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The disruption and dissolution of directed forgettingHarries, Kay January 1999 (has links)
No description available.
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Untersuchungen zur Anwendbarkeit und Validität von In-vitro-Methoden bezüglich der Inhibition von Cytochrom-P450-Enzymen durch Arzneipflanzenextrakte / Investigations on the applicability and validity of in vitro methods with respect to the inhibition of cytochrome P450 enzymes by plant extractsFrank, Andreas January 2009 (has links) (PDF)
Um Arzneimittelwechselwirkungen von Arzneistoffen sowie neuen Arzneistoffkandidaten zu vermeiden, werden zur Abschätzung des Interaktionsrisikos so genannte In-vitro-Interaktionsstudien durchgeführt. Hierfür werden vor allem Mikrotiterplatten-basierte Fluoreszenz- und LC/MS-Methoden verwendet. Das Ziel dieser Arbeit war die Untersuchung der Anwendbarkeit und Validität dieser In-vitro-Methoden bezüglich der Inhibition von CYP-Enzymen durch Arzneipflanzenextrakte. Die in dieser Arbeit erhaltenen Daten belegen, dass die verwendeten Fluoreszenz-Assays für Pflanzenextrakte keine validen Ergebnisse liefern und für die Bestimmung der inhibitorischen Aktivität von Pflanzenextrakten nur in wenigen Fällen geeignet sind. Bei einigen untersuchten Pflanzenextrakten wurden sehr starke inhibitorische Aktivitäten gefunden, da durch Quenching des Fluoreszenzsignals falsch positive Ergebnisse vorgetäuscht wurden. Ebenso war die Inhibition bei einigen Pflanzenextrakten aufgrund einer starken Eigenfluoreszenz sehr schwach oder konnte überhaupt nicht bestimmt werden. Des Weiteren wurden als Referenzmethoden für die Bestimmung der Inhibition von CYP-Enzymen LC/MS-basierte Methoden mit Online-Festphasenextraktion verwendet, die speziell für Pflanzenextrakte entwickelt und validiert wurden. Die Ergebnisse der LC/MS-basierten CYP-Assays wurden durch die Pflanzenmatrix nicht beeinflusst, so dass diese Assays hervorragend als Referenzmethoden für die Bestimmung der inhibitorischen Aktivität von Pflanzenextrakten geeignet sind. Bei sehr hohen Extraktkonzentrationen zeigten einige Pflanzenextrakte sehr starke Abweichungen der mittels LC/MS und Fluorimetrie in Mikrotiterplatten erhaltenen inhibitorischen Aktivität. Die Verwendung von niedrigen Extraktkonzentrationen führte zu einer besseren Übereinstimmung der erhaltenen Ergebnisse. D.h. vor allem bei hohen Extraktkonzentrationen sind starke Quenching- und Eigenfluoreszenz-Effekte zu erwarten. Dennoch sind auch bei niedrigen Extraktkonzentrationen diese Effekte nicht auszuschließen. In den meisten Veröffentlichungen wurden sehr hohe Testkonzentrationen für die Bestimmung der inhibitorischen Aktivität von Pflanzenextrakten verwendet, so dass mit hoher Wahrscheinlichkeit aufgrund von Quenching- und Eigenfluoreszenz-Effekten falsch positive bzw. negative Ergebnisse erhalten wurden. Untersuchungen zum Quenching haben gezeigt, dass die meisten Extrakte in den üblicherweise verwendeten Konzentrationen (ca. 10-1000 µg/ml) die Fluoreszenzintensität der Metabolite sehr stark reduzierten. Die Quenching-Effekte der Pflanzenextrakte beeinflussten das Fluoreszenzsignal aller enzymatisch gebildeten Metabolite (Cumarin-Derivate, Resorufin, Fluorescein), wobei die Quenching-Effekte bei Resorufin und Fluorescein in ihrer Stärke und Häufigkeit geringer ausfielen. Bei CYP2B6, CYP2C9 und CYP2D6 wurden in Verbindung mit Fluoreszenzsubstraten, die eine Cumarinstruktur aufweisen, sehr oft falsch negative oder gar keine Ergebnisse erhalten, weil die Eigenfluoreszenz der Extrakte die Metabolitenfluoreszenz überlagerte. Quenching-Effekte traten bei den untersuchten Pflanzenextrakten weitaus häufiger auf als eine Eigenfluoreszenz. Aufgrund dieser Tatsachen können die Mikrotiterplatten-basierten Fluoreszenz-Methoden nur eingesetzt werden, wenn vorher gezeigt wurde, dass die Pflanzenextrakte bei allen Testkonzentrationen sowie bei verschiedenen