662 research outputs found
Complex sequencing rules of birdsong can be explained by simple hidden Markov processes
Complex sequencing rules observed in birdsongs provide an opportunity to
investigate the neural mechanism for generating complex sequential behaviors.
To relate the findings from studying birdsongs to other sequential behaviors,
it is crucial to characterize the statistical properties of the sequencing
rules in birdsongs. However, the properties of the sequencing rules in
birdsongs have not yet been fully addressed. In this study, we investigate the
statistical propertiesof the complex birdsong of the Bengalese finch (Lonchura
striata var. domestica). Based on manual-annotated syllable sequences, we first
show that there are significant higher-order context dependencies in Bengalese
finch songs, that is, which syllable appears next depends on more than one
previous syllable. This property is shared with other complex sequential
behaviors. We then analyze acoustic features of the song and show that
higher-order context dependencies can be explained using first-order hidden
state transition dynamics with redundant hidden states. This model corresponds
to hidden Markov models (HMMs), well known statistical models with a large
range of application for time series modeling. The song annotation with these
models with first-order hidden state dynamics agreed well with manual
annotation, the score was comparable to that of a second-order HMM, and
surpassed the zeroth-order model (the Gaussian mixture model (GMM)), which does
not use context information. Our results imply that the hierarchical
representation with hidden state dynamics may underlie the neural
implementation for generating complex sequences with higher-order dependencies
Measuring affective well-being at work using short-form scales : implications for affective structures and participant instructions
Measuring affective well-being in organizational studies has become increasingly widespread, given its association with key work-performance and other markers of organizational functioning. As such, researchers and policy-makers need to be confident that well-being measures are valid, reliable and robust. To reduce the burden on participants in applied settings, short-form measures of affective well-being are proving popular. However, these scales are seldom validated as standalone, comprehensive measures in their own right. In this article, we used a short-form measure of affective well-being with 10 items: the Daniels five-factor measure of affective well-being (D-FAW). In Study 1, across six applied sample groups (N = 2624), we found that the factor structure of the short-form D-FAW is robust when issued as a standalone measure, and that it should be scored differently depending on the participant instruction used. When participant instructions focus on now or today, then affect is best represented by five discrete emotion factors. When participant instructions focus on the past week, then affect is best represented by two or three mood-based factors. In Study 2 (N = 39), we found good construct convergent validity of short-form D-FAW with another widely used scale (PANAS). Implications for the measurement and structure of affect are discussed
Weak Responses to Auditory Feedback Perturbation during Articulation in Persons Who Stutter: Evidence for Abnormal Auditory-Motor Transformation
Previous empirical observations have led researchers to propose that auditory feedback (the auditory perception of self-produced sounds when speaking) functions abnormally in the speech motor systems of persons who stutter (PWS). Researchers have theorized that an important neural basis of stuttering is the aberrant integration of auditory information into incipient speech motor commands. Because of the circumstantial support for these hypotheses and the differences and contradictions between them, there is a need for carefully designed experiments that directly examine auditory-motor integration during speech production in PWS. In the current study, we used real-time manipulation of auditory feedback to directly investigate whether the speech motor system of PWS utilizes auditory feedback abnormally during articulation and to characterize potential deficits of this auditory-motor integration. Twenty-one PWS and 18 fluent control participants were recruited. Using a short-latency formant-perturbation system, we examined participants’ compensatory responses to unanticipated perturbation of auditory feedback of the first formant frequency during the production of the monophthong [ε]. The PWS showed compensatory responses that were qualitatively similar to the controls’ and had close-to-normal latencies (~150 ms), but the magnitudes of their responses were substantially and significantly smaller than those of the control participants (by 47% on average, p<0.05). Measurements of auditory acuity indicate that the weaker-than-normal compensatory responses in PWS were not attributable to a deficit in low-level auditory processing. These findings are consistent with the hypothesis that stuttering is associated with functional defects in the inverse models responsible for the transformation from the domain of auditory targets and auditory error information into the domain of speech motor commands
The Effect of Azithromycin on Ivermectin Pharmacokinetics—A Population Pharmacokinetic Model Analysis
