Overview of ERA Integrated Technology Demonstration (ITD) 51A Ultra-High Bypass (UHB) Integration for Hybrid Wing Body (HWB)

NASA Technical Reports Server (NTRS)

Flamm, Jeffrey D.; James, Kevin D.; Bonet, John T.

2016-01-01

The NASA Environmentally Responsible Aircraft Project (ERA) was a ve year project broken into two phases. In phase II, high N+2 Technical Readiness Level demonstrations were grouped into Integrated Technology Demonstrations (ITD). This paper describes the work done on ITD-51A: the Vehicle Systems Integration, Engine Airframe Integration Demonstration. Refinement of a Hybrid Wing Body (HWB) aircraft from the possible candidates developed in ERA Phase I was continued. Scaled powered, and unpowered wind- tunnel testing, with and without acoustics, in the NASA LARC 14- by 22-foot Subsonic Tunnel, the NASA ARC Unitary Plan Wind Tunnel, and the 40- by 80-foot test section of the National Full-Scale Aerodynamics Complex (NFAC) in conjunction with very closely coupled Computational Fluid Dynamics was used to demonstrate the fuel burn and acoustic milestone targets of the ERA Project.

Transformation from a pure time delay to a mixed time and phase delay representation in the auditory forebrain pathway.

PubMed

Vonderschen, Katrin; Wagner, Hermann

2012-04-25

Birds and mammals exploit interaural time differences (ITDs) for sound localization. Subsequent to ITD detection by brainstem neurons, ITD processing continues in parallel midbrain and forebrain pathways. In the barn owl, both ITD detection and processing in the midbrain are specialized to extract ITDs independent of frequency, which amounts to a pure time delay representation. Recent results have elucidated different mechanisms of ITD detection in mammals, which lead to a representation of small ITDs in high-frequency channels and large ITDs in low-frequency channels, resembling a phase delay representation. However, the detection mechanism does not prevent a change in ITD representation at higher processing stages. Here we analyze ITD tuning across frequency channels with pure tone and noise stimuli in neurons of the barn owl's auditory arcopallium, a nucleus at the endpoint of the forebrain pathway. To extend the analysis of ITD representation across frequency bands to a large neural population, we employed Fourier analysis for the spectral decomposition of ITD curves recorded with noise stimuli. This method was validated using physiological as well as model data. We found that low frequencies convey sensitivity to large ITDs, whereas high frequencies convey sensitivity to small ITDs. Moreover, different linear phase frequency regimes in the high-frequency and low-frequency ranges suggested an independent convergence of inputs from these frequency channels. Our results are consistent with ITD being remodeled toward a phase delay representation along the forebrain pathway. This indicates that sensory representations may undergo substantial reorganization, presumably in relation to specific behavioral output.

Characteristics of stereo reproduction with parametric loudspeakers

NASA Astrophysics Data System (ADS)

Aoki, Shigeaki; Toba, Masayoshi; Tsujita, Norihisa

2012-05-01

A parametric loudspeaker utilizes nonlinearity of a medium and is known as a super-directivity loudspeaker. The parametric loudspeaker is one of the prominent applications of nonlinear ultrasonics. So far, the applications have been limited monaural reproduction sound system for public address in museum, station and street etc. In this paper, we discussed characteristics of stereo reproduction with two parametric loudspeakers by comparing with those with two ordinary dynamic loudspeakers. In subjective tests, three typical listening positions were selected to investigate the possibility of correct sound localization in a wide listening area. The binaural information was ILD (Interaural Level Difference) or ITD (Interaural Time Delay). The parametric loudspeaker was an equilateral hexagon. The inner and outer diameters were 99 and 112 mm, respectively. Signals were 500 Hz, 1 kHz, 2 kHz and 4 kHz pure tones and pink noise. Three young males listened to test signals 10 times in each listening condition. Subjective test results showed that listeners at the three typical listening positions perceived correct sound localization of all signals using the parametric loudspeakers. It was almost similar to those using the ordinary dynamic loudspeakers, however, except for the case of sinusoidal waves with ITD. It was determined the parametric loudspeaker could exclude the contradiction between the binaural information ILD and ITD that occurred in stereo reproduction with ordinary dynamic loudspeakers because the super directivity of parametric loudspeaker suppressed the cross talk components.

Combination of individual tree detection and area-based approach in imputation of forest variables using airborne laser data

NASA Astrophysics Data System (ADS)

Vastaranta, Mikko; Kankare, Ville; Holopainen, Markus; Yu, Xiaowei; Hyyppä, Juha; Hyyppä, Hannu

2012-01-01

The two main approaches to deriving forest variables from laser-scanning data are the statistical area-based approach (ABA) and individual tree detection (ITD). With ITD it is feasible to acquire single tree information, as in field measurements. Here, ITD was used for measuring training data for the ABA. In addition to automatic ITD (ITD auto), we tested a combination of ITD auto and visual interpretation (ITD visual). ITD visual had two stages: in the first, ITD auto was carried out and in the second, the results of the ITD auto were visually corrected by interpreting three-dimensional laser point clouds. The field data comprised 509 circular plots ( r = 10 m) that were divided equally for testing and training. ITD-derived forest variables were used for training the ABA and the accuracies of the k-most similar neighbor ( k-MSN) imputations were evaluated and compared with the ABA trained with traditional measurements. The root-mean-squared error (RMSE) in the mean volume was 24.8%, 25.9%, and 27.2% with the ABA trained with field measurements, ITD auto, and ITD visual, respectively. When ITD methods were applied in acquiring training data, the mean volume, basal area, and basal area-weighted mean diameter were underestimated in the ABA by 2.7-9.2%. This project constituted a pilot study for using ITD measurements as training data for the ABA. Further studies are needed to reduce the bias and to determine the accuracy obtained in imputation of species-specific variables. The method could be applied in areas with sparse road networks or when the costs of fieldwork must be minimized.

Internal Tandem Duplication in FLT3 Attenuates Proliferation and Regulates Resistance to the FLT3 Inhibitor AC220 by Modulating p21Cdkn1a and Pbx1 in Hematopoietic Cells

PubMed Central

Abe, Mariko; Pelus, Louis M.; Singh, Pratibha; Hirade, Tomohiro; Onishi, Chie; Purevsuren, Jamiyan; Taketani, Takeshi; Yamaguchi, Seiji; Fukuda, Seiji

2016-01-01

Internal tandem duplication (ITD) mutations in the Fms-related tyrosine kinase 3 (FLT3) gene (FLT3-ITD) are associated with poor prognosis in patients with acute myeloid leukemia (AML). Due to the development of drug resistance, few FLT3-ITD inhibitors are effective against FLT3-ITD+ AML. In this study, we show that FLT3-ITD activates a novel pathway involving p21Cdkn1a (p21) and pre-B cell leukemia transcription factor 1 (Pbx1) that attenuates FLT3-ITD cell proliferation and is involved in the development of drug resistance. FLT3-ITD up-regulated p21 expression in both mouse bone marrow c-kit+-Sca-1+-Lin- (KSL) cells and Ba/F3 cells. The loss of p21 expression enhanced growth factor-independent proliferation and sensitivity to cytarabine as a consequence of concomitantly enriching the S+G2/M phase population and significantly increasing the expression of Pbx1, but not Evi-1, in FLT3-ITD+ cells. This enhanced cell proliferation following the loss of p21 was partially abrogated when Pbx1 expression was silenced in FLT3-ITD+ primary bone marrow colony-forming cells and Ba/F3 cells. When FLT3-ITD was antagonized with AC220, a selective inhibitor of FLT3-ITD, p21 expression was decreased coincident with Pbx1 mRNA up-regulation and a rapid decline in the number of viable FLT3-ITD+ Ba/F3 cells; however, the cells eventually became refractory to AC220. Overexpressing p21 in FLT3-ITD+ Ba/F3 cells delayed the emergence of cells that were refractory to AC220, whereas p21 silencing accelerated their development. These data indicate that FLT3-ITD is capable of inhibiting FLT3-ITD+ cell proliferation through the p21/Pbx1 axis and that treatments that antagonize FLT3-ITD contribute to the subsequent development of cells that are refractory to a FLT3-ITD inhibitor by disrupting p21 expression. PMID:27387666

The acoustical bright spot and mislocalization of tones by human listeners.

PubMed

Macaulay, Eric J; Hartmann, William M; Rakerd, Brad

2010-03-01

Listeners attempted to localize 1500-Hz sine tones presented in free field from a loudspeaker array, spanning azimuths from 0 degrees (straight ahead) to 90 degrees (extreme right). During this task, the tone levels and phases were measured in the listeners' ear canals. Because of the acoustical bright spot, measured interaural level differences (ILD) were non-monotonic functions of azimuth with a maximum near 55 degrees . In a source-identification task, listeners' localization decisions closely tracked the non-monotonic ILD, and thus became inaccurate at large azimuths. When listeners received training and feedback, their accuracy improved only slightly. In an azimuth-discrimination task, listeners decided whether a first sound was to the left or to the right of a second. The discrimination results also reflected the confusion caused by the non-monotonic ILD, and they could be predicted approximately by a listener's identification results. When the sine tones were amplitude modulated or replaced by narrow bands of noise, interaural time difference (ITD) cues greatly reduced the confusion for most listeners, but not for all. Recognizing the important role of the bright spot requires a reevaluation of the transition between the low-frequency region for localization (mainly ITD) and the high-frequency region (mainly ILD).

Envelope contributions to the representation of interaural time difference in the forebrain of barn owls.

PubMed

Tellers, Philipp; Lehmann, Jessica; Führ, Hartmut; Wagner, Hermann

2017-09-01

Birds and mammals use the interaural time difference (ITD) for azimuthal sound localization. While barn owls can use the ITD of the stimulus carrier frequency over nearly their entire hearing range, mammals have to utilize the ITD of the stimulus envelope to extend the upper frequency limit of ITD-based sound localization. ITD is computed and processed in a dedicated neural circuit that consists of two pathways. In the barn owl, ITD representation is more complex in the forebrain than in the midbrain pathway because of the combination of two inputs that represent different ITDs. We speculated that one of the two inputs includes an envelope contribution. To estimate the envelope contribution, we recorded ITD response functions for correlated and anticorrelated noise stimuli in the barn owl's auditory arcopallium. Our findings indicate that barn owls, like mammals, represent both carrier and envelope ITDs of overlapping frequency ranges, supporting the hypothesis that carrier and envelope ITD-based localization are complementary beyond a mere extension of the upper frequency limit. NEW & NOTEWORTHY The results presented in this study show for the first time that the barn owl is able to extract and represent the interaural time difference (ITD) information conveyed by the envelope of a broadband acoustic signal. Like mammals, the barn owl extracts the ITD of the envelope and the carrier of a signal from the same frequency range. These results are of general interest, since they reinforce a trend found in neural signal processing across different species. Copyright © 2017 the American Physiological Society.

Effects of interaural time differences in fine structure and envelope on lateral discrimination in electric hearing.

PubMed

Majdak, Piotr; Laback, Bernhard; Baumgartner, Wolf-Dieter

2006-10-01

Bilateral cochlear implant (CI) listeners currently use stimulation strategies which encode interaural time differences (ITD) in the temporal envelope but which do not transmit ITD in the fine structure, due to the constant phase in the electric pulse train. To determine the utility of encoding ITD in the fine structure, ITD-based lateralization was investigated with four CI listeners and four normal hearing (NH) subjects listening to a simulation of electric stimulation. Lateralization discrimination was tested at different pulse rates for various combinations of independently controlled fine structure ITD and envelope ITD. Results for electric hearing show that the fine structure ITD had the strongest impact on lateralization at lower pulse rates, with significant effects for pulse rates up to 800 pulses per second. At higher pulse rates, lateralization discrimination depended solely on the envelope ITD. The data suggest that bilateral CI listeners benefit from transmitting fine structure ITD at lower pulse rates. However, there were strong interindividual differences: the better performing CI listeners performed comparably to the NH listeners.

Enhancing interaural-delay-based extents of laterality at high frequencies by using ``transposed stimuli''

NASA Astrophysics Data System (ADS)

Bernstein, Leslie R.; Trahiotis, Constantine

2003-06-01

An acoustic pointing task was used to determine whether interaural temporal disparities (ITDs) conveyed by high-frequency ``transposed'' stimuli would produce larger extents of laterality than ITDs conveyed by bands of high-frequency Gaussian noise. The envelopes of transposed stimuli are designed to provide high-frequency channels with information similar to that conveyed by the waveforms of low-frequency stimuli. Lateralization was measured for low-frequency Gaussian noises, the same noises transposed to 4 kHz, and high-frequency Gaussian bands of noise centered at 4 kHz. Extents of laterality obtained with the transposed stimuli were greater than those obtained with bands of Gaussian noise centered at 4 kHz and, in some cases, were equivalent to those obtained with low-frequency stimuli. In a second experiment, the general effects on lateral position produced by imposed combinations of bandwidth, ITD, and interaural phase disparities (IPDs) on low-frequency stimuli remained when those stimuli were transposed to 4 kHz. Overall, the data were fairly well accounted for by a model that computes the cross-correlation subsequent to known stages of peripheral auditory processing augmented by low-pass filtering of the envelopes within the high-frequency channels of each ear.

Dnmt3a deletion cooperates with the Flt3/ITD mutation to drive leukemogenesis in a murine model

PubMed Central

Poitras, Jennifer L.; Heiser, Diane; Li, Li; Nguyen, Bao; Nagai, Kozo; Duffield, Amy S.; Gamper, Christopher; Small, Donald

2016-01-01

Internal tandem duplications of the juxtamembrane domain of FLT3 (FLT3/ITD) are among the most common mutations in Acute Myeloid Leukemia (AML). Resulting in constitutive activation of the kinase, FLT3/ITD portends a particularly poor prognosis, with reduced overall survival and increased rates of relapse. We previously generated a knock-in mouse, harboring an internal tandem duplication at the endogenous Flt3 locus, which develops a fatal myeloproliferative neoplasm (MPN), but fails to develop acute leukemia, suggesting additional mutations are necessary for transformation. To investigate the potential cooperativity of FLT3/ITD and mutant DNMT3A, we bred a conditional Dnmt3a knockout to a substrain of our Flt3/ITD knock-in mice, and found deletion of Dnmt3a significantly reduced median survival of Flt3ITD/+ mice in a dose dependent manner. As expected, pIpC treated Flt3ITD/+ mice solely developed MPN, while Flt3ITD/+;Dnmt3af/f and Flt3ITD/+;Dnmt3af/+ developed a spectrum of neoplasms, including MPN, T-ALL, and AML. Functionally, FLT3/ITD and DNMT3A deletion cooperate to expand LT-HSCs, which exhibit enhanced self-renewal in serial re-plating assays. These results illustrate that DNMT3A loss cooperates with FLT3/ITD to generate hematopoietic neoplasms, including AML. In combination with FLT3/ITD, homozygous Dnmt3a knock-out results in reduced time to disease onset, LT-HSC expansion, and a higher incidence of T-ALL compared with loss of just one allele. The co-occurrence of FLT3 and DNMT3A mutations in AML, as well as subsets of T-ALL, suggests the Flt3ITD/+;Dnmt3af/f model may serve as a valuable resource for delineating effective therapeutic strategies in two clinically relevant contexts. PMID:27636998

The spatial unmasking of speech: evidence for within-channel processing of interaural time delay.

PubMed

Edmonds, Barrie A; Culling, John F

2005-05-01

Across-frequency processing by common interaural time delay (ITD) in spatial unmasking was investigated by measuring speech reception thresholds (SRTs) for high- and low-frequency bands of target speech presented against concurrent speech or a noise masker. Experiment 1 indicated that presenting one of these target bands with an ITD of +500 micros and the other with zero ITD (like the masker) provided some release from masking, but full binaural advantage was only measured when both target bands were given an ITD of + 500 micros. Experiment 2 showed that full binaural advantage could also be achieved when the high- and low-frequency bands were presented with ITDs of equal but opposite magnitude (+/- 500 micros). In experiment 3, the masker was also split into high- and low-frequency bands with ITDs of equal but opposite magnitude (+/-500 micros). The ITD of the low-frequency target band matched that of the high-frequency masking band and vice versa. SRTs indicated that, as long as the target and masker differed in ITD within each frequency band, full binaural advantage could be achieved. These results suggest that the mechanism underlying spatial unmasking exploits differences in ITD independently within each frequency channel.

Time-Varying Distortions of Binaural Information by Bilateral Hearing Aids: Effects of Nonlinear Frequency Compression.

PubMed

Brown, Andrew D; Rodriguez, Francisco A; Portnuff, Cory D F; Goupell, Matthew J; Tollin, Daniel J

2016-10-03

In patients with bilateral hearing loss, the use of two hearing aids (HAs) offers the potential to restore the benefits of binaural hearing, including sound source localization and segregation. However, existing evidence suggests that bilateral HA users' access to binaural information, namely interaural time and level differences (ITDs and ILDs), can be compromised by device processing. Our objective was to characterize the nature and magnitude of binaural distortions caused by modern digital behind-the-ear HAs using a variety of stimuli and HA program settings. Of particular interest was a common frequency-lowering algorithm known as nonlinear frequency compression, which has not previously been assessed for its effects on binaural information. A binaural beamforming algorithm was also assessed. Wide dynamic range compression was enabled in all programs. HAs were placed on a binaural manikin, and stimuli were presented from an arc of loudspeakers inside an anechoic chamber. Stimuli were broadband noise bursts, 10-Hz sinusoidally amplitude-modulated noise bursts, or consonant-vowel-consonant speech tokens. Binaural information was analyzed in terms of ITDs, ILDs, and interaural coherence, both for whole stimuli and in a time-varying sense (i.e., within a running temporal window) across four different frequency bands (1, 2, 4, and 6 kHz). Key findings were: (a) Nonlinear frequency compression caused distortions of high-frequency envelope ITDs and significantly reduced interaural coherence. (b) For modulated stimuli, all programs caused time-varying distortion of ILDs. (c) HAs altered the relationship between ITDs and ILDs, introducing large ITD-ILD conflicts in some cases. Potential perceptual consequences of measured distortions are discussed. © The Author(s) 2016.

The acoustical bright spot and mislocalization of tones by human listeners

PubMed Central

Macaulay, Eric J.; Hartmann, William M.; Rakerd, Brad

2010-01-01

Listeners attempted to localize 1500-Hz sine tones presented in free field from a loudspeaker array, spanning azimuths from 0° (straight ahead) to 90° (extreme right). During this task, the tone levels and phases were measured in the listeners’ ear canals. Because of the acoustical bright spot, measured interaural level differences (ILD) were non-monotonic functions of azimuth with a maximum near 55°. In a source-identification task, listeners’ localization decisions closely tracked the non-monotonic ILD, and thus became inaccurate at large azimuths. When listeners received training and feedback, their accuracy improved only slightly. In an azimuth-discrimination task, listeners decided whether a first sound was to the left or to the right of a second. The discrimination results also reflected the confusion caused by the non-monotonic ILD, and they could be predicted approximately by a listener’s identification results. When the sine tones were amplitude modulated or replaced by narrow bands of noise, interaural time difference (ITD) cues greatly reduced the confusion for most listeners, but not for all. Recognizing the important role of the bright spot requires a reevaluation of the transition between the low-frequency region for localization (mainly ITD) and the high-frequency region (mainly ILD). PMID:20329844

Behavioural sensitivity to binaural spatial cues in ferrets: evidence for plasticity in the duplex theory of sound localization

PubMed Central

Keating, Peter; Nodal, Fernando R; King, Andrew J

2014-01-01

For over a century, the duplex theory has guided our understanding of human sound localization in the horizontal plane. According to this theory, the auditory system uses interaural time differences (ITDs) and interaural level differences (ILDs) to localize low-frequency and high-frequency sounds, respectively. Whilst this theory successfully accounts for the localization of tones by humans, some species show very different behaviour. Ferrets are widely used for studying both clinical and fundamental aspects of spatial hearing, but it is not known whether the duplex theory applies to this species or, if so, to what extent the frequency range over which each binaural cue is used depends on acoustical or neurophysiological factors. To address these issues, we trained ferrets to lateralize tones presented over earphones and found that the frequency dependence of ITD and ILD sensitivity broadly paralleled that observed in humans. Compared with humans, however, the transition between ITD and ILD sensitivity was shifted toward higher frequencies. We found that the frequency dependence of ITD sensitivity in ferrets can partially be accounted for by acoustical factors, although neurophysiological mechanisms are also likely to be involved. Moreover, we show that binaural cue sensitivity can be shaped by experience, as training ferrets on a 1-kHz ILD task resulted in significant improvements in thresholds that were specific to the trained cue and frequency. Our results provide new insights into the factors limiting the use of different sound localization cues and highlight the importance of sensory experience in shaping the underlying neural mechanisms. PMID:24256073

An introduction to testing techniques in the Intelsat TDMA/DSI system

NASA Astrophysics Data System (ADS)

Colby, R. J.; Parthasarathy, R.; Prouse, D. W.

1983-09-01

The testing methods developed for the Intelsat TDMA/DSI system (ITDS) are surveyed. The ITDS is briefly characterized, and the system features and the reference-station and traffic-terminal functions are listed in tables and illustrated with block diagrams. The primary differences between the ITDS testing and the testing of conventional satellite-communication systems are outlined. The ITDS tests for new systems, new services, and fault isolation and the ITDS test situations and test paths are explained.

Temporal Changes in FLT3-ITD Regulation of Stem Cell Self-Renewal and Leukemogenesis

DTIC Science & Technology

2015-09-01

whether FLT3-ITD depletes HSCs, expands restricted progenitors and promotes a myeloproliferative neoplasm during the adult, but not fetal stage of...goals: Aim 1: To test whether FLT3-ITD depletes HSCs, expands restricted progenitors and promotes a myeloproliferative neoplasm during the adult, but...progenitor pool and myeloproliferative neoplasms (MPN) were also evident in 14 day old FLT3-ITD mice but not fetal mice (Fig. 1F and not shown). FLT3-ITD

Spectral composition of concurrent noise affects neuronal sensitivity to interaural time differences of tones in the dorsal nucleus of the lateral lemniscus.

PubMed

Siveke, Ida; Leibold, Christian; Grothe, Benedikt

2007-11-01

We are regularly exposed to several concurrent sounds, producing a mixture of binaural cues. The neuronal mechanisms underlying the localization of concurrent sounds are not well understood. The major binaural cues for localizing low-frequency sounds in the horizontal plane are interaural time differences (ITDs). Auditory brain stem neurons encode ITDs by firing maximally in response to "favorable" ITDs and weakly or not at all in response to "unfavorable" ITDs. We recorded from ITD-sensitive neurons in the dorsal nucleus of the lateral lemniscus (DNLL) while presenting pure tones at different ITDs embedded in noise. We found that increasing levels of concurrent white noise suppressed the maximal response rate to tones with favorable ITDs and slightly enhanced the response rate to tones with unfavorable ITDs. Nevertheless, most of the neurons maintained ITD sensitivity to tones even for noise intensities equal to that of the tone. Using concurrent noise with a spectral composition in which the neuron's excitatory frequencies are omitted reduced the maximal response similar to that obtained with concurrent white noise. This finding indicates that the decrease of the maximal rate is mediated by suppressive cross-frequency interactions, which we also observed during monaural stimulation with additional white noise. In contrast, the enhancement of the firing rate to tones at unfavorable ITD might be due to early binaural interactions (e.g., at the level of the superior olive). A simple simulation corroborates this interpretation. Taken together, these findings suggest that the spectral composition of a concurrent sound strongly influences the spatial processing of ITD-sensitive DNLL neurons.

Effect of an inspiratory impedance threshold device on hemodynamics during conventional manual cardiopulmonary resuscitation.

PubMed

Pirrallo, Ronald G; Aufderheide, Tom P; Provo, Terry A; Lurie, Keith G

2005-07-01

In animals in cardiac arrest, an inspiratory impedance threshold device (ITD) has been shown to improve hemodynamics and neurologically intact survival. The objective of this study was to determine whether an ITD would improve blood pressure (BP) in patients receiving CPR for out-of-hospital cardiac arrest. This prospective, randomized, double-blind, intention-to-treat study was conducted in the Milwaukee, WI, emergency medical services (EMS) system. EMS personnel used an active (functional) or sham (non-functional) ITD on a tracheal tube on adults in cardiac arrest of presumed cardiac etiology. Care between groups was similar except for ITD type. Low dose epinephrine (1mg) was used per American Heart Association Guidelines. Femoral arterial BP (mmHg) was measured invasively during CPR. Mean+/-S.D. time from ITD placement to first invasive BP recording was approximately 14 min. Twelve patients were treated with a sham ITD versus 10 patients with an active ITD. Systolic BPs (mean+/-S.D.) [number of patients treated at given time point] at T = 0 (time of first arterial BP measurement), and T=2, 5 and 7 min were 85+/-29 [10], 85+/-23 [10], 85+/-16 [9] and 69+/-22 [8] in the group receiving an active ITD compared with 43+/-15 [12], 47+/-16 [12], 47+/-20 [9], and 52+/-23 [9] in subjects treated with a sham ITD, respectively (p < 0.01 for all times). Diastolic BPs at T = 0, 2, 5 and 7 min were 20+/-12, 21+/-13, 23+/-15 and 25+/-14 in the group receiving an active ITD compared with 15+/-9, 17+/-8, 17+/-9 and 19+/-8 in subjects treated with a sham ITD, respectively (p = NS for all times). No significant adverse device events were reported. Use of the active ITD was found to increase systolic pressures safely and significantly in patients in cardiac arrest compared with sham controls.

Maps of interaural delay in the owl's nucleus laminaris

PubMed Central

Shah, Sahil; McColgan, Thomas; Ashida, Go; Kuokkanen, Paula T.; Brill, Sandra; Kempter, Richard; Wagner, Hermann

2015-01-01

Axons from the nucleus magnocellularis form a presynaptic map of interaural time differences (ITDs) in the nucleus laminaris (NL). These inputs generate a field potential that varies systematically with recording position and can be used to measure the map of ITDs. In the barn owl, the representation of best ITD shifts with mediolateral position in NL, so as to form continuous, smoothly overlapping maps of ITD with iso-ITD contours that are not parallel to the NL border. Frontal space (0°) is, however, represented throughout and thus overrepresented with respect to the periphery. Measurements of presynaptic conduction delay, combined with a model of delay line conduction velocity, reveal that conduction delays can account for the mediolateral shifts in the map of ITD. PMID:26224776

RNA-based FLT3-ITD allelic ratio is associated with outcome and ex vivo response to FLT3 inhibitors in pediatric AML.

PubMed

Cucchi, David G J; Denys, Barbara; Kaspers, Gertjan J L; Janssen, Jeroen J W M; Ossenkoppele, Gert J; de Haas, Valérie; Zwaan, C Michel; van den Heuvel-Eibrink, Marry M; Philippé, Jan; Csikós, Tamás; Kwidama, Zinia; de Moerloose, Barbara; de Bont, Eveline S J M; Lissenberg-Witte, Birgit I; Zweegman, Sonja; Verwer, Femke; Vandepoele, Karl; Schuurhuis, Gerrit Jan; Sonneveld, Edwin; Cloos, Jacqueline

2018-05-31

Controversy exists whether internal tandem duplication of FMS-like tyrosine kinase 3 ( FLT3- internal tandem duplication [ITD]) allelic ratio (AR) and/or length of the ITD should be taken into account for risk stratification of pediatric acute myeloid leukemia (AML) and whether it should be measured on RNA or DNA. Moreover, the ITD status may be of relevance for selecting patients eligible for FLT3 inhibitors. Here, we included 172 pediatric AML patients, of whom 36 (21%) harbored FLT3 -ITD as determined on both RNA and DNA. Although there was a good correlation between both parameters AR spearman = 0.62 (95% confidence interval, 0.22-0.87) and ITDlength spearman = 0.98 (95% confidence interval, 0.90-1.00), only AR ≥ 0.5 and length ≥48 base pairs (bps) based on RNA measurements were significantly associated with overall survival (AR: P logrank = .008; ITDlength: P logrank = .011). In large ITDs (>156 bp on DNA) a remarkable 90-bp difference exists between DNA and RNA, including intron 14, which is spliced out in RNA. Ex vivo exposure (n = 30) to FLT3 inhibitors, in particular to the FLT3-specific inhibitor gilteritinib, showed that colony-forming capacity was significantly more reduced in FLT3 -ITD-AR ≥ 0.5 compared with ITD-AR-low and ITD - patient samples ( P < .001). RNA-based FLT3 -ITD measurements are recommended for risk stratification, and the relevance of AR regarding eligibility for FLT3-targeted therapy warrants further study. © 2018 by The American Society of Hematology.

Characterisation and Clinical Significance of FLT3-ITD and non-ITD in Acute Myeloid Leukaemia Patients in Kelantan, Northeast Peninsular Malaysia.

PubMed

Yunus, Noraini Mat; Johan, Muhammad Farid; Ali Nagi Al-Jamal, Hamid; Husin, Azlan; Hussein, Abdul Rahim; Hassan, Rosline

2015-01-01

Mutations of the FMS-like tyrosine kinase-3 (FLT3) receptor gene may promote proliferation via activation of multiple signaling pathways. FLT3-internal tandem duplication (FLT3-ITD) is the most common gene alteration found in patients diagnosed with acute myeloid leukaemia (AML) and has been associated with poor prognosis. We performed mutational analysis of exons 14-15 and 20 of the FLT3 gene in 54 AML patients using PCR-CSGE (conformational sensitive gel electrophoresis) followed by sequencing analysis to characterise FLT3 mutations in adult patients diagnosed with AML at Hospital USM, Kelantan, Northeast Peninsular Malaysia. FLT3 exon 14-15 mutations were identified in 7 of 54 patients (13%) whereas no mutation was found in FLT3 exon 20. Six ITDs and one non-ITD mutation were found in exon 14 of the juxtamembrane (JM) domain of FLT3. FLT3-ITD mutations were associated with a significantly higher blast percentage (p-value=0.008) and white blood cell count (p-value=0.023) but there was no significant difference in median overall survival time for FLT3-ITD+/FLT3-ITD- within 2 years (p-value=0.374). The incidence of FLT3-ITD in AML patients in this particular region of Malaysia is low compared to the Western world and has a significant association with WBC and blast percentage.

SPECT System Optimization Against A Discrete Parameter Space

PubMed Central

Meng, L. J.; Li, N.

2013-01-01

In this paper, we present an analytical approach for optimizing the design of a static SPECT system or optimizing the sampling strategy with a variable/adaptive SPECT imaging hardware against an arbitrarily given set of system parameters. This approach has three key aspects. First, it is designed to operate over a discretized system parameter space. Second, we have introduced an artificial concept of virtual detector as the basic building block of an imaging system. With a SPECT system described as a collection of the virtual detectors, one can convert the task of system optimization into a process of finding the optimum imaging time distribution (ITD) across all virtual detectors. Thirdly, the optimization problem (finding the optimum ITD) could be solved with a block-iterative approach or other non-linear optimization algorithms. In essence, the resultant optimum ITD could provide a quantitative measure of the relative importance (or effectiveness) of the virtual detectors and help to identify the system configuration or sampling strategy that leads to an optimum imaging performance. Although we are using SPECT imaging as a platform to demonstrate the system optimization strategy, this development also provides a useful framework for system optimization problems in other modalities, such as positron emission tomography (PET) and X-ray computed tomography (CT) [1, 2]. PMID:23587609

Allogeneic Stem Cell Transplantation Improves Survival in Patients with Acute Myeloid Leukemia Characterized by a High Allelic Ratio of Mutant FLT3-ITD.

PubMed

Ho, Anthony D; Schetelig, Johannes; Bochtler, Tilmann; Schaich, Markus; Schäfer-Eckart, Kerstin; Hänel, Mathias; Rösler, Wolf; Einsele, Hermann; Kaufmann, Martin; Serve, Hubert; Berdel, Wolfgang E; Stelljes, Matthias; Mayer, Jiri; Reichle, Albrecht; Baldus, Claudia D; Schmitz, Norbert; Kramer, Michael; Röllig, Christoph; Bornhäuser, Martin; Thiede, Christian; Ehninger, Gerhard

2016-03-01

Allogeneic hematopoietic cell transplantation (alloHCT) as a postremission therapy in patients with FLT3-ITD-positive intermediate-risk acute myeloid leukemia (AML) remains controversial. FLT3-ITD mutations are heterogeneous with respect to allelic ratio, location, and length of the insertion, with a high mutant-to-wild-type ratio consistently associated with inferior prognosis. We retrospectively analyzed the role of alloHCT in first remission in relationship to the allelic ratio and presence or absence of nucleophosmin 1 mutations (NPM1) in the Study Alliance Leukemia AML2003 trial. FLT3-ITD mutations were detected in 209 patients and concomitant NPM1 mutations in 148 patients. Applying a predefined cutoff ratio of .8, AML was grouped into high- and low-ratio FLT3-ITD AML (HR(FLT3-ITD) and LR(FLT3-ITD)). Sixty-one patients (29%) were transplanted in first remission. Overall survival (OS) (HR, .3; 95% CI, .16 to .7; P = .004) and event-free survival (EFS) (HR, .4; 95% CI, .16 to .9; P = .02) were significantly increased in patients with HR(FLT3-ITD) AML who received alloHCT as consolidation treatment compared with patients who received consolidation chemotherapy. Patients with LR(FLT3-ITD) AML and wild-type NPM1 who received alloHCT in first remission had increased OS (HR, .3; 95% CI, .1 to .8; P = .02) and EFS (HR, .2; 95% CI, .1 to .8; P = .02), whereas alloHCT in first remission did not have a significant impact on OS and EFS in patients with LR(FLT3-ITD) AML and concomitant NPM1 mutation. In conclusion, our results provide additional evidence that alloHCT in first remission improves EFS and OS in patients with HR(FLT3-ITD) AML and in patients with LR(FLT3-ITD) AML and wild-type NPM1. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

SOCS1 cooperates with FLT3-ITD in the development of myeloproliferative disease by promoting the escape from external cytokine control.

PubMed

Reddy, Pavankumar N G; Sargin, Bülent; Choudhary, Chunaram; Stein, Stefan; Grez, Manuel; Müller-Tidow, Carsten; Berdel, Wolfgang E; Serve, Hubert; Brandts, Christian H

2012-08-23

Activating mutations in the receptor tyrosine kinase FLT3 are frequently found in acute myelogenous leukemia patients and confer poor clinical prognosis. It is unclear how leukemic blasts escape cytokine control that regulates normal hematopoiesis. We have recently demonstrated that FLT3-internal tandem duplication (ITD), when localized to the biosynthetic compartment, aberrantly activates STAT5. Here, we show that one of the target genes induced by STAT5 is suppressor of cytokine signaling (SOCS)1-a surprising finding for a known tumor suppressor. Although SOCS1 expression in murine bone marrow severely impaired cytokine-induced colony growth, it failed to inhibit FLT3-ITD-supported colony growth, indicating resistance of FLT3-ITD to SOCS1. In addition, SOCS1 coexpression did not affect FLT3-ITD-mediated signaling or proliferation. Importantly, SOCS1 coexpression inhibited interferon-α and interferon-γ signaling and protected FLT3-ITD hematopoietic cells from interferon-mediated growth inhibitory effects. In a murine bone marrow transplantation model, the coexpression of SOCS1 and FLT3-ITD significantly shortened the latency of a myeloproliferative disease compared with FLT3-ITD alone (P < .01). Mechanistically, SOCS proteins shield FLT3-ITD from external cytokine control, thereby promoting leukemogenesis. The data demonstrate that SOCS1 acts as a conditional oncogene, providing novel molecular insights into cytokine resistance in oncogenic transformation. Restoring cytokine control may provide a new way of therapeutic intervention.

How sensitivity to ongoing interaural temporal disparities is affected by manipulations of temporal features of the envelopes of high-frequency stimuli

PubMed Central

Bernstein, Leslie R.; Trahiotis, Constantine

2009-01-01

This study addressed how manipulating certain aspects of the envelopes of high-frequency stimuli affects sensitivity to envelope-based interaural temporal disparities (ITDs). Listener’s threshold ITDs were measured using an adaptive two-alternative paradigm employing “raised-sine” stimuli [John, M. S., et al. (2002). Ear Hear. 23, 106–117] which permit independent variation in their modulation frequency, modulation depth, and modulation exponent. Threshold ITDs were measured while manipulating modulation exponent for stimuli having modulation frequencies between 32 and 256 Hz. The results indicated that graded increases in the exponent led to graded decreases in envelope-based threshold ITDs. Threshold ITDs were also measured while parametrically varying modulation exponent and modulation depth. Overall, threshold ITDs decreased with increases in the modulation depth. Unexpectedly, increases in the exponent of the raised-sine led to especially large decreases in threshold ITD when the modulation depth was low. An interaural correlation-based model was generally able to capture changes in threshold ITD stemming from changes in the exponent, depth of modulation, and frequency of modulation of the raised-sine stimuli. The model (and several variations of it), however, could not account for the unexpected interaction between the value of raised-sine exponent and its modulation depth. PMID:19425666

Extraction of Inter-Aural Time Differences Using a Spiking Neuron Network Model of the Medial Superior Olive.

PubMed

Encke, Jörg; Hemmert, Werner

2018-01-01

The mammalian auditory system is able to extract temporal and spectral features from sound signals at the two ears. One important cue for localization of low-frequency sound sources in the horizontal plane are inter-aural time differences (ITDs) which are first analyzed in the medial superior olive (MSO) in the brainstem. Neural recordings of ITD tuning curves at various stages along the auditory pathway suggest that ITDs in the mammalian brainstem are not represented in form of a Jeffress-type place code. An alternative is the hemispheric opponent-channel code, according to which ITDs are encoded as the difference in the responses of the MSO nuclei in the two hemispheres. In this study, we present a physiologically-plausible, spiking neuron network model of the mammalian MSO circuit and apply two different methods of extracting ITDs from arbitrary sound signals. The network model is driven by a functional model of the auditory periphery and physiological models of the cochlear nucleus and the MSO. Using a linear opponent-channel decoder, we show that the network is able to detect changes in ITD with a precision down to 10 μs and that the sensitivity of the decoder depends on the slope of the ITD-rate functions. A second approach uses an artificial neuronal network to predict ITDs directly from the spiking output of the MSO and ANF model. Using this predictor, we show that the MSO-network is able to reliably encode static and time-dependent ITDs over a large frequency range, also for complex signals like speech.

Intratympanic steroids injection is effective for the treatment of drop attacks with Ménière's disease and delayed endolymphatic hydrops

PubMed Central

Liu, Bo; Leng, Yangming; Zhou, Renhong; Liu, Jingjing; Liu, Dongdong; Zhang, Su-Lin; Kong, Wei-Jia

2016-01-01

Abstract Drop attack (DA) associated with Ménière's disease (MD) and delayed endolymphatic hydrops (DEH) is not common and may cause life-threatening clinical problems. The intratympanic dexamethasone (ITD) is one of primary treatments for MD or DEH. Our study investigated the effect of ITD on the DA associated with endolymphatic hydrops (EH). We retrospectively reviewed 10 patients with MD- and DEH-associated DA between January 2009 and December 2013 in Outpatient Department of Otolaryngology, Union Hospital, Wuhan, China. Among them, 7 patients (5 cases with MD, 2 cases of DEH) received ITD (4 times, on weekly basis). Further repeated ITD courses or intratympanic gentamicin (ITG) were given if the vertigo was not satisfactorily controlled. The number of DA and status of vertigo control after intratympanic injection were evaluated. After a follow-up study lasting from 19 to 35 months, DA in 5 cases (71.4%) disappeared after initial ITD course. In 2 cases, DA was altogether controlled after an additional intratympanic injection (repeated ITD or/and ITG). This study showed that ITD promises to be a first-line conservative treatment for MD- or DEH-related DA since the steroid possesses no inner-ear toxicity. Furthermore, for MD- or DEH-related DA refractory to ITD, ITG can be an effective alternative. PMID:28033296

Detection of Interaural Time Differences in the Alligator

PubMed Central

Carr, Catherine E.; Soares, Daphne; Smolders, Jean; Simon, Jonathan Z.

2011-01-01

The auditory systems of birds and mammals use timing information from each ear to detect interaural time difference (ITD). To determine whether the Jeffress-type algorithms that underlie sensitivity to ITD in birds are an evolutionarily stable strategy, we recorded from the auditory nuclei of crocodilians, who are the sister group to the birds. In alligators, precisely timed spikes in the first-order nucleus magnocellularis (NM) encode the timing of sounds, and NM neurons project to neurons in the nucleus laminaris (NL) that detect interaural time differences. In vivo recordings from NL neurons show that the arrival time of phase-locked spikes differs between the ipsilateral and contralateral inputs. When this disparity is nullified by their best ITD, the neurons respond maximally. Thus NL neurons act as coincidence detectors. A biologically detailed model of NL with alligator parameters discriminated ITDs up to 1 kHz. The range of best ITDs represented in NL was much larger than in birds, however, and extended from 0 to 1000 μs contralateral, with a median ITD of 450 μs. Thus, crocodilians and birds employ similar algorithms for ITD detection, although crocodilians have larger heads. PMID:19553438

Low vision goggles: optical design studies

NASA Astrophysics Data System (ADS)

Levy, Ofer; Apter, Boris; Efron, Uzi

2006-08-01

Low Vision (LV) due to Age Related Macular Degeneration (AMD), Glaucoma or Retinitis Pigmentosa (RP) is a growing problem, which will affect more than 15 million people in the U.S alone in 2010. Low Vision Aid Goggles (LVG) have been under development at Ben-Gurion University and the Holon Institute of Technology. The device is based on a unique Image Transceiver Device (ITD), combining both functions of imaging and Display in a single chip. Using the ITD-based goggles, specifically designed for the visually impaired, our aim is to develop a head-mounted device that will allow the capture of the ambient scenery, perform the necessary image enhancement and processing, and re-direct it to the healthy part of the patient's retina. This design methodology will allow the Goggles to be mobile, multi-task and environmental-adaptive. In this paper we present the optical design considerations of the Goggles, including a preliminary performance analysis. Common vision deficiencies of LV patients are usually divided into two main categories: peripheral vision loss (PVL) and central vision loss (CVL), each requiring different Goggles design. A set of design principles had been defined for each category. Four main optical designs are presented and compared according to the design principles. Each of the designs is presented in two main optical configurations: See-through system and Video imaging system. The use of a full-color ITD-Based Goggles is also discussed.

Time-Varying Distortions of Binaural Information by Bilateral Hearing Aids

PubMed Central

Rodriguez, Francisco A.; Portnuff, Cory D. F.; Goupell, Matthew J.; Tollin, Daniel J.

2016-01-01

In patients with bilateral hearing loss, the use of two hearing aids (HAs) offers the potential to restore the benefits of binaural hearing, including sound source localization and segregation. However, existing evidence suggests that bilateral HA users’ access to binaural information, namely interaural time and level differences (ITDs and ILDs), can be compromised by device processing. Our objective was to characterize the nature and magnitude of binaural distortions caused by modern digital behind-the-ear HAs using a variety of stimuli and HA program settings. Of particular interest was a common frequency-lowering algorithm known as nonlinear frequency compression, which has not previously been assessed for its effects on binaural information. A binaural beamforming algorithm was also assessed. Wide dynamic range compression was enabled in all programs. HAs were placed on a binaural manikin, and stimuli were presented from an arc of loudspeakers inside an anechoic chamber. Stimuli were broadband noise bursts, 10-Hz sinusoidally amplitude-modulated noise bursts, or consonant–vowel–consonant speech tokens. Binaural information was analyzed in terms of ITDs, ILDs, and interaural coherence, both for whole stimuli and in a time-varying sense (i.e., within a running temporal window) across four different frequency bands (1, 2, 4, and 6 kHz). Key findings were: (a) Nonlinear frequency compression caused distortions of high-frequency envelope ITDs and significantly reduced interaural coherence. (b) For modulated stimuli, all programs caused time-varying distortion of ILDs. (c) HAs altered the relationship between ITDs and ILDs, introducing large ITD–ILD conflicts in some cases. Potential perceptual consequences of measured distortions are discussed. PMID:27698258

76 FR 46853 - International Business Machines Corporation, ITD Business Unit, Division 7, E-mail and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-03

...] International Business Machines Corporation, ITD Business Unit, Division 7, E-mail and Collaboration Group... Business Machines Corporation (IBM), ITD Business Unit, Division 7, E- mail and Collaboration Group... Business Unit, Division 7, E-mail and Collaboration [[Page 46854

Characterization of children with FLT3-ITD acute myeloid leukemia: a report from the AIEOP AML-2002 study group.

PubMed

Manara, E; Basso, G; Zampini, M; Buldini, B; Tregnago, C; Rondelli, R; Masetti, R; Bisio, V; Frison, M; Polato, K; Cazzaniga, G; Menna, G; Fagioli, F; Merli, P; Biondi, A; Pession, A; Locatelli, F; Pigazzi, M

2017-01-01

Recurrent molecular markers have been routinely used in acute myeloid leukemia (AML) for risk assessment at diagnosis, whereas their post-induction monitoring still represents a debated issue. We evaluated the prognostic value and biological impact of minimal residual disease (MRD) and of the allelic ratio (AR) of FLT3-internal-tandem duplication (ITD) in childhood AML. We retrospectively screened 494 children with de novo AML for FLT3-ITD mutation, identifying 54 harboring the mutation; 51% of them presented high ITD-AR at diagnosis and had worse event-free survival (EFS, 19.2 versus 63.5% for low ITD-AR, <0.05). Forty-one percent of children with high levels of MRD after the 1st induction course, measured by a patient-specific real-time-PCR, had worse EFS (22.2 versus 59.4% in low-MRD patients, P<0.05). Next, we correlated these parameters with gene expression, showing that patients with high ITD-AR or persistent MRD had characteristic expression profiles with deregulated genes involved in methylation and acetylation. Moreover, patients with high CyclinA1 expression presented an unfavorable EFS (20.3 versus 51.2% in low CyclinA1 group, P<0.01). Our results suggest that ITD-AR levels and molecular MRD should be considered in planning clinical management of FLT3-ITD patients. Different transcriptional activation of epigenetic and oncogenic profiles may explain variability in outcome among these patients, for whom novel therapeutic approaches are desirable.

Pim kinase inhibition sensitizes FLT3-ITD acute myeloid leukemia cells to topoisomerase 2 inhibitors through increased DNA damage and oxidative stress

PubMed Central

Doshi, Kshama A.; Trotta, Rossana; Natarajan, Karthika; Rassool, Feyruz V.; Tron, Adriana E.; Huszar, Dennis; Perrotti, Danilo; Baer, Maria R.

2016-01-01

Internal tandem duplication of fms-like tyrosine kinase-3 (FLT3-ITD) is frequent (30 percent) in acute myeloid leukemia (AML), and is associated with short disease-free survival following chemotherapy. The serine threonine kinase Pim-1 is a pro-survival oncogene transcriptionally upregulated by FLT3-ITD that also promotes its signaling in a positive feedback loop. Thus inhibiting Pim-1 represents an attractive approach in targeting FLT3-ITD cells. Indeed, co-treatment with the pan-Pim kinase inhibitor AZD1208 or expression of a kinase-dead Pim-1 mutant sensitized FLT3-ITD cell lines to apoptosis triggered by chemotherapy drugs including the topoisomerase 2 inhibitors daunorubicin, etoposide and mitoxantrone, but not the nucleoside analog cytarabine. AZD1208 sensitized primary AML cells with FLT3-ITD to topoisomerase 2 inhibitors, but did not sensitize AML cells with wild-type FLT3 or remission bone marrow cells, supporting a favorable therapeutic index. Mechanistically, the enhanced apoptosis observed with AZD1208 and topoisomerase 2 inhibitor combination treatment was associated with increased DNA double-strand breaks and increased levels of reactive oxygen species (ROS), and co-treatment with the ROS scavenger N-acetyl cysteine rescued FLT3-ITD cells from AZD1208 sensitization to topoisomerase 2 inhibitors. Our data support testing of Pim kinase inhibitors with topoisomerase 2 inhibitors, but not with cytarabine, to improve treatment outcomes in AML with FLT3-ITD. PMID:27374090

Dual sensitivity of inferior colliculus neurons to ITD in the envelopes of high-frequency sounds: experimental and modeling study

PubMed Central

Wang, Le; Devore, Sasha; Delgutte, Bertrand

2013-01-01

Human listeners are sensitive to interaural time differences (ITDs) in the envelopes of sounds, which can serve as a cue for sound localization. Many high-frequency neurons in the mammalian inferior colliculus (IC) are sensitive to envelope-ITDs of sinusoidally amplitude-modulated (SAM) sounds. Typically, envelope-ITD-sensitive IC neurons exhibit either peak-type sensitivity, discharging maximally at the same delay across frequencies, or trough-type sensitivity, discharging minimally at the same delay across frequencies, consistent with responses observed at the primary site of binaural interaction in the medial and lateral superior olives (MSO and LSO), respectively. However, some high-frequency IC neurons exhibit dual types of envelope-ITD sensitivity in their responses to SAM tones, that is, they exhibit peak-type sensitivity at some modulation frequencies and trough-type sensitivity at other frequencies. Here we show that high-frequency IC neurons in the unanesthetized rabbit can also exhibit dual types of envelope-ITD sensitivity in their responses to SAM noise. Such complex responses to SAM stimuli could be achieved by convergent inputs from MSO and LSO onto single IC neurons. We test this hypothesis by implementing a physiologically explicit, computational model of the binaural pathway. Specifically, we examined envelope-ITD sensitivity of a simple model IC neuron that receives convergent inputs from MSO and LSO model neurons. We show that dual envelope-ITD sensitivity emerges in the IC when convergent MSO and LSO inputs are differentially tuned for modulation frequency. PMID:24155013

Acoustic Database for Turbofan Engine Core-Noise Sources. I; Volume

NASA Technical Reports Server (NTRS)

Gordon, Grant

2015-01-01

In this program, a database of dynamic temperature and dynamic pressure measurements were acquired inside the core of a TECH977 turbofan engine to support investigations of indirect combustion noise. Dynamic temperature and pressure measurements were recorded for engine gas dynamics up to temperatures of 3100 degrees Fahrenheit and transient responses as high as 1000 hertz. These measurements were made at the entrance of the high pressure turbine (HPT) and at the entrance and exit of the low pressure turbine (LPT). Measurements were made at two circumferential clocking positions. In the combustor and inter-turbine duct (ITD), measurements were made at two axial locations to enable the exploration of time delays. The dynamic temperature measurements were made using dual thin-wire thermocouple probes. The dynamic pressure measurements were made using semi-infinite probes. Prior to the engine test, a series of bench, oven, and combustor rig tests were conducted to characterize the performance of the dual wire temperature probes and to define and characterize the data acquisition systems. A measurement solution for acquiring dynamic temperature and pressure data on the engine was defined. A suite of hardware modifications were designed to incorporate the dynamic temperature and pressure instrumentation into the TECH977 engine. In particular, a probe actuation system was developed to protect the delicate temperature probes during engine startup and transients in order to maximize sensor life. A set of temperature probes was procured and the TECH977 engine was assembled with the suite of new and modified hardware. The engine was tested at four steady state operating speeds, with repeats. Dynamic pressure and temperature data were acquired at each condition for at least one minute. At the two highest power settings, temperature data could not be obtained at the forward probe locations since the mean temperatures exceeded the capability of the probes. The temperature data were processed using software that accounts for the effects of convective and conductive heat transfer. The software was developed under previous NASA sponsored programs. Compensated temperature spectra and compensated time histories corresponding to the dynamic temperature of the gas stream were generated. Auto-spectral and cross-spectral analyses of the data were performed to investigate spectral features, acoustic circumferential mode content, signal coherence, and time delays. The dynamic temperature data exhibit a wideband and fairly flat spectral content. The temperature spectra do not change substantially with operating speed. The pressure spectra in the combustor and ITD exhibit generally similar shapes and amplitudes, making it difficult to identify any features that suggest the presence of indirect combustion noise. Cross-spectral analysis reveal a strong correlation between pressure and temperature fluctuations in the ITD, but little correlation between temperature fluctuations at the entrance of the HPT and pressure fluctuations downstream of it. Temperature fluctuations at the entrance of the low pressure turbine were an order of magnitude smaller than those at the entrance to the high pressure turbine. Time delay analysis of the temperature fluctuations in the combustor was inconclusive, perhaps due to the substantial mixing that occurs between the upstream and downstream locations. Time delay analysis of the temperature fluctuations in the ITD indicate that they convect at the mean flow speed. Analysis of the data did not reveal any convincing indications of the presence of indirect combustion noise. However, this analysis has been preliminary and additional exploration of the data is recommended including the use of more sophisticated signal processing to explore subtle issues that have been revealed but which are not yet fully understood or explained.

A method to enhance the use of interaural time differences for cochlear implants in reverberant environments

PubMed Central

Monaghan, Jessica J. M.; Seeber, Bernhard U.

2017-01-01

The ability of normal-hearing (NH) listeners to exploit interaural time difference (ITD) cues conveyed in the modulated envelopes of high-frequency sounds is poor compared to ITD cues transmitted in the temporal fine structure at low frequencies. Sensitivity to envelope ITDs is further degraded when envelopes become less steep, when modulation depth is reduced, and when envelopes become less similar between the ears, common factors when listening in reverberant environments. The vulnerability of envelope ITDs is particularly problematic for cochlear implant (CI) users, as they rely on information conveyed by slowly varying amplitude envelopes. Here, an approach to improve access to envelope ITDs for CIs is described in which, rather than attempting to reduce reverberation, the perceptual saliency of cues relating to the source is increased by selectively sharpening peaks in the amplitude envelope judged to contain reliable ITDs. Performance of the algorithm with room reverberation was assessed through simulating listening with bilateral CIs in headphone experiments with NH listeners. Relative to simulated standard CI processing, stimuli processed with the algorithm generated lower ITD discrimination thresholds and increased extents of laterality. Depending on parameterization, intelligibility was unchanged or somewhat reduced. The algorithm has the potential to improve spatial listening with CIs. PMID:27586742

A noncanonical Flt3ITD/NF-κB signaling pathway represses DAPK1 in acute myeloid leukemia.

PubMed

Shanmugam, Rajasubramaniam; Gade, Padmaja; Wilson-Weekes, Annique; Sayar, Hamid; Suvannasankha, Attaya; Goswami, Chirayu; Li, Lang; Gupta, Sushil; Cardoso, Angelo A; Baghdadi, Tareq Al; Sargent, Katie J; Cripe, Larry D; Kalvakolanu, Dhananjaya V; Boswell, H Scott

2012-01-15

Death-associated protein kinase 1 (DAPK1), a tumor suppressor, is a rate-limiting effector in an endoplasmic reticulum (ER) stress-dependent apoptotic pathway. Its expression is epigenetically suppressed in several tumors. A mechanistic basis for epigenetic/transcriptional repression of DAPK1 was investigated in certain forms of acute myeloid leukemia (AML) with poor prognosis, which lacked ER stress-induced apoptosis. Heterogeneous primary AMLs were screened to identify a subgroup with Flt3ITD in which repression of DAPK1, among NF-κB-and c-Jun-responsive genes, was studied. RNA interference knockdown studies were carried out in an Flt3ITD(+) cell line, MV-4-11, to establish genetic epistasis in the pathway Flt3ITD-TAK1-DAPK1 repression, and chromatin immunoprecipitations were carried out to identify proximate effector proteins, including TAK1-activated p52NF-κB, at the DAPK1 locus. AMLs characterized by normal karyotype with Flt3ITD were found to have 10- to 100-fold lower DAPK1 transcripts normalized to the expression of c-Jun, a transcriptional activator of DAPK1, as compared with a heterogeneous cytogenetic category. In addition, Meis1, a c-Jun-responsive adverse AML prognostic gene signature was measured as control. These Flt3ITD(+) AMLs overexpress relB, a transcriptional repressor, which forms active heterodimers with p52NF-κB. Chromatin immunoprecipitation assays identified p52NF-κB binding to the DAPK1 promoter together with histone deacetylase 2 (HDAC2) and HDAC6 in the Flt3ITD(+) human AML cell line MV-4-11. Knockdown of p52NF-κB or its upstream regulator, NF-κB-inducing kinase (NIK), de-repressed DAPK1. DAPK1-repressed primary Flt3ITD(+) AMLs had selective nuclear activation of p52NF-κB. Flt3ITD promotes a noncanonical pathway via TAK1 and p52NF-κB to suppress DAPK1 in association with HDACs, which explains DAPK1 repression in Flt3ITD(+) AML. ©2011 AACR.

A non-canonical Flt3ITD/NF-κB signaling pathway represses DAPK1 in acute myeloid leukemia (AML)

PubMed Central

Shanmugam, Rajasubramaniam; Sayar, Hamid; Suvannasankha, Attaya; Goswami, Chirayu; Li, Lang; Gupta, Sushil; Cardoso, Angelo A.; Baghdadi, Tareq Al; Sargent, Katie J.; Cripe, Larry D.; Kalvakolanu, Dhananjaya V.; Boswell, H. Scott

2014-01-01

Purpose DAPK1, a tumor suppressor, is a rate-limiting effector in an ER stress-dependent apoptotic pathway. Its expression is epigenetically suppressed in several tumors. A mechanistic basis for epigenetic/transcriptional repression of DAPK1 was investigated in certain forms of AML with poor prognosis, which lacked ER stress-induced apoptosis. Experimental Design Heterogeneous primary AMLs were screened to identify a subgroup with Flt3ITD in which repression of DAPK1, among NF-κB- and c- jun-responsive genes, was studied. RNAi knockdown studies were performed in Flt3ITD+ve cell line, MV-4-11, to establish genetic epistasis in the pathway Flt3ITD-TAK1-DAPK1 repression, and chromatin immunoprecipitations were performed to identify proximate effector proteins, including TAK1-activated p52NF-κB, at the DAPK1 locus. Results AMLs characterized by normal karyotype with Flt3ITD were found to have 10-100-fold lower DAPK1 transcripts normalized to the expression of c-jun, a transcriptional activator of DAPK1, as compared to a heterogeneous cytogenetic category. Meis1, a c-jun-responsive adverse AML prognostic gene signature was also measured as control. These Flt3ITD+ve AMLs over-express relB, a transcriptional repressor, which forms active heterodimers with p52NF-κB. Chromatin immunoprecipitation assays identified p52NF-κB binding to the DAPK1 promoter along with HDAC2 and HDAC6 in the Flt3ITD+ve human AML cell line MV-4-11. Knockdown of p52NF-κB or its upstream regulator, NIK, de-repressed DAPK1. DAPK1-repressed primary Flt3ITD+ve AMLs had selective nuclear activation of p52NF-κB. Conclusions Flt3ITD promotes a non-canonical pathway via TAK1 and p52NF-κB to suppress DAPK1 in association with HDACs, which explains DAPK1 repression in Flt3ITD+ve AML. PMID:22096027

Reperfusion injury protection during Basic Life Support improves circulation and survival outcomes in a porcine model of prolonged cardiac arrest.

PubMed

Debaty, Guillaume; Lurie, Keith; Metzger, Anja; Lick, Michael; Bartos, Jason A; Rees, Jennifer N; McKnite, Scott; Puertas, Laura; Pepe, Paul; Fowler, Raymond; Yannopoulos, Demetris

2016-08-01

Ischemic postconditioning (PC) using three intentional pauses at the start of cardiopulmonary resuscitation (CPR) improves outcomes after cardiac arrest in pigs when epinephrine (epi) is used before defibrillation. We hypothesized PC, performed during basic life support (BLS) in the absence of epinephrine, would reduce reperfusion injury and enhance 24h functional recovery. Prospective animal investigation. Animal laboratory Female farm pigs (n=46, 39±1kg). Protocol A: After 12min of ventricular fibrillation (VF), 28 pigs were randomized to four groups: (A) Standard CPR (SCPR), (B) active compression-decompression CPR with an impedance threshold device (ACD-ITD), (C) SCPR+PC (SCPR+PC) and (D) ACD-ITD CPR+PC. Protocol B: After 15min of VF, 18 pigs were randomized to ACD-ITD CPR or ACD-ITD+PC. The BLS duration was 2.75min in Protocol A and 5min in Protocol B. Following BLS, up to three shocks were delivered. Without return of spontaneous circulation (ROSC), CPR was resumed and epi (0.5mg) and defibrillation delivered. The primary end point was survival without major adverse events. Hemodynamic parameters and left ventricular ejection fraction (LVEF) were also measured. Data are presented as mean±SEM. Protocol A: ACD-ITD+PC (group D) improved coronary perfusion pressure after 3min of BLS versus the three other groups (28±6, 35±7, 23±5 and 47±7 for groups A, B, C, D respectively, p=0.05). There were no significant differences in 24h survival between groups. LVEF 4h post ROSC was significantly higher with ACD-ITD+PC vs ACD-ITD alone (52.5±3% vs. 37.5±6.6%, p=0.045). Survival rates were significantly higher with ACD-ITD+PC vs. ACD-ITD alone (p=0.027). BLS using ACD-ITD+PC reduced post resuscitation cardiac dysfunction and improved functional recovery after prolonged untreated VF in pigs. 12-11. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Attentional Bias to Negative Affect Moderates Negative Affect’s Relationship with Smoking Abstinence

PubMed Central

Etcheverry, Paul E.; Waters, Andrew J.; Lam, Cho; Correa-Fernandez, Virmarie; Vidrine, Jennifer Irvin; Cinciripini, Paul M.; Wetter, David W.

2016-01-01

Objective To examine whether initial orienting (IO) and inability to disengage attention (ITD) from negative affective stimuli moderate the association of negative affect with smoking abstinence during a quit attempt. Methods Data were from a longitudinal cohort study of smoking cessation (N=424). A negative affect modified Stroop was administered one week before and on quit day to measure IO and ITD. Ecological Momentary Assessments were used to create negative affect intercepts and linear slopes for the week before quitting and on quit day. Quit day and long-term abstinence measures were collected. Results Continuation ratio (CR) logit model analyses found significant interactions of pre-quit negative affect slope with pre-quit ITD [OR = .738(.57, .96), p= .02] and quit day negative affect intercept with quit day ITD [OR = .62(.41, 950), p= .03] predicting abstinence. The interaction of pre-quit negative affect intercept and pre-quit IO predicting quit day abstinence was significant [OR = 1.42(1.06, 1.90), p= .02], as was the interaction of quit day negative affect slope and quit day IO predicting long-term abstinence [OR = 1.45(1.02, 2.08), p= .04]. Conclusions The hypothesis that the association of negative affect with smoking abstinence would be moderated by ITD was generally supported. Among individuals with high ITD, negative affect was inversely related to abstinence, but unrelated to abstinence among individuals with lower levels of ITD. Unexpectedly, among individuals with low IO negative affect was inversely related to abstinence, but unrelated to abstinence among individuals with higher levels of ITD. PMID:27505211

Localization and interaural time difference (ITD) thresholds for cochlear implant recipients with preserved acoustic hearing in the implanted ear

PubMed Central

Gifford, René H.; Grantham, D. Wesley; Sheffield, Sterling W.; Davis, Timothy J.; Dwyer, Robert; Dorman, Michael F.

2014-01-01

The purpose of this study was to investigate horizontal plane localization and interaural time difference (ITD) thresholds for 14 adult cochlear implant recipients with hearing preservation in the implanted ear. Localization to broadband noise was assessed in an anechoic chamber with a 33-loudspeaker array extending from −90 to +90°. Three listening conditions were tested including bilateral hearing aids, bimodal (implant + contralateral hearing aid) and best aided (implant + bilateral hearing aids). ITD thresholds were assessed, under headphones, for low-frequency stimuli including a 250-Hz tone and bandpass noise (100–900 Hz). Localization, in overall rms error, was significantly poorer in the bimodal condition (mean: 60.2°) as compared to both bilateral hearing aids (mean: 46.1°) and the best-aided condition (mean: 43.4°). ITD thresholds were assessed for the same 14 adult implant recipients as well as 5 normal-hearing adults. ITD thresholds were highly variable across the implant recipients ranging from the range of normal to ITDs not present in real-world listening environments (range: 43 to over 1600 μs). ITD thresholds were significantly correlated with localization, the degree of interaural asymmetry in low-frequency hearing, and the degree of hearing preservation related benefit in the speech reception threshold (SRT). These data suggest that implant recipients with hearing preservation in the implanted ear have access to binaural cues and that the sensitivity to ITDs is significantly correlated with localization and degree of preserved hearing in the implanted ear. PMID:24607490

Prevalence of exon 11 internal tandem duplications in the C-KIT proto-oncogene in Australian canine mast cell tumours.

PubMed

Tamlin, V S; Kessell, A E; Mccoy, R J; Dobson, E C; Smith, T S; Hebart, M; Brown, L; Mitrovic, D; Peaston, A E

2017-10-01

To measure the prevalence of internal tandem duplications (ITDs) in exon 11 of the proto-oncogene C-KIT in a sample of Australian cutaneous canine mast cell tumours (MCTs) drawn from general practice and to evaluate relationships between tumour mutation status and prognostic factors including signalment, tumour histological grade, tumour anatomical location and tumour size. C-KIT exon 11 ITDs were detected by PCR in DNA extracted from formalin-fixed, paraffin-embedded canine MCTs sourced from three veterinary diagnostic laboratories in Adelaide and Melbourne. Tumours were graded according to two different systems (Patnaik and Kiupel systems) by board-certified anatomical pathologists blinded to the PCR results. Relationships between tumour mutation status and prognostic factors were evaluated using a generalised binary logistic regression analysis. ITDs were identified in 13 of 74 cutaneous canine MCT samples, giving an overall prevalence of 17.6% (95% confidence interval: 8.9-26.2%). ITDs were detected in 10 of 18 Patnaik grade III MCTs (55.6%) and 11 of 22 Kiupel high-grade MCTs (50%). Wald chi-square analysis revealed that detection of tumour ITDs was significantly associated with both Patnaik's and Kiupel's histologic grading systems (each: P < 0.001). The presence of the ITDs in MCTs was not associated with signalment, tumour anatomical location or tumour size. The prevalence of C-KIT exon 11 ITDs in Australian canine MCTs is similar to the prevalence in overseas canine populations (overall prevalence in Australia approximately 18%). ITDs were more frequently identified in higher grade MCTs. © 2017 Australian Veterinary Association.

Localization and interaural time difference (ITD) thresholds for cochlear implant recipients with preserved acoustic hearing in the implanted ear.

PubMed

Gifford, René H; Grantham, D Wesley; Sheffield, Sterling W; Davis, Timothy J; Dwyer, Robert; Dorman, Michael F

2014-06-01

The purpose of this study was to investigate horizontal plane localization and interaural time difference (ITD) thresholds for 14 adult cochlear implant recipients with hearing preservation in the implanted ear. Localization to broadband noise was assessed in an anechoic chamber with a 33-loudspeaker array extending from -90 to +90°. Three listening conditions were tested including bilateral hearing aids, bimodal (implant + contralateral hearing aid) and best aided (implant + bilateral hearing aids). ITD thresholds were assessed, under headphones, for low-frequency stimuli including a 250-Hz tone and bandpass noise (100-900 Hz). Localization, in overall rms error, was significantly poorer in the bimodal condition (mean: 60.2°) as compared to both bilateral hearing aids (mean: 46.1°) and the best-aided condition (mean: 43.4°). ITD thresholds were assessed for the same 14 adult implant recipients as well as 5 normal-hearing adults. ITD thresholds were highly variable across the implant recipients ranging from the range of normal to ITDs not present in real-world listening environments (range: 43 to over 1600 μs). ITD thresholds were significantly correlated with localization, the degree of interaural asymmetry in low-frequency hearing, and the degree of hearing preservation related benefit in the speech reception threshold (SRT). These data suggest that implant recipients with hearing preservation in the implanted ear have access to binaural cues and that the sensitivity to ITDs is significantly correlated with localization and degree of preserved hearing in the implanted ear. Copyright © 2014. Published by Elsevier B.V.

Localization of sound in rooms. V. Binaural coherence and human sensitivity to interaural time differences in noise

PubMed Central

Rakerd, Brad; Hartmann, William M.

2010-01-01

Binaural recordings of noise in rooms were used to determine the relationship between binaural coherence and the effectiveness of the interaural time difference (ITD) as a cue for human sound localization. Experiments showed a strong, monotonic relationship between the coherence and a listener’s ability to discriminate values of ITD. The relationship was found to be independent of other, widely varying acoustical properties of the rooms. However, the relationship varied dramatically with noise band center frequency. The ability to discriminate small ITD changes was greatest for a mid-frequency band. To achieve sensitivity comparable to mid-band, the binaural coherence had to be much larger at high frequency, where waveform ITD cues are imperceptible, and also at low frequency, where the binaural coherence in a room is necessarily large. Rivalry experiments with opposing interaural level differences (ILDs) found that the trading ratio between ITD and ILD increasingly favored the ILD as coherence decreased, suggesting that the perceptual weight of the ITD is decreased by increased reflections in rooms. PMID:21110600

FLT3-ITD confers resistance to the PI3K/Akt pathway inhibitors by protecting the mTOR/4EBP1/Mcl-1 pathway through STAT5 activation in acute myeloid leukemia

PubMed Central

Nogami, Ayako; Oshikawa, Gaku; Okada, Keigo; Fukutake, Shusaku; Umezawa, Yoshihiro; Nagao, Toshikage; Kurosu, Tetsuya; Miura, Osamu

2015-01-01

FLT3-ITD and FLT3-TKD are the most frequent tyrosine kinase mutations in acute myeloid leukemia (AML), with the former associated with poor prognosis. Here, we show that the PI3K inhibitor GDC-0941 or the Akt inhibitor MK-2206 induced apoptosis through the mitochondria-mediated intrinsic pathway more efficiently in hematopoietic 32D cells driven by FLT3-TKD (32D/TKD) than FLT3-ITD (32D/ITD), which robustly activated STAT5. The resistance to GDC-0941 and MK-2206 was gained by expression of the constitutively activated STAT5 mutant STAT5A1*6 in 32D/TKD cells, while it was abrogated by the STAT5 inhibitor pimozide in 32D/ITD cells or FLT3-ITD-expressing human leukemic MV4–11 cells. GDC-0941 or MK-2206 induced dephosphorylation of 4EBP1 more conspicuously in 32D/TKD than in 32D/ITD, which was prevented or augmented by STAT5A1*6 or pimozide, respectively, and correlated with downregulation of the eIF4E/eIF4G complex formation and Mcl-1 expression. Furthermore, exogenous expression of Mcl-1 endowed resistance to GDC-0941 and MK-2206 on 32D/TKD cells. Finally, it was confirmed in primary AML cells with FLT3-ITD that pimozide enhanced 4EBP1 dephosphorylation and Mcl-1 downregulation to augment cytotoxicity of GDC-0941. These data suggest that the robust STAT5 activation by FLT3-ITD protects cells treated with the PI3K/Akt pathway inhibitors from apoptosis by maintaining Mcl-1 expression through the mTORC1/4EBP1/eIF4E pathway. PMID:25826077

FLT3-ITD confers resistance to the PI3K/Akt pathway inhibitors by protecting the mTOR/4EBP1/Mcl-1 pathway through STAT5 activation in acute myeloid leukemia.

PubMed

Nogami, Ayako; Oshikawa, Gaku; Okada, Keigo; Fukutake, Shusaku; Umezawa, Yoshihiro; Nagao, Toshikage; Kurosu, Tetsuya; Miura, Osamu

2015-04-20

FLT3-ITD and FLT3-TKD are the most frequent tyrosine kinase mutations in acute myeloid leukemia (AML), with the former associated with poor prognosis. Here, we show that the PI3K inhibitor GDC-0941 or the Akt inhibitor MK-2206 induced apoptosis through the mitochondria-mediated intrinsic pathway more efficiently in hematopoietic 32D cells driven by FLT3-TKD (32D/TKD) than FLT3-ITD (32D/ITD), which robustly activated STAT5. The resistance to GDC-0941 and MK-2206 was gained by expression of the constitutively activated STAT5 mutant STAT5A1*6 in 32D/TKD cells, while it was abrogated by the STAT5 inhibitor pimozide in 32D/ITD cells or FLT3-ITD-expressing human leukemic MV4-11 cells. GDC-0941 or MK-2206 induced dephosphorylation of 4EBP1 more conspicuously in 32D/TKD than in 32D/ITD, which was prevented or augmented by STAT5A1*6 or pimozide, respectively, and correlated with downregulation of the eIF4E/eIF4G complex formation and Mcl-1 expression. Furthermore, exogenous expression of Mcl-1 endowed resistance to GDC-0941 and MK-2206 on 32D/TKD cells. Finally, it was confirmed in primary AML cells with FLT3-ITD that pimozide enhanced 4EBP1 dephosphorylation and Mcl-1 downregulation to augment cytotoxicity of GDC-0941. These data suggest that the robust STAT5 activation by FLT3-ITD protects cells treated with the PI3K/Akt pathway inhibitors from apoptosis by maintaining Mcl-1 expression through the mTORC1/4EBP1/eIF4E pathway.

