least one His was present in each monomer, suggesting that in wild-type (WT) HV1, Zn2+ binding between His of both monomers inhibits channel opening. In addition, monomeric channels opened exponentially, and dimeric channels opened sigmoidally. Monomeric channel gating had weaker temperature dependence than dimeric channels. Finally, monomeric channels opened 6.6 times faster than dimeric channels. Together, these observations suggest that in the proton channel dimer, the two monomers are closely apposed and interact during a cooperative gating process. Zn2+ appears to slow opening by preventing movement of the monomers relative to each other that is prerequisite to opening. These data also suggest that the association of the monomers is tenuous and allows substantial freedom of movement. The data support the idea that native proton channels are dimeric. Finally, the idea that monomer–dimer interconversion occurs during activation of phagocytes appears to be ruled out. PMID:20231140

  8. Strong interaction studies with kaonic atoms

    NASA Astrophysics Data System (ADS)

    Marton, J.; Bazzi, M.; Beer, G.; Berucci, C.; Bosnar, D.; Bragadireanu, A. M.; Cargnelli, M.; Clozza, A.; Curceanu, C.; d'Uffizi, A.; Fiorini, C.; Ghio, F.; Guaraldo, C.; Hayano, R.; Iliescu, M.; Ishiwatari, T.; Iwasaki, M.; Levi Sandri, P.; Okada, S.; Pietreanu, D.; Piscicchia, K.; Ponta, T.; Quaglia, R.; Romero Vidal, A.; Sbardella, E.; Scordo, A.; Shi, H.; Sirghi, D. L.; Sirghi, F.; Tatsuno, H.; Vazquez Doce, O.; Widmann, E.; Zmeskal, J.

    2016-03-01

    The strong interaction of antikaons (K-) with nucleons and nuclei in the low-energy regime represents an active research field connected intrinsically with few-body physics. There are important open questions like the question of antikaon nuclear bound states - the prototype system being K-pp. A unique and rather direct experimental access to the antikaon-nucleon scattering lengths is provided by precision X-ray spectroscopy of transitions in low-lying states of light kaonic atoms like kaonic hydrogen isotopes. In the SIDDHARTA experiment at the electron-positron collider DAΦNE of LNF-INFN we measured the most precise values of the strong interaction observables, i.e. the strong interaction on the 1s ground state of the electromagnetically bound K-p atom leading to a hadronic shift ɛ1s and a hadronic broadening Γ1s of the 1s state. The SIDDHARTA result triggered new theoretical work which achieved major progress in the understanding of the low-energy strong interaction with strangeness. Antikaon-nucleon scattering lengths have been calculated constrained by the SIDDHARTA data on kaonic hydrogen. For the extraction of the isospin-dependent scattering lengths a measurement of the hadronic shift and width of kaonic deuterium is necessary. Therefore, new X-ray studies with the focus on kaonic deuterium are in preparation (SIDDHARTA2). Many improvements in the experimental setup will allow to measure kaonic deuterium which is challenging due to the anticipated low X-ray yield. Especially important are the data on the X-ray yields of kaonic deuterium extracted from a exploratory experiment within SIDDHARTA.

  9. Communication: A Jastrow factor coupled cluster theory for weak and strong electron correlation

    SciTech Connect

    Neuscamman, Eric

    2013-11-14

    We present a Jastrow-factor-inspired variant of coupled cluster theory that accurately describes both weak and strong electron correlation. Compatibility with quantum Monte Carlo allows for variational energy evaluations and an antisymmetric geminal power reference, two features not present in traditional coupled cluster that facilitate a nearly exact description of the strong electron correlations in minimal-basis N{sub 2} bond breaking. In double-ζ treatments of the HF and H{sub 2}O bond dissociations, where both weak and strong correlations are important, this polynomial cost method proves more accurate than either traditional coupled cluster or complete active space perturbation theory. These preliminary successes suggest a deep connection between the ways in which cluster operators and Jastrow factors encode correlation.

  10. A systematic review of strong gravitational lens modeling software

    NASA Astrophysics Data System (ADS)

    Lefor, Alan T.; Futamase, Toshifumi; Akhlaghi, Mohammad

    2013-07-01

    Despite expanding research activity in gravitational lens modeling, there is no particular software which is considered a standard. Much of the gravitational lens modeling software is written by individual investigators for their own use. Some gravitational lens modeling software is freely available for download but is widely variable with regard to ease of use and quality of documentation. This review of 13 software packages was undertaken to provide a single source of information. Gravitational lens models are classified as parametric models or non-parametric models, and can be further divided into research and educational software. Software used in research includes the GRAVLENS package (with both gravlens and lensmodel), Lenstool, LensPerfect, glafic, PixeLens, SimpLens, Lensview, and GRALE. In this review, GravLensHD, G-Lens, Gravitational Lensing, lens and MOWGLI are categorized as educational programs that are useful for demonstrating various aspects of lensing. Each of the 13 software packages is reviewed with regard to software features (installation, documentation, files provided, etc.) and lensing features (type of model, input data, output data, etc.) as well as a brief review of studies where they have been used. Recent studies have demonstrated the utility of strong gravitational lensing data for mass mapping, and suggest increased use of these techniques in the future. Coupled with the advent of greatly improved imaging, new approaches to modeling of strong gravitational lens systems are needed. This is the first systematic review of strong gravitational lens modeling software, providing investigators with a starting point for future software development to further advance gravitational lens modeling research. http://www.ephysics.org/mowgli/

  11. Is It Possible to Predict Strong Earthquakes?

    NASA Astrophysics Data System (ADS)

    Polyakov, Y. S.; Ryabinin, G. V.; Solovyeva, A. B.; Timashev, S. F.

    2015-07-01

    The possibility of earthquake prediction is one of the key open questions in modern geophysics. We propose an approach based on the analysis of common short-term candidate precursors (2 weeks to 3 months prior to strong earthquake) with the subsequent processing of brain activity signals generated in specific types of rats (kept in laboratory settings) who reportedly sense an impending earthquake a few days prior to the event. We illustrate the identification of short-term precursors using the groundwater sodium-ion concentration data in the time frame from 2010 to 2014 (a major earthquake occurred on 28 February 2013) recorded at two different sites in the southeastern part of the Kamchatka Peninsula, Russia. The candidate precursors are observed as synchronized peaks in the nonstationarity factors, introduced within the flicker-noise spectroscopy framework for signal processing, for the high-frequency component of both time series. These peaks correspond to the local reorganizations of the underlying geophysical system that are believed to precede strong earthquakes. The rodent brain activity signals are selected as potential "immediate" (up to 2 weeks) deterministic precursors because of the recent scientific reports confirming that rodents sense imminent earthquakes and the population-genetic model of K irshvink (Soc Am 90, 312-323, 2000) showing how a reliable genetic seismic escape response system may have developed over the period of several hundred million years in certain animals. The use of brain activity signals, such as electroencephalograms, in contrast to conventional abnormal animal behavior observations, enables one to apply the standard "input-sensor-response" approach to determine what input signals trigger specific seismic escape brain activity responses.

  12. Myelin from MAG-deficient mice is a strong inhibitor of neurite outgrowth.

    PubMed

    Ng, W P; Cartel, N; Li, C; Roder, J; Lozano, A

    1996-03-22

    Myelin-associated glycoprotein (MAG) has potent neurite outgrowth inhibitory activity in vitro. To assess the importance of MAG in the neurite outgrowth inhibitory activity in CNS myelin, we used an in vitro bioassay to characterize neurite growth on CNS myelin derived from mice carrying a null mutation of the MAG gene. Myelin proteins from MAG-deficient mice inhibited neurite outgrowth to a similar degree to the wild-type CNS myelin. These results suggest that CNS myelin molecules other than MAG exert strong inhibitory effects on the growth of neurites. PMID:8724661

  13. Strong Winds over the Keel

    NASA Astrophysics Data System (ADS)

    2009-02-01

    The latest ESO image reveals amazing detail in the intricate structures of one of the largest and brightest nebulae in the sky, the Carina Nebula (NGC 3372), where strong winds and powerful radiation from an armada of massive stars are creating havoc in the large cloud of dust and gas from which the stars were born. ESO PR Photo 05a/09 The Carina Nebula ESO PR Video 05a/09 Pan over the Carina Nebula ESO PR Video 05b/09 Carina Nebula Zoom-in The large and beautiful image displays the full variety of this impressive skyscape, spattered with clusters of young stars, large nebulae of dust and gas, dust pillars, globules, and adorned by one of the Universe's most impressive binary stars. It was produced by combining exposures through six different filters from the Wide Field Imager (WFI), attached to the 2.2 m ESO/MPG telescope at ESO's La Silla Observatory, in Chile. The Carina Nebula is located about 7500 light-years away in the constellation of the same name (Carina; the Keel). Spanning about 100 light-years, it is four times larger than the famous Orion Nebula and far brighter. It is an intensive star-forming region with dark lanes of cool dust splitting up the glowing nebula gas that surrounds its many clusters of stars. The glow of the Carina Nebula comes mainly from hot hydrogen basking in the strong radiation of monster baby stars. The interaction between the hydrogen and the ultraviolet light results in its characteristic red and purple colour. The immense nebula contains over a dozen stars with at least 50 to 100 times the mass of our Sun. Such stars have a very short lifespan, a few million years at most, the blink of an eye compared with the Sun's expected lifetime of ten billion years. One of the Universe's most impressive stars, Eta Carinae, is found in the nebula. It is one of the most massive stars in our Milky Way, over 100 times the mass of the Sun and about four million times brighter, making it the most luminous star known. Eta Carinae is highly

  14. Prevention of strong earthquakes: Goal or utopia?

    NASA Astrophysics Data System (ADS)

    Mukhamediev, Sh. A.

    2010-11-01

    In the present paper, we consider ideas suggesting various kinds of industrial impact on the close-to-failure block of the Earth’s crust in order to break a pending strong earthquake (PSE) into a number of smaller quakes or aseismic slips. Among the published proposals on the prevention of a forthcoming strong earthquake, methods based on water injection and vibro influence merit greater attention as they are based on field observations and the results of laboratory tests. In spite of this, the cited proofs are, for various reasons, insufficient to acknowledge the proposed techniques as highly substantiated; in addition, the physical essence of these methods has still not been fully understood. First, the key concept of the methods, namely, the release of the accumulated stresses (or excessive elastic energy) in the source region of a forthcoming strong earthquake, is open to objection. If we treat an earthquake as a phenomenon of a loss in stability, then, the heterogeneities of the physicomechanical properties and stresses along the existing fault or its future trajectory, rather than the absolute values of stresses, play the most important role. In the present paper, this statement is illustrated by the classical examples of stable and unstable fractures and by the examples of the calculated stress fields, which were realized in the source regions of the tsunamigenic earthquakes of December 26, 2004 near the Sumatra Island and of September 29, 2009 near the Samoa Island. Here, just before the earthquakes, there were no excessive stresses in the source regions. Quite the opposite, the maximum shear stresses τmax were close to their minimum value, compared to τmax in the adjacent territory. In the present paper, we provide quantitative examples that falsify the theory of the prevention of PSE in its current form. It is shown that the measures for the prevention of PSE, even when successful for an already existing fault, can trigger or accelerate a catastrophic

  15. β-Catenin-dependent pathway activation by both promiscuous "canonical" WNT3a-, and specific "noncanonical" WNT4- and WNT5a-FZD receptor combinations with strong differences in LRP5 and LRP6 dependency.

