The Perception Of Rhythm And Tempo Modulation In Music

Research is presented on the perception of rhythm, specifically, the detection of changing or modulating inter-onset intervals in simple musical stimuli. The types of changes of rhythmic patterns examined are rhythm modulation and tempo modulation. These two terms are akin to the musician\u27s concepts of agogics, rubato, accelerando and ritardando, all being common expressive devices in musical performance. Rhythm modulation occurs when an initially even or isochronous rhythm becomes increasingly more uneven. Tempo modulation occurs when the beat rate of a rhythm accelerates or decelerates.;Two approaches are adopted to elucidate how such modulating patterns might be perceived, a theoretical one and an experimental one. Following a review of the pertinent literature, a theoretical model of time-interval perception in music is proposed that attempts to synthesize the findings of previous experimentation. The main thrust of the model is that rhythm perception is mediated by two complementary processes: (1) a so-called OSCILLATOR BANK that entrains to stimulus time-intervals on a note-to-note basis, and (2) a SHORT AUDITORY STORE that is responsible for integrating temporally separated events.;The model generates the hypothesis that rhythm modulation will be detected in the OSCILLATOR BANK, whereas tempo modulation will be detected in the SHORT AUDITORY STORE. This hypothesis is tested in three perceptual experiments. To compare the difficulty of detecting rhythm and tempo modulation under various conditions, certain variables are manipulated: the direction of modulation (whether a change onset occurs earlier or later than expected), the initial beat rate, the metrical location of modulation, and the presence or absence of beat subdivision. To measure perceptual difficulty, a type of reaction-time dependent variable and a modulation-type-identification dependent variable are used.;The following results are observed: (a) the direction of modulation is significant only for tempo modulation, (b) rhythm and tempo modulation exhibit contrasting trends across the musical initial-beat-rate range, (c) metrical location does not affect detection and (d) detection is easier with beat subdivision. These results are generally consistent with the hypothesis that rhythm and tempo modulation detection are mediated by contrasting perceptual processes

Characterizing Interactions of Thioflavin-T with Native Proteins Especially Bovine Serum Albumin

Thioflavin T is a fluorescent probe used to monitor formation of cross [beta]-sheet rich amyloid fibrils. Involvement of the amyloid fibrils is implicated in more than 50 human diseases, such as Alzheimer's, Parkinson's and Prion's. The proteins responsible for each of these diseases many as well as model proteins have been used to unravel the process involved in native protein to amyloid transformation, especially, for drug design but with little success thus far. Bovine serum albumin (BSA), predominantly [alpha]-helical in constitution, is one such protein that has been observed to transform to [beta]-sheet rich amyloid. For our thesis project, we set on with these basic lines of evidence for ThT and BSA and devised a study outline. The study was divided into sub sections for better redressal compared to what was reported in literature viz., 1) Characterizing the steps involved in the transformation of BSA from native to amyloid state, 2) Develop methodology to gain information of as many steps as possible, 3) Identify the structural changes triggering BSA on pathway to fibrillation, 4) Computational comparison of the sites with chaperone binding sites and finally 5) if from point 4 we could observe chaperones interfering the aggregation process of BSA. During this thesis work, we observed an unexpected interaction of the reporter ThT molecule with the native BSA. We expanded this further and used a suite of standard proteins and found that ThT has the unlikely affinity to bind to some of the proteins, which are predominantly helical in nature. The present study thus details the aspects of interaction of ThT with BSA. Briefly, our Fluorescence data indicated a strong binding of ThT with BSA, ovalbumin and Alcohol Dehydrogenase. The binding was confirmed with ELISA type binding assays. Further, Circular dichroism showed ThT binding caused a minor structural disruption in the alpha helical content of the BSA which was supported by melting curves where BSA in the presence of ThT was 4 degrees less stable than in the absence of ThT. A control run of myoglobin exhibited no changes in the Tm studies with ThT. In addition, FTIR data exhibited marked changes in the BSA profiles in the presence and absence of ThT. Based on these data we ran the molecular docking simulation on ThT and BSA crystal structure and shortlisted two most predictable binding sites of ThT on BSA

BRD4 inhibition for the treatment of pathological organ fibrosis [version 1; referees: 2 approved]

Fibrosis is defined as excess deposition of extracellular matrix, resulting in tissue scarring and organ dysfunction. It is estimated that 45% of deaths in the developed world are due to fibrosis-induced organ failure. Despite the well-accepted role of fibrosis in the pathogenesis of numerous diseases, there are only two US Food and Drug Administration–approved anti-fibrotic therapies, both of which are currently restricted to the treatment of pulmonary fibrosis. Thus, organ fibrosis represents a massive unmet medical need. Here, we review recent findings suggesting that an epigenetic regulatory protein, BRD4, is a nodal effector of organ fibrosis, and we highlight the potential of small-molecule BRD4 inhibitors for the treatment of diverse fibrotic diseases