A potential therapeutic target for FLT3-ITD AML: PIM1 Kinase

PubMed Central

Fathi, Amir T.; Arowojolu, Omotayo; Swinnen, Ian; Sato, Takashi; Rajkhowa, Trivikram; Small, Donald; Marmsater, Fredrik; Robinson, John E.; Gross, Stefan David; Martinson, Matthew; Allen, Shelley; Kallan, Nicholas C.; Levis, Mark

2011-01-01

Patients with acute myeloid leukemia (AML) and a FLT3 internal tandem duplication (ITD) mutation have a poor prognosis, and FLT3 inhibitors are now under clinical investigation. PIM1, a serine/threonine kinase, is up-regulated in FLT3-ITD AML and may be involved in FLT3-mediated leukemogenesis. We employed a PIM1 inhibitor, AR00459339 (Array Biopharma Inc.), to investigate the effect of PIM1 inhibition in FLT3-mutant AML. Like FLT3 inhibitors, AR00459339 was preferentially cytotoxic to FLT3-ITD cells, as demonstrated in the MV4-11, Molm-14, and TF/ITD cell lines, as well as 12 FLT3-ITD primary samples. Unlike FLT3 inhibitors, AR00459339 did not suppress phosphorylation of FLT3, but did promote the de-phosphorylation of downstream FLT3 targets, STAT5, AKT, and BAD. Combining AR00459339 with a FLT3 inhibitor resulted in additive to mildly synergistic cytotoxic effects. AR00459339 was cytotoxic to FLT3-ITD samples from patients with secondary resistance to FLT3 inhibitors, suggesting a novel benefit to combining these agents. We conclude that PIM1 appears to be closely associated with FLT3 signaling, and that inhibition of PIM1 may hold therapeutic promise, either as monotherapy, or by overcoming resistance to FLT3 inhibitors. PMID:21802138

Prognostic significance of FLT3 internal tandem repeat in patients with de novo acute myeloid leukemia treated with reinforced courses of chemotherapy.

PubMed

Boissel, N; Cayuela, J M; Preudhomme, C; Thomas, X; Grardel, N; Fund, X; Tigaud, I; Raffoux, E; Rousselot, P; Sigaux, F; Degos, L; Castaigne, S; Fenaux, P; Dombret, H

2002-09-01

FLT3 internal tandem duplications (FLT3-ITDs) are present in nearly 25% of patients with AML and have been associated with poor response to conventional therapy and poor outcome. We retrospectively evaluated the effect of reinforced courses of chemotherapy on the prognostic value of FLT3-ITDs in 159 AML patients prospectively enrolled in the ALFA-9000 trial, which randomly compared three reinforced induction regimens (standard 3+7 including high-dose daunorubicin, double induction, and timed-sequential therapy). FLT3-ITD was present in 40/159 (25%) blast samples and associated with high WBC (P = 0.002) and cytogenetics (P < 0.001) with a higher incidence (35%) in patients with a normal karyotype. There was no difference in CR rate between FLT3-wt and FLT3-ITD patients (80% vs 78%). Relapse-free survival (RFS) was similar in both groups (5-year RFS, 33% vs 32%; P = 0.41), even after adjustment for age, sex, WBC, cytogenetics, and treatment arm. A trend to a worse survival was observed in the FLT3-ITD group (estimated 5-year OS, 23% vs 37%; P = 0.09), mainly in patients with a normal karyotype. This was associated with a dramatic outcome in relapsing FLT3-ITD patients (estimated 3-year post-relapse survival, 0% vs 27%; P = 0.04). These results suggest that the bad prognosis associated with FLT3-ITDs in AML might be partly overcome using reinforced chemotherapy. Early detection of FLT3 mutations might thus be useful to intensify induction as well as post-remission therapy in FLT3-ITD patients.

Breakdown of the FLT3-ITD/STAT5 axis and synergistic apoptosis induction by the histone deacetylase inhibitor panobinostat and FLT3-specific inhibitors.

PubMed

Pietschmann, Kristin; Bolck, Hella Anna; Buchwald, Marc; Spielberg, Steffi; Polzer, Harald; Spiekermann, Karsten; Bug, Gesine; Heinzel, Thorsten; Böhmer, Frank-Dietmar; Krämer, Oliver H

2012-11-01

Activating mutations of the class III receptor tyrosine kinase FLT3 are the most frequent molecular aberration in acute myeloid leukemia (AML). Mutant FLT3 accelerates proliferation, suppresses apoptosis, and correlates with poor prognosis. Therefore, it is a promising therapeutic target. Here, we show that RNA interference against FLT3 with an internal tandem duplication (FLT3-ITD) potentiates the efficacy of the histone deacetylase inhibitor (HDACi) panobinostat (LBH589) against AML cells expressing FLT3-ITD. Similar to RNA interference, tyrosine kinase inhibitors (TKI; AC220/cpd.102/PKC412) in combination with LBH589 exhibit superior activity against AML cells. Median dose-effect analyses of drug-induced apoptosis rates of AML cells (MV4-11 and MOLM-13) revealed combination index (CI) values indicating strong synergism. AC220, the most potent and FLT3-specific TKI, shows highest synergism with LBH589 in the low nanomolar range. A 4-hour exposure to LBH589 + AC220 already generates more than 50% apoptosis after 24 hours. Different cell lines lacking FLT3-ITD as well as normal peripheral blood mononuclear cells are not significantly affected by LBH589 + TKI, showing the specificity of this treatment regimen. Immunoblot analyses show that LBH589 + TKI induce apoptosis via degradation of FLT3-ITD and its prosurvival target STAT5. Previously, we showed the LBH589-induced proteasomal degradation of FLT3-ITD. Here, we show that activated caspase-3 also contributes to the degradation of FLT3-ITD and that STAT5 is a direct target of this protease. Our data strongly emphasize HDACi/TKI drug combinations as promising modality for the treatment of FLT3-ITD-positive AMLs. ©2012 AACR.

A trial of an impedance threshold device in out-of-hospital cardiac arrest.

PubMed

Aufderheide, Tom P; Nichol, Graham; Rea, Thomas D; Brown, Siobhan P; Leroux, Brian G; Pepe, Paul E; Kudenchuk, Peter J; Christenson, Jim; Daya, Mohamud R; Dorian, Paul; Callaway, Clifton W; Idris, Ahamed H; Andrusiek, Douglas; Stephens, Shannon W; Hostler, David; Davis, Daniel P; Dunford, James V; Pirrallo, Ronald G; Stiell, Ian G; Clement, Catherine M; Craig, Alan; Van Ottingham, Lois; Schmidt, Terri A; Wang, Henry E; Weisfeldt, Myron L; Ornato, Joseph P; Sopko, George

2011-09-01

The impedance threshold device (ITD) is designed to enhance venous return and cardiac output during cardiopulmonary resuscitation (CPR) by increasing the degree of negative intrathoracic pressure. Previous studies have suggested that the use of an ITD during CPR may improve survival rates after cardiac arrest. We compared the use of an active ITD with that of a sham ITD in patients with out-of-hospital cardiac arrest who underwent standard CPR at 10 sites in the United States and Canada. Patients, investigators, study coordinators, and all care providers were unaware of the treatment assignments. The primary outcome was survival to hospital discharge with satisfactory function (i.e., a score of ≤3 on the modified Rankin scale, which ranges from 0 to 6, with higher scores indicating greater disability). Of 8718 patients included in the analysis, 4345 were randomly assigned to treatment with a sham ITD and 4373 to treatment with an active device. A total of 260 patients (6.0%) in the sham-ITD group and 254 patients (5.8%) in the active-ITD group met the primary outcome (risk difference adjusted for sequential monitoring, -0.1 percentage points; 95% confidence interval, -1.1 to 0.8; P=0.71). There were also no significant differences in the secondary outcomes, including rates of return of spontaneous circulation on arrival at the emergency department, survival to hospital admission, and survival to hospital discharge. Use of the ITD did not significantly improve survival with satisfactory function among patients with out-of-hospital cardiac arrest receiving standard CPR. (Funded by the National Heart, Lung, and Blood Institute and others; ROC PRIMED ClinicalTrials.gov number, NCT00394706.).

Resuscitation Outcomes Consortium (ROC) PRIMED cardiac arrest trial methods part 1: rationale and methodology for the impedance threshold device (ITD) protocol.

PubMed

Aufderheide, Tom P; Kudenchuk, Peter J; Hedges, Jerris R; Nichol, Graham; Kerber, Richard E; Dorian, Paul; Davis, Daniel P; Idris, Ahamed H; Callaway, Clifton W; Emerson, Scott; Stiell, Ian G; Terndrup, Thomas E

2008-08-01

The primary aim of this study is to compare survival to hospital discharge with a modified Rankin score (MRS)< or =3 between standard cardiopulmonary resuscitation (CPR) plus an active impedance threshold device (ITD) versus standard CPR plus a sham ITD in patients with out-of-hospital cardiac arrest. Secondary aims are to compare functional status and depression at discharge and at 3 and 6 months post-discharge in survivors. Prospective, double-blind, randomized, controlled, clinical trial. Patients with non-traumatic out-of-hospital cardiac arrest treated by emergency medical services (EMS) providers. EMS systems participating in the Resuscitation Outcomes Consortium. Based on a one-sided significance level of 0.025, power=0.90, a survival with MRS< or =3 to discharge rate of 5.33% with standard CPR and sham ITD, and two interim analyses, a maximum of 14,742 evaluable patients are needed to detect a 6.69% survival with MRS< or =3 to discharge with standard CPR and active ITD (1.36% absolute survival difference). If the ITD demonstrates the hypothesized improvement in survival, it is estimated that 2700 deaths from cardiac arrest per year would be averted in North America alone.

Adjustment of interaural time difference in head related transfer functions based on listeners' anthropometry and its effect on sound localization

NASA Astrophysics Data System (ADS)

Suzuki, Yôiti; Watanabe, Kanji; Iwaya, Yukio; Gyoba, Jiro; Takane, Shouichi

2005-04-01

Because the transfer functions governing subjective sound localization (HRTFs) show strong individuality, sound localization systems based on synthesis of HRTFs require suitable HRTFs for individual listeners. However, it is impractical to obtain HRTFs for all listeners based on measurements. Improving sound localization by adjusting non-individualized HRTFs to a specific listener based on that listener's anthropometry might be a practical method. This study first developed a new method to estimate interaural time differences (ITDs) using HRTFs. Then correlations between ITDs and anthropometric parameters were analyzed using the canonical correlation method. Results indicated that parameters relating to head size, and shoulder and ear positions are significant. Consequently, it was attempted to express ITDs based on listener's anthropometric data. In this process, the change of ITDs as a function of azimuth angle was parameterized as a sum of sine functions. Then the parameters were analyzed using multiple regression analysis, in which the anthropometric parameters were used as explanatory variables. The predicted or individualized ITDs were installed in the nonindividualized HRTFs to evaluate sound localization performance. Results showed that individualization of ITDs improved horizontal sound localization.

Why Internally Coupled Ears (ICE) Work Well

NASA Astrophysics Data System (ADS)

van Hemmen, J. Leo

2014-03-01

Many vertebrates, such as frogs and lizards, have an air-filled cavity between left and right eardrum, i.e., internally coupled ears (ICE). Depending on source direction, internal time (iTD) and level (iLD) difference as experienced by the animal's auditory system may greatly exceed [C. Vossen et al., JASA 128 (2010) 909-918] the external, or interaural, time and level difference (ITD and ILD). Sensory processing only encodes iTD and iLD. We present an extension of ICE theory so as to elucidate the underlying physics. First, the membrane properties of the eardrum explain why for low frequencies iTD dominates whereas iLD does so for higher frequencies. Second, the plateau of iTD = γ ITD for constant 1 < γ < 5 and variable input frequency <ν∘ follows; e.g., for the Tockay gecko ν∘ ~ 1 . 5 kHz. Third, we use a sectorial instead of circular membrane to quantify the effect of the extracolumella embedded in the tympanum and connecting with the cochlea. The main parameters can be adjusted so that the model is species independent. Work done in collaboration with A.P. Vedurmudi and J. Goulet; partially supported by BCCN-Munich.

Concurrent Inhibition of Pim and FLT3 Kinases Enhances Apoptosis of FLT3-ITD Acute Myeloid Leukemia Cells through Increased Mcl-1 Proteasomal Degradation.

PubMed

Kapoor, Shivani; Natarajan, Karthika; Baldwin, Patrick R; Doshi, Kshama A; Lapidus, Rena G; Mathias, Trevor J; Scarpa, Mario; Trotta, Rossana; Davila, Eduardo; Kraus, Manfred; Huszar, Dennis; Tron, Adriana E; Perrotti, Danilo; Baer, Maria R

2018-01-01

Purpose: fms -like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) is present in 30% of acute myeloid leukemia (AML), and these patients have short disease-free survival. FLT3 inhibitors have limited and transient clinical activity, and concurrent treatment with inhibitors of parallel or downstream signaling may improve responses. The oncogenic serine/threonine kinase Pim-1 is upregulated downstream of FLT3-ITD and also promotes its signaling in a positive feedback loop, suggesting benefit of combined Pim and FLT3 inhibition. Experimental Design: Combinations of clinically active Pim and FLT3 inhibitors were studied in vitro and in vivo Results: Concurrent treatment with the pan-Pim inhibitor AZD1208 and FLT3 inhibitors at clinically applicable concentrations abrogated in vitro growth of FLT3-ITD, but not wild-type FLT3 (FLT3-WT), cell lines. AZD1208 cotreatment increased FLT3 inhibitor-induced apoptosis of FLT3-ITD, but not FLT3-WT, cells measured by sub-G 1 fraction, annexin V labeling, mitochondrial membrane potential, and PARP and caspase-3 cleavage. Concurrent treatment with AZD1208 and the FLT3 inhibitor quizartinib decreased growth of MV4-11 cells, with FLT3-ITD, in mouse xenografts, and prolonged survival, enhanced apoptosis of FLT3-ITD primary AML blasts, but not FLT3-WT blasts or remission marrow cells, and decreased FLT3-ITD AML blast colony formation. Mechanistically, AZD1208 and quizartinib cotreatment decreased expression of the antiapoptotic protein Mcl-1. Decrease in Mcl-1 protein expression was abrogated by treatment with the proteasome inhibitor MG132, and was preceded by downregulation of the Mcl-1 deubiquitinase USP9X, a novel mechanism of Mcl-1 regulation in AML. Conclusions: The data support clinical testing of Pim and FLT3 inhibitor combination therapy for FLT3-ITD AML. Clin Cancer Res; 24(1); 234-47. ©2017 AACR . ©2017 American Association for Cancer Research.

Experimental study on the damping of FAST cabin suspension system

NASA Astrophysics Data System (ADS)

Li, Hui; Sun, Jing-hai; Zhang, Xin-yu; Zhu, Wen-bai; Pan, Gao-feng; Yang, Qing-ge

2012-09-01

The focus cabin suspension of the FAST telescope has structurally weak-stiffness dynamics with low damping performance, which makes it quite sensitive to wind-induced vibrations. A reasonable estimation about the damping is very important for the control performance evaluation of the prototype. It is a quite difficult task as the telescope is no at available yet. In the paper, a preliminary analysis is first made on the aerodynamic damping. Then a series of experimental models are tested for measuring the total damping. The scales of these models range from 10m to 50m in diameter while 6 test parameters are specially designed to check the damping sensitivity. The Ibrahim time domain (ITD) method is employed to identify the damping from the measured cabin response. The identification results indicate that the lowest damping ratio of the models is about 0.2%~0.4%. Friction-type cabin-cable joint seems to have main influence on the system damping.

The Shock and Vibration Bulletin. Part 3. Machinery Dynamics, System Identification and Structural Analysis

DTIC Science & Technology

1985-06-01

purposes. 55 15 525 + 2 225L L53 + L3 ) + 2G3(L 2 + L35L4 + L45)" For the present system identification + 2G(L45 2 + L45L5 + L5 "L 1 technique, the...orbital model is comprised of 257 nodes and 819 dynamic:"DOF’s. k; were compared to ITD results for a wide variety of TD input parameters. Overall, the

The relative immunity of high-frequency transposed stimuli to low-frequency binaural interference

NASA Astrophysics Data System (ADS)

Bernstein, Leslie R.; Trahiotis, Constantine

2004-05-01

We have recently demonstrated that high-frequency transposed stimuli, having envelopes designed to provide high-frequency channels with information similar to that normally available in only low-frequency channels, yield threshold-ITDs and extents of laterality comparable to those obtained with conventional low-frequency stimuli. This enhanced potency of ITDs conveyed by high-frequency transposed stimuli, as compared to conventional high-frequency stimuli, suggested to us that ITDs conveyed by transposed stimuli might be relatively immune to the presence of low-frequency binaural interferers. To investigate this issue, threshold-ITDs and extents of laterality were measured with a variety of conventional and transposed targets centered at 4 kHz. The targets were presented either in the presence or absence of a simultaneously gated diotic noise centered at 500 Hz, the interferer. As expected, the presence of the low-frequency interferer resulted in substantially elevated threshold-ITDs and reduced extents of laterality for the conventional high-frequency stimuli. In contrast, these interference effects were either greatly attenuated or absent for ITDs conveyed by the high-frequency transposed targets. The results will be discussed in the context of current models of binaural interference. [Work supported by NIH DC 04147, NIH DC04073, NIH DC 002304.

Dystonia gene in Ashkenazi Jewish population is located on chromosome 9q32-34.

PubMed

Kramer, P L; de Leon, D; Ozelius, L; Risch, N; Bressman, S B; Brin, M F; Schuback, D E; Burke, R E; Kwiatkowski, D J; Shale, H

1990-02-01

Idiopathic torsion dystonia (ITD) is a neurological disorder characterized by sustained muscle contractions that appear as twisting movements of the limbs, trunk, and/or neck, which can progress to abnormal postures. Most familial forms of ITD follow autosomal dominant transmission with reduced penetrance. The frequency of ITD in the Ashkenazi Jewish population is five to ten times greater than that in other groups. Recently, a gene for ITD (DYT1) in a non-Jewish kindred was located on chromosome 9q32-34, with tight linkage to the gene encoding gelsolin (GSN). In the present study linkage analysis using DNA polymorphisms is used to locate a gene responsible for susceptibility to ITD in 12 Ashkenazi Jewish families. This dystonia gene exhibits close linkage with the gene encoding argininosuccinate synthetase (ASS), and appears by multipoint analysis to lie in the q32-34 region of chromosome 9, a region that also contains the loci for gelsolin and dopamine-beta-hydroxylase. The same gene may be responsible for ITD both in the non-Jewish kindred mentioned above and in the Ashkenazi Jewish families presented here. However, because there is substantial difference between the penetrance of the dominant allele in these two groups, two different mutations may be operating to produce susceptibility to this disease in the two groups.

Resuscitation Outcomes Consortium (ROC) PRIMED Cardiac Arrest Trial Methods, Part 1: Rationale and Methodology for the Impedance Threshold Device (ITD) Protocol

PubMed Central

Aufderheide, Tom P.; Kudenchuk, Peter J.; Hedges, Jerris R.; Nichol, Graham; Kerber, Richard E.; Dorian, Paul; Davis, Daniel P.; Idris, Ahamed H.; Callaway, Clifton W.; Emerson, Scott; Stiell, Ian G.; Terndrup, Thomas E.

2013-01-01

Aim The primary aim of this study is to compare survival to hospital discharge with a modified Rankin score (MRS) ≤3 between standard cardiopulmonary resuscitation (CPR) plus an active impedance threshold device (ITD) versus standard CPR plus a sham ITD in patients with out-of-hospital cardiac arrest. Secondary aims are to compare functional status and depression at discharge and at 3 and 6 months post discharge in survivors. Materials and Methods Design Prospective, double-blind, randomized, controlled, clinical trial. Population Patients with non-traumatic out-of-hospital cardiac arrest treated by emergency medical services (EMS) providers. Setting EMS systems participating in the Resuscitation Outcomes Consortium. Sample Size Based on a one-sided significance level of 0.025, power = 0.90, a survival with MRS ≤ 3 to discharge rate of 5.33% with standard CPR and sham ITD, and two interim analyses, a maximum of 14,742 evaluable patients are needed to detect a 6.69% survival with MRS ≤ 3 to discharge with standard CPR and active ITD (1.36% absolute survival difference). Conclusion If the ITD demonstrates the hypothesized improvement in survival, it is estimated that2,700 deaths from cardiac arrest per year would be averted in North America alone. PMID:18487005

Oncogenic roles of PRL-3 in FLT3-ITD induced acute myeloid leukaemia

PubMed Central

Park, Jung Eun; Yuen, Hiu Fung; Zhou, Jian Biao; Al-aidaroos, Abdul Qader O; Guo, Ke; Valk, Peter J; Zhang, Shu Dong; Chng, Wee Joo; Hong, Cheng William; Mills, Ken; Zeng, Qi

2013-01-01

FLT3-ITD mutations are prevalent mutations in acute myeloid leukaemia (AML). PRL-3, a metastasis-associated phosphatase, is a downstream target of FLT3-ITD. This study investigates the regulation and function of PRL-3 in leukaemia cell lines and AML patients associated with FLT3-ITD mutations. PRL-3 expression is upregulated by the FLT3-STAT5 signalling pathway in leukaemia cells, leading an activation of AP-1 transcription factors via ERK and JNK pathways. PRL-3-depleted AML cells showed a significant decrease in cell growth. Clinically, high PRL-3 mRNA expression was associated with FLT3-ITD mutations in four independent AML datasets with 1158 patients. Multivariable Cox-regression analysis on our Cohort 1 with 221 patients identified PRL-3 as a novel prognostic marker independent of other clinical parameters. Kaplan–Meier analysis showed high PRL-3 mRNA expression was significantly associated with poorer survival among 491 patients with normal karyotype. Targeting PRL-3 reversed the oncogenic effects in FLT3-ITD AML models in vitro and in vivo. Herein, we suggest that PRL-3 could serve as a prognostic marker to predict poorer survival and as a promising novel therapeutic target for AML patients. PMID:23929599

Sensitivity to Envelope Interaural Time Differences at High Modulation Rates

PubMed Central

Bleeck, Stefan; McAlpine, David

2015-01-01

Sensitivity to interaural time differences (ITDs) conveyed in the temporal fine structure of low-frequency tones and the modulated envelopes of high-frequency sounds are considered comparable, particularly for envelopes shaped to transmit similar fidelity of temporal information normally present for low-frequency sounds. Nevertheless, discrimination performance for envelope modulation rates above a few hundred Hertz is reported to be poor—to the point of discrimination thresholds being unattainable—compared with the much higher (>1,000 Hz) limit for low-frequency ITD sensitivity, suggesting the presence of a low-pass filter in the envelope domain. Further, performance for identical modulation rates appears to decline with increasing carrier frequency, supporting the view that the low-pass characteristics observed for envelope ITD processing is carrier-frequency dependent. Here, we assessed listeners’ sensitivity to ITDs conveyed in pure tones and in the modulated envelopes of high-frequency tones. ITD discrimination for the modulated high-frequency tones was measured as a function of both modulation rate and carrier frequency. Some well-trained listeners appear able to discriminate ITDs extremely well, even at modulation rates well beyond 500 Hz, for 4-kHz carriers. For one listener, thresholds were even obtained for a modulation rate of 800 Hz. The highest modulation rate for which thresholds could be obtained declined with increasing carrier frequency for all listeners. At 10 kHz, the highest modulation rate at which thresholds could be obtained was 600 Hz. The upper limit of sensitivity to ITDs conveyed in the envelope of high-frequency modulated sounds appears to be higher than previously considered. PMID:26721926

Reduced temporal processing in older, normal-hearing listeners evident from electrophysiological responses to shifts in interaural time difference.

PubMed

Ozmeral, Erol J; Eddins, David A; Eddins, Ann C

2016-12-01

Previous electrophysiological studies of interaural time difference (ITD) processing have demonstrated that ITDs are represented by a nontopographic population rate code. Rather than narrow tuning to ITDs, neural channels have broad tuning to ITDs in either the left or right auditory hemifield, and the relative activity between the channels determines the perceived lateralization of the sound. With advancing age, spatial perception weakens and poor temporal processing contributes to declining spatial acuity. At present, it is unclear whether age-related temporal processing deficits are due to poor inhibitory controls in the auditory system or degraded neural synchrony at the periphery. Cortical processing of spatial cues based on a hemifield code are susceptible to potential age-related physiological changes. We consider two distinct predictions of age-related changes to ITD sensitivity: declines in inhibitory mechanisms would lead to increased excitation and medial shifts to rate-azimuth functions, whereas a general reduction in neural synchrony would lead to reduced excitation and shallower slopes in the rate-azimuth function. The current study tested these possibilities by measuring an evoked response to ITD shifts in a narrow-band noise. Results were more in line with the latter outcome, both from measured latencies and amplitudes of the global field potentials and source-localized waveforms in the left and right auditory cortices. The measured responses for older listeners also tended to have reduced asymmetric distribution of activity in response to ITD shifts, which is consistent with other sensory and cognitive processing models of aging. Copyright © 2016 the American Physiological Society.

Acidosis mediates recurrent hypoglycemia-induced increase in ischemic brain injury in treated diabetic rats.

PubMed

Rehni, Ashish K; Shukla, Vibha; Perez-Pinzon, Miguel A; Dave, Kunjan R

2018-03-15

Cerebral ischemia is a serious possible manifestation of diabetic vascular disease. Recurrent hypoglycemia (RH) enhances ischemic brain injury in insulin-treated diabetic (ITD) rats. In the present study, we determined the role of ischemic acidosis in enhanced ischemic brain damage in RH-exposed ITD rats. Diabetic rats were treated with insulin and mild/moderate RH was induced for 5 days. Three sets of experiments were performed. The first set evaluated the effects of RH exposure on global cerebral ischemia-induced acidosis in ITD rats. The second set evaluated the effect of an alkalizing agent (Tris-(hydroxymethyl)-aminomethane: THAM) on ischemic acidosis-induced brain injury in RH-exposed ITD rats. The third experiment evaluated the effect of the glucose transporter (GLUT) inhibitor on ischemic acidosis-induced brain injury in RH-exposed ITD rats. Hippocampal pH and lactate were measured during ischemia and early reperfusion for all three experiments. Neuronal survival in Cornu Ammonis 1 (CA1) hippocampus served as a measure of ischemic brain injury. Prior RH exposure increases lactate concentration and decreases pH during ischemia and early reperfusion when compared to controls. THAM and GLUT inhibitor treatments attenuated RH-induced increase in ischemic acidosis. GLUT inhibitor treatment reduced the RH-induced increase in lactate levels. Both THAM and GLUT inhibitor treatments significantly decreased ischemic damage in RH-exposed ITD rats. Ischemia causes increased acidosis in RH-exposed ITD rats via a GLUT-sensitive mechanism. Exploring downstream pathways may help understand mechanisms by which prior exposure to RH increases cerebral ischemic damage. Copyright © 2018 Elsevier Ltd. All rights reserved.

Tyrosine 842 in the activation loop is required for full transformation by the oncogenic mutant FLT3-ITD.

PubMed

Kazi, Julhash U; Chougule, Rohit A; Li, Tianfeng; Su, Xianwei; Moharram, Sausan A; Rupar, Kaja; Marhäll, Alissa; Gazi, Mohiuddin; Sun, Jianmin; Zhao, Hui; Rönnstrand, Lars

2017-07-01

The type III receptor tyrosine kinase FLT3 is frequently mutated in acute myeloid leukemia. Oncogenic FLT3 mutants display constitutive activity leading to aberrant cell proliferation and survival. Phosphorylation on several critical tyrosine residues is known to be essential for FLT3 signaling. Among these tyrosine residues, Y842 is located in the so-called activation loop. The position of this tyrosine residue is well conserved in all receptor tyrosine kinases. It has been reported that phosphorylation of the activation loop tyrosine is critical for catalytic activity for some but not all receptor tyrosine kinases. The role of Y842 residue in FLT3 signaling has not yet been studied. In this report, we show that Y842 is not important for FLT3 activation or ubiquitination but plays a critical role in regulating signaling downstream of the receptor as well as controlling receptor stability. We found that mutation of Y842 in the FLT3-ITD oncogenic mutant background reduced cell viability and increased apoptosis. Furthermore, the introduction of the Y842 mutation in the FLT3-ITD background led to a dramatic reduction in in vitro colony forming capacity. Additionally, mice injected with cells expressing FLT3-ITD/Y842F displayed a significant delay in tumor formation, compared to FLT3-ITD expressing cells. Microarray analysis comparing gene expression regulated by FLT3-ITD versus FLT3-ITD/Y842F demonstrated that mutation of Y842 causes suppression of anti-apoptotic genes. Furthermore, we showed that cells expressing FLT3-ITD/Y842F display impaired activity of the RAS/ERK pathway due to reduced interaction between FLT3 and SHP2 leading to reduced SHP2 activation. Thus, we suggest that Y842 is critical for FLT3-mediated RAS/ERK signaling and cellular transformation.

All-trans retinoic acid synergizes with FLT3 inhibition to eliminate FLT3/ITD+ leukemia stem cells in vitro and in vivo.

PubMed

Ma, Hayley S; Greenblatt, Sarah M; Shirley, Courtney M; Duffield, Amy S; Bruner, J Kyle; Li, Li; Nguyen, Bao; Jung, Eric; Aplan, Peter D; Ghiaur, Gabriel; Jones, Richard J; Small, Donald

2016-06-09

FMS-like tyrosine kinase 3 (FLT3)-mutant acute myeloid leukemia (AML) portends a poor prognosis, and ineffective targeting of the leukemic stem cell (LSC) population remains one of several obstacles in treating this disease. All-trans retinoic acid (ATRA) has been used in several clinical trials for the treatment of nonpromyelocytic AML with limited clinical activity observed. FLT3 tyrosine kinase inhibitors (TKIs) used as monotherapy also achieve limited clinical responses and are thus far unable to affect cure rates in AML patients. We explored the efficacy of combining ATRA and FLT3 TKIs to eliminate FLT3/internal tandem duplication (ITD)(+) LSCs. Our studies reveal highly synergistic drug activity, preferentially inducing apoptosis in FLT3/ITD(+) cell lines and patient samples. Colony-forming unit assays further demonstrate decreased clonogenicity of FLT3/ITD(+) cells upon treatment with ATRA and TKI. Most importantly, the drug combination depletes FLT3/ITD(+) LSCs in a genetic mouse model of AML, and prolongs survival of leukemic mice. Furthermore, engraftment of primary FLT3/ITD(+) patient samples is reduced in mice following treatment with FLT3 TKI and ATRA in combination, with evidence of cellular differentiation occurring in vivo. Mechanistically, we provide evidence that the synergism of ATRA and FLT3 TKIs is at least in part due to the observation that FLT3 TKI treatment upregulates the antiapoptotic protein Bcl6, limiting the drug's apoptotic effect. However, cotreatment with ATRA reduces Bcl6 expression to baseline levels through suppression of interleukin-6 receptor signaling. These studies provide evidence of the potential of this drug combination to eliminate FLT3/ITD(+) LSCs and reduce the rate of relapse in AML patients with FLT3 mutations.

Targeting BTK for the treatment of FLT3-ITD mutated acute myeloid leukemia.

PubMed

Pillinger, Genevra; Abdul-Aziz, Amina; Zaitseva, Lyubov; Lawes, Matthew; MacEwan, David J; Bowles, Kristian M; Rushworth, Stuart A

2015-08-21

Approximately 20% of patients with acute myeloid leukaemia (AML) have a mutation in FMS-like-tyrosine-kinase-3 (FLT3). FLT3 is a trans-membrane receptor with a tyrosine kinase domain which, when activated, initiates a cascade of phosphorylated proteins including the SRC family of kinases. Recently our group and others have shown that pharmacologic inhibition and genetic knockdown of Bruton's tyrosine kinase (BTK) blocks AML blast proliferation, leukaemic cell adhesion to bone marrow stromal cells as well as migration of AML blasts. The anti-proliferative effects of BTK inhibition in human AML are mediated via inhibition of downstream NF-κB pro-survival signalling however the upstream drivers of BTK activation in human AML have yet to be fully characterised. Here we place the FLT3-ITD upstream of BTK in AML and show that the BTK inhibitor ibrutinib inhibits the survival and proliferation of FLT3-ITD primary AML blasts and AML cell lines. Furthermore ibrutinib inhibits the activation of downstream kinases including MAPK, AKT and STAT5. In addition we show that BTK RNAi inhibits proliferation of FLT3-ITD AML cells. Finally we report that ibrutinib reverses the cyto-protective role of BMSC on FLT3-ITD AML survival. These results argue for the evaluation of ibrutinib in patients with FLT3-ITD mutated AML.

Modelling of human low frequency sound localization acuity demonstrates dominance of spatial variation of interaural time difference and suggests uniform just-noticeable differences in interaural time difference.

PubMed

Smith, Rosanna C G; Price, Stephen R

2014-01-01

Sound source localization is critical to animal survival and for identification of auditory objects. We investigated the acuity with which humans localize low frequency, pure tone sounds using timing differences between the ears. These small differences in time, known as interaural time differences or ITDs, are identified in a manner that allows localization acuity of around 1° at the midline. Acuity, a relative measure of localization ability, displays a non-linear variation as sound sources are positioned more laterally. All species studied localize sounds best at the midline and progressively worse as the sound is located out towards the side. To understand why sound localization displays this variation with azimuthal angle, we took a first-principles, systemic, analytical approach to model localization acuity. We calculated how ITDs vary with sound frequency, head size and sound source location for humans. This allowed us to model ITD variation for previously published experimental acuity data and determine the distribution of just-noticeable differences in ITD. Our results suggest that the best-fit model is one whereby just-noticeable differences in ITDs are identified with uniform or close to uniform sensitivity across the physiological range. We discuss how our results have several implications for neural ITD processing in different species as well as development of the auditory system.

Long-term survival of sorafenib-treated FLT3-ITD-positive acute myeloid leukaemia patients relapsing after allogeneic stem cell transplantation.

PubMed

Metzelder, S K; Schroeder, T; Lübbert, M; Ditschkowski, M; Götze, K; Scholl, S; Meyer, R G; Dreger, P; Basara, N; Fey, M F; Salih, H R; Finck, A; Pabst, T; Giagounidis, A; Kobbe, G; Wollmer, E; Finke, J; Neubauer, A; Burchert, A

2017-11-01

Fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD)-positive acute myeloid leukaemia (AML) relapsing after allogeneic stem cell transplantation (allo-SCT) has a dismal prognosis with limited therapeutic options. FLT3-ITD kinase inhibition is a reasonable but palliative experimental treatment alternative in this situation. Information on long-term outcome is not available. We performed a long-term follow-up analysis of a previously reported cohort of 29 FLT3-ITD-positive AML patients, which were treated in relapse after allo-SCT with sorafenib monotherapy. With a median follow-up of 7.5 years, 6 of 29 patients (21%) are still alive. Excluding one patient who received a second allo-SCT, five patients (17%) achieved sustained complete remissions with sorafenib. Four of these patients are in treatment-free remission for a median of 4.4 years. Sorafenib may enable cure of a proportion of very poor risk FLT3-ITD-positive AML relapsing after allo-SCT. Copyright © 2017 Elsevier Ltd. All rights reserved.

Chidamide in FLT3-ITD positive acute myeloid leukemia and the synergistic effect in combination with cytarabine.

PubMed

Li, Xia; Yan, Xiao; Guo, Wenjian; Huang, Xin; Huang, Jiansong; Yu, Mengxia; Ma, Zhixin; Xu, Yu; Huang, ShuJuan; Li, Chenying; Zhou, Yile; Jin, Jie

2017-06-01

Chidamide, a novel histone deacetylase inhibitor (HDACi), has been approved for treatment of T-cell lymphomas in multiple clinical trials. It has been demonstrated that chidamide can inhibit cell cycle, promote apoptosis and induce differentiation in leukemia cells, whereas its effect on acute myeloid leukemia (AML) patients with FLT3-ITD mutation has not been clarified. In this study, we found that chidamide specifically induced G0/G1 arrest and apoptosis in FLT3-ITD positive AML cells in a concentration and time-dependent manner. We also found chidamide had the cytotoxicity effect on FLT3-ITD positive and negative AML cells. Moreover, with respect to relapsed/refractory patients, chidamide showed the same effectiveness as that in de novo AML patients. Notably, chidamide synergistically enhanced apoptosis caused by cytarabine. Our results support chidamide alone or combine with cytarabine may be used as an alternative therapeutic choice for AML patients especially those with FLT3-ITD mutation or relapsed/refractory ones. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

FLT3-ITD induces expression of Pim kinases through STAT5 to confer resistance to the PI3K/Akt pathway inhibitors on leukemic cells by enhancing the mTORC1/Mcl-1 pathway.

PubMed

Okada, Keigo; Nogami, Ayako; Ishida, Shinya; Akiyama, Hiroki; Chen, Cheng; Umezawa, Yoshihiro; Miura, Osamu

2018-02-06

FLT3-ITD is the most frequent tyrosine kinase mutation in acute myeloid leukemia (AML) associated with poor prognosis. We previously reported that activation of STAT5 confers resistance to PI3K/Akt inhibitors on the FLT3-ITD-positive AML cell line MV4-11 and 32D cells driven by FLT3-ITD (32D/ITD) but not by FLT3 mutated in the tyrosine kinase domain (32D/TKD). Here, we report the involvement of Pim kinases expressed through STAT5 activation in acquisition of this resistance. The specific pan-Pim kinase inhibitor AZD1208 as well as PIM447 in combination with the PI3K inhibitor GDC-0941 or the Akt inhibitor MK-2206 cooperatively downregulated the mTORC1/4EBP1 pathway, formation of the eIF4E/eIF4G complex, and Mcl-1 expression leading to activation of Bak and Bax to induce caspase-dependent apoptosis synergistically in these cells. These cooperative effects were enhanced or inhibited by knock down of mTOR or expression of its activated mutant, respectively. Overexpression of Mcl-1 conferred the resistance on 32D/ITD cells to combined inhibition of the PI3K/Akt pathway and Pim kinases, while the Mcl-1-specific BH3 mimetic A-1210477 conquered the resistance of MV4-11 cells to GDC-0941. Furthermore, overexpression of Pim-1 in 32D/TKD enhanced the mTORC1/Mcl-1 pathway and partially protected it from the PI3K/Akt inhibitors or the FLT3 inhibitor gilteritinib to confer the resistance to PI3K/Akt inhibitors. Finally, AZD1208 and GDC-0941 cooperatively inhibited the mTORC1/Mcl-1 pathway and reduced viable cell numbers of primary AML cells from some FLT3-ITD positive cases. Thus, Pim kinases may protect the mTORC1/4EBP1/Mcl-1 pathway to confer the resistance to the PI3K/Akt inhibitors on FLT3-ITD cells and represent promising therapeutic targets.

Audiometric asymmetry and tinnitus laterality.

PubMed

Tsai, Betty S; Sweetow, Robert W; Cheung, Steven W

2012-05-01

To identify an optimal audiometric asymmetry index for predicting tinnitus laterality. Retrospective medical record review. Data from adult tinnitus patients (80 men and 44 women) were extracted for demographic, audiometric, tinnitus laterality, and related information. The main measures were sensitivity, specificity, positive predictive value (PPV), and receiver operating characteristic (ROC) curves. Three audiometric asymmetry indices were constructed using one, two, or three frequency elements to compute the average interaural threshold difference (aITD). Tinnitus laterality predictive performance of a particular index was assessed by increasing the cutoff or minimum magnitude of the aITD from 10 to 35 dB in 5-dB steps to determine its ROC curve. Single frequency index performance was inferior to the other two (P < .05). Double and triple frequency indices were indistinguishable (P > .05). Two adjoining frequency elements with aITD ≥ 15 dB performed optimally for predicting tinnitus laterality (sensitivity = 0.59, specificity = 0.71, and PPV = 0.76). Absolute and relative magnitudes of hearing loss in the poorer ear were uncorrelated with tinnitus distress. An optimal audiometric asymmetry index to predict tinnitus laterality is one whereby 15 dB is the minimum aITD of two adjoining frequencies, inclusive of the maximal ITD. Tinnitus laterality dependency on magnitude of interaural asymmetry may inform design and interpretation of neuroimaging studies. Monaural acoustic tinnitus therapy may be an initial consideration for asymmetric hearing loss meeting the criterion of aITD ≥ 15 dB. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

RSK2 is a new Pim2 target with pro-survival functions in FLT3-ITD-positive acute myeloid leukemia.

PubMed

Hospital, M-A; Jacquel, A; Mazed, F; Saland, E; Larrue, C; Mondesir, J; Birsen, R; Green, A S; Lambert, M; Sujobert, P; Gautier, E-F; Salnot, V; Le Gall, M; Decroocq, J; Poulain, L; Jacque, N; Fontenay, M; Kosmider, O; Récher, C; Auberger, P; Mayeux, P; Bouscary, D; Sarry, J-E; Tamburini, J

2018-03-01

Acute myeloid leukemia (AML) with the FLT3 internal tandem duplication (FLT3-ITD AML) accounts for 20-30% of AML cases. This subtype usually responds poorly to conventional therapies, and might become resistant to FLT3 tyrosine kinase inhibitors (TKIs) due to molecular bypass mechanisms. New therapeutic strategies focusing on resistance mechanisms are therefore urgently needed. Pim kinases are FLT3-ITD oncogenic targets that have been implicated in FLT3 TKI resistance. However, their precise biological function downstream of FLT3-ITD requires further investigation. We performed high-throughput transcriptomic and proteomic analyses in Pim2-depleted FLT3-ITD AML cells and found that Pim2 predominantly controlled apoptosis through Bax expression and mitochondria disruption. We identified ribosomal protein S6 kinase A3 (RSK2), a 90 kDa serine/threonine kinase involved in the mitogen-activated protein kinase cascade encoded by the RPS6KA3 gene, as a novel Pim2 target. Ectopic expression of an RPS6KA3 allele rescued the viability of Pim2-depleted cells, supporting the involvement of RSK2 in AML cell survival downstream of Pim2. Finally, we showed that RPS6KA3 knockdown reduced the propagation of human AML cells in vivo in mice. Our results point to RSK2 as a novel Pim2 target with translational therapeutic potential in FLT3-ITD AML.

Tyrosine Phosphorylation Regulates Maturation of Receptor Tyrosine Kinases

PubMed Central

Schmidt-Arras, Dirk-E.; Böhmer, Annette; Markova, Boyka; Choudhary, Chunaram; Serve, Hubert; Böhmer, Frank-D.

2005-01-01

Constitutive activation of receptor tyrosine kinases (RTKs) is a frequent event in human cancer cells. Activating mutations in Fms-like tyrosine kinase 3 (FLT-3), notably, internal tandem duplications in the juxtamembrane domain (FLT-3 ITD), have been causally linked to acute myeloid leukemia. As we describe here, FLT-3 ITD exists predominantly in an immature, underglycosylated 130-kDa form, whereas wild-type FLT-3 is expressed predominantly as a mature, complex glycosylated 150-kDa molecule. Endogenous FLT-3 ITD, but little wild-type FLT-3, is detectable in the endoplasmic reticulum (ER) compartment. Conversely, cell surface expression of FLT-3 ITD is less efficient than that of wild-type FLT-3. Inhibition of FLT-3 ITD kinase by small molecules, inactivating point mutations, or coexpression with the protein-tyrosine phosphatases (PTPs) SHP-1, PTP1B, and PTP-PEST but not RPTPα promotes complex glycosylation and surface localization. However, PTP coexpression has no effect on the maturation of a surface glycoprotein of vesicular stomatitis virus. The maturation of wild-type FLT-3 is impaired by general PTP inhibition or by suppression of endogenous PTP1B. Enhanced complex formation of FLT-3 ITD with the ER-resident chaperone calnexin indicates that its retention in the ER is related to inefficient folding. The regulation of RTK maturation by tyrosine phosphorylation was observed with other RTKs as well, defines a possible role for ER-resident PTPs, and may be related to the altered signaling quality of constitutively active, transforming RTK mutants. PMID:15831474

Favorable outcome of patients with acute myeloid leukemia harboring a low-allelic burden FLT3-ITD mutation and concomitant NPM1 mutation: relevance to post-remission therapy.

PubMed

Pratcorona, Marta; Brunet, Salut; Nomdedéu, Josep; Ribera, Josep Maria; Tormo, Mar; Duarte, Rafael; Escoda, Lourdes; Guàrdia, Ramon; Queipo de Llano, M Paz; Salamero, Olga; Bargay, Joan; Pedro, Carmen; Martí, Josep Maria; Torrebadell, Montserrat; Díaz-Beyá, Marina; Camós, Mireia; Colomer, Dolors; Hoyos, Montserrat; Sierra, Jorge; Esteve, Jordi

2013-04-04

Risk associated to FLT3 internal tandem duplication (FLT3-ITD) in patients with acute myeloid leukemia (AML) may depend on mutational burden and its interaction with other mutations. We analyzed the effect of FLT3-ITD/FLT3 wild-type (FLT3wt) ratio depending on NPM1 mutation (NPM1mut) in 303 patients with intermediate-risk cytogenetics AML treated with intensive chemotherapy. Among NPM1mut patients, FLT3wt and low ratio (<0.5) subgroups showed similar overall survival, relapse risk, and leukemia-free survival, whereas high ratio (≥0.5) patients had a worse outcome. In NPM1wt AML, FLT3-ITD subgroups showed a comparable outcome, with higher risk of relapse and shortened overall survival than FLT3wt patients. Allogeneic stem cell transplantation in CR1 was associated with a reduced relapse risk in all molecular subgroups with the exception of NPM1mut AML with absent or low ratio FLT3-ITD. In conclusion, effect of FLT3 burden is modulated by NPM1 mutation, especially in patients with a low ratio.

MIZMAS: Modeling the Evolution of Ice Thickness and Floe Size Distributions in the Marginal Ice Zone of the Chukchi and Beaufort Seas

DTIC Science & Technology

2015-09-30

ITD theory of Thorndike et al. (1975) in order to explicitly simulate the evolution of FSD and ITD jointly. The FSD theory includes a FSD function and...et al., 2015). 4 RESULTS Modeling: A FSD theory is developed and coupled to the ITD theory of Thorndike et al. (1975) in order to... Thorndike , A.S., D.A. Rothrock, G.A. Maykut, and R. Colony (1975), The thickness distribution of sea ice. J. Geophys. Res., 80, 4501–4513. Zhang

Idaho Transportation Department 2011 customer satisfaction survey.

DOT National Transportation Integrated Search

2011-10-01

In the spring and summer of 2011, the Idaho Transportation Department (ITD) commissioned a statewide customer satisfaction survey of Idaho residents to assess their perception of ITDs performance in several key areas of customer service. The areas...

Directional hearing by linear summation of binaural inputs at the medial superior olive

PubMed Central

van der Heijden, Marcel; Lorteije, Jeannette A. M.; Plauška, Andrius; Roberts, Michael T.; Golding, Nace L.; Borst, J. Gerard G.

2013-01-01

SUMMARY Neurons in the medial superior olive (MSO) enable sound localization by their remarkable sensitivity to submillisecond interaural time differences (ITDs). Each MSO neuron has its own “best ITD” to which it responds optimally. A difference in physical path length of the excitatory inputs from both ears cannot fully account for the ITD tuning of MSO neurons. As a result, it is still debated how these inputs interact and whether the segregation of inputs to opposite dendrites, well-timed synaptic inhibition, or asymmetries in synaptic potentials or cellular morphology further optimize coincidence detection or ITD tuning. Using in vivo whole-cell and juxtacellular recordings, we show here that ITD tuning of MSO neurons is determined by the timing of their excitatory inputs. The inputs from both ears sum linearly, whereas spike probability depends nonlinearly on the size of synaptic inputs. This simple coincidence detection scheme thus makes accurate sound localization possible. PMID:23764292

Numerical investigation of the effects of ITD length on low pressure nozzle

NASA Astrophysics Data System (ADS)

Liu, Guang; Liu, Jun; Liu, Hongrui; Wang, Pei; Du, Qiang

2017-06-01

The advantage of high efficiency, low SFC (Specific Fuel Consumption), ultra-high bypass ratio turbofan engine attracts more and more attention in modern commercial engine. The intermediate turbine duct (ITD), which connects high pressure turbine (HPT) with low pressure turbine (LPT), has a critical impact on the overall performance of turbine by guiding flow coming from HPT to LPT without too much loss. Therefore, it becomes more and more urgent to master the technique of designing aggressive, even super-aggressive ITD. Much more concerns have been concentrated on the duct. However, in order to further improve turbine, LPT nozzle is arranged into ITD to shorten low pressure axle. With such design concept, it is obvious that LPT nozzle flow field is easily influenced by upstream duct structure, but receives much less interests on the contrary. In this paper, numerical method is used to investigate the effects of length of ITD with upstream swirl blades on LPT nozzle. Nine models with the same swirl and nozzle blades, while the length of ITD is the only parameter to be changed, will be discussed. Finally, several conclusions and advices for designers are summarized. After changing axial length of ducts, inlet and outlet flow field of nozzle differs, correspondingly. On the other hand, the shearing stress on nozzle blade (suction and pressure) surface presents individual feature under various inlet flow. In addition to that, "Clocking-like effect" is described in this paper, which will contribute much to the pressure loss and should be paid enough attention.

Intratympanic treatment of intractable unilateral Meniere disease: gentamicin or dexamethasone? A randomized controlled trial.

PubMed

Casani, Augusto Pietro; Piaggi, Paolo; Cerchiai, Niccolò; Seccia, Veronica; Franceschini, Stefano Sellari; Dallan, Iacopo

2012-03-01

To determine the efficacy and safety of low-dose intratympanic gentamicin (ITG) compared with intratympanic dexamethasone (ITD) in patients with intractable unilateral Ménière disease (MD). Open prospective randomized controlled study. Tertiary referral center. Sixty patients affected by definite unilateral MD were enrolled between January 1, 2007, and June 30, 2008. Thirty-two patients were treated with a buffered gentamicin solution injected in the middle ear (maximum of 2 injections); 28 patients were treated with ITD (4 mg/mL, 3 injections at intervals of 1 every 3 days). Mean outcome measurements consisted of control of vertigo attacks, pure tone average (PTA), speech discrimination score, functional disability score, and statistical analysis using repeated measures analysis of variance. In the ITG group at 2-year follow-up, complete control of vertigo (class A) was achieved in 26 patients (81%) and substantial control of vertigo (class B) in 4 patients (12.5%). In the ITD group, class A was achieved in 12 (43%), and class B in 5 (18%) patients. In the gentamicin group, 4 patients showed a reduction in PTA of ≥10 dB. In the ITD group, PTA was unchanged or slightly improved in 16 patients (belonging to class A-B) and worse in 12. Low-dose ITG achieved better outcome than ITD in the control of vertigo attacks in patients suffering from unilateral MD, with a very low incidence of hearing deterioration. ITD offers poorer vertigo control rate, and hearing preservation is achieved only in cases with no vertigo recurrences.

Numerical investigation of the effects of rising angle on intermediate turbine duct and nearby turbines

NASA Astrophysics Data System (ADS)

Liu, Hongrui; Ji, Lucheng; Liu, Jun; Du, Qiang; Liu, Guang; Wang, Pei; Du, Meimei

2017-10-01

In order to improve the efficiency, ultra-high bypass ratio engine attracts more and more attention because of its huge advantage, which has larger diameter low pressure turbine (LPT). This trend will lead to aggressive (high diffusion) intermediate turbine duct (ITD) design. It is necessary to guide the flow leaving high pressure turbine (HPT) to LPT at a larger diameter without any severe loss generating separation or flow disturbances. In this paper, eight ITDs with upstream swirl vanes and downstream LPT nozzle are investigated with the aid of numerical method. These models are modified from a unique ITD prototype, which comes from a real engine. Key parameters like area ratio, inlet height, and non-dimensional length of the ITDs are kept unchanged, while the rising angle (radial offset) is the only changed parameter which ranges from 8 degrees to 45 degrees. In this paper, the effects of rising angle (RA) on ITD, as well as nearby turbines, will be analyzed in detail. According to the investigation results, RA could be as large as 40 degrees in such model of this paper to escape separation; When RA increases, local inlet flow field of LPT nozzle appears to be with apparent variation; while a positive result is that outlet flow field could be kept almost unchanged through modifying blade profile. On the other hand, it seems optimistic that the overall total pressure loss could be kept nearly equivalent among different RA cases. And a valuable conclusion is that outer wall curvature is more important for pressure loss, which advises a clear direction for optimizing ITD.

Evaluation of the Idaho Transportation Department integrated road-weather information system

DOT National Transportation Integrated Search

2005-02-02

This report presents the results of FHWA's evaluation of the Idaho Transportation Department's (ITD) integration of its Road-Weather Information System (RWIS). The ITD RWIS project was selected for evaluation because it held significant potential to ...

Use of impedance threshold device in conjunction with our novel adhesive glove device for ACD-CPR does not result in additional chest decompression.

PubMed

Shih, Andre; Udassi, Sharda; Porvasnik, Stacy L; Lamb, Melissa A; Badugu, Srinivasarao; Venkata, Giridhar Kaliki; Lopez-Colon, Dalia; Haque, Ikram U; Zaritsky, Arno L; Udassi, Jai P

2013-10-01

To evaluate the hemodynamic effects of using an adhesive glove device (AGD) to perform active compression-decompression CPR (AGD-CPR) in conjunction with an impedance threshold device (ITD) in a pediatric cardiac arrest model. Controlled, randomized animal study. In this study, 18 piglets were anesthetized, ventilated, and continuously monitored. After 3min of untreated ventricular fibrillation, animals were randomized (6/group) to receive either standard CPR (S-CPR), active compression-decompression CPR via adhesive glove device (AGD-CPR) or AGD-CPR along with an ITD (AGD-CPR+ITD) for 2min at 100-120compressions/min. AGD is delivered using a fingerless leather glove with a Velcro patch on the palmer aspect and the counter Velcro patch adhered to the pig's chest. Data (mean±SD) were analyzed using one-way ANOVA with pair wise multiple comparisons to assess differences between groups. p-Value≤0.05 was considered significant. Both AGD-CPR and AGD-CPR+ITD groups produced lower intrathoracic pressure (IttP, mmHg) during decompression phase (-13.4±6.7, p=0.01 and -11.9±6.5, p=0.01, respectively) in comparison to S-CPR (-0.3±4.2). Carotid blood flow (CBF, % of baseline mL/min) was higher in AGD-CPR and AGD-CPR+ITD (respectively 64.3±47.3%, p=0.03 and 67.5±33.1%, p=0.04) as compared with S-CPR (29.1±12.5%). Coronary perfusion pressure (CPP, mmHg) was higher in AGD-CPR and AGD-CPR+ITD (respectively 19.7±4.6, p=0.04 and 25.6±12.1, p=0.02) when compared to S-CPR (9.6±9.1). There was no statistically significant difference between AGD-CPR and AGD-CPR+ITD groups with reference to intra-thoracic pressure, carotid blood flow and coronary perfusion pressure. Active compression decompression delivered by this simple and inexpensive adhesive glove device resulted in improved cerebral blood flow and coronary perfusion pressure. There was no statistically significant added effect of ITD use along with AGD-CPR on the decompression of the chest. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

The effect of bridge deck design methodology on crack control.

DOT National Transportation Integrated Search

2010-01-30

At present, the Idaho Transportation Department (ITD) Bridge Design Manual allows engineers to use the AASHTO empirical method to : design concrete bridge decks. However, the ITD Bridge Section would like to compare their design practices to those em...

Identification of pyrrolo[2,3-d]pyrimidines as potent HCK and FLT3-ITD dual inhibitors.

PubMed

Koda, Yasuko; Kikuzato, Ko; Mikuni, Junko; Tanaka, Akiko; Yuki, Hitomi; Honma, Teruki; Tomabechi, Yuri; Kukimoto-Niino, Mutsuko; Shirouzu, Mikako; Shirai, Fumiyuki; Koyama, Hiroo

2017-11-15

A series of novel pyrrolo[2,3-d]pyrimidines were synthesized by introducing 15 different amino acids to 7-cyclohexyl-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidine-4-amine. Compounds with potent activities against HCK and FLT3-ITD were evaluated in viability studies with acute myeloid leukemia cell line MV4-11. Our structure activity relationship analyses lead to the identification of compound 31, which exhibited potent HCK and FLT3-ITD inhibition and activity against the MV4-11 cell line. Copyright © 2017 Elsevier Ltd. All rights reserved.

The role of HOXB2 and HOXB3 in acute myeloid leukemia.

PubMed

Lindblad, Oscar; Chougule, Rohit A; Moharram, Sausan A; Kabir, Nuzhat N; Sun, Jianmin; Kazi, Julhash U; Rönnstrand, Lars

2015-11-27

Acute myeloid leukemia (AML) is a heterogeneous aggressive disease and the most common form of adult leukemia. Mutations in the type III receptor tyrosine kinase FLT3 are found in more than 30% of AML patients. Drugs against FLT3 have been developed for the treatment of AML, but they lack specificity, show poor response and lead to the development of a resistant phenotype upon treatment. Therefore, a deeper understanding of FLT3 signaling will facilitate identification of additional pharmacological targets in FLT3-driven AML. In this report, we identify HOXB2 and HOXB3 as novel regulators of oncogenic FLT3-ITD-driven AML. We show that HOXB2 and HOXB3 expression is upregulated in a group of AML patients carrying FLT3-ITD. Overexpression of HOXB2 or HOXB3 in mouse pro-B cells resulted in decreased FLT3-ITD-dependent cell proliferation as well as colony formation and increased apoptosis. Expression of HOXB2 or HOXB3 resulted in a significant decrease in FLT3-ITD-induced AKT, ERK, p38 and STAT5 phosphorylation. Our data suggest that HOXB2 and HOXB3 act as tumor suppressors in FLT3-ITD driven AML. Copyright © 2015 Elsevier Inc. All rights reserved.

The role of HOXB2 and HOXB3 in acute myeloid leukemia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lindblad, Oscar; Lund Stem Cell Center, Department of Laboratory Medicine, Lund University, Lund; Department of Hematology and Vascular Disorders, Skåne University Hospital, Lund

2015-11-27

Acute myeloid leukemia (AML) is a heterogeneous aggressive disease and the most common form of adult leukemia. Mutations in the type III receptor tyrosine kinase FLT3 are found in more than 30% of AML patients. Drugs against FLT3 have been developed for the treatment of AML, but they lack specificity, show poor response and lead to the development of a resistant phenotype upon treatment. Therefore, a deeper understanding of FLT3 signaling will facilitate identification of additional pharmacological targets in FLT3-driven AML. In this report, we identify HOXB2 and HOXB3 as novel regulators of oncogenic FLT3-ITD-driven AML. We show that HOXB2more » and HOXB3 expression is upregulated in a group of AML patients carrying FLT3-ITD. Overexpression of HOXB2 or HOXB3 in mouse pro-B cells resulted in decreased FLT3-ITD-dependent cell proliferation as well as colony formation and increased apoptosis. Expression of HOXB2 or HOXB3 resulted in a significant decrease in FLT3-ITD-induced AKT, ERK, p38 and STAT5 phosphorylation. Our data suggest that HOXB2 and HOXB3 act as tumor suppressors in FLT3-ITD driven AML.« less

Lateralization of noise-burst trains based on onset and ongoing interaural delays.

PubMed

Freyman, Richard L; Balakrishnan, Uma; Zurek, Patrick M

2010-07-01

The lateralization of 250-ms trains of brief noise bursts was measured using an acoustic pointing technique. Stimuli were designed to assess the contribution of the interaural time delay (ITD) of the onset binaural burst relative to that of the ITDs in the ongoing part of the train. Lateralization was measured by listeners' adjustments of the ITD of a pointer stimulus, a 50-ms burst of noise, to match the lateral position of the target train. Results confirmed previous reports of lateralization dominance by the onset burst under conditions in which the train is composed of frozen tokens and the ongoing part contains multiple ambiguous interaural delays. In contrast, lateralization of ongoing trains in which fresh noise tokens were used for each set of two alternating (left-leading/right-leading) binaural pairs followed the ITD of the first pair in each set, regardless of the ITD of the onset burst of the entire stimulus and even when the onset burst was removed by gradual gating. This clear lateralization of a long-duration stimulus with ambiguous interaural delay cues suggests precedence mechanisms that involve not only the interaural cues at the beginning of a sound, but also the pattern of cues within an ongoing sound.

Speech segregation based-on binaural cue: interaural time difference (itd) and interaural level difference (ild)

NASA Astrophysics Data System (ADS)

Nur Farid, Mifta; Arifianto, Dhany

2016-11-01

A person who is suffering from hearing loss can be helped by using hearing aids and the most optimal performance of hearing aids are binaural hearing aids because it has similarities to human auditory system. In a conversation at a cocktail party, a person can focus on a single conversation even though the background sound and other people conversation is quite loud. This phenomenon is known as the cocktail party effect. In an early study, has been explained that binaural hearing have an important contribution to the cocktail party effect. So in this study, will be performed separation on the input binaural sound with 2 microphone sensors of two sound sources based on both the binaural cue, interaural time difference (ITD) and interaural level difference (ILD) using binary mask. To estimate value of ITD, is used cross-correlation method which the value of ITD represented as time delay of peak shifting at time-frequency unit. Binary mask is estimated based on pattern of ITD and ILD to relative strength of target that computed statistically using probability density estimation. Results of sound source separation performing well with the value of speech intelligibility using the percent correct word by 86% and 3 dB by SNR.

The Innovative Technology Deployment (ITD)/ Commercial Vehicle Information Systems and Networks (CVISN) Program, 2016 annual report.

DOT National Transportation Integrated Search

2017-06-01

On December 4, 2015, the Fixing Americas Surface Transportation Act, 2015 (FAST Act) (Pub. L. 114-94) established the Innovative Technology Deployment (ITD) Grant Program, replacing the long-standing Commercial Vehicle Information Systems and Netw...

The Innovative Technology Deployment (ITD) Grant Program, 2017 Annual Report

DOT National Transportation Integrated Search

2018-05-01

On December 4, 2015, the Fixing America's (FMCSA) works to reduce crashes, injuries, and Surface Transportation Act, 2015 (FAST Act) fatalities involving large trucks and buses. (Pub. L. 114-94) established the Innovative The ITD program is a key com...

Market research for Idaho Transportation Department linear referencing system.

DOT National Transportation Integrated Search

2009-09-02

For over 30 years, the Idaho Transportation Department (ITD) has had an LRS called MACS : (MilePoint And Coded Segment), which is being implemented on a mainframe using a : COBOL/CICS platform. As ITD began embracing newer technologies and moving tow...

A Wireless Magnetoresistive Sensing System for an Intraoral Tongue-Computer Interface

PubMed Central

Park, Hangue; Kiani, Mehdi; Lee, Hyung-Min; Kim, Jeonghee; Block, Jacob; Gosselin, Benoit; Ghovanloo, Maysam

2015-01-01

Tongue drive system (TDS) is a tongue-operated, minimally invasive, unobtrusive, and wireless assistive technology (AT) that infers users’ intentions by detecting their voluntary tongue motion and translating them into user-defined commands. Here we present the new intraoral version of the TDS (iTDS), which has been implemented in the form of a dental retainer. The iTDS system-on-a-chip (SoC) features a configurable analog front-end (AFE) that reads the magnetic field variations inside the mouth from four 3-axial magnetoresistive sensors located at four corners of the iTDS printed circuit board (PCB). A dual-band transmitter (Tx) on the same chip operates at 27 and 432 MHz in the Industrial/Scientific/Medical (ISM) band to allow users to switch in the presence of external interference. The Tx streams the digitized samples to a custom-designed TDS universal interface, built from commercial off-the-shelf (COTS) components, which delivers the iTDS data to other devices such as smartphones, personal computers (PC), and powered wheelchairs (PWC). Another key block on the iTDS SoC is the power management integrated circuit (PMIC), which provides individually regulated and duty-cycled 1.8 V supplies for sensors, AFE, Tx, and digital control blocks. The PMIC also charges a 50 mAh Li-ion battery with constant current up to 4.2 V, and recovers data and clock to update its configuration register through a 13.56 MHz inductive link. The iTDS SoC has been implemented in a 0.5-μm standard CMOS process and consumes 3.7 mW on average. PMID:23853258

FLT3 and JAK2 Mutations in Acute Myeloid Leukemia Promote Interchromosomal Homologous Recombination and the Potential for Copy Neutral Loss of Heterozygosity.

PubMed

Gaymes, Terry J; Mohamedali, Azim; Eiliazadeh, Anthony L; Darling, David; Mufti, Ghulam J

2017-04-01

Acquired copy neutral LOH (CN-LOH) is a frequent occurrence in myeloid malignancies and is often associated with resistance to standard therapeutic modalities and poor survival. Here, we show that constitutive signaling driven by mutated FLT3 and JAK2 confers interchromosomal homologous recombination (iHR), a precedent for CN-LOH. Using a targeted recombination assay, we determined significant iHR activity in internal tandem duplication FLT3 (FLT3-ITD) and JAK2V617F-mutated cells. Sister chromatid exchanges, a surrogate measure of iHR, was significantly elevated in primary FLT3-ITD normal karyotype acute myeloid leukemia (NK-AML) compared with wild-type FLT3 NK-AML. HR was harmonized to S phase of the cell cycle to repair broken chromatids and prevent iHR. Increased HR activity in G 0 arrested primary FLT3-ITD NK-AML in contrast to wild-type FLT3 NK-AML. Cells expressing mutated FLT3-ITD demonstrated a relative increase in mutation frequency as detected by thymidine kinase (TK) gene mutation assay. Moreover, resistance was associated with CN-LOH at the TK locus. Treatment of FLT3-ITD- and JAK2V617F-mutant cells with the antioxidant N -acetylcysteine diminished reactive oxygen species (ROS), restoring iHR and HR levels. Our findings show that mutated FLT3-ITD and JAK2 augment ROS production and HR, shifting the cellular milieu toward illegitimate recombination events such as iHR and CN-LOH. Therapeutic reduction of ROS may thus prevent leukemic progression and relapse in myeloid malignancies. Cancer Res; 77(7); 1697-708. ©2017 AACR . ©2017 American Association for Cancer Research.

Environmentally Responsible Aviation: Propulsion Research to Enable Fuel Burn, Noise and Emissions Reduction

NASA Technical Reports Server (NTRS)

Van Zante, Dale; Suder, Kenneth

2015-01-01

The NASA Environmentally Responsible Aviation (ERA) program is maturing technologies to enable simultaneous reduction of fuel burn, noise and emissions from an aircraft engine system. Three engine related Integrated Technology Demonstrations (ITDs) have been completed at Glenn Research Center in collaboration with Pratt Whitney, General Electric and the Federal Aviation Administration. The engine technologies being matured are: a low NOx, fuel flexible combustor in partnership with Pratt Whitney; an ultra-high bypass, ducted propulsor system in partnership with Pratt Whitney and FAA; and high pressure ratio, front-stage core compressor technology in partnership with General Electric. The technical rationale, test configurations and overall results from the test series in each ITD are described. ERA is using system analysis to project the benefits of the ITD technologies on potential aircraft systems in the 2025 timeframe. Data from the ITD experiments were used to guide the system analysis assumptions. Results from the current assessments for fuel burn, noise and oxides of nitrogen emissions are presented.

Survivin Selectively Modulates Genes Deregulated in Human Leukemia Stem Cells

PubMed Central

Fukuda, Seiji; Abe, Mariko; Onishi, Chie; Taketani, Takeshi; Purevsuren, Jamiyan; Yamaguchi, Seiji; Conway, Edward M.; Pelus, Louis M.

2011-01-01

ITD-Flt3 mutations are detected in leukemia stem cells (LSCs) in acute myeloid leukemia (AML) patients. While antagonizing Survivin normalizes ITD-Flt3-induced acute leukemia, it also impairs hematopoietic stem cell (HSC) function, indicating that identification of differences in signaling pathways downstream of Survivin between LSC and HSC are crucial to develop selective Survivin-based therapeutic strategies for AML. Using a Survivin-deletion model, we identified 1,096 genes regulated by Survivin in ITD-Flt3-transformed c-kit+, Sca-1+, and lineageneg (KSL) cells, of which 137 are deregulated in human LSC. Of the 137, 124 genes were regulated by Survivin exclusively in ITD-Flt3+ KSL cells but not in normal CD34neg KSL cells. Survivin-regulated genes in LSC connect through a network associated with the epidermal growth factor receptor signaling pathway and falls into various functional categories independent of effects on apoptosis. Pathways downstream of Survivin in LSC that are distinct from HSC can be potentially targeted for selective anti-LSC therapy. PMID:21253548

Environmentally Responsible Aviation: Propulsion Research to Enable Fuel Burn, Noise and Emissions Reduction

NASA Technical Reports Server (NTRS)

Van Zante, Dale E.; Suder, Kenneth L.

2015-01-01

The NASA Environmentally Responsible Aviation (ERA) program is maturing technologies to enable simultaneous reduction of fuel burn, noise and emissions from an aircraft engine system. Three engine related Integrated Technology Demonstrations (ITDs) have been completed at Glenn Research Center in collaboration with Pratt Whitney, General Electric and the Federal Aviation Administration. The engine technologies being matured are a low NOx, fuel flexible combustor in partnership with Pratt Whitney, an ultra-high bypass, ducted propulsor system in partnership with Pratt Whitney FAA and high pressure ratio, front-stage core compressor technology in partnership with General Electric. The technical rationale, test configurations and overall results from the test series in each ITD are described. ERA is using system analysis to project the benefits of the ITD technologies on potential aircraft systems in the 2025 timeframe. Data from the ITD experiments were used to guide the system analysis assumptions. Results from the current assessments for fuel burn, noise and oxides of nitrogen emissions are presented.

Lower frequency of NPM1 and FLT3-ITD mutations in a South African adult de novo AML cohort

PubMed Central

Marshall, R. C.; Tlagadi, A.; Bronze, M.; Kana, V.; Naidoo, S.; Wiggill, T. M.; Carmona, S. C.

2014-01-01

Introduction Acute myeloid leukemia (AML) is a heterogeneous clonal disorder of haemopoietic progenitor cells diagnosed in individuals of any age, but with a median age of 67 years at presentation in adults. Assessment of the mutation status of Nucleophosmin protein-1 (NPM1) and FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) are essential for the diagnosis, prognosis and treatment of AML. Methods A total of 160 de novo AML cases, both cytogenetically normal and abnormal, were analyzed for the presence of NPM1 and FLT3-ITD mutations and the results assessed in conjunction with epidemiological, clinical and laboratory findings. Results NPM1 mutations were found in 7.5%, while FLT3-ITD was present in 12% of these cases. Both of these were lower than expected. The median age at diagnosis of AML was 41 years and for the FLT3-ITD only cases, median age was 33 years; these ages were younger than expected. Conclusion The lower reported frequencies and younger median age at diagnosis of AML and these specific mutations may be contributed to by a number of factors including; effects of race on age of presentation, inclusion of patients diagnosed with de novo AML only and a generally younger median age of the South African population. PMID:24666762

Glutaminolysis is a metabolic dependency in FLT3ITD acute myeloid leukemia unmasked by FLT3 tyrosine kinase inhibition.

PubMed

Gallipoli, Paolo; Giotopoulos, George; Tzelepis, Konstantinos; Costa, Ana S H; Vohra, Shabana; Medina-Perez, Paula; Basheer, Faisal; Marando, Ludovica; Di Lisio, Lorena; Dias, Joao M L; Yun, Haiyang; Sasca, Daniel; Horton, Sarah J; Vassiliou, George; Frezza, Christian; Huntly, Brian J P

2018-04-12

FLT3 internal tandem duplication (FLT3 ITD ) mutations are common in acute myeloid leukemia (AML) associated with poor patient prognosis. Although new-generation FLT3 tyrosine kinase inhibitors (TKI) have shown promising results, the outcome of FLT3 ITD AML patients remains poor and demands the identification of novel, specific, and validated therapeutic targets for this highly aggressive AML subtype. Utilizing an unbiased genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 screen, we identify GLS, the first enzyme in glutamine metabolism, as synthetically lethal with FLT3-TKI treatment. Using complementary metabolomic and gene-expression analysis, we demonstrate that glutamine metabolism, through its ability to support both mitochondrial function and cellular redox metabolism, becomes a metabolic dependency of FLT3 ITD AML, specifically unmasked by FLT3-TKI treatment. We extend these findings to AML subtypes driven by other tyrosine kinase (TK) activating mutations and validate the role of GLS as a clinically actionable therapeutic target in both primary AML and in vivo models. Our work highlights the role of metabolic adaptations as a resistance mechanism to several TKI and suggests glutaminolysis as a therapeutically targetable vulnerability when combined with specific TKI in FLT3 ITD and other TK activating mutation-driven leukemias. © 2018 by The American Society of Hematology.

Trends in Instructional Technology and Distance Education.

ERIC Educational Resources Information Center

Abromitis, Jacky

This paper discusses trends in instructional technology and distance education (ITDE). The most notable trends are the lack of funding and resources for technology training, the lack of administrative support for ITDE issues, and faculty who are reluctant to adopt technology and distance learning. This paper identifies seven emerging trends as…

Interim Terrain Data (ITD) and Vector Product Interim Terrain Data (VITD) user's guide

DOT National Transportation Integrated Search

1996-09-01

This guide is intended to be a convenient reference for users of these types of terrain analysis data. ITD is a digitized version of the standard 1:50,000-scale tactical terrain analysis data base (TTADB) product produced by the Defense Mapping Agenc...

Reliability of Interaural Time Difference-Based Localization Training in Elderly Individuals with Speech-in-Noise Perception Disorder.

PubMed

Delphi, Maryam; Lotfi, M-Yones; Moossavi, Abdollah; Bakhshi, Enayatollah; Banimostafa, Maryam

2017-09-01

Previous studies have shown that interaural-time-difference (ITD) training can improve localization ability. Surprisingly little is, however, known about localization training vis-à-vis speech perception in noise based on interaural time difference in the envelope (ITD ENV). We sought to investigate the reliability of an ITD ENV-based training program in speech-in-noise perception among elderly individuals with normal hearing and speech-in-noise disorder. The present interventional study was performed during 2016. Sixteen elderly men between 55 and 65 years of age with the clinical diagnosis of normal hearing up to 2000 Hz and speech-in-noise perception disorder participated in this study. The training localization program was based on changes in ITD ENV. In order to evaluate the reliability of the training program, we performed speech-in-noise tests before the training program, immediately afterward, and then at 2 months' follow-up. The reliability of the training program was analyzed using the Friedman test and the SPSS software. Significant statistical differences were shown in the mean scores of speech-in-noise perception between the 3 time points (P=0.001). The results also indicated no difference in the mean scores of speech-in-noise perception between the 2 time points of immediately after the training program and 2 months' follow-up (P=0.212). The present study showed the reliability of an ITD ENV-based localization training in elderly individuals with speech-in-noise perception disorder.