    PubMed

    Ring, Larisa; Neth, Peter; Weber, Christian; Steffens, Sabine; Faussner, Alexander

    2014-02-01

    The WNT/β-catenin signalling cascade is the best-investigated frizzled receptor (FZD) pathway, however, whether and how specific combinations of WNT/FZD and co-receptors LRP5 and LRP6 differentially affect this pathway are not well understood. This is mostly due to the fact that there are 19 WNTs, 10 FZDs and at least two co-receptors. In our attempt to identify the signalling capabilities of specific WNT/FZD/LRP combinations we made use of our previously reported TCF/LEF Gaussia luciferase reporter gene HEK293 cell line (Ring et al., 2011). Generation of WNT/FZD fusion constructs - but not their separate transfection - without or with additional isogenic overexpression of LRP5 and LRP6 in our reporter cells permitted the investigation of specific WNT/FZD/LRP combinations. The canonical WNT3a in fusion to almost all FZDs was able to induce β-catenin-dependent signalling with strong dependency on LRP6 but not LRP5. Interestingly, noncanonical WNT ligands, WNT4 and WNT5a, were also able to act "canonically" but only in fusion with specific FZDs and with selective dependence on LRP5 or LRP6. These data and extension of this experimental setup to the poorly characterized other WNTs should facilitate deeper insight into the complex WNT/FZD signalling system and its function. PMID:24269653

  16. In-situ and theoretical studies for the dissociation of water on an active Ni/CeO₂ catalyst: Importance of strong metal-support interactions for the cleavage of O-H bonds

    DOE PAGESBeta

    Carrasco, Javier; Rodriguez, Jose A.; Lopez-Duran, David; Liu, Zongyuan; Duchon, Tomas; Evans, Jaime; Senanayake, Sanjaya D.; Crumlin, Ethan J.; Matolin, Vladimir; Ganduglia-Pirovano, M. Veronica

    2015-03-23

    Water dissociation is crucial in many catalytic reactions on oxide-supported transition-metal catalysts. Here, supported by experimental and density-functional theory results, we elucidate the effect of the support on O-H bond cleavage activity for nickel/ceria systems. Ambient-pressure O1s photoemission spectra at low Ni loadings on CeO₂(111) reveal a substantially larger amount of OH groups as compared to the bare support. Our computed activation energy barriers for water dissociation show an enhanced reactivity of Ni adatoms on CeO₂(111) compared with pyramidal Ni₄ particles with one Ni atom not in contact with the support, and extended Ni(111) surfaces. At the origin of thismore » support effect is the ability of ceria to stabilize oxidized Ni²⁺ species by accommodating electrons in localized f-states. The fast dissociation of water on Ni/CeO₂ has a dramatic effect on the activity and stability of this system as a catalyst for the water-gas shift and ethanol steam reforming reactions.« less

  17. In situ and theoretical studies for the dissociation of water on an active Ni/CeO2 catalyst: importance of strong metal-support interactions for the cleavage of O-H bonds.

    PubMed

    Carrasco, Javier; López-Durán, David; Liu, Zongyuan; Duchoň, Tomáš; Evans, Jaime; Senanayake, Sanjaya D; Crumlin, Ethan J; Matolín, Vladimir; Rodríguez, José A; Ganduglia-Pirovano, M Verónica

    2015-03-23

    Water dissociation is crucial in many catalytic reactions on oxide-supported transition-metal catalysts. Supported by experimental and density-functional theory results, the effect of the support on OH bond cleavage activity is elucidated for nickel/ceria systems. Ambient-pressure O 1s photoemission spectra at low Ni loadings on CeO2 (111) reveal a substantially larger amount of OH groups as compared to the bare support. Computed activation energy barriers for water dissociation show an enhanced reactivity of Ni adatoms on CeO2 (111) compared with pyramidal Ni4 particles with one Ni atom not in contact with the support, and extended Ni(111) surfaces. At the origin of this support effect is the ability of ceria to stabilize oxidized Ni(2+) species by accommodating electrons in localized f-states. The fast dissociation of water on Ni/CeO2 has a dramatic effect on the activity and stability of this system as a catalyst for the water-gas shift and ethanol steam reforming reactions. PMID:25651288

  18. Rcs signalling-activated transcription of rcsA induces strong anti-sense transcription of upstream fliPQR flagellar genes from a weak intergenic promoter: regulatory roles for the anti-sense transcript in virulence and motility.

    PubMed

    Wang, Qingfeng; Harshey, Rasika M

    2009-10-01

    In Salmonella enterica, an activated Rcs signalling system inhibits initiation of transcription of the flhD master operon. Under these conditions, where motility is shut down, microarray experiments showed an increased RNA signal for three flagellar genes -fliPQR- located upstream of rcsA. We show here that it is the anti-sense (AS) strand of these genes that is transcribed, originating at a weak promoter in the intergenic region between fliR and rcsA. RcsA is an auxiliary regulator for the Rcs system, whose transcription is dependent on the response regulator RcsB. Rcs-activated rightward transcription, but not translation, of rcsA is required for stimulation of leftward AS transcription. Our results implicate a combined action of RcsB and rcsA transcription in activating the AS promoter, likely by modulating DNA superhelicity in the intergenic region. We show that the AS transcript regulates many genes in the Rcs regulon, including SPI-1 and SPI-2 virulence and stress-response genes. In the wild-type strain the AS transcript is present in low amounts, independent of Rcs signalling. Here, AS transcription modulates complementary sense RNA levels and impacts swarming motility. It appears that the flagellar AS transcript has been co-opted by the Rcs system to regulate virulence. PMID:19703110

  19. In-situ and theoretical studies for the dissociation of water on an active Ni/CeO₂ catalyst: Importance of strong metal-support interactions for the cleavage of O-H bonds

    SciTech Connect

    Carrasco, Javier; Rodriguez, Jose A.; Lopez-Duran, David; Liu, Zongyuan; Duchon, Tomas; Evans, Jaime; Senanayake, Sanjaya D.; Crumlin, Ethan J.; Matolin, Vladimir; Ganduglia-Pirovano, M. Veronica

    2015-03-23

    Water dissociation is crucial in many catalytic reactions on oxide-supported transition-metal catalysts. Here, supported by experimental and density-functional theory results, we elucidate the effect of the support on O-H bond cleavage activity for nickel/ceria systems. Ambient-pressure O1s photoemission spectra at low Ni loadings on CeO₂(111) reveal a substantially larger amount of OH groups as compared to the bare support. Our computed activation energy barriers for water dissociation show an enhanced reactivity of Ni adatoms on CeO₂(111) compared with pyramidal Ni₄ particles with one Ni atom not in contact with the support, and extended Ni(111) surfaces. At the origin of this support effect is the ability of ceria to stabilize oxidized Ni²⁺ species by accommodating electrons in localized f-states. The fast dissociation of water on Ni/CeO₂ has a dramatic effect on the activity and stability of this system as a catalyst for the water-gas shift and ethanol steam reforming reactions.

  20. Rcs signaling-activated transcription of rcsA induces strong anti-sense transcription of upstream fliPQR flagellar genes from a weak intergenic promoter: regulatory roles for the anti-sense transcript in virulence and motility

    PubMed Central

    Wang, Qingfeng; Harshey, Rasika M.

    2009-01-01

    Summary In Salmonella enterica, an activated Rcs signaling system inhibits initiation of transcription of the flhD master operon. Under these conditions, where motility is shut down, microarray experiments showed an increased RNA signal for three flagellar genes - fliPQR - located upstream of rcsA. We show here that it is the anti-sense (AS) strand of these genes that is transcribed, originating at a weak promoter in the intergenic region between fliR and rcsA. RcsA is an auxiliary regulator for the Rcs system, whose transcription is dependent on the response regulator RcsB. Rcs-activated rightward transcription, but not translation, of rcsA is required for stimulation of leftward AS transcription. Our results implicate a combined action of RcsB and rcsA transcription in activating the AS promoter, likely by modulating DNA superhelicity in the intergenic region. We show that the AS transcript regulates many genes in the Rcs regulon, including SPI-1 and SPI-2 virulence and stress-response genes. In the wild-type strain the AS transcript is present in low amounts, independent of Rcs signaling. Here, AS transcription modulates complementary sense RNA levels and impacts swarming motility. It appears that the flagellar AS transcript has been co-opted by the Rcs system to regulate virulence. PMID:19703110

  1. Children's Memory for Their Mother's Murder: Accuracy, Suggestibility, and Resistance to Suggestion.

    PubMed

    McWilliams, Kelly; Narr, Rachel; Goodman, Gail S; Ruiz, Sandra; Mendoza, Macaria

    2013-01-31

    From its inception, child eyewitness memory research has been guided by dramatic legal cases that turn on the testimony of children. Decades of scientific research reveal that, under many conditions, children can provide veracious accounts of traumatic experiences. Scientific studies also document factors that lead children to make false statements. In this paper we describe a legal case in which children testified about their mother's murder. We discuss factors that may have influenced the accuracy of the children's eyewitness memory. Children's suggestibility and resistance to suggestion are illustrated. Expert testimony, based on scientific research, can aid the trier of fact when children provide crucial evidence in criminal investigations and courtroom trials about tragic events. PMID:23362807

  2. Effect of preoperative suggestion on postoperative gastrointestinal motility.

    PubMed Central

    Disbrow, E A; Bennett, H L; Owings, J T

    1993-01-01

    Autonomic behavior is subject to direct suggestion. We found that patients undergoing major operations benefit more from instruction than from information and reassurance. We compared the return of intestinal function after intra-abdominal operations in 2 groups of patients: the suggestion group received specific instructions for the early return of gastrointestinal motility, and the control group received an equal-length interview offering reassurance and nonspecific instructions. The suggestion group had a significantly shorter average time to the return of intestinal motility, 2.6 versus 4.1 days. Time to discharge was 6.5 versus 8.1 days. Covariates including duration of operation, amount of intraoperative bowel manipulation, and amount of postoperative narcotics were also examined using the statistical model analysis of covariance. An average savings of $1,200 per patient resulted from this simple 5-minute intervention. In summary, the use of specific physiologically active suggestions given preoperatively in a beleivable manner can reduce the morbidity associated with an intra-abdominal operation by reducing the duration of ileus. PMID:8342264

  3. Bodrum Strong Motion Network, Mugla, Turkey

    NASA Astrophysics Data System (ADS)

    Alcik, H. A.; Tanircan, G.; Korkmaz, A.

    2015-12-01

    The Gulf of Gökova is located in southwestern Turkey near the Aegean Sea and surrounded by Datça Peninsula to the south, the island of Kos to the west and Bodrum Peninsula to the north. The Bodrum peninsula with a population of one million in summer season is one of the most populated touristic centers of Turkey. This region is also surrounded by numerous active seismic entities such as Ula-Ören Fault Zone, Gökova Graben etc.. and demonstrates high seismic hazard. In the past, many destructive earthquakes have occurred in southwestern Turkey. One of the destructive historical earthquakes is 1493 Kos event (Mw=6.9) caused heavy damage in Bodrum. In the instrumental period seismic activity in the Gökova region includes the Ms>6.0 earthquakes of 23 April 1933 (Ms=6.4), 23 May 1941 (Ms=6.0), 13 December 1941 (Ms=6.5) events. Intense earthquake activity (Mw5+) occurred in Gulf of Gökova in August 2004 and January 2005. Considering the high seismicity and population of this region, a strong ground motion monitoring system stationed in dense settlements in the Bodrum Peninsula: Bodrum, Turgutreis, Yalıkavak, Çiftlik and Ortakent was deployed on June 2015. The network consists of 5 strong motion recorders, has been set up with the aim of monitoring of regional earthquakes, collecting accurate and reliable data for engineering and scientific research purposes, in particular to provide input for future earthquake rapid reporting and early warning implementation projects on urban environments in the Bodrum peninsula and the surrounding areas. In this poster presentation, we briefly introduce the Bodrum Network and discuss our future plans for further developments.