This paper describes the use of a modeling and simulation approach to explore a reported pharmacokinetic interaction between two drugs (ivermectin and azithromycin), which along with albendazole, are being developed for combination use in neglected tropical diseases. This approach is complementary to more traditional pharmacokinetic and safety studies that need to be conducted to support combined use of different health interventions. A mathematical model of ivermectin pharmacokinetics was created and used to simulate multiple trials, and the probability of certain outcomes (very high peak blood ivermectin levels when given in combination) was determined. All simulated peak blood levels were within ranges known to be safe and well tolerated. Additional field studies are needed to confirm these findings
Ribozyme-based insulator parts buffer synthetic circuits from genetic context
Synthetic genetic programs are built from circuits that integrate sensors and implement temporal control of gene expression. Transcriptional circuits are layered by using promoters to carry the signal between circuits. In other words, the output promoter of one circuit serves as the input promoter to the next. Thus, connecting circuits requires physically connecting a promoter to the next circuit. We show that the sequence at the junction between the input promoter and circuit can affect the input-output response (transfer function) of the circuit. A library of putative sequences that might reduce (or buffer) such context effects, which we refer to as 'insulator parts', is screened in Escherichia coli. We find that ribozymes that cleave the 5′ untranslated region (5′-UTR) of the mRNA are effective insulators. They generate quantitatively identical transfer functions, irrespective of the identity of the input promoter. When these insulators are used to join synthetic gene circuits, the behavior of layered circuits can be predicted using a mathematical model. The inclusion of insulators will be critical in reliably permuting circuits to build different programs.Life Technologies, Inc.United States. Defense Advanced Research Projects Agency (DARPA CLIO N66001-12-C-4018)United States. Office of Naval Research (N00014-10-1-0245)National Science Foundation (U.S.) (CCF-0943385)National Institutes of Health (U.S.) (AI067699)National Science Foundation (U.S.). Synthetic Biology Engineering Research Center (SynBERC, SA5284-11210
Passerine Exposure to Primarily PCDFs and PCDDs in the River Floodplains Near Midland, Michigan, USA
House wren (Troglodytes aedon), tree swallow (Tachycineta bicolor), and eastern bluebird (Sialia sialis) tissues collected in study areas (SAs) downstream of Midland, Michigan (USA) contained concentrations of polychlorinated dibenzofurans (PCDFs) and polychlorinated dibenzo-p-dioxins (PCDDs) greater than in upstream reference areas (RAs) in the region. The sum of concentrations of PCDD/DFs (ΣPCDD/DFs) in eggs of house wrens and eastern bluebirds from SAs were 4- to 22-fold greater compared to those from RAs, whereas concentrations in tree swallow eggs were similar among areas. Mean concentrations of ΣPCDD/DFs and sum 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (ΣTEQsWHO-Avian), based on 1998 WHO avian toxic equivalency factors, in house wren and eastern bluebird eggs ranged from 860 (430) to 1500 (910) ng/kg wet weight (ww) and 470 (150) to 1100 (510) ng/kg ww, respectively, at the most contaminated study areas along the Tittabawassee River, whereas mean concentrations in tree swallow eggs ranged from 280 (100) to 760 (280) ng/kg ww among all locations. Concentrations of ΣPCDD/DFs in nestlings of all studied species at SAs were 3- to 50-fold greater compared to RAs. Mean house wren, tree swallow, and eastern bluebird nestling concentrations of ΣPCDD/DFs and ΣTEQsWHO-Avian ranged from 350 (140) to 610 (300) ng/kg ww, 360 (240) to 1100 (860) ng/kg ww, and 330 (100) to 1200 (690) ng/kg ww, respectively, at SAs along the Tittabawassee River. Concentrations of ΣTEQsWHO-Avian were positively correlated with ΣPCDD/DF concentrations in both eggs and nestlings of all species studied. Profiles of relative concentrations of individual congeners were dominated by furan congeners (69–84%), primarily 2,3,7,8-tetrachlorodibenzofuran and 2,3,4,7,8-pentachlorodibenzofuran, for all species at SAs on the Tittabawassee and Saginaw rivers but were dominated by dioxin congeners at upstream RAs
Somatostatin Receptor 1 and 5 Double Knockout Mice Mimic Neurochemical Changes of Huntington's Disease Transgenic Mice
Selective degeneration of medium spiny neurons and preservation of medium sized aspiny interneurons in striatum has been implicated in excitotoxicity and pathophysiology of Huntington's disease (HD). However, the molecular mechanism for the selective sparing of medium sized aspiny neurons and vulnerability of projection neurons is still elusive. The pathological characteristic of HD is an extensive reduction of the striatal mass, affecting caudate putamen. Somatostatin (SST) positive neurons are selectively spared in HD and Quinolinic acid/N-methyl-D-aspartic acid induced excitotoxicity, mimic the model of HD. SST plays neuroprotective role in excitotoxicity and the biological effects of SST are mediated by five somatostatin receptor subtypes (SSTR1-5). and R6/2 mice. Conversely, the expression of somatostatin receptor subtypes, enkephalin and phosphatidylinositol 3-kinases were strain specific. SSTR1/5 appears to be important in regulating NMDARs, DARPP-32 and signaling molecules in similar fashion as seen in HD transgenic mice.This is the first comprehensive description of disease related changes upon ablation of G- protein coupled receptor gene. Our results indicate that SST and SSTRs might play an important role in regulation of neurodegeneration and targeting this pathway can provide a novel insight in understanding the pathophysiology of Huntington's disease
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