Consecutive epigenetically-active agent combinations act in ID1-RUNX3-TET2 and HOXA pathways for Flt3ITD+ve AML.

PubMed

Sayar, Hamid; Liu, Yan; Gao, Rui; Zaid, Mohammad Abu; Cripe, Larry D; Weisenbach, Jill; Sargent, Katie J; Nassiri, Mehdi; Li, Lang; Konig, Heiko; Suvannasankha, Attaya; Pan, Feng; Shanmugam, Rajasubramaniam; Goswami, Chirayu; Kapur, Reuben; Xu, Mingjiang; Boswell, H Scott

2018-01-19

Co-occurrence of Flt3ITD and TET2 mutations provoke an animal model of AML by epigenetic repression of Wnt pathway antagonists, including RUNX3, and by hyperexpression of ID1, encoding Wnt agonist. These affect HOXA over-expression and treatment resistance. A comparable epigenetic phenotype was identified among adult AML patients needing novel intervention. We chose combinations of targeted agents acting on distinct effectors, at the levels of both signal transduction and chromatin remodeling, in relapsed/refractory AML's, including Flt3ITD+ve, described with a signature of repressed tumor suppressor genes, involving Wnt antagonist RUNX3 , occurring along with ID1 and HOXA over-expressions. We tracked patient response to combination of Flt3/Raf inhibitor, Sorafenib, and Vorinostat, pan-histone deacetylase inhibitor, without or with added Bortezomib, in consecutive phase I trials. A striking association of rapid objective remissions (near-complete, complete responses) was noted to accompany induced early pharmacodynamic changes within patient blasts in situ, involving these effectors, significantly linking RUNX3 /Wnt antagonist de-repression (80%) and ID1 downregulation (85%), to a response, also preceded by profound HOXA9 repression. Response occurred in context of concurrent TET2 mutation/hypomorphy and Flt3ITD+ve mutation (83% of complete responses). Addition of Bortezomib to the combination was vital to attainment of complete response in Flt3ITD+ve cases exhibiting such Wnt pathway dysregulation.

Binaural sensitivity changes between cortical on and off responses

PubMed Central

Dahmen, Johannes C.; King, Andrew J.; Schnupp, Jan W. H.

2011-01-01

Neurons exhibiting on and off responses with different frequency tuning have previously been described in the primary auditory cortex (A1) of anesthetized and awake animals, but it is unknown whether other tuning properties, including sensitivity to binaural localization cues, also differ between on and off responses. We measured the sensitivity of A1 neurons in anesthetized ferrets to 1) interaural level differences (ILDs), using unmodulated broadband noise with varying ILDs and average binaural levels, and 2) interaural time delays (ITDs), using sinusoidally amplitude-modulated broadband noise with varying envelope ITDs. We also assessed fine-structure ITD sensitivity and frequency tuning, using pure-tone stimuli. Neurons most commonly responded to stimulus onset only, but purely off responses and on-off responses were also recorded. Of the units exhibiting significant binaural sensitivity nearly one-quarter showed binaural sensitivity in both on and off responses, but in almost all (∼97%) of these units the binaural tuning of the on responses differed significantly from that seen in the off responses. Moreover, averaged, normalized ILD and ITD tuning curves calculated from all units showing significant sensitivity to binaural cues indicated that on and off responses displayed different sensitivity patterns across the population. A principal component analysis of ITD response functions suggested a continuous cortical distribution of binaural sensitivity, rather than discrete response classes. Rather than reflecting a release from inhibition without any functional significance, we propose that binaural off responses may be important to cortical encoding of sound-source location. PMID:21562191

Crystallographic Texture and Elemental Composition Mapped in Bovine Root Dentin at the 200 nm Level

PubMed Central

Deymier-Black, A. C.; Veis, A.; Cai, Z.; Stock, S. R.

2015-01-01

Summary The relationship between the mineralization of peritubular dentin (PTD) and intertubular dentin (ITD) is not well understood. Tubules are quite small, diameter ~2 μm, and this makes the near-tubule region of dentin difficult to study. Here, advanced characterization techniques are applied in a novel way to examine what organic or nanostructural signatures may indicate the end of ITD or the beginning of PTD mineralization. X-ray fluorescence intensity (Ca, P, and Zn) and X-ray diffraction patterns from carbonated apatite (cAp) were mapped around dentintubules at resolutions ten times smaller than the feature size (200 nm pixels), representing a 36% increase in resolution over earlier work. In the near tubule volumes of near-pulp, root dentin, Zn intensity was higher than in ITD remote from the tubules. This increase in Zn2+, as determined by X-ray absorption near edge structure analysis, may indicate the presence of metalloenzymes or transcription factors important to ITD or PTD mineralization. The profiles of the cAp 00.2 X-ray diffraction rings were fitted with a pseudo-Voigt function, and the spatial and azimuthal distribution of these rings’ integrated intensities indicated that the cAp platelets were arranged with their c-axes aligned tangential to the edge of the tubule lumen. This texture was continuous throughout the dentin indicating a lack of structural difference between in the Zn rich near-tubular region and the remote ITD. PMID:23630059

Sea ice floe size distribution in the marginal ice zone: Theory and numerical experiments

NASA Astrophysics Data System (ADS)

Zhang, Jinlun; Schweiger, Axel; Steele, Michael; Stern, Harry

2015-05-01

To better describe the state of sea ice in the marginal ice zone (MIZ) with floes of varying thicknesses and sizes, both an ice thickness distribution (ITD) and a floe size distribution (FSD) are needed. In this work, we have developed a FSD theory that is coupled to the ITD theory of Thorndike et al. (1975) in order to explicitly simulate the evolution of FSD and ITD jointly. The FSD theory includes a FSD function and a FSD conservation equation in parallel with the ITD equation. The FSD equation takes into account changes in FSD due to ice advection, thermodynamic growth, and lateral melting. It also includes changes in FSD because of mechanical redistribution of floe size due to ice ridging and, particularly, ice fragmentation induced by stochastic ocean surface waves. The floe size redistribution due to ice fragmentation is based on the assumption that wave-induced breakup is a random process such that when an ice floe is broken, floes of any smaller sizes have an equal opportunity to form, without being either favored or excluded. To focus only on the properties of mechanical floe size redistribution, the FSD theory is implemented in a simplified ITD and FSD sea ice model for idealized numerical experiments. Model results show that the simulated cumulative floe number distribution (CFND) follows a power law as observed by satellites and airborne surveys. The simulated values of the exponent of the power law, with varying levels of ice breakups, are also in the range of the observations. It is found that floe size redistribution and the resulting FSD and mean floe size do not depend on how floe size categories are partitioned over a given floe size range. The ability to explicitly simulate multicategory FSD and ITD together may help to incorporate additional model physics, such as FSD-dependent ice mechanics, surface exchange of heat, mass, and momentum, and wave-ice interactions.

The representation of sound localization cues in the barn owl's inferior colliculus

PubMed Central

Singheiser, Martin; Gutfreund, Yoram; Wagner, Hermann

2012-01-01

The barn owl is a well-known model system for studying auditory processing and sound localization. This article reviews the morphological and functional organization, as well as the role of the underlying microcircuits, of the barn owl's inferior colliculus (IC). We focus on the processing of frequency and interaural time (ITD) and level differences (ILD). We first summarize the morphology of the sub-nuclei belonging to the IC and their differentiation by antero- and retrograde labeling and by staining with various antibodies. We then focus on the response properties of neurons in the three major sub-nuclei of IC [core of the central nucleus of the IC (ICCc), lateral shell of the central nucleus of the IC (ICCls), and the external nucleus of the IC (ICX)]. ICCc projects to ICCls, which in turn sends its information to ICX. The responses of neurons in ICCc are sensitive to changes in ITD but not to changes in ILD. The distribution of ITD sensitivity with frequency in ICCc can only partly be explained by optimal coding. We continue with the tuning properties of ICCls neurons, the first station in the midbrain where the ITD and ILD pathways merge after they have split at the level of the cochlear nucleus. The ICCc and ICCls share similar ITD and frequency tuning. By contrast, ICCls shows sigmoidal ILD tuning which is absent in ICCc. Both ICCc and ICCls project to the forebrain, and ICCls also projects to ICX, where space-specific neurons are found. Space-specific neurons exhibit side peak suppression in ITD tuning, bell-shaped ILD tuning, and are broadly tuned to frequency. These neurons respond only to restricted positions of auditory space and form a map of two-dimensional auditory space. Finally, we briefly review major IC features, including multiplication-like computations, correlates of echo suppression, plasticity, and adaptation. PMID:22798945

The effects of experimentally induced conductive hearing loss on spectral and temporal aspects of sound transmission through the ear.

PubMed

Eric Lupo, J; Koka, Kanthaiah; Thornton, Jennifer L; Tollin, Daniel J

2011-02-01

Conductive hearing loss (CHL) is known to produce hearing deficits, including deficits in sound localization ability. The differences in sound intensities and timing experienced between the two tympanic membranes are important cues to sound localization (ILD and ITD, respectively). Although much is known about the effect of CHL on hearing levels, little investigation has been conducted into the actual impact of CHL on sound location cues. This study investigated effects of CHL induced by earplugs on cochlear microphonic (CM) amplitude and timing and their corresponding effect on the ILD and ITD location cues. Acoustic and CM measurements were made in 5 chinchillas before and after earplug insertion, and again after earplug removal using pure tones (500 Hz to 24 kHz). ILDs in the unoccluded condition demonstrated position and frequency dependence where peak far-lateral ILDs approached 30 dB for high frequencies. Unoccluded ear ITD cues demonstrated positional and frequency dependence with increased ITD cue for both decreasing frequency (±420 μs at 500 Hz, ±310 μs for 1-4 kHz) and increasingly lateral sound source locations. Occlusion of the ear canal with foam plugs resulted in a mild, frequency-dependent conductive hearing loss of 10-38 dB (mean 31 ± 3.9 dB) leading to a concomitant frequency dependent increase in ILDs at all source locations. The effective ITDs increased in a frequency dependent manner with ear occlusion as a direct result of the acoustic properties of the plugging material, the latter confirmed via acoustical measurements using a model ear canal with varying volumes of acoustic foam. Upon ear plugging with acoustic foam, a mild CHL is induced. Furthermore, the CHL induced by acoustic foam results in substantial changes in the magnitudes of both the ITD and ILD cues to sound location. Copyright © 2010 Elsevier B.V. All rights reserved.

The effects of experimentally induced conductive hearing loss on spectral and temporal aspects of sound transmission through the ear

PubMed Central

Lupo, J. Eric; Koka, Kanthaiah; Thornton, Jennifer L.; Tollin, Daniel J.

2010-01-01

Conductive hearing loss (CHL) is known to produce hearing deficits, including deficits in sound localization ability. The differences in sound intensities and timing experienced between the two tympanic membranes are important cues to sound localization (ILD and ITD, respectively). Although much is known about the effect of CHL on hearing levels, little investigation has been conducted into the actual impact of CHL on sound location cues. This study investigated effects of CHL induced by earplugs on cochlear microphonic (CM) amplitude and timing and their corresponding effect on the ILD and ITD location cues. Acoustic and CM measurements were made in 5 chinchillas before and after earplug insertion, and again after earplug removal using pure tones (500 Hz to 24 kHz). ILDs in the unoccluded condition demonstrated position and frequency dependence where peak far-lateral ILDs approached 30 dB for high frequencies. Unoccluded ear ITD cues demonstrated positional and frequency dependence with increased ITD cue for both decreasing frequency (± 420 µs at 500 Hz, ± 310 µs for 1–4 kHz ) and increasingly lateral sound source locations. Occlusion of the ear canal with foam plugs resulted in a mild, frequency-dependent conductive hearing loss of 10–38 dB (mean 31 ± 3.9 dB) leading to a concomitant frequency dependent increase in ILDs at all source locations. The effective ITDs increased in a frequency dependent manner with ear occlusion as a direct result of the acoustic properties of the plugging material, the latter confirmed via acoustical measurements using a model ear canal with varying volumes of acoustic foam. Upon ear plugging with acoustic foam, a mild CHL is induced. Furthermore, the CHL induced by acoustic foam results in substantial changes in the magnitudes of both the ITD and ILD cues to sound location. PMID:21073935

Spatial selectivity and binaural responses in the inferior colliculus of the great horned owl.

PubMed

Volman, S F; Konishi, M

1989-09-01

In this study we have investigated the processing of auditory cues for sound localization in the great horned owl (Bubo virginianus). Previous studies have shown that the barn owl, whose ears are asymmetrically oriented in the vertical plane, has a 2-dimensional, topographic representation of auditory space in the external division of the inferior colliculus (ICx). As in the barn owl, the great horned owl's ICx is anatomically distinct and projects to the optic tectum. Neurons in ICx respond over only a small range of azimuths (mean = 32 degrees), and azimuth is topographically mapped. In contrast to the barn owl, the great horned owl has bilaterally symmetrical ears and its receptive fields are not restricted in elevation. The binaural cues available for sound localization were measured both with cochlear microphonic recordings and with a microphone attached to a probe tube in the auditory canal. Interaural time disparity (ITD) varied monotonically with azimuth. Interaural intensity differences (IID) also changed with azimuth, but the largest IIDs were less than 15 dB, and the variation was not monotonic. Neither ITD nor IID varied systematically with changes in the vertical position of a sound source. We used dichotic stimulation to determine the sensitivity of ICx neurons to these binaural cues. Best ITD of ICx units was topographically mapped and strongly correlated with receptive-field azimuth. The width of ITD tuning curves, measured at 50% of the maximum response, averaged 72 microseconds. All ICx neurons responded only to binaural stimulation and had nonmonotonic IID tuning curves. Best IID was weakly, but significantly, correlated with best ITD (r = 0.39, p less than 0.05). The IID tuning curves, however, were broad (mean 50% width = 24 dB), and 67% of the units had best IIDs within 5 dB of 0 dB IID. ITD tuning was sensitive to variations in IID in the direction opposite to that expected for time-intensity trading, but the magnitude of this effect was only 1.5 microseconds/dB IID. We conclude that, in the great horned owl, the spatial selectivity of ICx neurons arises primarily from their ITD tuning. Except for the absence of elevation selectivity and the narrow range of best IIDs, ICx in the great horned owl appears to be organized much the same as in the barn owl.

Evaluation of an Impedance Threshold Device as a VIIP Countermeasure

NASA Technical Reports Server (NTRS)

Ebert, D.; Macias, B.; Garcia, K.; Stenger, M.; Hargens, A.; Johnston, S.

2016-01-01

Visual Impairment /Intracranial Pressure (VIIP) is a top human spaceflight risk for which NASA does not currently have a proven mitigation strategy. Thigh cuffs (Braslets) and lower body negative pressure (LBNP; Chibis) devices have been or are currently being evaluated as a means to reduce VIIP signs and symptoms, but these methods alone may not provide sufficient relief of cephalic venous congestion and VIIP symptoms. Additionally, current LBNP devices are too large and cumbersome for their systematic use as a countermeasure. Therefore, a novel approach is needed that is easy to implement and provides specific relief of symptoms. This investigation will evaluate an impedance threshold device (ITD) as a VIIP countermeasure. The ITD works by providing up to 7 cm H2O (approximately 5 mmHg) resistance to inspiratory air flow, effectively turning the thorax into a vacuum pump upon each inhalation which lowers the intrathoracic pressure (ITP) and facilitates venous return to the heart. The ITD is FDA-approved and was developed to augment venous return to the central circulation and increase cardiac output during cardiopulmonary resuscitation (CPR) and in patients with hypotension. While the effect of ITD on CPR survival outcomes is controversial, the ITD's ability to lower ITP with a concomitant decrease in intracranial pressure (ICP) is well documented. A similar concept that creates negative ITP during exhalation (intrathoracic pressure regulator; ITPR) decreased ICP in 16 of 20 patients with elevated ICP in a hospital pilot study. ITP and central venous pressure (CVP) have been shown to decrease in microgravity however ITP drops more than CVP, indicating an increased transmural CVP. This could explain the paradoxical distention of jugular veins (JV) in microgravity despite lower absolute CVP and also suggests that JV transmural pressure is not dramatically elevated. Use of an ITD may lower JV pressure enough to remove or relieve cephalic venous congestion. During spaceflight experiments with Braslet thigh cuffs and modified (open-glottis) Mueller maneuvers, Braslets alone reduced cardiac preload but only reduced the internal JV (IJV) cross sectional area by 23%. The addition of Mueller maneuvers resulted in an IJV area reduction of 48%. This project will test if ITD essentially applies a Mueller maneuver with added negative ITP in every respiratory cycle, acting to: 1) reduce venous congestion in the neck and 2) potentially lower ICP. The expected mechanism of action is that in microgravity (or an analog) blood is relocated toward the heart from vasculature in the head and neck. Once validated, the ITD would be an exceptionally easy countermeasure to deploy and test on the ISS. Dosage could be altered though 1) duration of application and 2) inspiratory resistance set point. Effects could be additionally enhanced through co-application with other countermeasures such as thigh cuffs or LBNP.

Evaluation of an Impedance Threshold Device as a VIIP Countermeasure

NASA Technical Reports Server (NTRS)

Ebert, Douglas; Macias, Brandon; Sargsyan, Ashot; Garcia, Kathleen; Stenger, Michael; Hargens, Alan; Johnston, Smith; Kemp, David; Danielson, Richard

2016-01-01

Visual Impairment/Intracranial Pressure (VIIP) is a top human spaceflight risk for which NASA does not currently have a proven mitigation strategy. Thigh cuffs (Braslets) and lower body negative pressure (LBNP; Chibis) devices have been or are currently being evaluated as a means to reduce VIIP signs and symptoms, but these methods alone may not provide sufficient relief of cephalic venous congestion and VIIP symptoms. Additionally, current LBNP devices are too large and cumbersome for their systematic use as a countermeasure. Therefore, a novel approach is needed that is easy to implement and provides specific relief of symptoms. This investigation will evaluate an impedance threshold device (ITD) as a VIIP countermeasure. The ITD works by providing up to 7 cm H2O (approximately 5 mmHg) resistance to inspiratory air flow, effectively turning the thorax into a vacuum pump upon each inhalation which lowers the intrathoracic pressure (ITP) and facilitates venous return to the heart. The ITD is FDA-approved and was developed to augment venous return to the central circulation and increase cardiac output during cardiopulmonary resuscitation (CPR) and in patients with hypotension. While the effect of ITD on CPR survival outcomes is controversial, the ITD's ability to lower ITP with a concomitant decrease in intracranial pressure (ICP) is well documented. A similar concept that creates negative ITP during exhalation (intrathoracic pressure regulator; ITPR) decreased ICP in 16 of 20 patients with elevated ICP in a hospital pilot study. ITP and central venous pressure (CVP) have been shown to decrease in microgravity however ITP drops more than CVP, indicating an increased transmural CVP. This could explain the paradoxical distention of jugular veins (JV) in microgravity despite lower absolute CVP and also suggests that JV transmural pressure is not dramatically elevated. Use of an ITD may lower JV pressure enough to remove or relieve cephalic venous congestion. During spaceflight experiments with Braslet thigh cuffs and modified (open-glottis) Mueller maneuvers, Braslets alone reduced cardiac preload but only reduced the internal JV (IJV) cross sectional area by 23%. The addition of Mueller maneuvers resulted in an IJV area reduction of 48%. This project will test if ITD essentially applies a Mueller maneuver with added negative ITP in every respiratory cycle, acting to: 1) reduce venous congestion in the neck and 2) potentially lower ICP. The expected mechanism of action is that in microgravity (or an analog) blood is relocated toward the heart from vasculature in the head and neck. Once validated, the ITD would be an exceptionally easy countermeasure to deploy and test on the ISS. Dosage could be altered though 1) duration of application and 2) inspiratory resistance set point. Effects could be additionally enhanced through co-application with other countermeasures such as thigh cuffs or LBNP.

PML-RARα kinetics and impact of FLT3-ITD mutations in newly diagnosed acute promyelocytic leukaemia treated with ATRA and ATO or ATRA and chemotherapy.

PubMed

Cicconi, L; Divona, M; Ciardi, C; Ottone, T; Ferrantini, A; Lavorgna, S; Alfonso, V; Paoloni, F; Piciocchi, A; Avvisati, G; Ferrara, F; Di Bona, E; Albano, F; Breccia, M; Cerqui, E; Sborgia, M; Kropp, M G; Santoro, A; Levis, A; Sica, S; Amadori, S; Voso, M T; Mandelli, F; Lo-Coco, F

2016-10-01

The APL0406 study showed that arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) are not inferior to standard ATRA and chemotherapy (CHT) in newly diagnosed, low-intermediaterisk acute promyelocytic leukaemia (APL). We analysed the kinetics of promyelocytic leukaemia-retinoic acid receptor-α (PML-RARα) transcripts by real-time quantitative PCR (RQ-PCR) in bone marrow samples from 184 patients and assessed the prognostic impact of fms-related tyrosine kinase 3-internal tandem duplication (FLT3-ITD) in 159 patients enrolled in this trial in Italy. After induction therapy, the reduction of PML-RARα transcripts was significantly greater in patients receiving ATRA-CHT as compared with those treated with ATRA-ATO (3.4 vs 2.9 logs; P=0.0182). Conversely, at the end of consolidation, a greater log reduction of PML-RARα transcripts was detected in the ATRA-ATO as compared with the ATRA-CHT group (6.3 vs 5.3 logs; P=0.0024). FLT3-ITD mutations had no significant impact on either event-free survival (EFS) or cumulative incidence of relapse in patients receiving ATRA-ATO, whereas a trend for inferior EFS was observed in FLT3-ITD-positive patients receiving ATRA-CHT. Our study shows at the molecular level that ATRA-ATO exerts at least equal and probably superior antileukaemic efficacy compared with ATRA-CHT in low-intermediaterisk APL. The data also suggest that ATRA-ATO may abrogate the negative prognostic impact of FLT3-ITD.

Predicting binaural responses from monaural responses in the gerbil medial superior olive

PubMed Central

Plauška, Andrius; Borst, J. Gerard

2016-01-01

Accurate sound source localization of low-frequency sounds in the horizontal plane depends critically on the comparison of arrival times at both ears. A specialized brainstem circuit containing the principal neurons of the medial superior olive (MSO) is dedicated to this comparison. MSO neurons are innervated by segregated inputs from both ears. The coincident arrival of excitatory inputs from both ears is thought to trigger action potentials, with differences in internal delays creating a unique sensitivity to interaural time differences (ITDs) for each cell. How the inputs from both ears are integrated by the MSO neurons is still debated. Using juxtacellular recordings, we tested to what extent MSO neurons from anesthetized Mongolian gerbils function as simple cross-correlators of their bilateral inputs. From the measured subthreshold responses to monaural wideband stimuli we predicted the rate-ITD functions obtained from the same MSO neuron, which have a damped oscillatory shape. The rate of the oscillations and the position of the peaks and troughs were accurately predicted. The amplitude ratio between dominant and secondary peaks of the rate-ITD function, captured in the width of its envelope, was not always exactly reproduced. This minor imperfection pointed to the methodological limitation of using a linear representation of the monaural inputs, which disregards any temporal sharpening occurring in the cochlear nucleus. The successful prediction of the major aspects of rate-ITD curves supports a simple scheme in which the ITD sensitivity of MSO neurons is realized by the coincidence detection of excitatory monaural inputs. PMID:27009164

Axonal recordings from medial superior olive neurons obtained from the lateral lemniscus of the chinchilla (Chinchilla laniger).

PubMed

Bremen, Peter; Joris, Philip X

2013-10-30

Interaural time differences (ITDs) are a major cue for localizing low-frequency (<1.5 kHz) sounds. Sensitivity to this cue first occurs in the medial superior olive (MSO), which is thought to perform a coincidence analysis on its monaural inputs. Extracellular single-neuron recordings in MSO are difficult to obtain because (1) MSO action potentials are small and (2) a large field potential locked to the stimulus waveform hampers spike isolation. Consequently, only a limited number of studies report MSO data, and even in these studies data are limited in the variety of stimuli used, in the number of neurons studied, and in spike isolation. More high-quality data are needed to better understand the mechanisms underlying neuronal ITD-sensitivity. We circumvented these difficulties by recording from the axons of MSO neurons in the lateral lemniscus (LL) of the chinchilla, a species with pronounced low-frequency sensitivity. Employing sharp glass electrodes we successfully recorded from neurons with ITD sensitivity: the location, response properties, latency, and spike shape were consistent with an MSO axonal origin. The main difficulty encountered was mechanical stability. We obtained responses to binaural beats and dichotic noise bursts to characterize the best delay versus characteristic frequency distribution, and compared the data to recordings we obtained in the inferior colliculus (IC). In contrast to most reports in other rodents, many best delays were close to zero ITD, both in MSO and IC, with a majority of the neurons recorded in the LL firing maximally within the presumed ethological ITD range.

Effects of rising angle on upstream blades and intermediate turbine duct

NASA Astrophysics Data System (ADS)

Liu, Jun; Wang, Pei; Du, Qiang; Liu, Guang; Zhu, Junqiang

2016-08-01

With the improvement of requirement, design and manufacture technology, aero-engines for the future are characterized by further reduction in fuel consumption, cost, but increment in propulsion efficiency, which leads to ultra-high bypass ratio. The intermediate turbine duct (ITD), which connects the high pressure turbine (HPT) with the low pressure turbine (LPT), has a critical impact on the overall performances of such future engines. Therefore, it becomes more and more urgent to master the design technique of aggressive, even super-aggressive ITDs. Over the last years, a lot of research works about the flow mechanism in the diffuser ducts were carried out. Many achievements were reported, but further investigation should be performed. With the aid of numerical method, this paper focuses on the change of performance and flow field of ITD, as well as nearby turbines, brought by rising angle (RA). Eight ITDs with the same area ratio and length, but different RAs ranges from 8 degrees to 45 degrees, are compared. According to the investigation, flow field, especially outlet Ma of swirl blade is influenced by RA under potential effect, which is advisable for designers to modify HPT rotor blades after changing ITD. In addition to that, low velocity area moves towards upstream until the first bend as RA increases, while pressure loss distribution at S2 stream surface shows that hub boundary layer is more sensitive to RA, and casing layer keeps almost constant. On the other hand, the overall total pressure loss could keep nearly equivalent among different RA cases, which implies the importance of optimization.

Updating a Strategic Highway Safety Plan : Learning from the Idaho Transportation Department (ITD) - Proceedings from the Federal Highway Administration's (FHWA) Highway Safety Peer-to-Peer Exchange Program

DOT National Transportation Integrated Search

2009-10-01

On November 4, 2009, ITDs Office of Highway Operations and Safety partnered with the FHWA Office of Safety to host a one-day peer exchange. This event focused on the update of Idahos Strategic Highway Safety Plan (SHSP), entitled Toward Zero...

Lateralization of high-frequency transposed stimuli under conditions of binaural interference

NASA Astrophysics Data System (ADS)

Bernstein, Leslie R.; Trahiotis, Constantine

2005-04-01

The purpose of this study was to determine whether binaural interference would occur if ITD-based extents of laterality were measured using high-frequency transposed stimuli as targets. The results of an earlier study [L. R. Bernstein and C. Trahiotis, J. Acoust. Soc. Am. 116, 3062-3069 (2004)], which focused on threshold-ITDs rather than extents of laterality, suggested that high-frequency transposed stimuli might be immune to binaural interference effects resulting from the addition of a spectrally-remote, low-frequency interferer. In contrast to the earlier findings, the data from this study indicate that high-frequency transposed targets can, indeed, be susceptible to binaural interference. High-frequency transposed targets, even when presented along with an interferer, yielded greater extents of ITD-based laterality than did Gaussian noise targets presented in isolation. That is, the enhanced potency of ITDs conveyed by transposed stimuli persisted even in the presence of a low-frequency interferer. Predictions made using an extension of the model of Heller and Trahiotis [L. M. Heller and C. Trahiotis, J. Acoust. Soc. Am. 99, 3632-3637 (1996)] accounted well for binaural interference obtained with conventional Gaussian noise targets but generally over-predicted the amounts of interference found with the transposed targets.

Spatial hearing benefits demonstrated with presentation of acoustic temporal fine structure cues in bilateral cochlear implant listeners.

PubMed

Churchill, Tyler H; Kan, Alan; Goupell, Matthew J; Litovsky, Ruth Y

2014-09-01

Most contemporary cochlear implant (CI) processing strategies discard acoustic temporal fine structure (TFS) information, and this may contribute to the observed deficits in bilateral CI listeners' ability to localize sounds when compared to normal hearing listeners. Additionally, for best speech envelope representation, most contemporary speech processing strategies use high-rate carriers (≥900 Hz) that exceed the limit for interaural pulse timing to provide useful binaural information. Many bilateral CI listeners are sensitive to interaural time differences (ITDs) in low-rate (<300 Hz) constant-amplitude pulse trains. This study explored the trade-off between superior speech temporal envelope representation with high-rate carriers and binaural pulse timing sensitivity with low-rate carriers. The effects of carrier pulse rate and pulse timing on ITD discrimination, ITD lateralization, and speech recognition in quiet were examined in eight bilateral CI listeners. Stimuli consisted of speech tokens processed at different electrical stimulation rates, and pulse timings that either preserved or did not preserve acoustic TFS cues. Results showed that CI listeners were able to use low-rate pulse timing cues derived from acoustic TFS when presented redundantly on multiple electrodes for ITD discrimination and lateralization of speech stimuli.

Sensitivity to envelope-based interaural delays at high frequencies: center frequency affects the envelope rate-limitation.

PubMed

Bernstein, Leslie R; Trahiotis, Constantine

2014-02-01

Sensitivity to ongoing interaural temporal disparities (ITDs) was measured using bandpass-filtered pulse trains centered at 4600, 6500, or 9200 Hz. Save for minor differences in the exact center frequencies, those target stimuli were those employed by Majdak and Laback [J. Acoust. Soc. Am. 125, 3903-3913 (2009)]. At each center frequency, threshold ITD was measured for pulse repetition rates ranging from 64 to 609 Hz. The results and quantitative predictions by a cross-correlation-based model indicated that (1) at most pulse repetition rates, threshold ITD increased with center frequency, (2) the cutoff frequency of the putative envelope low-pass filter that determines sensitivity to ITD at high envelope rates appears to be inversely related to center frequency, and (3) both outcomes were accounted for by assuming that, independent of the center frequency, the listeners' decision variable was a constant criterion change in interaural correlation of the stimuli as processed internally. The finding of an inverse relation between center frequency and the envelope rate limitation, while consistent with much prior literature, runs counter to the conclusion reached by Majdak and Laback.

Flight Services and Aircraft Access: Active Flow Control Vertical Tail and Insect Accretion and Mitigation Flight Test

NASA Technical Reports Server (NTRS)

Whalen, Edward A.

2016-01-01

This document serves as the final report for the Flight Services and Aircraft Access task order NNL14AA57T as part of NASA Environmentally Responsible Aviation (ERA) Project ITD12A+. It includes descriptions of flight test preparations and execution for the Active Flow Control (AFC) Vertical Tail and Insect Accretion and Mitigation (IAM) experiments conducted on the 757 ecoDemonstrator. For the AFC Vertical Tail, this is the culmination of efforts under two task orders. The task order was managed by Boeing Research & Technology and executed by an enterprise-wide Boeing team that included Boeing Research & Technology, Boeing Commercial Airplanes, Boeing Defense and Space and Boeing Test and Evaluation. Boeing BR&T in St. Louis was responsible for overall Boeing project management and coordination with NASA. The 757 flight test asset was provided and managed by the BCA ecoDemonstrator Program, in partnership with Stifel Aircraft Leasing and the TUI Group. With this report, all of the required deliverables related to management of this task order have been met and delivered to NASA as summarized in Table 1. In addition, this task order is part of a broader collaboration between NASA and Boeing.

78 FR 59008 - Grant of Interim Extension of the Term of U.S. Patent No. 5,454,779; ResQPump®/ResQPOD® ITD

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-25

... of the application indicates that, except for permission to market or use the product commercially... University of California timely filed an application under 35 U.S.C. 156(d)(5) for a second interim extension... connection with the ResQPOD[supreg] ITD. The application indicates that a Premarket Approval Application, PMA...

Molecular synergy underlies the co-occurrence patterns and phenotype of NPM1-mutant acute myeloid leukemia

PubMed Central

Dovey, Oliver M.; Cooper, Jonathan L.; Mupo, Annalisa; Grove, Carolyn S.; Lynn, Claire; Conte, Nathalie; Andrews, Robert M.; Pacharne, Suruchi; Tzelepis, Konstantinos; Vijayabaskar, M. S.; Green, Paul; Rad, Roland; Arends, Mark; Wright, Penny; Yusa, Kosuke; Bradley, Allan; Varela, Ignacio

2017-01-01

NPM1 mutations define the commonest subgroup of acute myeloid leukemia (AML) and frequently co-occur with FLT3 internal tandem duplications (ITD) or, less commonly, NRAS or KRAS mutations. Co-occurrence of mutant NPM1 with FLT3-ITD carries a significantly worse prognosis than NPM1-RAS combinations. To understand the molecular basis of these observations, we compare the effects of the 2 combinations on hematopoiesis and leukemogenesis in knock-in mice. Early effects of these mutations on hematopoiesis show that compound Npm1cA/+;NrasG12D/+ or Npm1cA;Flt3ITD share a number of features: Hox gene overexpression, enhanced self-renewal, expansion of hematopoietic progenitors, and myeloid differentiation bias. However, Npm1cA;Flt3ITD mutants displayed significantly higher peripheral leukocyte counts, early depletion of common lymphoid progenitors, and a monocytic bias in comparison with the granulocytic bias in Npm1cA/+;NrasG12D/+ mutants. Underlying this was a striking molecular synergy manifested as a dramatically altered gene expression profile in Npm1cA;Flt3ITD, but not Npm1cA/+;NrasG12D/+, progenitors compared with wild-type. Both double-mutant models developed high-penetrance AML, although latency was significantly longer with Npm1cA/+;NrasG12D/+. During AML evolution, both models acquired additional copies of the mutant Flt3 or Nras alleles, but only Npm1cA/+;NrasG12D/+ mice showed acquisition of other human AML mutations, including IDH1 R132Q. We also find, using primary Cas9-expressing AMLs, that Hoxa genes and selected interactors or downstream targets are required for survival of both types of double-mutant AML. Our results show that molecular complementarity underlies the higher frequency and significantly worse prognosis associated with NPM1c/FLT3-ITD vs NPM1/NRAS-G12D-mutant AML and functionally confirm the role of HOXA genes in NPM1c-driven AML. PMID:28835438

The acoustical cues to sound location in the Guinea pig (cavia porcellus)

PubMed Central

Greene, Nathanial T; Anbuhl, Kelsey L; Williams, Whitney; Tollin, Daniel J.

2014-01-01

There are three main acoustical cues to sound location, each attributable to space-and frequency-dependent filtering of the propagating sound waves by the outer ears, head, and torso: Interaural differences in time (ITD) and level (ILD) as well as monaural spectral shape cues. While the guinea pig has been a common model for studying the anatomy, physiology, and behavior of binaural and spatial hearing, extensive measurements of their available acoustical cues are lacking. Here, these cues were determined from directional transfer functions (DTFs), the directional components of the head-related transfer functions, for eleven adult guinea pigs. In the frontal hemisphere, monaural spectral notches were present for frequencies from ~10 to 20 kHz; in general, the notch frequency increased with increasing sound source elevation and in azimuth toward the contralateral ear. The maximum ITDs calculated from low-pass filtered (2 kHz cutoff frequency) DTFs were ~250 µs, whereas the maximum ITD measured with low frequency tone pips was over 320 µs. A spherical head model underestimates ITD magnitude under normal conditions, but closely approximates values when the pinnae were removed. Interaural level differences (ILDs) strongly depended on location and frequency; maximum ILDs were < 10 dB for frequencies < 4 kHz and were as large as 40 dB for frequencies > 10 kHz. Removal of the pinna reduced the depth and sharpness of spectral notches, altered the acoustical axis, and reduced the acoustical gain, ITDs, and ILDs; however, spectral shape features and acoustical gain were not completely eliminated, suggesting a substantial contribution of the head and torso in altering the sounds present at the tympanic membrane. PMID:25051197

Tonotopic tuning in a sound localization circuit.

PubMed

Slee, Sean J; Higgs, Matthew H; Fairhall, Adrienne L; Spain, William J

2010-05-01

Nucleus laminaris (NL) neurons encode interaural time difference (ITD), the cue used to localize low-frequency sounds. A physiologically based model of NL input suggests that ITD information is contained in narrow frequency bands around harmonics of the sound frequency. This suggested a theory, which predicts that, for each tone frequency, there is an optimal time course for synaptic inputs to NL that will elicit the largest modulation of NL firing rate as a function of ITD. The theory also suggested that neurons in different tonotopic regions of NL require specialized tuning to take advantage of the input gradient. Tonotopic tuning in NL was investigated in brain slices by separating the nucleus into three regions based on its anatomical tonotopic map. Patch-clamp recordings in each region were used to measure both the synaptic and the intrinsic electrical properties. The data revealed a tonotopic gradient of synaptic time course that closely matched the theoretical predictions. We also found postsynaptic band-pass filtering. Analysis of the combined synaptic and postsynaptic filters revealed a frequency-dependent gradient of gain for the transformation of tone amplitude to NL firing rate modulation. Models constructed from the experimental data for each tonotopic region demonstrate that the tonotopic tuning measured in NL can improve ITD encoding across sound frequencies.

Measures of extents of laterality for high-frequency ``transposed'' stimuli under conditions of binaural interference

NASA Astrophysics Data System (ADS)

Bernstein, Leslie R.; Trahiotis, Constantine

2005-09-01

Our purpose in this study was to determine whether across-frequency binaural interference would occur if ITD-based extents of laterality were measured using high-frequency transposed stimuli as targets. The results of an earlier study [L. R. Bernstein and C. Trahiotis, J. Acoust. Soc. Am. 116, 3062-3069 (2004)], which focused on threshold-ITDs, rather than extents of laterality, suggested that high-frequency transposed stimuli might be ``immune'' to binaural interference effects resulting from the addition of a spectrally remote, low-frequency interferer. In contrast to the earlier findings, the data from this study indicate that high-frequency transposed targets are susceptible to binaural interference. Nevertheless, high-frequency transposed targets, even when presented along with an interferer, yielded greater extents of ITD-based laterality than did high-frequency Gaussian noise targets presented in isolation. That is, the ``enhanced potency'' of ITDs conveyed by transposed stimuli persisted, even in the presence of a low-frequency interferer. Predictions made using an extension of the model of Heller and Trahiotis [L. M. Heller and C. Trahiotis, J. Acoust. Soc. Am. 99, 3632-3637 (1996)] accounted well for across-frequency binaural interference obtained with conventional Gaussian noise targets but, in all but one case, overpredicted the amounts of interference found with the transposed targets.

A circuit for detection of interaural time differences in the nucleus laminaris of turtles.

PubMed

Willis, Katie L; Carr, Catherine E

2017-11-15

The physiological hearing range of turtles is approximately 50-1000 Hz, as determined by cochlear microphonics ( Wever and Vernon, 1956a). These low frequencies can constrain sound localization, particularly in red-eared slider turtles, which are freshwater turtles with small heads and isolated middle ears. To determine if these turtles were sensitive to interaural time differences (ITDs), we investigated the connections and physiology of their auditory brainstem nuclei. Tract tracing experiments showed that cranial nerve VIII bifurcated to terminate in the first-order nucleus magnocellularis (NM) and nucleus angularis (NA), and the NM projected bilaterally to the nucleus laminaris (NL). As the NL received inputs from each side, we developed an isolated head preparation to examine responses to binaural auditory stimulation. Magnocellularis and laminaris units responded to frequencies from 100 to 600 Hz, and phase-locked reliably to the auditory stimulus. Responses from the NL were binaural, and sensitive to ITD. Measures of characteristic delay revealed best ITDs around ±200 μs, and NL neurons typically had characteristic phases close to 0, consistent with binaural excitation. Thus, turtles encode ITDs within their physiological range, and their auditory brainstem nuclei have similar connections and cell types to other reptiles. © 2017. Published by The Company of Biologists Ltd.

The favorable impact of CEBPA mutations in patients with acute myeloid leukemia is only observed in the absence of associated cytogenetic abnormalities and FLT3 internal duplication.

PubMed

Renneville, Aline; Boissel, Nicolas; Gachard, Nathalie; Naguib, Dina; Bastard, Christian; de Botton, Stéphane; Nibourel, Olivier; Pautas, Cécile; Reman, Oumedaly; Thomas, Xavier; Gardin, Claude; Terré, Christine; Castaigne, Sylvie; Preudhomme, Claude; Dombret, Hervé

2009-05-21

Mutations of the CCAAT/enhancer binding protein alpha (CEBPA) gene have been associated with a favorable outcome in patients with acute myeloid leukemia (AML), but mainly in those with a normal karyotype. Here, we analyzed the impact of associated cytogenetic abnormalities or bad-prognosis fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) in 53 patients with CEBPA(+) de novo AML treated in the Acute Leukemia French Association trials. We found that only those with a normal karyotype and no FLT3-ITD displayed the expected favorable outcome. In this context, relapse-free, disease-free, and overall survival were significantly longer than in corresponding patients without the CEBPA mutation (P = .035, .016, and .047, respectively). This was not observed in the context of an abnormal karyotype or associated FLT3-ITD. Furthermore, after adjustment on age, trial, and mutation type, these features were independently predictive of shorter overall survival in the subset of patients with CEBPA(+) AML (multivariate hazard ratio = 2.7; 95% confidence interval, 1.08-6.7; and 2.9; 95% confidence interval, 1.01-8.2; with P = .034 and .05, for abnormal karyotype and FLT3-ITD, respectively).

FLT3-regulated antigens as targets for leukemia-reactive cytotoxic T lymphocytes

PubMed Central

Brackertz, B; Conrad, H; Daniel, J; Kast, B; Krönig, H; Busch, D H; Adamski, J; Peschel, C; Bernhard, H

2011-01-01

The FMS-like tyrosine kinase 3 (FLT3) is highly expressed in acute myeloid leukemia (AML). Internal tandem duplications (ITD) of the juxtamembrane domain lead to the constitutive activation of the FLT3 kinase inducing the activation of multiple genes, which may result in the expression of leukemia-associated antigens (LAAs). We analyzed the regulation of LAA in FLT3-wild-type (WT)- and FLT3-ITD+ myeloid cells to identify potential targets for antigen-specific immunotherapy for AML patients. Antigens, such as PR-3, RHAMM, Survivin, WT-1 and PRAME, were upregulated by constitutively active FLT3-ITD as well as FLT3-WT activated by FLT3 ligand (FL). Cytotoxic T-cell (CTL) clones against PR-3, RHAMM, Survivin and an AML-directed CTL clone recognized AML cell lines and primary AML blasts expressing FLT3-ITD, as well as FLT3-WT+ myeloid dendritic cells in the presence of FL. Downregulation of FLT3 led to the abolishment of CTL recognition. Comparing our findings concerning LAA upregulation by the FLT3 kinase with those already made for the Bcr-Abl kinase, we found analogies in the LAA expression pattern. Antigens upregulated by both FLT3 and Bcr-Abl may be promising targets for the development of immunotherapeutical approaches against myeloid leukemia of different origin. PMID:22829124

Quizartinib, an FLT3 inhibitor, as monotherapy in patients with relapsed or refractory acute myeloid leukaemia: an open-label, multicentre, single-arm, phase 2 trial.

PubMed

Cortes, Jorge; Perl, Alexander E; Döhner, Hartmut; Kantarjian, Hagop; Martinelli, Giovanni; Kovacsovics, Tibor; Rousselot, Philippe; Steffen, Björn; Dombret, Hervé; Estey, Elihu; Strickland, Stephen; Altman, Jessica K; Baldus, Claudia D; Burnett, Alan; Krämer, Alwin; Russell, Nigel; Shah, Neil P; Smith, Catherine C; Wang, Eunice S; Ifrah, Norbert; Gammon, Guy; Trone, Denise; Lazzaretto, Deborah; Levis, Mark

2018-05-30

Old age and FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) mutations in patients with acute myeloid leukaemia are associated with early relapse and poor survival. Quizartinib is an oral, highly potent, and selective next-generation FLT3 inhibitor with clinical antileukaemic activity in relapsed or refractory acute myeloid leukaemia. We aimed to assess the efficacy and safety of single-agent quizartinib in patients with relapsed or refractory acute myeloid leukaemia. We did an open-label, multicentre, single-arm, phase 2 trial at 76 hospitals and cancer centres in the USA, Europe, and Canada. We enrolled patients with morphologically documented primary acute myeloid leukaemia or acute myeloid leukaemia secondary to myelodysplastic syndromes and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 into two predefined, independent cohorts: patients who were aged 60 years or older with relapsed or refractory acute myeloid leukaemia within 1 year after first-line therapy (cohort 1), and those who were 18 years or older with relapsed or refractory disease following salvage chemotherapy or haemopoietic stem cell transplantation (cohort 2). Patients with an FLT3-ITD allelic frequency of more than 10% were considered as FLT3-ITD positive, whereas all other patients were considered as FLT3-ITD negative. Patients received quizartinib once daily as an oral solution; the initial 17 patients received 200 mg per day but the QTcF interval was prolonged for more than 60 ms above baseline in some of these patients. Subsequently, doses were amended for all patients to 135 mg per day for men and 90 mg per day for women. The co-primary endpoints were the proportion of patients who achieved a composite complete remission (defined as complete remission + complete remission with incomplete platelet recovery + complete remission with incomplete haematological recovery) and the proportion of patients who achieved a complete remission. Efficacy and safety analyses included all patients who received at least one dose of quizartinib (ie, the intention-to-treat population). Patients with a locally assessed post-treatment bone marrow aspirate or biopsy were included in efficacy analyses by response; all other patients were considered to have an unknown response. This study is registered with ClinicalTrials.gov, number NCT00989261, and with the European Clinical Trials Database, EudraCT 2009-013093-41, and is completed. Between Nov 19, 2009, and Oct 31, 2011, a total of 333 patients were enrolled (157 in cohort 1 and 176 in cohort 2). In cohort 1, 63 (56%) of 112 FLT3-ITD-positive patients and 16 (36%) of 44 FLT3-ITD-negative patients achieved composite complete remission, with three (3%) FLT3-ITD-positive patients and two (5%) FLT3-ITD-negative patients achieving complete remission. In cohort 2, 62 (46%) of 136 FLT3-ITD-positive patients achieved composite complete remission with five (4%) achieving complete remission, whereas 12 (30%) of 40 FLT3-ITD-negative patients achieved composite complete remission with one (3%) achieving complete remission. Across both cohorts (ie, the intention-to-treat population of 333 patients), grade 3 or worse treatment-related treatment-emergent adverse events in 5% or more of patients were febrile neutropenia (76 [23%] of 333), anaemia (75 [23%]), thrombocytopenia (39 [12%]), QT interval corrected using Fridericia's formula (QTcF) prolongation (33 [10%]), neutropenia (31 [9%]), leucopenia (22 [7%]), decreased platelet count (20 [6%]), and pneumonia (17 [5%]). Serious adverse events occurring in 5% or more of patients were febrile neutropenia (126 [38%] of 333; 76 treatment related), acute myeloid leukaemia progression (73 [22%]), pneumonia (40 [12%]; 14 treatment related), QTcF prolongation (33 [10%]; 32 treatment related), sepsis (25 [8%]; eight treatment related), and pyrexia (18 [5%]; nine treatment related). Notable serious adverse events occurring in less than 5% of patients were torsades de pointes (one [<1%]) and hepatic failure (two [1%]). In total, 125 (38%) of 333 patients died within the study treatment period, including the 30-day follow-up. 18 (5%) patients died because of an adverse event considered by the investigator to be treatment related (ten [6%] of 157 patients in cohort 1 and eight [5%] of 176 in cohort 2. Single-agent quizartinib was shown to be highly active and generally well tolerated in patients with relapsed or refractory acute myeloid leukaemia, particularly those with FLT3-ITD mutations. These findings confirm that targeting the FLT3-ITD driver mutation with a highly potent and selective FLT3 inhibitor is a promising clinical strategy to help improve clinical outcomes in patients with very few options. Phase 3 studies (NCT02039726; NCT02668653) will examine quizartinib at lower starting doses. Ambit Biosciences/Daiichi Sankyo. Copyright © 2018 Elsevier Ltd. All rights reserved.

JNDS of interaural time delay (ITD) of selected frequency bands in speech and music signals

NASA Astrophysics Data System (ADS)

Aliphas, Avner; Colburn, H. Steven; Ghitza, Oded

2002-05-01

JNDS of interaural time delay (ITD) of selected frequency bands in the presence of other frequency bands have been reported for noiseband stimuli [Zurek (1985); Trahiotis and Bernstein (1990)]. Similar measurements will be reported for speech and music signals. When stimuli are synthesized with bandpass/band-stop operations, performance with complex stimuli are similar to noisebands (JNDS in tens or hundreds of microseconds); however, the resulting waveforms, when viewed through a model of the auditory periphery, show distortions (irregularities in phase and level) at the boundaries of the target band of frequencies. An alternate synthesis method based upon group-delay filtering operations does not show these distortions and is being used for the current measurements. Preliminary measurements indicate that when music stimuli are created using the new techniques, JNDS of ITDs are increased significantly compared to previous studies, with values on the order of milliseconds.

Multispectral diagnostic imaging of the iris in pigment dispersion syndrome.

PubMed

Roberts, Daniel K; Lukic, Ana; Yang, Yongyi; Wilensky, Jacob T; Wernick, Miles N

2012-08-01

To determine if wavelength selection with near infrared iris imaging may enhance iris transillumination defects (ITDs) in pigment dispersion syndrome. An experimental apparatus was used to acquire iris images in 6 African-American (AA) and 6 White patients with pigment dispersion syndrome. Light-emitting diode probes of 6 different spectral bands (700 to 950 nm) were used to project light into patients' eyes. Iris patterns were photographed, ITD regions of interest were outlined, and region of interest contrasts were calculated for each spectral band. Contrasts varied as a function of wavelength (P<0.0001) for both groups, but tended to be highest in the 700 to 800 nm range. Contrasts were higher in Whites than AAs at 700 nm but the opposite was found at 810 nm (P<0.001). Optimized near infrared iris imaging may be wavelength dependent. Ideal wavelength to image ITDs in more pigmented eyes may be slightly longer than for less pigmented eyes.

FLT3-ITD and MLL-PTD influence the expression of MDR-1, MRP-1, and BCRP mRNA but not LRP mRNA assessed with RQ-PCR method in adult acute myeloid leukemia.

PubMed

Nasilowska-Adamska, Barbara; Solarska, Iwona; Paluszewska, Monika; Malinowska, Iwona; Jedrzejczak, Wieslaw W; Warzocha, Krzysztof

2014-04-01

Fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) and mixed-lineage leukemia gene-partial tandem duplication (MLL-PTD) are aberrations associated with leukemia which indicate unsatisfactory prognosis. Downstream regulatory targets of FLT3-ITD and MLL-PTD are not well defined. We have analyzed the expression of MDR-1, multidrug resistant protein-1 (MRP-1), breast cancer resistance protein (BCRP), and lung resistance protein (LRP) messenger RNA (mRNA) in relation to the mutational status of FLT3-ITD and MLL-PTD in 185 acute myeloid leukemia (AML) adult patients. The real-time quantitative polymerase chain reaction method was performed to assess the expression of the MDR-1, MRP-1, BCRP, and LRP mRNA, and the results were presented as coefficients calculated using an intermediate method according to Pfaffl's rule. Significantly higher expressions of MDR-1 mRNA were found in patients who did not harbor FLT3-ITD (0.20 vs. 0.05; p = 0.0001) and MRP-1 mRNA in patients with this mutation (0.96 vs. 0.70; p = 0.002) and of BCRP mRNA in patients with MLL-PTD (0.61 vs. 0.38; p = 0.03). In univariate analysis, the high expression of MDR-1 mRNA (≥0.1317) negatively influenced the outcome of induction therapy (p = 0.05), whereas the high expression of BCRP mRNA (≥1.1487) was associated with a high relapse rate (RR) (p = 0.013). We found that the high expression of MDR-1 (≥0.1317), MRP-1 (≥0.8409), and BCRP mRNA (≥1.1487) significantly influenced disease-free survival (DFS; p = 0.059, 0.032, and 0.009, respectively) and overall survival (0.048, 0.014, and 0.059, respectively). Moreover, a high expression of BCRP mRNA (≥1.1487) proved to be an independent prognostic factor for RR (p = 0.01) and DFS (p = 0.002) in multivariate analysis. The significant correlation between the expression of MDR-1, MRP-1, and BCRP mRNA and FLT3-ITD or MLL-PTD in AML patients requires further investigation.

Using individual differences to test the role of temporal and place cues in coding frequency modulation

PubMed Central

Whiteford, Kelly L.; Oxenham, Andrew J.

2015-01-01

The question of how frequency is coded in the peripheral auditory system remains unresolved. Previous research has suggested that slow rates of frequency modulation (FM) of a low carrier frequency may be coded via phase-locked temporal information in the auditory nerve, whereas FM at higher rates and/or high carrier frequencies may be coded via a rate-place (tonotopic) code. This hypothesis was tested in a cohort of 100 young normal-hearing listeners by comparing individual sensitivity to slow-rate (1-Hz) and fast-rate (20-Hz) FM at a carrier frequency of 500 Hz with independent measures of phase-locking (using dynamic interaural time difference, ITD, discrimination), level coding (using amplitude modulation, AM, detection), and frequency selectivity (using forward-masking patterns). All FM and AM thresholds were highly correlated with each other. However, no evidence was obtained for stronger correlations between measures thought to reflect phase-locking (e.g., slow-rate FM and ITD sensitivity), or between measures thought to reflect tonotopic coding (fast-rate FM and forward-masking patterns). The results suggest that either psychoacoustic performance in young normal-hearing listeners is not limited by peripheral coding, or that similar peripheral mechanisms limit both high- and low-rate FM coding. PMID:26627783

Using individual differences to test the role of temporal and place cues in coding frequency modulation.

PubMed

Whiteford, Kelly L; Oxenham, Andrew J

2015-11-01

The question of how frequency is coded in the peripheral auditory system remains unresolved. Previous research has suggested that slow rates of frequency modulation (FM) of a low carrier frequency may be coded via phase-locked temporal information in the auditory nerve, whereas FM at higher rates and/or high carrier frequencies may be coded via a rate-place (tonotopic) code. This hypothesis was tested in a cohort of 100 young normal-hearing listeners by comparing individual sensitivity to slow-rate (1-Hz) and fast-rate (20-Hz) FM at a carrier frequency of 500 Hz with independent measures of phase-locking (using dynamic interaural time difference, ITD, discrimination), level coding (using amplitude modulation, AM, detection), and frequency selectivity (using forward-masking patterns). All FM and AM thresholds were highly correlated with each other. However, no evidence was obtained for stronger correlations between measures thought to reflect phase-locking (e.g., slow-rate FM and ITD sensitivity), or between measures thought to reflect tonotopic coding (fast-rate FM and forward-masking patterns). The results suggest that either psychoacoustic performance in young normal-hearing listeners is not limited by peripheral coding, or that similar peripheral mechanisms limit both high- and low-rate FM coding.

Enhancing Communication in Noisy Environments

DTIC Science & Technology

2009-10-01

derived from the ITD and ILD cues, which are binaural . ITD depends on the azimuthal position of the source. Similarly, ILD refers to the fact...4.4 dB No Perceptual Binaural Speech Enhancement [42] 4.5 dB Yes Fuzzy Cocktail Party Processor [25] 7.5 dB Yes Binaural segregation [43] 8.9 dB No...modulation. IEEE Transactions on Neural Networks. 15 (2004): 1135-50. [42] Dong R. Perceptual Binaural Speech Enhancement in Noisy Environments. M.A.Sc

T-LAK cell-originated protein kinase presents a novel therapeutic target in FLT3-ITD mutated acute myeloid leukemia.

PubMed

Alachkar, Houda; Mutonga, Martin; Malnassy, Gregory; Park, Jae-Hyun; Fulton, Noreen; Woods, Alex; Meng, Liping; Kline, Justin; Raca, Gordana; Odenike, Olatoyosi; Takamatsu, Naofumi; Miyamoto, Takashi; Matsuo, Yo; Stock, Wendy; Nakamura, Yusuke

2015-10-20

Gain-of-function mutations of FLT3 (FLT3-ITD), comprises up to 30% of normal karyotype acute myeloid leukemia (AML) and is associated with an adverse prognosis. Current FLT3 kinase inhibitors have been tested extensively, but have not yet resulted in a survival benefit and novel therapies are awaited. Here we show that T-LAK cell-originated protein kinase (TOPK), a mitotic kinase highly expressed in and correlated with more aggressive phenotype in several types of cancer, is expressed in AML but not in normal CD34+ cells and that TOPK knockdown decreased cell viability and induced apoptosis. Treatment of AML cells with TOPK inhibitor (OTS514) resulted in a dose-dependent decrease in cell viability with lower IC50 in FLT3-mutated cells, including blasts obtained from patients relapsed after FLT3-inhibitor treatment. Using a MV4-11-engrafted mouse model, we found that mice treated with 7.5 mg/kg IV daily for 3 weeks survived significantly longer than vehicle treated mice (median survival 46 vs 29 days, P < 0.001). Importantly, we identified TOPK as a FLT3-ITD and CEBPA regulated kinase, and that modulating TOPK expression or activity resulted in significant decrease of FLT3 expression and CEBPA phosphorylation. Thus, targeting TOPK in FLT3-ITD AML represents a novel therapeutic approach for this adverse risk subset of AML.

Treatment of non-traumatic out-of-hospital cardiac arrest with active compression decompression cardiopulmonary resuscitation plus an impedance threshold device.

PubMed

Frascone, Ralph J; Wayne, Marvin A; Swor, Robert A; Mahoney, Brian D; Domeier, Robert M; Olinger, Michael L; Tupper, David E; Setum, Cindy M; Burkhart, Nathan; Klann, Lucinda; Salzman, Joshua G; Wewerka, Sandi S; Yannopoulos, Demetris; Lurie, Keith G; O'Neil, Brian J; Holcomb, Richard G; Aufderheide, Tom P

2013-09-01

A recent out-of-hospital cardiac arrest (OHCA) clinical trial showed improved survival to hospital discharge (HD) with favorable neurologic function for patients with cardiac arrest of cardiac origin treated with active compression decompression cardiopulmonary resuscitation (CPR) plus an impedance threshold device (ACD+ICD) versus standard (S) CPR. The current analysis examined whether treatment with ACD+ITD is more effective than standard (S-CPR) for all cardiac arrests of non-traumatic origin, regardless of the etiology. This is a secondary analysis of data from a randomized, prospective, multicenter, intention-to-treat, OHCA clinical trial. Adults with presumed non-traumatic cardiac arrest were enrolled and followed for one year post arrest. The primary endpoint was survival to hospital discharge (HD) with favorable neurologic function (Modified Rankin Scale score ≤ 3). Between October 2005 and July 2009, 2738 patients were enrolled (S-CPR=1335; ACD+ITD=1403). Survival to HD with favorable neurologic function was greater with ACD+ITD compared with S-CPR: 7.9% versus 5.7%, (OR 1.42, 95% CI 1.04, 1.95, p=0.027). One-year survival was also greater: 7.9% versus 5.7%, (OR 1.43, 95% CI 1.04, 1.96, p=0.026). Nearly all survivors in both groups had returned to their baseline neurological function by one year. Major adverse event rates were similar between groups. Treatment of out-of-hospital non-traumatic cardiac arrest patients with ACD+ITD resulted in a significant increase in survival to hospital discharge with favorable neurological function when compared with S-CPR. A significant increase survival rates was observed up to one year after arrest in subjects treated with ACD+ITD, regardless of the etiology of the cardiac arrest. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Feature genes predicting the FLT3/ITD mutation in acute myeloid leukemia

PubMed Central

LI, CHENGLONG; ZHU, BIAO; CHEN, JIAO; HUANG, XIAOBING

2016-01-01

In the present study, gene expression profiles of acute myeloid leukemia (AML) samples were analyzed to identify feature genes with the capacity to predict the mutation status of FLT3/ITD. Two machine learning models, namely the support vector machine (SVM) and random forest (RF) methods, were used for classification. Four datasets were downloaded from the European Bioinformatics Institute, two of which (containing 371 samples, including 281 FLT3/ITD mutation-negative and 90 mutation-positive samples) were randomly defined as the training group, while the other two datasets (containing 488 samples, including 350 FLT3/ITD mutation-negative and 138 mutation-positive samples) were defined as the test group. Differentially expressed genes (DEGs) were identified by significance analysis of the micro-array data by using the training samples. The classification efficiency of the SCM and RF methods was evaluated using the following parameters: Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and the area under the receiver operating characteristic curve. Functional enrichment analysis was performed for the feature genes with DAVID. A total of 585 DEGs were identified in the training group, of which 580 were upregulated and five were downregulated. The classification accuracy rates of the two methods for the training group, the test group and the combined group using the 585 feature genes were >90%. For the SVM and RF methods, the rates of correct determination, specificity and PPV were >90%, while the sensitivity and NPV were >80%. The SVM method produced a slightly better classification effect than the RF method. A total of 13 biological pathways were overrepresented by the feature genes, mainly involving energy metabolism, chromatin organization and translation. The feature genes identified in the present study may be used to predict the mutation status of FLT3/ITD in patients with AML. PMID:27177049

Functional Pathway Analysis Using SCNP of FLT3 Receptor Pathway Deregulation in AML Provides Prognostic Information Independent from Mutational Status

PubMed Central

Cesano, Alessandra; Putta, Santosh; Rosen, David B.; Cohen, Aileen C.; Gayko, Urte; Mathi, Kavita; Woronicz, John; Hawtin, Rachael E.; Cripe, Larry; Sun, Zhuoxin; Tallman, Martin S.; Paietta, Elisabeth

2013-01-01

FMS-like tyrosine kinase 3 receptor (FLT3) internal tandem duplication (ITD) mutations result in constitutive activation of this receptor and have been shown to increase the risk of relapse in patients with acute myeloid leukemia (AML); however, substantial heterogeneity in clinical outcomes still exists within both the ITD mutated and unmutated AML subgroups, suggesting alternative mechanisms of disease relapse not accounted by FLT3 mutational status. Single cell network profiling (SCNP) is a multiparametric flow cytometry based assay that simultaneously measures, in a quantitative fashion and at the single cell level, both extracellular surface marker levels and changes in intracellular signaling proteins in response to extracellular modulators. We previously reported an initial characterization of FLT3 ITD-mediated signaling using SCNP. Herein SCNP was applied sequentially to two separate cohorts of samples collected from elderly AML patients at diagnosis. In the first (training) study, AML samples carrying unmutated, wild-type FLT3 (FLT3 WT) displayed a wide range of induced signaling, with a fraction having signaling profiles comparable to FLT3 ITD AML samples. Conversely, the FLT3 ITD AML samples displayed more homogeneous induced signaling, with the exception of patients with low (<40%) mutational load, which had profiles comparable to FLT3 WT AML samples. This observation was then confirmed in an independent (verification) cohort. Data from the second cohort were also used to assess the association between SCNP data and disease-free survival (DFS) in the context of FLT3 and nucleophosmin (NPM1) mutational status among patients who achieved complete remission (CR) to induction chemotherapy. The combination of SCNP read outs together with FLT3 and NPM1 molecular status improved the DFS prediction accuracy of the latter. Taken together, these results emphasize the value of comprehensive functional assessment of biologically relevant signaling pathways in AML as a basis for the development of highly predictive tests for guidance of post-remission therapy. PMID:23431389

Phase I Trial of Maintenance Sorafenib after Allogeneic Hematopoietic Stem Cell Transplantation for FLT3-ITD AML

PubMed Central

Chen, Yi-Bin; Li, Shuli; Lane, Andrew A.; Connolly, Christine; Del Rio, Candice; Valles, Betsy; Curtis, Morgan; Ballen, Karen; Cutler, Corey; Dey, Bimalangshu R.; El-Jawahri, Areej; Fathi, Amir T.; Ho, Vincent T.; Joyce, Amy; McAfee, Steven; Rudek, Michelle; Rajkhowa, Trivikram; Verselis, Sigitas; Antin, Joseph H.; Spitzer, Thomas R.; Levis, Mark; Soiffer, Robert

2014-01-01

The FLT3-ITD mutation is associated with a high relapse rate for patients with AML even after allogeneic hematopoietic stem cell transplantation (HSCT). Sorafenib is a tyrosine kinase inhibitor which inhibits the FLT3 tyrosine kinase and has shown encouraging activity in FLT3-ITD AML. We conducted a phase I trial of maintenance sorafenib after HSCT in patients with FLT3-ITD AML (ClinicalTrials.gov NCT01398501). Patients received a variety of conditioning regimens and graft sources. A dose escalation 3+3 cohort design was used to define the maximum tolerated dose (MTD) with an additional 10 patients treated at the MTD. Sorafenib was initiated between days 45 and 120 after HSCT continued for twelve 28-day cycles. Twenty-two patients were enrolled (status at HSCT: CR1=16, CR2=3, refractory=3). The MTD was established at 400 mg BID with one DLT observed (pericardial effusion). Two patients died of transplant-related causes, both unrelated to sorafenib. Two patients stopped sorafenib after relapse and 5 stopped due to attributable toxicities after the DLT period. Median follow-up for surviving patients is 16.7 months after HSCT (range, 8.1–35.0). There was one case of grade II acute GVHD after starting sorafenib and the 12-month cumulative incidence of chronic GVHD was 38% (90% CI, 21%–56%). For all patients, one-year progression-free survival (PFS) is 85% (90% CI, 66%–94%) and one-year overall survival (OS) is 95% (90% CI, 79%–99%) after HSCT. For patients in CR1 / CR2 prior to HSCT (n=19), one-year PFS is 95% (90% CI, 76%–99%) and one-year OS is 100% with only one patient who has relapsed. Sorafenib is safe after HSCT for FLT3-ITD AML and merits further investigation for the prevention of relapse. PMID:25239228

Feature genes predicting the FLT3/ITD mutation in acute myeloid leukemia.

PubMed

Li, Chenglong; Zhu, Biao; Chen, Jiao; Huang, Xiaobing

2016-07-01

In the present study, gene expression profiles of acute myeloid leukemia (AML) samples were analyzed to identify feature genes with the capacity to predict the mutation status of FLT3/ITD. Two machine learning models, namely the support vector machine (SVM) and random forest (RF) methods, were used for classification. Four datasets were downloaded from the European Bioinformatics Institute, two of which (containing 371 samples, including 281 FLT3/ITD mutation-negative and 90 mutation‑positive samples) were randomly defined as the training group, while the other two datasets (containing 488 samples, including 350 FLT3/ITD mutation-negative and 138 mutation-positive samples) were defined as the test group. Differentially expressed genes (DEGs) were identified by significance analysis of the microarray data by using the training samples. The classification efficiency of the SCM and RF methods was evaluated using the following parameters: Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and the area under the receiver operating characteristic curve. Functional enrichment analysis was performed for the feature genes with DAVID. A total of 585 DEGs were identified in the training group, of which 580 were upregulated and five were downregulated. The classification accuracy rates of the two methods for the training group, the test group and the combined group using the 585 feature genes were >90%. For the SVM and RF methods, the rates of correct determination, specificity and PPV were >90%, while the sensitivity and NPV were >80%. The SVM method produced a slightly better classification effect than the RF method. A total of 13 biological pathways were overrepresented by the feature genes, mainly involving energy metabolism, chromatin organization and translation. The feature genes identified in the present study may be used to predict the mutation status of FLT3/ITD in patients with AML.

Treatment of Non-Traumatic Out-of-Hospital Cardiac Arrest with Active Compression Decompression Cardiopulmonary Resuscitation plus an Impedance Threshold Device

PubMed Central

Frascone, Ralph J; Wayne, Marvin A; Swor, Robert A; Mahoney, Brian D; Domeier, Robert M; Olinger, Michael L; Tupper, David E; Setum, Cindy M; Burkhart, Nathan; Klann, Lucinda; Salzman, Joshua G; Wewerka, Sandi S; Yannopoulos, Demetris; Lurie, Keith G; O’Neil, Brian J.; Holcomb, Richard G; Aufderheide, Tom P

2013-01-01

Background A recent out-of-hospital cardiac arrest (OHCA) clinical trial showed improved survival to hospital discharge (HD) with favorable neurologic function for patients with cardiac arrest of cardiac origin treated with active compression decompression cardiopulmonary resuscitation (CPR) plus an impedance threshold device (ACD+ICD) versus standard (S) CPR. The current analysis examined whether treatment with ACD+ITD is more effective than standard (S-CPR) for all cardiac arrests of non-traumatic origin, regardless of the aetiology. Methods This is a secondary analysis of data from a randomized, prospective, multicenter, intention-to-treat, OHCA clinical trial. Adults with presumed non-traumatic cardiac arrest were enrolled and followed for one year post arrest. The primary endpoint was survival to hospital discharge (HD) with favorable neurologic function (modified Rankin Scale score ≤3). Results Between October 2005 to July 2009, 2738 patients were enrolled (S-CPR = 1335; ACD+ITD =1403). Survival to HD with favorable neurologic function was greater with ACD+ITD compared with S-CPR: 7.9% versus 5.7%, (OR 1.42, 95% CI 1.04, 1.95, p=0.027). One-year survival was also greater: 7.9% versus 5.7%, (OR 1.43, 95% CI 1.04, 1.96, p=0.026). Nearly all survivors in both groups had returned to their baseline neurological function by one year. Major adverse event rates were similar between groups. Conclusions Treatment of out-of-hospital non-traumatic cardiac arrest patients with ACD+ITD resulted in a significant increase in survival to hospital discharge with favorable neurological function when compared with S-CPR. A significant increase survival rates was observed up to one year after arrest in subjects treated with ACD+ITD, regardless of the etiology of the cardiac arrest. Clinical Trial Registration NCT 00189423 (http://www.clinicaltrials.gov) PMID:23669489

Temporal Changes in FLT3 ITD Regulation of Stem Cell Self Renewal and Leukemogenesis

DTIC Science & Technology

2016-11-01

JAM is a 661   scholar of the Child Health Research Center for Excellence in Developmental 662   Biology at Washington University (K12-HD076224...SUPPLEMENTARY NOTES 14. ABSTRACT My goal is to understand how mechanisms that regulate normal hematopoietic development can also influence the mutation...pathways) in fetal, neonatal and adult progenitors. STAT5 was activated by FLT3-ITD at all stages of development , but MAPK was activated only in post

Use of an Impedance Threshold Device in Spontaneously Breathing Patients with Hypotension Secondary to Trauma: An Observational Cohort Feasibility Study

DTIC Science & Technology

2014-09-09

hypotensive patient. Crystalloid infusion is not necessarily benign.1,2 Difficult vascular access, hemodilution, acidosis , decreased oxygen delivery, and...blood pressure, heart rate (HR), respiratory rate, and arterial oxygen saturation (SpO2) were recorded im- mediately before application of the ITD...per minute (p = 0.007). The respiratory rate was constant: 19 (7) breaths before to 18 (4) breaths (p = 0.31) per minute after ITD use. Oxygen

T-LAK cell-originated protein kinase presents a novel therapeutic target in FLT3-ITD mutated acute myeloid leukemia

PubMed Central

Alachkar, Houda; Mutonga, Martin; Malnassy, Gregory; Park, Jae-Hyun; Fulton, Noreen; Woods, Alex; Meng, Liping; Kline, Justin; Raca, Gordana; Odenike, Olatoyosi; Takamatsu, Naofumi; Miyamoto, Takashi; Matsuo, Yo; Stock, Wendy; Nakamura, Yusuke

2015-01-01

Gain-of-function mutations of FLT3 (FLT3-ITD), comprises up to 30% of normal karyotype acute myeloid leukemia (AML) and is associated with an adverse prognosis. Current FLT3 kinase inhibitors have been tested extensively, but have not yet resulted in a survival benefit and novel therapies are awaited. Here we show that T-LAK cell-originated protein kinase (TOPK), a mitotic kinase highly expressed in and correlated with more aggressive phenotype in several types of cancer, is expressed in AML but not in normal CD34+ cells and that TOPK knockdown decreased cell viability and induced apoptosis. Treatment of AML cells with TOPK inhibitor (OTS514) resulted in a dose-dependent decrease in cell viability with lower IC50 in FLT3-mutated cells, including blasts obtained from patients relapsed after FLT3-inhibitor treatment. Using a MV4-11-engrafted mouse model, we found that mice treated with 7.5 mg/kg IV daily for 3 weeks survived significantly longer than vehicle treated mice (median survival 46 vs 29 days, P < 0.001). Importantly, we identified TOPK as a FLT3-ITD and CEBPA regulated kinase, and that modulating TOPK expression or activity resulted in significant decrease of FLT3 expression and CEBPA phosphorylation. Thus, targeting TOPK in FLT3-ITD AML represents a novel therapeutic approach for this adverse risk subset of AML. PMID:26450903

FLT3-ITD cooperates with inv(16) to promote progression to acute myeloid leukemia

PubMed Central

Kim, Hyung-Gyoon; Kojima, Kyoko; Swindle, C. Scott; Cotta, Claudiu V.; Huo, Yongliang; Reddy, Vishnu

2008-01-01

The inversion of chromosome 16 in the inv(16)(p13q22) is one of the most frequent cytogenetic abnormalities observed in acute myeloid leukemia (AML). The inv(16) fuses the core binding factor (CBF) beta subunit with the coiled-coil rod domain of smooth muscle myosin heavy chain (SMMHC). Expression of CBFβ-SMMHC in mice does not promote AML in the absence of secondary mutations. Patient samples with the inv(16) also possess mutually exclusive activating mutations in either N-RAS, K-RAS, or the receptor tyrosine kinases, c-KIT and FLT3, in almost 70% of cases. To test whether an activating mutation of FLT3 (FLT3-ITD) would cooperate with CBFβ-SMMHC to promote AML, we coexpressed both mutations in hematopoietic progenitor cells used to reconstitute lethally irradiated mice. Analysis of transplanted animals showed strong selection for CBFβ-SMMHC/FLT3-ITD–expressing cells in bone marrow and peripheral blood. Compared with animals transplanted with only CBFβ-SMMHC–expressing cells, FLT3-ITD further restricted early myeloid differentiation and promoted peripheralization of primitive myeloblasts as early as 2.5 weeks after transplantation. FLT3-ITD also accelerated disease progression in all CBFβ-SMMHC/FLT3-ITD–reconstituted animals, which died of a highly aggressive and transplantable AML within 3 to 5 months. These results indicate that FLT3-activating mutations can cooperate with CBFβ-SMMHC in an animal model of inv(16)-associated AML. PMID:17967943

Matrix isolation with an ion transfer device for interference-free simultaneous spectrophotometric determinations of hexavalent and trivalent chromium in a flow-based system.