  4. CNX-012-570, a direct AMPK activator provides strong glycemic and lipid control along with significant reduction in body weight; studies from both diet-induced obese mice and db/db mice models

    PubMed Central

    2014-01-01

    Objectives AMP activated protein kinase (AMPK) regulates the coordination of anabolic and catabolic processes and is an attractive therapeutic target for T2DM, obesity and metabolic syndrome. We report the anti-hyperglycemic and anti-hyperlipidemic effects of CNX-012-570 is an orally bioavailable small molecule (molecular weight of 530 Daltons) that directly activates AMPK in DIO and db/db animal models of diabetes. Methods Activity and efficacy of the compound was tested in cell based as well as cell free systems in vitro. Male C57BL/6 mice fed with high fat diet (HFD) were assigned to either vehicle or CNX-012-570 (3 mg/kg, orally once a day) for 8 weeks (n = 8). Genetically diabetic db/db mice on chow diet were dosed with vehicle control or CNX-012-570 (2.5 mg/kg, orally once a day) for 6 weeks (n = 8). Results CNX-012-570 is a highly potent and orally bioavailable compound activating AMPK in both cell and cell free systems. It inhibits lipolysis (33%) and gluconeogenesis (28%) in 3T3L1 cells and rat primary hepatocytes respectively. The efficacy of the molecule was translated to both DIO and db/db animal models of diabetes. CNX-012-570 has reduced fasting blood glucose levels by 14%, body weight by 24% and fasting serum triglycerides (TG) by 24%. CNX-012-570 showed a 22% reduction in fed serum cholesterol levels and 19% increase in HDL levels. In db/db mice model, CNX-012-570 has shown 18% decrease in fed glucose and 32% decrease in fasting glucose with a 2.57% reduction in absolute HbA1c. Decrease in serum insulin and glucose AUC indicates the increased insulin sensitivity. Body weight was reduced by 13% with increased browning of adipose tissue and decreased inguinal and mesenteric fat mass. There was significant reduction in liver TG and liver total cholesterol. Conclusions CNX-012-570 has the potential to control hyperglycemia and hyperlipidemia. It also reduces body weight gain with an additional benefit of minimizing cardiovascular risks in

  5. Possible adaptation to strong magnetic fields

    NASA Astrophysics Data System (ADS)

    Nakhilnitskaya, Z. N.; Klimovskaya, L. D.; Kuzmina, Z. F.; Mastryukova, V. M.; Smirnova, N. P.; Strzhizhovsky, A. D.; Cherkasov, G. V.

    Animal adaptation to a strong magnetic field was investigated. Mice were exposed to 30-day total-body continuous effects of a constant magnetic field (CMF) of 1.6 T, and their physiological responses were assessed. Analysis of the data obtained showed that different parameters varied in a dissimilar manner. Red blood changes returned to normal in the course of the experiment. Leucocytosis and increased content of catecholamines and corticosterone of blood and adrenals persisted throughout the exposure. Changes in the spermatogenic epithelium were most distinct after the exposure. The recovery of certain parameters during the CMF exposure is indicative of adaptation of some physiological systems. The adaptation is, however, incomplete as suggested by the long persisting stress manifestations. Reticulocytopenia and spermatogenetic abnormalities found after the exposure are of particular importance.

  6. Designing asymmetric multiferroics with strong magnetoelectric coupling

    NASA Astrophysics Data System (ADS)

    Lu, X. Z.; Xiang, H. J.

    2014-09-01

    Multiferroics offer exciting opportunities for electric-field control of magnetism. Single-phase multiferroics suitable for such applications at room temperature need much more study. Here, we propose the concept of an alternative type of multiferroics, namely, the "asymmetric multiferroic." In asymmetric multiferroics, two locally stable ferroelectric states are not symmetrically equivalent, leading to different magnetic properties between these two states. Furthermore, we predict from first principles that a Fe-Cr-Mo superlattice with the LiNbO3-type structure is such an asymmetric multiferroic. The strong ferrimagnetism, high ferroelectric polarization, and significant dependence of the magnetic transition temperature on polarization make this asymmetric multiferroic an ideal candidate for realizing electric-field control of magnetism at room temperature. Our study suggests that the asymmetric multiferroic may provide an alternative playground for voltage control of magnetism and find its applications in spintronics and quantum computing.

  7. Designing asymmetric multiferroics with strong magnetoelectric coupling

    NASA Astrophysics Data System (ADS)

    Lu, Xuezeng; Xiang, Hongjun; Rondinelli, James; Materials Theory; Design Group Team

    2015-03-01

    Multiferroics offer exciting opportunities for electric-field control of magnetism. Single-phase multiferroics suitable for such applications at room temperature need much more study. Here, we propose the concept of an alternative type of multiferroics, namely, the ``asymmetric multiferroic.'' In asymmetric multiferroics, two locally stable ferroelectric states are not symmetrically equivalent, leading to different magnetic properties between these two states. Furthermore, we predict from first principles that a Fe-Cr-Mo superlattice with the LiNbO3-type structure is such an asymmetric multiferroic. The strong ferrimagnetism, high ferroelectric polarization, and significant dependence of the magnetic transition temperature on polarization make this asymmetric multiferroic an ideal candidate for realizing electric-field control of magnetism at room temperature. Our study suggests that the asymmetric multiferroic may provide an alternative playground for voltage control of magnetism and find its applications in spintronics and quantum computing.

  8. Strong Localization of Positive Charge in DNA

    NASA Astrophysics Data System (ADS)

    Uskov, Dmitry; Burin, Alex

    2008-05-01

    The positive charge transfer in a DNA molecule is determined by two main factors: the structure and composition of specific DNA strand, and interaction of a positive charge with the DNA environment. In this letter we present results of microscopic linear response theory for balance of charge transfer reaction in synthetic strands GAGG and GAGGG, where experimental data on the rates of electron hole migration has been reported by Lewis et al Nature, 406, 51-53 (2000). Our theoretical predictions, based on experimental data for the ratio of reaction rates G^+A(G)n<->GA(G)n^+ , n=2,3, suggest that charge in DNA is strongly localized within the single base pair because of the self-induced reorganization of classical environment. The onset of localization has a threshold behavior characteristic to quantum bistability. We also demonstrate that our conclusion does not depend on details of the model.

  9. Strongly Interacting Matter at High Energy Density

    SciTech Connect

    McLerran,L.

    2008-09-07

    This lecture concerns the properties of strongly interacting matter (which is described by Quantum Chromodynamics) at very high energy density. I review the properties of matter at high temperature, discussing the deconfinement phase transition. At high baryon density and low temperature, large N{sub c} arguments are developed which suggest that high baryonic density matter is a third form of matter, Quarkyonic Matter, that is distinct from confined hadronic matter and deconfined matter. I finally discuss the Color Glass Condensate which controls the high energy limit of QCD, and forms the low x part of a hadron wavefunction. The Glasma is introduced as matter formed by the Color Glass Condensate which eventually thermalizes into a Quark Gluon Plasma.

  10. Strong gravity and structure of topological solitons

    NASA Astrophysics Data System (ADS)

    Rybakov, Yu. P.

    The unification of Skyrme and Faddeev chiral models describing baryons and leptons respectively as topological solitons is suggested within the framework of 16-spinor field ψ = ψ1 ⊕ ψ2 nonlinear model containing two 8-semispinors ψ1 and ψ2. Using Brioschi identity for 8-spinors and special structure of the Higgs potential V implying the spontaneous symmetry breaking, it is possible to realize topological soliton-like excitations of two kinds due to the choice of S2- or S3- manifolds as phase spaces. The interactions with electromagnetic, Yang--Mills and gravitational fields are exhibited through the extention of derivatives via gauge invariance principle. Specific inclusion in the Higgs potential of the Kretschmann gravitational invariant K = RμνσλRμνσλ/48 permits one to obtain the strong gravity behavior at small distances and guarantee the correspondence with Quantum Mechanics at large distances.

  11. Identification of a Novel Strong and Ubiquitous Promoter/Enhancer in the Silkworm Bombyx mori

    PubMed Central

    Tsubota, Takuya; Uchino, Keiro; Suzuki, Takao K; Tanaka, Hiromitsu; Kayukawa, Takumi; Shinoda, Tetsuro; Sezutsu, Hideki

    2014-01-01

    Transgenic techniques offer a valuable tool for determining gene functions. Although various promoters are available for use in gene overexpression, gene knockdown, and identification of transgenic individuals, there is nevertheless a lack of versatile promoters for such studies, and this dearth acts as a bottleneck, especially with regard to nonmodel organisms. Here, we succeeded in identifying a novel strong and ubiquitous promoter/enhancer in the silkworm. We identified a unique silkworm strain whose reporter gene showed strong and ubiquitous expression during the establishment of enhancer trap strains. In this strain, the transposon was inserted into the 5′UTR of hsp90, a housekeeping gene that is abundantly expressed in a range of tissues. To determine whether the promoter/enhancer of hsp90 could be used to induce strong gene expression, a 2.9-kb upstream genomic fragment of hsp90 was isolated (hsp90P2.9k), and its transcriptional activation activity was examined. Strikingly, hsp90P2.9k induced strong gene expression in silkworm cell cultures and also strongly induced gene expression in various tissues and developmental stages of the silkworm. hsp90P2.9k also exhibited significant promoter/enhancer activity in Sf9, a cell culture from the armyworm, suggesting that this fragment might possibly be used as a gene expression tool in other Lepidoptera. We further found that 2.0 kb of hsp90P2.9k is sufficient for the induction of strong gene expression. We believe that this element will be of value for a range of studies such as targeted gene overexpression, gene knockdown and marker gene expression, not only in the silkworm but also in other insect species. PMID:24875626

  12. Fast Crystals and Strong Glasses

    SciTech Connect

    Weitz, David

    2009-11-04

    This talk describes new results on model colloid systems that provide insight into the behavior of fundamental problems in colloid physics, and more generally, for other materials as well. By visualizing the nucleation and growth of colloid crystals, we find that the incipient crystallites are much more disordered than expected, leading to a larger diversity of crystal morphologies. When the entropic contribution of these diverse morphologies is included in the free energy, we are able to describe the behavior very well, and can predict the nucleation rate surprisingly accurately. The talk also describes the glass transition in deformable colloidal particles, and will show that when the internal elasticity of the particles is included, the colloidal glass transition mimics that of molecular glass formers much more completely. These results also suggest that the elasticity at the scale of the fundamental unit, either colloid particle or molecule, determines the nature of the glass transition, as described by the "fragility."

  13. Formation and High Reactivity of the anti-Dioxo Form of High-Spin μ-Oxodioxodiiron(IV) as the Active Species That Cleaves Strong C-H Bonds.

    PubMed

    Kodera, Masahito; Ishiga, Shin; Tsuji, Tomokazu; Sakurai, Katsutoshi; Hitomi, Yutaka; Shiota, Yoshihito; Sajith, P K; Yoshizawa, Kazunari; Mieda, Kaoru; Ogura, Takashi

    2016-04-18

    Recently, it was shown that μ-oxo-μ-peroxodiiron(III) is converted to high-spin μ-oxodioxodiiron(IV) through O-O bond scission. Herein, the formation and high reactivity of the anti-dioxo form of high-spin μ-oxodioxodiiron(IV) as the active oxidant are demonstrated on the basis of resonance Raman and electronic-absorption spectral changes, detailed kinetic studies, DFT calculations, activation parameters, kinetic isotope effects (KIE), and catalytic oxidation of alkanes. Decay of μ-oxodioxodiiron(IV) was greatly accelerated on addition of substrate. The reactivity order of substrates is toluene

  14. Recent cyanobacterial Kai protein structures suggest a rotary clock.

    PubMed

    Wang, Jimin

    2005-05-01

    The cyanobacterial circadian oscillator consists of three Kai proteins, KaiA, KaiB, and KaiC, in its oscillation feedback loop. Structural comparison reveals that the Kai system resembles the F1-ATPase system in which KaiC is equivalent to alpha(3)beta(3), KaiA to gammadelta, and KaiB to its inhibitory factor. It also suggests that there exists a possible haemagglutinin-like spring-loaded mechanism for the activation of KaiA during the formation of Kai complexes. PMID:15893664

  15. Strong earthquakes, novae and cosmic ray environment

    NASA Technical Reports Server (NTRS)

    Yu, Z. D.