Metabolitenkonzentrationen weder Quenching- noch Eigenfluoreszenz-Effekte zeigen. Ebenso wurde in dieser Arbeit gezeigt, dass die bisher in Veröffentlichungen durchgeführten Kontrollinkubationen nur bedingt zur Kompensation von Quenching- und Eigenfluoreszenz-Effekten geeignet sind. Das Auftreten und Ausmaß der Quenching- und Eigenfluoreszenz-Effekte sind abhängig vom Inhibitor (Pflanzenextrakt), der Inhibitorkonzentration, dem Metaboliten und dessen Anregungs- und Emissionswellenlänge sowie der Metabolitenkonzentration, die durch die enzymatische Umsetzung des Substrats und der inhibitorischen Aktivität des Inhibitors bestimmt wird. Während der Inhibitor, die zu testenden Inhibitorkonzentrationen, der Metabolit sowie dessen Anregungs- und Emissionswellenlänge eine feste Größe darstellen, ist die Metabolitenkonzentration je nach inhibitorischer Aktivität des Inhibitors sehr unterschiedlich. D. h. letztendlich hängt das genaue Ausmaß der Eigenfluoreszenz- und Quenching-Effekte von der inhibitorischen Aktivität der Pflanzenextrakte ab. Es konnte gezeigt werden, dass je geringer die Metabolitenkonzentration ist, desto stärker wird das Fluoreszenzsignal reduziert (Quenching) bzw. erhöht (Eigenfluoreszenz). Eine sinnvolle Kontrollinkubation zur Kompensation von Quenching- und Eigenfluoreszenz-Effekten kann also gar nicht durchgeführt werden. Bei In-vitro-Untersuchungen zur Bestimmung der inhibitorischen Aktivität ist die Metabolitenkonzentration nicht bekannt und somit der Einfluss der Effekte nicht bestimmbar. / To avoid interactions with drugs or new drug candidates, in vitro interaction studies are performed for the assessment of their drug interaction potential. For this purpose, microtiterplate-based fluorimetric and LC/MS-based methods are used. The goal of this work was to investigate the applicability and validity of the microtiterplate-based fluorescence methods with respect to the inhibition of CYP enzymes by plant extracts. The results show that the microtiterplate-based fluorimetric assays do not provide reliable results for plant extracts and that these assays are only suitable for the determination of the inhibitory activities of plant extracts in some cases. Several of the tested plant extracts showed very strong inhibitory activities. But, due to quenching effects, the extracts additionally reduced the fluorescence signals of the metabolites thereby pretending false positive results. Also, the inhibition of CYP enzymes by some plant extracts was very weak or even not determinable due to intrinsic fluorescence. Additionally, LC/MS-based methods with online solid phase extraction were developed and validated as reference methods for the determination of the inhibition of CYP enzymes. Since the results of the LC/MS-based assays were not affected by the matrix of the plant extracts, these assays are suitable reference methods for the determination of the inhibitory activities of plant extracts. At high extract concentrations some plant extracts showed strong deviations of the inhibitory activities using LC/MS- and microtiterplate-based fluorimetric assays. The use of low extract concentrations provided a good correlation of the obtained inhibitory activities. That means, especially high extract concentrations are responsible for strong quenching effects and intrinsic fluorescence thereby pretending false positive or negative results. Nevertheless, also at low extract concentrations these effects were observed. Interestingly, in most publications very high concentrations of plant extracts were used for the determination of the inhibitory activities, so that reduced or increased IC50 values were obtained due to quenching and intrinsic fluorescence. Analyses of the quenching effects showed that most extracts strongly reduced the fluorescence intensity of the metabolites at frequently used concentrations (ca. 10-1000 µg/ml). The quenching effects of the plant extracts decreased the