PubMed

Ohira, Shin-Ichi; Nakamura, Koretaka; Chiba, Mitsuki; Dasgupta, Purnendu K; Toda, Kei

2017-03-01

Chromium speciation by spectrophotometric determination of hexavalent chromium (Cr(VI)) with diphenylcarbazide (DPC) has several problems. These include: (1) the inability to directly detect trivalent chromium (Cr(III)) with DPC, (2) positive interference in Cr(VI) determination by other metal cations and (3) negative interference by any reducing agent present in the sample. These are addressed with an ion transfer device (ITD) in a flow injection analysis system. We previously developed the ITD for electrodialytic separations. Here we separate oppositely charged Cr(III) and Cr(VI) species by the ITD into two different acceptor solutions within ~5 s. The acceptor solutions consist of buffered H 2 O 2 to oxidize the Cr(III) to Cr(VI). Then DPC is added to either acceptor to measure Cr(III) and Cr(VI) spectrophotometrically. The system was optimized to provide the same response for Cr(VI) and Cr(III) with limits of detection (LODs, S/N=3) of 0.5 μg L -1 for each and a throughput rate of 30 samples h -1 . The ITD separation was also effective for matrix isolation and reduction of interferences. Potential cationic interferences were not transferred into the anionic Cr(VI) acceptor stream. Much of the organic compounds in soil extracts were also eliminated as evidenced from standard addition and recovery studies. Copyright © 2016 Elsevier B.V. All rights reserved.

CAR T-cells targeting FLT3 have potent activity against FLT3-ITD+ AML and act synergistically with the FLT3-inhibitor crenolanib.

PubMed

Jetani, Hardikkumar; Garcia-Cadenas, Irene; Nerreter, Thomas; Thomas, Simone; Rydzek, Julian; Meijide, Javier Briones; Bonig, Halvard; Herr, Wolfgang; Sierra, Jordi; Einsele, Hermann; Hudecek, Michael

2018-05-01

FMS-like tyrosine kinase 3 (FLT3) is a transmembrane protein expressed on normal hematopoietic stem and progenitor cells (HSC) and retained on malignant blasts in acute myeloid leukemia (AML). We engineered CD8 + and CD4 + T-cells expressing a FLT3-specific chimeric antigen receptor (CAR) and demonstrate they confer potent reactivity against AML cell lines and primary AML blasts that express either wild-type FLT3 or FLT3 with internal tandem duplication (FLT3-ITD). We also show that treatment with the FLT3-inhibitor crenolanib leads to increased surface expression of FLT3 specifically on FLT3-ITD + AML cells and consecutively, enhanced recognition by FLT3-CAR T-cells in vitro and in vivo. As anticipated, we found that FLT3-CAR T-cells recognize normal HSCs in vitro and in vivo, and disrupt normal hematopoiesis in colony-formation assays, suggesting that adoptive therapy with FLT3-CAR T-cells will require subsequent CAR T-cell depletion and allogeneic HSC transplantation to reconstitute the hematopoietic system. Collectively, our data establish FLT3 as a novel CAR target in AML with particular relevance in high-risk FLT3-ITD + AML. Further, our data provide the first proof-of-concept that CAR T-cell immunotherapy and small molecule inhibition can be used synergistically, as exemplified by our data showing superior antileukemia efficacy of FLT3-CAR T-cells in combination with crenolanib.

STAT5 Is Crucial to Maintain Leukemic Stem Cells in Acute Myelogenous Leukemias Induced by MOZ-TIF2

PubMed Central

Tam, Winnie F.; Hähnel, Patricia S.; Schüler, Andrea; Lee, Benjamin H.; Okabe, Rachel; Zhu, Nan; Pante, Saskia V.; Raffel, Glen; Mercher, Thomas; Wernig, Gerlinde; Bockamp, Ernesto; Sasca, Daniel; Kreft, Andreas; Robinson, Gertraud W.; Hennighausen, Lothar; Gilliland, D. Gary; Kindler, Thomas

2014-01-01

MOZ-TIF2 is a leukemogenic fusion oncoprotein that confers self-renewal capability to hematopoietic progenitor cells and induces acute myelogenous leukemia (AML) with long latency in bone marrow transplantation assays. Here, we report that FLT3-ITD transforms hematopoietic cells in cooperation with MOZ-TIF2 in vitro and in vivo. Coexpression of FLT3-ITD confers growth factor independent survival/proliferation, shortens disease latency, and results in an increase in the number of leukemic stem cells (LSC). We show that STAT5, a major effector of aberrant FLT3-ITD signal transduction, is both necessary and sufficient for this cooperative effect. In addition, STAT5 signaling is essential for MOZ-TIF2–induced leukemic transformation itself. Lack of STAT5 in fetal liver cells caused rapid differentiation and loss of replating capacity of MOZ-TIF2–transduced cells enriched for LSCs. Furthermore, mice serially transplanted with Stat5−/− MOZ-TIF2 leukemic cells develop AML with longer disease latency and finally incomplete penetrance when compared with mice transplanted with Stat5+/+ MOZ-TIF2 leukemic cells. These data suggest that STAT5AB is required for the self-renewal of LSCs and represents a combined signaling node of FLT3-ITD and MOZ-TIF2 driven leukemogenesis. Therefore, targeting aberrantly activated STAT5 or rewired downstream signaling pathways may be a promising therapeutic option. PMID:23149921

BCOR Overexpression Is a Highly Sensitive Marker in Round Cell Sarcomas With BCOR Genetic Abnormalities.

PubMed

Kao, Yu-Chien; Sung, Yun-Shao; Zhang, Lei; Jungbluth, Achim A; Huang, Shih-Chiang; Argani, Pedram; Agaram, Narasimhan P; Zin, Angelica; Alaggio, Rita; Antonescu, Cristina R

2016-12-01

With the advent of next-generation sequencing, an increasing number of novel gene fusions and other abnormalities have emerged recently in the spectrum of EWSR1-negative small blue round cell tumors (SBRCTs). In this regard, a subset of SBRCTs harboring either BCOR gene fusions (BCOR-CCNB3, BCOR-MAML3), BCOR internal tandem duplications (ITD), or YWHAE-NUTM2B share a transcriptional signature including high BCOR mRNA expression, as well as similar histologic features. Furthermore, other tumors such as clear cell sarcoma of kidney (CCSK) and primitive myxoid mesenchymal tumor of infancy also demonstrate BCOR ITDs and high BCOR gene expression. The molecular diagnosis of these various BCOR genetic alterations requires an elaborate methodology including custom BAC fluorescence in situ hybridization (FISH) probes and reverse transcription polymerase chain reaction assays. As these tumors show high level of BCOR overexpression regardless of the genetic mechanism involved, either conventional gene fusion or ITD, we sought to investigate the performance of an anti-BCOR monoclonal antibody clone C-10 (sc-514576) as an immunohistochemical marker for sarcomas with BCOR gene abnormalities. Thus we assessed the BCOR expression in a pathologically and genetically well-characterized cohort of 25 SBRCTs, spanning various BCOR-related fusions and ITDs and YWHAE-NUTM2B fusion. In addition, we included related pathologic entities such as 8 CCSKs and other sarcomas with BCOR gene fusions. As a control group we included 20 SBRCTs with various (non-BCOR) genetic abnormalities, 10 fusion-negative SBRCTs, 74 synovial sarcomas, 29 rhabdomyosarcomas, and other sarcoma types. In addition, we evaluated the same study group for SATB2 immunoreactivity, as these tumors also showed SATB2 mRNA upregulation. All SBRCTs with BCOR-MAML3 and BCOR-CCNB3 fusions, as well as most with BCOR ITD (93%), and all CCSKs showed strong and diffuse nuclear BCOR immunoreactivity. Furthermore, all SBRCTs with YWHAE-NUTM2B also were positive. SATB2 stain was also positive in tumors with YWHAE-NUTM2B, BCOR-MAML3, BCOR ITD (75%), BCOR-CCNB3 (71%), and a subset of CCSKs (33%). In conclusion, BCOR immunohistochemical stain is a highly sensitive marker for SBRCTs and CCSKs with BCOR abnormalities and YWHAE-rearrangements and can be used as a useful diagnostic marker in these various molecular subsets. SATB2 immunoreactivity is also present in the majority of this group of tumors.

Quality of CPR: An important effect modifier in cardiac arrest clinical outcomes and intervention effectiveness trials.

PubMed

Yannopoulos, Demetris; Aufderheide, Tom P; Abella, Benjamin S; Duval, Sue; Frascone, Ralph J; Goodloe, Jeffrey M; Mahoney, Brian D; Nadkarni, Vinay M; Halperin, Henry R; O'Connor, Robert; Idris, Ahamed H; Becker, Lance B; Pepe, Paul E

2015-09-01

To determine if the quality of CPR had a significant interaction with the primary study intervention in the NIH PRIMED trial. The public access database from the NIH PRIMED trial was accessed to determine if there was an interaction between quality of CPR performance, intervention, and outcome (survival to hospital discharge with modified Rankin Score (mRS) ≤ 3). Multi-centered prehospital care systems across North America. Of 8719 adult patients enrolled, CPR quality was electronically recorded for compression rate, depth, and fraction in 6199 (71.1%), 3750 (43.0%) and 6204 (71.2%) subjects, respectively. "Acceptable" quality CPR was defined prospectively as simultaneous provision of a compression rate of 100/min (± 20%), depth of 5 cm (± 20%) and fraction of > 50%. Significant interaction was considered as p < 0.05. Standard CPR with an activated versus sham (inactivated) ITD. Overall, 848 and 827 patients, respectively, in the active and sham-ITD groups had "acceptable" CPR quality performed (n = 1675). There was a significant interaction between the active and sham-ITD and compression rate, depth and fraction as well as their combinations. The strongest interaction was seen with all three parameters combined (unadjusted and adjusted interaction p-value, < 0.001). For all presenting rhythms, when "acceptable" quality of CPR was performed, use of an active-ITD increased survival to hospital discharge with mRS ≤ 3 compared to sham (61/848 [7.2%] versus 34/827 [4.1%], respectively; p = 0.006). The opposite was true for patients that did not receive "acceptable" quality of CPR. In those patients, use of an active - ITD led to significantly worse survival to hospital discharge with mRS ≤ 3 compared to sham (34/1012 [3.4%] versus 62/1061 [5.8%], p = 0.007). There was a statistically significant interaction between the quality of CPR provided, intervention, and survival to hospital discharge with mRS ≤ 3 in the NIH PRIMED trial. Quality of CPR delivered can be an underestimated effect modifier in CPR clinical trials. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Functional Characterization of FLT3 Receptor Signaling Deregulation in Acute Myeloid Leukemia by Single Cell Network Profiling (SCNP)

PubMed Central

Rosen, David B.; Minden, Mark D.; Kornblau, Steven M.; Cohen, Aileen; Gayko, Urte; Putta, Santosh; Woronicz, John; Evensen, Erik; Fantl, Wendy J.; Cesano, Alessandra

2010-01-01

Background Molecular characterization of the FMS-like tyrosine kinase 3 receptor (FLT3) in cytogenetically normal acute myeloid leukemia (AML) has recently been incorporated into clinical guidelines based on correlations between FLT3 internal tandem duplications (FLT3-ITD) and decreased disease-free and overall survival. These mutations result in constitutive activation of FLT3, and FLT3 inhibitors are currently undergoing trials in AML patients selected on FLT3 molecular status. However, the transient and partial responses observed suggest that FLT3 mutational status alone does not provide complete information on FLT3 biological activity at the individual patient level. Examination of variation in cellular responsiveness to signaling modulation may be more informative. Methodology/Principal Findings Using single cell network profiling (SCNP), cells were treated with extracellular modulators and their functional responses were quantified by multiparametric flow cytometry. Intracellular signaling responses were compared between healthy bone marrow myeloblasts (BMMb) and AML leukemic blasts characterized as FLT3 wild type (FLT3-WT) or FLT3-ITD. Compared to healthy BMMb, FLT3-WT leukemic blasts demonstrated a wide range of signaling responses to FLT3 ligand (FLT3L), including elevated and sustained PI3K and Ras/Raf/Erk signaling. Distinct signaling and apoptosis profiles were observed in FLT3-WT and FLT3-ITD AML samples, with more uniform signaling observed in FLT3-ITD AML samples. Specifically, increased basal p-Stat5 levels, decreased FLT3L induced activation of the PI3K and Ras/Raf/Erk pathways, decreased IL-27 induced activation of the Jak/Stat pathway, and heightened apoptotic responses to agents inducing DNA damage were observed in FLT3-ITD AML samples. Preliminary analysis correlating these findings with clinical outcomes suggests that classification of patient samples based on signaling profiles may more accurately reflect FLT3 signaling deregulation and provide additional information for disease characterization and management. Conclusions/Significance These studies show the feasibility of SCNP to assess modulated intracellular signaling pathways and characterize the biology of individual AML samples in the context of genetic alterations. PMID:21048955

Assessment of an Electronic Intervention in Young Women with Heavy Menstrual Bleeding.

PubMed

Dietrich, Jennifer E; Yee, Donald L; Santos, Xiomara M; Bercaw-Pratt, Jennifer L; Kurkowski, Jennifer; Soni, Heather; Lee-Kim, Youngna J; Shah, Mona D; Mahoney, Donald; Srivaths, Lakshmi V

2017-04-01

STUDY OBJECTIVE, DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: Bleeding disorders (BD) occur in up to 50% of adolescents with heavy menstrual bleeding (HMB). This presents unique challenges to health care providers because of the complexity of treating the condition and such complexity can result in difficulty with patients understanding basic information about their condition, limit communication with medical providers, and patient compliance. The aim of the study was to use an electronic approach to enhance patient compliance with medications used to treat their HMB, and to provide educational access to adolescents with BD. This was a prospective cohort study involving patients in a Young Women's Bleeding Disorder Clinic at a single children's hospital. Subjects were given an iPod Touch (Apple Inc, Cupertino, CA) device (ITD), preloaded with the iPeriod (Winkpass Creations) application. Participants recorded information about their BD that they learned about on BD Web sites, and menses, and medications. Electronic and charted data were collected to monitor compliance with prescribed treatment regimens. All ITD allowed Wi-Fi access to allow teens to explore BD Web sites and knowledge was assessed. Twenty-three of 45 subjects completed the study. The mean age was 14.1 ± 1.9 years. Subjects who were compliant with the ITD (group 1), charted on baseline symptoms, menstrual flow (83.3%), cramps (100%, 23/23), breakthrough bleeding (95.6%, 22/23), mood (95.6%, 22/23), and medication use (91.7%) for a mean of 9.3 ± 3.1 months. Subjects who were nonusers (group 2) did not report on symptoms, their condition, or medication use in the device (n = 22). More than 75% (17/23) of subjects in group 1 used hormones alone or hormones with antifibrinolytic agents to control HMB. No subjects stopped or missed medications who were in group 1 intentionally, and also there were 9 enrollees within this same group who missed a medication related to awaiting the prescription to be filled from pharmacy. In group 2, 17 enrollees missed medications, resulting in 19% (4/22) of these enrollees being admitted to hospital for 1-2 days. In addition, enrollees in group 2 missed more medications on average compared with group 1. No subjects in group 1 required admission for HMB treatment failure during the study period, compared with those in group 2 (P = .006). All subjects in group 1 reported accessing Web sites using their ITD to learn about their BD. Groups 1 and 2 did not differ in the number of medications that were prescribed during the time frame (P = .77) or the number of follow-up clinic visits (P = .49). Furthermore, those in group 1 reported fewer breakthrough bleeding episodes than those in group 2 according to clinic notes (P = .03). Users of the ITD were given a set of knowledge questions. Group 2 subjects were not consistent users of the ITD use and did not complete the knowledge questions. Group 1 and 2 could not be compared with regard to knowledge as a result. ITD is an excellent tool for adolescents with HMB and BD to allow self-monitoring, provider monitoring, and improve educational access through engaging technology; compliance with device use was associated with several parameters suggestive of improved clinical outcomes. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Biometric and structural ocular manifestations of Marfan syndrome.

PubMed

Gehle, Petra; Goergen, Barbara; Pilger, Daniel; Ruokonen, Peter; Robinson, Peter N; Salchow, Daniel J

2017-01-01

To study biometric and structural ocular manifestations of Marfan syndrome (MFS). Observational, retrospective, comparative cohort study in a tertiary referral center on 285 MFS patients and 267 controls. Structural and biometric ocular characteristic were compared. MFS eyes were longer (axial length 24.25 ± 1.74 mm versus 23.89 ± 1.31 mm, p < 0.001) and had a flatter cornea than control eyes (mean keratometry 41.78 ± 1.80 diopters (D) versus 43.05 ± 1.51 D, p < 0.001). Corneal astigmatism was greater and the central cornea was thinner in MFS eyes (530.14 ± 41.31 μm versus 547.02 ± 39.18 μm, p < 0.001). MFS eyes were more myopic than control eyes (spherical equivalent -2.16 ± 3.75 D versus -1.17 ± 2.58 D, p < 0.001). Visual acuity was reduced (0.13 ± 0.25 logMAR versus 0.05 ± 0.18 logMAR, p < 0.001) and intraocular pressure was lower in MFS eyes (14.6 ± 3.4 mmHg versus 15.1 ± 3.2 mmHg, p = 0.01). Iris transillumination defects (ITD) were significantly more common in MFS eyes (odds ratio for MFS in the presence of ITD, 3.7). Ectopia lentis (EL) was only present in MFS eyes (33.4%). History of retinal detachment was significantly more common in MFS eyes. Glaucoma was equally common in both groups. ITD and EL are most characteristic findings in MFS. ITD and corneal curvature should be studied as diagnostic criteria for MFS. Visual acuity is reduced in MFS. MFS patients need regular eye exams to identify serious ocular complications.

Biometric and structural ocular manifestations of Marfan syndrome

PubMed Central

Gehle, Petra; Goergen, Barbara; Pilger, Daniel; Ruokonen, Peter; Robinson, Peter N.

2017-01-01

Background To study biometric and structural ocular manifestations of Marfan syndrome (MFS). Methods Observational, retrospective, comparative cohort study in a tertiary referral center on 285 MFS patients and 267 controls. Structural and biometric ocular characteristic were compared. Results MFS eyes were longer (axial length 24.25 ± 1.74 mm versus 23.89 ± 1.31 mm, p < 0.001) and had a flatter cornea than control eyes (mean keratometry 41.78 ± 1.80 diopters (D) versus 43.05 ± 1.51 D, p < 0.001). Corneal astigmatism was greater and the central cornea was thinner in MFS eyes (530.14 ± 41.31 μm versus 547.02 ± 39.18 μm, p < 0.001). MFS eyes were more myopic than control eyes (spherical equivalent -2.16 ± 3.75 D versus -1.17 ± 2.58 D, p < 0.001). Visual acuity was reduced (0.13 ± 0.25 logMAR versus 0.05 ± 0.18 logMAR, p < 0.001) and intraocular pressure was lower in MFS eyes (14.6 ± 3.4 mmHg versus 15.1 ± 3.2 mmHg, p = 0.01). Iris transillumination defects (ITD) were significantly more common in MFS eyes (odds ratio for MFS in the presence of ITD, 3.7). Ectopia lentis (EL) was only present in MFS eyes (33.4%). History of retinal detachment was significantly more common in MFS eyes. Glaucoma was equally common in both groups. Conclusions ITD and EL are most characteristic findings in MFS. ITD and corneal curvature should be studied as diagnostic criteria for MFS. Visual acuity is reduced in MFS. MFS patients need regular eye exams to identify serious ocular complications. PMID:28931008

Evaluation of the kinase domain of c-KIT in canine cutaneous mast cell tumors

PubMed Central

Webster, Joshua D; Kiupel, Matti; Yuzbasiyan-Gurkan, Vilma

2006-01-01

Background Mutations in the c-KIT proto-oncogene have been implicated in the progression of several neoplastic diseases, including gastrointestinal stromal tumors and mastocytosis in humans, and cutaneous mast cell tumors (MCTs) in canines. Mutations in human mastocytosis patients primarily occur in c-KIT exon 17, which encodes a portion of its kinase domain. In contrast, deletions and internal tandem duplication (ITD) mutations are found in the juxtamembrane domain of c-KIT in approximately 15% of canine MCTs. In addition, ITD c-KIT mutations are significantly associated with aberrant KIT protein localization in canine MCTs. However, some canine MCTs have aberrant KIT localization but lack ITD c-KIT mutations, suggesting that other mutations or other factors may be responsible for aberrant KIT localization in these tumors. Methods In order to characterize the prevalence of mutations in the phospho-transferase portion of c-KIT's kinase domain in canine MCTs exons 16–20 of 33 canine MCTs from 33 dogs were amplified and sequenced. Additionally, in order to determine if mutations in c-KIT exon 17 are responsible for aberrant KIT localization in MCTs that lack juxtamembrane domain c-KIT mutations, c-KIT exon 17 was amplified and sequenced from 18 canine MCTs that showed an aberrant KIT localization pattern but did not have ITD c-KIT mutations. Results No mutations or polymorphisms were identified in exons 16–20 of any of the MCTs examined. Conclusion In conclusion, mutations in the phospho-transferase portion of c-KIT's kinase domain do not play an important role in the progression of canine cutaneous MCTs, or in the aberrant localization of KIT in canine MCTs. PMID:16579858

The DYT1 gene on 9q34 is responsible for most cases of early limb-onset idiopathic torsion dystonia in non-Jews

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kramer, P.L.; Heiman, G.A.; Leon, D. de

1994-09-01

Idiopathic torsion dystonia (ITD) is characterized by involuntary twisting movements and postures. A gene for this disorder, DYT1, was mapped to chromosome 9q34 in 12 Ashkenazi Jewish (AJ) families and one large non-Jewish kindred. In the AJ population, strong linkage disequilibrium exists between DYT1 and adjacent markers within a 2-cM region. The associated haplotype occurs in >90% of early limb-onset AJ cases. The authors examined seven non-Jewish ITD families of northern European and French Canadian descent to determine the extent to which early-onset ITD in non-Jews maps to DYT1. Results are consistent with linkage to the DYT1 region. Affected individualsmore » in these families are clinically similar to the AJ cases, i.e., the site of onset is predominantly in the limbs and at least one individual in each pedigree had onset before age 12 years. None carries the AJ haplotype; therefore, they probably represent different mutations in the DYT1 gene. The two French Canadian families, however, display the same haplotype. Estimates of penetrance in non-Jewish families range from .40 to .75. They identified disease gene carriers and, with adjustments for age at onset, obtained a direct estimate of penetrance of .46. This is consistent with estimates of 30%-40% in the AJ population. Two other non-Jewish families with atypical ITD (later onset and/or cranial or cervical involvement) are not linked to DYT1, which indicates involvement of other genes in dystonia. 26 refs., 1 fig., 3 tabs.« less

Development of the sound localization cues in cats

NASA Astrophysics Data System (ADS)

Tollin, Daniel J.

2004-05-01

Cats are a common model for developmental studies of the psychophysical and physiological mechanisms of sound localization. Yet, there are few studies on the development of the acoustical cues to location in cats. The magnitude of the three main cues, interaural differences in time (ITDs) and level (ILDs), and monaural spectral shape cues, vary with location in adults. However, the increasing interaural distance associated with a growing head and pinnae during development will result in cues that change continuously until maturation is complete. Here, we report measurements, in cats aged 1 week to adulthood, of the physical dimensions of the head and pinnae and the localization cues, computed from measurements of directional transfer functions. At 1 week, ILD depended little on azimuth for frequencies <6-7 kHz, maximum ITD was 175 μs, and for sources varying in elevation, a prominent spectral notch was located at higher frequencies than in the older cats. As cats develop, the spectral cues and the frequencies at which ILDs become substantial (>10 dB) shift to lower frequencies, and the maximum ITD increases to nearly 370 μs. Changes in the cues are correlated with the increasing size of the head and pinnae. [Work supported by NIDCD DC05122.

Tympanic-response transition in ICE: Dependence upon the interaural cavity's shape

NASA Astrophysics Data System (ADS)

van Hemmen, J. Leo

More than half of the terrestrial vertebrates have internally coupled ears (ICE), where an interaural cavity of some shape acoustically couples the eardrums. Hence what the animal's auditory system perceives is not the outside stimulus but the superposition of outside and internal pressure on the two eardrums, resulting in so-called internal time and level difference, iTD and iLD, which are keys to sound localization. For a cylindrical shape, it is known that on the frequency axis two domains with appreciably increased iTD and iLD values occur, segregated by the eardrum's fundamental frequency. Here we analyze the case where, as in nature, two or more canals couple the eardrums so that, by opening one of the canals, the animal can switch from coupled to two independent ears. We analyze the iTD/iLD transition and its dependence upon the interaural cavity's size and shape. As compared to a single connection, the iTD performance is preserved to a large extent. Nonetheless, the price to pay for freedom of choice is a reduced frequency range with high-iTD plateau. Work done in collaboration with A.P. Vedurmudi; partially supported by BCCN-Munich.

Partonic quasidistributions of the proton and pion from transverse-momentum distributions

NASA Astrophysics Data System (ADS)

Broniowski, Wojciech; Arriola, Enrique Ruiz

2018-02-01

The parton quasidistribution functions (QDFs) of Ji have been found by Radyushkin to be directly related to the transverse momentum distributions (TMDs), to the pseudodistributions, and to the Ioffe-time distributions (ITDs). This makes the QDF results at finite longitudinal momentum of the hadron interesting in their own right. Moreover, the QDF-TMD relation provides a gateway to the pertinent QCD evolution, with respect to the resolution scale Q , for the QDFs. Using the Kwieciński evolution equations and well established parametrizations at a low initial scale, we analyze the QCD evolution of quark and gluon QDF components of the proton and the pion. We discuss the resulting breaking of the longitudinal-transverse factorization and show that it has little impact on QDFs at the relatively low scales presently accessible on the lattice, but the effect is visible in reduced ITDs at sufficiently large values of the Ioffe time. Sum rules involving derivatives of ITDs and moments of the parton distribution functions (PDFs) are applied to the European Twisted Mass Collaboration lattice data. This allows us for a lattice determination of the transverse-momentum width of the TMDs from QDF studies.

Slow Temporal Integration Enables Robust Neural Coding and Perception of a Cue to Sound Source Location.

PubMed

Brown, Andrew D; Tollin, Daniel J

2016-09-21

In mammals, localization of sound sources in azimuth depends on sensitivity to interaural differences in sound timing (ITD) and level (ILD). Paradoxically, while typical ILD-sensitive neurons of the auditory brainstem require millisecond synchrony of excitatory and inhibitory inputs for the encoding of ILDs, human and animal behavioral ILD sensitivity is robust to temporal stimulus degradations (e.g., interaural decorrelation due to reverberation), or, in humans, bilateral clinical device processing. Here we demonstrate that behavioral ILD sensitivity is only modestly degraded with even complete decorrelation of left- and right-ear signals, suggesting the existence of a highly integrative ILD-coding mechanism. Correspondingly, we find that a majority of auditory midbrain neurons in the central nucleus of the inferior colliculus (of chinchilla) effectively encode ILDs despite complete decorrelation of left- and right-ear signals. We show that such responses can be accounted for by relatively long windows of bilateral excitatory-inhibitory interaction, which we explicitly measure using trains of narrowband clicks. Neural and behavioral data are compared with the outputs of a simple model of ILD processing with a single free parameter, the duration of excitatory-inhibitory interaction. Behavioral, neural, and modeling data collectively suggest that ILD sensitivity depends on binaural integration of excitation and inhibition within a ≳3 ms temporal window, significantly longer than observed in lower brainstem neurons. This relatively slow integration potentiates a unique role for the ILD system in spatial hearing that may be of particular importance when informative ITD cues are unavailable. In mammalian hearing, interaural differences in the timing (ITD) and level (ILD) of impinging sounds carry critical information about source location. However, natural sounds are often decorrelated between the ears by reverberation and background noise, degrading the fidelity of both ITD and ILD cues. Here we demonstrate that behavioral ILD sensitivity (in humans) and neural ILD sensitivity (in single neurons of the chinchilla auditory midbrain) remain robust under stimulus conditions that render ITD cues undetectable. This result can be explained by "slow" temporal integration arising from several-millisecond-long windows of excitatory-inhibitory interaction evident in midbrain, but not brainstem, neurons. Such integrative coding can account for the preservation of ILD sensitivity despite even extreme temporal degradations in ecological acoustic stimuli. Copyright © 2016 the authors 0270-6474/16/369908-14$15.00/0.

The relation between working memory capacity and auditory lateralization in children with auditory processing disorders.

PubMed

Moossavi, Abdollah; Mehrkian, Saiedeh; Lotfi, Yones; Faghihzadeh, Soghrat; sajedi, Hamed

2014-11-01

Auditory processing disorder (APD) describes a complex and heterogeneous disorder characterized by poor speech perception, especially in noisy environments. APD may be responsible for a range of sensory processing deficits associated with learning difficulties. There is no general consensus about the nature of APD and how the disorder should be assessed or managed. This study assessed the effect of cognition abilities (working memory capacity) on sound lateralization in children with auditory processing disorders, in order to determine how "auditory cognition" interacts with APD. The participants in this cross-sectional comparative study were 20 typically developing and 17 children with a diagnosed auditory processing disorder (9-11 years old). Sound lateralization abilities investigated using inter-aural time (ITD) differences and inter-aural intensity (IID) differences with two stimuli (high pass and low pass noise) in nine perceived positions. Working memory capacity was evaluated using the non-word repetition, and forward and backward digits span tasks. Linear regression was employed to measure the degree of association between working memory capacity and localization tests between the two groups. Children in the APD group had consistently lower scores than typically developing subjects in lateralization and working memory capacity measures. The results showed working memory capacity had significantly negative correlation with ITD errors especially with high pass noise stimulus but not with IID errors in APD children. The study highlights the impact of working memory capacity on auditory lateralization. The finding of this research indicates that the extent to which working memory influences auditory processing depend on the type of auditory processing and the nature of stimulus/listening situation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Evolution of the Sabin Vaccine into Pathogenic Derivatives without Appreciable Changes in Antigenic Properties: Need for Improvement of Current Poliovirus Surveillance▿

PubMed Central

Yakovenko, Maria L.; Korotkova, Ekaterina A.; Ivanova, Olga E.; Eremeeva, Tatyana P.; Samoilovich, Elena; Uhova, Iryna; Gavrilin, Gene V.; Agol, Vadim I.

2009-01-01

The Sabin oral polio vaccine (OPV) may evolve into pathogenic viruses, causing sporadic cases and outbreaks of poliomyelitis. Such vaccine-derived polioviruses (VDPV) generally exhibit altered antigenicity. The current paradigm to distinguish VDPV from OPV and wild polioviruses is to characterize primarily those poliovirus isolates that demonstrate deviations from OPV in antigenic and genetic intratypic differentiation (ITD) tests. Here we report on two independent cases of poliomyelitis caused by VDPVs with “Sabin-like” properties in several ITD assays. The results suggest the existence of diverse pathways of OPV evolution and necessitate improvement of poliovirus surveillance, which currently potentially misses this class of VDPV. PMID:19129444

Evolution of the Sabin vaccine into pathogenic derivatives without appreciable changes in antigenic properties: need for improvement of current poliovirus surveillance.

PubMed

Yakovenko, Maria L; Korotkova, Ekaterina A; Ivanova, Olga E; Eremeeva, Tatyana P; Samoilovich, Elena; Uhova, Iryna; Gavrilin, Gene V; Agol, Vadim I

2009-04-01

The Sabin oral polio vaccine (OPV) may evolve into pathogenic viruses, causing sporadic cases and outbreaks of poliomyelitis. Such vaccine-derived polioviruses (VDPV) generally exhibit altered antigenicity. The current paradigm to distinguish VDPV from OPV and wild polioviruses is to characterize primarily those poliovirus isolates that demonstrate deviations from OPV in antigenic and genetic intratypic differentiation (ITD) tests. Here we report on two independent cases of poliomyelitis caused by VDPVs with "Sabin-like" properties in several ITD assays. The results suggest the existence of diverse pathways of OPV evolution and necessitate improvement of poliovirus surveillance, which currently potentially misses this class of VDPV.

Anatomical limits on interaural time differences: an ecological perspective

PubMed Central

Hartmann, William M.; Macaulay, Eric J.

2013-01-01

Human listeners, and other animals too, use interaural time differences (ITD) to localize sounds. If the sounds are pure tones, a simple frequency factor relates the ITD to the interaural phase difference (IPD), for which there are known iso-IPD boundaries, 90°, 180°… defining regions of spatial perception. In this article, iso-IPD boundaries for humans are translated into azimuths using a spherical head model (SHM), and the calculations are checked by free-field measurements. The translated boundaries provide quantitative tests of an ecological interpretation for the dramatic onset of ITD insensitivity at high frequencies. According to this interpretation, the insensitivity serves as a defense against misinformation and can be attributed to limits on binaural processing in the brainstem. Calculations show that the ecological explanation passes the tests only if the binaural brainstem properties evolved or developed consistent with heads that are 50% smaller than current adult heads. Measurements on more realistic head shapes relax that requirement only slightly. The problem posed by the discrepancy between the current head size and a smaller, ideal head size was apparently solved by the evolution or development of central processes that discount large IPDs in favor of interaural level differences. The latter become more important with increasing head size. PMID:24592209

Sorafenib Dose Recommendation in Acute Myeloid Leukemia Based on Exposure-FLT3 Relationship.

PubMed

Liu, Tao; Ivaturi, Vijay; Sabato, Philip; Gobburu, Jogarao V S; Greer, Jacqueline M; Wright, John J; Smith, B Douglas; Pratz, Keith W; Rudek, Michelle A

2018-04-27

Sorafenib administered at the approved dose continuously is not tolerated long-term in patients with acute myeloid leukemia (AML). The purpose of this study was to optimize the dosing regimen by characterizing the sorafenib exposure-response relationship in patients with AML. A one-compartment model with a transit absorption compartment and enterohepatic recirculation described the exposure. The relationship between sorafenib exposure and target modulation of kinase targets (FMS-like tyrosine kinase 3 (FLT3)-ITD and extracellular signal-regulated kinase (ERK)) were described by an inhibitory maximum effect (E max ) model. Sorafenib could inhibit FLT3-ITD activity by 100% with an IC 50 of 69.3 ng/mL and ERK activity by 84% with an IC 50 of 85.7 ng/mL (both adjusted for metabolite potency). Different dosing regimens utilizing 200 or 400 mg at varying frequencies were simulated based on the exposure-response relationship. Simulations demonstrate that a 200 mg twice daily (b.i.d.) dosing regimen showed similar FLT3-ITD and ERK inhibitory activity compared with 400 mg b.i.d. and is recommended in further clinical trials in patients with AML. © 2018 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Lateralization and Binaural Interaction of Middle-Latency and Late-Brainstem Components of the Auditory Evoked Response.

PubMed

Dykstra, Andrew R; Burchard, Daniel; Starzynski, Christian; Riedel, Helmut; Rupp, Andre; Gutschalk, Alexander

2016-08-01

We used magnetoencephalography to examine lateralization and binaural interaction of the middle-latency and late-brainstem components of the auditory evoked response (the MLR and SN10, respectively). Click stimuli were presented either monaurally, or binaurally with left- or right-leading interaural time differences (ITDs). While early MLR components, including the N19 and P30, were larger for monaural stimuli presented contralaterally (by approximately 30 and 36 % in the left and right hemispheres, respectively), later components, including the N40 and P50, were larger ipsilaterally. In contrast, MLRs elicited by binaural clicks with left- or right-leading ITDs did not differ. Depending on filter settings, weak binaural interaction could be observed as early as the P13 but was clearly much larger for later components, beginning at the P30, indicating some degree of binaural linearity up to early stages of cortical processing. The SN10, an obscure late-brainstem component, was observed consistently in individuals and showed linear binaural additivity. The results indicate that while the MLR is lateralized in response to monaural stimuli-and not ITDs-this lateralization reverses from primarily contralateral to primarily ipsilateral as early as 40 ms post stimulus and is never as large as that seen with fMRI.

Binaural hearing in children using Gaussian enveloped and transposed tones.

PubMed

Ehlers, Erica; Kan, Alan; Winn, Matthew B; Stoelb, Corey; Litovsky, Ruth Y

2016-04-01

Children who use bilateral cochlear implants (BiCIs) show significantly poorer sound localization skills than their normal hearing (NH) peers. This difference has been attributed, in part, to the fact that cochlear implants (CIs) do not faithfully transmit interaural time differences (ITDs) and interaural level differences (ILDs), which are known to be important cues for sound localization. Interestingly, little is known about binaural sensitivity in NH children, in particular, with stimuli that constrain acoustic cues in a manner representative of CI processing. In order to better understand and evaluate binaural hearing in children with BiCIs, the authors first undertook a study on binaural sensitivity in NH children ages 8-10, and in adults. Experiments evaluated sound discrimination and lateralization using ITD and ILD cues, for stimuli with robust envelope cues, but poor representation of temporal fine structure. Stimuli were spondaic words, Gaussian-enveloped tone pulse trains (100 pulse-per-second), and transposed tones. Results showed that discrimination thresholds in children were adult-like (15-389 μs for ITDs and 0.5-6.0 dB for ILDs). However, lateralization based on the same binaural cues showed higher variability than seen in adults. Results are discussed in the context of factors that may be responsible for poor representation of binaural cues in bilaterally implanted children.

Lestaurtinib, a multitargeted tyrosine kinase inhibitor: from bench to bedside.

PubMed

Shabbir, Munira; Stuart, Robert

2010-03-01

Internal tandem duplication of the fms-like tyrosine kinase 3 (FLT3) gene (FLT3-ITD) is a common recurring mutation in acute myeloid leukemia (AML) with normal karyotype, and the presence of FLT3-ITD confers a poor prognosis on this large subgroup of AML patients. Since the discovery of lestaurtinib as a potent FLT3 inhibitor, in 1985, there has been considerable interest in the development of this agent (CEP-701, Cephalon, Frazer, PA, USA) for treatment of this population. An extensive literature search was conducted that included published articles and abstracts on the preclinical and clinical development of this agent spanning the last decade. The review describes the historical development of this agent and reviews the available preclinical and clinical data on lestaurtinib and expands on potential future directions in development of this agent. Lestaurtinib is a multi targeted tyrosine kinase inhibitor which has been shown to potently inhibit FLT3 at nanomolar concentrations in preclinical studies, leading to its rapid development as a potential targeted agent for treatment of AML. Phase I studies have shown lestaturtinib to be an active agent particularly when used in combination with cytotoxic drugs. Currently, Phase II and Phase III studies are underway aiming to establish the future of this agent as a treatment option for patients with FLT3-ITD AML.

Comparison of Interaural Electrode Pairing Methods for Bilateral Cochlear Implants

PubMed Central

Dietz, Mathias

2015-01-01

In patients with bilateral cochlear implants (CIs), pairing matched interaural electrodes and stimulating them with the same frequency band is expected to facilitate binaural functions such as binaural fusion, localization, and spatial release from masking. Because clinical procedures typically do not include patient-specific interaural electrode pairing, it remains the case that each electrode is allocated to a generic frequency range, based simply on the electrode number. Two psychoacoustic techniques for determining interaurally paired electrodes have been demonstrated in several studies: interaural pitch comparison and interaural time difference (ITD) sensitivity. However, these two methods are rarely, if ever, compared directly. A third, more objective method is to assess the amplitude of the binaural interaction component (BIC) derived from electrically evoked auditory brainstem responses for different electrode pairings; a method has been demonstrated to be a potential candidate for bilateral CI users. Here, we tested all three measures in the same eight CI users. We found good correspondence between the electrode pair producing the largest BIC and the electrode pair producing the maximum ITD sensitivity. The correspondence between the pairs producing the largest BIC and the pitch-matched electrode pairs was considerably weaker, supporting the previously proposed hypothesis that whilst place pitch might adapt over time to accommodate mismatched inputs, sensitivity to ITDs does not adapt to the same degree. PMID:26631108

The outcome of allogeneic hematopoietic cell transplantation for children with FMS-like tyrosine kinase 3 internal tandem duplication-positive acute myelogenous leukemia.

PubMed

Schechter, Tal; Gassas, Adam; Chen, Heidi; Pollard, Jessica; Meshinchi, Soheil; Zaidman, Irina; Hitzler, Johann; Abdelhaleem, Mohamed; Ho, Richard; Domm, Jennifer; Woolfrey, Ann; Frangoul, Haydar

2015-01-01

FMS-like tyrosine kinase 3 (FLT3) internal tandem duplication (ITD) is a somatic mutation associated with poor outcome when treated with chemotherapy alone. In children, hematopoietic stem cell transplantation (HSCT) is recommended, but very limited data on outcome are reported. We determined the outcome of 29 children with FLT3/ITD-positive acute myelogenous leukemia (AML) who underwent allogeneic HSCT in 4 pediatric centers. Eleven patients (38%) received matched related donor hematopoietic stem cells and 18 (62%) received alternative donors. Eighteen patients (62%) received total body irradiation (TBI)-based regimens. No patients experienced transplantation-related mortality. Eleven patients (38%) experienced relapsed disease. The cumulative incidence of relapse at 2 years was 34.7% (95% confidence interval [CI], 20.4% to 54.9%). Two-year disease-free survival (DFS) and overall survival (OS) were 65.3% (95% CI, 45.1% to 79.6%) and 82.2% (95% CI, 58.5% to 91.3%), respectively. There was no difference in the DFS of patients who received transplants from related donors versus the DFS of those who received transplants from alternative donors (hazard ratio [HR], 2.64; 95% CI, .79 to 8.76; P = .10), using univariate analysis. Patients with higher FLT3/ITD ratio at diagnosis had significantly worse DFS (HR, 1.42; 95% CI, 1.04 to 1.93; P = .03). The use of TBI in the preparative regimen was associated with superior DFS (HR, .29; 95% CI, .08 to .99; P = .04) and OS (HR, .07; 95% CI, .01 to .62; P = .002). We conclude that allogeneic HSCT improves DFS and OS in children with FLT3/ITD-positive AML compared with what has been reported in those treated with chemotherapy alone. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Clinical and hemodynamic comparison of 15:2 and 30:2 compression-to-ventilation ratios for cardiopulmonary resuscitation.

PubMed

Yannopoulos, Demetris; Aufderheide, Tom P; Gabrielli, Andrea; Beiser, David G; McKnite, Scott H; Pirrallo, Ronald G; Wigginton, Jane; Becker, Lance; Vanden Hoek, Terry; Tang, Wanchun; Nadkarni, Vinay M; Klein, John P; Idris, Ahamed H; Lurie, Keith G

2006-05-01

To compare cardiopulmonary resuscitation (CPR) with a compression to ventilation (C:V) ratio of 15:2 vs. 30:2, with and without use of an impedance threshold device (ITD). Prospective randomized animal and manikin study. Animal laboratory and emergency medical technician training facilities. Twenty female pigs and 20 Basic Life Support (BLS)-certified rescuers. Acid-base status, cerebral, and cardiovascular hemodynamics were evaluated in 18 pigs in cardiac arrest randomized to a C:V ratio of 15:2 or 30:2. After 6 mins of cardiac arrest and 6 mins of CPR, an ITD was added. Compared to 15:2, 30:2 significantly increased diastolic blood pressure (20 +/- 1 to 26 +/- 1; p < .01); coronary perfusion pressure (18 +/- 1 to 25 +/- 2; p = .04); cerebral perfusion pressure (16 +/- 3 to 18 +/- 3; p = .07); common carotid blood flow (48 +/- 5 to 82 +/- 5 mL/min; p < .001); end-tidal CO2 (7.7 +/- 0.9 to 15.7 +/- 2.4; p < .0001); and mixed venous oxygen saturation (26 +/- 5 to 36 +/- 5, p < .05). Hemodynamics improved further with the ITD. Oxygenation and arterial pH were similar. Only one of nine pigs had return of spontaneous circulation with 15:2, vs. six of nine with 30:2 (p < 0.03). HUMANS: Fatigue and quality of CPR performance were evaluated in 20 BLS-certified rescuers randomized to perform CPR for 5 mins at 15:2 or 30:2 on a recording CPR manikin. There were no significant differences in the quality of CPR performance or measurement of fatigue. Significantly more compressions per minute were delivered with 30:2 in both the animal and human studies. These data strongly support the contention that a ratio of 30:2 is superior to 15:2 during manual CPR and that the ITD further enhances circulation with both C:V ratios.

Toward an Ultralow-Power Onboard Processor for Tongue Drive System

PubMed Central

Viseh, Sina; Ghovanloo, Maysam; Mohsenin, Tinoosh

2015-01-01

The Tongue Drive System (TDS) is a new unobtrusive, wireless, and wearable assistive device that allows for real-time tracking of the voluntary tongue motion in the oral space for communication, control, and navigation applications. The latest TDS prototype appears as a wireless headphone and has been tested in human subject trials. However, the robustness of the external TDS (eTDS) in real-life outdoor conditions may not meet safety regulations because of the limited mechanical stability of the headset. The intraoral TDS (iTDS), which is in the shape of a dental retainer, firmly clasps to the upper teeth and resists sensor misplacement. However, the iTDS has more restrictions on its dimensions, limiting the battery size and consequently requiring a considerable reduction in its power consumption to operate over an extended period of two days on a single charge. In this brief, we propose an ultralow-power local processor for the TDS that performs all signal processing on the transmitter side, following the sensors. Assuming the TDS user on average issuing one command/s, implementing the computational engine reduces the data volume that needs to be wirelessly transmitted to a PC or smartphone by a factor of 1500×, from 12 kb/s to ~8 b/s. The proposed design is implemented on an ultralow-power IGLOO nano field-programmable gate array (FPGA) and is tested on AGLN250 prototype board. According to our post-place-and-route results, implementing the engine on the FPGA significantly drops the required data transmission, while an application-specific integrated circuit (ASIC) implementation in a 65-nm CMOS results in a 15× power saving compared to the FPGA solution and occupies a 0.02-mm2 footprint. As a result, the power consumption and size of the iTDS will be significantly reduced through the use of a much smaller rechargeable battery. Moreover, the system can operate longer following every recharge, improving the iTDS usability. PMID:26185489

Toward an Ultralow-Power Onboard Processor for Tongue Drive System.

PubMed

Viseh, Sina; Ghovanloo, Maysam; Mohsenin, Tinoosh

2015-02-01

The Tongue Drive System (TDS) is a new unobtrusive, wireless, and wearable assistive device that allows for real-time tracking of the voluntary tongue motion in the oral space for communication, control, and navigation applications. The latest TDS prototype appears as a wireless headphone and has been tested in human subject trials. However, the robustness of the external TDS (eTDS) in real-life outdoor conditions may not meet safety regulations because of the limited mechanical stability of the headset. The intraoral TDS (iTDS), which is in the shape of a dental retainer, firmly clasps to the upper teeth and resists sensor misplacement. However, the iTDS has more restrictions on its dimensions, limiting the battery size and consequently requiring a considerable reduction in its power consumption to operate over an extended period of two days on a single charge. In this brief, we propose an ultralow-power local processor for the TDS that performs all signal processing on the transmitter side, following the sensors. Assuming the TDS user on average issuing one command/s, implementing the computational engine reduces the data volume that needs to be wirelessly transmitted to a PC or smartphone by a factor of 1500×, from 12 kb/s to ~8 b/s. The proposed design is implemented on an ultralow-power IGLOO nano field-programmable gate array (FPGA) and is tested on AGLN250 prototype board. According to our post-place-and-route results, implementing the engine on the FPGA significantly drops the required data transmission, while an application-specific integrated circuit (ASIC) implementation in a 65-nm CMOS results in a 15× power saving compared to the FPGA solution and occupies a 0.02-mm 2 footprint. As a result, the power consumption and size of the iTDS will be significantly reduced through the use of a much smaller rechargeable battery. Moreover, the system can operate longer following every recharge, improving the iTDS usability.

Effect of 3 Different Doses of Intrathecal Dexmedetomidine (2.5µg, 5µg, and 10 µg) on Subarachnoid Block Characteristics: A Prospective Randomized Double Blind Dose-Response Trial.

PubMed

Gupta, Mayank; Gupta, Priyanka; Singh, Dhananjay Kumar

2016-03-01

The extended analgesic efficacy of intrathecal dexmedetomidine (ITD) has been investigated in a few clinical trials; however, there is a lack of conclusive evidence upon its ideal dosage. To elucidate the dose-response relationship between ITD and subarachnoid block characteristics, particularly the duration of analgesia and differential analgesia (DA: defined as time difference from the offset of motor blockade to the first analgesic requirement on numerical rating scale = 4.0). Prospective, randomized double blind active control trial. Medical college teaching hospital. Ninety adult (18 - 60 years) patients undergoing elective lower abdominal and lower limb surgeries were randomized into 3 groups to receive intrathecal 0.5% bupivacaine 3 mL with 2.5 µg (group BD2.5), 5µg (group BD5), or 10 µg (group BD10) dexmedetomidine in 0.5 mL normal saline. The 2 segment sensory regression times (TSSRT), duration of motor blockade analgesia, DA, and perioperative adverse effects were assessed. The primary outcome was duration of analgesia and DA. ANOVA, Kruskal Wallis test, Chi-square (x2), and Fisher's exact test, significance: P < 0.05. The onset of sensory block was significantly earlier in group BD10 compared with group BD5 (P = 0.035) and BD2.5 (P = 0.010) while the onset of motor block was significantly earlier in group BD10 compared with BD2.5 (P = 0.020). There was a significant and dose-dependent prolongation of the duration of sensory block (127.50, 149.17, and 187.50 minutes; P < 0.001), motor block (258.50, 331, and 365 minutes; P < 0.001), analgesia (306.17, 396.50, and 512 minutes; P < 0.001), and DA (47.67, 65.50, and147 minutes; P < 0.001) with escalating doses of ITD, respectively. Group BD10 required significantly fewer rescue analgesics compared with other 2 groups (P = 0.001). Except for mild sedation which was significantly higher in group BD10; all the groups were comparable with respect to hemodynamic and other adverse effects. Lack of placebo group, exclusion of higher doses (15µg) of ITD, and short duration of postoperative follow-up. The addition of 10 µg compared with 2.5 µg or 5µg ITD to 0.5% hyperbaric bupivacaine is associated with significantly earlier onset of sensory and motor block as well as prolonged duration of sensory block, motor block, analgesia, and DA with a comparable adverse effect profile.

Neuromagnetic recordings reveal the temporal dynamics of auditory spatial processing in the human cortex.

PubMed

Tiitinen, Hannu; Salminen, Nelli H; Palomäki, Kalle J; Mäkinen, Ville T; Alku, Paavo; May, Patrick J C

2006-03-20

In an attempt to delineate the assumed 'what' and 'where' processing streams, we studied the processing of spatial sound in the human cortex by using magnetoencephalography in the passive and active recording conditions and two kinds of spatial stimuli: individually constructed, highly realistic spatial (3D) stimuli and stimuli containing interaural time difference (ITD) cues only. The auditory P1m, N1m, and P2m responses of the event-related field were found to be sensitive to the direction of sound source in the azimuthal plane. In general, the right-hemispheric responses to spatial sounds were more prominent than the left-hemispheric ones. The right-hemispheric P1m and N1m responses peaked earlier for sound sources in the contralateral than for sources in the ipsilateral hemifield and the peak amplitudes of all responses reached their maxima for contralateral sound sources. The amplitude of the right-hemispheric P2m response reflected the degree of spatiality of sound, being twice as large for the 3D than ITD stimuli. The results indicate that the right hemisphere is specialized in the processing of spatial cues in the passive recording condition. Minimum current estimate (MCE) localization revealed that temporal areas were activated both in the active and passive condition. This initial activation, taking place at around 100 ms, was followed by parietal and frontal activity at 180 and 200 ms, respectively. The latter activations, however, were specific to attentional engagement and motor responding. This suggests that parietal activation reflects active responding to a spatial sound rather than auditory spatial processing as such.

Performance Analysis of IIUM Wireless Campus Network

NASA Astrophysics Data System (ADS)

Abd Latif, Suhaimi; Masud, Mosharrof H.; Anwar, Farhat

2013-12-01

International Islamic University Malaysia (IIUM) is one of the leading universities in the world in terms of quality of education that has been achieved due to providing numerous facilities including wireless services to every enrolled student. The quality of this wireless service is controlled and monitored by Information Technology Division (ITD), an ISO standardized organization under the university. This paper aims to investigate the constraints of wireless campus network of IIUM. It evaluates the performance of the IIUM wireless campus network in terms of delay, throughput and jitter. QualNet 5.2 simulator tool has employed to measure these performances of IIUM wireless campus network. The observation from the simulation result could be one of the influencing factors in improving wireless services for ITD and further improvement.

Investigating chaotic features in solar radiation over a tropical station using recurrence quantification analysis

NASA Astrophysics Data System (ADS)

Ogunjo, Samuel T.; Adediji, Adekunle T.; Dada, Joseph B.

2017-01-01

The use of solar energy for power generation and other uses is on the increase. This demand necessitate a better understanding of the underlying dynamics for better prediction. Nonlinear dynamics and its associated tools readily lend itself for such analysis. In this paper, nonlinearity in solar radiation data is tested using recurrence plot (RP) and recurrence quantification analysis (RQA) in a tropical station. The data used was obtained from an ongoing campaign at the Federal University of Technology, Akure, Southwestern Nigeria using an Integrated Sensor Suite (Vantage2 Pro). Half hourly and daily values were tested for each month of the year. Both were found to be nonlinear. The dry months of the year exhibit higher chaoticity compared to the wet months of the year. The daily average values were found to be mildly chaotic. Using RQA, features due to external effects such as harmattan and intertropical discontinuity (ITD) on solar radiation data were uniquely identified.

Localization by interaural time difference (ITD): Effects of interaural frequency mismatch

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bonham, B.H.; Lewis, E.R.

1999-07-01

A commonly accepted physiological model for lateralization of low-frequency sounds by interaural time delay (ITD) stipulates that binaural comparison neurons receive input from frequency-matched channels from each ear. Here, the effects of hypothetical interaural frequency mismatches on this model are reported. For this study, the cat{close_quote}s auditory system peripheral to the binaural comparison neurons was represented by a neurophysiologically derived model, and binaural comparison neurons were represented by cross-correlators. The results of the study indicate that, for binaural comparison neurons receiving input from one cochlear channel from each ear, interaural CF mismatches may serve to either augment or diminish themore » effective difference in ipsilateral and contralateral axonal time delays from the periphery to the binaural comparison neuron. The magnitude of this increase or decrease in the effective time delay difference can be up to 400 {mu}s for CF mismatches of 0.2 octaves or less for binaural neurons with CFs between 250 Hz and 2.5 kHz. For binaural comparison neurons with nominal CFs near 500 Hz, the 25-{mu}s effective time delay difference caused by a 0.012-octave CF mismatch is equal to the ITD previously shown to be behaviorally sufficient for the cat to lateralize a low-frequency sound source. {copyright} {ital 1999 Acoustical Society of America.}« less

Mechanisms for Adjusting Interaural Time Differences to Achieve Binaural Coincidence Detection

PubMed Central

Seidl, Armin H.; Rubel, Edwin W; Harris, David M.

2010-01-01

Understanding binaural perception requires detailed analyses of the neural circuitry responsible for the computation of interaural time differences (ITDs). In the avian brainstem, this circuit consists of internal axonal delay lines innervating an array of coincidence detector neurons that encode external ITDs. Nucleus magnocellularis (NM) neurons project to the dorsal dendritic field of the ipsilateral nucleus laminaris (NL) and to the ventral field of the contralateral NL. Contralateral-projecting axons form a delay line system along a band of NL neurons. Binaural acoustic signals in the form of phase-locked action potentials from NM cells arrive at NL and establish a topographic map of sound source location along the azimuth. These pathways are assumed to represent a circuit similar to the Jeffress model of sound localization, establishing a place code along an isofrequency contour of NL. Three-dimensional measurements of axon lengths reveal major discrepancies with the current model; the temporal offset based on conduction length alone makes encoding of physiological ITDs impossible. However, axon diameter and distances between Nodes of Ranvier also influence signal propagation times along an axon. Our measurements of these parameters reveal that diameter and internode distance can compensate for the temporal offset inferred from axon lengths alone. Together with other recent studies these unexpected results should inspire new thinking on the cellular biology, evolution and plasticity of the circuitry underlying low frequency sound localization in both birds and mammals. PMID:20053889

Optimization of Imidazo[4,5-b]pyridine-Based Kinase Inhibitors: Identification of a Dual FLT3/Aurora Kinase Inhibitor as an Orally Bioavailable Preclinical Development Candidate for the Treatment of Acute Myeloid Leukemia

PubMed Central

2012-01-01

Optimization of the imidazo[4,5-b]pyridine-based series of Aurora kinase inhibitors led to the identification of 6-chloro-7-(4-(4-chlorobenzyl)piperazin-1-yl)-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine (27e), a potent inhibitor of Aurora kinases (Aurora-A Kd = 7.5 nM, Aurora-B Kd = 48 nM), FLT3 kinase (Kd = 6.2 nM), and FLT3 mutants including FLT3-ITD (Kd = 38 nM) and FLT3(D835Y) (Kd = 14 nM). FLT3-ITD causes constitutive FLT3 kinase activation and is detected in 20–35% of adults and 15% of children with acute myeloid leukemia (AML), conferring a poor prognosis in both age groups. In an in vivo setting, 27e strongly inhibited the growth of a FLT3-ITD-positive AML human tumor xenograft (MV4–11) following oral administration, with in vivo biomarker modulation and plasma free drug exposures consistent with dual FLT3 and Aurora kinase inhibition. Compound 27e, an orally bioavailable dual FLT3 and Aurora kinase inhibitor, was selected as a preclinical development candidate for the treatment of human malignancies, in particular AML, in adults and children. PMID:23043539

Aging effects on the Binaural Interaction Component of the Auditory Brainstem Response in the Mongolian Gerbil: Effects of Interaural Time and Level Differences

PubMed Central

Laumen, Geneviève; Tollin, Daniel J.; Beutelmann, Rainer; Klump, Georg M.

2016-01-01

The effect of interaural time difference (ITD) and interaural level difference (ILD) on wave 4 of the binaural and summed monaural auditory brainstem responses (ABRs) as well as on the DN1 component of the binaural interaction component (BIC) of the ABR in young and old Mongolian gerbils (Meriones unguiculatus) was investigated. Measurements were made at a fixed sound pressure level (SPL) and a fixed level above visually detected ABR threshold to compensate for individual hearing threshold differences. In both stimulation modes (fixed SPL and fixed level above visually detected ABR threshold) an effect of ITD on the latency and the amplitude of wave 4 as well as of the BIC was observed. With increasing absolute ITD values BIC latencies were increased and amplitudes were decreased. ILD had a much smaller effect on these measures. Old animals showed a reduced amplitude of the DN1 component. This difference was due to a smaller wave 4 in the summed monaural ABRs of old animals compared to young animals whereas wave 4 in the binaural-evoked ABR showed no age-related difference. In old animals the small amplitude of the DN1 component was correlated with small binaural-evoked wave 1 and wave 3 amplitudes. This suggests that the reduced peripheral input affects central binaural processing which is reflected in the BIC. PMID:27173973

Mechanisms of apoptosis induction by simultaneous inhibition of PI3K and FLT3-ITD in AML cells in the hypoxic bone marrow microenvironment

PubMed Central

Jin, Linhua; Tabe, Yoko; Lu, Hongbo; Borthakur, Gautam; Miida, Takashi; Kantarjian, Hagop; Andreeff, Michael; Konopleva, Marina

2013-01-01

We investigated the antileukemia effects and molecular mechanisms of apoptosis induction by simultaneous blockade of PI3K and mutant FLT3 in AML cells grown under hypoxia in co-cultures with bone marrow stromal cells. Combined treatment with selective class I PI3K inhibitor GDC-0941 and sorafenib reversed the protective effects of bone marrow stromal cells on FLT3-mutant AML cells in hypoxia, which was associated with downregulation of Pim-1 and Mcl-1 expression levels. These findings suggest that combined inhibition of PI3K and FLT3-ITD may constitute a targeted approach to eradicating chemoresistant AML cells sequestered in hypoxic bone marrow niches. PMID:23036488

Mechanisms of apoptosis induction by simultaneous inhibition of PI3K and FLT3-ITD in AML cells in the hypoxic bone marrow microenvironment.

PubMed

Jin, Linhua; Tabe, Yoko; Lu, Hongbo; Borthakur, Gautam; Miida, Takashi; Kantarjian, Hagop; Andreeff, Michael; Konopleva, Marina

2013-02-01

We investigated the antileukemia effects and molecular mechanisms of apoptosis induction by simultaneous blockade of PI3K and mutant FLT3 in AML cells grown under hypoxia in co-cultures with bone marrow stromal cells. Combined treatment with selective class I PI3K inhibitor GDC-0941 and sorafenib reversed the protective effects of bone marrow stromal cells on FLT3-mutant AML cells in hypoxia, which was associated with downregulation of Pim-1 and Mcl-1 expression levels. These findings suggest that combined inhibition of PI3K and FLT3-ITD may constitute a targeted approach to eradicating chemoresistant AML cells sequestered in hypoxic bone marrow niches. Copyright © 2012 Elsevier Ltd. All rights reserved.

Linkage analysis with chromosome 9 markers in hereditary essential tremor.

PubMed

Conway, D; Bain, P G; Warner, T T; Davis, M B; Findley, L J; Thompson, P D; Marsden, C D; Harding, A E

1993-07-01

Hereditary essential tremor (ET) is an autosomal dominant disorder with variable expression and reduced penetrance. A tremor indistinguishable from ET may be observed in patients with autosomal dominant idiopathic torsion dystonia (ITD), in which the disease locus has been mapped to 9q32-34 in some kindreds, tightly linked to the argininosuccinate synthetase (ASS) locus. We performed linkage analysis in 15 families with ET containing 60 definitely affected individuals, using dinucleotide repeat polymorphisms at the ASS locus and the Abelson locus (ABL). Cumulative lod scores were -19.5 for ASS and -10.8 for ABL at a recombination fraction of 0.01, and tight linkage to ASS was excluded individually in 11 of the families. These data indicate that the ET gene is not allelic to that causing ITD.

Speech-on-speech masking in a front-back dimension and analysis of binaural parameters in rooms using MLS methods

NASA Astrophysics Data System (ADS)

Aaronson, Neil L.

This dissertation deals with questions important to the problem of human sound source localization in rooms, starting with perceptual studies and moving on to physical measurements made in rooms. In Chapter 1, a perceptual study is performed relevant to a specific phenomenon the effect of speech reflections occurring in the front-back dimension and the ability of humans to segregate that from unreflected speech. Distracters were presented from the same source as the target speech, a loudspeaker directly in front of the listener, and also from a loudspeaker directly behind the listener, delayed relative to the front loudspeaker. Steps were taken to minimize the contributions of binaural difference cues. For all delays within +/-32 ms, a release from informational masking of about 2 dB occurred. This suggested that human listeners are able to segregate speech sources based on spatial cues, even with minimal binaural cues. In moving on to physical measurements in rooms, a method was sought for simultaneous measurement of room characteristics such as impulse response (IR) and reverberation time (RT60), and binaural parameters such as interaural time difference (ITD), interaural level difference (ILD), and the interaural cross-correlation function and coherence. Chapter 2 involves investigations into the usefulness of maximum length sequences (MLS) for these purposes. Comparisons to random telegraph noise (RTN) show that MLS performs better in the measurement of stationary and room transfer functions, IR, and RT60 by an order of magnitude in RMS percent error, even after Wiener filtering and exponential time-domain filtering have improved the accuracy of RTN measurements. Measurements were taken in real rooms in an effort to understand how the reverberant characteristics of rooms affect binaural parameters important to sound source localization. Chapter 3 deals with interaural coherence, a parameter important for localization and perception of auditory source width. MLS were used to measure waveform and envelope coherences in two rooms for various source distances and 0° azimuth through a head-and-torso simulator (KEMAR). A relationship is sought that relates these two types of coherence, since envelope coherence, while an important quantity, is generally less accessible than waveform coherence. A power law relationship is shown to exist between the two that works well within and across bands, for any source distance, and is robust to reverberant conditions of the room. Measurements of ITD, ILD, and coherence in rooms give insight into the way rooms affect these parameters, and in turn, the ability of listeners to localize sounds in rooms. Such measurements, along with room properties, are made and analyzed using MLS methods in Chapter 4. It was found that the pinnae cause incoherence for sound sources incident between 30° and 90°. In human listeners, this does not seem to adversely affect performance in lateralization experiments. The cause of poor coherence in rooms was studied as part of Chapter 4 as well. It was found that rooms affect coherence by introducing variance into the ITD spectra within the bands in which it is measured. A mathematical model to predict the interaural coherence within a band given the standard deviation of the ITD spectrum and the center frequency of the band gives an exponential relationship. This is found to work well in predicting measured coherence given ITD spectrum variance. The pinnae seem to affect the ITD spectrum in a similar way at incident sound angles for which coherence is poor in an anechoic environment.

Detection and localization of sounds: Virtual tones and virtual reality

NASA Astrophysics Data System (ADS)

Zhang, Peter Xinya

Modern physiologically based binaural models employ internal delay lines in the pathways from left and right peripheries to central processing nuclei. Various models apply the delay lines differently, and give different predictions for the detection of dichotic pitches, wherein listeners hear a virtual tone in the noise background. Two dichotic pitch stimuli (Huggins pitch and binaural coherence edge pitch) with low boundary frequencies were used to test the predictions by two different models. The results from five experiments show that the relative dichotic pitch strengths support the equalization-cancellation model and disfavor the central activity pattern (CAP) model. The CAP model makes predictions for the lateralization of Huggins pitch based on interaural time differences (ITD). By measuring human lateralization for Huggins pitches with two different types of phase boundaries (linear-phase and stepped phase), and by comparing with lateralization of sine-tones, it was shown that the lateralization of Huggins pitch stimuli is similar to that of the corresponding sine-tones, and the lateralizations of Huggins pitch stimuli with the two different boundaries were even more similar to one another. The results agreed roughly with the CAP model predictions. Agreement was significantly improved by incorporating individualized scale factors and offsets into the model, and was further unproved with a model including compression at large ITDs. Furthermore, ambiguous stimuli, with an interaural phase difference of 180 degrees, were consistently lateralized on the left or right based on individual asymmetries---which introduces the concept of "earedness". Interaural phase difference (IPD) and interaural time difference (ITD) are two different forms of temporal cues. With varying frequency, an auditory system based on IPD or ITD gives different quantitative predictions on lateralization. A lateralization experiment with sine tones tested whether human auditory system is an IPD-meter or an ITD-meter. Listeners estimated the lateral positions of 50 sine tones with IPDs ranging from -150° to +150° and with different frequencies, all in the range where signal fine structure supports lateralization. The estimates indicated that listeners lateralize sine tones on the basis of ITD and not IPD. In order to distinguish between sound sources in front and in back, listeners use spectral cues caused by the diffraction by pinna, head, neck and torso. To study this effect, the VRX technique was developed based on transaural technology. The technique was successful in presenting desired spectra into listeners' ears with high accuracy up to 16 kHz. When presented with real source and simulated virtual signal, listeners in an anechoic room could not distinguish between them. Eleven experiments on discrimination between front and back sources were carried out in an anechoic room. The results show several findings. First, the results support a multiple band comparison model, and disfavor a necessary band(s) model. Second, it was found that preserving the spectral dips was more important than preserving the spectral peaks for successful front/back discrimination. Moreover, it was confirmed that neither monaural cues nor interaural spectral level difference cues were adequate for front/back discrimination. Furthermore, listeners' performance did not deteriorate when presented with sharpened spectra. Finally, when presented with an interaural delay less than 200 mus, listeners could succeed to discriminate front from back, although the image was pulled to the side, which suggests that the localizations in azimuthal plane and in sagittal plane are independent within certain limits.

Haematopoietic cell transplantation with and without sorafenib maintenance for patients with FLT3-ITD acute myeloid leukaemia in first complete remission.

PubMed

Brunner, Andrew M; Li, Shuli; Fathi, Amir T; Wadleigh, Martha; Ho, Vincent T; Collier, Kerry; Connolly, Christine; Ballen, Karen K; Cutler, Corey S; Dey, Bimalangshu R; El-Jawahri, Areej; Nikiforow, Sarah; McAfee, Steven L; Koreth, John; Deangelo, Daniel J; Alyea, Edwin P; Antin, Joseph H; Spitzer, Thomas R; Stone, Richard M; Soiffer, Robert J; Chen, Yi-Bin

2016-11-01

We performed a retrospective study analysing the effect of sorafenib, an oral fms-Like Tyrosine Kinase 3 (FLT3)/multikinase inhibitor, as post-transplant maintenance in adult patients with FLT3-internal tandem duplication (ITD) acute myeloid leukaemia (AML). We identified consecutive patients with FLT3-ITD AML diagnosed between 2008 and 2014 who received haematopoietic cell transplantation (HCT) in first complete remission (CR1). Post-HCT initiation of sorafenib (yes/no) was evaluated as a time-varying covariate in the overall survival/progression-free survival (OS/PFS) analysis and we performed a landmark analysis of controls alive without relapse at the median date of sorafenib initiation. We identified 26 sorafenib patients and 55 controls. Median follow-up was 27·2 months post-HCT for sorafenib survivors, and 38·4 months for controls (P = 0·021). The median time to initiating sorafenib was 68 days post-HCT; 43 controls were alive without relapse at this cut-off. Sorafenib patients had improved 2-year OS in the d+68 landmark analysis (81% vs. 62%, P = 0·029). Sorafenib was associated with improved 2-year PFS (82% vs. 53%, P = 0·0081) and lower 2-year cumulative incidence of relapse (8·2% vs. 37·7%, P = 0·0077). In multivariate analysis, sorafenib significantly improved OS [Hazard ratio (HR) 0·26, P = 0·021] and PFS (HR 0·25, P = 0·016). There was no difference in 2-year non-relapse mortality (9·8% vs. 9·3%, P = 0·82) or 1-year chronic graft-versus-host disease (55·5% vs. 37·2%, P = 0·28). These findings suggest potential benefit of post-HCT sorafenib in FLT3-ITD AML, and support further evaluation of post-HCT FLT3 inhibition. © 2016 John Wiley & Sons Ltd.

Investigations in mechanisms and strategies to enhance hearing with cochlear implants

NASA Astrophysics Data System (ADS)

Churchill, Tyler H.

Cochlear implants (CIs) produce hearing sensations by stimulating the auditory nerve (AN) with current pulses whose amplitudes are modulated by filtered acoustic temporal envelopes. While this technology has provided hearing for multitudinous CI recipients, even bilaterally-implanted listeners have more difficulty understanding speech in noise and localizing sounds than normal hearing (NH) listeners. Three studies reported here have explored ways to improve electric hearing abilities. Vocoders are often used to simulate CIs for NH listeners. Study 1 was a psychoacoustic vocoder study examining the effects of harmonic carrier phase dispersion and simulated CI current spread on speech intelligibility in noise. Results showed that simulated current spread was detrimental to speech understanding and that speech vocoded with carriers whose components' starting phases were equal was the least intelligible. Cross-correlogram analyses of AN model simulations confirmed that carrier component phase dispersion resulted in better neural envelope representation. Localization abilities rely on binaural processing mechanisms in the brainstem and mid-brain that are not fully understood. In Study 2, several potential mechanisms were evaluated based on the ability of metrics extracted from stereo AN simulations to predict azimuthal locations. Results suggest that unique across-frequency patterns of binaural cross-correlation may provide a strong cue set for lateralization and that interaural level differences alone cannot explain NH sensitivity to lateral position. While it is known that many bilateral CI users are sensitive to interaural time differences (ITDs) in low-rate pulsatile stimulation, most contemporary CI processing strategies use high-rate, constant-rate pulse trains. In Study 3, we examined the effects of pulse rate and pulse timing on ITD discrimination, ITD lateralization, and speech recognition by bilateral CI listeners. Results showed that listeners were able to use low-rate pulse timing cues presented redundantly on multiple electrodes for ITD discrimination and lateralization of speech stimuli even when mixed with high rates on other electrodes. These results have contributed to a better understanding of those aspects of the auditory system that support speech understanding and binaural hearing, suggested vocoder parameters that may simulate aspects of electric hearing, and shown that redundant, low-rate pulse timing supports improved spatial hearing for bilateral CI listeners.