    1985-01-01

    Observations about the relationship between seismic activity and astronomical phenomena are discussed. First, after investigating the seismic data (magnitude 7.0 and over) with the method of superposed epochs it is found that world seismicity evidently increased after the occurring of novae with apparent magnitude brighter than 2.2. Second, a great many earthquakes of magnitude 7.0 and over occurred in the 13th month after two of the largest ground level solar cosmic ray events (GLEs). The causes of three high level phenomena of global seismic activity in 1918-1965 can be related to these, and it is suggested that according to the information of large GLE or bright nova predictions of the times of global intense seismic activity can be made.

  16. Some suggestions for the DSM-5 schizotypal personality disorder construct.

    PubMed

    Hummelen, Benjamin; Pedersen, Geir; Karterud, Sigmund

    2012-05-01

    This study relates to the schizotypal personality disorder (SPD) proposal of the upcoming fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) by investigating the construct validity of SPD as defined by DSM-IV in a large sample of patients from the Norwegian Network of Personality-Focused Treatment Programs (N = 2619), assessed by structured diagnostic interviews and the Longitudinal, Expert All Data standard. We investigated factor structure and psychometric properties of the SPD criteria, as well as co-occurrence patterns between SPD and other PDs. Thirty-six patients were diagnosed with SPD and 513 patients (21%) endorsed at least 2 schizotypal criteria. We found that 2 factors were specific for SPD, a cognitive-perceptual factor (ideas of reference, magical thinking, and unusual perceptual experiences) and an oddness factor (odd thinking and speech, constricted affect, and odd appearance or behavior). The criteria belonging to these factors had appropriate psychometric properties. The criteria of the cognitive-perceptual factor were more strongly associated with borderline personality disorder (PD) than with the other PDs. We did not find support for a consistent factor that reflected interpersonal problems. The criteria that used to be part of this factor (suspiciousness, lack of friends or confidants, and excessive social anxiety) performed poorly as specific SPD criteria. SPD was more strongly associated with antisocial PD and paranoid PD than with the other PDs. We suggest that ideas of reference should be included explicitly under the schizotypal facet of cognitive dysregulation in DSM-5, with less emphasis on the social phobic aspects of this feature. Furthermore, there should be more emphasis on the cognitive aspects of suspiciousness in SPD, and it should be considered to split up the affectivity criterion into constricted affect and inappropriate affect, with the latter type of affect being the expression of problems with

  17. Strongly Acidic Auxin Indole-3-Methanesulfonic Acid

    PubMed Central

    Cohen, Jerry D.; Baldi, Bruce G.; Bialek, Krystyna

    1985-01-01

    A radiochemical synthesis is described for [14C]indole-3-methanesulfonic acid (IMS), a strongly acidic auxin analog. Techniques were developed for fractionation and purification of IMS using normal and reverse phase chromatography. In addition, the utility of both Fourier transform infrared spectrometry and fast atom bombardment mass spectrometry for analysis of IMS has been demonstrated. IMS was shown to be an active auxin, stimulating soybean hypocotyl elongation, bean first internode curvature, and ethylene production. IMS uptake by thin sections of soybean hypocotyl was essentially independent of solution pH and, when applied at a 100 micromolar concentration, IMS exhibited a basipetal polarity in its transport in both corn coleoptile and soybean hypocotyl sections. [14C]IMS should, therefore, be a useful compound to study fundamental processes related to the movement of auxins in plant tissues and organelles. PMID:16664007

  18. Increasing spin-flips and decreasing cost: Perturbative corrections for external singles to the complete active space spin flip model for low-lying excited states and strong correlation

    SciTech Connect

    Mayhall, Nicholas J.; Head-Gordon, Martin

    2014-07-28

    An approximation to the spin-flip extended configuration interaction singles method is developed using a second-order perturbation theory approach. In addition to providing significant efficiency advantages, the new framework is general for an arbitrary number of spin-flips, with the current implementation being applicable for up to around 4 spin-flips. Two new methods are introduced: one which is developed using non-degenerate perturbation theory, spin-flip complete active-space (SF-CAS(S)), and a second quasidegenerate perturbation theory method, SF-CAS(S){sub 1}. These two approaches take the SF-CAS wavefunction as the reference, and then perturbatively includes the effect of single excitations. For the quasidegenerate perturbation theory method, SF-CAS(S){sub 1}, the subscripted “1” in the acronym indicates that a truncated denominator expansion is used to obtain an energy-independent down-folded Hamiltonian. We also show how this can alternatively be formulated in terms of an extended Lagrangian, by introducing an orthonormality constraint on the first-order wavefunction. Several numerical examples are provided, which demonstrate the ability of SF-CAS(S) and SF-CAS(S){sub 1} to describe bond dissociations, singlet-triplet gaps of organic molecules, and exchange coupling parameters for binuclear transition metal complexes.

  19. Strong anticipation: complexity matching in interpersonal coordination.

    PubMed

    Marmelat, Vivien; Delignières, Didier

    2012-10-01

    A subtle coordination occurs within complex systems, between multiple nested sub-systems. This intra-system coordination can be detected by the presence of 1/f fluctuations produced by the system. But coordination can occur also between systems. Interpersonal coordination has been studied from a local point of view until now, focusing on macroscopic interactions. But the recent concept of strong anticipation introduced by Dubois (Lect Notes Comput Sci 2684:110-132, 2003) suggests that interactions could occur on multiple levels between complex systems. The hypothesis is that time series in interpersonal synchronization present a matching of the complexity index (fractal exponent). Moreover, it is argued that this matching is not a consequence of short-term adaptations but reveals a global coordination between participants. Eleven pairs of participants oscillated a hand-held pendulum in the in-phase pattern for 11 min, in three conditions where the coupling strength was manipulated by the perceptual feedbacks. The results show a high correlation between fractal exponents irrespective of the coupling strength, and a very low percentage of local cross-correlations between time series appear at lag 0 and lag 1. These results suggest that interpersonal coordination, and more globally synchronization of participants with natural environments, is based on non-local time scales. PMID:22865163

  20. Strong metal-support interactions

    NASA Technical Reports Server (NTRS)

    Vannice, M. Albert

    1987-01-01

    It has been demonstrated that synergistic metal-support effects can occur which markedly enhance specific activity and alter selectivity in certain reactions. Because of the presence of such effects in certain reactions conducted under reducing conditions (that is, under H2 pressure), but not others, the creation of unique sites at the metal-support interface seems to be the best model at the present time to explain this behavior. The postulation of these sites, which are specific for a certain reactant such as CO, provides an effective explanation for the higher methanation rates that have been reported over some catalysts. The creation of these sites in the adlineation zone is facilitated by hydrogen spillover from the metal surface, and this same process can also enhance the reduction of many oxide supports. Although oxygen spillover is much less probable due to its higher heat of adsorption, it is much less well understood and the possibility of rate enhancements in CO oxidation caused by special interface sites cannot be discounted at the present time. Consequently, this seems to be an important area of future research.

  1. Cross Fostering Experiments Suggest That Mice Songs Are Innate

    PubMed Central

    Kikusui, Takefumi; Nakanishi, Kaori; Nakagawa, Ryoko; Nagasawa, Miho; Mogi, Kazutaka; Okanoya, Kazuo

    2011-01-01

    Background Vocal learning is a central functional constituent of human speech, and recent studies showing that adult male mice emit ultrasonic sound sequences characterized as “songs” have suggested that the ultrasonic courtship sounds of mice provide a mammalian model of vocal learning. Objectives We tested whether mouse songs are learned, by examining the relative role of rearing environment in a cross-fostering experiment. Methods and Findings We found that C57BL/6 and BALB/c males emit a clearly different pattern of songs with different frequency and syllable compositions; C57BL/6 males showed a higher peak frequency of syllables, shorter intervals between syllables, and more upward frequency modulations with jumps, whereas BALB/c males produced more “chevron” and “harmonics” syllables. To establish the degree of environmental influences in mouse song development, sons of these two strains were cross-fostered to another strain of parents. Songs were recorded when these cross-fostered pups were fully developed and their songs were compared with those of male mice reared by the genetic parents. The cross-fostered animals sang songs with acoustic characteristics - including syllable interval, peak frequency, and modulation patterns - similar to those of their genetic parents. In addition their song elements retained sequential characteristics similar to those of their genetic parents' songs. Conclusion These results do not support the hypothesis that mouse “song” is learned; we found no evidence for vocal learning of any sort under the conditions of this experiment. Our observation that the strain-specific character of the song profile persisted even after changing the developmental auditory environment suggests that the structure of these courtship sound sequences is under strong genetic control. Thus, the usefulness of mouse “song” as a model of mammalian vocal learning is limited, but mouse song has the potential to be an indispensable model

  2. Developing Strong Geoscience Programs and Departments

    NASA Astrophysics Data System (ADS)

    MacDonald, R.; Manduca, C. A.

    2002-12-01

    Strong geoscience programs are essential for preparing future geoscientists and developing a broad public understanding of our science. Faculty working as a department team can create stronger programs than individual faculty working alone. Workshops sponsored by Project Kaleidoscope (www.pkal.org) on departmental planning in the geosciences have emphasized the importance of designing programs in the context of both departmental and student goals. Well-articulated goals form a foundation for designing curriculum, courses, and other departmental activities. Course/skill matrices have emerged as particularly valuable tools for analyzing how individual courses combine in a curriculum to meet learning goals. Integrated programs where students have opportunities to learn and use skills in multiple contexts have been developed at several institutions. Departments are leveraging synergies between courses to more effectively reach departmental goals and capitalize on opportunities in the larger campus environment. A full departmental program extends beyond courses and curriculum. Studies in physics (National Task Force on Undergraduate Physics, Hilborne, 2002) indicate the importance of activities such as recruiting able students, mentoring students, providing courses appropriate for pre-service K-12 teachers, assisting with professional development for a diversity of careers, providing opportunities for undergraduates to participate in research, and making connections with the local industries and businesses that employ graduates. PKAL workshop participants have articulated a wide variety of approaches to undergraduate research opportunities within and outside of class based on their departmental goals, faculty goals, and resources. Similarly, departments have a wide variety of strategies for developing productive synergies with campus-wide programs including those emphasizing writing skills, quantitative skills, and environmental studies. Mentoring and advising

  3. The hippocampus supports both recollection and familiarity when memories are strong

    PubMed Central

    Smith, Christine N.; Wixted, John T.; Squire, Larry R.