fluorescence signal of all enzymatically produced metabolites (coumarin derivatives, resorufin and fluorescein), whereas the quenching effects for resorufin and fluorescein were much less potent and frequent. By using coumarin derivatives as substrates for CYP2B6, CYP2C9 und CYP2D6 often false negative or no results were obtained, because the intrinsic fluorescence of the extracts interfered with the metabolite fluorescence. Finally, quenching effects occurred more often than intrinsic fluorescence. Due to these facts, microtiterplate based fluorimetric methods are only useable if the plant extracts show neither quenching nor intrinsic fluorescence for all inhibitor concentrations at various metabolite concentrations. Also, analyses of this work showed that control incubations performed in recently published studies are only of limited use for the compensation of quenching effects and intrinsic fluorescence. The occurrence and the extent of quenching effects and intrinsic fluorescence depend on the inhibitor (plant extract), the inhibitor concentration, the metabolite and its excitation and emission wavelength as well as the metabolite concentration, which is determined by the inhibitory activity of the inhibitor. Whereas the inhibitor, the inhibitor concentration, the metabolite as well as its excitation and emission wavelength are constant parameters, the metabolite concentration depends on the inhibitory activity of the inhibitor. That means, the extent of quenching and intrinsic fluorescence depends mainly on the inhibitory activity of the plant extracts. Studies in this work showed that the lower the metabolite concentration the more the fluorescence signal is decreased (quenching) or increased (intrinsic fluorescence). Thus, control incubations to compensate quenching effects and intrinsic fluorescence are not valid, because the metabolite concentration is unknown and thus the influence of the effects is not determinable.
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The relative sensitivity of algae to inhibitors from plant litterMartin, Derek January 1999 (has links)
Decomposing barley straw (Hordeum vulgare) and oak leaves (Quercus robur) have previously been shown to inhibit the growth of a limited number of algae and cyanobacteria. Bioassays were conducted on a range of algae and cyanobacteria to evaluate their relative sensitivities to litter-derived inhibitor(s). A range of sensitivities were found, including some species that were stimulated by litter-derived inhibitor(s). Susceptibility to decomposing plant litter did not appear to be related to general taxonomic or structural features since susceptibility differed widely, even amongst members of the same genus. A microcystin-producing strain of Microcystis aeruginosa was very susceptible to decomposing barley straw. No specific effect on cell structure or morphology could be attributed solely to the litter-derived inhibitor(s). Evidence suggested that cell division, rather than cell expansion, was slowed or inhibited. Bioassays using Euglena gracilis showed the inhibitory compounds were not derived from the phototransformation of litter decomposition products and were not acting primarily by inhibiting photosynthesis. Barley straw inhibited the growth of filamentous algae in a drainage channel and, subsequently, the channel was recolonized by macrophytes. A one-year treatment with barley straw inhibited algal growth, but this reduction in growth was not maintained when the straw was removed. After three-years treatment with barley straw, macrophytes retained dominance after the removal of the straw. No inhibition of algal growth was observed in a different straw-treated drainage channel. The implications for water management are discussed.
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Amygdaloid lesions and behavioral inhibition in the rat.Pellegrino, Louis J. January 1967 (has links)
No description available.
