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Permanent URI for this collectionhttps://hdl.handle.net/20.500.14288/6

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    PublicationOpen Access
    Significant variations in Weber fraction for changes in inter-onset interval of a click train over the range of intervals between 5 ms and 300 ms
    (Frontiers, 2014) Yağcıoğlu, Süha; (TBD); Ungan, Pekcan; Faculty Member; (TBD); School of Medicine
    It is a common psychophysical experience that a train of clicks faster than ca. 30/s is heard as one steady sound, whereas temporal patterns occurring on a slower time scale are perceptually resolved as individual auditory events. This phenomenon suggests the existence of two different neural mechanisms for processing of auditory sequences with fast and slow repetition rates. To test this hypothesis we used Weber's law, which is known to be valid for perception of time intervals. Discrimination thresholds and Weber fractions (WFs) for 12 base inter click intervals (ICIs) between 5 and 300 ms were measured from 10 normal hearing subjects by using an ""up-down staircase"" algorithm. The mean WE which is supposed to be constant for any perceptual mechanism according to Weber's law, displayed significant variation with click rate. WFs decreased sharply from an average value of around 5% at repetition rates below 20 Hz to about 0.5% at rates above 67 Hz. Parallel to this steep transition, subjects reported that at rates below 20 Hz they perceived periodicity as a fast tapping rhythm, whereas at rates above 50 Hz the perceived quality was a pitch. Such a dramatic change in WE indicated the existence of two separate mechanisms for processing the click rate for long and short ICIs, based on temporal and spectral features, respectively. A range of rates between 20 and 33 Hz, in which the rate discrimination threshold was maximum, appears to be a region where both of the presumed time and pitch mechanisms are relatively insensitive to rate alterations. Based on this finding, we speculate that the interval-based perception mechanism ceases to function at around 20 Hz and the spectrum based mechanism takes over at around 33 Hz; leaving a transitional gap in between, where neither of the two mechanisms is as sensitive. Another notable finding was a significant drop in WE for ICI = 100 ms, suggesting a connection of time perception to the electroencephalography alpha rhythm.
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    PublicationOpen Access
    The structural pathway of interleukin 1 (IL-1) initiated signaling reveals mechanisms of oncogenic mutations and SNPs in inflammation and cancer
    (Public Library of Science, 2014) Nussinov, Ruth; (TBD); Gürsoy, Attila; Özbabacan, Saliha Ece Acuner; Keskin, Özlem; Faculty Member; (TBD); The Center for Computational Biology and Bioinformatics (CCBB); College of Engineering; 8745; N/A; 26605
    Structural pathways are important because they provide insight into signaling mechanisms; help understand the mechanism of disease-related mutations; and help in drug discovery. While extremely useful, common pathway diagrams lacking structural data are unable to provide mechanistic insight to explain oncogenic mutations or SNPs. Here we focus on the construction of the IL-1 structural pathway and map oncogenic mutations and SNPs to complexes in this pathway. Our results indicate that computational modeling of protein-protein interactions on a large scale can provide accurate, structural atom-level detail of signaling pathways in the human cell and help delineate the mechanism through which a mutation leads to disease. We show that the mutations either thwart the interactions, activating the proteins even in their absence or stabilize them, leading to the same uncontrolled outcome. Computational mapping of mutations on the interface of the predicted complexes may constitute an effective strategy to explain the mechanisms of mutations- constitutive activation or deactivation.