    2011-01-01

    Recognition memory is thought to consist of two component processes – recollection and familiarity. It has been suggested that the hippocampus supports recollection, while adjacent cortex supports familiarity. However, the qualitative experiences of recollection and familiarity are typically confounded with a quantitative difference in memory strength (recollection > familiarity). Thus, the question remains whether the hippocampus might in fact support familiarity-based memories whenever they are as strong as recollection-based memories. We addressed this problem in a novel way using the Remember/Know procedure where we could explicitly match the confidence and accuracy of Remember and Know decisions. As in earlier studies, recollected items had higher accuracy and confidence than familiar items, and hippocampal activity was higher for recollected items than for familiar items. Furthermore hippocampal activity was similar for familiar items, misses, and correct rejections. When the accuracy and confidence of recollected and familiar items were matched, the findings were dramatically different. Hippocampal activity was now similar for recollected and familiar items. Importantly, hippocampal activity was also greater for familiar items than for misses or correct rejections (as well as for recollected items vs. misses or correct rejections). Our findings suggest that the hippocampus supports both recollection and familiarity when memories are strong. PMID:22049412

  4. Precise Synaptic Efficacy Alignment Suggests Potentiation Dominated Learning.

    PubMed

    Hartmann, Christoph; Miner, Daniel C; Triesch, Jochen

    2015-01-01

    Recent evidence suggests that parallel synapses from the same axonal branch onto the same dendritic branch have almost identical strength. It has been proposed that this alignment is only possible through learning rules that integrate activity over long time spans. However, learning mechanisms such as spike-timing-dependent plasticity (STDP) are commonly assumed to be temporally local. Here, we propose that the combination of temporally local STDP and a multiplicative synaptic normalization mechanism is sufficient to explain the alignment of parallel synapses. To address this issue, we introduce three increasingly complex models: First, we model the idealized interaction of STDP and synaptic normalization in a single neuron as a simple stochastic process and derive analytically that the alignment effect can be described by a so-called Kesten process. From this we can derive that synaptic efficacy alignment requires potentiation-dominated learning regimes. We verify these conditions in a single-neuron model with independent spiking activities but more realistic synapses. As expected, we only observe synaptic efficacy alignment for long-term potentiation-biased STDP. Finally, we explore how well the findings transfer to recurrent neural networks where the learning mechanisms interact with the correlated activity of the network. We find that due to the self-reinforcing correlations in recurrent circuits under STDP, alignment occurs for both long-term potentiation- and depression-biased STDP, because the learning will be potentiation dominated in both cases due to the potentiating events induced by correlated activity. This is in line with recent results demonstrating a dominance of potentiation over depression during waking and normalization during sleep. This leads us to predict that individual spine pairs will be more similar after sleep compared to after sleep deprivation. In conclusion, we show that synaptic normalization in conjunction with coordinated

  5. Intein Clustering Suggests Functional Importance in Different Domains of Life

    PubMed Central

    Novikova, Olga; Jayachandran, Pradeepa; Kelley, Danielle S.; Morton, Zachary; Merwin, Samantha; Topilina, Natalya I.; Belfort, Marlene

    2016-01-01

    Inteins, also called protein introns, are self-splicing mobile elements found in all domains of life. A bioinformatic survey of genomic data highlights a biased distribution of inteins among functional categories of proteins in both bacteria and archaea, with a strong preference for a single network of functions containing replisome proteins. Many nonorthologous, functionally equivalent replicative proteins in bacteria and archaea carry inteins, suggesting a selective retention of inteins in proteins of particular functions across domains of life. Inteins cluster not only in proteins with related roles but also in specific functional units of those proteins, like ATPase domains. This peculiar bias does not fully fit the models describing inteins exclusively as parasitic elements. In such models, evolutionary dynamics of inteins is viewed primarily through their mobility with the intein homing endonuclease (HEN) as the major factor of intein acquisition and loss. Although the HEN is essential for intein invasion and spread in populations, HEN dynamics does not explain the observed biased distribution of inteins among proteins in specific functional categories. We propose that the protein splicing domain of the intein can act as an environmental sensor that adapts to a particular niche and could increase the chance of the intein becoming fixed in a population. We argue that selective retention of some inteins might be beneficial under certain environmental stresses, to act as panic buttons that reversibly inhibit specific networks, consistent with the observed intein distribution. PMID:26609079

  6. Self-directed attention, awareness of bodily states, and suggestibility.

    PubMed

    Scheier, M F; Carver, C S; Gibbons, F X

    1979-09-01

    Two studies tested the hypothesis that self-directed attention would cause increased awareness of internal states and would thus reduce suggestibility effects. Experiment 1 applied this reasoning to the experience of an emotion. Males viewed moderately arousing slides of female nudes after being led to expect the slides to be either highly arousing or nonarousing. As predicted, ratings of the slides corresponded less with these experimentally-manipulated anticipations when self-focus was heightened by the presence of a mirror than when it was not. Experiment 2 examined a different internal experience: the perception of taste. Some subjects were led to expect a strong flavor as part of a test series, and other subjects were led to expect a weak flavor. Subjects high in private self-consciousness were less affected by this expectancy manipulation and more accurate in reporting their actual internal state than were subjects low in private self-consciousness. Discussion centers on the theoretical implications of the findings. PMID:501522

  7. Intein Clustering Suggests Functional Importance in Different Domains of Life.

    PubMed

    Novikova, Olga; Jayachandran, Pradeepa; Kelley, Danielle S; Morton, Zachary; Merwin, Samantha; Topilina, Natalya I; Belfort, Marlene

    2016-03-01

    Inteins, also called protein introns, are self-splicing mobile elements found in all domains of life. A bioinformatic survey of genomic data highlights a biased distribution of inteins among functional categories of proteins in both bacteria and archaea, with a strong preference for a single network of functions containing replisome proteins. Many nonorthologous, functionally equivalent replicative proteins in bacteria and archaea carry inteins, suggesting a selective retention of inteins in proteins of particular functions across domains of life. Inteins cluster not only in proteins with related roles but also in specific functional units of those proteins, like ATPase domains. This peculiar bias does not fully fit the models describing inteins exclusively as parasitic elements. In such models, evolutionary dynamics of inteins is viewed primarily through their mobility with the intein homing endonuclease (HEN) as the major factor of intein acquisition and loss. Although the HEN is essential for intein invasion and spread in populations, HEN dynamics does not explain the observed biased distribution of inteins among proteins in specific functional categories. We propose that the protein splicing domain of the intein can act as an environmental sensor that adapts to a particular niche and could increase the chance of the intein becoming fixed in a population. We argue that selective retention of some inteins might be beneficial under certain environmental stresses, to act as panic buttons that reversibly inhibit specific networks, consistent with the observed intein distribution. PMID:26609079

  8. Woody Vegetation on Levees? - Research Experiences and Design Suggestions

    NASA Astrophysics Data System (ADS)

    Lammeranner, Walter

    2013-04-01

    Recent flood events in Austria have reawakened practical and scientific interest in the stability of levees. One focus amongst others has been taken on the relationship between vegetation and levee stability with special reference to the role of woody plants. The effects of woody plants are undoubtedly manifold: On the one hand they can potentially have a negative influence and endanger levees, which is why many guidelines ban woody vegetation to preserve stability, visual inspection and unhindered flood-fight access. On the other hand woody vegetation can have several positive impacts on soil stability and which effects prevail depends largely on types and characteristics of plants. This shows how controversially woody plants on levees can be discussed and the strong need for further research in this field. In order to obtain new insights and widen horizons for this controversial issue, a research project carried out by the Institute of Soil Bioengineering and Landscape Construction - at the University of Natural Resources and Life Sciences, Vienna - was launched. This project deals with several aspects of effects of woody plants have on levees and focuses particularly on shrubby woody plants. The examined vegetation type is a dense stand of willows - Purple-Willows (Salix purpurea L.) - commonly used for stabilization of river embankments. The proposed contribution discusses the gained results with reference to levee stability and existing levee vegetation guidelines and gives design suggestions for compatible woody vegetation on levees.

  9. Unsaturated and Saturated Permeabilities of Fiber Reinforcement: Critics and Suggestions

    NASA Astrophysics Data System (ADS)

    Park, Chung Hae; Krawczak, Patricia

    2015-04-01

    In general, permeability measurement results show a strong scattering according to the measurement method, the type of test fluid and the fluid injection condition, even though permeability is regarded as a unique property of porous medium. In particular, the discrepancy between the unsaturated and saturated permeabilities for the same fabric has been widely reported. In the literature, relative permeability has been adopted to model the unsaturated flow. This approach has some limits in the modeling of double-scale porosity medium. We address this issue of permeability measurement by rigorously examining the mass conservation condition. Finally, we identify that the pressure gradient is non-linear with positive curvature in the unsaturated flow and a misinterpretation of pressure gradient is the main reason for the difference between the saturated and unsaturated permeabilities of the same fiber reinforcement. We propose to use a fixed value of permeability and to modify the mass conservation equation if there are air voids which are entrapped inside the fiber tow. Finally, we also suggest some guidelines and future perspectives to obtain more consistent permeability measurement results.

  10. The etiology of prostate cancer: what does the epidemiology suggest

    SciTech Connect

    Ross, R.K.; Paganini-Hill, A.; Henderson, B.E.

    1983-01-01

    The two most important demographic characteristics of prostate cancer in Los Angeles are the high rates among blacks, which are two times those among whites and four times those among Asians, and the rapid increase in rates with age after age 40. Despite the high rates among blacks, a birth cohort analysis indicates that mortality rates among black men born after 1900 have decreased. In this report, epidemiologic and experimental evidence supporting each of three etiologic hypotheses--industrial exposure to cadmium, sexual transmission by an infectious agent, and endocrine factors--are reviewed. Evidence from descriptive data in Los Angeles suggests that only a small portion of cases might be attributable to industrial exposures. In a cohort study of Catholic priests, we found no deficit of prostate cancer mortality, strong evidence against sexual transmission of the disease. Experimental evidence and a limited amount of human data support an endocrine hypothesis. Preliminary results of a case-control study of prostate cancer are presented, but these results are unable to distinguish among these hypotheses further. This study finds a substantial protective effect of vasectomy, an event that is accompanied by reduced prostatic function and size, but this result is thus far statistically insignificant.

  11. Intragenomic distribution of RTE retroelements suggests intrachromosomal movement.

    PubMed

    Montiel, Eugenia E; Ruiz-Ruano, Francisco J; Cabrero, Josefa; Marchal, Juan Alberto; Sánchez, Antonio; Perfectti, Francisco; López-León, María Dolores; Camacho, Juan Pedro M

    2015-06-01

    Much is known about the abundance of transposable elements (TEs) in eukaryotic genomes, but much is still unknown on their behaviour within cells. We employ here a combination of cytological, molecular and genomic approaches providing information on the intragenomic distribution and behaviour of non-long terminal repeat (LTR) retrotransposon-like elements (RTE). We microdissected every chromosome in a single first meiotic metaphase cell of the grasshopper Eyprepocnemis plorans and polymerase chain reaction (PCR) amplified a fragment of the RTE reverse transcriptase gene with specific primers. PCR products were cloned and 139 clones were sequenced. Analysis of molecular variance (AMOVA) showed significant intragenomic structure for these elements, with 4.6 % of molecular variance being found between chromosomes. A maximum likelihood tree built with the RTE sequences revealed the frequent presence of two or more elements showing very high similarity and being located on the same chromosome, thus suggesting intrachromosome movement. The 454 pyrosequencing of genomic DNA gave strong support to the microdissection results and provided evidence for the existence of 5' truncated elements. Our results thus indicate a tendency of RTE elements to reinsert into the same chromosome from where they were transcribed, which could be achieved if retrotranscription and insertion takes place immediately after transcription. PMID:25605325

  12. Attributes of γδ intraepithelial lymphocytes as suggested by their transcriptional profile

    PubMed Central

    Fahrer, Aude M.; Konigshofer, Yves; Kerr, Elizabeth M.; Ghandour, Ghassan; Mack, David H.; Davis, Mark M.; Chien, Yueh-hsiu

    2001-01-01

    γδ T lymphocytes in the intestinal intraepithelial layer (γδ IELs) are thought to contribute to immune competence, but their actual function remains poorly understood. Here we used DNA microarrays to study the gene expression profile of γδ IELs in a Yersinia infection system to better define their roles. To validate this approach, mesenteric lymph node CD8+ αβ T cells were similarly analyzed. The transcription profiles show that, whereas lymph node CD8+ αβ T cells must be activated to become cytotoxic effectors, γδ IELs are constitutively activated and appear to use different signaling cascades. Our data suggest that γδ IELs may respond efficiently to a broad range of pathological situations irrespective of their diverse T cell antigen receptor repertoire. γδ IELs may modulate local immune responses and participate in intestinal lipid metabolism, cholesterol homeostasis, and physiology. This study provides a strong basis for further investigations of the roles of these cells as well as mucosal immune defense in general. PMID:11526237