Microwave transmission through a single subwavelength annular aperture in a metal plate

Matthew J. Lockyear, Alastair P. Hibbins, J. Roy Sambles, and Christopher R. Lawrence. Physical Review Letters, Vol. 94, article 193902 (2005). "Copyright © 2005 by the American Physical Society."The resonant transmission of a small annular aperture, with a diameter much smaller than the radiation wavelength, in a thin metal plate is studied at microwave frequencies. It transpires that such an annular aperture supports several resonant guided modes, including those that are not quantized in the azimuthal direction. Such modes have resonant frequencies that are largely independent of the diameter of the annular aperture, thus being supported by annular apertures that tend to zero radius. The transmittance of such a structure at microwave frequencies is detailed and compared with the predictions of a finite element method model

Should Histologic Grade Be Incorporated into the TNM Classification System for Small (T1, T2) Node-Negative Breast Adenocarcinomas?

Prognosis of invasive ductal carcinoma (IDC) strongly correlates with tumor grade as determined by Nottingham combined histologic grade. While reporting grade as low grade/favorable (G1), intermediate grade/moderately favorable (G2), and high grade/unfavorable (G3) is recommended by American Joint Committee on Cancer (AJCC) staging system, existing TNM (Primary Tumor/Regional Lymph Nodes/Distant Metastasis) classification does not directly incorporate these data. For large tumors (T3, T4), significance of histologic grade may be clinically moot as those are nearly always candidates for adjuvant therapy. However, for small (T1, T2) node-negative (N0) tumors, grade may be clinically relevant in influencing treatment decisions, but data on outcomes are sparse and controversial. This retrospective study analyzes clinical outcome in patients with small N0 IDC on the basis of tumor grade. Our results suggest that the grade does not impact clinical outcome in T1N0 tumors. In T2N0 tumors, however, it might be prognostically significant and relevant in influencing decisions regarding the need for additional adjuvant therapy and optimal management

Treatment of depressed mothers with disruptive children: A controlled evaluation of cognitive behavioral family intervention

This study compared the effects of two forms of behavioral family intervention in reducing mothers' depression and disruptive behavior problems in families with a clinically depressed parent and a child with significant conduct problems. Fortyseven parents were randomly assigned to either a Behavioral Family Intervention (BFI) or to Cognitive Behavioral Family Intervention (CBFI) which integrated cognitive therapy strategies to treat depression and teaching of parenting skills. Both treatments were equally effective in reducing mothers' depression and child disruptive behavior on observational and self-report measures at postintervention. However, at 6-month follow-up more families in CBFI (53%) compared to BFI (13%) experienced concurrent clinically reliable reductions in maternal depression and child disruptive behavior. These findings support the value of CBFI in reducing depression in mothers of children with disruptive behavior problems

Promiscuous actions of small molecule inhibitors of the protein kinase D-class IIa HDAC axis in striated muscle

AbstractPKD-mediated phosphorylation of class IIa HDACs frees the MEF2 transcription factor to activate genes that govern muscle differentiation and growth. Studies of the regulation and function of this signaling axis have involved MC1568 and Gö-6976, which are small molecule inhibitors of class IIa HDAC and PKD catalytic activity, respectively. We describe unanticipated effects of these compounds. MC1568 failed to inhibit class IIa HDAC catalytic activity in vitro, and exerted divergent effects on skeletal muscle differentiation compared to a bona fide inhibitor of these HDACs. In cardiomyocytes, Gö-6976 triggered calcium signaling and activated stress-inducible kinases. Based on these findings, caution is warranted when employing MC1568 and Gö-6976 as pharmacological tool compounds to assess functions of class IIa HDACs and PKD

Motion analysis of match-play in elite U12 to U16 age-group soccer players

The aim of this study was to quantify the motion demands of match-play in elite U12 to U16 age-group soccer players. Altogether, 112 players from two professional soccer clubs at five age-group levels (U12–U16) were monitored during competitive matches (n=14) using a 5 Hz non-differential global positioning system (NdGPS). Velocity thresholds were normalized for each age-group using the mean squad times for a flying 10 m sprint test as a reference point. Match performance was reported as total distance, high-intensity distance, very high-intensity distance, and sprint distance. Data were reported both in absolute (m) and relative (m min-1) terms due to a rolling substitute policy. The U15 (1.35±0.09 s) and U16 (1.31±0.06 s) players were significantly quicker than the U12 (1.58±0.10 s), U13 (1.52±0.07 s), and U14 (1.51±0.08 s) players in the flying 10 m sprint test (P U12, U13, U14), high-intensity distance (U16 > U12, U13, U14, U15), very high-intensity distance (U16 4 U12, U13), and sprint distance (U16 > U12, U13) than their younger counterparts (P<0.05). When the data are considered relative to match exposure, few differences are apparent. Training prescription for youth soccer players should consider the specific demands of competitive match-play in each age-group