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1.
PLoS One ; 5(9): e12645, 2010 Sep 14.
Article in English | MEDLINE | ID: mdl-20856854

ABSTRACT

BACKGROUND: When two targets are presented in close temporal proximity amongst a rapid serial visual stream of distractors, a period of disrupted attention and attenuated awareness lasting 200-500 ms follows identification of the first target (T1). This phenomenon is known as the "attentional blink" (AB) and is generally attributed to a failure to consolidate information in visual short-term memory due to depleted or disrupted attentional resources. Previous research has shown that items presented during the AB that fail to reach conscious awareness are still processed to relatively high levels, including the level of meaning. For example, missed word stimuli have been shown to prime later targets that are closely associated words. Although these findings have been interpreted as evidence for semantic processing during the AB, closely associated words (e.g., day-night) may also rely on specific, well-worn, lexical associative links which enhance attention to the relevant target. METHODOLOGY/PRINCIPAL FINDINGS: We used a measure of semantic distance to create prime-target pairs that are conceptually close, but have low word associations (e.g., wagon and van) and investigated priming from a distractor stimulus presented during the AB to a subsequent target (T2). The stimuli were words (concrete nouns) in Experiment 1 and the corresponding pictures of objects in Experiment 2. In both experiments, report of T2 was facilitated when this item was preceded by a semantically-related distractor. CONCLUSIONS/SIGNIFICANCE: This study is the first to show conclusively that conceptual information is extracted from distractor stimuli presented during a period of attenuated awareness and that this information spreads to neighbouring concepts within a semantic network.


Subject(s)
Attentional Blink , Semantics , Adolescent , Adult , Attention , Awareness , Female , Humans , Male , Residence Characteristics , Young Adult
2.
J Pharm Biomed Anal ; 43(4): 1324-30, 2007 Mar 12.
Article in English | MEDLINE | ID: mdl-17145157

ABSTRACT

Drug discovery compounds are often isolated as salts of trifluoroacetate from preparative high performance liquid chromatography, which are then used for biological assays in order to assess their efficacy against the biochemical target of interest. It is, therefore, imperative to determine the TFA content in order to ascertain the correct formula weight and when required, to ensure that the TFA has been completely exchanged for another counterion in order to have superior pharmacokinetic properties and to avoid potential toxicity effects. In this paper, we present capillary electrophoresis and (19)F nuclear magnetic resonance methods for determining the TFA content of drug discovery compounds. Furthermore, these methods have been successfully applied in a high-throughput fashion, which is a key feature for general applicability in a pharmaceutical setting.


Subject(s)
Drug Design , Electrophoresis, Capillary/methods , Magnetic Resonance Spectroscopy/methods , Trifluoroacetic Acid/analysis , Cations , Electrophoresis, Capillary/instrumentation , Inhibitory Concentration 50 , Magnetic Resonance Spectroscopy/instrumentation , Molecular Structure , Neutron Activation Analysis/methods , Reproducibility of Results , Sensitivity and Specificity , Trifluoroacetic Acid/chemistry
3.
Electrophoresis ; 27(12): 2477-85, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16718720

ABSTRACT

The biotechnology industry has undergone rapid growth in recent years largely due to the development and success of protein-based therapeutics for a wide range of disorders. Similar to traditional pharmaceuticals, characterization of a therapeutic protein for its physicochemical properties, process monitoring and lot release is crucial. Electrophoresis in the slab-gel format has and continues to be a mainstay of the protein laboratory; and more recently, CE has begun to make significant inroads for protein analysis in industrial settings. This review focuses on the electrophoresis of proteins with an emphasis on protein-based therapeutics in the capillary, slab-gel and to a lesser extent, the microchip format. Reported applications of electrophoresis at several stages of the biopharmaceutical industry covering the period of 2000-2005 will be discussed.


Subject(s)
Electrophoresis, Capillary/methods , Electrophoresis, Microchip/methods , Pharmaceutical Preparations/analysis , Recombinant Proteins/analysis , Biotechnology
4.
Biochem Biophys Res Commun ; 295(3): 682-8, 2002 Jul 19.
Article in English | MEDLINE | ID: mdl-12099694

ABSTRACT

A variety of 3'-untranslated regions (UTRs) were cloned from infectious hepatitis C virus human samples and examined in NS5B polymerase de novo initiation reactions. We isolated and characterized four distinct 3'-UTRs that harbor the conserved terminal 98 nucleotides, but have poly(U/UC) tracts of 25, 93, 98, and 101 nucleotides, respectively. Reconstitution of de novo initiation by the mature NS5B with the different 3'-UTR RNA substrates revealed distinctively sized products that are consistent with internal initiation at specific sites within the polypyrimidine tract. These sites were further mapped by demonstrating that nucleotide substitutions of the cytidylate stretches within the poly(U/UC) template eliminate specific products of de novo synthesis and by showing that these products could be radiolabeled by [gamma-32P]GTP. We also examine analogs that can substitute for GTP in this reaction.


Subject(s)
3' Untranslated Regions , Hepacivirus/genetics , RNA/metabolism , Repetitive Sequences, Nucleic Acid , Viral Nonstructural Proteins/genetics , Base Sequence , Cloning, Molecular , Dose-Response Relationship, Drug , Guanosine Triphosphate/metabolism , Models, Genetic , Molecular Sequence Data , Plasmids/metabolism , Reverse Transcriptase Polymerase Chain Reaction
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