  13. Drug screen in patient cells suggests quinacrine to be repositioned for treatment of acute myeloid leukemia

    PubMed Central

    Eriksson, A; Österroos, A; Hassan, S; Gullbo, J; Rickardson, L; Jarvius, M; Nygren, P; Fryknäs, M; Höglund, M; Larsson, R

    2015-01-01

    To find drugs suitable for repositioning for use against leukemia, samples from patients with chronic lymphocytic, acute myeloid and lymphocytic leukemias as well as peripheral blood mononuclear cells (PBMC) were tested in response to 1266 compounds from the LOPAC1280 library (Sigma). Twenty-five compounds were defined as hits with activity in all leukemia subgroups (<50% cell survival compared with control) at 10 μM drug concentration. Only one of these compounds, quinacrine, showed low activity in normal PBMCs and was therefore selected for further preclinical evaluation. Mining the NCI-60 and the NextBio databases demonstrated leukemia sensitivity and the ability of quinacrine to reverse myeloid leukemia gene expression. Mechanistic exploration was performed using the NextBio bioinformatic software using gene expression analysis of drug exposed acute myeloid leukemia cultures (HL-60) in the database. Analysis of gene enrichment and drug correlations revealed strong connections to ribosomal biogenesis nucleoli and translation initiation. The highest drug–drug correlation was to ellipticine, a known RNA polymerase I inhibitor. These results were validated by additional gene expression analysis performed in-house. Quinacrine induced early inhibition of protein synthesis supporting these predictions. The results suggest that quinacrine have repositioning potential for treatment of acute myeloid leukemia by targeting of ribosomal biogenesis. PMID:25885427

  14. Preparing gender inclusive science teachers: Suggestions from the literature

    NASA Astrophysics Data System (ADS)

    Weinburgh, Molly

    1995-03-01

    It is imperative that the education given to United States children include adequate science taught in a way that will encourage the retention of all students; however, as half the population is female and females are underrepresented in the fields of mathematics and science, it is especially important that females be encouraged in these areas. Teacher education has been challenged to develop programs that produce teachers who understand the need for equitable science classrooms and who have the skills necessary to produce them. Several suggestions have been given for teacher education programs in science. First, college professors must examine their courses for gender bias. They must model equitable classroom strategies by planning activities that encourage the females to become active participants in the learning process and by using language that is gender inclusive. Second, definite instruction should be given to help the preservice and inservice teachers address their own attitudes toward science and children. Third, specific attention must be paid to assessing teachers in the following areas: (a) developing active, inquiry-based instruction; (b) developing classrooms in which constructive talking is the norm; (c) using cooperative groups correctly; (d) decreasing stereotyping of males, females, and scientists; and (e) using language that is gender inclusive.

  15. Transcriptome Variability in Keratocystic Odontogenic Tumor Suggests Distinct Molecular Subtypes

    PubMed Central

    Hu, Shijia; Divaris, Kimon; Parker, Joel; Padilla, Ricardo; Murrah, Valerie; Wright, John Timothy

    2016-01-01

    Keratocystic Odontogenic Tumor (KCOT) is a locally aggressive developmental cystic neoplasm thought to arise from the odontogenic epithelium. A high recurrence rate of up to 30% has been found following conservative treatment. Aggressive tumor resection can lead to the need for extensive reconstructive surgery, resulting in significant morbidity and impacting quality of life. Most research has focused on candidate-genes with a handful of studies employing whole transcriptome approaches. There is also the question of which reference tissue is most biologically-relevant. This study characterizes the transcriptome of KCOT using whole genome microarray and compare it with gene expression of different odontogenic tissues (“dentome”). Laser capture microdissection was used to isolate the neoplastic epithelial tissue in 20 cases. KCOT gene expression was compared with the “dentome” and relevant pathways were examined. Cluster analysis revealed 2 distinct molecular subtypes of KCOT. Several inflammatory pathways were activated in both subtypes. The AKT pathway was activated in one subtype while MAP kinase pathway was activated in the other. Additionally, PTCH1 expression was downregulated in both clusters suggesting involvement in KCOT tumorigenesis. In conclusion, this study provides new insights into the transcriptome of KCOT and highlights pathways that could be of diagnostic and prognostic value. PMID:27066764

  16. How interviewers' nonverbal behaviors can affect children's perceptions and suggestibility.

    PubMed

    Almerigogna, Jehanne; Ost, James; Akehurst, Lucy; Fluck, Mike

    2008-05-01

    We conducted two studies to examine how interviewers' nonverbal behaviors affect children's perceptions and suggestibility. In the first study, 42 8- to 10-year-olds watched video clips showing an interviewer displaying combinations of supportive and nonsupportive nonverbal behaviors and were asked to rate the interviewer on six attributes (e.g., friendliness, strictness). Smiling received high ratings on the positive attributes (i.e., friendly, helpful, and sincere), and fidgeting received high ratings on the negative attributes (i.e., strict, bored, and stressed). For the second study, 86 8- to 10-year-olds participated in a learning activity about the vocal chords. One week later, they were interviewed individually about the activity by an interviewer adopting either the supportive (i.e., smiling) or nonsupportive (i.e., fidgeting) behavior. Children questioned by the nonsupportive interviewer were less accurate and more likely to falsely report having been touched than were those questioned by the supportive interviewer. Children questioned by the supportive interviewer were also more likely to say that they did not know an answer than were children questioned by the nonsupportive interviewer. Participants in both conditions gave more correct answers to questions about central, as opposed to peripheral, details of the activity. Implications of these findings for the appropriate interviewing of child witnesses are discussed. PMID:18316091

  17. Fate of the Bose insulator in the limit of strong localization and low Cooper-pair density in ultrathin films

    NASA Astrophysics Data System (ADS)

    Hollen, S. M.; Fernandes, G. E.; Xu, J. M.; Valles, J. M.

    2014-10-01

    A Bose insulator composed of a low density of strongly localized Cooper pairs develops at the two-dimensional superconductor to insulator transition (SIT) in a number of thin film systems. Investigations of ultrathin amorphous PbBi films far from the SIT described here provide evidence that the Bose insulator gives way to a second insulating phase with decreasing film thickness. At a critical film thickness dc the magnetoresistance changes sign from positive, as expected for boson transport, to negative, as expected for fermion transport, signs of local Cooper-pair phase coherence effects on transport vanish, and the transport activation energy exhibits a kink. Below dc pairing fluctuation effects remain visible in the high-temperature transport while the activation energy continues to rise. These features show that Cooper pairing persists and suggest that the localized unpaired electron states involved in transport are interspersed among regions of strongly localized Cooper pairs in this strongly localized, low Cooper-pair density phase.

  18. Strong correlations in gravity and biophysics

    NASA Astrophysics Data System (ADS)

    Krotov, Dmitry

    The unifying theme of this dissertation is the use of correlations. In the first part (chapter 2), we investigate correlations in quantum field theories in de Sitter space. In the second part (chapters 3,4,5), we use correlations to investigate a theoretical proposal that real (observed in nature) transcriptional networks of biological organisms are operating at a critical point in their phase diagram. In chapter 2 we study the infrared dependence of correlators in various external backgrounds. Using the Schwinger-Keldysh formalism we calculate loop corrections to the correlators in the case of the Poincare patch and the complete de Sitter space. In the case of the Poincare patch, the loop correction modifies the behavior of the correlator at large distances. In the case of the complete de Sitter space, the loop correction has a strong dependence on the infrared cutoff in the past. It grows linearly with time, suggesting that at some point the correlations become strong and break the symmetry of the classical background. In chapter 3 we derive the signatures of critical behavior in a model organism, the embryo of Drosophila melanogaster. They are: strong correlations in the fluctuations of different genes, a slowing of dynamics, long range correlations in space, and departures from a Gaussian distribution of these fluctuations. We argue that these signatures are observed experimentally. In chapter 4 we construct an effective theory for the zero mode in this system. This theory is different from the standard Landau-Ginsburg description. It contains gauge fields (the result of the broken translational symmetry inside the cell), which produce observable contributions to the two-point function of the order parameter. We show that the behavior of the two-point function for the network of N genes is described by the action of a relativistic particle moving on the surface of the N - 1 dimensional sphere. We derive a theoretical bound on the decay of the correlations and

  19. Strong washout approximation to resonant leptogenesis

    NASA Astrophysics Data System (ADS)

    Garbrecht, Björn; Gautier, Florian; Klaric, Juraj

    2014-09-01

    We show that the effective decay asymmetry for resonant Leptogenesis in the strong washout regime with two sterile neutrinos and a single active flavour can in wide regions of parameter space be approximated by its late-time limit ɛ=Xsin(2varphi)/(X2+sin2varphi), where X=8πΔ/(|Y1|2+|Y2|2), Δ=4(M1-M2)/(M1+M2), varphi=arg(Y2/Y1), and M1,2, Y1,2 are the masses and Yukawa couplings of the sterile neutrinos. This approximation in particular extends to parametric regions where |Y1,2|2gg Δ, i.e. where the width dominates the mass splitting. We generalise the formula for the effective decay asymmetry to the case of several flavours of active leptons and demonstrate how this quantity can be used to calculate the lepton asymmetry for phenomenological scenarios that are in agreement with the observed neutrino oscillations. We establish analytic criteria for the validity of the late-time approximation for the decay asymmetry and compare these with numerical results that are obtained by solving for the mixing and the oscillations of the sterile neutrinos. For phenomenologically viable models with two sterile neutrinos, we find that the flavoured effective late-time decay asymmetry can be applied throughout parameter space.

  20. Precise Synaptic Efficacy Alignment Suggests Potentiation Dominated Learning

    PubMed Central

    Hartmann, Christoph; Miner, Daniel C.; Triesch, Jochen

    2016-01-01

    Recent evidence suggests that parallel synapses from the same axonal branch onto the same dendritic branch have almost identical strength. It has been proposed that this alignment is only possible through learning rules that integrate activity over long time spans. However, learning mechanisms such as spike-timing-dependent plasticity (STDP) are commonly assumed to be temporally local. Here, we propose that the combination of temporally local STDP and a multiplicative synaptic normalization mechanism is sufficient to explain the alignment of parallel synapses. To address this issue, we introduce three increasingly complex models: First, we model the idealized interaction of STDP and synaptic normalization in a single neuron as a simple stochastic process and derive analytically that the alignment effect can be described by a so-called Kesten process. From this we can derive that synaptic efficacy alignment requires potentiation-dominated learning regimes. We verify these conditions in a single-neuron model with independent spiking activities but more realistic synapses. As expected, we only observe synaptic efficacy alignment for long-term potentiation-biased STDP. Finally, we explore how well the findings transfer to recurrent neural networks where the learning mechanisms interact with the correlated activity of the network. We find that due to the self-reinforcing correlations in recurrent circuits under STDP, alignment occurs for both long-term potentiation- and depression-biased STDP, because the learning will be potentiation dominated in both cases due to the potentiating events induced by correlated activity. This is in line with recent results demonstrating a dominance of potentiation over depression during waking and normalization during sleep. This leads us to predict that individual spine pairs will be more similar after sleep compared to after sleep deprivation. In conclusion, we show that synaptic normalization in conjunction with coordinated