FLT3 mutation and expression did not adversely affect clinical outcome of childhood acute leukaemia: a study of 531 Southeast Asian children by the Ma-Spore study group.

PubMed

Leow, Shuangjie; Kham, Shirley Kow-Yin; Ariffin, Hany; Quah, Thuan Chong; Yeoh, Allen Eng-Juh

2011-12-01

FMS-like tyrosine kinase 3 (FLT3) is critical for normal haematopoiesis and have been reported to be expressed in the majority of acute myeloid and lymphoid malignancies. We correlated the impact of FLT3 mutations and its expression with age, WHO 2008 classification and treatment outcome in 531 childhood acute leukaemias. Of 150 acute myeloid leukaemia (AMLs), 18 (12%) harboured FLT3-ITD while nine (6%) had FLT3-TKD. FLT3-ITD and -TKD were rare in acute megakaryoblastic leukaemia (AMKL; FLT3-ITD 0/26, FLT3-TKD 1/26) and children below 3 years (n = 2/48). Acute promyelocytic leukaemia (APL) with t(15;17);PML-RARα (n = 7/18; 39%) harboured the highest frequency of FLT3 mutations, followed by myelomonocytic (n = 4/18; 22%) and AML with t(8;21);RUNX1-RUNX1T1 (n = 2/21; 9%). FLT3 expression levels were also lowest in AMKL, both in Down's and non-Down's (p = 0.002) followed by patients <3 years (p = 0.001). The rarity of FLT3 mutations and expression levels in AMKL were independent of age. Conversely, only 2% of childhood acute lymphoblastic leukaemia (ALL) harboured FLT3 mutations (ITD = 1/381; TKD = 6/381). FLT3 was highly expressed in hyperdiploid ALL (p < 0.001). Of the 121 AMLs with clinical history, there were no significant differences in 4-year event-free survival (EFS) (46% vs. 38%; p = 0.46) and overall-survival (OS) (55% vs. 43%; p = 0.30) between FLT3-wildtype and ITD+ patients. Similarly, FLT3 expression levels did not influence survival in AML in both the good risk and non-good risk subgroups. FLT3 does not appear to be involved in the pathogenesis of AMKL, both in Down's and non-Down's. Therapeutic targets using FLT3 inhibitors may not be useful in AMKL and in young children with AML. Copyright © 2011 John Wiley & Sons, Ltd.

CRISPR/Cas9 gene drives in genetically variable and nonrandomly mating wild populations

PubMed Central

Drury, Douglas W.; Dapper, Amy L.; Siniard, Dylan J.; Zentner, Gabriel E.; Wade, Michael J.

2017-01-01

Synthetic gene drives based on CRISPR/Cas9 have the potential to control, alter, or suppress populations of crop pests and disease vectors, but it is unclear how they will function in wild populations. Using genetic data from four populations of the flour beetle Tribolium castaneum, we show that most populations harbor genetic variants in Cas9 target sites, some of which would render them immune to drive (ITD). We show that even a rare ITD allele can reduce or eliminate the efficacy of a CRISPR/Cas9-based synthetic gene drive. This effect is equivalent to and accentuated by mild inbreeding, which is a characteristic of many disease-vectoring arthropods. We conclude that designing such drives will require characterization of genetic variability and the mating system within and among targeted populations. PMID:28560324

Computation of interaural time difference in the owl's coincidence detector neurons.

PubMed

Funabiki, Kazuo; Ashida, Go; Konishi, Masakazu

2011-10-26

Both the mammalian and avian auditory systems localize sound sources by computing the interaural time difference (ITD) with submillisecond accuracy. The neural circuits for this computation in birds consist of axonal delay lines and coincidence detector neurons. Here, we report the first in vivo intracellular recordings from coincidence detectors in the nucleus laminaris of barn owls. Binaural tonal stimuli induced sustained depolarizations (DC) and oscillating potentials whose waveforms reflected the stimulus. The amplitude of this sound analog potential (SAP) varied with ITD, whereas DC potentials did not. The amplitude of the SAP was correlated with firing rate in a linear fashion. Spike shape, synaptic noise, the amplitude of SAP, and responsiveness to current pulses differed between cells at different frequencies, suggesting an optimization strategy for sensing sound signals in neurons tuned to different frequencies.

CRISPR/Cas9 gene drives in genetically variable and nonrandomly mating wild populations.

PubMed

Drury, Douglas W; Dapper, Amy L; Siniard, Dylan J; Zentner, Gabriel E; Wade, Michael J

2017-05-01

Synthetic gene drives based on CRISPR/Cas9 have the potential to control, alter, or suppress populations of crop pests and disease vectors, but it is unclear how they will function in wild populations. Using genetic data from four populations of the flour beetle Tribolium castaneum , we show that most populations harbor genetic variants in Cas9 target sites, some of which would render them immune to drive (ITD). We show that even a rare ITD allele can reduce or eliminate the efficacy of a CRISPR/Cas9-based synthetic gene drive. This effect is equivalent to and accentuated by mild inbreeding, which is a characteristic of many disease-vectoring arthropods. We conclude that designing such drives will require characterization of genetic variability and the mating system within and among targeted populations.

HGNET-BCOR Tumors of the Cerebellum: Clinicopathologic and Molecular Characterization of 3 Cases.

PubMed

Appay, Romain; Macagno, Nicolas; Padovani, Laetitia; Korshunov, Andrey; Kool, Marcel; André, Nicolas; Scavarda, Didier; Pietsch, Torsten; Figarella-Branger, Dominique

2017-09-01

The central nervous system (CNS) high-grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR) is a recently described molecular entity. We report 3 new CNS HGNET-BCOR cases sharing common clinical presentation and pathologic features. The 3 cases concerned children aged 3 to 7 years who presented with a voluminous mass of the cerebellum. Pathologic features included proliferation of uniform spindle to ovoid cells with fine chromatin associated with a rich arborizing capillary network. Methylation profiling classified these cases as CNS HGNET-BCOR tumors. Polymerase chain reaction analysis confirmed the presence of internal tandem duplications in the C-terminus of BCOR (BCOR-ITD), a characteristic of these tumors, in all 3 cases. Immunohistochemistry showed a strong nuclear BCOR expression. In 2 cases, local recurrence occurred within 6 months. The third case, a patient who received a craniospinal irradiation after total surgical removal followed by a metronomics maintenance with irinotecan, temozolomide, and itraconazole, is still free of disease 14 months after diagnosis. In summary, CNS HGNET-BCOR represents a rare tumor occurring in young patients with dismal prognosis. BCOR nuclear immunoreactivity is highly suggestive of a BCOR-ITD. Whether CNS HGNET-BCOR should be classified among the category of "embryonal tumors" or within the category of "mesenchymal, nonmeningothelial tumors" remains to be clarified. Because CNS HGNET-BCOR share pathologic features and characteristic BCOR-ITD with clear cell sarcoma of the kidney, these tumors may represent local variants of the same entity.

Effects of nozzle-strut integrated design concepton on the subsonic turbine stage flowfield

NASA Astrophysics Data System (ADS)

Liu, Jun; Du, Qiang; Liu, Guang; Wang, Pei; Zhu, Junqiang

2014-10-01

In order to shorten aero-engine axial length, substituting the traditional long chord thick strut design accompanied with the traditional low pressure(LP) stage nozzle, LP turbine is integrated with intermediate turbine duct (ITD). In the current paper, five vanes of the first stage LP turbine nozzle is replaced with loaded struts for supporting the engine shaft, and providing oil pipes circumferentially which fulfilled the areo-engine structure requirement. However, their bulky geometric size represents a more effective obstacle to flow from high pressure (HP) turbine rotor. These five struts give obvious influence for not only the LP turbine nozzle but also the flowfield within the ITD, and hence cause higher loss. Numerical investigation has been undertaken to observe the influence of the Nozzle-Strut integrated design concept on the flowfield within the ITD and the nearby nozzle blades. According to the computational results, three main conclusions are finally obtained. Firstly, a noticeable low speed area is formed near the strut's leading edge, which is no doubt caused by the potential flow effects. Secondly, more severe radial migration of boundary layer flow adjacent to the strut's pressure side have been found near the nozzle's trailing edge. Such boundary layer migration is obvious, especially close to the shroud domain. Meanwhile, radial pressure gradient aggravates this phenomenon. Thirdly, velocity distribution along the strut's pressure side on nozzle's suction surface differs, which means loading variation of the nozzle. And it will no doubt cause nonuniform flowfield faced by the downstream rotor blade.

Aging effects on the binaural interaction component of the auditory brainstem response in the Mongolian gerbil: Effects of interaural time and level differences.

PubMed

Laumen, Geneviève; Tollin, Daniel J; Beutelmann, Rainer; Klump, Georg M

2016-07-01

The effect of interaural time difference (ITD) and interaural level difference (ILD) on wave 4 of the binaural and summed monaural auditory brainstem responses (ABRs) as well as on the DN1 component of the binaural interaction component (BIC) of the ABR in young and old Mongolian gerbils (Meriones unguiculatus) was investigated. Measurements were made at a fixed sound pressure level (SPL) and a fixed level above visually detected ABR threshold to compensate for individual hearing threshold differences. In both stimulation modes (fixed SPL and fixed level above visually detected ABR threshold) an effect of ITD on the latency and the amplitude of wave 4 as well as of the BIC was observed. With increasing absolute ITD values BIC latencies were increased and amplitudes were decreased. ILD had a much smaller effect on these measures. Old animals showed a reduced amplitude of the DN1 component. This difference was due to a smaller wave 4 in the summed monaural ABRs of old animals compared to young animals whereas wave 4 in the binaural-evoked ABR showed no age-related difference. In old animals the small amplitude of the DN1 component was correlated with small binaural-evoked wave 1 and wave 3 amplitudes. This suggests that the reduced peripheral input affects central binaural processing which is reflected in the BIC. Copyright © 2016 Elsevier B.V. All rights reserved.

Idaho Transportation Department : 2010 research program peer exchange.

DOT National Transportation Integrated Search

2010-05-01

The objectives of the peer exchange were to: : 1. Identify strengths, challenges, and opportunities for program and project management; : 2. Understand management expectations of the ITD Research Program; : 3. Review processes for project selection a...

Evaluating Performance of Highway Safety Projects

DOT National Transportation Integrated Search

2016-12-01

The purpose of this project was to investigate and document methods that the Idaho Transportation Department (ITD) and Local Highway Technical Assistance Council (LHTAC) can use to evaluate the performance of safety projects that have been implemente...

Growing a Constructive Culture at ITD

DOT National Transportation Integrated Search

2016-06-01

The Center for Health and Safety Culture evaluated the progress of the Idaho Transportation Departments effort to transform its culture. In 2012, a representative sample of employees identified a constructive culture as the ideal culture that woul...

Idaho Transportation Department 2009 partnership survey.

DOT National Transportation Integrated Search

2010-06-01

The report discusses the results of an electronic survey of 1,500 individual stakeholders of the Idaho Transportation Department (ITD). The purpose of this survey, which was conducted in August and September 2009, was to gauge stakeholders satisfa...

Influence of Reynolds Number on the Unsteady Aerodynamics of Integrated Aggressive Intermediate Turbine Duct

NASA Astrophysics Data System (ADS)

Liu, Hongrui; Liu, Jun; Ji, Lucheng; Du, Qiang; Liu, Guang; Wang, Pei

2018-06-01

The ultra-high bypass ratio turbofan engine attracts more and more attention in modern commercial engine due to advantages of high efficiency and low Specific Fuel Consumption (SFC). One of the characteristics of ultra-high bypass ratio turbofan is the intermediate turbine duct which guides the flow leaving high pressure turbine (HPT) to low pressure turbine (LPT) at a larger diameter, and this kind of design will lead to aggressive intermediate turbine duct (AITD) design concept. Thus, it is important to design the AITD without any severe loss. From the unsteady flow's point of view, in actual operating conditions, the incoming wake generated by HPT is unsteady which will take influence on boundary layer's transition within the ITD and LPT. In this paper, the three-dimensional unsteady aerodynamics of an AITD taken from a real engine is studied. The results of fully unsteady three-dimensional numerical simulations, performed with ANSYS-CFX (RANS simulation with transitional model), are critically evaluated against experimental data. After validation of the numerical model, the physical mechanisms inside the flow channel are analyzed, with an aim to quantify the sensitivities of different Reynolds number effect on both the ITD and LPT nozzle. Some general physical mechanisms can be recognized in the unsteady environment. It is recognized that wake characteristics plays a crucial role on the loss within both the ITD and LPT nozzle section, determining both time-averaged and time-resolved characteristics of the flow field. Meanwhile, particular attention needs to be paid to the unsteady effect on the boundary layer of LPT nozzle's suction side surface.

Bundled Postconditioning Therapies Improve Hemodynamics and Neurologic Recovery after 17 Minutes of Untreated Cardiac Arrest

PubMed Central

Bartos, Jason A.; Matsuura, Timothy R.; Sarraf, Mohammad; Youngquist, Scott T.; McKnite, Scott H.; Rees, Jennifer N.; Sloper, Daniel T.; Bates, Frank S.; Segal, Nicolas; Debaty, Guillaume; Lurie, Keith G.; Neumar, Robert W.; Metzger, Joseph M.; Riess, Matthias L.; Yannopoulos, Demetris

2014-01-01

Objective Ischemic postconditioning (stutter CPR) and sevoflurane have been shown to mitigate the effects of reperfusion injury in cardiac tissue after 15 minutes of ventricular fibrillation (VF) cardiac arrest. Poloxamer 188 (P188) has also proven beneficial to neuronal and cardiac tissue during reperfusion injury in human and animal models. We hypothesized that the use of stutter CPR, sevoflurane, and P188 combined with standard advanced life support would improve post-resuscitation cardiac and neurologic function after prolonged VF arrest. Methods Following 17 minutes of untreated VF, 20 pigs were randomized to Control treatment with active compression/decompression (ACD) CPR and impedance threshold device (ITD) (n=8) or Bundle therapy with stutter ACD CPR + ITD + sevoflurane + P188 (n=12). Epinephrine and post-resuscitation hypothermia were given in both groups per standard protocol. Animals that achieved return of spontaneous circulation (ROSC) were evaluated with echocardiography, biomarkers, and a blinded neurologic assessment with a cerebral performance category score. Results Bundle therapy improved hemodynamics during resuscitation, reduced need for epinephrine and repeated defibrillation, reduced biomarkers of cardiac injury and end-organ dysfunction, and increased left ventricular ejection fraction compared to Controls. Bundle therapy also improved rates of ROSC (100% vs. 50%), freedom from major adverse events (50% vs. 0% at 48 hours), and neurologic function (42% with mild or no neurologic deficit and 17% achieving normal function at 48 hours). Conclusions Bundle therapy with a combination of stutter ACD CPR, ITD, sevoflurane, and P188 improved cardiac and neurologic function after 17 minutes of untreated cardiac arrest in pigs. PMID:25447036

Potent Activity of Ponatinib (AP24534) in Models of FLT3-Driven Acute Myeloid Leukemia and Other Hematologic Malignancies

PubMed Central

Gozgit, Joseph M.; Wong, Matthew J.; Wardwell, Scott; Tyner, Jeffrey W.; Loriaux, Marc M.; Mohemmad, Qurish K.; Narasimhan, Narayana I.; Shakespeare, William C.; Wang, Frank; Druker, Brian J.; Clackson, Tim; Rivera, Victor M.

2011-01-01

Ponatinib (AP24534) is a novel multitargeted kinase inhibitor that potently inhibits native and mutant BCR-ABL at clinically achievable drug levels. Ponatinib also has in vitro inhibitory activity against a discrete set of kinases implicated in the pathogenesis of other hematologic malignancies, including FLT3, KIT, fibroblast growth factor receptor 1 (FGFR1), and platelet derived growth factor receptor α (PDGFRα). Here, using leukemic cell lines containing activated forms of each of these receptors, we show that ponatinib potently inhibits receptor phosphorylation and cellular proliferation with IC50 values comparable to those required for inhibition of BCR-ABL (0.3 to 20 nmol/L). The activity of ponatinib against the FLT3-ITD mutant, found in up to 30% of acute myeloid leukemia (AML) patients, was particularly notable. In MV4-11 (FLT3-ITD+/+) but not RS4;11 (FLT3-ITD−/−) AML cells, ponatinib inhibited FLT3 signaling and induced apoptosis at concentrations of less than 10 nmol/L. In an MV4-11 mouse xenograft model, once daily oral dosing of ponatinib led to a dose-dependent inhibition of signaling and tumor regression. Ponatinib inhibited viability of primary leukemic blasts from a FLT3-ITD positive AML patient (IC50 4 nmol/L) but not those isolated from 3 patients with AML expressing native FLT3. Overall, these results support the investigation of ponatinib in patients with FLT3-ITD–driven AML and other hematologic malignancies driven by KIT, FGFR1, or PDGFRα. PMID:21482694

Clinical characteristics of pigment dispersion syndrome in Chinese patients.

PubMed

Qing, G; Wang, N; Tang, X; Zhang, S; Chen, H

2009-08-01

To report clinical findings and characteristics of pigment dispersion syndrome (PDS) in Chinese patients. PDS suspects with any one of the following signs: corneal endothelial pigmentation, iris transillumination defects (ITDs), pigment granule dusting on anterior iris surface, posterior iris bowing, trabecular meshwork (TM) pigmentation, and lenticular or zonular pigmentation were evaluated for PDS at the glaucoma specialty clinic at Beijing Tongren Eye Centre. Diagnosis of PDS required at least two of the following signs: Krukenberg spindle, moderate-to-heavy TM pigmentation (>or=Scheie II) and any degree of lenticular and/or zonular pigmentation. Eighteen patients (12 males and six females) were identified as having PDS during a 1-year period, with mean age of 35.5+/-7.0 years (range, 22-49). All but two eyes from two patients had myopia of -0.5 D or greater, with mean spherical equivalent power of -5.20+/-5.80 D (range, -24.75+/-0.5). The average IOP at initial diagnosis was 33.7+/-10.5 mm Hg (range, 16-56). Fifteen patients (83.3%) were found to have pigmentary glaucoma at their initial diagnosis. All patients showed homogenous increased TM pigmentation as well as lenticular and/or zonular pigmentation. 61.1% of patients (11 of 18) had Krukenberg spindle. None of the patients exhibited spoke-like midperipheral ITDs except for trace-isolated transillumination in both eyes of the two patients. The most common clinical findings in Chinese PDS patients include homogeneous TM pigmentation and pigment granule dusting on lens zonules and/or posterior peripheral lens surface. ITDs are uncommon in Chinese patients with PDS.

Implementation of the MEPDG for flexible pavements in Idaho.

DOT National Transportation Integrated Search

2012-05-01

This study was conducted to assist the Idaho Transportation Department (ITD) in the implementation of the Mechanistic-Empirical Pavement Design Guide (MEPDG) for flexible pavements. The main research work in this study focused on establishing a mater...

Midostaurin and Decitabine in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia and FLT3 Mutation

ClinicalTrials.gov

2017-11-29

Acute Myeloid Leukemia With FLT3/ITD Mutation; Acute Myeloid Leukemia With Gene Mutations; FLT3 Tyrosine Kinase Domain Point Mutation; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

Idaho Transportation Department 2009 customer satisfaction survey.

DOT National Transportation Integrated Search

2010-02-01

In the summer and fall of 2009, the Idaho Transportation Department (ITD) commissioned a statewide customer satisfaction survey of Idaho residents in order to assess the overall level of satisfaction with several key areas of service provided by the ...

Evaluation of Fiber-Reinforced Asphalt Pavements : Laboratory Study

DOT National Transportation Integrated Search

2016-06-01

The Idaho Transportation Department (ITD) initiated a field project to evaluate the effectiveness of using fibers to mitigate rutting and fatigue distresses at US-30 east of Montpelier in south Idaho. The project was constructed in August 2014 to add...

Highway user expectations for ITD winter maintenance.

DOT National Transportation Integrated Search

2014-07-01

Providing a high Level of Service (LOS) to ensure the safety and mobility for the traveling public is a key objective for winter : maintenance operations. The goal of this research was to obtain a better understanding of Idaho highway users expect...

Methodology for prioritizing appropriate mitigation actions to reduce wildlife-vehicle collisions on Idaho highways.

DOT National Transportation Integrated Search

2014-08-01

Vehicle collisions with large wild animals are a safety issue for motorists and an ecological concern for : wildlife populations. The objective of this research was to advance the efficacy of Idaho Transportation : Departments (ITDs) project pl...

77 FR 15181 - Notice To Rescind the Notice of Intent To Prepare an Environmental Impact Statement, Valley...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-14

... cooperation with Idaho Transportation Department (ITD) published a Notice of Intent (NOI) on January 24, 2000... Valley, on SH-55. A series of project team meetings/ public workshops were held and a range of...

Methodology for prioritizing appropriate mitigation actions to reduce wildlife-vehicle collisions on Idaho highways.

DOT National Transportation Integrated Search

2014-08-01

Vehicle collisions with large wild animals are a safety issue for motorists and an ecological concern for wildlife populations. The objective of this research was to advance the efficacy of Idaho Transportation Departments (ITDs) project planni...

Impacts of using salt and salt brine for roadway deicing.

DOT National Transportation Integrated Search

2014-06-01

Idaho Transportation Department (ITD) uses a variety of methods to help ensure safe travel on the state highway system : following winter storm events. These methods include plowing, use of sand to improve traction, and use of salt and chemical : com...

Remote sensing of soil moisture using airborne hyperspectral data

USDA-ARS?s Scientific Manuscript database

The Institute for Technology Development (ITD) has developed an airborne hyperspectral sensor system that collects electromagnetic reflectance data of the terrain. The system consists of sensors for three different sections of the electromagnetic spectrum; the Ultra-Violet (UV), Visible/Near Infrare...

Information Technology and Disabilities, 1995.

ERIC Educational Resources Information Center

McNulty, Tom, Ed.

1995-01-01

Four issues of this newsletter on information technology and disabilities (ITD) contain the following articles: "Developing an Accessible Online Public Access Catalog at the Washington Talking Book and Braille Library" (Charles Hamilton); "Assistive Technology in the Science Laboratory: A Talking Laboratory Work Station for Visually Impaired…

Lithologic characterization of active ITD aggregate sources and implications for aggregate quality.

DOT National Transportation Integrated Search

2014-03-01

Aggregate from 40 material sources across Idaho were sampled and the lithologies identified quantitatively. Aggregate compositions are compared with commercial AASHTO T 303 and ASTM C1293 results and the geologic map of Idaho to identify those rock t...

Material acceptance risk analysis : superpave hot mix asphalt.

DOT National Transportation Integrated Search

2010-09-01

The objective of this study is to review Superpave Hot Mix asphalt used by other state DOTs and make recommendation to Idaho Transportation Department (ITD) in using this product in its roadways and in particular in low-traffic roadways. Based on the...

[Validation of an instrument for screening cases of type 2 diabetes and monitoring at-risk individuals in Mexico].

PubMed

Guerrero-Romero, Fernando; Rodríguez-Morán, Martha

2010-03-01

To validate a method for screening cases of type 2 diabetes and monitoring at-risk people in a community in northern Mexico. The screening instrument for type 2 diabetes (ITD, for its Spanish acronym) was developed using a multiple logistic regression analysis that made it possible to determine the association between a new diagnosis of diabetes (a dependent variable) and 11 known risk factors. Internal validations were performed (through v-fold cross-validation), together with external validations (through the monitoring of a cohort of healthy individuals). In order to estimate the relative risk (RR) of developing type 2 diabetes, the total ITD score is calculated on the basis of an individual's risk factors and compared against a curve that shows the probability of that individual developing the disease. Of the 525 people in the cohort, 438 (83.4%) were followed for an average of 7 years (4.5 to 10 years), for a total of 2 696 person-years; 62 (14.2%) people developed diabetes during the time they were followed. Individuals scoring 55 points based on their risk factors demonstrated a significantly higher risk of developing diabetes in 7 years (RR = 6.1; IC95%: 1.7 to 11.1); the risk was even higher for those with a score of 75 points (RR = 9.4; IC95%: 2.1 to 11.5). The ITD is easy to use and a valid screening alternative for type 2 diabetes. Its use will allow more individuals to benefit from disease prevention methods and early diagnosis without substantially increasing costs and with minimal use of laboratory resources.

Evaluation of the Boussignac Cardiac arrest device (B-card) during cardiopulmonary resuscitation in an animal model.

PubMed

Moore, Johanna C; Lamhaut, Lionel; Hutin, Alice; Dodd, Kenneth W; Robinson, Aaron E; Lick, Michael C; Salverda, Bayert J; Hinke, Mason B; Labarere, José; Debaty, Guillaume; Segal, Nicolas

2017-10-01

The purpose of this study was to examine continuous oxygen insufflation (COI) in a swine model of cardiac arrest. The primary hypothesis was COI during standard CPR (S-CPR) should result in higher intrathoracic pressure (ITP) during chest compression and lower ITP during decompression versus S-CPR alone. These changes with COI were hypothesized to improve hemodynamics. The second hypothesis was that changes in ITP with S-CPR+COI would result in superior hemodynamics compared with active compression decompression (ACD) + impedance threshold device (ITD) CPR, as this method primarily lowers ITP during chest decompression. After 6min of untreated ventricular fibrillation, S-CPR was initiated in 8 female swine for 4min, then 3min of S-CPR+COI, then 3min of ACD+ITD CPR, then 3min of S-CPR+COI. ITP and hemodynamics were continuously monitored. During S-CPR+COI, ITP was always positive during the CPR compression and decompression phases. ITP compression values with S-CPR+COI versus S-CPR alone were 5.5±3 versus 0.2±2 (p<0.001) and decompression values were 2.8±2 versus -1.3±2 (p<0.001), respectively. With S-CPR+COI versus ACD+ITD the ITP compression values were 5.5±3 versus 1.5±2 (p<0.01) and decompression values were 2.8±2 versus -4.7±3 (p<0.001), respectively. COI during S-CPR created a continuous positive pressure in the airway during both the compression and decompression phase of CPR. At no point in time did COI generate a negative intrathoracic pressures during CPR in this swine model of cardiac arrest. Copyright © 2017 Elsevier B.V. All rights reserved.

Allogeneic stem cell transplantation benefits for patients ≥ 60 years with acute myeloid leukemia and FLT3 internal tandem duplication: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

PubMed Central

Poiré, Xavier; Labopin, Myriam; Polge, Emmanuelle; Passweg, Jakob; Craddock, Charles; Blaise, Didier; Cornelissen, Jan J.; Volin, Liisa; Russell, Nigel H.; Socié, Gérard; Michallet, Mauricette; Fegueux, Nathalie; Chevallier, Patrice; Brecht, Arne; Hunault-Berger, Mathilde; Mohty, Mohamad; Esteve, Jordi; Nagler, Arnon

2018-01-01

Intermediate-risk cytogenetic acute myeloid leukemia with an internal tandem duplication of FLT3 (FLT3-ITD) is associated with a high risk of relapse, and is now a standard indication for allogeneic stem cell transplantation. Nevertheless, most studies supporting this strategy have been performed in young patients. To address the benefit of allogeneic transplantation in the elderly, we made a selection from the European Society for Blood and Marrow Transplantation registry of de novo intermediate-risk cytogenetic acute myeloid leukemia harboring FLT3-ITD in patients aged 60 or over and transplanted from a related or unrelated donor between January 2000 and December 2015. Two hundred and ninety-one patients were identified. Most patients received a reduced-intensity conditioning (82%), while donors consisted of an unrelated donor in 161 (55%) patients. Two hundred and twelve patients received their transplantation in first remission, 37 in second remission and 42 in a more advanced stage of the disease. The 2-year leukemia-free survival rate was 56% in patients in first remission, 22% in those in second remission and 10% in patients with active disease, respectively (P<0.005). Non-relapse mortality for the entire cohort was 20%. In multivariate analysis, disease status at transplantation was the most powerful predictor of worse leukemia-free survival, graft-versus-host disease and relapse-free survival, and overall survival. In this elderly population, age was not associated with outcome. Based on the current results, allogeneic transplantation translates into a favorable outcome in fit patients ≥ 60 with FLT3-ITD acute myeloid leukemia in first remission, similarly to current treatment recommendations for younger patients. PMID:29242299

Clinical Outcome of Inter-Proximal Papilla between a Tooth and a Single Implant Treated with CAD/CAM Abutments: a Cross-Sectional Study

PubMed Central

Lima, Tiago; Carvalho, Ágata; Carvalho, Vasco

2012-01-01

ABSTRACT Objectives The aim of this study was to assess the clinical outcomes achieved with Computer-Assisted Design/Computer-Assisted Manufacturing implant abutments in the anterior maxilla. Material and Methods Nineteen patients with a mean age of 41 (range form 26 to 63) years, treated with 21 single tooth implants and 21 Computer-Assisted Design/Computer-Assisted Manufacturing (CAD/CAM) abutments in the anterior maxillary region were included in this study. The patients followed 4 criteria of inclusion: (1) had a single-tooth implant in the anterior maxilla, (2) had a CAD/CAM abutment, (3) had a contralateral natural tooth, (4) the implant was restored and in function for at least 6 months up to 2 years. Cases without contact point were excluded. Presence/absence of the interproximal papilla, inter tooth-implant distance (ITD) and distance from the base of the contact point to dental crest bone of adjacent tooth (CPB) were accessed. Results Forty interproximal spaces were evaluated, with an average mesial CPB of 5.65 (SD 1.65) mm and distal CPB of 4.65 (SD 1.98) mm. An average mesial ITD of 2.49 (SD 0.69) mm and an average distal ITD of 1.89 (SD 0.63) mm were achieved. Papilla was present in all the interproximal spaces accessed. Conclusions The restoration of dental implants using CAD/CAM abutments is a predictable treatment with improved aesthetic results. These type of abutments seem to help maintaining a regular papillary filling although the variations of the implant positioning or the restoration teeth relation. PMID:24422016

Does the relief of glucose toxicity act as a mediator in proliferative actions of vanadium on pancreatic islet beta cells in streptozocin diabetic rats?

PubMed

Pirmoradi, Leila; Mohammadi, Mohammad Taghi; Safaei, Akbar; Mesbah, Fakhardin; Dehghani, Gholam Abbas

2014-07-01

Data shows vanadium protects pancreatic beta cells (BC) from diabetic animals. Whether this effect is direct or through the relief of glucose toxicity is not clear. This study evaluated the potential effect of oral vanadyl sulfate (vanadium) on glycemic status and pancreatic BC of normal and diabetic rats. Rats were divided into five groups of normal and diabetic. Diabetes was induced with streptozocin (40 mg/kg, i.v.). Normal rats used water (CN) or vanadium (1 mg/ml VOSO4, VTN). Diabetic rats used water (CD), water plus daily neutral protamine Hagedorn insulin injection (80 U/kg, ITD) or vanadium (VTD). Blood samples were taken for blood glucose (BG, mg/dL) and insulin (ng/dL) measurements. After two months, the pancreata of sacrificed rats were prepared for islet staining. Pre-treated normal BG was 88 ± 2, and diabetic BG was 395 ± 9. The final BG in CD, VTD, and ITD was 509 ± 22, 138 ± 14, and 141 ± 14, respectively. Insulin in VTN (0.75 ± 0.01) and VTD (0.78 ± 0.01) was similar, higher than CD (0.51 ± 0.07) but lower than CN (2.51 ± 0.02). VTN islets compared to CN had larger size and denser central core insulin immunoreactivity with plentiful BC. CD and ITD islets were atrophied and had scattered insulin immunoreactivity spots and low BC mass. VTD islets were almost similar to CN. Besides insulin-like activity, vanadium protected pancreatic islet BC, and the relief of glucose toxicity happening with vanadium had a little role in this action.

Does the Relief of Glucose Toxicity Act As a Mediator in Proliferative Actions of Vanadium on Pancreatic Islet Beta Cells in Streptozocin Diabetic Rats?

PubMed Central

Pirmoradi, Leila; Mohammadi, Mohammad Taghi; Safaei, Akbar; Mesbah, Fakhardin; Dehghani, Gholam Abbas

2014-01-01

Background: Data shows vanadium protects pancreatic beta cells (BC) from diabetic animals. Whether this effect is direct or through the relief of glucose toxicity is not clear. This study evaluated the potential effect of oral vanadyl sulfate (vanadium) on glycemic status and pancreatic BC of normal and diabetic rats. Methods: Rats were divided into five groups of normal and diabetic. Diabetes was induced with streptozocin (40 mg/kg, i.v.). Normal rats used water (CN) or vanadium (1 mg/ml VOSO4, VTN). Diabetic rats used water (CD), water plus daily neutral protamine Hagedorn insulin injection (80 U/kg, ITD) or vanadium (VTD). Blood samples were taken for blood glucose (BG, mg/dL) and insulin (ng/dL) measurements. After two months, the pancreata of sacrificed rats were prepared for islet staining. Results: Pre-treated normal BG was 88 ± 2, and diabetic BG was 395 ± 9. The final BG in CD, VTD, and ITD was 509 ± 22, 138 ± 14, and 141 ± 14, respectively. Insulin in VTN (0.75 ± 0.01) and VTD (0.78 ± 0.01) was similar, higher than CD (0.51 ± 0.07) but lower than CN (2.51 ± 0.02). VTN islets compared to CN had larger size and denser central core insulin immunoreactivity with plentiful BC. CD and ITD islets were atrophied and had scattered insulin immunoreactivity spots and low BC mass. VTD islets were almost similar to CN. Conclusion: Besides insulin-like activity, vanadium protected pancreatic islet BC, and the relief of glucose toxicity happening with vanadium had a little role in this action. PMID:24842144

Pelvimetry in nulliparous and primiparous women using 3 Tesla magnetic resonance imaging.

PubMed

Hampel, Franziska; Hallscheidt, Peter; Sohn, Christof; Schlehe, Bettina; Brocker, Kerstin A

2018-02-21

To perform pelvimetry in nulliparous and primiparous women using 3 Tesla magnetic resonance imaging (3T MRI). Twenty-five nulliparous volunteers and 25 primiparous women underwent pelvic 3T MRI within one week after vaginal childbirth in a prospective clinical single-center trial. The pelvimetric parameters interspinous distance (ISD), intertuberous distance (ITD), sagittal outlet (SO), obstetric conjugate (OC), and coccygeal curved length (CCL) were adapted from anthropometric measurements as well as from sonographic and computed tomography-based pelvimetry performed on high-resolution T2-weighted images. We compared the results of the two study groups to one another, recent literature and postpartum-diagnosed levator ani muscle (LAM) injuries. The mean values for primipara/nullipara were ISD 107 ± 8.3/105 ± 8.4 mm, ITD 119.8 ± 10.2/118.4 ± 13.1 mm, OC 129.4 ± 10/130.8 ± 6.9 mm, SO 114.3 ± 7.8/112.5 ± 8.9 mm, and CCL 37.3 ± 7.4/39 ± 8 mm. Significant differences (P < 0.05) were found between the results for OC, SO, and CCL (primipara) and ISD, ITD and OC (nullipara) and the values in the literature. No significant difference in pelvimetric values was found between the groups. A significant correlation was found between the pelvimetric parameters and five types of LAM injuries. Two-dimensional 3T MRI combines high-resolution images with objective pelvimetric measurements applicable in a postpartum setting. Our results provide a good foundation for further MRI-based studies evaluating the bony pelvis and its relation to LAM injuries during vaginal childbirth. © 2018 Wiley Periodicals, Inc.

Relative size of auditory pathways in symmetrically and asymmetrically eared owls.

PubMed

Gutiérrez-Ibáñez, Cristián; Iwaniuk, Andrew N; Wylie, Douglas R

2011-01-01

Owls are highly efficient predators with a specialized auditory system designed to aid in the localization of prey. One of the most unique anatomical features of the owl auditory system is the evolution of vertically asymmetrical ears in some species, which improves their ability to localize the elevational component of a sound stimulus. In the asymmetrically eared barn owl, interaural time differences (ITD) are used to localize sounds in azimuth, whereas interaural level differences (ILD) are used to localize sounds in elevation. These two features are processed independently in two separate neural pathways that converge in the external nucleus of the inferior colliculus to form an auditory map of space. Here, we present a comparison of the relative volume of 11 auditory nuclei in both the ITD and the ILD pathways of 8 species of symmetrically and asymmetrically eared owls in order to investigate evolutionary changes in the auditory pathways in relation to ear asymmetry. Overall, our results indicate that asymmetrically eared owls have much larger auditory nuclei than owls with symmetrical ears. In asymmetrically eared owls we found that both the ITD and ILD pathways are equally enlarged, and other auditory nuclei, not directly involved in binaural comparisons, are also enlarged. We suggest that the hypertrophy of auditory nuclei in asymmetrically eared owls likely reflects both an improved ability to precisely locate sounds in space and an expansion of the hearing range. Additionally, our results suggest that the hypertrophy of nuclei that compute space may have preceded that of the expansion of the hearing range and evolutionary changes in the size of the auditory system occurred independently of phylogeny. Copyright © 2011 S. Karger AG, Basel.

The influence of imagery vividness on cognitive and perceptual cues in circular auditorily-induced vection.

PubMed

Väljamäe, Aleksander; Sell, Sara

2014-01-01

In the absence of other congruent multisensory motion cues, sound contribution to illusions of self-motion (vection) is relatively weak and often attributed to purely cognitive, top-down processes. The present study addressed the influence of cognitive and perceptual factors in the experience of circular, yaw auditorily-induced vection (AIV), focusing on participants imagery vividness scores. We used different rotating sound sources (acoustic landmark vs. movable types) and their filtered versions that provided different binaural cues (interaural time or level differences, ITD vs. ILD) when delivering via loudspeaker array. The significant differences in circular vection intensity showed that (1) AIV was stronger for rotating sound fields containing auditory landmarks as compared to movable sound objects; (2) ITD based acoustic cues were more instrumental than ILD based ones for horizontal AIV; and (3) individual differences in imagery vividness significantly influenced the effects of contextual and perceptual cues. While participants with high scores of kinesthetic and visual imagery were helped by vection "rich" cues, i.e., acoustic landmarks and ITD cues, the participants from the low-vivid imagery group did not benefit from these cues automatically. Only when specifically asked to use their imagination intentionally did these external cues start influencing vection sensation in a similar way to high-vivid imagers. These findings are in line with the recent fMRI work which suggested that high-vivid imagers employ automatic, almost unconscious mechanisms in imagery generation, while low-vivid imagers rely on more schematic and conscious framework. Consequently, our results provide an additional insight into the interaction between perceptual and contextual cues when experiencing purely auditorily or multisensory induced vection.

The influence of imagery vividness on cognitive and perceptual cues in circular auditorily-induced vection

PubMed Central

Väljamäe, Aleksander; Sell, Sara

2014-01-01

In the absence of other congruent multisensory motion cues, sound contribution to illusions of self-motion (vection) is relatively weak and often attributed to purely cognitive, top-down processes. The present study addressed the influence of cognitive and perceptual factors in the experience of circular, yaw auditorily-induced vection (AIV), focusing on participants imagery vividness scores. We used different rotating sound sources (acoustic landmark vs. movable types) and their filtered versions that provided different binaural cues (interaural time or level differences, ITD vs. ILD) when delivering via loudspeaker array. The significant differences in circular vection intensity showed that (1) AIV was stronger for rotating sound fields containing auditory landmarks as compared to movable sound objects; (2) ITD based acoustic cues were more instrumental than ILD based ones for horizontal AIV; and (3) individual differences in imagery vividness significantly influenced the effects of contextual and perceptual cues. While participants with high scores of kinesthetic and visual imagery were helped by vection “rich” cues, i.e., acoustic landmarks and ITD cues, the participants from the low-vivid imagery group did not benefit from these cues automatically. Only when specifically asked to use their imagination intentionally did these external cues start influencing vection sensation in a similar way to high-vivid imagers. These findings are in line with the recent fMRI work which suggested that high-vivid imagers employ automatic, almost unconscious mechanisms in imagery generation, while low-vivid imagers rely on more schematic and conscious framework. Consequently, our results provide an additional insight into the interaction between perceptual and contextual cues when experiencing purely auditorily or multisensory induced vection. PMID:25520683

Weed-Suppressive Soil Bacteria to Reduce Cheatgrass and Improve Vegetation Diversity on ITD Rights-of-Way

DOT National Transportation Integrated Search

2017-06-01

Transportation departments are challenged by the invasion of downy brome (cheatgrass) and medusahead. The reduction of downy brome (cheat grass) by Weed Suppressive Bacteria (WSB) Pseudomonas fluorescens strain ACK55 was evaluated on roadsides of I-8...

Review of non-nuclear density gauges as possible replacements for ITD's nuclear density gauges.

DOT National Transportation Integrated Search

2015-01-01

This report examines the possibility of replacing nuclear density gauges (NDGs) with non-nuclear density gauges (NNDGs) to : measure density of hot mix asphalt (HMA) and unbound pavement layers in the field. The research team evaluated the : effectiv...

Information Technology and Disabilities, 1996.

ERIC Educational Resources Information Center

McNulty, Tom, Ed.

1996-01-01

This document consists of all issues/pages of the electronic journal "Information Technology and Disabilities" published during 1996, i.e., a total of 13 ITD articles: (1) "New CSUF (California State University at Fullerton) Braille Transcription Center Promotes Access to Postsecondary Instructional Materials for the California State University…

Seasonal evolution of the Arctic marginal ice zone and its power-law obeying floe size distribution

NASA Astrophysics Data System (ADS)

Zhang, J.; Stern, H. L., III; Schweiger, A. J. B.; Steele, M.; Hwang, P. B.

2017-12-01

A thickness, floe size, and enthalpy distribution (TFED) sea ice model, implemented numerically into the Pan-arctic Ice-Ocean Modeling and Assimilation System (PIOMAS), is used to investigate the seasonal evolution of the Arctic marginal ice zone (MIZ) and its floe size distribution. The TFED sea ice model, by coupling the Zhang et al. [2015] sea ice floe size distribution (FSD) theory with the Thorndike et al. [1975] ice thickness distribution (ITD) theory, simulates 12-category FSD and ITD explicitly and jointly. A range of ice thickness and floe size observations were used for model calibration and validation. The model creates FSDs that generally obey a power law or upper truncated power law, as observed by satellites and aerial surveys. In this study, we will examine the role of ice fragmentation and lateral melting in altering FSDs in the Arctic MIZ. We will also investigate how changes in FSD impact the seasonal evolution of the MIZ by modifying the thermodynamic processes.

Spatial cue reliability drives frequency tuning in the barn Owl's midbrain

PubMed Central

Cazettes, Fanny; Fischer, Brian J; Pena, Jose L

2014-01-01

The robust representation of the environment from unreliable sensory cues is vital for the efficient function of the brain. However, how the neural processing captures the most reliable cues is unknown. The interaural time difference (ITD) is the primary cue to localize sound in horizontal space. ITD is encoded in the firing rate of neurons that detect interaural phase difference (IPD). Due to the filtering effect of the head, IPD for a given location varies depending on the environmental context. We found that, in barn owls, at each location there is a frequency range where the head filtering yields the most reliable IPDs across contexts. Remarkably, the frequency tuning of space-specific neurons in the owl's midbrain varies with their preferred sound location, matching the range that carries the most reliable IPD. Thus, frequency tuning in the owl's space-specific neurons reflects a higher-order feature of the code that captures cue reliability. DOI: http://dx.doi.org/10.7554/eLife.04854.001 PMID:25531067

Physiological models of the lateral superior olive

PubMed Central

2017-01-01

In computational biology, modeling is a fundamental tool for formulating, analyzing and predicting complex phenomena. Most neuron models, however, are designed to reproduce certain small sets of empirical data. Hence their outcome is usually not compatible or comparable with other models or datasets, making it unclear how widely applicable such models are. In this study, we investigate these aspects of modeling, namely credibility and generalizability, with a specific focus on auditory neurons involved in the localization of sound sources. The primary cues for binaural sound localization are comprised of interaural time and level differences (ITD/ILD), which are the timing and intensity differences of the sound waves arriving at the two ears. The lateral superior olive (LSO) in the auditory brainstem is one of the locations where such acoustic information is first computed. An LSO neuron receives temporally structured excitatory and inhibitory synaptic inputs that are driven by ipsi- and contralateral sound stimuli, respectively, and changes its spike rate according to binaural acoustic differences. Here we examine seven contemporary models of LSO neurons with different levels of biophysical complexity, from predominantly functional ones (‘shot-noise’ models) to those with more detailed physiological components (variations of integrate-and-fire and Hodgkin-Huxley-type). These models, calibrated to reproduce known monaural and binaural characteristics of LSO, generate largely similar results to each other in simulating ITD and ILD coding. Our comparisons of physiological detail, computational efficiency, predictive performances, and further expandability of the models demonstrate (1) that the simplistic, functional LSO models are suitable for applications where low computational costs and mathematical transparency are needed, (2) that more complex models with detailed membrane potential dynamics are necessary for simulation studies where sub-neuronal nonlinear processes play important roles, and (3) that, for general purposes, intermediate models might be a reasonable compromise between simplicity and biological plausibility. PMID:29281618

ACHP | Working Together to Build a More Inclusive Preservation Program

Science.gov Websites

either work in a museum or teach. I was home for the summer and thought it'd be a good opportunity to even thought about the East Kong Yick Building as its possible new home, it was powerful to know that

76 FR 50268 - Amended Certification Regarding Eligibility To Apply for Worker Adjustment Assistance

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-12

... Certification Regarding Eligibility To Apply for Worker Adjustment Assistance TA-W-73,218 International Business... International Business Machines Corporation (IBM), ITD Business Unit, Division 7, Email and Collaboration Group..., the Department is amending this certification to include workers of International Business Machines...

Changes in Arctic Sea Ice Floe Size Distribution in the Marginal Ice Zone in a Thickness and Floe Size Distribution Model

NASA Astrophysics Data System (ADS)

Zhang, J.; Stern, H. L., III; Hwang, P. B.; Schweiger, A. J. B.; Stark, M.; Steele, M.

2015-12-01

To better describe the state of sea ice in the marginal ice zone (MIZ) with floes of varying thicknesses and sizes, both an ice thickness distribution (ITD) and a floe size distribution (FSD) are needed. We have developed a FSD theory [Zhang et al., 2015] that is coupled to the ITD theory of Thorndike et al. [1975] in order to explicitly simulate the evolution of FSD and ITD jointly. The FSD theory includes a FSD function and a FSD conservation equation in parallel with the ITD equation. The FSD equation takes into account changes in FSD due to ice advection, thermodynamic growth, and lateral melting. It also includes changes in FSD because of mechanical redistribution of floe size due to ice opening, ridging and, particularly, ice fragmentation induced by stochastic ocean surface waves. The floe size redistribution due to ice fragmentation is based on the assumption that wave-induced breakup is a random process such that when an ice floe is broken, floes of any smaller sizes have an equal opportunity to form, without being either favored or excluded. It is also based on the assumption that floes of larger sizes are easier to break because they are subject to larger flexure-induced stresses and strains than smaller floes that are easier to ride with waves with little bending; larger floes also have higher areal coverages and therefore higher probabilities to break. These assumptions with corresponding formulations ensure that the simulated FSD follows a power law as observed by satellites and airborne surveys. The FSD theory has been tested in the Pan-arctic Ice/Ocean Modeling and Assimilation System (PIOMAS). The existing PIOMAS has 12 categories each for ice thickness, ice enthalpy, and snow depth. With the implementation of the FSD theory, PIOMAS is able to represent 12 categories of floe sizes ranging from 0.1 m to ~3000 m. It is found that the simulated 12-category FSD agrees reasonably well with FSD derived from SAR and MODIS images. In this study, we will examine PIOMAS-estimated variability and changes in Arctic FSD over the period 1979-present. Thorndike, A. S., D. A. Rothrock, G. A. Maykut, and R. Colony, The thickness distribution of sea ice. J. Geophys. Res., 80, 1975. Zhang, J., A. Schweiger, M. Steele, and H. Stern, Sea ice floe size distribution in the marginal ice zone: Theory and numerical experiments, J. Geophys. Res., 120, 2015.

Information Technology and Disabilities, 1994.

ERIC Educational Resources Information Center

McNulty, Tom, Ed.

1994-01-01

Four issues of this newsletter on information technology and disabilities (ITD) contain the following articles: "Building an Accessible CD-ROM Reference Station" (Rochelle Wyatt and Charles Hamilton); "Development of an Accessible User Interface for People Who Are Blind or Vision Impaired as Part of the Re-Computerisation of Royal Blind Society…

Alternative Fuels Data Center

Science.gov Websites

Transportation Department (ITD) established the Connected and Autonomous Vehicle (CAV) Testing and Deployment testing and deployment of CAVs, coordinate with the identified agencies about how to administer the testing of CAVs on roads, review existing state statues and administrative rules that impede the testing

Road map for implementing the AASHTO pavement ME design software for the Idaho Transportation Department.

DOT National Transportation Integrated Search

2014-04-01

This report provides a Road Map for implementing the AASHTOWare Pavement ME Design software for the Idaho Transportation Department (ITD). The Road Map calls for a series of three stages: Stage 1 - Immediate, Stage 2 - Near Term, and Stage 3 - Future...

Changes in Arctic Sea Ice Thickness and Floe Size

NASA Astrophysics Data System (ADS)

Zhang, J.; Schweiger, A. J. B.; Stern, H. L., III; Steele, M.

2016-12-01

A thickness, floe size, and enthalpy distribution sea ice model was implemented into the Pan-arctic Ice-Ocean Modeling and Assimilation System (PIOMAS) by coupling the Zhang et al. [2015] sea ice floe size distribution (FSD) theory with the Thorndike et al. [1975] ice thickness distribution (ITD) theory in order to explicitly simulate multicategory FSD and ITD simultaneously. A range of ice thickness and floe size observations were used for model calibration and validation. The expanded, validated PIOMAS was used to study sea ice response to atmospheric and oceanic changes in the Arctic, focusing on the interannual variability and trends of ice thickness and floe size over the period 1979-2015. It is found that over the study period both ice thickness and floe size have been decreasing steadily in the Arctic. The simulated ice thickness shows considerable spatiotemporal variability in recent years. As the ice cover becomes thinner and weaker, the model simulates an increasing number of small floes (at the low end of the FSD), which affects sea ice properties, particularly in the marginal ice zone.

[Research activities in Kobe-Indonesia Collaborative Research Centers].

PubMed

Utsumi, Takako; Hayashi, Yoshitake; Hotta, Hak

2013-01-01

Kobe-Indonesia Collaborative Research Center was established in Institute of Tropical Disease (ITD), Airlangga University, Surabaya, Indonesia in 2007 under the program of ''Founding Research Centers for Emerging and Reemerging Infectious Diseases'' supported by the Ministry of Education, Culture, Sports, Science and Technology, Japan, and then it has been under the Japan Initiative for Global Research Network on Infectious Diseases (J-GRID) since 2010. Japanese researchers have been stationed at ITD, conducting joint researches on influenza, viral hepatitis, dengue and infectious diarrhea. Also, another Japanese researcher has been stationed at Faculty of Medicine, University of Indonesia, Jakarta, carrying out joint researches on'' Identification of anti-hepatitis C virus (HCV) substances and development of HCV and dengue vaccines'' in collaboration with University of Indonesia and Airlangga University through the Science and Technology Research Partnership for Sustainable Development (SATREPS) supported by the Japan Science and Technology Agency (JST) and Japan International Cooperation Agency (JICA) since 2009. In this article, we briefly introduce the background history of Kobe University Research Center in Indonesia, and discuss the research themes and outcomes of J-GRID and SATREPS activities.

Configuration Aerodynamics: Past - Present - Future

NASA Technical Reports Server (NTRS)

Wood, Richard M.; Agrawal, Shreekant; Bencze, Daniel P.; Kulfan, Robert M.; Wilson, Douglas L.

1999-01-01

The Configuration Aerodynamics (CA) element of the High Speed Research (HSR) program is managed by a joint NASA and Industry team, referred to as the Technology Integration Development (ITD) team. This team is responsible for the development of a broad range of technologies for improved aerodynamic performance and stability and control characteristics at subsonic to supersonic flight conditions. These objectives are pursued through the aggressive use of advanced experimental test techniques and state of the art computational methods. As the HSR program matures and transitions into the next phase the objectives of the Configuration Aerodynamics ITD are being refined to address the drag reduction needs and stability and control requirements of High Speed Civil Transport (HSCT) aircraft. In addition, the experimental and computational tools are being refined and improved to meet these challenges. The presentation will review the work performed within the Configuration Aerodynamics element in 1994 and 1995 and then discuss the plans for the 1996-1998 time period. The final portion of the presentation will review several observations of the HSR program and the design activity within Configuration Aerodynamics.

Allogeneic stem cell transplantation benefits for patients ≥ 60 years with acute myeloid leukemia and FLT3 internal tandem duplication: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.

PubMed

Poiré, Xavier; Labopin, Myriam; Polge, Emmanuelle; Passweg, Jakob; Craddock, Charles; Blaise, Didier; Cornelissen, Jan J; Volin, Liisa; Russell, Nigel H; Socié, Gérard; Michallet, Mauricette; Fegueux, Nathalie; Chevallier, Patrice; Brecht, Arne; Hunault-Berger, Mathilde; Mohty, Mohamad; Esteve, Jordi; Nagler, Arnon

2018-02-01

Intermediate-risk cytogenetic acute myeloid leukemia with an internal tandem duplication of FLT3 ( FLT3 -ITD) is associated with a high risk of relapse, and is now a standard indication for allogeneic stem cell transplantation. Nevertheless, most studies supporting this strategy have been performed in young patients. To address the benefit of allogeneic transplantation in the elderly, we made a selection from the European Society for Blood and Marrow Transplantation registry of de novo intermediate-risk cytogenetic acute myeloid leukemia harboring FLT3 -ITD in patients aged 60 or over and transplanted from a related or unrelated donor between January 2000 and December 2015. Two hundred and ninety-one patients were identified. Most patients received a reduced-intensity conditioning (82%), while donors consisted of an unrelated donor in 161 (55%) patients. Two hundred and twelve patients received their transplantation in first remission, 37 in second remission and 42 in a more advanced stage of the disease. The 2-year leukemia-free survival rate was 56% in patients in first remission, 22% in those in second remission and 10% in patients with active disease, respectively ( P <0.005). Non-relapse mortality for the entire cohort was 20%. In multivariate analysis, disease status at transplantation was the most powerful predictor of worse leukemia-free survival, graft- versus -host disease and relapse-free survival, and overall survival. In this elderly population, age was not associated with outcome. Based on the current results, allogeneic transplantation translates into a favorable outcome in fit patients ≥ 60 with FLT3 -ITD acute myeloid leukemia in first remission, similarly to current treatment recommendations for younger patients. Copyright© 2018 Ferrata Storti Foundation.

Impact of pre-transplantation minimal residual disease determined by multiparameter flow cytometry on the outcome of AML patients with FLT3-ITD after allogeneic stem cell transplantation.

PubMed

Zhao, Xiaosu; Wang, Zhidong; Ruan, Guorui; Liu, Yanrong; Wang, Yu; Zhang, Xiaohui; Xu, Lanping; Huang, Xiaojun; Chang, Yingjun

2018-06-01

In this study, using multiparameter flow cytometry (FCM), we investigate the impact of minimal residual disease prior to transplantation (pre-MRD) on the transplant outcomes of AML patients with fms-related tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) mutation. A total of 20 patients who received HLA-matched sibling donor transplantation (MSDT) and 63 patients who received unmanipulated haploidentical hematopoietic stem cell transplantation (haplo-HSCT) were enrolled. Patients were classified into four groups based on the status of pre-FCM: group 1 with positive pre-FCM before MSDT, group 2 with negative pre-FCM before MSDT, group 3 with positive pre-FCM before haplo-HSCT, and group 4 with positive pre-FCM before haplo-HSCT. The results showed that patients in group 1 had the highest cumulative incidence of relapse (2-year CIR, 75.0%), the lowest leukemia-free survival (2-year LFS, 33.3%), and the overall survival (2-year OS, 25.0%) among all four groups. The other three groups of patients had comparable CIR (2-year CIR: group 2 vs. 3 vs. 4, 12.5% vs. 31.3% vs. 22.2%, P > 0.05) and LFS (2-year LFS: group 2 vs. 3 vs. 4, 87.5% vs. 62.5% vs. 66.5%, P > 0.05). Multivariate analysis indicated that disease status (> CR) and pre-MRD were associated with a higher CIR and a lower LFS when patients were classified by pre-MRD and transplant type. Our results suggested that AML patients with FLT3-ITD were able to be separated into high-risk and low-risk relapse groups based on pre-MRD, as determined by multiparameter FCM. Haplo-HSCT might overcome the negative impact of pre-MRD on patient outcomes compared to MSDT. These results require further investigation in prospective study with large numbers of cases.

Coincidence detection in the medial superior olive: mechanistic implications of an analysis of input spiking patterns

PubMed Central

Franken, Tom P.; Bremen, Peter; Joris, Philip X.

2014-01-01

Coincidence detection by binaural neurons in the medial superior olive underlies sensitivity to interaural time difference (ITD) and interaural correlation (ρ). It is unclear whether this process is akin to a counting of individual coinciding spikes, or rather to a correlation of membrane potential waveforms resulting from converging inputs from each side. We analyzed spike trains of axons of the cat trapezoid body (TB) and auditory nerve (AN) in a binaural coincidence scheme. ITD was studied by delaying “ipsi-” vs. “contralateral” inputs; ρ was studied by using responses to different noises. We varied the number of inputs; the monaural and binaural threshold and the coincidence window duration. We examined physiological plausibility of output “spike trains” by comparing their rate and tuning to ITD and ρ to those of binaural cells. We found that multiple inputs are required to obtain a plausible output spike rate. In contrast to previous suggestions, monaural threshold almost invariably needed to exceed binaural threshold. Elevation of the binaural threshold to values larger than 2 spikes caused a drastic decrease in rate for a short coincidence window. Longer coincidence windows allowed a lower number of inputs and higher binaural thresholds, but decreased the depth of modulation. Compared to AN fibers, TB fibers allowed higher output spike rates for a low number of inputs, but also generated more monaural coincidences. We conclude that, within the parameter space explored, the temporal patterns of monaural fibers require convergence of multiple inputs to achieve physiological binaural spike rates; that monaural coincidences have to be suppressed relative to binaural ones; and that the neuron has to be sensitive to single binaural coincidences of spikes, for a number of excitatory inputs per side of 10 or less. These findings suggest that the fundamental operation in the mammalian binaural circuit is coincidence counting of single binaural input spikes. PMID:24822037

The Binaural Interaction Component in Barn Owl (Tyto alba) Presents few Differences to Mammalian Data.

PubMed

Palanca-Castan, Nicolas; Laumen, Geneviève; Reed, Darrin; Köppl, Christine

2016-12-01

The auditory brainstem response (ABR) is an evoked potential that reflects the responses to sound by brainstem neural centers. The binaural interaction component (BIC) is obtained by subtracting the sum of the monaural ABR responses from the binaural response. Its latency and amplitude change in response to variations in binaural cues. The BIC is thus thought to reflect the activity of binaural nuclei and is used to non-invasively test binaural processing. However, any conclusions are limited by a lack of knowledge of the relevant processes at the level of individual neurons. The aim of this study was to characterize the ABR and BIC in the barn owl, an animal where the ITD-processing neural circuits are known in great detail. We recorded ABR responses to chirps and to 1 and 4 kHz tones from anesthetized barn owls. General characteristics of the barn owl ABR were similar to those observed in other bird species. The most prominent peak of the BIC was associated with nucleus laminaris and is thus likely to reflect the known processes of ITD computation in this nucleus. However, the properties of the BIC were very similar to previously published mammalian data and did not reveal any specific diagnostic features. For example, the polarity of the BIC was negative, which indicates a smaller response to binaural stimulation than predicted by the sum of monaural responses. This is contrary to previous predictions for an excitatory-excitatory system such as nucleus laminaris. Similarly, the change in BIC latency with varying ITD was not distinguishable from mammalian data. Contrary to previous predictions, this behavior appears unrelated to the known underlying neural delay-line circuitry. In conclusion, the generation of the BIC is currently inadequately understood and common assumptions about the BIC need to be reconsidered when interpreting such measurements.

Does hemipelvis structure and position influence acetabulum orientation?

PubMed

Musielak, Bartosz; Jóźwiak, Marek; Rychlik, Michał; Chen, Brian Po-Jung; Idzior, Maciej; Grzegorzewski, Andrzej

2016-03-16

Although acetabulum orientation is well established anatomically and radiographically, its relation to the innominate bone has rarely been addressed. If explored, it could open the discussion on patomechanisms of such complex disorders as femoroacetabular impingement (FAI). We therefore evaluated the influence of pelvic bone position and structure on acetabular spatial orientation. We describe this relation and its clinical implications. This retrospective study was based on computed tomography scanning of three-dimensional models of 31 consecutive male pelvises (62 acetabulums). All measurements were based on CT spatial reconstruction with the use of highly specialized software (Rhinoceros). Relations between acetabular orientation (inclination, tilt, anteversion angles) and pelvic structure were evaluated. The following parameters were evaluated to assess the pelvic structure: iliac opening angle, iliac tilt angle, interspinous distance (ISD), intertuberous distance (ITD), height of the pelvis (HP), and the ISD/ITD/HP ratio. The linear and nonlinear dependence of the acetabular angles and hemipelvic measurements were examined with Pearson's product - moment correlation and Spearman's rank correlation coefficient. Correlations different from 0 with p < 0.05 were considered statistically significant. Comparison of the axis position with pelvis structure with orientation in the horizontal plane revealed a significant positive correlation between the acetabular anteversion angle and the iliac opening angle (p = 0.041 and 0.008, respectively). In the frontal plane, there was a positive correlation between the acetabular inclination angle and the iliac tilt angle (p = 0.025 and 0.014, respectively) and the acetabular inclination angle and the ISD/ITD/HP ratio (both p = 0.048). There is a significant correlation of the hemipelvic structure and acetabular orientation under anatomic conditions, especially in the frontal and horizontal planes. In the anteroposterior view, the more tilted-down innominate bone causes a more caudally oriented acetabulum axis, whereas in the horizontal view this relation is reversed. This study may serve as a basis for the discussion on the role of the pelvis in common disorders of the hip.

Monaural and binaural response properties of neurons in the inferior colliculus of the rabbit: effects of sodium pentobarbital.

PubMed

Kuwada, S; Batra, R; Stanford, T R

1989-02-01

1. We studied the effects of sodium pentobarbital on 22 neurons in the inferior colliculus (IC) of the rabbit. We recorded changes in the sensitivity of these neurons to monaural stimulation and to ongoing interaural time differences (ITDs). Monaural stimuli were tone bursts at or near the neuron's best frequency. The ITD was varied by delivering tones that differed by 1 Hz to the two ears, resulting in a 1-Hz binaural beat. 2. We assessed a neuron's ITD sensitivity by calculating three measures from the responses to binaural beats: composite delay, characteristic delay (CD), and characteristic phase (CP). To obtain the composite delay, we first derived period histograms by averaging, showing the response at each stimulating frequency over one period of the beat frequency. Second, the period histograms were replotted as a function of their equivalent interaural delay and then averaged together to yield the composite delay curve. Last, we calculated the composite peak or trough delay by fitting a parabola to the peak or trough of this composite curve. The composite delay curve represents the average response to all frequencies within the neuron's responsive range, and the peak reflects the interaural delay that produces the maximum response. The CD and CP were estimated from a weighted fit of a regression line to the plot of the mean interaural phase of the response versus the stimulating frequency. The slope and phase intercept of this regression line yielded estimates of CD and CP, respectively. These two quantities are thought to reflect the mechanism of ITD sensitivity, which involves the convergence of phase-locked inputs on a binaural cell. The CD estimates the difference in the time required for the two inputs to travel from either ear to this cell, whereas the CP reflects the interaural phase difference of the inputs at this cell. 3. Injections of sodium pentobarbital at subsurgical dosages (less than 25 mg/kg) almost invariably altered the neuron's response rate, response latency, response pattern, and spontaneous activity. Most of these changes were predictable and consistent with an enhancement of inhibitory influences. For example, if the earliest response was inhibitory, later excitation was usually reduced and latency increased. If the earliest response was excitatory, the level of this excitation was unaltered or slightly enhanced, and changes in latency were minimal. 4. The neuron's response pattern also changed in a predictable way. For example, a response with an inhibitory pause could either change to a response with a longer pause or to a response with an onset only.(ABSTRACT TRUNCATED AT 400 WORDS)

A Scheduling Algorithm for Cloud Computing System Based on the Driver of Dynamic Essential Path.

PubMed

Xie, Zhiqiang; Shao, Xia; Xin, Yu

2016-01-01

To solve the problem of task scheduling in the cloud computing system, this paper proposes a scheduling algorithm for cloud computing based on the driver of dynamic essential path (DDEP). This algorithm applies a predecessor-task layer priority strategy to solve the problem of constraint relations among task nodes. The strategy assigns different priority values to every task node based on the scheduling order of task node as affected by the constraint relations among task nodes, and the task node list is generated by the different priority value. To address the scheduling order problem in which task nodes have the same priority value, the dynamic essential long path strategy is proposed. This strategy computes the dynamic essential path of the pre-scheduling task nodes based on the actual computation cost and communication cost of task node in the scheduling process. The task node that has the longest dynamic essential path is scheduled first as the completion time of task graph is indirectly influenced by the finishing time of task nodes in the longest dynamic essential path. Finally, we demonstrate the proposed algorithm via simulation experiments using Matlab tools. The experimental results indicate that the proposed algorithm can effectively reduce the task Makespan in most cases and meet a high quality performance objective.

A Scheduling Algorithm for Cloud Computing System Based on the Driver of Dynamic Essential Path

PubMed Central

Xie, Zhiqiang; Shao, Xia; Xin, Yu

2016-01-01

To solve the problem of task scheduling in the cloud computing system, this paper proposes a scheduling algorithm for cloud computing based on the driver of dynamic essential path (DDEP). This algorithm applies a predecessor-task layer priority strategy to solve the problem of constraint relations among task nodes. The strategy assigns different priority values to every task node based on the scheduling order of task node as affected by the constraint relations among task nodes, and the task node list is generated by the different priority value. To address the scheduling order problem in which task nodes have the same priority value, the dynamic essential long path strategy is proposed. This strategy computes the dynamic essential path of the pre-scheduling task nodes based on the actual computation cost and communication cost of task node in the scheduling process. The task node that has the longest dynamic essential path is scheduled first as the completion time of task graph is indirectly influenced by the finishing time of task nodes in the longest dynamic essential path. Finally, we demonstrate the proposed algorithm via simulation experiments using Matlab tools. The experimental results indicate that the proposed algorithm can effectively reduce the task Makespan in most cases and meet a high quality performance objective. PMID:27490901

Software Independent Verification and Validation (SIV&V) Simplified

DTIC Science & Technology

2006-12-01

Configuration Item I/O Input/Output I2V2 Independent Integrated Verification and Validation IBM International Business Machines ICD Interface...IPT Integrated Product Team IRS Interface Requirements Specification ISD Integrated System Diagram ITD Integrated Test Description ITP ...programming languages such as COBOL (Common Business Oriented Language) (Codasyl committee 1960), and FORTRAN (FORmula TRANslator) ( IBM 1952) (Robat 11

Ballet as Somatic Practice: A Case Study Exploring the Integration of Somatic Practices in Ballet Pedagogy

ERIC Educational Resources Information Center

Berg, Tanya

2017-01-01

This case study explores one teacher's integration of Alexander Technique and the work of neuromuscular retrainer Irene Dowd in ballet pedagogy to establish a somatic approach to teaching, learning, and performing ballet technique. This case study highlights the teacher's unique teaching method called IMAGE TECH for dancers (ITD) and offers…

U.S. EPA, Pesticide Product Label, ALL SEASON SPRAYABLE WEED & FEED, 10/04/1991

EPA Pesticide Factsheets

2011-04-21

... ltifo ~tdt~U4:tl\\. "tl(, ~(\\t ~lt:p'.\\ nlr~Ltl) to ""II" 1u '11(';,\\ etf' ~ur·t~(f. "'ilter '\\ r,t,.,Stl1t \\.or to I,'t'd1.,O')1 at «.;~ lr I"" Ir,£ I',tan r II/I: If<1ter .:ar ... • ...

Use of Respiratory Impedance in Prehospital Care of Hypotensive Patients Associated with Hemorrhage and Trauma: A Case Series

DTIC Science & Technology

2012-01-01

Additional patients were included, who had trauma and/or blood loss from Cypress Creek, Texas, and Empress , New York, where the ITD was more recently...respon ders from Lucas County, Ohio, Empress EMS from Yonkers, New York, Eastchester EMS from Eastchester, New York, and Cypress Creek EMS from Spring

Estimating individual tree mid- and understory rank-size distributions from airborne laser scanning in semi-arid forests

Treesearch

Tyson L. Swetnam; Donald A. Falk; Ann M. Lynch; Stephen R. Yool

2014-01-01

Limitations inherent to airborne laser scanning (ALS) technology and the complex sorting and packing relationships of forests complicate accurate remote sensing of mid- and understory trees, especially in denser forest stands. Self-similarities in rank-sized individual tree distributions (ITD), e.g. bole diameter or height, are a well-understood property of natural,...

Large modal survey testing using the Ibrahim time domain /ITD/ identification technique

NASA Technical Reports Server (NTRS)

Ibrahim, S. R.; Pappa, R. S.

1981-01-01

The ability of the ITD identification algorithm in identifying a complete set of structural modal parameters using a large number of free-response time histories simultaneously in one analysis, assuming a math model with a high number of degrees-of-freedom, has been studied. Identification results using simulated free responses of a uniform rectangular plate, with 225 measurement stations, and experimental responses from a ground vibration test of the Long Duration Exposure Facility (LDEF) Space Shuttle payload, with 142 measurement stations, are presented. As many as 300 degrees-of-freedom were allowed in analyzing these data. In general, the use of a significantly oversized math model in the identification process was found to maintain or increase identification accuracy and to identify modes of low response level that are not identified with smaller math model sizes. The concept of a Mode Shape Correlation Constant is introduced for use when more than one identification analysis of the same structure are conducted. This constant quantifies the degree of correlation between any two sets of complex mode shapes identified using different excitation conditions, different user-selectable algorithm constants, or overlapping sets of measurements.

Computer-guided design, synthesis, and biological evaluation of quinoxalinebisarylureas as FLT3 inhibitors.

PubMed

Göring, Stefan; Bensinger, Dennis; Naumann, Eva C; Schmidt, Boris

2015-03-01

Activating mutations of FMS-like tyrosine kinase 3 (FLT3) are present in ∼30 % of patients with acute myeloid leukemia (AML) and are associated with poor prognosis. Point mutations in the tyrosine kinase domain (TKD) are observed as primary mutations or are acquired as secondary mutations in FLT3 with internal tandem duplications (ITDs) after treatment with tyrosine kinase inhibitors (TKIs). Although dozens of potent inhibitors against FLT3 ITD have been reported, activating TKD point mutations, especially at residues F691 and D835, remain the leading cause for therapy resistance, highlighting the consistent need for new potent inhibitors. Herein we report the identification and characterization of novel quinoxaline-based FLT3 inhibitors. We used the pharmacophore features of diverse known inhibitors as a starting point for a new optimization algorithm for type II TKIs, starting from an in silico library pharmacophore search and induced-fit docking in the known FLT3 structure. This led to the design of a set of diverse quinoxalinebisarylureas, which were profiled in an FLT3 kinase activity assay. The most promising compounds were further evaluated in a zebrafish embryo phenotype assay. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Models of the electrically stimulated binaural system: A review.

PubMed

Dietz, Mathias

2016-01-01

In an increasing number of countries, the standard treatment for deaf individuals is moving toward the implantation of two cochlear implants. Today's device technology and fitting procedure, however, appears as if the two implants would serve two independent ears and brains. Many experimental studies have demonstrated that after careful matching and balancing of left and right stimulation in controlled laboratory studies most patients have almost normal sensitivity to interaural level differences and some sensitivity to interaural time differences (ITDs). Mechanisms underlying the limited ITD sensitivity are still poorly understood and many different aspects may contribute. Recent pioneering computational approaches identified some of the functional implications the electric input imposes on the neural brainstem circuits. Simultaneously these studies have raised new questions and certainly demonstrated that further refinement of the model stages is necessary. They join the experimental study's conclusions that binaural device technology, binaural fitting, specific speech coding strategies, and binaural signal processing algorithms are obviously missing components to maximize the benefit of bilateral implantation. Within this review, the existing models of the electrically stimulated binaural system are explained, compared, and discussed from a viewpoint of a "CI device with auditory system" and from that of neurophysiological research.

Efficacy of a Mer and Flt3 tyrosine kinase small molecule inhibitor, UNC1666, in acute myeloid leukemia

PubMed Central

Lee-Sherick, Alisa B.; Zhang, Weihe; Menachof, Kelly K.; Hill, Amanda A.; Rinella, Sean; Kirkpatrick, Gregory; Page, Lauren S.; Stashko, Michael A.; Jordan, Craig T.; Wei, Qi; Liu, Jing; Zhang, Dehui; DeRyckere, Deborah; Wang, Xiaodong; Frye, Stephen; Earp, H. Shelton; Graham, Douglas K.