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Inhibitory Account of Semantic Interference Resolution in Memory: Suppression of Competing InformationNgo, Ka Wai Joan 15 December 2011 (has links)
Using a novel paradigm, we provide direct evidence for the role of inhibition during semantic interference resolution in memory. In Experiment 1, target words were primed via a naming task. Then, a cue word prompted participants to generate either a meaningfully related or unrelated word. Producing an unrelated word should require suppression of the cue's closest associates, which were the primed targets. Finally, participants read a list of words including the suppressed targets. Participants were slower to name targets in the unrelated condition than in the related condition, indicating that generating an unrelated word required suppression of competitors. Experiment 2 eliminated the initial priming phase, and a robust suppression effect was observed. Both studies showed that naming targets in the unrelated condition was even slower than controls. These results reflect that resolving semantic competition entails suppression of rejected competitors to below baseline levels, supporting an inhibitory account of interference resolution.
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Inhibitory Account of Semantic Interference Resolution in Memory: Suppression of Competing InformationNgo, Ka Wai Joan 15 December 2011 (has links)
Using a novel paradigm, we provide direct evidence for the role of inhibition during semantic interference resolution in memory. In Experiment 1, target words were primed via a naming task. Then, a cue word prompted participants to generate either a meaningfully related or unrelated word. Producing an unrelated word should require suppression of the cue's closest associates, which were the primed targets. Finally, participants read a list of words including the suppressed targets. Participants were slower to name targets in the unrelated condition than in the related condition, indicating that generating an unrelated word required suppression of competitors. Experiment 2 eliminated the initial priming phase, and a robust suppression effect was observed. Both studies showed that naming targets in the unrelated condition was even slower than controls. These results reflect that resolving semantic competition entails suppression of rejected competitors to below baseline levels, supporting an inhibitory account of interference resolution.
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Inhibition of Telomerase Activity by hTR Gene in Human J5 Hepatoma Cell LineChao, Shou-Bin 22 July 2000 (has links)
Telomerase, a ribonucleoprotein enzyme has its own internal RNA template that elongates telomeres and stabilizes chromosome structure. The mayority of hepatoma express high levels of human telomerase template RNA ( hTR ) that is essential for cellular telomerase activity. In this study, we examined whether hTR¡Bantisence hTR and IFN£\ gene had a telomerase activity inhibitory effect on J5 hepatoma cell line, through transfection via an expression vector . The expression of mRNAs for hTERT¡BhTR¡Bc-myc¡BIFN£\¡Bp16 and p27 were also detected.
The results suggested that inhibition of telomerase activity and overexpression of hTR gene were observed in FhTR-treated J5 cells. The expression of mRNAs for hTERT¡Bc-myc¡BIFN£\¡Bp16 and p27 genes were not changed whether telomerase was inhibited or not. In addition, genomic DNA fragmentation was observed in telomerase inhibited J5 cells indicating that apoptosis was undergoing in these cells.
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Inhibition studies of carbamoyl phosphate synthetase from Escherichia coliTripathi, Neha 25 April 2007 (has links)
Carbamoyl phosphate synthetase (CPS) catalyzes the formation of carbamoyl
phosphate (CP) from MgATP, bicarbonate, and glutamine. It has three active sites, one
present on the small subunit and the two phosphorylation sites present on the large
subunit. These two nucleotide binding sites are homologous. Six compounds were
designed to mimic the reactive intermediate species carboxy phosphate, and product
cabamoyl phosphate. The apparent Ki values calculated estimated the inhibitory strengths
of these compounds. These plots were also utilized in identifying the linear inhibitors,
nonlinear inhibitors and partial inhibitors. Inhibition patterns were obtained with these
compounds using various assay formats. Partial inhibition displayed by phosphono
formate for the full biosynthetic reaction can be utilized in support of the sequential
mechanism for CPS.
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Die Rolle der Blätter bei der korrelativen Hemmung von Seitentrieben /Töpperwein, Heinrich. January 1992 (has links) (PDF)
Univ., FB Gartenbau, Diss.--Hannover, 1992.
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Effects of visual cortex lesions on modulation of the cutaneous and acoustic blink reflexes and choice reaction time /Sonnenberg, Douglas C. January 2003 (has links)
Thesis (M.S.)--University of Missouri-Columbia, 2003. / Figure 1 referred to on leaf 2 is shown on leaf 20. Typescript. Includes bibliographical references (leaves 35-36). Also available on the Internet.
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