  1. Molecular spectroscopic study for suggested mechanism of chrome tanned leather.

    PubMed

    Nashy, Elshahat H A; Osman, Osama; Mahmoud, Abdel Aziz; Ibrahim, Medhat

    2012-03-01

    Collagen represents the structural protein of the extracellular matrix, which gives strength of hides and/or skin under tanning process. Chrome tan is the most important tanning agent all over the world. The methods for production of leather evolved over several centuries as art and engineering with little understanding of the underlying science. The present work is devoted to suggest the most probable mechanistic action of chrome tan on hide proteins. First the affect of Cr upon hide protein is indicated by the studied mechanical properties. Then the spectroscopic characterization of the hide protein as well as chrome tanned leather was carried out with Horizontal Attenuated Total Reflection (HATR) FT-IR. The obtained results indicate how the chromium can attached with the active sites of collagen. Molecular modeling confirms that chromium can react with amino as well as carboxylate groups. Four schemes were obtained to describe the possible interactions of chrome tan with hide proteins. PMID:22225606

  2. Molecular spectroscopic study for suggested mechanism of chrome tanned leather

    NASA Astrophysics Data System (ADS)

    Nashy, Elshahat H. A.; Osman, Osama; Mahmoud, Abdel Aziz; Ibrahim, Medhat

    2012-03-01

    Collagen represents the structural protein of the extracellular matrix, which gives strength of hides and/or skin under tanning process. Chrome tan is the most important tanning agent all over the world. The methods for production of leather evolved over several centuries as art and engineering with little understanding of the underlying science. The present work is devoted to suggest the most probable mechanistic action of chrome tan on hide proteins. First the affect of Cr upon hide protein is indicated by the studied mechanical properties. Then the spectroscopic characterization of the hide protein as well as chrome tanned leather was carried out with Horizontal Attenuated Total Reflection (HATR) FT-IR. The obtained results indicate how the chromium can attached with the active sites of collagen. Molecular modeling confirms that chromium can react with amino as well as carboxylate groups. Four schemes were obtained to describe the possible interactions of chrome tan with hide proteins.

  3. Strong selection barriers explain microgeographic adaptation in wild salamander populations.

    PubMed

    Richardson, Jonathan L; Urban, Mark C

    2013-06-01

    Microgeographic adaptation occurs when populations evolve divergent fitness advantages across the spatial scales at which focal organisms regularly disperse. Although an increasing number of studies find evidence for microgeographic adaptation, the underlying causes often remain unknown. Adaptive divergence requires some combination of limited gene flow and strong divergent natural selection among populations. In this study, we estimated the relative influence of selection, gene flow, and the spatial arrangement of populations in shaping patterns of adaptive divergence in natural populations of the spotted salamander (Ambystoma maculatum). Within the study region, A. maculatum co-occur with the predatory marbled salamander (Ambystoma opacum) in some ponds, and past studies have established a link between predation risk and adaptive trait variation in A. maculatum. Using 14 microsatellite loci, we found a significant pattern of genetic divergence among A. maculatum populations corresponding to levels of A. opacum predation risk. Additionally, A. maculatum foraging rate was strongly associated with predation risk, genetic divergence, and the spatial relationship of ponds on the landscape. Our results indicate the sorting of adaptive genotypes by selection regime and strongly suggest that substantial selective barriers operate against gene flow. This outcome suggests that microgeographic adaptation in A. maculatum is possible because strong antagonistic selection quickly eliminates maladapted phenotypes despite ongoing and substantial immigration. Increasing evidence for microgeographic adaptation suggests a strong role for selective barriers in counteracting the homogenizing influence of gene flow. PMID:23730765

  4. Influence of strong static magnetic field on human cancer HT 1080 cells

    NASA Astrophysics Data System (ADS)

    Rodins, Juris; Korhovs, Vadims; Freivalds, Talivaldis; Buikis, Indulis; Ivanova, Tatjana

    2001-10-01

    The aim of this study was to investigate strong uniform magnetic field influence on the human cancer cells HT 1080. The cells were treated with magnetic field of intensity 1,16 Tesla and with anticancer agent - cis-platinum 0.025 mg/ml or vincristinum 2-3 ng/ml. The intact and the treated cell samples were incubated in a medium with acridine orange (AO). The magnetic field after 15 minutes of influence significantly increased cytoplasmic red fluorescence. Increased AO accumulation in lysosomes suggested to cancer cell metabolic activity stimulation.

  5. Activity.

    ERIC Educational Resources Information Center

    Clearing: Nature and Learning in the Pacific Northwest, 1984

    1984-01-01

    Presents three activities: (1) investigating succession in a schoolground; (2) investigating oak galls; and (3) making sun prints (photographs made without camera or darkroom). Each activity includes a list of materials needed and procedures used. (JN)

  6. Observation of Pairing Correlations in Strongly Localized Amorphous Films

    NASA Astrophysics Data System (ADS)

    Stewart, M. D., Jr.; Valles, J. M., Jr.; Yin, Aijun; Xu, J. M.

    2007-03-01

    We have measured the Superconductor to Insulator Transition (SIT) as a function of thickness at dilution refrigerator temperatures in ultrathin Bi/Sb films perforated with a regular honeycomb array of holes separated by 100 nm. The presence of these perforations profoundly influences the character of the transition. In particular, on the insulating side of the SIT, the resistance as a function of temperature, R(T), rises monotonically and becomes activated below 1K. Closer to the SIT, a minimum develops in the R(T) suggestive of strong superconducting fluctuations and the onset of Cooper pairing. Simultaneously, the perpendicular field magnetoresistance begins to oscillate with a period that corresponds to the superconducting flux quantum. Yet thicker films exhibit a relatively broad R(T) transition toward a zero resistance state. This behavior constitutes direct evidence that the superconducting ground state of this amorphous film system emerges from an insulating state containing localized Cooper pairs. This work has been supported by the NSF through DMR-0203608, and DMR-0605797, AFRL, and ONR.

  7. Linkage study of fibrinogen levels: the Strong Heart Family Study

    PubMed Central

    Best, Lyle G; North, Kari E; Li, Xia; Palmieri, Vittorio; Umans, Jason G; MacCluer, Jean; Laston, Sandy; Haack, Karin; Goring, Harald; Diego, Vincent P; Almasy, Laura; Lee, Elisa T; Tracy, Russell P; Cole, Shelley

    2008-01-01

    Background The pathogenesis of atherosclerosis involves both hemostatic and inflammatory mechanisms. Fibrinogen is associated with both risk of thrombosis and inflammation. A recent meta-analysis showed that risk of coronary heart disease may increase 1.8 fold for 1 g/L of increased fibrinogen, independent of traditional risk factors. It is known that fibrinogen levels may be influenced by demographic, environmental and genetic factors. Epidemiologic and candidate gene studies are available; but few genome-wide linkage studies have been conducted, particularly in minority populations. The Strong Heart Study has demonstrated an increased incidence of cardiovascular disease in the American Indian population, and therefore represents an important source for genetic-epidemiological investigations. Methods The Strong Heart Family Study enrolled over 3,600 American Indian participants in large, multi-generational families, ascertained from an ongoing population-based study in the same communities. Fibrinogen was determined using standard technique in a central laboratory and extensive additional phenotypic measures were obtained. Participants were genotyped for 382 short tandem repeat markers distributed throughout the genome; and results were analyzed using a variance decomposition method, as implemented in the SOLAR 2.0 program. Results Data from 3535 participants were included and after step-wise, linear regression analysis, two models were selected for investigation. Basic demographic adjustments constituted model 1, while model 2 considered waist circumference, diabetes mellitus and postmenopausal status as additional covariates. Five LOD scores between 1.82 and 3.02 were identified, with the maximally adjusted model showing the highest score on chromosome 7 at 28 cM. Genes for two key components of the inflammatory response, i.e. interleukin-6 and "signal transducer and activator of transcription 3" (STAT3), were identified within 2 and 8 Mb of this 1 LOD drop

  8. Towards an integrated European strong motion data distribution

    NASA Astrophysics Data System (ADS)

    Luzi, Lucia; Clinton, John; Cauzzi, Carlo; Puglia, Rodolfo; Michelini, Alberto; Van Eck, Torild; Sleeman, Reinhoud; Akkar, Sinan

    2013-04-01

    Recent decades have seen a significant increase in the quality and quantity of strong motion data collected in Europe, as dense and often real-time and continuously monitored broadband strong motion networks have been constructed in many nations. There has been a concurrent increase in demand for access to strong motion data not only from researchers for engineering and seismological studies, but also from civil authorities and seismic networks for the rapid assessment of ground motion and shaking intensity following significant earthquakes (e.g. ShakeMaps). Aside from a few notable exceptions on the national scale, databases providing access to strong motion data has not appeared to keep pace with these developments. In the framework of the EC infrastructure project NERA (2010 - 2014), that integrates key research infrastructures in Europe for monitoring earthquakes and assessing their hazard and risk, the network activity NA3 deals with the networking of acceleration networks and SM data. Within the NA3 activity two infrastructures are being constructed: i) a Rapid Response Strong Motion (RRSM) database, that following a strong event, automatically parameterises all available on-scale waveform data within the European Integrated waveform Data Archives (EIDA) and makes the waveforms easily available to the seismological community within minutes of an event; and ii) a European Strong Motion (ESM) database of accelerometric records, with associated metadata relevant to earthquake engineering and seismology research communities, using standard, manual processing that reflects the state of the art and research needs in these fields. These two separate repositories form the core infrastructures being built to distribute strong motion data in Europe in order to guarantee rapid and long-term availability of high quality waveform data to both the international scientific community and the hazard mitigation communities. These infrastructures will provide the access to

  9. A new polyphenolics with strong radical scavenging activity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Oxidative stress and antioxidant are believed to be involved in aging process. Dietary antioxidant may delay the onset of aging and progression of chronic disease associated with aging. Herbal medicines are still the mainstay of about 75–80 percent of the world population. We have identified and iso...

  10. Predictive Capability for Strongly Correlated Systems

    SciTech Connect

    Cyrus Umrigar

    2012-05-09

    Diffusion Monte Carlo methods can give highly accurate results for correlated systems, provided that well optimized trial wave functions with accurate nodal surfaces are employed. The Cornell team developed powerful methods for optimizing all the parameters within a multi-determinant Slater-Jastrow form of the wave function. These include the Jastrow parameters within a flexible electron-electron-nucleus form of the Jastrow function, the parameters multiplying the configuration state functions, the orbital parameters and the basis exponents. The method optimizes a linear combination of the energy and the variance of the local energy. The optimal parameters are found iteratively by diagonalizing the Hamiltonian matrix in the space spanned by the wave function and its first-order derivatives, making use of a strong zero-variance principle. It is highly robust, has become the method of choice for correlated wave function optimization and has been adopted by other QMC groups. This optimization method was used on the first-row atoms and homonuclear diatomic molecules, demonstrating that molecular well depths can be obtained with near chemical accuracy quite systematically at the diffusion Monte Carlo level for these systems. In addition the complete ground-state potential energy curve of the C{sub 2} molecule up to the dissociation limit was obtained, and, size consistency and broken spin-symmetry issues in quantum Monte Carlo calculations were studied. The method was used with a eight-electrons-in-eight-orbitals complete active space CAS(8,8) wave function to study the relative energies of the monocyclic and bicyclic forms of m-benzyne. The DMC calculations show that the monocyclic structure is lower in energy than the bicyclic structure by 1.92 kcal/ mole, which is in excellent agreement with the best coupled cluster results (CCSD(T)) and in disagreement with the CCSD results. QMC methods have for the most part been used only for ground states of a given symmetry. We

  11. Suggestions for Teaching 4th Grade LD Students the Concept of Longitude and Latitude in Geography.

    ERIC Educational Resources Information Center

    Holley, Cherie M.