2015-01-01

Mer and Flt3 receptor tyrosine kinases have been implicated as therapeutic targets in acute myeloid leukemia (AML). In this manuscript we describe UNC1666, a novel ATP-competitive small molecule tyrosine kinase inhibitor, which potently diminishes Mer and Flt3 phosphorylation in AML. Treatment with UNC1666 mediated biochemical and functional effects in AML cell lines expressing Mer or Flt3 internal tandem duplication (ITD), including decreased phosphorylation of Mer, Flt3 and downstream effectors Stat, Akt and Erk, induction of apoptosis in up to 98% of cells, and reduction of colony formation by greater than 90%, compared to treatment with vehicle. These effects were dose-dependent, with inhibition of downstream signaling and functional effects correlating with the degree of Mer or Flt3 kinase inhibition. Treatment of primary AML patient samples expressing Mer and/or Flt3-ITD with UNC1666 also inhibited Mer and Flt3 intracellular signaling, induced apoptosis, and inhibited colony formation. In summary, UNC1666 is a novel potent small molecule tyrosine kinase inhibitor that decreases oncogenic signaling and myeloblast survival, thereby validating dual Mer/Flt3 inhibition as an attractive treatment strategy for AML. PMID:25762638

Working-Memory Load and Temporal Myopia in Dynamic Decision Making

ERIC Educational Resources Information Center

Worthy, Darrell A.; Otto, A. Ross; Maddox, W. Todd

2012-01-01

We examined the role of working memory (WM) in dynamic decision making by having participants perform decision-making tasks under single-task or dual-task conditions. In 2 experiments participants performed dynamic decision-making tasks in which they chose 1 of 2 options on each trial. The decreasing option always gave a larger immediate reward…

DOE Office of Scientific and Technical Information (OSTI.GOV)

Edwards, Harold C.; Ibanez, Daniel Alejandro

This report documents the ASC/ATDM Kokkos deliverable "Production Portable Dy- namic Task DAG Capability." This capability enables applications to create and execute a dynamic task DAG ; a collection of heterogeneous computational tasks with a directed acyclic graph (DAG) of "execute after" dependencies where tasks and their dependencies are dynamically created and destroyed as tasks execute. The Kokkos task scheduler executes the dynamic task DAG on the target execution resource; e.g. a multicore CPU, a manycore CPU such as Intel's Knights Landing (KNL), or an NVIDIA GPU. Several major technical challenges had to be addressed during development of Kokkos' Taskmore » DAG capability: (1) portability to a GPU with it's simplified hardware and micro- runtime, (2) thread-scalable memory allocation and deallocation from a bounded pool of memory, (3) thread-scalable scheduler for dynamic task DAG, (4) usability by applications.« less

Human Autonomic and Cerebrovascular Responses to Inspiratory Impedance

DTIC Science & Technology

2006-06-01

recorded the ECG, finger photoplethysmographic arterial pressure , cerebral blood flow velocity, and muscle sympathetic nerve activity (MSNA). In a... pressures and R-R intervals, or between arterial pres- sures and cerebral blood flow velocities at the LF (p > 0.05). Conclusions: Our results demonstrate...that the ITD increases arterial pressure , heart rate, and cerebral blood flow velocity independent of changes in autonomic car- diovascular control or

Is It Time to Designate Coast Guard Special Operations Forces

DTIC Science & Technology

2005-06-17

174 Commander Matthew Creelman , USCG Division Chief........................................ 174...February 2005. 9Pailliotet and Phelan. 10Ibid. 11Matthew Creelman , interview by author, Yorktown, VA, 25 January 2005. 12James Perry Stevenson, The $5...doing some research for my master’s thesis at the Army Command and General Staff College. I found out from CDR Creelman that G-CI has ended ITD’s long

IDH1 and IDH2 mutations are frequent genetic alterations in acute myeloid leukemia and confer adverse prognosis in cytogenetically normal acute myeloid leukemia with NPM1 mutation without FLT3 internal tandem duplication.

PubMed

Paschka, Peter; Schlenk, Richard F; Gaidzik, Verena I; Habdank, Marianne; Krönke, Jan; Bullinger, Lars; Späth, Daniela; Kayser, Sabine; Zucknick, Manuela; Götze, Katharina; Horst, Heinz-A; Germing, Ulrich; Döhner, Hartmut; Döhner, Konstanze

2010-08-01

To analyze the frequency and prognostic impact of isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) mutations in acute myeloid leukemia (AML). We studied 805 adults (age range, 16 to 60 years) with AML enrolled on German-Austrian AML Study Group (AMLSG) treatment trials AML HD98A and APL HD95 for mutations in exon 4 of IDH1 and IDH2. Patients were also studied for NPM1, FLT3, MLL, and CEBPA mutations. The median follow-up for survival was 6.3 years. IDH mutations were found in 129 patients (16.0%) -IDH1 in 61 patients (7.6%), and IDH2 in 70 patients (8.7%). Two patients had both IDH1 and IDH2 mutations. All but one IDH1 mutation caused substitutions of residue R132; IDH2 mutations caused changes of R140 (n = 48) or R172 (n = 22). IDH mutations were associated with older age (P < .001; effect conferred by IDH2 only); lower WBC (P = .04); higher platelets (P < .001); cytogenetically normal (CN) -AML (P< .001); and NPM1 mutations, in particular with the genotype of mutated NPM1 without FLT3 internal tandem duplication (ITD; P < .001). In patients with CN-AML with the latter genotype, IDH mutations adversely impacted relapse-free survival (RFS; P = .02) and overall survival (P = .03), whereas outcome was not affected in patients with CN-AML who lacked this genotype. In CN-AML, multivariable analyses revealed a significant interaction between IDH mutation and the genotype of mutated NPM1 without FLT3-ITD (ie, the adverse impact of IDH mutation [RFS]; P = .046 was restricted to this patient subset). IDH1 and IDH2 mutations are recurring genetic changes in AML. They constitute a poor prognostic factor in CN-AML with mutated NPM1 without FLT3-ITD, which allows refined risk stratification of this AML subset.

Wilms’ Tumor 1 Gene Mutations Independently Predict Poor Outcome in Adults With Cytogenetically Normal Acute Myeloid Leukemia: A Cancer and Leukemia Group B Study

PubMed Central

Paschka, Peter; Marcucci, Guido; Ruppert, Amy S.; Whitman, Susan P.; Mrózek, Krzysztof; Maharry, Kati; Langer, Christian; Baldus, Claudia D.; Zhao, Weiqiang; Powell, Bayard L.; Baer, Maria R.; Carroll, Andrew J.; Caligiuri, Michael A.; Kolitz, Jonathan E.; Larson, Richard A.; Bloomfield, Clara D.

2008-01-01

Purpose To analyze the prognostic impact of Wilms’ tumor 1 (WT1) gene mutations in cytogenetically normal acute myeloid leukemia (CN-AML). Patients and Methods We studied 196 adults younger than 60 years with newly diagnosed primary CN-AML, who were treated similarly on Cancer and Leukemia Group B (CALGB) protocols 9621 and 19808, for WT1 mutations in exons 7 and 9. The patients also were assessed for the presence of FLT3 internal tandem duplications (FLT3-ITD), FLT3 tyrosine kinase domain mutations (FLT3-TKD), MLL partial tandem duplications (MLL-PTD), NPM1 and CEBPA mutations, and for the expression levels of ERG and BAALC. Results Twenty-one patients (10.7%) harbored WT1 mutations. Complete remission rates were not significantly different between patients with WT1 mutations and those with unmutated WT1 (P = .36; 76% v 84%). Patients with WT1 mutations had worse disease-free survival (DFS; P < .001; 3-year rates, 13% v 50%) and overall survival (OS; P < .001; 3-year rates, 10% v 56%) than patients with unmutated WT1. In multivariable analyses, WT1 mutations independently predicted worse DFS (P = .009; hazard ratio [HR] = 2.7) when controlling for CEBPA mutational status, ERG expression level, and FLT3-ITD/NPM1 molecular-risk group (ie, FLT3-ITDnegative/NPM1mutated as low risk v FLT3-ITDpositive and/or NPM1wild-type as high risk). WT1 mutations also independently predicted worse OS (P < .001; HR = 3.2) when controlling for CEBPA mutational status, FLT3-ITD/NPM1 molecular-risk group, and white blood cell count. Conclusion We report the first evidence that WT1 mutations independently predict extremely poor outcome in intensively treated, younger patients with CN-AML. Future trials should include testing for WT1 mutations as part of molecularly based risk assessment and risk-adapted treatment stratification of patients with CN-AML. PMID:18559874

Postinduction Minimal Residual Disease Predicts Outcome and Benefit From Allogeneic Stem Cell Transplantation in Acute Myeloid Leukemia With NPM1 Mutation: A Study by the Acute Leukemia French Association Group.

PubMed

Balsat, Marie; Renneville, Aline; Thomas, Xavier; de Botton, Stéphane; Caillot, Denis; Marceau, Alice; Lemasle, Emilie; Marolleau, Jean-Pierre; Nibourel, Olivier; Berthon, Céline; Raffoux, Emmanuel; Pigneux, Arnaud; Rodriguez, Céline; Vey, Norbert; Cayuela, Jean-Michel; Hayette, Sandrine; Braun, Thorsten; Coudé, Marie Magdeleine; Terre, Christine; Celli-Lebras, Karine; Dombret, Hervé; Preudhomme, Claude; Boissel, Nicolas

2017-01-10

Purpose This study assessed the prognostic impact of postinduction NPM1-mutated ( NPM1m) minimal residual disease (MRD) in young adult patients (age, 18 to 60 years) with acute myeloid leukemia, and addressed the question of whether NPM1m MRD may be used as a predictive factor of allogeneic stem cell transplantation (ASCT) benefit. Patients and Methods Among 229 patients with NPM1m who were treated in the Acute Leukemia French Association 0702 (ALFA-0702) trial, MRD evaluation was available in 152 patients in first remission. Patients with nonfavorable AML according to the European LeukemiaNet (ELN) classification were eligible for ASCT in first remission. Results After induction therapy, patients who did not achieve a 4-log reduction in NPM1m peripheral blood-MRD (PB-MRD) had a higher cumulative incidence of relapse (subhazard ratio [SHR], 5.83; P < .001) and a shorter overall survival (OS; hazard ratio [HR], 10.99; P < .001). In multivariable analysis, an abnormal karyotype, the presence of FLT3-internal tandem duplication (ITD), and a < 4-log reduction in PB-MRD were significantly associated with a higher relapse incidence and shorter OS. In the subset of patients with FLT3-ITD, only age, white blood cell count, and < 4-log reduction in PB-MRD, but not FLT3-ITD allelic ratio, remained of significant prognostic value. In these patients with nonfavorable AML according to European LeukemiaNet, disease-free survival and OS were significantly improved by ASCT in those with a < 4-log reduction in PB-MRD. This benefit was not observed in those with a > 4-log reduction in PB-MRD, with a significant interaction between ASCT effect and PB-MRD response ( P = .024 and .027 for disease-free survival and OS, respectively). Conclusion Our study supports the strong prognostic significance of early NPM1m PB-MRD, independent of the cytogenetic and molecular context. Moreover, NPM1m PB-MRD may be used as a predictive factor for ASCT indication.

Improvements of sound localization abilities by the facial ruff of the barn owl (Tyto alba) as demonstrated by virtual ruff removal.

PubMed

Hausmann, Laura; von Campenhausen, Mark; Endler, Frank; Singheiser, Martin; Wagner, Hermann

2009-11-05

When sound arrives at the eardrum it has already been filtered by the body, head, and outer ear. This process is mathematically described by the head-related transfer functions (HRTFs), which are characteristic for the spatial position of a sound source and for the individual ear. HRTFs in the barn owl (Tyto alba) are also shaped by the facial ruff, a specialization that alters interaural time differences (ITD), interaural intensity differences (ILD), and the frequency spectrum of the incoming sound to improve sound localization. Here we created novel stimuli to simulate the removal of the barn owl's ruff in a virtual acoustic environment, thus creating a situation similar to passive listening in other animals, and used these stimuli in behavioral tests. HRTFs were recorded from an owl before and after removal of the ruff feathers. Normal and ruff-removed conditions were created by filtering broadband noise with the HRTFs. Under normal virtual conditions, no differences in azimuthal head-turning behavior between individualized and non-individualized HRTFs were observed. The owls were able to respond differently to stimuli from the back than to stimuli from the front having the same ITD. By contrast, such a discrimination was not possible after the virtual removal of the ruff. Elevational head-turn angles were (slightly) smaller with non-individualized than with individualized HRTFs. The removal of the ruff resulted in a large decrease in elevational head-turning amplitudes. The facial ruff a) improves azimuthal sound localization by increasing the ITD range and b) improves elevational sound localization in the frontal field by introducing a shift of iso-ILD lines out of the midsagittal plane, which causes ILDs to increase with increasing stimulus elevation. The changes at the behavioral level could be related to the changes in the binaural physical parameters that occurred after the virtual removal of the ruff. These data provide new insights into the function of external hearing structures and open up the possibility to apply the results on autonomous agents, creation of virtual auditory environments for humans, or in hearing aids.

Intrathoracic pressure regulation during cardiopulmonary resuscitation: a feasibility case-series.

PubMed

Segal, Nicolas; Parquette, Brent; Ziehr, Jonathon; Yannopoulos, Demetris; Lindstrom, David

2013-04-01

Intrathoracic pressure regulation (IPR) is a novel, noninvasive therapy intended to increase cardiac output and blood pressure in hypotensive states by generating a negative end expiratory pressure of -12 cm H2O between positive pressure ventilations. In this first feasibility case-series, we tested the hypothesis that IPR improves End tidal (ET) CO2 during cardiopulmonary resuscitation (CPR). ETCO2 was used as a surrogate measure for circulation. All patients were treated initially with manual CPR and an impedance threshold device (ITD). When IPR-trained medics arrived on scene the ITD was removed and an IPR device (CirQLATOR™) was attached to the patient's advanced airway (intervention group). The IPR device lowered airway pressures to -9 mmHg after each positive pressure ventilation for the duration of the expiratory phase. ETCO2, was measured using a capnometer incorporated into the defibrillator system (LifePak™). Values are expressed as mean ± SEM. Results were compared using paired and unpaired Student's t test. p values of <0.05 were considered statistically significant. ETCO2 values in 11 patients in the case series were compared pre and during IPR therapy and also compared to 74 patients in the control group not treated with the new IPR device. ETCO2 values increased from an average of 21 ± 1 mmHg immediately before IPR application to an average value of 32 ± 5 mmHg and to a maximum value of 45 ± 5mmHg during IPR treatment (p<0.001). In the control group ETCO2 values did not change significantly. Return of spontaneous circulation (ROSC) rates were 46% (34/74) with standard CPR and ITD versus 73% (8/11) with standard CPR and the IPR device (p<0.001). ETCO2 levels and ROSC rates were significantly higher in the study intervention group. These findings demonstrate that during CPR circulation may be significantly augmented by generation of a negative end expiratory pressure between each breath. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Age-related Multiscale Changes in Brain Signal Variability in Pre-task versus Post-task Resting-state EEG.

PubMed

Wang, Hongye; McIntosh, Anthony R; Kovacevic, Natasa; Karachalios, Maria; Protzner, Andrea B

2016-07-01

Recent empirical work suggests that, during healthy aging, the variability of network dynamics changes during task performance. Such variability appears to reflect the spontaneous formation and dissolution of different functional networks. We sought to extend these observations into resting-state dynamics. We recorded EEG in young, middle-aged, and older adults during a "rest-task-rest" design and investigated if aging modifies the interaction between resting-state activity and external stimulus-induced activity. Using multiscale entropy as our measure of variability, we found that, with increasing age, resting-state dynamics shifts from distributed to more local neural processing, especially at posterior sources. In the young group, resting-state dynamics also changed from pre- to post-task, where fine-scale entropy increased in task-positive regions and coarse-scale entropy increased in the posterior cingulate, a key region associated with the default mode network. Lastly, pre- and post-task resting-state dynamics were linked to performance on the intervening task for all age groups, but this relationship became weaker with increasing age. Our results suggest that age-related changes in resting-state dynamics occur across different spatial and temporal scales and have consequences for information processing capacity.

Biologically plausible learning in recurrent neural networks reproduces neural dynamics observed during cognitive tasks

PubMed Central

Miconi, Thomas

2017-01-01

Neural activity during cognitive tasks exhibits complex dynamics that flexibly encode task-relevant variables. Chaotic recurrent networks, which spontaneously generate rich dynamics, have been proposed as a model of cortical computation during cognitive tasks. However, existing methods for training these networks are either biologically implausible, and/or require a continuous, real-time error signal to guide learning. Here we show that a biologically plausible learning rule can train such recurrent networks, guided solely by delayed, phasic rewards at the end of each trial. Networks endowed with this learning rule can successfully learn nontrivial tasks requiring flexible (context-dependent) associations, memory maintenance, nonlinear mixed selectivities, and coordination among multiple outputs. The resulting networks replicate complex dynamics previously observed in animal cortex, such as dynamic encoding of task features and selective integration of sensory inputs. We conclude that recurrent neural networks offer a plausible model of cortical dynamics during both learning and performance of flexible behavior. DOI: http://dx.doi.org/10.7554/eLife.20899.001 PMID:28230528

Biologically plausible learning in recurrent neural networks reproduces neural dynamics observed during cognitive tasks.

PubMed

Miconi, Thomas

2017-02-23

Neural activity during cognitive tasks exhibits complex dynamics that flexibly encode task-relevant variables. Chaotic recurrent networks, which spontaneously generate rich dynamics, have been proposed as a model of cortical computation during cognitive tasks. However, existing methods for training these networks are either biologically implausible, and/or require a continuous, real-time error signal to guide learning. Here we show that a biologically plausible learning rule can train such recurrent networks, guided solely by delayed, phasic rewards at the end of each trial. Networks endowed with this learning rule can successfully learn nontrivial tasks requiring flexible (context-dependent) associations, memory maintenance, nonlinear mixed selectivities, and coordination among multiple outputs. The resulting networks replicate complex dynamics previously observed in animal cortex, such as dynamic encoding of task features and selective integration of sensory inputs. We conclude that recurrent neural networks offer a plausible model of cortical dynamics during both learning and performance of flexible behavior.

Low NOx Fuel Flexible Combustor Integration Project Overview

NASA Technical Reports Server (NTRS)

Walton, Joanne C.; Chang, Clarence T.; Lee, Chi-Ming; Kramer, Stephen

2015-01-01

The Integrated Technology Demonstration (ITD) 40A Low NOx Fuel Flexible Combustor Integration development is being conducted as part of the NASA Environmentally Responsible Aviation (ERA) Project. Phase 2 of this effort began in 2012 and will end in 2015. This document describes the ERA goals, how the fuel flexible combustor integration development fulfills the ERA combustor goals, and outlines the work to be conducted during project execution.

Using ILD or ITD Cues for Sound Source Localization and Speech Understanding in a Complex Listening Environment by Listeners with Bilateral and with Hearing-Preservation Cochlear Implants

ERIC Educational Resources Information Center

Loiselle, Louise H.; Dorman, Michael F.; Yost, William A.; Cook, Sarah J.; Gifford, Rene H.

2016-01-01

Purpose: To assess the role of interaural time differences and interaural level differences in (a) sound-source localization, and (b) speech understanding in a cocktail party listening environment for listeners with bilateral cochlear implants (CIs) and for listeners with hearing-preservation CIs. Methods: Eleven bilateral listeners with MED-EL…

A Logical Approach to Multilevel Security of Probabilistic Systems

DTIC Science & Technology

1998-01-01

their usefulness in security analysis. Key Words: Formal modeling, Veri cation, Knowledge, Security, Probabilistic Systems Supported by grant HKUST 608...94E from the Hong Kong Research Grants Council. yAuthor for correspondence (syverson@itd.nrl.navy.mil). Supported by ONR. 1 Report Documentation Page...Form ApprovedOMB No. 0704-0188 Public reporting burden for the collection of information is estimated to average 1 hour per response, including the

Testing Experimental Compounds against Leishmaniasis in Laboratory Animal Model Systems.

DTIC Science & Technology

1983-09-01

respiratory chain or pyrimidine biosynthesis. A new compound, alpha difluromethylornithine (RMI 71,782), is a highly specific inhibitor of polyamine...no a;pn-r-nt liff-r-ncp in s’imor-;sion, heli~,or cre when nl crt’ vosu s1 -se lesio)ns w-r- -va-i i-t-d. mai- nln i nbrI f3cmc ro i " iv-r , "ilm-in

Failure of the precedence effect with a noise-band vocoder

PubMed Central

Seeber, Bernhard U.; Hafter, Ervin R.

2011-01-01

The precedence effect (PE) describes the ability to localize a direct, leading sound correctly when its delayed copy (lag) is present, though not separately audible. The relative contribution of binaural cues in the temporal fine structure (TFS) of lead–lag signals was compared to that of interaural level differences (ILDs) and interaural time differences (ITDs) carried in the envelope. In a localization dominance paradigm participants indicated the spatial location of lead–lag stimuli processed with a binaural noise-band vocoder whose noise carriers introduced random TFS. The PE appeared for noise bursts of 10 ms duration, indicating dominance of envelope information. However, for three test words the PE often failed even at short lead–lag delays, producing two images, one toward the lead and one toward the lag. When interaural correlation in the carrier was increased, the images appeared more centered, but often remained split. Although previous studies suggest dominance of TFS cues, no image is lateralized in accord with the ITD in the TFS. An interpretation in the context of auditory scene analysis is proposed: By replacing the TFS with that of noise the auditory system loses the ability to fuse lead and lag into one object, and thus to show the PE. PMID:21428515

Physiological and content considerations for a second low frequency channel for bass management, subwoofers, and low frequency enhancement (LFE)

NASA Astrophysics Data System (ADS)

Miller, Robert E. (Robin)

2005-04-01

Perception of very low frequencies (VLF) below 125 Hz reproduced by large woofers and subwoofers (SW), encompassing 3 octaves of the 10 regarded as audible, has physiological and content aspects. Large room acoustics and vibrato add VLF fluctuations, modulating audible carrier frequencies to >1 Hz. By convention, sounds below 90 Hz produce no interaural cues useful for spatial perception or localization, therefore bass management redirects the VLF range from main channels to a single (monaural) subwoofer channel, even if to more than one subwoofer. Yet subjects claim they hear a difference between a single subwoofer channel and two (stereo bass). If recordings contain spatial VLF content, is it possible physiologically to perceive interaural time/phase difference (ITD/IPD) between 16 and 125 Hz? To what extent does this perception have a lifelike quality; to what extent is it localization? If a first approximation of localization, would binaural SWs allow a higher crossover frequency (smaller satellite speakers)? Reported research supports the Jeffress model of ITD determination in brain structures, and extending the accepted lower frequency limit of IPD. Meanwhile, uncorrelated very low frequencies exist in all tested multi-channel music and movie content. The audibility, recording, and reproduction of uncorrelated VLF are explored in theory and experiments.

Attentional synchrony and the influence of viewing task on gaze behavior in static and dynamic scenes.

PubMed

Smith, Tim J; Mital, Parag K

2013-07-17

Does viewing task influence gaze during dynamic scene viewing? Research into the factors influencing gaze allocation during free viewing of dynamic scenes has reported that the gaze of multiple viewers clusters around points of high motion (attentional synchrony), suggesting that gaze may be primarily under exogenous control. However, the influence of viewing task on gaze behavior in static scenes and during real-world interaction has been widely demonstrated. To dissociate exogenous from endogenous factors during dynamic scene viewing we tracked participants' eye movements while they (a) freely watched unedited videos of real-world scenes (free viewing) or (b) quickly identified where the video was filmed (spot-the-location). Static scenes were also presented as controls for scene dynamics. Free viewing of dynamic scenes showed greater attentional synchrony, longer fixations, and more gaze to people and areas of high flicker compared with static scenes. These differences were minimized by the viewing task. In comparison with the free viewing of dynamic scenes, during the spot-the-location task fixation durations were shorter, saccade amplitudes were longer, and gaze exhibited less attentional synchrony and was biased away from areas of flicker and people. These results suggest that the viewing task can have a significant influence on gaze during a dynamic scene but that endogenous control is slow to kick in as initial saccades default toward the screen center, areas of high motion and people before shifting to task-relevant features. This default-like viewing behavior returns after the viewing task is completed, confirming that gaze behavior is more predictable during free viewing of dynamic than static scenes but that this may be due to natural correlation between regions of interest (e.g., people) and motion.

Dynamics of Cooperation in a Task Completion Social Dilemma

PubMed Central

Passino, Kevin M.

2017-01-01

We study the situation where the members of a community have the choice to participate in the completion of a common task. The process of completing the task involves only costs and no benefits to the individuals that participate in this process. However, completing the task results in changes that significantly benefit the community and that exceed the participation efforts. A task completion social dilemma arises when the short-term participation costs dissipate any interest in the community members to contribute to the task completion process and therefore to obtain the benefits that result from completing the task. In this work, we model the task completion problem using a dynamical system that characterizes the participation dynamics in the community and the task completion process. We show how this model naturally allows for the incorporation of several mechanisms that facilitate the emergence of cooperation and that have been studied in previous research on social dilemmas, including communication across a network, and indirect reciprocity through relative reputation. We provide mathematical analyses and computer simulations to study the qualitative properties of the participation dynamics in the community for different scenarios. PMID:28125721

Stable and Dynamic Coding for Working Memory in Primate Prefrontal Cortex

PubMed Central

Watanabe, Kei; Funahashi, Shintaro; Stokes, Mark G.

2017-01-01

Working memory (WM) provides the stability necessary for high-level cognition. Influential theories typically assume that WM depends on the persistence of stable neural representations, yet increasing evidence suggests that neural states are highly dynamic. Here we apply multivariate pattern analysis to explore the population dynamics in primate lateral prefrontal cortex (PFC) during three variants of the classic memory-guided saccade task (recorded in four animals). We observed the hallmark of dynamic population coding across key phases of a working memory task: sensory processing, memory encoding, and response execution. Throughout both these dynamic epochs and the memory delay period, however, the neural representational geometry remained stable. We identified two characteristics that jointly explain these dynamics: (1) time-varying changes in the subpopulation of neurons coding for task variables (i.e., dynamic subpopulations); and (2) time-varying selectivity within neurons (i.e., dynamic selectivity). These results indicate that even in a very simple memory-guided saccade task, PFC neurons display complex dynamics to support stable representations for WM. SIGNIFICANCE STATEMENT Flexible, intelligent behavior requires the maintenance and manipulation of incoming information over various time spans. For short time spans, this faculty is labeled “working memory” (WM). Dominant models propose that WM is maintained by stable, persistent patterns of neural activity in prefrontal cortex (PFC). However, recent evidence suggests that neural activity in PFC is dynamic, even while the contents of WM remain stably represented. Here, we explored the neural dynamics in PFC during a memory-guided saccade task. We found evidence for dynamic population coding in various task epochs, despite striking stability in the neural representational geometry of WM. Furthermore, we identified two distinct cellular mechanisms that contribute to dynamic population coding. PMID:28559375

Fatigability and Recovery of Arm Muscles with Advanced Age for Dynamic and Isometric Contractions

PubMed Central

Yoon, Tejin; Schlinder-Delap, Bonnie; Hunter, Sandra K.

2012-01-01

This study determined whether age-related mechanisms can increase fatigue of arm muscles during maximal velocity dynamic contractions, as occurs in the lower limb. We compared elbow flexor fatigue of young (n=10, 20.8 ± 2.7 years) and old men (n=16, 73.8 ± 6.1 years) during and in recovery from a dynamic and an isometric postural fatiguing task. Each task was maintained until failure while supporting a load equivalent to 20% of maximal voluntary isometric contraction (MVIC) torque. Transcranial magnetic stimulation (TMS) was used to assess supraspinal fatigue (superimposed twitch, SIT) and muscle relaxation. Time to failure was longer for old men than young for the isometric task (9.5±3.1 vs. 17.2±7.0 min, P=0.01) but similar for the dynamic task (6.3±2.4 min vs. 6.0±2.0 min, P = 0.73). Initial peak rate of relaxation was slower for the old men than young, and associated with a longer time to failure for both tasks (P<0.05). Low initial power during elbow flexion was associated with the greatest difference (reduction) in time to failure between the isometric task and dynamic task (r =−0.54, P=0.015). SIT declined after both fatigue tasks similarly with age, although recovery of SIT was associated with MVIC recovery for the old (both sessions) but not the young. Biceps brachii and brachioradialis EMG activity (%MVIC) of old men were greater than young during the dynamic fatiguing task (P<0.05), but similar during the isometric task. Muscular mechanisms and greater relative muscle activity (EMG activity) explain the greater fatigue during dynamic task for the old men compared with young in elbow flexor muscles. Recovery of MVC torque however relies more on recovery of supraspinal fatigue among older men than the young men. PMID:23103238

Dynamical signatures of isometric force control as a function of age, expertise, and task constraints.

PubMed

Vieluf, Solveig; Sleimen-Malkoun, Rita; Voelcker-Rehage, Claudia; Jirsa, Viktor; Reuter, Eva-Maria; Godde, Ben; Temprado, Jean-Jacques; Huys, Raoul

2017-07-01

From the conceptual and methodological framework of the dynamical systems approach, force control results from complex interactions of various subsystems yielding observable behavioral fluctuations, which comprise both deterministic (predictable) and stochastic (noise-like) dynamical components. Here, we investigated these components contributing to the observed variability in force control in groups of participants differing in age and expertise level. To this aim, young (18-25 yr) as well as late middle-aged (55-65 yr) novices and experts (precision mechanics) performed a force maintenance and a force modulation task. Results showed that whereas the amplitude of force variability did not differ across groups in the maintenance tasks, in the modulation task it was higher for late middle-aged novices than for experts and higher for both these groups than for young participants. Within both tasks and for all groups, stochastic fluctuations were lowest where the deterministic influence was smallest. However, although all groups showed similar dynamics underlying force control in the maintenance task, a group effect was found for deterministic and stochastic fluctuations in the modulation task. The latter findings imply that both components were involved in the observed group differences in the variability of force fluctuations in the modulation task. These findings suggest that between groups the general characteristics of the dynamics do not differ in either task and that force control is more affected by age than by expertise. However, expertise seems to counteract some of the age effects. NEW & NOTEWORTHY Stochastic and deterministic dynamical components contribute to force production. Dynamical signatures differ between force maintenance and cyclic force modulation tasks but hardly between age and expertise groups. Differences in both stochastic and deterministic components are associated with group differences in behavioral variability, and observed behavioral variability is more strongly task dependent than person dependent. Copyright © 2017 the American Physiological Society.

The Developmental Dynamics of Task-Avoidant Behavior and Math Performance in Kindergarten and Elementary School

ERIC Educational Resources Information Center

Hirvonen, Riikka; Tolvanen, Asko; Aunola, Kaisa; Nurmi, Jari-Erik

2012-01-01

Besides cognitive factors, children's learning at school may be influenced by more dynamic phenomena, such as motivation and achievement-related task-avoidant behavior. The present study examined the developmental dynamics of task-avoidant behavior and math performance from kindergarten to Grade 4. A total of 225 children were tested for their…

A Steganographic Embedding Undetectable by JPEG Compatibility Steganalysis

DTIC Science & Technology

2002-01-01

itd.nrl.navy.mil Abstract. Steganography and steganalysis of digital images is a cat- and-mouse game. In recent work, Fridrich, Goljan and Du introduced a method...proposed embedding method. 1 Introduction Steganography and steganalysis of digital images is a cat-and-mouse game. Ever since Kurak and McHugh’s seminal...paper on LSB embeddings in images [10], various researchers have published work on either increasing the payload, im- proving the resistance to

A Calculus of Macro-Events: Progress Report

DTIC Science & Technology

2000-01-01

1410, USA iliano@itd.nrl.navy.mil Angelo Montanari Dipartimento di Matematica e Informatica Universita di Udine Via delle Scienze, 206 { 33100 Udine...and process iteration. This proposal builds on work by Chittaro and Montanari [10] on mod- eling discrete processes. The set of constructors of the...situations, in many cases the occurrence of an event happens over a period of time [24]. Capturing this possibility enables ner mod- els , as we can now

Task-dependent recurrent dynamics in visual cortex

PubMed Central

Tajima, Satohiro; Koida, Kowa; Tajima, Chihiro I; Suzuki, Hideyuki; Aihara, Kazuyuki; Komatsu, Hidehiko

2017-01-01

The capacity for flexible sensory-action association in animals has been related to context-dependent attractor dynamics outside the sensory cortices. Here, we report a line of evidence that flexibly modulated attractor dynamics during task switching are already present in the higher visual cortex in macaque monkeys. With a nonlinear decoding approach, we can extract the particular aspect of the neural population response that reflects the task-induced emergence of bistable attractor dynamics in a neural population, which could be obscured by standard unsupervised dimensionality reductions such as PCA. The dynamical modulation selectively increases the information relevant to task demands, indicating that such modulation is beneficial for perceptual decisions. A computational model that features nonlinear recurrent interaction among neurons with a task-dependent background input replicates the key properties observed in the experimental data. These results suggest that the context-dependent attractor dynamics involving the sensory cortex can underlie flexible perceptual abilities. DOI: http://dx.doi.org/10.7554/eLife.26868.001 PMID:28737487

Modeling and simulation of dynamic ant colony's labor division for task allocation of UAV swarm

NASA Astrophysics Data System (ADS)

Wu, Husheng; Li, Hao; Xiao, Renbin; Liu, Jie

2018-02-01

The problem of unmanned aerial vehicle (UAV) task allocation not only has the intrinsic attribute of complexity, such as highly nonlinear, dynamic, highly adversarial and multi-modal, but also has a better practicability in various multi-agent systems, which makes it more and more attractive recently. In this paper, based on the classic fixed response threshold model (FRTM), under the idea of "problem centered + evolutionary solution" and by a bottom-up way, the new dynamic environmental stimulus, response threshold and transition probability are designed, and a dynamic ant colony's labor division (DACLD) model is proposed. DACLD allows a swarm of agents with a relatively low-level of intelligence to perform complex tasks, and has the characteristic of distributed framework, multi-tasks with execution order, multi-state, adaptive response threshold and multi-individual response. With the proposed model, numerical simulations are performed to illustrate the effectiveness of the distributed task allocation scheme in two situations of UAV swarm combat (dynamic task allocation with a certain number of enemy targets and task re-allocation due to unexpected threats). Results show that our model can get both the heterogeneous UAVs' real-time positions and states at the same time, and has high degree of self-organization, flexibility and real-time response to dynamic environments.

Dynamic task allocation for a man-machine symbiotic system

NASA Technical Reports Server (NTRS)

Parker, L. E.; Pin, F. G.

1987-01-01

This report presents a methodological approach to the dynamic allocation of tasks in a man-machine symbiotic system in the context of dexterous manipulation and teleoperation. This report addresses a symbiotic system containing two symbiotic partners which work toward controlling a single manipulator arm for the execution of a series of sequential manipulation tasks. It is proposed that an automated task allocator use knowledge about the constraints/criteria of the problem, the available resources, the tasks to be performed, and the environment to dynamically allocate task recommendations for the man and the machine. The presentation of the methodology includes discussions concerning the interaction of the knowledge areas, the flow of control, the necessary communication links, and the replanning of the task allocation. Examples of task allocation are presented to illustrate the results of this methodolgy.

Mental Effort and Performance as Determinants for the Dynamic Selection of Learning Tasks in Air Traffic Control Training

ERIC Educational Resources Information Center

Salden, Ron J.C.M.; Paas, Fred; Broers, Nick J.; van Merrienboer, Jeroen J. G.

2004-01-01

The differential effects of four task selection methods on training efficiency and transfer in computer-based training for Air Traffic Control were investigated. A non-dynamic condition, in which the learning tasks were presented to the participants in a fixed, predetermined sequence, was compared to three dynamic conditions, in which learning…

Evaluation of a conceptual framework for predicting navigation performance in virtual reality.

PubMed

Grübel, Jascha; Thrash, Tyler; Hölscher, Christoph; Schinazi, Victor R

2017-01-01

Previous research in spatial cognition has often relied on simple spatial tasks in static environments in order to draw inferences regarding navigation performance. These tasks are typically divided into categories (e.g., egocentric or allocentric) that reflect different two-systems theories. Unfortunately, this two-systems approach has been insufficient for reliably predicting navigation performance in virtual reality (VR). In the present experiment, participants were asked to learn and navigate towards goal locations in a virtual city and then perform eight simple spatial tasks in a separate environment. These eight tasks were organised along four orthogonal dimensions (static/dynamic, perceived/remembered, egocentric/allocentric, and distance/direction). We employed confirmatory and exploratory analyses in order to assess the relationship between navigation performance and performances on these simple tasks. We provide evidence that a dynamic task (i.e., intercepting a moving object) is capable of predicting navigation performance in a familiar virtual environment better than several categories of static tasks. These results have important implications for studies on navigation in VR that tend to over-emphasise the role of spatial memory. Given that our dynamic tasks required efficient interaction with the human interface device (HID), they were more closely aligned with the perceptuomotor processes associated with locomotion than wayfinding. In the future, researchers should consider training participants on HIDs using a dynamic task prior to conducting a navigation experiment. Performances on dynamic tasks should also be assessed in order to avoid confounding skill with an HID and spatial knowledge acquisition.

Evaluation of a conceptual framework for predicting navigation performance in virtual reality

PubMed Central

Thrash, Tyler; Hölscher, Christoph; Schinazi, Victor R.

2017-01-01

Previous research in spatial cognition has often relied on simple spatial tasks in static environments in order to draw inferences regarding navigation performance. These tasks are typically divided into categories (e.g., egocentric or allocentric) that reflect different two-systems theories. Unfortunately, this two-systems approach has been insufficient for reliably predicting navigation performance in virtual reality (VR). In the present experiment, participants were asked to learn and navigate towards goal locations in a virtual city and then perform eight simple spatial tasks in a separate environment. These eight tasks were organised along four orthogonal dimensions (static/dynamic, perceived/remembered, egocentric/allocentric, and distance/direction). We employed confirmatory and exploratory analyses in order to assess the relationship between navigation performance and performances on these simple tasks. We provide evidence that a dynamic task (i.e., intercepting a moving object) is capable of predicting navigation performance in a familiar virtual environment better than several categories of static tasks. These results have important implications for studies on navigation in VR that tend to over-emphasise the role of spatial memory. Given that our dynamic tasks required efficient interaction with the human interface device (HID), they were more closely aligned with the perceptuomotor processes associated with locomotion than wayfinding. In the future, researchers should consider training participants on HIDs using a dynamic task prior to conducting a navigation experiment. Performances on dynamic tasks should also be assessed in order to avoid confounding skill with an HID and spatial knowledge acquisition. PMID:28915266

Emotion recognition in Parkinson's disease: Static and dynamic factors.

PubMed

Wasser, Cory I; Evans, Felicity; Kempnich, Clare; Glikmann-Johnston, Yifat; Andrews, Sophie C; Thyagarajan, Dominic; Stout, Julie C

2018-02-01

The authors tested the hypothesis that Parkinson's disease (PD) participants would perform better in an emotion recognition task with dynamic (video) stimuli compared to a task using only static (photograph) stimuli and compared performances on both tasks to healthy control participants. In a within-subjects study, 21 PD participants and 20 age-matched healthy controls performed both static and dynamic emotion recognition tasks. The authors used a 2-way analysis of variance (controlling for individual participant variance) to determine the effect of group (PD, control) on emotion recognition performance in static and dynamic facial recognition tasks. Groups did not significantly differ in their performances on the static and dynamic tasks; however, the trend was suggestive that PD participants performed worse than controls. PD participants may have subtle emotion recognition deficits that are not ameliorated by the addition of contextual cues, similar to those found in everyday scenarios. Consistent with previous literature, the results suggest that PD participants may have underlying emotion recognition deficits, which may impact their social functioning. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Principal States of Dynamic Functional Connectivity Reveal the Link Between Resting-State and Task-State Brain: An fMRI Study.

PubMed

Cheng, Lin; Zhu, Yang; Sun, Junfeng; Deng, Lifu; He, Naying; Yang, Yang; Ling, Huawei; Ayaz, Hasan; Fu, Yi; Tong, Shanbao

2018-01-25

Task-related reorganization of functional connectivity (FC) has been widely investigated. Under classic static FC analysis, brain networks under task and rest have been demonstrated a general similarity. However, brain activity and cognitive process are believed to be dynamic and adaptive. Since static FC inherently ignores the distinct temporal patterns between rest and task, dynamic FC may be more a suitable technique to characterize the brain's dynamic and adaptive activities. In this study, we adopted [Formula: see text]-means clustering to investigate task-related spatiotemporal reorganization of dynamic brain networks and hypothesized that dynamic FC would be able to reveal the link between resting-state and task-state brain organization, including broadly similar spatial patterns but distinct temporal patterns. In order to test this hypothesis, this study examined the dynamic FC in default-mode network (DMN) and motor-related network (MN) using Blood-Oxygenation-Level-Dependent (BOLD)-fMRI data from 26 healthy subjects during rest (REST) and a hand closing-and-opening (HCO) task. Two principal FC states in REST and one principal FC state in HCO were identified. The first principal FC state in REST was found similar to that in HCO, which appeared to represent intrinsic network architecture and validated the broadly similar spatial patterns between REST and HCO. However, the second FC principal state in REST with much shorter "dwell time" implied the transient functional relationship between DMN and MN during REST. In addition, a more frequent shifting between two principal FC states indicated that brain network dynamically maintained a "default mode" in the motor system during REST, whereas the presence of a single principal FC state and reduced FC variability implied a more temporally stable connectivity during HCO, validating the distinct temporal patterns between REST and HCO. Our results further demonstrated that dynamic FC analysis could offer unique insights in understanding how the brain reorganizes itself during rest and task states, and the ways in which the brain adaptively responds to the cognitive requirements of tasks.

Explaining Dynamic Interactions in Wiki-Based Collaborative Writing

ERIC Educational Resources Information Center

Li, Mimi; Zhu, Wei

2017-01-01

This article reports a case study that examined dynamic patterns of interaction that two small groups (Group A and Group B) of ESL students exemplified when they performed two writing tasks: a research proposal (Task 1) and an annotated bibliography (Task 2) in a wiki site. Group A demonstrated a collective pattern in Task 1, but switched to an…

Individual Differences in Dynamic Functional Brain Connectivity across the Human Lifespan.

PubMed

Davison, Elizabeth N; Turner, Benjamin O; Schlesinger, Kimberly J; Miller, Michael B; Grafton, Scott T; Bassett, Danielle S; Carlson, Jean M

2016-11-01

Individual differences in brain functional networks may be related to complex personal identifiers, including health, age, and ability. Dynamic network theory has been used to identify properties of dynamic brain function from fMRI data, but the majority of analyses and findings remain at the level of the group. Here, we apply hypergraph analysis, a method from dynamic network theory, to quantify individual differences in brain functional dynamics. Using a summary metric derived from the hypergraph formalism-hypergraph cardinality-we investigate individual variations in two separate, complementary data sets. The first data set ("multi-task") consists of 77 individuals engaging in four consecutive cognitive tasks. We observe that hypergraph cardinality exhibits variation across individuals while remaining consistent within individuals between tasks; moreover, the analysis of one of the memory tasks revealed a marginally significant correspondence between hypergraph cardinality and age. This finding motivated a similar analysis of the second data set ("age-memory"), in which 95 individuals, aged 18-75, performed a memory task with a similar structure to the multi-task memory task. With the increased age range in the age-memory data set, the correlation between hypergraph cardinality and age correspondence becomes significant. We discuss these results in the context of the well-known finding linking age with network structure, and suggest that hypergraph analysis should serve as a useful tool in furthering our understanding of the dynamic network structure of the brain.

History-Based Response Threshold Model for Division of Labor in Multi-Agent Systems

PubMed Central

Lee, Wonki; Kim, DaeEun

2017-01-01

Dynamic task allocation is a necessity in a group of robots. Each member should decide its own task such that it is most commensurate with its current state in the overall system. In this work, the response threshold model is applied to a dynamic foraging task. Each robot employs a task switching function based on the local task demand obtained from the surrounding environment, and no communication occurs between the robots. Each individual member has a constant-sized task demand history that reflects the global demand. In addition, it has response threshold values for all of the tasks and manages the task switching process depending on the stimuli of the task demands. The robot then determines the task to be executed to regulate the overall division of labor. This task selection induces a specialized tendency for performing a specific task and regulates the division of labor. In particular, maintaining a history of the task demands is very effective for the dynamic foraging task. Various experiments are performed using a simulation with multiple robots, and the results show that the proposed algorithm is more effective as compared to the conventional model. PMID:28555031

MIZMAS: Modeling the Evolution of Ice Thickness and Floe Size Distributions in the Marginal Ice Zone of the Chukchi and Beaufort Seas

DTIC Science & Technology

2014-09-30

existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of information. Send comments regarding this...through downscaling future projection simulations. APPROACH To address the scientific objectives, we plan to develop, implement, and validate a...ITD and FSD at the same time. The development of MIZMAS will be based on systematic model parameterization, calibration, and validation, and data

Acute myeloid leukaemia with myelodysplastic features in children: a report of Japanese Paediatric Leukaemia/Lymphoma Study Group.

PubMed

Kinoshita, Akitoshi; Miyachi, Hayato; Matsushita, Hiromichi; Yabe, Miharu; Taki, Tomohiko; Watanabe, Tomoyuki; Saito, Akiko M; Tomizawa, Daisuke; Taga, Takashi; Takahashi, Hiroyuki; Matsuo, Hidemasa; Kodama, Kumi; Ohki, Kentaro; Hayashi, Yasuhide; Tawa, Akio; Horibe, Keizo; Adachi, Souichi

2014-10-01

The clinical characteristics and prognostic relevance of acute myeloid leukaemia (AML) with myelodysplastic features remains to be clarified in children. We prospectively examined 443 newly diagnosed patients in a multicentre clinical trial for paediatric de novo AML, and found 'AML with myelodysplasia-related changes' (AML-MRC) according to the 2008 World Health Organization classification in 93 (21·0%), in whom 59 were diagnosed from myelodysplasia-related cytogenetics alone, 28 from multilineage dysplasia alone and six from a combination of both. Compared with 111 patients with 'AML, not otherwise specified' (AML-NOS), patients with 'AML-MRC' presented at a younger age, with a lower white blood cell count, higher incidence of 20-30% bone marrow blasts, unfavourable cytogenetics and a lower frequency of Fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD), NPM1 and CEBPA mutations. Complete remission rate and 3-year probability of event-free survival were significantly worse in 'AML-MRC' patients (67·7 vs. 85·6%, P < 0·01, 37·1% vs. 53·8%, P = 0·02, respectively), but 3-year overall survival and relapse-free survival were comparable with 'AML-NOS' patients. By multivariate analysis, FLT3-ITD was solely associated with worse overall survival. These results support the distinctive features of the category 'AML-MRC' even in children. © 2014 John Wiley & Sons Ltd.

Revision of Import and Export Requirements for Controlled Substances, Listed Chemicals, and Tableting and Encapsulating Machines, Including Changes To Implement the International Trade Data System (ITDS); Revision of Reporting Requirements for Domestic Transactions in Listed Chemicals and Tableting and Encapsulating Machines; and Technical Amendments. Final rule.

PubMed

2016-12-30

The Drug Enforcement Administration is updating its regulations for the import and export of tableting and encapsulating machines, controlled substances, and listed chemicals, and its regulations relating to reports required for domestic transactions in listed chemicals, gamma-hydroxybutyric acid, and tableting and encapsulating machines. In accordance with Executive Order 13563, the Drug Enforcement Administration has reviewed its import and export regulations and reporting requirements for domestic transactions in listed chemicals (and gamma-hydroxybutyric acid) and tableting and encapsulating machines, and evaluated them for clarity, consistency, continued accuracy, and effectiveness. The amendments clarify certain policies and reflect current procedures and technological advancements. The amendments also allow for the implementation, as applicable to tableting and encapsulating machines, controlled substances, and listed chemicals, of the President's Executive Order 13659 on streamlining the export/import process and requiring the government-wide utilization of the International Trade Data System (ITDS). This rule additionally contains amendments that implement recent changes to the Controlled Substances Import and Export Act (CSIEA) for reexportation of controlled substances among members of the European Economic Area made by the Improving Regulatory Transparency for New Medical Therapies Act. The rule also includes additional substantive and technical and stylistic amendments.

An extremely high dietary iodide supply forestalls severe hypothyroidism in Na+/I- symporter (NIS) knockout mice.

PubMed

Ferrandino, Giuseppe; Kaspari, Rachel R; Reyna-Neyra, Andrea; Boutagy, Nabil E; Sinusas, Albert J; Carrasco, Nancy

2017-07-13

The sodium/iodide symporter (NIS) mediates active iodide (I - ) accumulation in the thyroid, the first step in thyroid hormone (TH) biosynthesis. Mutations in the SLC5A5 gene encoding NIS that result in a non-functional protein lead to congenital hypothyroidism due to I - transport defect (ITD). ITD is a rare autosomal disorder that, if not treated promptly in infancy, can cause mental retardation, as the TH decrease results in improper development of the nervous system. However, in some patients, hypothyroidism has been ameliorated by unusually large amounts of dietary I - . Here we report the first NIS knockout (KO) mouse model, obtained by targeting exons 6 and 7 of the Slc5a5 gene. In NIS KO mice, in the thyroid, stomach, and salivary gland, NIS is absent, and hence there is no active accumulation of the NIS substrate pertechnetate ( 99m TcO 4 - ). NIS KO mice showed undetectable serum T 4 and very low serum T 3 levels when fed a diet supplying the minimum I - requirement for rodents. These hypothyroid mice displayed oxidative stress in the thyroid, but not in the brown adipose tissue or liver. Feeding the mice a high-I - diet partially rescued TH biosynthesis, demonstrating that, at high I - concentrations, I - enters the thyroid through routes other than NIS.

Genetic instability in inherited and sporadic leukemias.

PubMed

Popp, Henning D; Bohlander, Stefan K

2010-12-01

Genetic instability due to increased DNA damage and altered DNA repair is of central significance in the initiation and progression of inherited and sporadic human leukemias. Although very rare, some inherited DNA repair insufficiency syndromes (e.g., Fanconi anemia, Bloom's syndrome) have added substantially to our understanding of crucial mechanisms of leukemogenesis in recent years. Conversely, sporadic leukemias account for the main proportion of leukemias and here DNA damaging reactive oxygen species (ROS) play a central role. Although the exact mechanisms of increased ROS production remain largely unknown and no single pathway has been detected thus far, some oncogenic proteins (e.g., the activated tyrosine kinases BCR-ABL1 and FLT3-ITD) seem to play a key role in driving genetic instability by increased ROS generation which influences the disease course (e.g., blast crisis in chronic myeloid leukemia or relapse in FLT3-ITD positive acute myeloid leukemia). Of course other mechanisms, which promote genetic instability in leukemia also exist. A newly emerging mechanism is the genome-wide alteration of epigenetic marks (e.g., hypomethylation of histone H3K79), which promotes chromosomal instability. Taken together genetic instability plays a critical role both in inherited and sporadic leukemias and emerges as a common theme in both inherited and sporadic leukemias. Beyond its theoretical impact, the analysis of genetic instability may lead the way to the development of innovative therapy strategies. © 2010 Wiley-Liss, Inc.

Underwater localization of pure tones by harbor seals (Phoca vitulina).

PubMed

Bodson, Anaïs; Miersch, Lars; Dehnhardt, Guido

2007-10-01

The underwater sound localization acuity of harbor seals (Phoca vitulina) was measured in the horizontal plane. Minimum audible angles (MAAs) of pure tones were determined as a function of frequency from 0.2 to 16 kHz for two seals. Testing was conducted in a 10-m-diam underwater half circle using a right/left psychophysical procedure. The results indicate that for both harbor seals, MAAs were large at high frequencies (13.5 degrees and 17.4 degrees at 16 kHz), transitional at intermediate frequencies (9.6 degrees and 10.1 degrees at 4 kHz), and particularly small at low frequencies (3.2 degrees and 3.1 degrees at 0.2 kHz). Harbor seals seem to be able to utilize both binaural cues, interaural time differences (ITDs) and interaural intensity differences (IIDs), but a significant decrease in the sound localization acuity with increasing frequency suggests that IID cues may not be as robust as ITD cues under water. These results suggest that the harbor seal can be regarded as a low-frequency specialist. Additionally, to obtain a MAA more representative of the species, the horizontal underwater MAA of six adult harbor seals was measured at 2 kHz under identical conditions. The MAAs of the six animals ranged from 8.8 degrees to 11.7 degrees , resulting in a mean MAA of 10.3 degrees .

FLT3 Inhibitors in Acute Myeloid Leukemia: Current Status and Future Directions.

PubMed

Larrosa-Garcia, Maria; Baer, Maria R

2017-06-01

The receptor tyrosine kinase fms -like tyrosine kinase 3 (FLT3), involved in regulating survival, proliferation, and differentiation of hematopoietic stem/progenitor cells, is expressed on acute myeloid leukemia (AML) cells in most patients. Mutations of FLT3 resulting in constitutive signaling are common in AML, including internal tandem duplication (ITD) in the juxtamembrane domain in 25% of patients and point mutations in the tyrosine kinase domain in 5%. Patients with AML with FLT3-ITD have a high relapse rate and short relapse-free and overall survival after chemotherapy and after transplant. A number of inhibitors of FLT3 signaling have been identified and are in clinical trials, both alone and with chemotherapy, with the goal of improving clinical outcomes in patients with AML with FLT3 mutations. While inhibitor monotherapy produces clinical responses, they are usually incomplete and transient, and resistance develops rapidly. Diverse combination therapies have been suggested to potentiate the efficacy of FLT3 inhibitors and to prevent development of resistance or overcome resistance. Combinations with epigenetic therapies, proteasome inhibitors, downstream kinase inhibitors, phosphatase activators, and other drugs that alter signaling are being explored. This review summarizes the current status of translational and clinical research on FLT3 inhibitors in AML, and discusses novel combination approaches. Mol Cancer Ther; 16(6); 991-1001. ©2017 AACR . ©2017 American Association for Cancer Research.

To Pass or Not to Pass: Modeling the Movement and Affordance Dynamics of a Pick and Place Task

PubMed Central

Lamb, Maurice; Kallen, Rachel W.; Harrison, Steven J.; Di Bernardo, Mario; Minai, Ali; Richardson, Michael J.

2017-01-01

Humans commonly engage in tasks that require or are made more efficient by coordinating with other humans. In this paper we introduce a task dynamics approach for modeling multi-agent interaction and decision making in a pick and place task where an agent must move an object from one location to another and decide whether to act alone or with a partner. Our aims were to identify and model (1) the affordance related dynamics that define an actor's choice to move an object alone or to pass it to their co-actor and (2) the trajectory dynamics of an actor's hand movements when moving to grasp, relocate, or pass the object. Using a virtual reality pick and place task, we demonstrate that both the decision to pass or not pass an object and the movement trajectories of the participants can be characterized in terms of a behavioral dynamics model. Simulations suggest that the proposed behavioral dynamics model exhibits features observed in human participants including hysteresis in decision making, non-straight line trajectories, and non-constant velocity profiles. The proposed model highlights how the same low-dimensional behavioral dynamics can operate to constrain multiple (and often nested) levels of human activity and suggests that knowledge of what, when, where and how to move or act during pick and place behavior may be defined by these low dimensional task dynamics and, thus, can emerge spontaneously and in real-time with little a priori planning. PMID:28701975

Fatigability and recovery of arm muscles with advanced age for dynamic and isometric contractions.

PubMed

Yoon, Tejin; Schlinder-Delap, Bonnie; Hunter, Sandra K

2013-02-01

This study determined whether age-related mechanisms can increase fatigue of arm muscles during maximal velocity dynamic contractions, as it occurs in the lower limb. We compared elbow flexor fatigue of young (n=10, 20.8±2.7 years) and old men (n=16, 73.8±6.1 years) during and in recovery from a dynamic and an isometric postural fatiguing task. Each task was maintained until failure while supporting a load equivalent to 20% of maximal voluntary isometric contraction (MVIC) torque. Transcranial magnetic stimulation (TMS) was used to assess supraspinal fatigue (superimposed twitch, SIT) and muscle relaxation. Time to failure was longer for the old men than for the young men for the isometric task (9.5±3.1 vs. 17.2±7.0 min, P=0.01) but similar for the dynamic task (6.3±2.4 min vs. 6.0±2.0 min, P=0.73). Initial peak rate of relaxation was slower for the old men than for the young men, and was associated with a longer time to failure for both tasks (P<0.05). Low initial power during elbow flexion was associated with the greatest difference (reduction) in time to failure between the isometric task and the dynamic task (r=-0.54, P=0.015). SIT declined after both fatigue tasks similarly with age, although the recovery of SIT was associated with MVIC recovery for the old (both sessions) but not for the young men. Biceps brachii and brachioradialis EMG activity (% MVIC) of the old men were greater than that of the young men during the dynamic fatiguing task (P<0.05), but were similar during the isometric task. Muscular mechanisms and greater relative muscle activity (EMG activity) explain the greater fatigue during the dynamic task for the old men compared with the young men in the elbow flexor muscles. Recovery of MVC torque however relies more on the recovery of supraspinal fatigue among the old men than among the young men. Copyright © 2012 Elsevier Inc. All rights reserved.

Dynamic balance during walking adaptability tasks in individuals post-stroke.

PubMed

Vistamehr, Arian; Balasubramanian, Chitralakshmi K; Clark, David J; Neptune, Richard R; Fox, Emily J

2018-06-06

Maintaining dynamic balance during community ambulation is a major challenge post-stroke. Community ambulation requires performance of steady-state level walking as well as tasks that require walking adaptability. Prior studies on balance control post-stroke have mainly focused on steady-state walking, but walking adaptability tasks have received little attention. The purpose of this study was to quantify and compare dynamic balance requirements during common walking adaptability tasks post-stroke and in healthy adults and identify differences in underlying mechanisms used for maintaining dynamic balance. Kinematic data were collected from fifteen individuals with post-stroke hemiparesis during steady-state forward and backward walking, obstacle negotiation, and step-up tasks. In addition, data from ten healthy adults provided the basis for comparison. Dynamic balance was quantified using the peak-to-peak range of whole-body angular-momentum in each anatomical plane during the paretic, nonparetic and healthy control single-leg-stance phase of the gait cycle. To understand differences in some of the key underlying mechanisms for maintaining dynamic balance, foot placement and plantarflexor muscle activation were examined. Individuals post-stroke had significant dynamic balance deficits in the frontal plane across most tasks, particularly during the paretic single-leg-stance. Frontal plane balance deficits were associated with wider paretic foot placement, elevated body center-of-mass, and lower soleus activity. Further, the obstacle negotiation task imposed a higher balance requirement, particularly during the trailing leg single-stance. Thus, improving paretic foot placement and ankle plantarflexor activity, particularly during obstacle negotiation, may be important rehabilitation targets to enhance dynamic balance during post-stroke community ambulation. Copyright © 2018 Elsevier Ltd. All rights reserved.

Age-related effects on postural control under multi-task conditions.

PubMed

Granacher, Urs; Bridenbaugh, Stephanie A; Muehlbauer, Thomas; Wehrle, Anja; Kressig, Reto W

2011-01-01

Changes in postural sway and gait patterns due to simultaneously performed cognitive (CI) and/or motor interference (MI) tasks have previously been reported and are associated with an increased risk of falling in older adults. The objectives of this study were to investigate the effects of a CI and/or MI task on static and dynamic postural control in young and elderly subjects, and to find out whether there is an association between measures of static and dynamic postural control while concurrently performing the CI and/or MI task. A total of 36 healthy young (n = 18; age: 22.3 ± 3.0 years; BMI: 21.0 ± 1.6 kg/m(2)) and elderly adults (n = 18; age: 73.5 ± 5.5 years; BMI: 24.2 ± 2.9 kg/m(2)) participated in this study. Static postural control was measured during bipedal stance, and dynamic postural control was obtained while walking on an instrumented walkway. Irrespective of the task condition, i.e. single-task or multiple tasks, elderly participants showed larger center-of-pressure displacements and greater stride-to-stride variability than younger participants. Associations between measures of static and dynamic postural control were found only under the single-task condition in the elderly. Age-related deficits in the postural control system seem to be primarily responsible for the observed results. The weak correlations detected between static and dynamic measures could indicate that fall-risk assessment should incorporate dynamic measures under multi-task conditions, and that skills like erect standing and walking are independent of each other and may have to be trained complementarily. Copyright © 2010 S. Karger AG, Basel.

Inattentional Blindness and Individual Differences in Cognitive Abilities.

PubMed

Kreitz, Carina; Furley, Philip; Memmert, Daniel; Simons, Daniel J

2015-01-01

People sometimes fail to notice salient unexpected objects when their attention is otherwise occupied, a phenomenon known as inattentional blindness. To explore individual differences in inattentional blindness, we employed both static and dynamic tasks that either presented the unexpected object away from the focus of attention (spatial) or near the focus of attention (central). We hypothesized that noticing in central tasks might be driven by the availability of cognitive resources like working memory, and that noticing in spatial tasks might be driven by the limits on spatial attention like attention breadth. However, none of the cognitive measures predicted noticing in the dynamic central task or in either the static or dynamic spatial task. Only in the central static task did working memory capacity predict noticing, and that relationship was fairly weak. Furthermore, whether or not participants noticed an unexpected object in a static task was only weakly associated with their odds of noticing an unexpected object in a dynamic task. Taken together, our results are largely consistent with the notion that noticing unexpected objects is driven more by stochastic processes common to all people than by stable individual differences in cognitive abilities.

Inattentional Blindness and Individual Differences in Cognitive Abilities

PubMed Central

Kreitz, Carina; Furley, Philip; Memmert, Daniel; Simons, Daniel J.

2015-01-01

People sometimes fail to notice salient unexpected objects when their attention is otherwise occupied, a phenomenon known as inattentional blindness. To explore individual differences in inattentional blindness, we employed both static and dynamic tasks that either presented the unexpected object away from the focus of attention (spatial) or near the focus of attention (central). We hypothesized that noticing in central tasks might be driven by the availability of cognitive resources like working memory, and that noticing in spatial tasks might be driven by the limits on spatial attention like attention breadth. However, none of the cognitive measures predicted noticing in the dynamic central task or in either the static or dynamic spatial task. Only in the central static task did working memory capacity predict noticing, and that relationship was fairly weak. Furthermore, whether or not participants noticed an unexpected object in a static task was only weakly associated with their odds of noticing an unexpected object in a dynamic task. Taken together, our results are largely consistent with the notion that noticing unexpected objects is driven more by stochastic processes common to all people than by stable individual differences in cognitive abilities. PMID:26258545

Effect of aging on dynamic postural stability and variability during a multi-directional lean and reach object transportation task.

PubMed

Huntley, Andrew H; Zettel, John L; Vallis, Lori Ann

2016-01-01

A "reach and transport object" task that represents common activities of daily living may provide improved insight into dynamic postural stability and movement variability deficits in older adults compared to previous lean to reach and functional reach tests. Healthy young and older, community dwelling adults performed three same elevation object transport tasks and two multiple elevation object transport tasks under two self-selected speeds, self-paced and fast-paced. Dynamic postural stability and movement variability was quantified by whole-body center of mass motion. Older adults demonstrated significant decrements in frontal plane stability during the multiple elevation tasks while exhibiting the same movement variability as their younger counterparts, regardless of task speed. Interestingly, older adults did not exhibit a tradeoff in maneuverability in favour of maintaining stability throughout the tasks, as has previously been reported. In conclusion, the multi-planar, ecologically relevant tasks employed in the current study were specific enough to elucidate decrements in dynamic stability, and thus may be useful for assessing fall risk in older adults with suspected postural instability. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Dynamic Multiple Work Stealing Strategy for Flexible Load Balancing

NASA Astrophysics Data System (ADS)

Adnan; Sato, Mitsuhisa

Lazy-task creation is an efficient method of overcoming the overhead of the grain-size problem in parallel computing. Work stealing is an effective load balancing strategy for parallel computing. In this paper, we present dynamic work stealing strategies in a lazy-task creation technique for efficient fine-grain task scheduling. The basic idea is to control load balancing granularity depending on the number of task parents in a stack. The dynamic-length strategy of work stealing uses run-time information, which is information on the load of the victim, to determine the number of tasks that a thief is allowed to steal. We compare it with the bottommost first work stealing strategy used in StackThread/MP, and the fixed-length strategy of work stealing, where a thief requests to steal a fixed number of tasks, as well as other multithreaded frameworks such as Cilk and OpenMP task implementations. The experiments show that the dynamic-length strategy of work stealing performs well in irregular workloads such as in UTS benchmarks, as well as in regular workloads such as Fibonacci, Strassen's matrix multiplication, FFT, and Sparse-LU factorization. The dynamic-length strategy works better than the fixed-length strategy because it is more flexible than the latter; this strategy can avoid load imbalance due to overstealing.

Solution strategies as possible explanations of individual and sex differences in a dynamic spatial task.

PubMed

Peña, Daniel; Contreras, María José; Shih, Pei Chun; Santacreu, José

2008-05-01

When individuals perform spatial tasks, individual differences emerge in accuracy and speed as well as in the response patterns used to cope with the task. The purpose of this study is to identify, through empirical criteria, the different response patterns or strategies used by individuals when performing the dynamic spatial task presented in the Spatial Orientation Dynamic Test-Revised (SODT-R). Results show that participants can be classified according to their response patterns. Three different ways of solving a task are described, and their relation to (a) performance factors (response latency, response frequency, and invested time) and (b) ability tests (analytical reasoning, verbal reasoning, and spatial estimation) are investigated. Sex differences in response patterns and performance are also analyzed. It is found that the frequency with which men and women employ each one of the strategies described here, is different and statistically significant. Thus, employed strategy plays an important role when interpreting sex differences on dynamic spatial tasks.

A nonlinear dynamics of trunk kinematics during manual lifting tasks.

PubMed

Khalaf, Tamer; Karwowski, Waldemar; Sapkota, Nabin

2015-01-01

Human responses at work may exhibit nonlinear properties where small changes in the initial task conditions can lead to large changes in system behavior. Therefore, it is important to study such nonlinearity to gain a better understanding of human performance under a variety of physical, perceptual, and cognitive tasks conditions. The main objective of this study was to investigate whether the human trunk kinematics data during a manual lifting task exhibits nonlinear behavior in terms of determinist chaos. Data related to kinematics of the trunk with respect to the pelvis were collected using Industrial Lumbar Motion Monitor (ILMM), and analyzed applying the nonlinear dynamical systems methodology. Nonlinear dynamics quantifiers of Lyapunov exponents and Kaplan-Yorke dimensions were calculated and analyzed under different task conditions. The study showed that human trunk kinematics during manual lifting exhibits chaotic behavior in terms of trunk sagittal angular displacement, velocity and acceleration. The findings support the importance of accounting for nonlinear dynamical properties of biomechanical responses to lifting tasks.

Acute myeloid leukemia: 2013 update on risk-stratification and management.

PubMed

Estey, Elihu H

2013-04-01

Acute myeloid leukemia (AML) results from accumulation of abnormal blasts in the marrow. These cells interfere with normal hematopoiesis, can escape into the peripheral blood, and infiltrate CSF and lung. It is likely that many different mutations, epigenetic aberrations, or abnormalities in micro RNA expression can produce the same morphologic disease with these differences responsible for the very variable response to therapy, which is AMLs principal feature. This rests on demonstration that the marrow or blood has > 20% blasts of myeloid lineage. Blast lineage is assessed by multiparameter flow cytometry, with CD33 and CD13 being surface markers typically expressed by myeloid blasts. It should be realized that clinical/prognostic considerations, not the blast % per se, should be the main factor determining how a patient is treated. Two features determine risk: the probability of treatment-related mortality (TRM) and, more important, even in patients aged >75 with Zubrod performance status 1, the probability of resistance to standard therapy despite not incurring TRM. The chief predictor of resistance is cytogenetics, with a monosomal karyotype (MK) denoting the disease is essentially incurable with standard therapy even if followed by a standard allogeneic transplant (HCT). The most common cytogentic finding is a normal karyotype(NK) and those of such patients with an NPM1 mutation but no FLT3 internal tandem duplication (ITD), or with a CEBPA mutation, have a prognosis similar to that of patients with the most favorable cytogenetics (inv 16 or t[8;21]) (60-70% cure rate). In contrast, NK patients with a FLT3 ITD have only a 30-40% chance of cure even after HCT. Accordingly analyses of NPM1, FLT3, and CEBPA should be part of routine evaluation, much as is cytogenetics. Risk is best assessed considering several variables simultaneously rather than, for example, only age. Increasing evidence indicates that other mutations and abnormalities in microRNA (miRNA) expression also affect resistance as do post treatment factors, in particular the presence of minimal residual disease. These newer mutations and MRD are discussed in this update. Patients with inv (16) or t(8;21) or who are NPM1+/FLT3ITD-can receive standard therapy (daunorubicin + cytarabine) and should not receive HCT in first CR. It seems likely that use of a daily daunorubicin dose of 90 mg/m(2) will further improve outcome in these patients. There appears no reason to use doses of cytarabine > 1 g/m(2) (for example bid X 6 days), as opposed to the more commonly used 3 g/m(2) . Patients with an unfavorable karyotype (particularly MK) are unlikely to benefit from standard therapy (even with dose escalation) and are thus prime candidates for clinical trials of new drugs or new approaches to HCT; the latter should be done in first CR. Patients with intermediate prognoses (for example NK and NPM and FLT3ITD negative) should also receive HCT in first CR and can plausibly receive either investigational or standard induction therapy, with the same prognostic information about standard therapy leading one patient to choose the standard and another an investigational option. This update discusses results with newer agents: quizartinib and crenolanib, gemtuzumab ozogamicin, clofarabine and cladribine, azacitidine and decitabine, volasertib, and means to prevent relapse after allogeneic transplant. The diagnosis of AML essentially is made as it was in 2012. Thus this review will emphasize new developments in risk stratification and treatment using as references many papers published in 2012. Copyright © 2013 Wiley Periodicals, Inc.

Sound-direction identification, interaural time delay discrimination, and speech intelligibility advantages in noise for a bilateral cochlear implant user.

PubMed

Van Hoesel, Richard; Ramsden, Richard; Odriscoll, Martin

2002-04-01

To characterize some of the benefits available from using two cochlear implants compared with just one, sound-direction identification (ID) abilities, sensitivity to interaural time delays (ITDs) and speech intelligibility in noise were measured for a bilateral multi-channel cochlear implant user. Sound-direction ID in the horizontal plane was tested with a bilateral cochlear implant user. The subject was tested both unilaterally and bilaterally using two independent behind-the-ear ESPRIT (Cochlear Ltd.) processors, as well as bilaterally using custom research processors. Pink noise bursts were presented using an 11-loudspeaker array spanning the subject's frontal 180 degrees arc in an anechoic room. After each burst, the subject was asked to identify which loudspeaker had produced the sound. No explicit training, and no feedback were given. Presentation levels were nominally at 70 dB SPL, except for a repeat experiment using the clinical devices where the presentation levels were reduced to 60 dB SPL to avoid activation of the devices' automatic gain control (AGC) circuits. Overall presentation levels were randomly varied by +/- 3 dB. For the research processor, a "low-update-rate" and a "high-update-rate" strategy were tested. Direct measurements of ITD just noticeable differences (JNDs) were made using a 3 AFC paradigm targeting 70% correct performance on the psychometric function. Stimuli included simple, low-rate electrical pulse trains as well as high-rate pulse trains modulated at 100 Hz. Speech data comparing monaural and binaural performance in noise were also collected with both low, and high update-rate strategies on the research processors. Open-set sentences were presented from directly in front of the subject and competing multi-talker babble noise was presented from the same loudspeaker, or from a loudspeaker placed 90 degrees to the left or right of the subject. For the sound-direction ID task, monaural performance using the clinical devices showed large mean absolute errors of 81 degrees and 73 degrees, with standard deviations (averaged across all 11 loud-speakers) of 10 degrees and 17 degrees, for left and right ears, respectively. Fore bilateral device use at a presentation level of 70 dB SPL, the mean error improved to about 16 degrees with an average standard deviation of 18 degrees. When the presentation level was decreased to 60 dB SPL to avoid activation of the automatic gain control (AGC) circuits in the clinical processors, the mean response error improved further to 8 degrees with a standard deviation of 13 degrees. Further tests with the custom research processors, which had a higher stimulation rate and did not include AGCs, showed comparable response errors: around 8 or 9 degrees and a standard deviation of about 11 degrees for both update rates. The best ITD JNDs measured for this subject were between 350 to 400 microsec for simple low-rate pulse trains. Speech results showed a substantial headshadow advantage for bilateral device use when speech and noise were spatially separated, but little evidence of binaural unmasking. For spatially coincident speech and noise, listening with both ears showed similar results to listening with either side alone when loudness summation was compensated for. No significant differences were observed between binaural results for high and low update-rates in any test configuration. Only for monaural listening in one test configuration did the high rate show a small significant improvement over the low rate. Results show that even if interaural time delay cues are not well coded or perceived, bilateral implants can offer important advantages, both for speech in noise as well as for sound-direction identification.

Degradation of learned skills: Effectiveness of practice methods on visual approach and landing skill retention

NASA Technical Reports Server (NTRS)

Sitterley, T. E.; Zaitzeff, L. P.; Berge, W. A.

1972-01-01

Flight control and procedural task skill degradation, and the effectiveness of retraining methods were evaluated for a simulated space vehicle approach and landing under instrument and visual flight conditions. Fifteen experienced pilots were trained and then tested after 4 months either without the benefits of practice or with static rehearsal, dynamic rehearsal or with dynamic warmup practice. Performance on both the flight control and procedure tasks degraded significantly after 4 months. The rehearsal methods effectively countered procedure task skill degradation, while dynamic rehearsal or a combination of static rehearsal and dynamic warmup practice was required for the flight control tasks. The quality of the retraining methods appeared to be primarily dependent on the efficiency of visual cue reinforcement.

Analysis of tasks for dynamic man/machine load balancing in advanced helicopters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jorgensen, C.C.

