Optical emission and electron capture of rare-earth trivalent ions located at distinct sites in SnO(2) thin films

We present photoluminescence and decay of photo excited conductivity data for sol-gel SnO(2) thin films doped with rare earth ions Eu(3+) and Er(3+), a material with nanoscopic crystallites. Photoluminescence spectra are obtained under excitation with several monochromatic light sources, such as Kr(+) and Ar(+) lasers, Xe lamp plus a selective monochromator with UV grating, and the fourth harmonic of a Nd: YAG laser (4.65eV), which assures band-to-band transition and energy transfer to the ion located at matrix sites, substitutional to Sn(4+). The luminescence structure is rather different depending on the location of the rare-earth doping, at lattice symmetric sites or segregated at grain boundary layer, where it is placed in asymmetric sites. The decay of photo-excited conductivity also shows different trapping rate depending on the rare-earth concentration. For Er-doped films, above the saturation limit, the evaluated capture energy is higher than for films with concentration below the limit, in good agreement with the different behaviour obtained from luminescence data. For Eu-doped films, the difference between capture energy and grain boundary barrier is not so evident, even though the luminescence spectra are rather distinct.

Analysis of HCV quasispecies dynamic under selective pressure of combined therapy

Background: The quasispecies composition of Hepatitis C virus (HCV) could have important implications with regard to viral persistence and response to interferon-based therapy. The complete NS5A was analyzed to evaluate whether the composition of NS5A quasispecies of HCV 1a/1b is related to responsiveness to combined interferon pegylated (PEG-IFN) and ribavirin therapy.Methods: Viral RNA was isolated from serum samples collected before, during and after treatment from virological sustained responder (SVR), non-responder (NR) and the end-of-treatment responder patients (ETR). NS5A region was amplified, cloned and sequenced. Six hundred and ninety full-length NS5A sequences were analyzed.Results: This study provides evidence that lower nucleotide diversity of the NS5A region pre-therapy is associated with viral clearance. Analysis of samples of NRs and the ETRs time points showed that genetic diversity of populations tend to decrease over time. Post-therapy population of ETRs presented higher genetic distance from baseline probably due to the bottleneck phenomenon observed for those patients in the end of treatment. The viral effective population of those patients also showed a strong decrease after therapy. Otherwise, NRs demonstrated a continuous variation or stability of effective populations and genetic diversity over time that did not seem to be related to therapy. Phylogenetic relationships concerning complete NS5A sequences obtained from patients did not demonstrate clustering associated with specific response patterns. However, distinctive clustering of pre/post-therapy sequences was observed. In addition, the evolution of quasispecies over time was subjected to purifying or relaxed purifying selection. Codons 157 (P03), 182 and 440 (P42), 62 and 404 (P44) were found to be under positive selective pressure but it failed to be related to the therapy.Conclusion: These results confirm the hypothesis that a relationship exists between NS5A heterogeneity and response to therapy in patients infected with chronic hepatitis C. © 2013 Jardim et al.; licensee BioMed Central Ltd.

Selective inhibition of Alzheimer disease-like tau aggregation by phenothiazines.

In Alzheimer disease (AD) the microtubule-associated protein tau is redistributed exponentially into paired helical filaments (PHFs) forming neurofibrillary tangles, which correlate with pyramidal cell destruction and dementia. Amorphous neuronal deposits and PHFs in AD are characterized by aggregation through the repeat domain and C-terminal truncation at Glu-391 by endogenous proteases. We show that a similar proteolytically stable complex can be generated in vitro following the self-aggregation of tau protein through a high-affinity binding site in the repeat domain. Once started, tau capture can be propagated by seeding the further accumulation of truncated tau in the presence of proteases. We have identified a nonneuroleptic phenothiazine previously used in man (methylene blue, MB), which reverses the proteolytic stability of protease-resistant PHFs by blocking the tau-tau binding interaction through the repeat domain. Although MB is inhibitory at a higher concentration than may be achieved clinically, the tau-tau binding assay was used to identify desmethyl derivatives of MB that have Ki values in the nanomolar range. Neuroleptic phenothiazines are inactive. Tau aggregation inhibitors do not affect the tau-tubulin interaction, which also occurs through the repeat domain. Our findings demonstrate that biologically selective pharmaceutical agents could be developed to facilitate the proteolytic degradation of tau aggregates and prevent the further propagation of tau capture in AD.

Identification of interdomain sequences promoting the intronless evolution of a bacterial protein family.