    The paper suggests appropriate activities for teaching learning disabled fourth graders in a regular class the concepts of geographical latitude and longitude. Application of the learning principles identified in a review of the literature suggests the need to include visual, auditory, kinesthetic, and tactile activities of benefit to the entire…

  12. Strong washout approximation to resonant leptogenesis

    SciTech Connect

    Garbrecht, Björn; Gautier, Florian; Klaric, Juraj E-mail: florian.gautier@tum.de

    2014-09-01

    We show that the effective decay asymmetry for resonant Leptogenesis in the strong washout regime with two sterile neutrinos and a single active flavour can in wide regions of parameter space be approximated by its late-time limit ε=Xsin(2φ)/(X{sup 2}+sin{sup 2}φ), where X=8πΔ/(|Y{sub 1}|{sup 2}+|Y{sub 2}|{sup 2}), Δ=4(M{sub 1}-M{sub 2})/(M{sub 1}+M{sub 2}), φ=arg(Y{sub 2}/Y{sub 1}), and M{sub 1,2}, Y{sub 1,2} are the masses and Yukawa couplings of the sterile neutrinos. This approximation in particular extends to parametric regions where |Y{sub 1,2}|{sup 2}>> Δ, i.e. where the width dominates the mass splitting. We generalise the formula for the effective decay asymmetry to the case of several flavours of active leptons and demonstrate how this quantity can be used to calculate the lepton asymmetry for phenomenological scenarios that are in agreement with the observed neutrino oscillations. We establish analytic criteria for the validity of the late-time approximation for the decay asymmetry and compare these with numerical results that are obtained by solving for the mixing and the oscillations of the sterile neutrinos. For phenomenologically viable models with two sterile neutrinos, we find that the flavoured effective late-time decay asymmetry can be applied throughout parameter space.

  13. Why do asthmatic subjects respond so strongly to inhaled adenosine?

    PubMed

    Meade, C J; Dumont, I; Worrall, L

    2001-08-01

    Bronchospasm induced by adenosine is blocked by representatives of all the major classes of drugs used in the treatment of asthma. Understanding the mechanism of this bronchospasm may help understand the way these drugs work. Clinical studies have suggested involvement of neural pathways, mast-like cells and mediators such as histamine, serotonin and lipoxygenase products. There is a strong link between responsiveness to adenosine and eosinophilia. In different animal models A1, A2b and A3 adenosine receptor subclasses have all been implicated in inducing bronchospasm. whilst occupation of the A2a receptor generally has no, or the opposite effect. At least two different mechanisms, both involving neural pathways, exist. One, involving the adenosine A1 receptor, functions in mast cell depleted animals; the other requires interaction with a population of mast-like cells activated over A2b or A3 receptors. Not only histamine but also serotonin and lipoxygenase products released from the mast-like cells are potential mediators. In animal models good reactivity to adenosine receptor agonists is generally only found when the animals are first sensitized and exposed to allergen in ways likely to induce an allergic inflammation. An exception is the BDE rat, which reacts to adenosine receptor agonists such as APNEA or NECA even without allergen exposure. This rat strain does however show evidence of spontaneous eosinophilic inflammation in the lung even without immunization. As mast cells both release adenosine and respond to adenosine, adenosine provides a non-specific method of amplifying specific signals resulting from IgE/antigen interaction. This mechanism may not only have a pathological significance in asthma; it may be part of a normal bodily defense response that in asthmatic subjects is inappropriately activated. PMID:11521747

  14. Strong interactions between spinal cord networks for locomotion and scratching.

    PubMed

    Hao, Zhao-Zhe; Spardy, Lucy E; Nguyen, Edward B L; Rubin, Jonathan E; Berkowitz, Ari

    2011-10-01

    Distinct rhythmic behaviors involving a common set of motoneurons and muscles can be generated by separate central nervous system (CNS) networks, a single network, or partly overlapping networks in invertebrates. Less is known for vertebrates. Simultaneous activation of two networks can reveal overlap or interactions between them. The turtle spinal cord contains networks that generate locomotion and three forms of scratching (rostral, pocket, and caudal), having different knee-hip synergies. Here, we report that in immobilized spinal turtles, simultaneous delivery of types of stimulation, which individually evoked forward swimming and one form of scratching, could 1) increase the rhythm frequency; 2) evoke switches, hybrids, and intermediate motor patterns; 3) recruit a swim motor pattern even when the swim stimulation was reduced to subthreshold intensity; and 4) disrupt rhythm generation entirely. The strength of swim stimulation could influence the result. Thus even pocket scratching and caudal scratching, which do not share a knee-hip synergy with forward swimming, can interact with swim stimulation to alter both rhythm and pattern generation. Model simulations were used to explore the compatibility of our experimental results with hypothetical network architectures for rhythm generation. Models could reproduce experimental observations only if they included interactions between neurons involved in swim and scratch rhythm generation, with maximal consistency between simulations and experiments attained using a model architecture in which certain neurons participated actively in both swim and scratch rhythmogenesis. Collectively, these findings suggest that the spinal cord networks that generate locomotion and scratching have important shared components or strong interactions between them. PMID:21734103

  15. Strong-field approximation for ionization of a diatomic molecule by a strong laser field

    SciTech Connect

    Milosevic, D. B.

    2006-12-15

    We present a theory of ionization of diatomic molecules by a strong laser field. A diatomic molecule is considered as a three-particle system, which consists of two heavy atomic (ionic) centers and an electron. After the separation of the center-of-mass coordinate, the dynamics of this system is reduced to the relative electronic and nuclear coordinates. The exact S-matrix element for ionization is presented in a form in which the laser-molecule interaction is emphasized. This form is useful for application of the molecular strong-field approximation (SFA). We introduced two forms of the molecular SFA, one with the field-free and the other with the field-dressed initial molecular bound state. We relate these two forms of our modified molecular SFA to the standard molecular SFAs, introduced previously using the length gauge and the velocity gauge. Numerical examples of the ionization rates of N{sub 2} and O{sub 2} molecules are shown and compared for all four versions of the molecular SFA and we suggest that our modified molecular SFA should be used instead of the standard molecular SFA.

  16. Activities.

    ERIC Educational Resources Information Center

    Moody, Mally

    1992-01-01

    A series of four activities are presented to enhance students' abilities to appreciate and use trigonometry as a tool in problem solving. Activities cover problems applying the law of sines, the law of cosines, and matching equivalent trigonometric expressions. A teacher's guide, worksheets, and answers are provided. (MDH)

  17. The Healthy Children, Strong Families Intervention: Design and Community Participation

    ERIC Educational Resources Information Center

    Adams, Alexandra K.; LaRowe, Tara L.; Cronin, Kate A.; Prince, Ronald J.; Wubben, Deborah P.; Parker, Tassy; Jobe, Jared B.

    2012-01-01

    Healthy Children, Strong Families (HCSF) is a 2-year, community-driven, family-based randomized controlled trial of a healthy lifestyles intervention conducted in partnership with four Wisconsin American Indian tribes. HCSF is composed of 1 year of targeted home visits to deliver nutritional and physical activity curricula. During Year 1, trained…

  18. New, non-quinone fluorogeldanamycin derivatives strongly inhibit Hsp90.

    PubMed

    Hermane, Jekaterina; Bułyszko, Ilona; Eichner, Simone; Sasse, Florenz; Collisi, Wera; Poso, Antti; Schax, Emilia; Walter, Johanna-Gabriela; Scheper, Thomas; Kock, Klaus; Herrmann, Christian; Aliuos, Pooyan; Reuter, Günter; Zeilinger, Carsten; Kirschning, Andreas

    2015-01-19

    Streptomyces hygroscopicus is a natural producer of geldanamycin. Mutasynthetic supplementation of an AHBA-blocked mutant with all possible monofluoro 3-aminobenzoic acids provided new fluorogeldanamycins. These showed strong antiproliferative activity and inhibitory effects on human heat shock protein Hsp90. Binding to Hsp90 in the low nanomolar range was determined from molecular modelling, AFM analysis and by calorimetric studies. PMID:25572106

  19. Antimicrobial Protegrin-1 Forms Amyloid-Like Fibrils with Rapid Kinetics Suggesting a Functional Link

    PubMed Central

    Jang, Hyunbum; Arce, Fernando Teran; Mustata, Mirela; Ramachandran, Srinivasan; Capone, Ricardo; Nussinov, Ruth; Lal, Ratnesh

    2011-01-01

    Protegrin-1 (PG-1) is an 18 residues long, cysteine-rich β-sheet antimicrobial peptide (AMP). PG-1 induces strong cytotoxic activities on cell membrane and acts as a potent antibiotic agent. Earlier we reported that its cytotoxicity is mediated by its channel-forming ability. In this study, we have examined the amyloidogenic fibril formation properties of PG-1 in comparison with a well-defined amyloid, the amyloid-β (Aβ1–42) peptide. We have used atomic force microscopy (AFM) and thioflavin-T staining to investigate the kinetics of PG-1 fibrils growth and molecular dynamics simulations to elucidate the underlying mechanism. AFM images of PG-1 on a highly hydrophilic surface (mica) show fibrils with morphological similarities to Aβ1–42 fibrils. Real-time AFM imaging of fibril growth suggests that PG-1 fibril growth follows a relatively fast kinetics compared to the Aβ1–42 fibrils. The AFM results are in close agreement with results from thioflavin-T staining data. Furthermore, the results indicate that PG-1 forms fibrils in solution. Significantly, in contrast, we do not detect fibrillar structures of PG-1 on an anionic lipid bilayer 2-dioleoyl-sn-glycero-3-phospho-L-serine/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine; only small PG-1 oligomers can be observed. Molecular dynamics simulations are able to identify the presence of these small oligomers on the membrane bilayer. Thus, our current results show that cytotoxic AMP PG-1 is amyloidogenic and capable of forming fibrils. Overall, comparing β-rich AMPs and amyloids such as Aβ, in addition to cytotoxicity and amyloidogenicity, they share a common structural motif, and are channel forming. These combined properties support a functional relationship between amyloidogenic peptides and β-sheet-rich cytolytic AMPs, suggesting that amyloids channels may have an antimicrobial function. PMID:21463591

  20. Thienoquinolins exert diuresis by strongly inhibiting UT-A urea transporters.

    PubMed

    Ren, Huiwen; Wang, Yanhua; Xing, Yongning; Ran, Jianhua; Liu, Ming; Lei, Tianluo; Zhou, Hong; Li, Runtao; Sands, Jeff M; Yang, Baoxue

    2014-12-15

    Urea transporters (UT) play an important role in the urine concentration mechanism by mediating intrarenal urea recycling, suggesting that UT inhibitors could have therapeutic use as a novel class of diuretic. Recently, we found a thienoquinolin UT inhibitor, PU-14, that exhibited diuretic activity. The purpose of this study was to identify more potent UT inhibitors that strongly inhibit UT-A isoforms in the inner medullary collecting duct (IMCD). Efficient thienoquinolin UT inhibitors were identified by structure-activity relationship analysis. Urea transport inhibition activity was assayed in perfused rat terminal IMCDs. Diuretic activity of the compound was determined in rats and mice using metabolic cages. The results show that the compound PU-48 exhibited potent UT-A inhibition activity. The inhibition was 69.5% with an IC50 of 0.32 μM. PU-48 significantly inhibited urea transport in perfused rat terminal IMCDs. PU-48 caused significant diuresis in UT-B null mice, which indicates that UT-A is the target of PU-48. The diuresis caused by PU-48 did not change blood Na(+), K(+), or Cl(-) levels or nonurea solute excretion in rats and mice. No toxicity was detected in cells or animals treated with PU-48. The results indicate that thienoquinolin UT inhibitors induce a diuresis by inhibiting UT-A in the IMCD. This suggests that they may have the potential to be developed as a novel class of diuretics with fewer side effects than classical diuretics. PMID:25298523