1987-10-01

This report considers task allocation requirements imposed by advanced helicopter designs incorporating mixes of human pilots and intelligent machines. Specifically, it develops an analogy between load balancing using distributed non-homogeneous multiprocessors and human team functions. A taxonomy is presented which can be used to identify task combinations likely to cause overload for dynamic scheduling and process allocation mechanisms. Designer criteria are given for function decomposition, separation of control from data, and communication handling for dynamic tasks. Possible effects of n-p complete scheduling problems are noted and a class of combinatorial optimization methods are examined.

Linear and Logarithmic Speed-Accuracy Trade-Offs in Reciprocal Aiming Result from Task-Specific Parameterization of an Invariant Underlying Dynamics

ERIC Educational Resources Information Center

Bongers, Raoul M.; Fernandez, Laure; Bootsma, Reinoud J.

2009-01-01

The authors examined the origins of linear and logarithmic speed-accuracy trade-offs from a dynamic systems perspective on motor control. In each experiment, participants performed 2 reciprocal aiming tasks: (a) a velocity-constrained task in which movement time was imposed and accuracy had to be maximized, and (b) a distance-constrained task in…

Evaluation of linearly solvable Markov decision process with dynamic model learning in a mobile robot navigation task.

PubMed

Kinjo, Ken; Uchibe, Eiji; Doya, Kenji

2013-01-01

Linearly solvable Markov Decision Process (LMDP) is a class of optimal control problem in which the Bellman's equation can be converted into a linear equation by an exponential transformation of the state value function (Todorov, 2009b). In an LMDP, the optimal value function and the corresponding control policy are obtained by solving an eigenvalue problem in a discrete state space or an eigenfunction problem in a continuous state using the knowledge of the system dynamics and the action, state, and terminal cost functions. In this study, we evaluate the effectiveness of the LMDP framework in real robot control, in which the dynamics of the body and the environment have to be learned from experience. We first perform a simulation study of a pole swing-up task to evaluate the effect of the accuracy of the learned dynamics model on the derived the action policy. The result shows that a crude linear approximation of the non-linear dynamics can still allow solution of the task, despite with a higher total cost. We then perform real robot experiments of a battery-catching task using our Spring Dog mobile robot platform. The state is given by the position and the size of a battery in its camera view and two neck joint angles. The action is the velocities of two wheels, while the neck joints were controlled by a visual servo controller. We test linear and bilinear dynamic models in tasks with quadratic and Guassian state cost functions. In the quadratic cost task, the LMDP controller derived from a learned linear dynamics model performed equivalently with the optimal linear quadratic regulator (LQR). In the non-quadratic task, the LMDP controller with a linear dynamics model showed the best performance. The results demonstrate the usefulness of the LMDP framework in real robot control even when simple linear models are used for dynamics learning.

Devices and tasks involved in the objective assessment of standing dynamic balancing - A systematic literature review.

PubMed

Petró, Bálint; Papachatzopoulou, Alexandra; Kiss, Rita M

2017-01-01

Static balancing assessment is often complemented with dynamic balancing tasks. Numerous dynamic balancing assessment methods have been developed in recent decades with their corresponding balancing devices and tasks. The aim of this systematic literature review is to identify and categorize existing objective methods of standing dynamic balancing ability assessment with an emphasis on the balancing devices and tasks being used. Three major scientific literature databases (Science Direct, Web of Science, PLoS ONE) and additional sources were used. Studies had to use a dynamic balancing device and a task described in detail. Evaluation had to be based on objectively measureable parameters. Functional tests without instrumentation evaluated exclusively by a clinician were excluded. A total of 63 articles were included. The data extracted during full-text assessment were: author and date; the balancing device with the balancing task and the measured parameters; the health conditions, size, age and sex of participant groups; and follow-up measurements. A variety of dynamic balancing assessment devices were identified and categorized as 1) Solid ground, 2) Balance board, 3) Rotating platform, 4) Horizontal translational platform, 5) Treadmill, 6) Computerized Dynamic Posturography, and 7) Other devices. The group discrimination ability of the methods was explored and the conclusions of the studies were briefly summarized. Due to the wide scope of this search, it provides an overview of balancing devices and do not represent the state-of-the-art of any single method. The identified dynamic balancing assessment methods are offered as a catalogue of candidate methods to complement static assessments used in studies involving postural control.

Using ILD or ITD Cues for Sound Source Localization and Speech Understanding in a Complex Listening Environment by Listeners With Bilateral and With Hearing-Preservation Cochlear Implants.

PubMed

Loiselle, Louise H; Dorman, Michael F; Yost, William A; Cook, Sarah J; Gifford, Rene H

2016-08-01

To assess the role of interaural time differences and interaural level differences in (a) sound-source localization, and (b) speech understanding in a cocktail party listening environment for listeners with bilateral cochlear implants (CIs) and for listeners with hearing-preservation CIs. Eleven bilateral listeners with MED-EL (Durham, NC) CIs and 8 listeners with hearing-preservation CIs with symmetrical low frequency, acoustic hearing using the MED-EL or Cochlear device were evaluated using 2 tests designed to task binaural hearing, localization, and a simulated cocktail party. Access to interaural cues for localization was constrained by the use of low-pass, high-pass, and wideband noise stimuli. Sound-source localization accuracy for listeners with bilateral CIs in response to the high-pass noise stimulus and sound-source localization accuracy for the listeners with hearing-preservation CIs in response to the low-pass noise stimulus did not differ significantly. Speech understanding in a cocktail party listening environment improved for all listeners when interaural cues, either interaural time difference or interaural level difference, were available. The findings of the current study indicate that similar degrees of benefit to sound-source localization and speech understanding in complex listening environments are possible with 2 very different rehabilitation strategies: the provision of bilateral CIs and the preservation of hearing.

Microcomputer-controlled world time display for public area viewing

NASA Astrophysics Data System (ADS)

Yep, S.; Rashidian, M.

1982-05-01

The design, development, and implementation of a microcomputer-controlled world clock is discussed. The system, designated international Time Display System (ITDS), integrates a Geochron Calendar Map and a microcomputer-based digital display to automatically compensate for daylight savings time, leap year, and time zone differences. An in-depth technical description of the design and development of the electronic hardware, firmware, and software systems is provided. Reference material on the time zones, fabrication techniques, and electronic subsystems are also provided.

Radiometric Measurements by the MIDAS III System at Key West. Volume I. Cloud Backgrounds.

DTIC Science & Technology

1979-09-01

13 13.3 System Relative Spectral Response - Filter No. 2 5(4.4-4.77 pim ) ............................................. 14 3.4 System Relative Spectral...Response - Filter No. 5 (3.8-4.2 pim ) .............................................. 15 3.5 System Relative Spectral Response - Filter No. 6 (3.4-4.3...5 dat a was recorded dirtxet l ott t he recordinig osc ml logrtt1 Witereis tilt- 8-13 data was recorded on t tiet I ape, recorders i xst itd laxter p

Genetic disorders of the anterior pituitary gland.

PubMed

Teller, W M

1985-01-01

This survey deals with disorders caused by genetically disturbed function of the anterior pituitary gland. Genetic Dwarfism may be caused by isolated growth hormone deficiency (IGHD) or panpituitary diseases, such as congenital absence of the pituitary or familial panhypopituitarism. Genetic disturbances of isolated pituitary hormone secretion without dwarfism may occur as isolated gonadotropin deficiency (IGD), isolated luteinizing hormone deficiency ("fertile eunuch"), Kallmann syndrome (olfactogenital dysplasia), isolated thyrotropin deficiency (ITD) and isolated corticotropin deficiency (ICD). Pituitary dysfunction may also be associated with other genetic disease entities.

Prospective Memory and Task Interference in a Continuous Monitoring Dynamic Display Task

ERIC Educational Resources Information Center

Loft, Shayne; Remington, Roger W.

2010-01-01

Theories and methods from the prospective memory literature were used to anticipate how individuals would maintain and retrieve intentions in a continuous monitoring dynamic display task. Participants accepted aircraft into sectors and detected aircraft conflicts during an air traffic control simulation. They were sometimes required to substitute…

Behavioral compliance for dynamic versus static signs in an immersive virtual environment.

PubMed

Duarte, Emília; Rebelo, Francisco; Teles, Júlia; Wogalter, Michael S

2014-09-01

This study used an immersive virtual environment (IVE) to examine how dynamic features in signage affect behavioral compliance during a work-related task and an emergency egress. Ninety participants performed a work-related task followed by an emergency egress. Compliance with uncued and cued safety signs was assessed prior to an explosion/fire involving egress with exit signs. Although dynamic presentation produced the highest compliance, the difference between dynamic and static presentation was only statistically significant for uncued signs. Uncued signs, both static and dynamic, were effective in changing behavior compared to no/minimal signs. Findings are explained based on sign salience and on task differences. If signs must capture attention while individuals are attending to other tasks, salient (e.g., dynamic) signs are useful in benefiting compliance. This study demonstrates the potential for IVEs to serve as a useful tool in behavioral compliance research. Copyright © 2013 Elsevier Ltd and The Ergonomics Society. All rights reserved.

Effects of a cognitive dual task on variability and local dynamic stability in sustained repetitive arm movements using principal component analysis: a pilot study.

PubMed

Longo, Alessia; Federolf, Peter; Haid, Thomas; Meulenbroek, Ruud

2018-06-01

In many daily jobs, repetitive arm movements are performed for extended periods of time under continuous cognitive demands. Even highly monotonous tasks exhibit an inherent motor variability and subtle fluctuations in movement stability. Variability and stability are different aspects of system dynamics, whose magnitude may be further affected by a cognitive load. Thus, the aim of the study was to explore and compare the effects of a cognitive dual task on the variability and local dynamic stability in a repetitive bimanual task. Thirteen healthy volunteers performed the repetitive motor task with and without a concurrent cognitive task of counting aloud backwards in multiples of three. Upper-body 3D kinematics were collected and postural reconfigurations-the variability related to the volunteer's postural change-were determined through a principal component analysis-based procedure. Subsequently, the most salient component was selected for the analysis of (1) cycle-to-cycle spatial and temporal variability, and (2) local dynamic stability as reflected by the largest Lyapunov exponent. Finally, end-point variability was evaluated as a control measure. The dual cognitive task proved to increase the temporal variability and reduce the local dynamic stability, marginally decrease endpoint variability, and substantially lower the incidence of postural reconfigurations. Particularly, the latter effect is considered to be relevant for the prevention of work-related musculoskeletal disorders since reduced variability in sustained repetitive tasks might increase the risk of overuse injuries.

Age-Related Differences in Cortical and Subcortical Activities during Observation and Motor Imagery of Dynamic Postural Tasks: An fMRI Study.

PubMed

Mouthon, A; Ruffieux, J; Mouthon, M; Hoogewoud, H-M; Annoni, J-M; Taube, W

2018-01-01

Age-related changes in brain activation other than in the primary motor cortex are not well known with respect to dynamic balance control. Therefore, the current study aimed to explore age-related differences in the control of static and dynamic postural tasks using fMRI during mental simulation of balance tasks. For this purpose, 16 elderly (72 ± 5 years) and 16 young adults (27 ± 5 years) were asked to mentally simulate a static and a dynamic balance task by motor imagery (MI), action observation (AO), or the combination of AO and MI (AO + MI). Age-related differences were detected in the form of larger brain activations in elderly compared to young participants, especially in the challenging dynamic task when applying AO + MI. Interestingly, when MI (no visual input) was contrasted to AO (visual input), elderly participants revealed deactivation of subcortical areas. The finding that the elderly demonstrated overactivation in mostly cortical areas in challenging postural conditions with visual input (AO + MI and AO) but deactivation in subcortical areas during MI (no vision) may indicate that elderly individuals allocate more cortical resources to the internal representation of dynamic postural tasks. Furthermore, it might be assumed that they depend more strongly on visual input to activate subcortical internal representations.

Age-Related Differences in Cortical and Subcortical Activities during Observation and Motor Imagery of Dynamic Postural Tasks: An fMRI Study

PubMed Central

Ruffieux, J.; Mouthon, M.; Hoogewoud, H.-M.; Taube, W.

2018-01-01

Age-related changes in brain activation other than in the primary motor cortex are not well known with respect to dynamic balance control. Therefore, the current study aimed to explore age-related differences in the control of static and dynamic postural tasks using fMRI during mental simulation of balance tasks. For this purpose, 16 elderly (72 ± 5 years) and 16 young adults (27 ± 5 years) were asked to mentally simulate a static and a dynamic balance task by motor imagery (MI), action observation (AO), or the combination of AO and MI (AO + MI). Age-related differences were detected in the form of larger brain activations in elderly compared to young participants, especially in the challenging dynamic task when applying AO + MI. Interestingly, when MI (no visual input) was contrasted to AO (visual input), elderly participants revealed deactivation of subcortical areas. The finding that the elderly demonstrated overactivation in mostly cortical areas in challenging postural conditions with visual input (AO + MI and AO) but deactivation in subcortical areas during MI (no vision) may indicate that elderly individuals allocate more cortical resources to the internal representation of dynamic postural tasks. Furthermore, it might be assumed that they depend more strongly on visual input to activate subcortical internal representations. PMID:29675037

Dynamic Trial-by-Trial Recoding of Task-Set Representations in the Frontoparietal Cortex Mediates Behavioral Flexibility

PubMed Central

Qiao, Lei; Zhang, Lijie

2017-01-01

Cognitive flexibility forms the core of the extraordinary ability of humans to adapt, but the precise neural mechanisms underlying our ability to nimbly shift between task sets remain poorly understood. Recent functional magnetic resonance imaging (fMRI) studies employing multivoxel pattern analysis (MVPA) have shown that a currently relevant task set can be decoded from activity patterns in the frontoparietal cortex, but whether these regions support the dynamic transformation of task sets from trial to trial is not clear. Here, we combined a cued task-switching protocol with human (both sexes) fMRI, and harnessed representational similarity analysis (RSA) to facilitate a novel assessment of trial-by-trial changes in neural task-set representations. We first used MVPA to define task-sensitive frontoparietal and visual regions and found that neural task-set representations on switch trials are less stably encoded than on repeat trials. We then exploited RSA to show that the neural representational pattern dissimilarity across consecutive trials is greater for switch trials than for repeat trials, and that the degree of this pattern dissimilarity predicts behavior. Moreover, the overall neural pattern of representational dissimilarities followed from the assumption that repeating sets, compared with switching sets, results in stronger neural task representations. Finally, when moving from cue to target phase within a trial, pattern dissimilarities tracked the transformation from previous-trial task representations to the currently relevant set. These results provide neural evidence for the longstanding assumptions of an effortful task-set reconfiguration process hampered by task-set inertia, and they demonstrate that frontoparietal and stimulus processing regions support “dynamic adaptive coding,” flexibly representing changing task sets in a trial-by-trial fashion. SIGNIFICANCE STATEMENT Humans can fluently switch between different tasks, reflecting an ability to dynamically configure “task sets,” rule representations that link stimuli to appropriate responses. Recent studies show that neural signals in frontal and parietal brain regions can tell us which of two tasks a person is currently performing. However, it is not known whether these regions are also involved in dynamically reconfiguring task-set representations when switching between tasks. Here we measured human brain activity during task switching and tracked the similarity of neural task-set representations from trial to trial. We show that frontal and parietal brain regions flexibly recode changing task sets in a trial-by-trial fashion, and that task-set similarity over consecutive trials predicts behavior. PMID:28972126

Lifelong Transfer Learning for Heterogeneous Teams of Agents in Sequential Decision Processes

DTIC Science & Technology

2016-06-01

making (SDM) tasks in dynamic environments with simulated and physical robots . 15. SUBJECT TERMS Sequential decision making, lifelong learning, transfer...sequential decision-making (SDM) tasks in dynamic environments with both simple benchmark tasks and more complex aerial and ground robot tasks. Our work...and ground robots in the presence of disturbances: We applied our methods to the problem of learning controllers for robots with novel disturbances in

Applying dynamic priority scheduling scheme to static systems of pinwheel task model in power-aware scheduling.

PubMed

Seol, Ye-In; Kim, Young-Kuk

2014-01-01

Power-aware scheduling reduces CPU energy consumption in hard real-time systems through dynamic voltage scaling (DVS). In this paper, we deal with pinwheel task model which is known as static and predictable task model and could be applied to various embedded or ubiquitous systems. In pinwheel task model, each task's priority is static and its execution sequence could be predetermined. There have been many static approaches to power-aware scheduling in pinwheel task model. But, in this paper, we will show that the dynamic priority scheduling results in power-aware scheduling could be applied to pinwheel task model. This method is more effective than adopting the previous static priority scheduling methods in saving energy consumption and, for the system being still static, it is more tractable and applicable to small sized embedded or ubiquitous computing. Also, we introduce a novel power-aware scheduling algorithm which exploits all slacks under preemptive earliest-deadline first scheduling which is optimal in uniprocessor system. The dynamic priority method presented in this paper could be applied directly to static systems of pinwheel task model. The simulation results show that the proposed algorithm with the algorithmic complexity of O(n) reduces the energy consumption by 10-80% over the existing algorithms.

Applying Dynamic Priority Scheduling Scheme to Static Systems of Pinwheel Task Model in Power-Aware Scheduling

PubMed Central

2014-01-01

Power-aware scheduling reduces CPU energy consumption in hard real-time systems through dynamic voltage scaling (DVS). In this paper, we deal with pinwheel task model which is known as static and predictable task model and could be applied to various embedded or ubiquitous systems. In pinwheel task model, each task's priority is static and its execution sequence could be predetermined. There have been many static approaches to power-aware scheduling in pinwheel task model. But, in this paper, we will show that the dynamic priority scheduling results in power-aware scheduling could be applied to pinwheel task model. This method is more effective than adopting the previous static priority scheduling methods in saving energy consumption and, for the system being still static, it is more tractable and applicable to small sized embedded or ubiquitous computing. Also, we introduce a novel power-aware scheduling algorithm which exploits all slacks under preemptive earliest-deadline first scheduling which is optimal in uniprocessor system. The dynamic priority method presented in this paper could be applied directly to static systems of pinwheel task model. The simulation results show that the proposed algorithm with the algorithmic complexity of O(n) reduces the energy consumption by 10–80% over the existing algorithms. PMID:25121126

Modeling Personnel Turnover in the Parametric Organization

NASA Technical Reports Server (NTRS)

Dean, Edwin B.

1991-01-01

A primary issue in organizing a new parametric cost analysis function is to determine the skill mix and number of personnel required. The skill mix can be obtained by a functional decomposition of the tasks required within the organization and a matrixed correlation with educational or experience backgrounds. The number of personnel is a function of the skills required to cover all tasks, personnel skill background and cross training, the intensity of the workload for each task, migration through various tasks by personnel along a career path, personnel hiring limitations imposed by management and the applicant marketplace, personnel training limitations imposed by management and personnel capability, and the rate at which personnel leave the organization for whatever reason. Faced with the task of relating all of these organizational facets in order to grow a parametric cost analysis (PCA) organization from scratch, it was decided that a dynamic model was required in order to account for the obvious dynamics of the forming organization. The challenge was to create such a simple model which would be credible during all phases of organizational development. The model development process was broken down into the activities of determining the tasks required for PCA, determining the skills required for each PCA task, determining the skills available in the applicant marketplace, determining the structure of the dynamic model, implementing the dynamic model, and testing the dynamic model.

The effects of smartphone multitasking on gait and dynamic balance.

PubMed

Lee, Jeon Hyeong; Lee, Myoung Hee

2018-02-01

[Purpose] This study was performed to analyze the influence of smartphone multitasking on gait and dynamic balance. [Subjects and Methods] The subjects were 19 male and 20 female university students. There were 4 types of gait tasks: General Gait (walking without a task), Task Gait 1 (walking while writing a message), Task Gait 2 (walking while writing a message and listening to music), Task Gait 3 (walking while writing a message and having a conversation). To exclude the learning effect, the order of tasks was randomized. The Zebris FDM-T treadmill system (Zebris Medical GmbH, Germany) was used to measure left and right step length and width, and a 10 m walking test (10MWT) was conducted for gait velocity. In addition, a Timed Up and Go test (TUG) was used to measure dynamic balance. All the tasks were performed 3 times, and the mean of the measured values was analyzed. [Results] There were no statistically significant differences in step length and width. There were statistically significant differences in the 10MWT and TUG tests. [Conclusion] Using a smartphone while walking decreases a person's dynamic balance and walking ability. It is considered that accident rates are higher when using a smartphone.

Role of optimization in the human dynamics of task execution

NASA Astrophysics Data System (ADS)

Cajueiro, Daniel O.; Maldonado, Wilfredo L.

2008-03-01

In order to explain the empirical evidence that the dynamics of human activity may not be well modeled by Poisson processes, a model based on queuing processes was built in the literature [A. L. Barabasi, Nature (London) 435, 207 (2005)]. The main assumption behind that model is that people execute their tasks based on a protocol that first executes the high priority item. In this context, the purpose of this paper is to analyze the validity of that hypothesis assuming that people are rational agents that make their decisions in order to minimize the cost of keeping nonexecuted tasks on the list. Therefore, we build and analytically solve a dynamic programming model with two priority types of tasks and show that the validity of this hypothesis depends strongly on the structure of the instantaneous costs that a person has to face if a given task is kept on the list for more than one period. Moreover, one interesting finding is that in one of the situations the protocol used to execute the tasks generates complex one-dimensional dynamics.

A Framework for Load Balancing of Tensor Contraction Expressions via Dynamic Task Partitioning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lai, Pai-Wei; Stock, Kevin; Rajbhandari, Samyam

In this paper, we introduce the Dynamic Load-balanced Tensor Contractions (DLTC), a domain-specific library for efficient task parallel execution of tensor contraction expressions, a class of computation encountered in quantum chemistry and physics. Our framework decomposes each contraction into smaller unit of tasks, represented by an abstraction referred to as iterators. We exploit an extra level of parallelism by having tasks across independent contractions executed concurrently through a dynamic load balancing run- time. We demonstrate the improved performance, scalability, and flexibility for the computation of tensor contraction expressions on parallel computers using examples from coupled cluster methods.

How Temporal and Spatial Aspects of Presenting Visualizations Affect Learning about Locomotion Patterns

ERIC Educational Resources Information Center

Imhof, Birgit; Scheiter, Katharina; Edelmann, Jorg; Gerjets, Peter

2012-01-01

Two studies investigated the effectiveness of dynamic and static visualizations for a perceptual learning task (locomotion pattern classification). In Study 1, seventy-five students viewed either dynamic, static-sequential, or static-simultaneous visualizations. For tasks of intermediate difficulty, dynamic visualizations led to better…

Age-Related Changes in Dynamic Postural Control and Attentional Demands are Minimally Affected by Local Muscle Fatigue

PubMed Central

Remaud, Anthony; Thuong-Cong, Cécile; Bilodeau, Martin

2016-01-01

Normal aging results in alterations in the visual, vestibular and somtaosensory systems, which in turn modify the control of balance. Muscle fatigue may exacerbate these age-related changes in sensory and motor functions, and also increase the attentional demands associated with dynamic postural control. The purpose of this study was to investigate the effect of aging on dynamic postural control and posture-related attentional demands before and after a plantar flexor fatigue protocol. Participants (young adults: n = 15; healthy seniors: n = 13) performed a dynamic postural task along the antero-posterior (AP) and the medio-lateral (ML) axes, with and without the addition of a simple reaction time (RT) task. The dynamic postural task consisted in following a moving circle on a computer screen with the representation of the center of pressure (COP). This protocol was repeated before and after a fatigue task where ankle plantar flexor muscles were targeted. The mean COP-target distance and the mean COP velocity were calculated for each trial. Cross-correlation analyses between the COP and target displacements were also performed. RTs were recorded during dual-task trials. Results showed that while young adults adopted an anticipatory control mode to move their COP as close as possible to the target center, seniors adopted a reactive control mode, lagging behind the target center. This resulted in longer COP-target distance and higher COP velocity in the latter group. Concurrently, RT increased more in seniors when switching from static stance to dynamic postural conditions, suggesting potential alterations in the central nervous system (CNS) functions. Finally, plantar flexor muscle fatigue and dual-tasking had only minor effects on dynamic postural control of both young adults and seniors. Future studies should investigate why the fatigue-induced changes in quiet standing postural control do not seem to transfer to dynamic balance tasks. PMID:26834626

Dynamic Task Optimization in Remote Diabetes Monitoring Systems.

PubMed

Suh, Myung-Kyung; Woodbridge, Jonathan; Moin, Tannaz; Lan, Mars; Alshurafa, Nabil; Samy, Lauren; Mortazavi, Bobak; Ghasemzadeh, Hassan; Bui, Alex; Ahmadi, Sheila; Sarrafzadeh, Majid

2012-09-01

Diabetes is the seventh leading cause of death in the United States, but careful symptom monitoring can prevent adverse events. A real-time patient monitoring and feedback system is one of the solutions to help patients with diabetes and their healthcare professionals monitor health-related measurements and provide dynamic feedback. However, data-driven methods to dynamically prioritize and generate tasks are not well investigated in the domain of remote health monitoring. This paper presents a wireless health project (WANDA) that leverages sensor technology and wireless communication to monitor the health status of patients with diabetes. The WANDA dynamic task management function applies data analytics in real-time to discretize continuous features, applying data clustering and association rule mining techniques to manage a sliding window size dynamically and to prioritize required user tasks. The developed algorithm minimizes the number of daily action items required by patients with diabetes using association rules that satisfy a minimum support, confidence and conditional probability thresholds. Each of these tasks maximizes information gain, thereby improving the overall level of patient adherence and satisfaction. Experimental results from applying EM-based clustering and Apriori algorithms show that the developed algorithm can predict further events with higher confidence levels and reduce the number of user tasks by up to 76.19 %.

Dynamic Task Optimization in Remote Diabetes Monitoring Systems

PubMed Central

Suh, Myung-kyung; Woodbridge, Jonathan; Moin, Tannaz; Lan, Mars; Alshurafa, Nabil; Samy, Lauren; Mortazavi, Bobak; Ghasemzadeh, Hassan; Bui, Alex; Ahmadi, Sheila; Sarrafzadeh, Majid

2016-01-01

Diabetes is the seventh leading cause of death in the United States, but careful symptom monitoring can prevent adverse events. A real-time patient monitoring and feedback system is one of the solutions to help patients with diabetes and their healthcare professionals monitor health-related measurements and provide dynamic feedback. However, data-driven methods to dynamically prioritize and generate tasks are not well investigated in the domain of remote health monitoring. This paper presents a wireless health project (WANDA) that leverages sensor technology and wireless communication to monitor the health status of patients with diabetes. The WANDA dynamic task management function applies data analytics in real-time to discretize continuous features, applying data clustering and association rule mining techniques to manage a sliding window size dynamically and to prioritize required user tasks. The developed algorithm minimizes the number of daily action items required by patients with diabetes using association rules that satisfy a minimum support, confidence and conditional probability thresholds. Each of these tasks maximizes information gain, thereby improving the overall level of patient adherence and satisfaction. Experimental results from applying EM-based clustering and Apriori algorithms show that the developed algorithm can predict further events with higher confidence levels and reduce the number of user tasks by up to 76.19 %. PMID:27617297

A Functional Cartography of Cognitive Systems

PubMed Central

Mattar, Marcelo G.; Cole, Michael W.; Thompson-Schill, Sharon L.; Bassett, Danielle S.

2015-01-01

One of the most remarkable features of the human brain is its ability to adapt rapidly and efficiently to external task demands. Novel and non-routine tasks, for example, are implemented faster than structural connections can be formed. The neural underpinnings of these dynamics are far from understood. Here we develop and apply novel methods in network science to quantify how patterns of functional connectivity between brain regions reconfigure as human subjects perform 64 different tasks. By applying dynamic community detection algorithms, we identify groups of brain regions that form putative functional communities, and we uncover changes in these groups across the 64-task battery. We summarize these reconfiguration patterns by quantifying the probability that two brain regions engage in the same network community (or putative functional module) across tasks. These tools enable us to demonstrate that classically defined cognitive systems—including visual, sensorimotor, auditory, default mode, fronto-parietal, cingulo-opercular and salience systems—engage dynamically in cohesive network communities across tasks. We define the network role that a cognitive system plays in these dynamics along the following two dimensions: (i) stability vs. flexibility and (ii) connected vs. isolated. The role of each system is therefore summarized by how stably that system is recruited over the 64 tasks, and how consistently that system interacts with other systems. Using this cartography, classically defined cognitive systems can be categorized as ephemeral integrators, stable loners, and anything in between. Our results provide a new conceptual framework for understanding the dynamic integration and recruitment of cognitive systems in enabling behavioral adaptability across both task and rest conditions. This work has important implications for understanding cognitive network reconfiguration during different task sets and its relationship to cognitive effort, individual variation in cognitive performance, and fatigue. PMID:26629847

Using the Networked Fire Chief for ego-depletion research: measuring dynamic decision-making effort and performance.

PubMed

Barber, Larissa K; Smit, Brandon W

2014-01-01

This study replicated ego-depletion predictions from the self-control literature in a computer simulation task that requires ongoing decision-making in relation to constantly changing environmental information: the Network Fire Chief (NFC). Ego-depletion led to decreased self-regulatory effort, but not performance, on the NFC task. These effects were also buffered by task enjoyment so that individuals who enjoyed the dynamic decision-making task did not experience ego-depletion effects. These findings confirm that past ego-depletion effects on decision-making are not limited to static or isolated decision-making tasks and can be extended to dynamic, naturalistic decision-making processes more common to naturalistic settings. Furthermore, the NFC simulation provides a methodological mechanism for independently measuring effort and performance when studying ego-depletion.

Dynamic clearance measure to evaluate locomotor and perceptuo-motor strategies used for obstacle circumvention in a virtual environment.

PubMed

Darekar, Anuja; Lamontagne, Anouk; Fung, Joyce

2015-04-01

Circumvention around an obstacle entails a dynamic interaction with the obstacle to maintain a safe clearance. We used a novel mathematical interpolation method based on the modified Shepard's method of Inverse Distance Weighting to compute dynamic clearance that reflected this interaction as well as minimal clearance. This proof-of-principle study included seven young healthy, four post-stroke and four healthy age-matched individuals. A virtual environment designed to assess obstacle circumvention was used to administer a locomotor (walking) and a perceptuo-motor (navigation with a joystick) task. In both tasks, participants were asked to navigate towards a target while avoiding collision with a moving obstacle that approached from either head-on, or 30° left or right. Among young individuals, dynamic clearance did not differ significantly between obstacle approach directions in both tasks. Post-stroke individuals maintained larger and smaller dynamic clearance during the locomotor and the perceptuo-motor task respectively as compared to age-matched controls. Dynamic clearance was larger than minimal distance from the obstacle irrespective of the group, task and obstacle approach direction. Also, in contrast to minimal distance, dynamic clearance can respond differently to different avoidance behaviors. Such a measure can be beneficial in contrasting obstacle avoidance behaviors in different populations with mobility problems. Copyright © 2015 Elsevier B.V. All rights reserved.

Brain dynamics of post-task resting state are influenced by expertise: Insights from baseball players.

PubMed

Muraskin, Jordan; Dodhia, Sonam; Lieberman, Gregory; Garcia, Javier O; Verstynen, Timothy; Vettel, Jean M; Sherwin, Jason; Sajda, Paul

2016-12-01

Post-task resting state dynamics can be viewed as a task-driven state where behavioral performance is improved through endogenous, non-explicit learning. Tasks that have intrinsic value for individuals are hypothesized to produce post-task resting state dynamics that promote learning. We measured simultaneous fMRI/EEG and DTI in Division-1 collegiate baseball players and compared to a group of controls, examining differences in both functional and structural connectivity. Participants performed a surrogate baseball pitch Go/No-Go task before a resting state scan, and we compared post-task resting state connectivity using a seed-based analysis from the supplementary motor area (SMA), an area whose activity discriminated players and controls in our previous results using this task. Although both groups were equally trained on the task, the experts showed differential activity in their post-task resting state consistent with motor learning. Specifically, we found (1) differences in bilateral SMA-L Insula functional connectivity between experts and controls that may reflect group differences in motor learning, (2) differences in BOLD-alpha oscillation correlations between groups suggests variability in modulatory attention in the post-task state, and (3) group differences between BOLD-beta oscillations that may indicate cognitive processing of motor inhibition. Structural connectivity analysis identified group differences in portions of the functionally derived network, suggesting that functional differences may also partially arise from variability in the underlying white matter pathways. Generally, we find that brain dynamics in the post-task resting state differ as a function of subject expertise and potentially result from differences in both functional and structural connectivity. Hum Brain Mapp 37:4454-4471, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Maintenance lenalidomide in combination with 5-azacitidine as post-remission therapy for acute myeloid leukaemia.

PubMed

Wei, Andrew; Tan, Peter; Perruzza, Sarah; Govindaraj, Chindu; Fleming, Shaun; McManus, Julie; Avery, Sharon; Patil, Sushrut; Stevenson, William; Plebanski, Magdalena; Spencer, Andrew

2015-04-01

In this Phase 1b study, the safety and tolerability of maintenance therapy, comprising lenalidomide (0-25 mg, days 5-25) in combination with azacitidine (50-75 mg/m(2) , days 1-5) every 28 d, was explored in 40 patients with acute myeloid leukaemia (AML) in complete remission after chemotherapy. Eligibility included AML in first complete remission (CR1) with adverse risk karyotype (n = 8), fms-related tyrosine kinase 3-internal tandem duplication (FLT3-ITD) (n = 5), age ≥60 years (n = 31) or AML in second remission (CR2) (n = 14). Dose-limiting toxicity was not reached. Common toxicities were haematological, infection, injection pain, constipation, fatigue and diarrhoea. In CR1, median relapse-free (RFS) and overall survival (OS) was 12 and 20 months, respectively. In CR2, median RFS was 11 months, with median OS not yet reached. Among 29 patients with intermediate cytogenetic risk, RFS was 50% at 24 months. There were five patients with concomitant FLT3-ITD and nucleophosmin (NPM1) mutation; none have relapsed and all are still alive after 17-39 months. Maintenance lenalidomide/azacitidine augmented the function of cytotoxic T lymphocytes, particularly in patients with NPM1 mutation. The lenalidomide/azacitidine maintenance combination was effective in suppressing residual DNA (cytosine-5-)-methyltransferase 3 alpha (DNMT3A)-positive disease, resulting in sustained remission in patients with concurrent NPM1 mutation. Azacitidine/lenalidomide as maintenance therapy for high-risk AML warrants further exploration. © 2015 John Wiley & Sons Ltd.

Usefulness of BCOR gene mutation as a prognostic factor in acute myeloid leukemia with intermediate cytogenetic prognosis.

PubMed

Terada, Kazuki; Yamaguchi, Hiroki; Ueki, Toshimitsu; Usuki, Kensuke; Kobayashi, Yutaka; Tajika, Kenji; Gomi, Seiji; Kurosawa, Saiko; Saito, Riho; Furuta, Yutaka; Miyadera, Keiki; Tokura, Taichiro; Marumo, Atushi; Omori, Ikuko; Sakaguchi, Masahiro; Fujiwara, Yusuke; Yui, Shunsuke; Ryotokuji, Takeshi; Arai, Kunihito; Kitano, Tomoaki; Wakita, Satoshi; Fukuda, Takahiro; Inokuchi, Koiti

2018-04-16

BCOR gene is a transcription regulatory factor that plays an essential role in normal hematopoiesis. The wider introduction of next-generation sequencing technology has led to reports in recent years of mutations in the BCOR gene in acute myeloid leukemia (AML), but the related clinical characteristics and prognosis are not sufficiently understood. We investigated the clinical characteristics and prognosis of 377 de novo AML cases with BCOR or BCORL1 mutation. BCOR or BCORL1 gene mutations were found in 28 cases (7.4%). Among cases aged 65 years or below that were also FLT3-ITD-negative and in the intermediate cytogenetic prognosis group, BCOR or BCORL1 gene mutations were observed in 11% of cases (12 of 111 cases), and this group had significantly lower 5-year overall survival (OS) (13.6% vs. 55.0%, P=0.0021) and relapse-free survival (RFS) (14.3% vs. 44.5%, P=0.0168) compared to cases without BCOR or BCORL1 gene mutations. Multivariate analysis demonstrated that BCOR mutations were an independent unfavorable prognostic factor (P=0.0038, P=0.0463) for both OS and RFS. In cases of AML that are FLT3-ITD-negative, aged 65 years or below, and in the intermediate cytogenetic prognosis group, which are considered to have relatively favorable prognosis, BCOR gene mutations appear to be an important prognostic factor. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

Theoretical foundations of the sound analog membrane potential that underlies coincidence detection in the barn owl

PubMed Central

Ashida, Go; Funabiki, Kazuo; Carr, Catherine E.

2013-01-01

A wide variety of neurons encode temporal information via phase-locked spikes. In the avian auditory brainstem, neurons in the cochlear nucleus magnocellularis (NM) send phase-locked synaptic inputs to coincidence detector neurons in the nucleus laminaris (NL) that mediate sound localization. Previous modeling studies suggested that converging phase-locked synaptic inputs may give rise to a periodic oscillation in the membrane potential of their target neuron. Recent physiological recordings in vivo revealed that owl NL neurons changed their spike rates almost linearly with the amplitude of this oscillatory potential. The oscillatory potential was termed the sound analog potential, because of its resemblance to the waveform of the stimulus tone. The amplitude of the sound analog potential recorded in NL varied systematically with the interaural time difference (ITD), which is one of the most important cues for sound localization. In order to investigate the mechanisms underlying ITD computation in the NM-NL circuit, we provide detailed theoretical descriptions of how phase-locked inputs form oscillating membrane potentials. We derive analytical expressions that relate presynaptic, synaptic, and postsynaptic factors to the signal and noise components of the oscillation in both the synaptic conductance and the membrane potential. Numerical simulations demonstrate the validity of the theoretical formulations for the entire frequency ranges tested (1–8 kHz) and potential effects of higher harmonics on NL neurons with low best frequencies (<2 kHz). PMID:24265616

Comparison of various treatment modalities for acute tinnitus.

PubMed

Shim, Hyun Joon; Song, Seong Jun; Choi, A Young; Hyung Lee, Rae; Yoon, Sang Won

2011-12-01

Because in most cases the development of tinnitus is triggered by cochlear damage, there exists the opportunity to eliminate tinnitus while the cochlear lesion is still reversible. Therefore, we evaluated the therapeutic effects of various treatment modalities on acute subjective idiopathic tinnitus (SIT) and investigated prognostic factors affecting the treatment outcome. Prospective, controlled, double-blind trial. A total 107 patients who underwent treatment for unilateral SIT that had developed within the previous 3 months completed the study. The patients were randomly assigned into three groups according to the treatment modality: group I (n = 32), alprazolam orally for 3 months; group II (n = 35), as for group I plus four intratympanic dexamethasone (ITD) injections; and group III (n = 40), as for group II plus four intravenous injections of lipo-prostaglandin E(1) . The improvement rate of group II (75.8%) was significantly higher than that of group I (40.3%; P < .05), and there was no significant difference in the improvement rate of group III (50.0%) compared with groups I and II (P > .05). The cure rates of group II (25.8%) and group III (20.0%) were significantly higher than that of group I (9.8%; P < .05). There was a significant correlation between the cure rate and duration of symptoms. The results of the present study indicate that ITD injection plus alprazolam medication is the best treatment choice for acute SIT within 3 months of development. Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.

Mutation profiling of 16 candidate genes in de novo acute myeloid leukemia patients.

PubMed

Zhang, Yang; Wang, Fang; Chen, Xue; Liu, Wenjing; Fang, Jiancheng; Wang, Mingyu; Teng, Wen; Cao, Panxiang; Liu, Hongxing

2018-05-26

This retrospective analysis aimed to investigate the mutation profile of 16 common mutated genes in de novo acute myeloid leukemia (AML) patients. A total of 259 patients who were diagnosed of de novo AML were enrolled in this study. Mutation profiling of 16 candidate genes were performed in bone marrow samples by using Sanger sequencing.We identified at least 1 mutation in 199 of the 259 samples (76.8%), and 2 or more mutations in 31.7% of samples. FLT3-ITD was the most common mutated gene (16.2%, 42/259), followed by CEBPA (15.1%, 39/259), NRAS (14.7%, 38/259), and NPM1 (13.5%, 35/259). Concurrence was observed in 97.1% of the NPM1 mutated cases and in 29.6% of the double mutated CEBPA cases. Distinct patterns of co-occurrence were observed for different hotspot mutations within the IDH2 gene: R140 mutations were associated with NPM1 and/or FLT3-ITD mutations, whereas R172 mutations co-occurred with DNMT3A mutations only. Concurrence was also observed in 86.6% of epigenetic regulation genes, most of which co-occurred with NPM1 mutations. The results showed certain rules in the mutation profiling and concurrence of AML patients, which was related to the function classification of genes. Defining the mutation spectrum and mutation pattern of AML will contribute to the comprehensive assessment of patients and identification of new therapeutic targets.

Evaluation of a dynamic arm support for seated and standing tasks: a laboratory study of electromyography and subjective feedback.

PubMed

Odell, Dan; Barr, Alan; Goldberg, Robert; Chung, Jeffrey; Rempel, David

2007-04-01

The goal of this study was to determine whether a new dynamic arm support system reduced shoulder and arm muscle load for seated and standing hand/ arm tasks. The new system provides support for both horizontal and vertical arm motion. A total of 11 participants performed ten tasks (five seated and five standing) both with and without the arm support. Outcomes were assessed with electromyography and subjective feedback. Muscle activity was measured over the dominant side supraspinatus, triceps and forearm extensor muscles. Significant (p < 0.01) reductions in static muscle activity were observed in one of ten tasks performed with the support device for the supraspinatus muscle, in five tasks for the triceps and in one task for forearm extensor muscles. Likewise, a significant improvement in subjective measures was reported with the support device for 'ease of task' for two of ten tasks, for 'forearm comfort' for three of ten tasks and for 'shoulder effort' for six of ten tasks. The results suggest that a dynamic forearm support may improve subjective comfort and reduce static muscle loads in the upper extremity for tasks that involve horizontal movement of the arms. For rapid motions, the value of the support is limited due to internal inertia and friction.

Individual Differences in Dynamic Functional Brain Connectivity across the Human Lifespan

PubMed Central

Davison, Elizabeth N.; Turner, Benjamin O.; Miller, Michael B.; Carlson, Jean M.

2016-01-01

Individual differences in brain functional networks may be related to complex personal identifiers, including health, age, and ability. Dynamic network theory has been used to identify properties of dynamic brain function from fMRI data, but the majority of analyses and findings remain at the level of the group. Here, we apply hypergraph analysis, a method from dynamic network theory, to quantify individual differences in brain functional dynamics. Using a summary metric derived from the hypergraph formalism—hypergraph cardinality—we investigate individual variations in two separate, complementary data sets. The first data set (“multi-task”) consists of 77 individuals engaging in four consecutive cognitive tasks. We observe that hypergraph cardinality exhibits variation across individuals while remaining consistent within individuals between tasks; moreover, the analysis of one of the memory tasks revealed a marginally significant correspondence between hypergraph cardinality and age. This finding motivated a similar analysis of the second data set (“age-memory”), in which 95 individuals, aged 18–75, performed a memory task with a similar structure to the multi-task memory task. With the increased age range in the age-memory data set, the correlation between hypergraph cardinality and age correspondence becomes significant. We discuss these results in the context of the well-known finding linking age with network structure, and suggest that hypergraph analysis should serve as a useful tool in furthering our understanding of the dynamic network structure of the brain. PMID:27880785

Musing on the Use of Dynamic Software and Mathematics Epistemology

ERIC Educational Resources Information Center

Santos-Trigo, Manuel; Reyes-Rodriguez, Aaron; Espinosa-Perez, Hugo

2007-01-01

Different computational tools may offer teachers and students distinct opportunities in representing, exploring and solving mathematical tasks. In this context, we illustrate that the use of dynamic software (Cabri Geometry) helped high school teachers to think of and represent a particular task dynamically. In this process, the teachers had the…

Dynamic postural control and associated attentional demands in contemporary dancers versus non-dancers

PubMed Central

Sirois-Leclerc, Geneviève; Remaud, Anthony

2017-01-01

Postural control is not a fully automatic process, but requires a certain level of attention, particularly as the difficulty of the postural task increases. This study aimed at testing whether experienced contemporary dancers, because of their specialized training involving the control of posture/balance, would present with a dual-task performance suggesting lesser attentional demands associated with dynamic postural control compared with non-dancers. Twenty dancers and 16 non-dancers performed a dynamic postural tracking task in both antero-posterior and side-to-side directions, while standing on a force platform. The postural task was performed, in turn, 1) as a stand-alone task, and concurrently with both 2) a simple reaction time task and 3) a choice reaction time task. Postural control performance was estimated through variables calculated from centre of pressure movements. Although no overall group difference was found in reaction time values, we found a better ability to control the side to side movements of the centre of pressure during the tracking task in dancers compared with non-dancers, which was dependent on the secondary task. This suggests that such increased ability is influenced by available attentional resources. PMID:28323843

Dynamic postural control and associated attentional demands in contemporary dancers versus non-dancers.

PubMed

Sirois-Leclerc, Geneviève; Remaud, Anthony; Bilodeau, Martin

2017-01-01

Postural control is not a fully automatic process, but requires a certain level of attention, particularly as the difficulty of the postural task increases. This study aimed at testing whether experienced contemporary dancers, because of their specialized training involving the control of posture/balance, would present with a dual-task performance suggesting lesser attentional demands associated with dynamic postural control compared with non-dancers. Twenty dancers and 16 non-dancers performed a dynamic postural tracking task in both antero-posterior and side-to-side directions, while standing on a force platform. The postural task was performed, in turn, 1) as a stand-alone task, and concurrently with both 2) a simple reaction time task and 3) a choice reaction time task. Postural control performance was estimated through variables calculated from centre of pressure movements. Although no overall group difference was found in reaction time values, we found a better ability to control the side to side movements of the centre of pressure during the tracking task in dancers compared with non-dancers, which was dependent on the secondary task. This suggests that such increased ability is influenced by available attentional resources.

Divided visual attention: A comparison of patients with multiple sclerosis and controls, assessed with an optokinetic nystagmus suppression task.

PubMed

Williams, Isla M; Schofield, Peter; Khade, Neha; Abel, Larry A

2016-12-01

Multiple sclerosis (MS) frequently causes impairment of cognitive function. We compared patients with MS with controls on divided visual attention tasks. The MS patients' and controls' stare optokinetic nystagmus (OKN) was recorded in response to a 24°/s full field stimulus. Suppression of the OKN response, judged by the gain, was measured during tasks dividing visual attention between the fixation target and a second stimulus, central or peripheral, static or dynamic. All participants completed the Audio Recorded Cognitive Screen. MS patients had lower gain on the baseline stare OKN. OKN suppression in divided attention tasks was the same in MS patients as in controls but in both groups was better maintained in static than in dynamic tasks. In only dynamic tasks, older age was associated with less effective OKN suppression. MS patients had lower scores on a timed attention task and on memory. There was no significant correlation between attention or memory and eye movement parameters. Attention, a complex multifaceted construct, has different neural combinations for each task. Despite impairments on some measures of attention, MS patients completed the divided visual attention tasks normally. Copyright © 2016 Elsevier Ltd. All rights reserved.

The effects of smartphone multitasking on gait and dynamic balance

PubMed Central

Lee, Jeon Hyeong; Lee, Myoung Hee

2018-01-01

[Purpose] This study was performed to analyze the influence of smartphone multitasking on gait and dynamic balance. [Subjects and Methods] The subjects were 19 male and 20 female university students. There were 4 types of gait tasks: General Gait (walking without a task), Task Gait 1 (walking while writing a message), Task Gait 2 (walking while writing a message and listening to music), Task Gait 3 (walking while writing a message and having a conversation). To exclude the learning effect, the order of tasks was randomized. The Zebris FDM-T treadmill system (Zebris Medical GmbH, Germany) was used to measure left and right step length and width, and a 10 m walking test (10MWT) was conducted for gait velocity. In addition, a Timed Up and Go test (TUG) was used to measure dynamic balance. All the tasks were performed 3 times, and the mean of the measured values was analyzed. [Results] There were no statistically significant differences in step length and width. There were statistically significant differences in the 10MWT and TUG tests. [Conclusion] Using a smartphone while walking decreases a person’s dynamic balance and walking ability. It is considered that accident rates are higher when using a smartphone. PMID:29545698

The Dynamics of Development on the Dimensional Change Card Sorting Task

ERIC Educational Resources Information Center

van Bers, Bianca M. C. W.; Visser, Ingmar; van Schijndel, Tessa J. P.; Mandell, Dorothy J.; Raijmakers, Maartje E. J.

2011-01-01

A widely used paradigm to study cognitive flexibility in preschoolers is the Dimensional Change Card Sorting (DCCS) task. The developmental dynamics of DCCS performance was studied in a cross-sectional design (N = 93, 3 to 5 years of age) using a computerized version of the standard DCCS task. A model-based analysis of the data showed that…

Dynamic, continuous multitasking training leads to task-specific improvements but does not transfer across action selection tasks

NASA Astrophysics Data System (ADS)

Bender, Angela D.; Filmer, Hannah L.; Naughtin, Claire K.; Dux, Paul E.

2017-12-01

The ability to perform multiple tasks concurrently is an ever-increasing requirement in our information-rich world. Despite this, multitasking typically compromises performance due to the processing limitations associated with cognitive control and decision-making. While intensive dual-task training is known to improve multitasking performance, only limited evidence suggests that training-related performance benefits can transfer to untrained tasks that share overlapping processes. In the real world, however, coordinating and selecting several responses within close temporal proximity will often occur in high-interference environments. Over the last decade, there have been notable reports that training on video action games that require dynamic multitasking in a demanding environment can lead to transfer effects on aspects of cognition such as attention and working memory. Here, we asked whether continuous and dynamic multitasking training extends benefits to tasks that are theoretically related to the trained tasks. To examine this issue, we asked a group of participants to train on a combined continuous visuomotor tracking task and a perceptual discrimination task for six sessions, while an active control group practiced the component tasks in isolation. A battery of tests measuring response selection, response inhibition, and spatial attention was administered before and immediately after training to investigate transfer. Multitasking training resulted in substantial, task-specific gains in dual-task ability, but there was no evidence that these benefits generalized to other action control tasks. The findings suggest that training on a combined visuomotor tracking and discrimination task results in task-specific benefits but provides no additional value for untrained action selection tasks.

Monitoring cognitive and emotional processes through pupil and cardiac response during dynamic versus logical task.

PubMed

Causse, Mickaël; Sénard, Jean-Michel; Démonet, Jean François; Pastor, Josette

2010-06-01

The paper deals with the links between physiological measurements and cognitive and emotional functioning. As long as the operator is a key agent in charge of complex systems, the definition of metrics able to predict his performance is a great challenge. The measurement of the physiological state is a very promising way but a very acute comprehension is required; in particular few studies compare autonomous nervous system reactivity according to specific cognitive processes during task performance and task related psychological stress is often ignored. We compared physiological parameters recorded on 24 healthy subjects facing two neuropsychological tasks: a dynamic task that require problem solving in a world that continually evolves over time and a logical task representative of cognitive processes performed by operators facing everyday problem solving. Results showed that the mean pupil diameter change was higher during the dynamic task; conversely, the heart rate was more elevated during the logical task. Finally, the systolic blood pressure seemed to be strongly sensitive to psychological stress. A better taking into account of the precise influence of a given cognitive activity and both workload and related task-induced psychological stress during task performance is a promising way to better monitor operators in complex working situations to detect mental overload or pejorative stress factor of error.

An Analysis of How and Why High School Geometry Teachers Implement Dynamic Geometry Software Tasks for Student Engagement

ERIC Educational Resources Information Center

Nirode, Wayne

2012-01-01

This study examined teachers' use of student tasks involving dynamic geometry software, in which a figure is constructed then altered while maintaining its constructed properties. Although researchers, professional organizations, and policy makers generally have been proponents of dynamic geometry for instruction, there is little research about…

Integrating the behavioral and neural dynamics of response selection in a dual-task paradigm: a dynamic neural field model of Dux et al. (2009).

PubMed

Buss, Aaron T; Wifall, Tim; Hazeltine, Eliot; Spencer, John P

2014-02-01

People are typically slower when executing two tasks than when only performing a single task. These dual-task costs are initially robust but are reduced with practice. Dux et al. (2009) explored the neural basis of dual-task costs and learning using fMRI. Inferior frontal junction (IFJ) showed a larger hemodynamic response on dual-task trials compared with single-task trial early in learning. As dual-task costs were eliminated, dual-task hemodynamics in IFJ reduced to single-task levels. Dux and colleagues concluded that the reduction of dual-task costs is accomplished through increased efficiency of information processing in IFJ. We present a dynamic field theory of response selection that addresses two questions regarding these results. First, what mechanism leads to the reduction of dual-task costs and associated changes in hemodynamics? We show that a simple Hebbian learning mechanism is able to capture the quantitative details of learning at both the behavioral and neural levels. Second, is efficiency isolated to cognitive control areas such as IFJ, or is it also evident in sensory motor areas? To investigate this, we restrict Hebbian learning to different parts of the neural model. None of the restricted learning models showed the same reductions in dual-task costs as the unrestricted learning model, suggesting that efficiency is distributed across cognitive control and sensory motor processing systems.

From homeostasis to behavior: Balanced activity in an exploration of embodied dynamic environmental-neural interaction.

PubMed

Hellyer, Peter John; Clopath, Claudia; Kehagia, Angie A; Turkheimer, Federico E; Leech, Robert

2017-08-01

In recent years, there have been many computational simulations of spontaneous neural dynamics. Here, we describe a simple model of spontaneous neural dynamics that controls an agent moving in a simple virtual environment. These dynamics generate interesting brain-environment feedback interactions that rapidly destabilize neural and behavioral dynamics demonstrating the need for homeostatic mechanisms. We investigate roles for homeostatic plasticity both locally (local inhibition adjusting to balance excitatory input) as well as more globally (regional "task negative" activity that compensates for "task positive", sensory input in another region) balancing neural activity and leading to more stable behavior (trajectories through the environment). Our results suggest complementary functional roles for both local and macroscale mechanisms in maintaining neural and behavioral dynamics and a novel functional role for macroscopic "task-negative" patterns of activity (e.g., the default mode network).

Neuro-cognitive mechanisms of decision making in joint action: a human-robot interaction study.

PubMed

Bicho, Estela; Erlhagen, Wolfram; Louro, Luis; e Silva, Eliana Costa

2011-10-01

In this paper we present a model for action preparation and decision making in cooperative tasks that is inspired by recent experimental findings about the neuro-cognitive mechanisms supporting joint action in humans. It implements the coordination of actions and goals among the partners as a dynamic process that integrates contextual cues, shared task knowledge and predicted outcome of others' motor behavior. The control architecture is formalized by a system of coupled dynamic neural fields representing a distributed network of local but connected neural populations. Different pools of neurons encode task-relevant information about action means, task goals and context in the form of self-sustained activation patterns. These patterns are triggered by input from connected populations and evolve continuously in time under the influence of recurrent interactions. The dynamic model of joint action is evaluated in a task in which a robot and a human jointly construct a toy object. We show that the highly context sensitive mapping from action observation onto appropriate complementary actions allows coping with dynamically changing joint action situations. Copyright © 2010 Elsevier B.V. All rights reserved.

A systematic approach to selecting task relevant neurons.

PubMed

Kahn, Kevin; Saxena, Shreya; Eskandar, Emad; Thakor, Nitish; Schieber, Marc; Gale, John T; Averbeck, Bruno; Eden, Uri; Sarma, Sridevi V

2015-04-30

Since task related neurons cannot be specifically targeted during surgery, a critical decision to make is to select which neurons are task-related when performing data analysis. Including neurons unrelated to the task degrade decoding accuracy and confound neurophysiological results. Traditionally, task-related neurons are selected as those with significant changes in firing rate when a stimulus is applied. However, this assumes that neurons' encoding of stimuli are dominated by their firing rate with little regard to temporal dynamics. This paper proposes a systematic approach for neuron selection, which uses a likelihood ratio test to capture the contribution of stimulus to spiking activity while taking into account task-irrelevant intrinsic dynamics that affect firing rates. This approach is denoted as the model deterioration excluding stimulus (MDES) test. MDES is compared to firing rate selection in four case studies: a simulation, a decoding example, and two neurophysiology examples. The MDES rankings in the simulation match closely with ideal rankings, while firing rate rankings are skewed by task-irrelevant parameters. For decoding, 95% accuracy is achieved using the top 8 MDES-ranked neurons, while the top 12 firing-rate ranked neurons are needed. In the neurophysiological examples, MDES matches published results when firing rates do encode salient stimulus information, and uncovers oscillatory modulations in task-related neurons that are not captured when neurons are selected using firing rates. These case studies illustrate the importance of accounting for intrinsic dynamics when selecting task-related neurons and following the MDES approach accomplishes that. MDES selects neurons that encode task-related information irrespective of these intrinsic dynamics which can bias firing rate based selection. Copyright © 2015 Elsevier B.V. All rights reserved.

Understanding balance differences in individuals with multiple sclerosis with mild disability: An investigation of differences in sensory feedback on postural and dynamic balance control

NASA Astrophysics Data System (ADS)

Denomme, Luke T.

Multiple sclerosis (MS) is an autoimmune disease that affects the central nervous system (CNS) and causes a broad range of neurological symptoms. One of the most common symptoms experienced by individuals with MS is poor balance control during standing and walking. The main mechanism underlying impaired balance control in MS appears to result from slowed somatosensory conduction and impaired central integration. The current thesis assessed postural and dynamic control of balance of 'individuals with MS with mild disability' (IwMS). IwMS were compared to 'healthy age-matched individuals' (HAMI) and community-dwelling 'older adults' (OA). The purpose of this thesis was to quantify differences in postural and dynamic control of balance in IwMS to the two populations who display balance control differences across the lifespan and represent two extreme ends of the balance control continuum due to natural aging. IwMS (n = 12, x¯age: 44 +/- 9.4 years), HAMI (n = 12, x¯age: 45 +/- 9.9 years) and community-dwelling OA (n = 12, x¯ age: 68.1 +/- 4.5 years) postural and dynamic balance control were evaluated during a Romberg task as well as a dynamic steering task. The Romberg task required participants to stand with their feet together and hands by their sides for 45 seconds with either their eyes open or closed. The dynamic steering task required participants to walk and change direction along the M-L plane towards a visual goal. Results from these two tasks reveal that IwMS display differences in postural control when compared to HAMI when vision was removed as well as differences in dynamic stability margin during steering situations. During the postural control task IwMS displayed faster A-P and M-L COP velocities when vision was removed and their COP position was closer to their self-selected maximum stability limits compared to HAMI. Assessment of dynamic stability during the steering task revealed that IwMS displayed reduced walking speed and cadence during the straight walking portion of the task in addition to a smaller DSM range (i.e., COM remained close to lateral BOS) during the entire steering task. These results suggest that IwMS adopt postural and dynamic control strategies (i.e., increased COP velocity, smaller self-selected maximal sway comfort zones and reduced walking speed) in order to maintain stability and complete the tasks. Results further revealed that IwMS display similar levels of postural and dynamic stability to OA despite differences in the type of sensory impairment possessed by each group. The findings also provide insights into the comparison of IwMS to two populations who represent the two extreme ends of the balance control continuum: HAMI and OA. Our data indicates that the level of postural and dynamic balance control in IwMS appears to express similar characteristics and may be located closer to the OA population on this continuum. Future research should evaluate the level of somatosensory impairment (i.e., monofilament testing and tuning fork tendon tap testing) between IwMS and OA in order to better differentiate levels of postural and dynamic balance control between groups and to gain a better understanding of where each group may be specifically located on the age-related balance control continuum.

Fault-tolerant dynamic task graph scheduling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kurt, Mehmet C.; Krishnamoorthy, Sriram; Agrawal, Kunal

2014-11-16

In this paper, we present an approach to fault tolerant execution of dynamic task graphs scheduled using work stealing. In particular, we focus on selective and localized recovery of tasks in the presence of soft faults. We elicit from the user the basic task graph structure in terms of successor and predecessor relationships. The work stealing-based algorithm to schedule such a task graph is augmented to enable recovery when the data and meta-data associated with a task get corrupted. We use this redundancy, and the knowledge of the task graph structure, to selectively recover from faults with low space andmore » time overheads. We show that the fault tolerant design retains the essential properties of the underlying work stealing-based task scheduling algorithm, and that the fault tolerant execution is asymptotically optimal when task re-execution is taken into account. Experimental evaluation demonstrates the low cost of recovery under various fault scenarios.« less

Improving balance, mobility, and dual-task performance in an adolescent with cerebral palsy: A case report.

PubMed

Fisher-Pipher, Sarah; Kenyon, Lisa K; Westman, Marci

2017-07-01

Improving functional mobility is often a desired outcome for adolescents with cerebral palsy (CP). Traditional neurorehabilitation approaches are frequently directed at impairments; however, improvements may not be carried over into functional mobility. The purpose of this case report was to describe the examination, intervention, and outcomes of a task-oriented physical therapy intervention program to improve dynamic balance, functional mobility, and dual-task performance in an adolescent with CP. The participant was a 15-year-old girl with spastic triplegic CP (Gross Motor Classification System Level II). Examination procedures included the Canadian Occupational Performance Measure, 6-minute walk test, Muscle Power Sprint Test, 10 x 5-meter sprint test, Timed Up and Down Stairs Test, Gross Motor Function Measure, Gillette Functional Assessment Questionnaire, and functional lower extremity strength tests. Intervention focused on task-oriented dynamic balance and mobility tasks that incorporated coordination and speed demands as well as task-specific lower extremity and trunk strengthening activities. Dual task demands were integrated into all intervention activities. Post-intervention testing revealed improvements in cardiovascular endurance, anaerobic power, agility, stair climbing, gross motor skills, and mobility. The participant appeared to benefit from a task-oriented program to improve dynamic balance, functional mobility, and dual-task performance.

Multiobjective Resource-Constrained Project Scheduling with a Time-Varying Number of Tasks

PubMed Central

Abello, Manuel Blanco

2014-01-01

In resource-constrained project scheduling (RCPS) problems, ongoing tasks are restricted to utilizing a fixed number of resources. This paper investigates a dynamic version of the RCPS problem where the number of tasks varies in time. Our previous work investigated a technique called mapping of task IDs for centroid-based approach with random immigrants (McBAR) that was used to solve the dynamic problem. However, the solution-searching ability of McBAR was investigated over only a few instances of the dynamic problem. As a consequence, only a small number of characteristics of McBAR, under the dynamics of the RCPS problem, were found. Further, only a few techniques were compared to McBAR with respect to its solution-searching ability for solving the dynamic problem. In this paper, (a) the significance of the subalgorithms of McBAR is investigated by comparing McBAR to several other techniques; and (b) the scope of investigation in the previous work is extended. In particular, McBAR is compared to a technique called, Estimation Distribution Algorithm (EDA). As with McBAR, EDA is applied to solve the dynamic problem, an application that is unique in the literature. PMID:24883398

Multi-heuristic dynamic task allocation using genetic algorithms in a heterogeneous distributed system

PubMed Central

Page, Andrew J.; Keane, Thomas M.; Naughton, Thomas J.

2010-01-01

We present a multi-heuristic evolutionary task allocation algorithm to dynamically map tasks to processors in a heterogeneous distributed system. It utilizes a genetic algorithm, combined with eight common heuristics, in an effort to minimize the total execution time. It operates on batches of unmapped tasks and can preemptively remap tasks to processors. The algorithm has been implemented on a Java distributed system and evaluated with a set of six problems from the areas of bioinformatics, biomedical engineering, computer science and cryptography. Experiments using up to 150 heterogeneous processors show that the algorithm achieves better efficiency than other state-of-the-art heuristic algorithms. PMID:20862190

Interplay between Functional Connectivity and Scale-Free Dynamics in Intrinsic fMRI Networks

PubMed Central

Ciuciu, Philippe; Abry, Patrice; He, Biyu J.

2014-01-01

Studies employing functional connectivity-type analyses have established that spontaneous fluctuations in functional magnetic resonance imaging (fMRI) signals are organized within large-scale brain networks. Meanwhile, fMRI signals have been shown to exhibit 1/f-type power spectra – a hallmark of scale-free dynamics. We studied the interplay between functional connectivity and scale-free dynamics in fMRI signals, utilizing the fractal connectivity framework – a multivariate extension of the univariate fractional Gaussian noise model, which relies on a wavelet formulation for robust parameter estimation. We applied this framework to fMRI data acquired from healthy young adults at rest and performing a visual detection task. First, we found that scale-invariance existed beyond univariate dynamics, being present also in bivariate cross-temporal dynamics. Second, we observed that frequencies within the scale-free range do not contribute evenly to inter-regional connectivity, with a systematically stronger contribution of the lowest frequencies, both at rest and during task. Third, in addition to a decrease of the Hurst exponent and inter-regional correlations, task performance modified cross-temporal dynamics, inducing a larger contribution of the highest frequencies within the scale-free range to global correlation. Lastly, we found that across individuals, a weaker task modulation of the frequency contribution to inter-regional connectivity was associated with better task performance manifesting as shorter and less variable reaction times. These findings bring together two related fields that have hitherto been studied separately – resting-state networks and scale-free dynamics, and show that scale-free dynamics of human brain activity manifest in cross-regional interactions as well. PMID:24675649

Dealing with task interruptions in complex dynamic environments: are two heads better than one?

PubMed

Tremblay, Sébastien; Vachon, François; Lafond, Daniel; Kramer, Chelsea

2012-02-01

This study examined whether teaming up mitigates individual vulnerability to task interruptions in complex dynamic situations. Omnipresent in everyday multitasking environments, task interruptions are usually detrimental to individual performance. This is particularly crucial in dynamic command and control (C2) safety-critical contexts because of the additional challenge imposed by the continually evolving situation during the interruption. We employed a firefighting microworld to simulate C2 in the context of supervisory control to examine the relative impact of interruptions on participants working in a functional dyad versus operators working alone. Although task interruption was detrimental to participants' efficacy of monitoring resources, the negative impact of interruption was reduced for those working in teams. Teaming up translated into faster resumption time, but only if both teammates were interrupted simultaneously. Interrupting only one team member was associated with increased postinterruption communications and slower resumption time. These findings suggest that in complex dynamic situations working in a small team confers more resistance to task interruption than working alone by virtue of the reduced individual workload typical of teamwork. The benefit of collaborative work seems nevertheless mediated by the coordination and communication overhead associated with teamwork. The present findings have practical implications for operators dealing with unexpected events such as task interruptions in C2 environments.

Dynamic Task Performance, Cohesion, and Communications in Human Groups.

PubMed

Giraldo, Luis Felipe; Passino, Kevin M

2016-10-01

In the study of the behavior of human groups, it has been observed that there is a strong interaction between the cohesiveness of the group, its performance when the group has to solve a task, and the patterns of communication between the members of the group. Developing mathematical and computational tools for the analysis and design of task-solving groups that are not only cohesive but also perform well is of importance in social sciences, organizational management, and engineering. In this paper, we model a human group as a dynamical system whose behavior is driven by a task optimization process and the interaction between subsystems that represent the members of the group interconnected according to a given communication network. These interactions are described as attractions and repulsions among members. We show that the dynamics characterized by the proposed mathematical model are qualitatively consistent with those observed in real-human groups, where the key aspect is that the attraction patterns in the group and the commitment to solve the task are not static but change over time. Through a theoretical analysis of the system we provide conditions on the parameters that allow the group to have cohesive behaviors, and Monte Carlo simulations are used to study group dynamics for different sets of parameters, communication topologies, and tasks to solve.

Cloud computing task scheduling strategy based on improved differential evolution algorithm

NASA Astrophysics Data System (ADS)

Ge, Junwei; He, Qian; Fang, Yiqiu

2017-04-01

In order to optimize the cloud computing task scheduling scheme, an improved differential evolution algorithm for cloud computing task scheduling is proposed. Firstly, the cloud computing task scheduling model, according to the model of the fitness function, and then used improved optimization calculation of the fitness function of the evolutionary algorithm, according to the evolution of generation of dynamic selection strategy through dynamic mutation strategy to ensure the global and local search ability. The performance test experiment was carried out in the CloudSim simulation platform, the experimental results show that the improved differential evolution algorithm can reduce the cloud computing task execution time and user cost saving, good implementation of the optimal scheduling of cloud computing tasks.

Predictive significance of the European LeukemiaNet classification of genetic aberrations in patients with acute myeloid leukaemia undergoing allogeneic stem cell transplantation.

PubMed

Hemmati, Philipp G; Vuong, Lam G; Terwey, Theis H; Jehn, Christian F; le Coutre, Philipp; Penack, Olaf; Na, Il-Kang; Dörken, Bernd; Arnold, Renate

2017-02-01

The purpose of this study was to evaluate the predictive capacity of the European LeukemiaNet (ELN) classification of genetic risk in patients with acute myeloid leukaemia (AML) undergoing allogeneic stem cell transplantation (alloSCT). We retrospectively analysed 274 patients transplanted at our centre between 2004 and 2014. The ELN grouping is comparable to the Southwest Oncology Group/Eastern Cooperative Oncology Group (SWOG/ECOG) stratification in predicting the outcome after alloSCT [overall P = 0.0064 for disease-free survival (DFS), overall P = 0.003 for relapse]. Patients with an intermediate-1 profile have a significantly elevated 5-yr relapse incidence as compared to favourable risk patients, that is 40% vs. 15%, [hazard ratio (HR) 2.58, P = 0.048]. An intermediate-1 risk profile is an independent predictor for relapse as determined by multivariate Cox regression analysis (HR 3.05, P = 0.023). In intermediate-1 patients, the presence of an FLT3 internal tandem duplication (FLT3-ITD) is associated with a significantly increased relapse incidence (P = 0.0323), and a lower DFS (P = 0.0465). FLT3-ITD is an independent predictor for overall survival, DFS and relapse incidence in the intermediate-1 subgroup. The ELN stratification of genetic risk predicts the outcome of patients with AML undergoing alloSCT. Patients with an intermediate-1 profile have a high risk for treatment failure due to relapse, which prompts the development of alternative treatment strategies. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The oral HDAC inhibitor pracinostat (SB939) is efficacious and synergistic with the JAK2 inhibitor pacritinib (SB1518) in preclinical models of AML

PubMed Central

Novotny-Diermayr, V; Hart, S; Goh, K C; Cheong, A; Ong, L-C; Hentze, H; Pasha, M K; Jayaraman, R; Ethirajulu, K; Wood, J M

2012-01-01

Acute myeloid leukemia (AML) is currently treated with aggressive chemotherapy that is not well tolerated in many elderly patients, hence the unmet medical need for effective therapies with less toxicity and better tolerability. Inhibitors of FMS-like tyrosine kinase 3 (FLT3), JAK2 and histone deacetylase inhibitors (HDACi) have been tested in clinical studies, but showed only moderate single-agent activity. High efficacy of the HDACi pracinostat treating AML and synergy with the JAK2/FLT3 inhibitor pacritinib is demonstrated. Both compounds inhibit JAK-signal transducer and activator of transcription (STAT) signaling in AML cells with JAK2V617F mutations, but also diminish FLT3 signaling, particularly in FLT3-ITD (internal tandem duplication) cell lines. In vitro, this combination led to decreased cell proliferation and increased apoptosis. The synergy translated in vivo in two different AML models, the SET-2 megakaryoblastic AML mouse model carrying a JAK2V617F mutation, and the MOLM-13 model of FLT3-ITD-driven AML. Pracinostat and pacritinib in combination showed synergy on tumor growth, reduction of metastases and synergistically decreased JAK2 or FLT signaling, depending on the cellular context. In addition, several plasma cytokines/growth factors/chemokines triggered by the tumor growth were normalized, providing a rationale for combination therapy with an HDACi and a JAK2/FLT3 inhibitor for the treatment of AML patients, particularly those with FLT3 or JAK2 mutations. PMID:22829971

Response Properties of Neighboring Neurons in the Auditory Midbrain for Pure-Tone Stimulation: A Tetrode Study

PubMed Central

Seshagiri, Chandran V.; Delgutte, Bertrand

2007-01-01

The complex anatomical structure of the central nucleus of the inferior colliculus (ICC), the principal auditory nucleus in the midbrain, may provide the basis for functional organization of auditory information. To investigate this organization, we used tetrodes to record from neighboring neurons in the ICC of anesthetized cats and studied the similarity and difference among the responses of these neurons to pure-tone stimuli using widely used physiological characterizations. Consistent with the tonotopic arrangement of neurons in the ICC and reports of a threshold map, we found a high degree of correlation in the best frequencies (BFs) of neighboring neurons, which were mostly <3 kHz in our sample, and the pure-tone thresholds among neighboring neurons. However, width of frequency tuning, shapes of the frequency response areas, and temporal discharge patterns showed little or no correlation among neighboring neurons. Because the BF and threshold are measured at levels near the threshold and the characteristic frequency (CF), neighboring neurons may receive similar primary inputs tuned to their CF; however, at higher levels, additional inputs from other frequency channels may be recruited, introducing greater variability in the responses. There was also no correlation among neighboring neurons' sensitivity to interaural time differences (ITD) measured with binaural beats. However, the characteristic phases (CPs) of neighboring neurons revealed a significant correlation. Because the CP is related to the neural mechanisms generating the ITD sensitivity, this result is consistent with segregation of inputs to the ICC from the lateral and medial superior olives. PMID:17671101

Response properties of neighboring neurons in the auditory midbrain for pure-tone stimulation: a tetrode study.