In the evolution of eukaryotic genes, introns are believed to have played a major role in increasing the probability of favorable duplication events, chance recombinations, and exon shuffling resulting in functional hybrid proteins. As a rule, prokaryotic genes lack introns, and the examples of prokaryotic introns described do not seem to have contributed to gene evolution by exon shuffling. Still, certain protein families in modern bacteria evolve rapidly by recombination of genes, duplication of functional domains, and as shown for protein PAB of the anaerobic bacterial species Peptostreptococcus magnus, by the shuffling of an albumin-binding protein module from group C and G streptococci. Characterization of a protein PAB-related gene in a P. magnus strain with less albumin-binding activity revealed that the shuffled module was missing. Based on this fact and observations made when comparing gene sequences of this family of bacterial surface proteins interacting with albumin and/or immunoglobulin, a model is presented that can explain how this rapid intronless evolution takes place. A new kind of genetic element is introduced: the recer sequence promoting interdomain, in frame recombination and acting as a structure-less flexibility-promoting spacer in the corresponding protein. The data presented also suggest that antibiotics could represent the selective pressure behind the shuffling of protein modules in P. magnus, a member of the indigenous bacterial flora.

Isolation of multiple sequences from the Plasmodium falciparum genome that encode conserved domains homologous to those in erythrocyte-binding proteins.

Open reading frames in the Plasmodium falciparum genome encode domains homologous to the adhesive domains of the P. falciparum EBA-175 erythrocyte-binding protein (eba-175 gene product) and those of the Plasmodium vivax and Plasmodium knowlesi Duffy antigen-binding proteins. These domains are referred to as Duffy binding-like (DBL), after the receptor that determines P. vivax invasion of Duffy blood group-positive human erythrocytes. Using oligonucleotide primers derived from short regions of conserved sequence, we have developed a reverse transcription-PCR method that amplifies sequences encoding the DBL domains of expressed genes. Products of these reverse transcription-PCR amplifications include sequences of single-copy genes (including eba-175) and variably transcribed genes that cross-hybridize to multiple regions of the genome. Restriction patterns of the multicopy genes show a high degree of polymorphism among different parasite lines, whereas single-copy genes are generally conserved. Characterization of the single-copy genes has identified a gene (ebl-1) that is related to eba-175 and is likely to be involved in erythrocyte invasion.

Conotoxins as selective inhibitors of neuronal ion channels, receptors and transporters

Cone snails have evolved a vast array of peptide toxins for prey capture and defence. These peptides are directed against a wide variety of pharmacological targets, making them an invaluable source of ligands for studying the properties of these targets in normal and diseased states. A number of these peptides have shown efficacy in vivo, including inhibitors of calcium channels, the norepinephrine transporter, nicotinic acetylcholine receptors, NMDA receptors and neurotensin receptors, with several having undergone pre-clinical or clinical development for the treatment of pain.

UML approach to the generation of test sequences for Java-based concurrent systems

Starting with a UML specification that captures the underlying functionality of some given Java-based concurrent system, we describe a systematic way to construct, from this specification, test sequences for validating an implementation of the system. The approach is to first extend the specification to create UML state machines that directly address those aspects of the system we wish to test. To be specific, the extended UML state machines can capture state information about the number of waiting threads or the number of threads blocked on a given object. Using the SAL model checker we can generate from the extended UML state machines sequences that cover all the various possibilities of events and states. These sequences can then be directly transformed into test sequences suitable for input into a testing tool such as ConAn. As an illustration, the methodology is applied to generate sequences for testing a Java implementation of the producer-consumer system. © 2005 IEEE

The role of prior exposure on the capture of attention by items in working memory

The Biased Competition Model (BCM) suggests both top-down and bottom-up biases operate on selective attention (e.g., Desimone & Duncan, 1995). It has been suggested that top-down control signals may arise from working memory. In support, Downing (2000) found faster responses to probes presented in the location of stimuli held vs. not held in working memory. Soto, Heinke, Humphreys, and Blanco (2005) showed the involuntary nature of this effect and that shared features between stimuli were sufficient to attract attention. Here we show that stimuli held in working memory had an influence on the deployment of attentional resources even when: (1) It was detrimental to the task, (2) there was equal prior exposure, and (3) there was no bottom-up priming. These results provide further support for involuntary top-down guidance of attention from working memory and the basic tenets of the BCM, but further discredit the notion that bottom-up priming is necessary for the effect to occur.

A deficit in encoding the order of visual sequences in developmental dyslexia: a non -phonological deficit

The present thesis tested the hypothesis of Stanovich, Siegel, & Gottardo (1997) that surface dyslexia is the result of a milder phonological deficit than that seen in phonological dyslexia coupled with reduced reading experience. We found that a group of adults with surface dyslexia showed a phonological deficit that was commensurate with that shown by a group of adults with phonological dyslexia (matched for chronological age and verbal and non-verbal IQ) and normal reading experience. We also showed that surface dyslexia cannot be accounted for by a semantic impairment or a deficit in the verbal learning and recall of lexical-semantic information (such as meaningful words), as both dyslexic subgroups performed the same. This study has replicated the results of our published study that surface dyslexia is not the consequence of a mild retardation or reduced learning opportunities but a separate impairment linked to a deficit in written lexical learning, an ability needed to create novel lexical representations from a series of unrelated visual units, which is independent from the phonological deficit (Romani, Di Betta, Tsouknida & Olson, 2008). This thesis also provided evidence that a selective nonword reading deficit in developmental dyslexia persists beyond poor phonology. This was shown by finding a nonword reading deficit even in the presence of normal regularity effects in the dyslexics (when compared to both reading and spelling-age matched controls). A nonword reading deficit was also found in the surface dyslexics. Crucially, this deficit was as strong as in the phonological dyslexics despite better functioning of the sublexical route for the former. These results suggest that a nonword reading deficit cannot be solely explained by a phonological impairment. We, thus, suggested that nonword reading should also involve another ability relating to the processing of novel visual orthographic strings, which we called 'orthographic coding'. We then investigated the ability to process series of independent units within multi-element visual arrays and its relationship with reading and spelling problems. We identified a deficit in encoding the order of visual sequences (involving both linguistic and nonlinguistic information) which was significantly associated with word and nonword processing. More importantly, we revealed significant contributions to orthographic skills in both dyslexic and control individuals, even after age, performance IQ and phonological skills were controlled. These results suggest that spelling and reading do not only tap phonological skills but also order encoding skills.

Diversity of luciferase sequences and bioluminescence production in Baltic Sea Alexandrium ostenfeldii

The toxic dinoflagellate Alexandrium ostenfeldii is the only bioluminescent bloom-forming phytoplankton in coastal waters of the Baltic Sea. We analysed partial luciferase gene (lcf) sequences and bioluminescence production in Baltic A. ostenfeldii bloom populations to assess the distribution and consistency of the trait in the Baltic Sea, and to evaluate applications for early detection of toxic blooms. Lcf was consistently present in 61 Baltic Sea A. ostenfeldii strains isolated from six separate bloom sites. All Baltic Sea strains except one produced bioluminescence. In contrast, the presence of lcf and the ability to produce bioluminescence did vary among strains from other parts of Europe. In phylogenetic analyses, lcf sequences of Baltic Sea strains clustered separately from North Sea strains, but variation between Baltic Sea strains was not sufficient to distinguish between bloom populations. Clustering of the lcf marker was similar to internal transcribed spacer (ITS) sequences with differences being minor and limited to the lowest hierarchical clusters, indicating a similar rate of evolution of the two genes. In relation to monitoring, the consistent presence of lcf and close coupling of lcf with bioluminescence suggests that bioluminescence can be used to reliably monitor toxic bloom-forming A. ostenfeldii in the Baltic Sea.

Diversity of luciferase sequences and bioluminescence production in Baltic Sea Alexandrium ostenfeldii

The toxic dinoflagellate Alexandrium ostenfeldii is the only bioluminescent bloom-forming phytoplankton in coastal waters of the Baltic Sea. We analysed partial luciferase gene (lcf) sequences and bioluminescence production in Baltic A. ostenfeldii bloom populations to assess the distribution and consistency of the trait in the Baltic Sea, and to evaluate applications for early detection of toxic blooms. Lcf was consistently present in 61 Baltic Sea A. ostenfeldii strains isolated from six separate bloom sites. All Baltic Sea strains except one produced bioluminescence. In contrast, the presence of lcf and the ability to produce bioluminescence did vary among strains from other parts of Europe. In phylogenetic analyses, lcf sequences of Baltic Sea strains clustered separately from North Sea strains, but variation between Baltic Sea strains was not sufficient to distinguish between bloom populations. Clustering of the lcf marker was similar to internal transcribed spacer (ITS) sequences with differences being minor and limited to the lowest hierarchical clusters, indicating a similar rate of evolution of the two genes. In relation to monitoring, the consistent presence of lcf and close coupling of lcf with bioluminescence suggests that bioluminescence can be used to reliably monitor toxic bloom-forming A. ostenfeldii in the Baltic Sea.

Role of corporate governance in mitigating the selective disclosure of executive stock option information

We examine the nature and extent of statutory executive stock option (ESO) disclosures by Australian listed companies over the 2001 to 2004 period, and the influence of corporate governance mechanisms on these disclosures. Our results show a progressive increase in overall compliance from 2001 to 2004. However, despite the improved compliance, the results reveal managements’ continued reluctance to disclose more sensitive ESO information. Factors associated with good internal governance, including board independence, audit committee independence and effectiveness, and compensation committee independence and effectiveness are found to contribute to improved compliance. Similarly, certain external governance factors are associated with improved disclosure, including external auditor quality, shareholder activism (as proxied by companies identified as poor performers by the Australian Shareholders’ Association), and regulatory intervention.