PubMed

Seshagiri, Chandran V; Delgutte, Bertrand

2007-10-01

The complex anatomical structure of the central nucleus of the inferior colliculus (ICC), the principal auditory nucleus in the midbrain, may provide the basis for functional organization of auditory information. To investigate this organization, we used tetrodes to record from neighboring neurons in the ICC of anesthetized cats and studied the similarity and difference among the responses of these neurons to pure-tone stimuli using widely used physiological characterizations. Consistent with the tonotopic arrangement of neurons in the ICC and reports of a threshold map, we found a high degree of correlation in the best frequencies (BFs) of neighboring neurons, which were mostly <3 kHz in our sample, and the pure-tone thresholds among neighboring neurons. However, width of frequency tuning, shapes of the frequency response areas, and temporal discharge patterns showed little or no correlation among neighboring neurons. Because the BF and threshold are measured at levels near the threshold and the characteristic frequency (CF), neighboring neurons may receive similar primary inputs tuned to their CF; however, at higher levels, additional inputs from other frequency channels may be recruited, introducing greater variability in the responses. There was also no correlation among neighboring neurons' sensitivity to interaural time differences (ITD) measured with binaural beats. However, the characteristic phases (CPs) of neighboring neurons revealed a significant correlation. Because the CP is related to the neural mechanisms generating the ITD sensitivity, this result is consistent with segregation of inputs to the ICC from the lateral and medial superior olives.

High BAALC expression associates with other molecular prognostic markers, poor outcome, and a distinct gene-expression signature in cytogenetically normal patients younger than 60 years with acute myeloid leukemia: a Cancer and Leukemia Group B (CALGB) study

PubMed Central

Langer, Christian; Radmacher, Michael D.; Ruppert, Amy S.; Whitman, Susan P.; Paschka, Peter; Mrózek, Krzysztof; Baldus, Claudia D.; Vukosavljevic, Tamara; Liu, Chang-Gong; Ross, Mary E.; Powell, Bayard L.; de la Chapelle, Albert; Kolitz, Jonathan E.; Larson, Richard A.; Marcucci, Guido

2008-01-01

BAALC expression is considered an independent prognostic factor in cytogenetically normal acute myeloid leukemia (CN-AML), but has yet to be investigated together with multiple other established prognostic molecular markers in CN-AML. We analyzed BAALC expression in 172 primary CN-AML patients younger than 60 years of age, treated similarly on CALGB protocols. High BAALC expression was associated with FLT3-ITD (P = .04), wild-type NPM1 (P < .001), mutated CEBPA (P = .003), MLL-PTD (P = .009), absent FLT3-TKD (P = .005), and high ERG expression (P = .05). In multivariable analysis, high BAALC expression independently predicted lower complete remission rates (P = .04) when adjusting for ERG expression and age, and shorter survival (P = .04) when adjusting for FLT3-ITD, NPM1, CEBPA, and white blood cell count. A gene-expression signature of 312 probe sets differentiating high from low BAALC expressers was identified. High BAALC expression was associated with overexpression of genes involved in drug resistance (MDR1) and stem cell markers (CD133, CD34, KIT). Global microRNA-expression analysis did not reveal significant differences between BAALC expression groups. However, an analysis of microRNAs that putatively target BAALC revealed a potentially interesting inverse association between expression of miR-148a and BAALC. We conclude that high BAALC expression is an independent adverse prognostic factor and is associated with a specific gene-expression profile. PMID:18378853

Factors influencing analysis of complex cognitive tasks: a framework and example from industrial process control.

PubMed

Prietula, M J; Feltovich, P J; Marchak, F

2000-01-01

We propose that considering four categories of task factors can facilitate knowledge elicitation efforts in the analysis of complex cognitive tasks: materials, strategies, knowledge characteristics, and goals. A study was conducted to examine the effects of altering aspects of two of these task categories on problem-solving behavior across skill levels: materials and goals. Two versions of an applied engineering problem were presented to expert, intermediate, and novice participants. Participants were to minimize the cost of running a steam generation facility by adjusting steam generation levels and flows. One version was cast in the form of a dynamic, computer-based simulation that provided immediate feedback on flows, costs, and constraint violations, thus incorporating key variable dynamics of the problem context. The other version was cast as a static computer-based model, with no dynamic components, cost feedback, or constraint checking. Experts performed better than the other groups across material conditions, and, when required, the presentation of the goal assisted the experts more than the other groups. The static group generated richer protocols than the dynamic group, but the dynamic group solved the problem in significantly less time. Little effect of feedback was found for intermediates, and none for novices. We conclude that demonstrating differences in performance in this task requires different materials than explicating underlying knowledge that leads to performance. We also conclude that substantial knowledge is required to exploit the information yielded by the dynamic form of the task or the explicit solution goal. This simple model can help to identify the contextual factors that influence elicitation and specification of knowledge, which is essential in the engineering of joint cognitive systems.

The capability of static and dynamic features to distinguish competent from genuinely expert practitioners in pediatric diagnosis.

PubMed

Loveday, Thomas; Wiggins, Mark W; Searle, Ben J; Festa, Marino; Schell, David

2013-02-01

The authors describe the development of a new, more objective method of distinguishing experienced competent nonexpert from expert practitioners within pediatric intensive care. Expert performance involves the acquisition and use of refined feature-event associations (cues) in the operational environment. Competent non-experts, although experienced, possess rudimentary cue associations in memory. Thus, they cannot respond as efficiently or as reliably as their expert counterparts, particularly when key diagnostic information is unavailable, such as that provided by dynamic cues. This study involved the application of four distinct tasks in which the use of relevant cues could be expected to increase both the accuracy and the efficiency of diagnostic performance. These tasks included both static and dynamic stimuli that were varied systematically. A total of 50 experienced pediatric intensive staff took part in the study. The sample clustered into two levels across the tasks: Participants who performed at a consistently high level throughout the four tasks were labeled experts, and participants who performed at a lower level throughout the tasks were labeled competent nonexperts. The groups differed in their responses to the diagnostic scenarios presented in two of the tasks and their ability to maintain performance in the absence of dynamic features. Experienced pediatricians can be decomposed into two groups on the basis of their capacity to acquire and use cues; these groups differ in their diagnostic accuracy and in their ability to maintain performance in the absence of dynamic features. The tasks may be used to identify practitioners who are failing to acquire expertise at a rate consistent with their experience, position, or training. This information may be used to guide targeted training efforts.

Shared internal models for feedforward and feedback control.

PubMed

Wagner, Mark J; Smith, Maurice A

2008-10-15

A child often learns to ride a bicycle in the driveway, free of unforeseen obstacles. Yet when she first rides in the street, we hope that if a car suddenly pulls out in front of her, she will combine her innate goal of avoiding an accident with her learned knowledge of the bicycle, and steer away or brake. In general, when we train to perform a new motor task, our learning is most robust if it updates the rules of online error correction to reflect the rules and goals of the new task. Here we provide direct evidence that, after a new feedforward motor adaptation, motor feedback responses to unanticipated errors become precisely task appropriate, even when such errors were never experienced during training. To study this ability, we asked how, if at all, do online responses to occasional, unanticipated force pulses during reaching arm movements change after adapting to altered arm dynamics? Specifically, do they change in a task-appropriate manner? In our task, subjects learned novel velocity-dependent dynamics. However, occasional force-pulse perturbations produced unanticipated changes in velocity. Therefore, after adaptation, task-appropriate responses to unanticipated pulses should compensate corresponding changes in velocity-dependent dynamics. We found that after adaptation, pulse responses precisely compensated these changes, although they were never trained to do so. These results provide evidence for a smart feedback controller which automatically produces responses specific to the learned dynamics of the current task. To accomplish this, the neural processes underlying feedback control must (1) be capable of accurate real-time state prediction for velocity via a forward model and (2) have access to recently learned changes in internal models of limb dynamics.

Static and dynamic single leg postural control performance during dual-task paradigms.

PubMed

Talarico, Maria K; Lynall, Robert C; Mauntel, Timothy C; Weinhold, Paul S; Padua, Darin A; Mihalik, Jason P

2017-06-01

Combining dynamic postural control assessments and cognitive tasks may give clinicians a more accurate indication of postural control under sport-like conditions compared to single-task assessments. We examined postural control, cognitive and squatting performance of healthy individuals during static and dynamic postural control assessments in single- and dual-task paradigms. Thirty participants (female = 22, male = 8; age = 20.8 ± 1.6 years, height = 157.9 ± 13.0 cm, mass = 67.8 ± 20.6 kg) completed single-leg stance and single-leg squat assessments on a force plate individually (single-task) and concurrently (dual-task) with two cognitive assessments, a modified Stroop test and the Brooks Spatial Memory Test. Outcomes included centre of pressure speed, 95% confidence ellipse, squat depth and speed and cognitive test measures (percentage of correct answers and reaction time). Postural control performance varied between postural control assessments and testing paradigms. Participants did not squat as deep and squatted slower (P < 0.001) during dual-task paradigms (≤12.69 ± 3.4 cm squat depth, ≤16.20 ± 4.6 cm · s -1 squat speed) compared to single-task paradigms (14.57 ± 3.6 cm squat depth, 19.65 ± 5.5 cm · s -1 squat speed). The percentage of correct answers did not change across testing conditions, but Stroop reaction time (725.81 ± 59.2 ms; F 2,58  = 7.725, P = 0.001) was slowest during single-leg squats compared to baseline (691.64 ± 80.1 ms; P = 0.038) and single-task paradigms (681.33 ± 51.5 ms; P < 0.001). Dynamic dual-task assessments may be more challenging to the postural control system and may better represent postural control performance during dynamic activities.

Transfer of short-term motor learning across the lower limbs as a function of task conception and practice order.

PubMed

Stöckel, Tino; Wang, Jinsung

2011-11-01

Interlimb transfer of motor learning, indicating an improvement in performance with one limb following training with the other, often occurs asymmetrically (i.e., from non-dominant to dominant limb or vice versa, but not both). In the present study, we examined whether interlimb transfer of the same motor task could occur asymmetrically and in opposite directions (i.e., from right to left leg vs. left to right leg) depending on individuals' conception of the task. Two experimental conditions were tested: In a dynamic control condition, the process of learning was facilitated by providing the subjects with a type of information that forced them to focus on dynamic features of a given task (force impulse); and in a spatial control condition, it was done with another type of information that forced them to focus on visuomotor features of the same task (distance). Both conditions employed the same leg extension task. In addition, a fully-crossed transfer paradigm was used in which one group of subjects initially practiced with the right leg and were tested with the left leg for a transfer test, while the other group used the two legs in the opposite order. The results showed that the direction of interlimb transfer varied depending on the condition, such that the right and the left leg benefited from initial training with the opposite leg only in the spatial and the dynamic condition, respectively. Our finding suggests that manipulating the conception of a leg extension task has a substantial influence on the pattern of interlimb transfer in such a way that the direction of transfer can even be opposite depending on whether the task is conceived as a dynamic or spatial control task. Copyright © 2011 Elsevier Inc. All rights reserved.

A dynamic model of stress and sustained attention

NASA Technical Reports Server (NTRS)

Hancock, Peter A.; Warm, Joel S.

2003-01-01

This paper examines the effects of stress on sustained attention. With recognition of the task itself as the major source of cognitive stress, a dynamic model is presented that addresses the effects of stress on vigilance and, potentially, a wide variety of attention performance tasks.

Markov Task Network: A Framework for Service Composition under Uncertainty in Cyber-Physical Systems.

PubMed

Mohammed, Abdul-Wahid; Xu, Yang; Hu, Haixiao; Agyemang, Brighter

2016-09-21

In novel collaborative systems, cooperative entities collaborate services to achieve local and global objectives. With the growing pervasiveness of cyber-physical systems, however, such collaboration is hampered by differences in the operations of the cyber and physical objects, and the need for the dynamic formation of collaborative functionality given high-level system goals has become practical. In this paper, we propose a cross-layer automation and management model for cyber-physical systems. This models the dynamic formation of collaborative services pursuing laid-down system goals as an ontology-oriented hierarchical task network. Ontological intelligence provides the semantic technology of this model, and through semantic reasoning, primitive tasks can be dynamically composed from high-level system goals. In dealing with uncertainty, we further propose a novel bridge between hierarchical task networks and Markov logic networks, called the Markov task network. This leverages the efficient inference algorithms of Markov logic networks to reduce both computational and inferential loads in task decomposition. From the results of our experiments, high-precision service composition under uncertainty can be achieved using this approach.

Age Differences between Children and Young Adults in the Dynamics of Dual-Task Prioritization: Body (Balance) versus Mind (Memory)

ERIC Educational Resources Information Center

Schaefer, Sabine; Krampe, Ralf Th.; Lindenberger, Ulman; Baltes, Paul B.

2008-01-01

Task prioritization can lead to trade-off patterns in dual-task situations. The authors compared dual-task performances in 9- and 11-year-old children and young adults performing a cognitive task and a motor task concurrently. The motor task required balancing on an ankle-disc board. Two cognitive tasks measured working memory and episodic memory…

User-Assisted Store Recycling for Dynamic Task Graph Schedulers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kurt, Mehmet Can; Krishnamoorthy, Sriram; Agrawal, Gagan

The emergence of the multi-core era has led to increased interest in designing effective yet practical parallel programming models. Models based on task graphs that operate on single-assignment data are attractive in several ways: they can support dynamic applications and precisely represent the available concurrency. However, they also require nuanced algorithms for scheduling and memory management for efficient execution. In this paper, we consider memory-efficient dynamic scheduling of task graphs. Specifically, we present a novel approach for dynamically recycling the memory locations assigned to data items as they are produced by tasks. We develop algorithms to identify memory-efficient store recyclingmore » functions by systematically evaluating the validity of a set of (user-provided or automatically generated) alternatives. Because recycling function can be input data-dependent, we have also developed support for continued correct execution of a task graph in the presence of a potentially incorrect store recycling function. Experimental evaluation demonstrates that our approach to automatic store recycling incurs little to no overheads, achieves memory usage comparable to the best manually derived solutions, often produces recycling functions valid across problem sizes and input parameters, and efficiently recovers from an incorrect choice of store recycling functions.« less

The dynamics of perception and action.

PubMed

Warren, William H

2006-04-01

How might one account for the organization in behavior without attributing it to an internal control structure? The present article develops a theoretical framework called behavioral dynamics that integrates an information-based approach to perception with a dynamical systems approach to action. For a given task, the agent and its environment are treated as a pair of dynamical systems that are coupled mechanically and informationally. Their interactions give rise to the behavioral dynamics, a vector field with attractors that correspond to stable task solutions, repellers that correspond to avoided states, and bifurcations that correspond to behavioral transitions. The framework is used to develop theories of several tasks in which a human agent interacts with the physical environment, including bouncing a ball on a racquet, balancing an object, braking a vehicle, and guiding locomotion. Stable, adaptive behavior emerges from the dynamics of the interaction between a structured environment and an agent with simple control laws, under physical and informational constraints. ((c) 2006 APA, all rights reserved).

Research on a dynamic workflow access control model

NASA Astrophysics Data System (ADS)

Liu, Yiliang; Deng, Jinxia

2007-12-01

In recent years, the access control technology has been researched widely in workflow system, two typical technologies of that are RBAC (Role-Based Access Control) and TBAC (Task-Based Access Control) model, which has been successfully used in the role authorizing and assigning in a certain extent. However, during the process of complicating a system's structure, these two types of technology can not be used in minimizing privileges and separating duties, and they are inapplicable when users have a request of frequently changing on the workflow's process. In order to avoid having these weakness during the applying, a variable flow dynamic role_task_view (briefly as DRTVBAC) of fine-grained access control model is constructed on the basis existed model. During the process of this model applying, an algorithm is constructed to solve users' requirements of application and security needs on fine-grained principle of privileges minimum and principle of dynamic separation of duties. The DRTVBAC model is implemented in the actual system, the figure shows that the task associated with the dynamic management of role and the role assignment is more flexible on authority and recovery, it can be met the principle of least privilege on the role implement of a specific task permission activated; separated the authority from the process of the duties completing in the workflow; prevented sensitive information discovering from concise and dynamic view interface; satisfied with the requirement of the variable task-flow frequently.

Behavioral and functional strategies during tool use tasks in bonobos.

PubMed

Bardo, Ameline; Borel, Antony; Meunier, Hélène; Guéry, Jean-Pascal; Pouydebat, Emmanuelle

2016-09-01

Different primate species have developed extensive capacities for grasping and manipulating objects. However, the manual abilities of primates remain poorly known from a dynamic point of view. The aim of the present study was to quantify the functional and behavioral strategies used by captive bonobos (Pan paniscus) during tool use tasks. The study was conducted on eight captive bonobos which we observed during two tool use tasks: food extraction from a large piece of wood and food recovery from a maze. We focused on grasping postures, in-hand movements, the sequences of grasp postures used that have not been studied in bonobos, and the kind of tools selected. Bonobos used a great variety of grasping postures during both tool use tasks. They were capable of in-hand movement, demonstrated complex sequences of contacts, and showed more dynamic manipulation during the maze task than during the extraction task. They arrived on the location of the task with the tool already modified and used different kinds of tools according to the task. We also observed individual manual strategies. Bonobos were thus able to develop in-hand movements similar to humans and chimpanzees, demonstrated dynamic manipulation, and they responded to task constraints by selecting and modifying tools appropriately, usually before they started the tasks. These results show the necessity to quantify object manipulation in different species to better understand their real manual specificities, which is essential to reconstruct the evolution of primate manual abilities. © 2016 Wiley Periodicals, Inc.

Dynamic stability requirements during gait and standing exergames on the wii fit® system in the elderly

PubMed Central

2012-01-01

Background In rehabilitation, training intensity is usually adapted to optimize the trained system to attain better performance (overload principle). However, in balance rehabilitation, the level of intensity required during training exercises to optimize improvement in balance has rarely been studied, probably due to the difficulty in quantifying the stability level during these exercises. The goal of the present study was to test whether the stabilizing/destabilizing forces model could be used to analyze how stability is challenged during several exergames, that are more and more used in balance rehabilitation, and a dynamic functional task, such as gait. Methods Seven healthy older adults were evaluated with three-dimensional motion analysis during gait at natural and fast speed, and during three balance exergames (50/50 Challenge, Ski Slalom and Soccer). Mean and extreme values for stabilizing force, destabilizing force and the ratio of the two forces (stability index) were computed from kinematic and kinetic data to determine the mean and least level of dynamic, postural and overall balance stability, respectively. Results Mean postural stability was lower (lower mean destabilizing force) during the 50/50 Challenge game than during all the other tasks, but peak postural instability moments were less challenging during this game than during any of the other tasks, as shown by the minimum destabilizing force values. Dynamic stability was progressively more challenged (higher mean and maximum stabilizing force) from the 50/50 Challenge to the Soccer and Slalom games, to the natural gait speed task and to the fast gait speed task, increasing the overall stability difficulty (mean and minimum stability index) in the same manner. Conclusions The stabilizing/destabilizing forces model can be used to rate the level of balance requirements during different tasks such as gait or exergames. The results of our study showed that postural stability did not differ much between the evaluated tasks (except for the 50/50 Challenge), compared to dynamic stability, which was significantly less challenged during the games than during the functional tasks. Games with greater centre of mass displacements and changes in the base of support are likely to stimulate balance control enough to see improvements in balance during dynamic functional tasks, and could be tested in pathological populations with the approach used here. PMID:22607025

The heart of parenting: Parent HR dynamics and negative parenting while resolving conflict with child.

PubMed

Zhang, Xutong; Cui, Lixian; Han, Zhuo Rachel; Yan, Jia

2017-03-01

The current study examined parent heart rate (HR) dynamic changing patterns and their links to observed negative parenting (i.e., emotional unavailability and psychological control) during a parent-child conflict resolution task among 150 parent-child dyads (child age ranged from 6 to 12 years, Mage = 8.54 ± 1.67). Parent HR was obtained from electrocardiogram (ECG) data collected during the parent-child conflict resolution task. Negative parenting was coded offline based on the video recording of the same task. Results revealed that emotionally sensitive parents during the task showed greater HR increases while discussing a conflict and greater HR decreases while resolving the conflict, whereas emotionally unavailable parents showed no changes in HR. However, parent psychological control was not associated with HR dynamics during the task. These findings indicated the physiological underpinnings of parent emotional sensitivity and responsiveness during parent-child interactions. The potential association between HR baseline levels and parenting behaviors was also discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Role of dopamine D2 receptors in optimizing choice strategy in a dynamic and uncertain environment

PubMed Central

Kwak, Shinae; Huh, Namjung; Seo, Ji-Seon; Lee, Jung-Eun; Han, Pyung-Lim; Jung, Min W.

2014-01-01

In order to investigate roles of dopamine receptor subtypes in reward-based learning, we examined choice behavior of dopamine D1 and D2 receptor-knockout (D1R-KO and D2R-KO, respectively) mice in an instrumental learning task with progressively increasing reversal frequency and a dynamic two-armed bandit task. Performance of D2R-KO mice was progressively impaired in the former as the frequency of reversal increased and profoundly impaired in the latter even with prolonged training, whereas D1R-KO mice showed relatively minor performance deficits. Choice behavior in the dynamic two-armed bandit task was well explained by a hybrid model including win-stay-lose-switch and reinforcement learning terms. A model-based analysis revealed increased win-stay, but impaired value updating and decreased value-dependent action selection in D2R-KO mice, which were detrimental to maximizing rewards in the dynamic two-armed bandit task. These results suggest an important role of dopamine D2 receptors in learning from past choice outcomes for rapid adjustment of choice behavior in a dynamic and uncertain environment. PMID:25389395

Impacts Assessment of Dynamic Speed Harmonization with Queue Warning : Task 3, Impacts Assessment Report. [supporting datasets

DOT National Transportation Integrated Search

2015-05-31

The datasets in the .pdf and .zip attached to this record are in support of Intelligent Transportation Systems Joint Program Office (ITS JPO) report FHWA-JPO-15-222, "Impacts Assessment of Dynamic Speed Harmonization with Queue Warning : Task 3, Impa...

Cortical Spatio-Temporal Dynamics Underlying Phonological Target Detection in Humans

ERIC Educational Resources Information Center

Chang, Edward F.; Edwards, Erik; Nagarajan, Srikantan S.; Fogelson, Noa; Dalal, Sarang S.; Canolty, Ryan T.; Kirsch, Heidi E.; Barbaro, Nicholas M.; Knight, Robert T.

2011-01-01

Selective processing of task-relevant stimuli is critical for goal-directed behavior. We used electrocorticography to assess the spatio-temporal dynamics of cortical activation during a simple phonological target detection task, in which subjects press a button when a prespecified target syllable sound is heard. Simultaneous surface potential…

Reservoir Computing Beyond Memory-Nonlinearity Trade-off.

PubMed

Inubushi, Masanobu; Yoshimura, Kazuyuki

2017-08-31

Reservoir computing is a brain-inspired machine learning framework that employs a signal-driven dynamical system, in particular harnessing common-signal-induced synchronization which is a widely observed nonlinear phenomenon. Basic understanding of a working principle in reservoir computing can be expected to shed light on how information is stored and processed in nonlinear dynamical systems, potentially leading to progress in a broad range of nonlinear sciences. As a first step toward this goal, from the viewpoint of nonlinear physics and information theory, we study the memory-nonlinearity trade-off uncovered by Dambre et al. (2012). Focusing on a variational equation, we clarify a dynamical mechanism behind the trade-off, which illustrates why nonlinear dynamics degrades memory stored in dynamical system in general. Moreover, based on the trade-off, we propose a mixture reservoir endowed with both linear and nonlinear dynamics and show that it improves the performance of information processing. Interestingly, for some tasks, significant improvements are observed by adding a few linear dynamics to the nonlinear dynamical system. By employing the echo state network model, the effect of the mixture reservoir is numerically verified for a simple function approximation task and for more complex tasks.

Using Grid Benchmarks for Dynamic Scheduling of Grid Applications

NASA Technical Reports Server (NTRS)

Frumkin, Michael; Hood, Robert

2003-01-01

Navigation or dynamic scheduling of applications on computational grids can be improved through the use of an application-specific characterization of grid resources. Current grid information systems provide a description of the resources, but do not contain any application-specific information. We define a GridScape as dynamic state of the grid resources. We measure the dynamic performance of these resources using the grid benchmarks. Then we use the GridScape for automatic assignment of the tasks of a grid application to grid resources. The scalability of the system is achieved by limiting the navigation overhead to a few percent of the application resource requirements. Our task submission and assignment protocol guarantees that the navigation system does not cause grid congestion. On a synthetic data mining application we demonstrate that Gridscape-based task assignment reduces the application tunaround time.

Interactions Dominate the Dynamics of Visual Cognition

PubMed Central

Stephen, Damian G.; Mirman, Daniel

2010-01-01

Many cognitive theories have described behavior as the summation of independent contributions from separate components. Contrasting views have emphasized the importance of multiplicative interactions and emergent structure. We describe a statistical approach to distinguishing additive and multiplicative processes and apply it to the dynamics of eye movements during classic visual cognitive tasks. The results reveal interaction-dominant dynamics in eye movements in each of the three tasks, and that fine-grained eye movements are modulated by task constraints. These findings reveal the interactive nature of cognitive processing and are consistent with theories that view cognition as an emergent property of processes that are broadly distributed over many scales of space and time rather than a componential assembly line. PMID:20070957

Effects of automobile steering characteristics on driver vehicle system dynamics in regulation tasks

NASA Technical Reports Server (NTRS)

Mcruer, D. T.; Klein, R.

1975-01-01

A regulation task which subjected the automobile to a random gust disturbance which is countered by driver control action is used to study the effects of various automobile steering characteristics on the driver/vehicle system. The experiments used a variable stability automobile specially configured to permit insertion of the simulated gust disturbance and the measurement of the driver/vehicle system characteristics. Driver/vehicle system dynamics were measured and interpreted as an effective open loop system describing function. Objective measures of system bandwidth, stability, and time delays were deduced and compared. These objective measures were supplemented by driver ratings. A tentative optimum range of vehicle dynamics for the directional regulation task was established.

Regulation of dynamic postural control to attend manual steadiness constraints.

PubMed

Teixeira, Luis Augusto; Coutinho, Joane Figueiredo Serpa; Coelho, Daniel Boari

2018-05-02

In daily living activities, performance of spatially accurate manual movements in upright stance depends on postural stability. In the present investigation, we aimed to evaluate the effect of the required manual steadiness (task constraint) on the regulation of dynamic postural control. A single group of young participants (n=20) were evaluated in the performance of a dual posturo-manual task of balancing on a platform oscillating in sinusoidal translations at 0.4 Hz (low) or 1 Hz (high) frequencies while stabilizing a cylinder on a handheld tray. Manual task constraint was manipulated by comparing the conditions of keeping the cylinder stationary on its flat or round side, corresponding to low and high manual task constraints, respectively. Results showed that in the low oscillation frequency the high manual task constraint led to lower oscillation amplitudes of the head, center of mass, and tray, in addition to higher relative phase values between ankle/hip-shoulder oscillatory rotations and between center of mass/center of pressure-feet oscillations as compared to values observed in the low manual task constraint. Further analyses showed that the high manual task constraint also affected variables related to both postural (increased amplitudes of center of pressure oscillation) and manual (increased amplitude of shoulder rotations) task components in the high oscillation frequency. These results suggest that control of a dynamic posturo-manual task is modulated in distinct parameters to attend the required manual steadiness in a complex and flexible way.

Integration of domain and resource-based reasoning for real-time control in dynamic environments

NASA Technical Reports Server (NTRS)

Morgan, Keith; Whitebread, Kenneth R.; Kendus, Michael; Cromarty, Andrew S.

1993-01-01

A real-time software controller that successfully integrates domain-based and resource-based control reasoning to perform task execution in a dynamically changing environment is described. The design of the controller is based on the concept of partitioning the process to be controlled into a set of tasks, each of which achieves some process goal. It is assumed that, in general, there are multiple ways (tasks) to achieve a goal. The controller dynamically determines current goals and their current criticality, choosing and scheduling tasks to achieve those goals in the time available. It incorporates rule-based goal reasoning, a TMS-based criticality propagation mechanism, and a real-time scheduler. The controller has been used to build a knowledge-based situation assessment system that formed a major component of a real-time, distributed, cooperative problem solving system built under DARPA contract. It is also being employed in other applications now in progress.

Reciprocity-based experimental determination of dynamic forces and moments: A feasibility study

NASA Technical Reports Server (NTRS)

Ver, Istvan L.; Howe, Michael S.

1994-01-01

BBN Systems and Technologies has been tasked by the Georgia Tech Research Center to carry Task Assignment No. 7 for the NASA Langley Research Center to explore the feasibility of 'In-Situ Experimental Evaluation of the Source Strength of Complex Vibration Sources Utilizing Reciprocity.' The task was carried out under NASA Contract No. NAS1-19061. In flight it is not feasible to connect the vibration sources to their mounting points on the fuselage through force gauges to measure dynamic forces and moments directly. However, it is possible to measure the interior sound field or vibration response caused by these structureborne sound sources at many locations and invoke principle of reciprocity to predict the dynamic forces and moments. The work carried out in the framework of Task 7 was directed to explore the feasibility of reciprocity-based measurements of vibration forces and moments.

Executive Functions and Prefrontal Cortex: A Matter of Persistence?

PubMed Central

Ball, Gareth; Stokes, Paul R.; Rhodes, Rebecca A.; Bose, Subrata K.; Rezek, Iead; Wink, Alle-Meije; Lord, Louis-David; Mehta, Mitul A.; Grasby, Paul M.; Turkheimer, Federico E.

2011-01-01

Executive function is thought to originates from the dynamics of frontal cortical networks. We examined the dynamic properties of the blood oxygen level dependent time-series measured with functional MRI (fMRI) within the prefrontal cortex (PFC) to test the hypothesis that temporally persistent neural activity underlies performance in three tasks of executive function. A numerical estimate of signal persistence, the Hurst exponent, postulated to represent the coherent firing of cortical networks, was determined and correlated with task performance. Increasing persistence in the lateral PFC was shown to correlate with improved performance during an n-back task. Conversely, we observed a correlation between persistence and increasing commission error – indicating a failure to inhibit a prepotent response – during a Go/No-Go task. We propose that persistence within the PFC reflects dynamic network formation and these findings underline the importance of frequency analysis of fMRI time-series in the study of executive functions. PMID:21286223

Model task for the dynamics of an underwater two-legged walker

NASA Technical Reports Server (NTRS)

Beletskiy, V. V.; Golubkov, V. V.; Stepanova, Y. A.

1979-01-01

A model task of two-legged underwater walking was examined. Characteristics of the walking were established. The underwater walking device is a substantial sphere, which moves on dual-member legs. The dynamics of the device were investigated with the calculation of the buoyancy of Archimedes, and the force of hydrodynamic resistance.

Examining the Developmental Dynamics between Achievement Strategies and Different Literacy Skills

ERIC Educational Resources Information Center

Georgiou, George K.; Manolitsis, George; Zhang, Xiao; Parrila, Rauno; Nurmi, Jari-Erik

2013-01-01

We examined the developmental dynamics between task-avoidant behavior and different literacy outcomes, and possible precursors of task-avoidant behavior. Seventy Greek children were followed from Grade 4 until Grade 6 and were assessed every year on reading fluency, spelling, and reading comprehension. The teachers assessed the children's…

Learning to Manage Intergroup Dynamics in Changing Task Environments: An Experiential Exercise

ERIC Educational Resources Information Center

Hunsaker, Phillip L.

2004-01-01

This article describes an exercise that allows participants to experience the challenges of managing intergroup behavior as an organization's task environment grows and becomes more complex. The article begins with a brief review of models and concepts relating to intergroup dynamics, intergroup conflict, and interventions for effectively managing…

Dynamic Assessment of School-Age Children's Narrative Ability: An Experimental Investigation of Classification Accuracy

ERIC Educational Resources Information Center

Pena, Elizabeth D.; Gillam, Ronald B.; Malek, Melynn; Ruiz-Felter, Roxanna; Resendiz, Maria; Fiestas, Christine; Sabel, Tracy

2006-01-01

Two experiments examined reliability and classification accuracy of a narration-based dynamic assessment task. Purpose: The first experiment evaluated whether parallel results were obtained from stories created in response to 2 different wordless picture books. If so, the tasks and measures would be appropriate for assessing pretest and posttest…

Vigilance on the move: video game-based measurement of sustained attention.

PubMed

Szalma, J L; Schmidt, T N; Teo, G W L; Hancock, P A

2014-01-01

Vigilance represents the capacity to sustain attention to any environmental source of information over prolonged periods on watch. Most stimuli used in vigilance research over the previous six decades have been relatively simple and often purport to represent important aspects of detection and discrimination tasks in real-world settings. Such displays are most frequently composed of single stimulus presentations in discrete trials against a uniform, often uncluttered background. The present experiment establishes a dynamic, first-person perspective vigilance task in motion using a video-game environment. 'Vigilance on the move' is thus a new paradigm for the study of sustained attention. We conclude that the stress of vigilance extends to the new paradigm, but whether the performance decrement emerges depends upon specific task parameters. The development of the task, the issues to be resolved and the pattern of performance, perceived workload and stress associated with performing such dynamic vigilance are reported. The present experiment establishes a dynamic, first-person perspective movement-based vigilance task using a video-game environment. 'Vigilance on the move' is thus a new paradigm for the evaluation of sustained attention in operational environments in which individuals move as they monitor their environment. Issues addressed in task development are described.

Dynamic modulation of the perceptual load on microsaccades during a selective spatial attention task.

PubMed

Xue, Linyan; Huang, Dan; Wang, Tong; Hu, Qiyi; Chai, Xinyu; Li, Liming; Chen, Yao

2017-11-28

Selective spatial attention enhances task performance at restricted regions within the visual field. The magnitude of this effect depends on the level of attentional load, which determines the efficiency of distractor rejection. Mechanisms of attentional load include perceptual selection and/or cognitive control involving working memory. Recent studies have provided evidence that microsaccades are influenced by spatial attention. Therefore, microsaccade activities may be exploited to help understand the dynamic control of selective attention under different load levels. However, previous reports in humans on the effect of attentional load on microsaccades are inconsistent, and it is not clear to what extent these results and the dynamic changes of microsaccade activities are similar in monkeys. We trained monkeys to perform a color detection task in which the perceptual load was manipulated by task difficulty with limited involvement of working memory. Our results indicate that during the task with high perceptual load, the rate and amplitude of microsaccades immediately before the target color change were significantly suppressed. We also found that the occurrence of microsaccades before the monkeys' detection response deteriorated their performance, especially in the hard task. We propose that the activity of microsaccades might be an efficacious indicator of the perceptual load.

Scaffolding Interaction in Parent-Child Dyads: Multimodal Analysis of Parental Scaffolding with Task and Non-Task Oriented Children

ERIC Educational Resources Information Center

Salonen, Pekka; Lepola, Janne; Vauras, Marja

2007-01-01

In this exploratory study we conceptualized and explored socio-cognitive, emotional and motivational regulatory processes displayed in scaffolding interaction between parents and their non-task and task-oriented children. Based on the dynamic systems view and findings from developmental research, we assumed that parents with non-task oriented and…

Mathematical Tasks and the Student: Navigating "Tensions of Intentions" between Designers, Teachers, and Students

ERIC Educational Resources Information Center

Johnson, Heather Lynn; Coles, Alf; Clarke, David

2017-01-01

We articulate a student perspective on task design in mathematics education, foregrounding a dynamic relationship between intentions of task designers, teachers, and students. First, we characterize a student perspective on task design. Second, we provide theoretical perspectives that we use as tools to account for different facets of task design…

Acquisition and production of skilled behavior in dynamic decision-making tasks: Modeling strategic behavior in human-automation interaction: Why and aid can (and should) go unused

NASA Technical Reports Server (NTRS)

Kirlik, Alex

1991-01-01

Advances in computer and control technology offer the opportunity for task-offload aiding in human-machine systems. A task-offload aid (e.g., an autopilot, an intelligent assistant) can be selectively engaged by the human operator to dynamically delegate tasks to an automated system. Successful design and performance prediction in such systems requires knowledge of the factors influencing the strategy the operator develops and uses for managing interaction with the task-offload aid. A model is presented that shows how such strategies can be predicted as a function of three task context properties (frequency and duration of secondary tasks and costs of delaying secondary tasks) and three aid design properties (aid engagement and disengagement times, aid performance relative to human performance). Sensitivity analysis indicates how each of these contextual and design factors affect the optimal aid aid usage strategy and attainable system performance. The model is applied to understanding human-automation interaction in laboratory experiments on human supervisory control behavior. The laboratory task allowed subjects freedom to determine strategies for using an autopilot in a dynamic, multi-task environment. Modeling results suggested that many subjects may indeed have been acting appropriately by not using the autopilot in the way its designers intended. Although autopilot function was technically sound, this aid was not designed with due regard to the overall task context in which it was placed. These results demonstrate the need for additional research on how people may strategically manage their own resources, as well as those provided by automation, in an effort to keep workload and performance at acceptable levels.

Cortical subnetwork dynamics during human language tasks.

PubMed

Collard, Maxwell J; Fifer, Matthew S; Benz, Heather L; McMullen, David P; Wang, Yujing; Milsap, Griffin W; Korzeniewska, Anna; Crone, Nathan E

2016-07-15

Language tasks require the coordinated activation of multiple subnetworks-groups of related cortical interactions involved in specific components of task processing. Although electrocorticography (ECoG) has sufficient temporal and spatial resolution to capture the dynamics of event-related interactions between cortical sites, it is difficult to decompose these complex spatiotemporal patterns into functionally discrete subnetworks without explicit knowledge of each subnetwork's timing. We hypothesized that subnetworks corresponding to distinct components of task-related processing could be identified as groups of interactions with co-varying strengths. In this study, five subjects implanted with ECoG grids over language areas performed word repetition and picture naming. We estimated the interaction strength between each pair of electrodes during each task using a time-varying dynamic Bayesian network (tvDBN) model constructed from the power of high gamma (70-110Hz) activity, a surrogate for population firing rates. We then reduced the dimensionality of this model using principal component analysis (PCA) to identify groups of interactions with co-varying strengths, which we term functional network components (FNCs). This data-driven technique estimates both the weight of each interaction's contribution to a particular subnetwork, and the temporal profile of each subnetwork's activation during the task. We found FNCs with temporal and anatomical features consistent with articulatory preparation in both tasks, and with auditory and visual processing in the word repetition and picture naming tasks, respectively. These FNCs were highly consistent between subjects with similar electrode placement, and were robust enough to be characterized in single trials. Furthermore, the interaction patterns uncovered by FNC analysis correlated well with recent literature suggesting important functional-anatomical distinctions between processing external and self-produced speech. Our results demonstrate that subnetwork decomposition of event-related cortical interactions is a powerful paradigm for interpreting the rich dynamics of large-scale, distributed cortical networks during human cognitive tasks. Copyright © 2016 Elsevier Inc. All rights reserved.

Isolation of sabin-like polioviruses from wastewater in a country using inactivated polio vaccine.

PubMed

Zurbriggen, Sebastian; Tobler, Kurt; Abril, Carlos; Diedrich, Sabine; Ackermann, Mathias; Pallansch, Mark A; Metzler, Alfred

2008-09-01

From 2001 to 2004, Switzerland switched from routine vaccination with oral polio vaccine (OPV) to inactivated polio vaccine (IPV), using both vaccines in the intervening period. Since IPV is less effective at inducing mucosal immunity than OPV, this change might allow imported poliovirus to circulate undetected more easily in an increasingly IPV-immunized population. Environmental monitoring is a recognized tool for identifying polioviruses in a community. To look for evidence of poliovirus circulation following cessation of OPV use, two sewage treatment plants located in the Zurich area were sampled from 2004 to 2006. Following virus isolation using either RD or L20B cells, enteroviruses and polioviruses were identified by reverse transcription-PCR. A total of 20 out of 174 wastewater samples were positive for 62 Sabin-like isolates. One isolate from each poliovirus-positive sample was analyzed in more detail. Sequencing the complete viral protein 1 (VP1) capsid coding region, as well as intratypic differentiation (ITD), identified 3 Sabin type 1, 13 Sabin type 2, and 4 Sabin type 3 strains. One serotype 1 strain showed a discordant result in the ITD. Three-quarters of the strains showed mutations within the 5' untranslated region and VP1, known to be associated with reversion to virulence. Moreover, three strains showed heterotypic recombination (S2/S1 and S3/S2/S3). The low number of synonymous mutations and the partial temperature sensitivity are not consistent with extended circulation of these Sabin virus strains. Nevertheless, the continuous introduction of polioviruses into the community emphasizes the necessity for uninterrupted child vaccination to maintain high herd immunity.

Influence of aging on human sound localization

PubMed Central

Dobreva, Marina S.; O'Neill, William E.

2011-01-01

Errors in sound localization, associated with age-related changes in peripheral and central auditory function, can pose threats to self and others in a commonly encountered environment such as a busy traffic intersection. This study aimed to quantify the accuracy and precision (repeatability) of free-field human sound localization as a function of advancing age. Head-fixed young, middle-aged, and elderly listeners localized band-passed targets using visually guided manual laser pointing in a darkened room. Targets were presented in the frontal field by a robotically controlled loudspeaker assembly hidden behind a screen. Broadband targets (0.1–20 kHz) activated all auditory spatial channels, whereas low-pass and high-pass targets selectively isolated interaural time and intensity difference cues (ITDs and IIDs) for azimuth and high-frequency spectral cues for elevation. In addition, to assess the upper frequency limit of ITD utilization across age groups more thoroughly, narrowband targets were presented at 250-Hz intervals from 250 Hz up to ∼2 kHz. Young subjects generally showed horizontal overestimation (overshoot) and vertical underestimation (undershoot) of auditory target location, and this effect varied with frequency band. Accuracy and/or precision worsened in older individuals for broadband, high-pass, and low-pass targets, reflective of peripheral but also central auditory aging. In addition, compared with young adults, middle-aged, and elderly listeners showed pronounced horizontal localization deficiencies (imprecision) for narrowband targets within 1,250–1,575 Hz, congruent with age-related central decline in auditory temporal processing. Findings underscore the distinct neural processing of the auditory spatial cues in sound localization and their selective deterioration with advancing age. PMID:21368004

Fragment length analysis screening for detection of CEBPA mutations in intermediate-risk karyotype acute myeloid leukemia.

PubMed

Fuster, Oscar; Barragán, Eva; Bolufer, Pascual; Such, Esperanza; Valencia, Ana; Ibáñez, Mariam; Dolz, Sandra; de Juan, Inmaculada; Jiménez, Antonio; Gómez, Maria Teresa; Buño, Ismael; Martínez, Joaquín; Cervera, José; Montesinos, Pau; Moscardó, Federico; Sanz, Miguel Ángel

2012-01-01

During last years, molecular markers have been increased as prognostic factors routinely screened in acute myeloid leukemia (AML). Recently, an increasing interest has been reported in introducing to clinical practice screening for mutations in the CCAAT/enhancer-binding protein α (CEBPA) gene in AML, as it seems to be a good prognostic factor. However, there is no reliable established method for assessing CEBPA mutations during the diagnostic work-up of AMLs. We describe here a straightforward and reliable fragment analysis method based in PCR capillary electrophoresis (PCR-CE) for screening of CEBPA mutations; moreover, we present the results obtained in 151 intermediate-risk karyotype AML patients (aged 16-80 years). The method gave a specificity of 100% and sensitivity of 93% with a lower detection limit of 1-5% for CEBPA mutations. The series found 19 mutations and four polymorphisms in 12 patients, seven of whom (58%) presented two mutations. The overall frequency of CEBPA mutations in AML was 8% (n = 12). CEBPA mutations showed no coincidence with FLT3-ITD or NPM1 mutations. CEBPA mutation predicted better disease-free survival in the group of patients without FLT3-ITD, NPM, or both genes mutated (HR 3.6, IC 95%; 1.0-13.2, p = 0.05) and better overall survival in patients younger than 65 of this group without molecular markers (HR 4.0, IC 95%; 1.0-17.4, p = 0.05). In conclusion, the fragment analysis method based in PCR-CE is a rapid, specific, and sensitive method for CEBPA mutation screening and our results confirm that CEBPA mutations can identify a subgroup of patients with favorable prognosis in AML with intermediate-risk karyotype.

Use of Wilms Tumor 1 Gene Expression as a Reliable Marker for Prognosis and Minimal Residual Disease Monitoring in Acute Myeloid Leukemia With Normal Karyotype Patients.

PubMed

Marjanovic, Irena; Karan-Djurasevic, Teodora; Ugrin, Milena; Virijevic, Marijana; Vidovic, Ana; Tomin, Dragica; Suvajdzic Vukovic, Nada; Pavlovic, Sonja; Tosic, Natasa

2017-05-01

Acute myeloid leukemia with normal karyotype (AML-NK) represents the largest group of AML patients classified with an intermediate prognosis. A constant need exists to introduce new molecular markers for more precise risk stratification and for minimal residual disease (MRD) monitoring. Quantitative assessment of Wilms tumor 1 (WT1) gene transcripts was performed using real-time polymerase chain reaction. The bone marrow samples were collected at the diagnosis from 104 AML-NK patients and from 34 of these patients during follow-up or disease relapse. We found that overexpression of the WT1 gene (WT1 high status), present in 25.5% of patients, was an independent unfavorable factor for achieving complete remission. WT1 high status was also associated with resistance to therapy and shorter disease-free survival and overall survival. Assessment of the log reduction value of WT1 expression, measured in paired diagnosis/complete remission samples, revealed that patients with a log reduction of < 2 had a tendency toward shorter disease-free survival and overall survival and a greater incidence of disease relapse. Combining WT1 gene expression status with NPM1 and FLT3-ITD mutational status, we found that the tumor behavior of intermediate patients (FLT3-ITD - /NPM1 - double negative) with WT1 high status is almost the same as the tumor behavior of the adverse risk group. WT1 expression status represents a good molecular marker of prognosis, response to treatment, and MRD monitoring. Above all, the usage of the WT1 expression level as an additional marker for more precise risk stratification of AML-NK patients could lead to more adapted, personalized treatment protocols. Copyright © 2017 Elsevier Inc. All rights reserved.

Which AML subsets benefit from leukemic cell priming during chemotherapy? Long-term analysis of the ALFA-9802 GM-CSF study.

PubMed

Thomas, Xavier; Raffoux, Emmanuel; Renneville, Aline; Pautas, Cecile; de Botton, Stephane; Terre, Christine; Gardin, Claude; Hayette, Sandrine; Preudhomme, Claude; Dombret, Herve

2010-04-01

: Priming with granulocytic hematopoietic growth factors may modulate cell cycle kinetics of leukemic cells and render them more susceptible to phase-specific chemotherapeutic agents. In a first report, we have shown that priming with granulocyte-macrophage colony-stimulating factor (GM-CSF) may enhance complete remission (CR) rate and event-free survival (EFS) in younger adults with acute myeloid leukemia (AML). : In this randomized trial, 259 patients with AML were randomized at baseline to receive or not receive GM-CSF concurrently with all cycles of chemotherapy. The effects of GM-CSF on survival were reported herein with a long-term follow-up and studied according to distinct biological subgroups defined on cytogenetics and molecular markers. : The EFS rate was better in the GM-CSF group (43% vs 34%; P = .04). GM-CSF did not improve the outcome in patients from good risk subgroups, while patients from poor risk subgroups benefited from GM-CSF therapy. In this population, the difference in terms of EFS probability was mainly observed in patients with high initial white blood cell count and in those with FLT3-ITD or MLL rearrangement. When combining these 2 molecular abnormalities for comparison of the effect of GM-CSF priming, the difference in terms of EFS was highly significant (5-year EFS, 39% with GM-CSF vs 8% without GM-CSF; P = .007). : Sensitization of leukemic cells and their progenitors by GM-CSF appears as a plausible strategy for improving the outcome of patients with newly diagnosed AML. Patients with poor-prognosis FLT3-ITD or MLL rearrangement might be a good target population to further investigate priming strategies. Cancer 2010. (c) 2010 American Cancer Society.

Assessing dynamics, spatial scale, and uncertainty in task-related brain network analyses

PubMed Central

Stephen, Emily P.; Lepage, Kyle Q.; Eden, Uri T.; Brunner, Peter; Schalk, Gerwin; Brumberg, Jonathan S.; Guenther, Frank H.; Kramer, Mark A.

2014-01-01

The brain is a complex network of interconnected elements, whose interactions evolve dynamically in time to cooperatively perform specific functions. A common technique to probe these interactions involves multi-sensor recordings of brain activity during a repeated task. Many techniques exist to characterize the resulting task-related activity, including establishing functional networks, which represent the statistical associations between brain areas. Although functional network inference is commonly employed to analyze neural time series data, techniques to assess the uncertainty—both in the functional network edges and the corresponding aggregate measures of network topology—are lacking. To address this, we describe a statistically principled approach for computing uncertainty in functional networks and aggregate network measures in task-related data. The approach is based on a resampling procedure that utilizes the trial structure common in experimental recordings. We show in simulations that this approach successfully identifies functional networks and associated measures of confidence emergent during a task in a variety of scenarios, including dynamically evolving networks. In addition, we describe a principled technique for establishing functional networks based on predetermined regions of interest using canonical correlation. Doing so provides additional robustness to the functional network inference. Finally, we illustrate the use of these methods on example invasive brain voltage recordings collected during an overt speech task. The general strategy described here—appropriate for static and dynamic network inference and different statistical measures of coupling—permits the evaluation of confidence in network measures in a variety of settings common to neuroscience. PMID:24678295

Assessing dynamics, spatial scale, and uncertainty in task-related brain network analyses.

PubMed

Stephen, Emily P; Lepage, Kyle Q; Eden, Uri T; Brunner, Peter; Schalk, Gerwin; Brumberg, Jonathan S; Guenther, Frank H; Kramer, Mark A

2014-01-01

The brain is a complex network of interconnected elements, whose interactions evolve dynamically in time to cooperatively perform specific functions. A common technique to probe these interactions involves multi-sensor recordings of brain activity during a repeated task. Many techniques exist to characterize the resulting task-related activity, including establishing functional networks, which represent the statistical associations between brain areas. Although functional network inference is commonly employed to analyze neural time series data, techniques to assess the uncertainty-both in the functional network edges and the corresponding aggregate measures of network topology-are lacking. To address this, we describe a statistically principled approach for computing uncertainty in functional networks and aggregate network measures in task-related data. The approach is based on a resampling procedure that utilizes the trial structure common in experimental recordings. We show in simulations that this approach successfully identifies functional networks and associated measures of confidence emergent during a task in a variety of scenarios, including dynamically evolving networks. In addition, we describe a principled technique for establishing functional networks based on predetermined regions of interest using canonical correlation. Doing so provides additional robustness to the functional network inference. Finally, we illustrate the use of these methods on example invasive brain voltage recordings collected during an overt speech task. The general strategy described here-appropriate for static and dynamic network inference and different statistical measures of coupling-permits the evaluation of confidence in network measures in a variety of settings common to neuroscience.

Active listening: task-dependent plasticity of spectrotemporal receptive fields in primary auditory cortex.

PubMed

Fritz, Jonathan; Elhilali, Mounya; Shamma, Shihab

2005-08-01

Listening is an active process in which attentive focus on salient acoustic features in auditory tasks can influence receptive field properties of cortical neurons. Recent studies showing rapid task-related changes in neuronal spectrotemporal receptive fields (STRFs) in primary auditory cortex of the behaving ferret are reviewed in the context of current research on cortical plasticity. Ferrets were trained on spectral tasks, including tone detection and two-tone discrimination, and on temporal tasks, including gap detection and click-rate discrimination. STRF changes could be measured on-line during task performance and occurred within minutes of task onset. During spectral tasks, there were specific spectral changes (enhanced response to tonal target frequency in tone detection and discrimination, suppressed response to tonal reference frequency in tone discrimination). However, only in the temporal tasks, the STRF was changed along the temporal dimension by sharpening temporal dynamics. In ferrets trained on multiple tasks, distinctive and task-specific STRF changes could be observed in the same cortical neurons in successive behavioral sessions. These results suggest that rapid task-related plasticity is an ongoing process that occurs at a network and single unit level as the animal switches between different tasks and dynamically adapts cortical STRFs in response to changing acoustic demands.

Artificial Epigenetic Networks: Automatic Decomposition of Dynamical Control Tasks Using Topological Self-Modification.

PubMed

Turner, Alexander P; Caves, Leo S D; Stepney, Susan; Tyrrell, Andy M; Lones, Michael A

2017-01-01

This paper describes the artificial epigenetic network, a recurrent connectionist architecture that is able to dynamically modify its topology in order to automatically decompose and solve dynamical problems. The approach is motivated by the behavior of gene regulatory networks, particularly the epigenetic process of chromatin remodeling that leads to topological change and which underlies the differentiation of cells within complex biological organisms. We expected this approach to be useful in situations where there is a need to switch between different dynamical behaviors, and do so in a sensitive and robust manner in the absence of a priori information about problem structure. This hypothesis was tested using a series of dynamical control tasks, each requiring solutions that could express different dynamical behaviors at different stages within the task. In each case, the addition of topological self-modification was shown to improve the performance and robustness of controllers. We believe this is due to the ability of topological changes to stabilize attractors, promoting stability within a dynamical regime while allowing rapid switching between different regimes. Post hoc analysis of the controllers also demonstrated how the partitioning of the networks could provide new insights into problem structure.

The auditory dynamic attending theory revisited: A closer look at the pitch comparison task.

PubMed

Bauer, Anna-Katharina R; Jaeger, Manuela; Thorne, Jeremy D; Bendixen, Alexandra; Debener, Stefan

2015-11-11

The dynamic attending theory as originally proposed by Jones, 1976. Psychol. Rev. 83(5), 323-355 posits that tone sequences presented at a regular rhythm entrain attentional oscillations and thereby facilitate the processing of sounds presented in phase with this rhythm. The increased interest in neural correlates of dynamic attending requires robust behavioral indicators of the phenomenon. Here we aimed to replicate and complement the most prominent experimental implementation of dynamic attending (Jones et al., 2002. Psychol. Sci. 13(4), 313-319). The paradigm uses a pitch comparison task in which two tones, the initial and the last of a longer series, have to be compared. In-between the two, distractor tones with variable pitch are presented, at a regular pace. A comparison tone presented in phase with the entrained rhythm is hypothesized to lead to better behavioral performance. Aiming for a conceptual replication, four different variations of the original paradigm were created which were followed by an exact replication attempt. Across all five experiments, only 40 of the 140 tested participants showed the hypothesized pattern of an inverted U-shaped profile in task accuracy, and the group average effects did not replicate the pattern reported by Jones et al., 2002. Psychol. Sci. 13(4), 313-319 in any of the five experiments. However, clear evidence for a relationship between musicality and overall behavioral performance was found. This study casts doubt on the suitability of the pitch comparison task for demonstrating auditory dynamic attending. We discuss alternative tasks that have been shown to support dynamic attending theory, thus lending themselves more readily to studying its neural correlates. This article is part of a Special Issue entitled SI: Prediction and Attention. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Dynamic sound localization in cats

PubMed Central

Ruhland, Janet L.; Jones, Amy E.

2015-01-01

Sound localization in cats and humans relies on head-centered acoustic cues. Studies have shown that humans are able to localize sounds during rapid head movements that are directed toward the target or other objects of interest. We studied whether cats are able to utilize similar dynamic acoustic cues to localize acoustic targets delivered during rapid eye-head gaze shifts. We trained cats with visual-auditory two-step tasks in which we presented a brief sound burst during saccadic eye-head gaze shifts toward a prior visual target. No consistent or significant differences in accuracy or precision were found between this dynamic task (2-step saccade) and the comparable static task (single saccade when the head is stable) in either horizontal or vertical direction. Cats appear to be able to process dynamic auditory cues and execute complex motor adjustments to accurately localize auditory targets during rapid eye-head gaze shifts. PMID:26063772

Framing of task performance strategies: effects on performance in a multiattribute dynamic decision making environment.

PubMed

Nygren, T E

1997-09-01

It is well documented that the way a static choice task is "framed" can dramatically alter choice behavior, often leading to observable preference reversals. This framing effect appears to result from perceived changes in the nature or location of a person's initial reference point, but it is not clear how framing effects might generalize to performance on dynamic decision making tasks that are characterized by high workload, time constraints, risk, or stress. A study was conducted to examine the hypothesis that framing can introduce affective components to the decision making process and can influence, either favorably (positive frame) or adversely (negative frame), the implementation and use of decision making strategies in dynamic high-workload environments. Results indicated that negative frame participants were significantly impaired in developing and employing a simple optimal decision strategy relative to a positive frame group. Discussion focuses on implications of these results for models of dynamic decision making.

Team structure and regulatory focus: the impact of regulatory fit on team dynamic.

PubMed

Dimotakis, Nikolaos; Davison, Robert B; Hollenbeck, John R

2012-03-01

We report a within-teams experiment testing the effects of fit between team structure and regulatory task demands on task performance and satisfaction through average team member positive affect and helping behaviors. We used a completely crossed repeated-observations design in which 21 teams enacted 2 tasks with different regulatory focus characteristics (prevention and promotion) in 2 organizational structures (functional and divisional), resulting in 84 observations. Results suggested that salient regulatory demands inherent in the task interacted with structure to determine objective and subjective team-level outcomes, such that functional structures were best suited to (i.e., had best fit with) tasks with a prevention regulatory focus and divisional structures were best suited to tasks with a promotion regulatory focus. This contingency finding integrates regulatory focus and structural contingency theories, and extends them to the team level with implications for models of performance, satisfaction, and team dynamics.

A Model for Task Design with Focus on Exploration, Explanation, and Generalization in a Dynamic Geometry Environment

ERIC Educational Resources Information Center

Fahlgren, Maria; Brunström, Mats

2014-01-01

The increasing availability of new technologies in schools provides new possibilities for the integration of technology in mathematics education. However, research has shown that there is a need for new kinds of task that utilize the affordances provided by new technology. Numerous studies have demonstrated that dynamic geometry environments…

A Complex Systems Investigation of Group Work Dynamics in L2 Interactive Tasks

ERIC Educational Resources Information Center

Poupore, Glen

2018-01-01

Working with Korean university-level learners of English, this study provides a detailed analytical comparison of 2 task work groups that were video-recorded, with 1 group scoring very high and the other relatively low based on the results of a Group Work Dynamic (GWD) measuring instrument. Adopting a complexity theory (CT) perspective and…

Interactions dominate the dynamics of visual cognition.

PubMed

Stephen, Damian G; Mirman, Daniel

2010-04-01

Many cognitive theories have described behavior as the summation of independent contributions from separate components. Contrasting views have emphasized the importance of multiplicative interactions and emergent structure. We describe a statistical approach to distinguishing additive and multiplicative processes and apply it to the dynamics of eye movements during classic visual cognitive tasks. The results reveal interaction-dominant dynamics in eye movements in each of the three tasks, and that fine-grained eye movements are modulated by task constraints. These findings reveal the interactive nature of cognitive processing and are consistent with theories that view cognition as an emergent property of processes that are broadly distributed over many scales of space and time rather than a componential assembly line. Copyright 2009 Elsevier B.V. All rights reserved.

Neural Computations in a Dynamical System with Multiple Time Scales.

PubMed

Mi, Yuanyuan; Lin, Xiaohan; Wu, Si

2016-01-01

Neural systems display rich short-term dynamics at various levels, e.g., spike-frequency adaptation (SFA) at the single-neuron level, and short-term facilitation (STF) and depression (STD) at the synapse level. These dynamical features typically cover a broad range of time scales and exhibit large diversity in different brain regions. It remains unclear what is the computational benefit for the brain to have such variability in short-term dynamics. In this study, we propose that the brain can exploit such dynamical features to implement multiple seemingly contradictory computations in a single neural circuit. To demonstrate this idea, we use continuous attractor neural network (CANN) as a working model and include STF, SFA and STD with increasing time constants in its dynamics. Three computational tasks are considered, which are persistent activity, adaptation, and anticipative tracking. These tasks require conflicting neural mechanisms, and hence cannot be implemented by a single dynamical feature or any combination with similar time constants. However, with properly coordinated STF, SFA and STD, we show that the network is able to implement the three computational tasks concurrently. We hope this study will shed light on the understanding of how the brain orchestrates its rich dynamics at various levels to realize diverse cognitive functions.

The effect of single-task and dual-task balance exercise programs on balance performance in adults with osteoporosis: a randomized controlled preliminary trial.

PubMed

Konak, H E; Kibar, S; Ergin, E S

2016-11-01

Osteoporosis is a serious disease characterized by muscle weakness in the lower extremities, shortened length of trunk, and increased dorsal kyphosis leading to poor balance performance. Although balance impairment increases in adults with osteoporosis, falls and fall-related injuries have been shown to occur mainly during the dual-task performance. Several studies have shown that dual-task performance was improved with specific repetitive dual-task exercises. The aims of this study were to compare the effect of single- and dual-task balance exercise programs on static balance, dynamic balance, and activity-specific balance confidence in adults with osteoporosis and to assess the effectiveness of dual-task balance training on gait speed under dual-task conditions. Older adults (N = 42) (age range, 45-88 years) with osteoporosis were randomly assigned into two groups. Single-task balance training group was given single-task balance exercises for 4 weeks, whereas dual-task balance training group received dual-task balance exercises. Participants received 45-min individualized training session, three times a week. Static balance was evaluated by one-leg stance (OLS) and a kinesthetic ability trainer (KAT) device. Dynamic balance was measured by the Berg Balance Scale (BBS), Time Up and Go (TUG) test, and gait speed. Self-confidence was assessed with the Activities-specific Balance Confidence (ABC-6) scale. Assessments were performed at baseline and after the 4-week program. At the end of the treatment periods, KAT score, BBS score, time in OLS and TUG, gait speeds under single- and dual-task conditions, and ABC-6 scale scores improved significantly in all patients (p < 0.05). However, BBS and gait speeds under single- and dual-task conditions showed significantly greater improvement in the dual-task balance training group than in the single-task balance training group (p < 0.05). ABC-6 scale scores improved more in the single-task balance training group than in the dual-task balance training group (p < 0.05). A 4-week single- and dual-task balance exercise programs are effective in improving static balance, dynamic balance, and balance confidence during daily activities in older adults with osteoporosis. However, single- and dual-task gait speeds showed greater improvement following the application of a specific type of dual-task exercise programs. 24102014-2.

Molecular dynamics simulations of large macromolecular complexes.

PubMed

Perilla, Juan R; Goh, Boon Chong; Cassidy, C Keith; Liu, Bo; Bernardi, Rafael C; Rudack, Till; Yu, Hang; Wu, Zhe; Schulten, Klaus

2015-04-01

Connecting dynamics to structural data from diverse experimental sources, molecular dynamics simulations permit the exploration of biological phenomena in unparalleled detail. Advances in simulations are moving the atomic resolution descriptions of biological systems into the million-to-billion atom regime, in which numerous cell functions reside. In this opinion, we review the progress, driven by large-scale molecular dynamics simulations, in the study of viruses, ribosomes, bioenergetic systems, and other diverse applications. These examples highlight the utility of molecular dynamics simulations in the critical task of relating atomic detail to the function of supramolecular complexes, a task that cannot be achieved by smaller-scale simulations or existing experimental approaches alone. Copyright © 2015 Elsevier Ltd. All rights reserved.

Task-Driven Activity Reduces the Cortical Activity Space of the Brain: Experiment and Whole-Brain Modeling

PubMed Central

Hagmann, Patric; Deco, Gustavo

2015-01-01

How a stimulus or a task alters the spontaneous dynamics of the brain remains a fundamental open question in neuroscience. One of the most robust hallmarks of task/stimulus-driven brain dynamics is the decrease of variability with respect to the spontaneous level, an effect seen across multiple experimental conditions and in brain signals observed at different spatiotemporal scales. Recently, it was observed that the trial-to-trial variability and temporal variance of functional magnetic resonance imaging (fMRI) signals decrease in the task-driven activity. Here we examined the dynamics of a large-scale model of the human cortex to provide a mechanistic understanding of these observations. The model allows computing the statistics of synaptic activity in the spontaneous condition and in putative tasks determined by external inputs to a given subset of brain regions. We demonstrated that external inputs decrease the variance, increase the covariances, and decrease the autocovariance of synaptic activity as a consequence of single node and large-scale network dynamics. Altogether, these changes in network statistics imply a reduction of entropy, meaning that the spontaneous synaptic activity outlines a larger multidimensional activity space than does the task-driven activity. We tested this model’s prediction on fMRI signals from healthy humans acquired during rest and task conditions and found a significant decrease of entropy in the stimulus-driven activity. Altogether, our study proposes a mechanism for increasing the information capacity of brain networks by enlarging the volume of possible activity configurations at rest and reliably settling into a confined stimulus-driven state to allow better transmission of stimulus-related information. PMID:26317432

Multiloop Manual Control of Dynamic Systems

NASA Technical Reports Server (NTRS)

Hess, R. A.; Mcnally, B. D.

1984-01-01

Human interaction with a simple, multiloop dynamic system in which the human's activity was systematically varied by changing the levels of automation was studied. The control loop structure resulting from the task definition parallels that for any multiloop manual control system, is considered a sterotype. Simple models of the human in the task, and upon extending a technique for describing the manner in which the human subjectively quantifies his opinion of task difficulty were developed. A man in the loop simulation which provides data to support and direct the analytical effort is presented.

Functional Connectivity among Spikes in Low Dimensional Space during Working Memory Task in Rat

PubMed Central

Tian, Xin

2014-01-01

Working memory (WM) is critically important in cognitive tasks. The functional connectivity has been a powerful tool for understanding the mechanism underlying the information processing during WM tasks. The aim of this study is to investigate how to effectively characterize the dynamic variations of the functional connectivity in low dimensional space among the principal components (PCs) which were extracted from the instantaneous firing rate series. Spikes were obtained from medial prefrontal cortex (mPFC) of rats with implanted microelectrode array and then transformed into continuous series via instantaneous firing rate method. Granger causality method is proposed to study the functional connectivity. Then three scalar metrics were applied to identify the changes of the reduced dimensionality functional network during working memory tasks: functional connectivity (GC), global efficiency (E) and casual density (CD). As a comparison, GC, E and CD were also calculated to describe the functional connectivity in the original space. The results showed that these network characteristics dynamically changed during the correct WM tasks. The measure values increased to maximum, and then decreased both in the original and in the reduced dimensionality. Besides, the feature values of the reduced dimensionality were significantly higher during the WM tasks than they were in the original space. These findings suggested that functional connectivity among the spikes varied dynamically during the WM tasks and could be described effectively in the low dimensional space. PMID:24658291

How do task characteristics affect learning and performance? The roles of variably mapped and dynamic tasks.

PubMed

Macnamara, Brooke N; Frank, David J

2018-05-01

For well over a century, scientists have investigated individual differences in performance. The majority of studies have focused on either differences in practice, or differences in cognitive resources. However, the predictive ability of either practice or cognitive resources varies considerably across tasks. We are the first to examine task characteristics' impact on learning and performance in a complex task while controlling for other task characteristics. In 2 experiments we test key theoretical task characteristic thought to moderate the relationship between practice, cognitive resources, and performance. We devised a task where each of several key task characteristics can be manipulated independently. Participants played 5 rounds of a game similar to the popular tower defense videogame Plants vs. Zombies where both cognitive load and game characteristics were manipulated. In Experiment 1, participants either played a consistently mapped version-the stimuli and the associated meaning of their properties were constant across the 5 rounds-or played a variably mapped version-the stimuli and the associated meaning of their properties changed every few minutes. In Experiment 2, participants either played a static version-that is, turn taking with no time pressure-or played a dynamic version-that is, the stimuli moved regardless of participants' response rates. In Experiment 1, participants' accuracy and efficiency were substantially hindered in the variably mapped conditions. In Experiment 2, learning and performance accuracy were hindered in the dynamic conditions, especially when under cognitive load. Our results suggest that task characteristics impact the relative importance of cognitive resources and practice on predicting learning and performance. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Unintentional force changes in cyclical tasks performed by an abundant system: Empirical observations and a dynamical model.

PubMed

Reschechtko, Sasha; Hasanbarani, Fariba; Akulin, Vladimir M; Latash, Mark L

2017-05-14

The study explored unintentional force changes elicited by removing visual feedback during cyclical, two-finger isometric force production tasks. Subjects performed two types of tasks at 1Hz, paced by an auditory metronome. One - Force task - required cyclical changes in total force while maintaining the sharing, defined as relative contribution of a finger to total force. The other task - Share task - required cyclical changes in sharing while keeping total force unchanged. Each trial started under full visual feedback on both force and sharing; subsequently, feedback on the variable that was instructed to stay constant was frozen, and finally feedback on the other variable was also removed. In both tasks, turning off visual feedback on total force elicited a drop in the mid-point of the force cycle and an increase in the peak-to-peak force amplitude. Turning off visual feedback on sharing led to a drift of mean share toward 50:50 across both tasks. Without visual feedback there was consistent deviation of the two force time series from the in-phase pattern (typical of the Force task) and from the out-of-phase pattern (typical of the Share task). This finding is in contrast to most earlier studies that demonstrated only two stable patterns, in-phase and out-of-phase. We interpret the results as consequences of drifts of parameters in a dynamical system leading in particular to drifts in the referent finger coordinates toward their actual coordinates. The relative phase desynchronization is caused by the right-left differences in the hypothesized drift processes, consistent with the dynamic dominance hypothesis. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Working-memory load and temporal myopia in dynamic decision making.

PubMed

Worthy, Darrell A; Otto, A Ross; Maddox, W Todd

2012-11-01

We examined the role of working memory (WM) in dynamic decision making by having participants perform decision-making tasks under single-task or dual-task conditions. In 2 experiments participants performed dynamic decision-making tasks in which they chose 1 of 2 options on each trial. The decreasing option always gave a larger immediate reward but caused future rewards for both options to decrease. The increasing option always gave a smaller immediate reward but caused future rewards for both options to increase. In each experiment we manipulated the reward structure such that the decreasing option was the optimal choice in 1 condition and the increasing option was the optimal choice in the other condition. Behavioral results indicated that dual-task participants selected the immediately rewarding decreasing option more often, and single-task participants selected the increasing option more often, regardless of which option was optimal. Thus, dual-task participants performed worse on 1 type of task but better on the other type. Modeling results showed that single-task participants' data were most often best fit by a win-stay, lose-shift (WSLS) rule-based model that tracked differences across trials, and dual-task participants' data were most often best fit by a Softmax reinforcement learning model that tracked recency-weighted average rewards for each option. This suggests that manipulating WM load affects the degree to which participants focus on the immediate versus delayed consequences of their actions and whether they employ a rule-based WSLS strategy, but it does not necessarily affect how well people weigh the immediate versus delayed benefits when determining the long-term utility of each option.

Long-range functional interactions of anterior insula and medial frontal cortex are differently modulated by visuospatial and inductive reasoning tasks.

PubMed

Ebisch, Sjoerd J H; Mantini, Dante; Romanelli, Roberta; Tommasi, Marco; Perrucci, Mauro G; Romani, Gian Luca; Colom, Roberto; Saggino, Aristide

2013-09-01

The brain is organized into functionally specific networks as characterized by intrinsic functional relationships within discrete sets of brain regions. However, it is poorly understood whether such functional networks are dynamically organized according to specific task-states. The anterior insular cortex (aIC)-dorsal anterior cingulate cortex (dACC)/medial frontal cortex (mFC) network has been proposed to play a central role in human cognitive abilities. The present functional magnetic resonance imaging (fMRI) study aimed at testing whether functional interactions of the aIC-dACC/mFC network in terms of temporally correlated patterns of neural activity across brain regions are dynamically modulated by transitory, ongoing task demands. For this purpose, functional interactions of the aIC-dACC/mFC network are compared during two distinguishable fluid reasoning tasks, Visualization and Induction. The results show an increased functional coupling of bilateral aIC with visual cortices in the occipital lobe during the Visualization task, whereas coupling of mFC with right anterior frontal cortex was enhanced during the Induction task. These task-specific modulations of functional interactions likely reflect ability related neural processing. Furthermore, functional connectivity strength between right aIC and right dACC/mFC reliably predicts general task performance. The findings suggest that the analysis of long-range functional interactions may provide complementary information about brain-behavior relationships. On the basis of our results, it is proposed that the aIC-dACC/mFC network contributes to the integration of task-common and task-specific information based on its within-network as well as its between-network dynamic functional interactions. Copyright © 2013 Elsevier Inc. All rights reserved.

Unintentional force changes in cyclical tasks performed by an abundant system: Empirical observations and a dynamical model

PubMed Central

Reschechtko, Sasha; Hasanbarani, Fariba; Akulin, Vladimir M.; Latash, Mark L.

2017-01-01

The study explored unintentional force changes elicited by removing visual feedback during cyclical, two-finger isometric force production tasks. Subjects performed two types of tasks at 1 Hz, paced by an auditory metronome. One – Force task – required cyclical changes in total force while maintaining the sharing, defined as relative contribution of a finger to total force. The other task – Share task – required cyclical changes in sharing while keeping total force unchanged. Each trial started under full visual feedback on both force and sharing; subsequently, feedback on the variable that was instructed to stay constant was frozen, and finally feedback on the other variable was also removed. In both tasks, turning off visual feedback on total force elicited a drop in the mid-point of the force cycle and an increase in the peak-to-peak force amplitude. Turning off visual feedback on sharing led to a drift of mean share toward 50:50 across both tasks. Without visual feedback there was consistent deviation of the two force time series from the in-phase pattern (typical of the Force task) and from the out-of-phase pattern (typical of the Share task). This finding is in contrast to most earlier studies that demonstrated only two stable patterns, in-phase and out-of-phase. We interpret the results as consequences of drifts of parameters in a dynamical system leading in particular to drifts in the referent finger coordinates toward their actual coordinates. The relative phase desynchronization is caused by the right-left differences in the hypothesized drift processes, consistent with the dynamic dominance hypothesis. PMID:28344070

Safety margins in older adults increase with improved control of a dynamic object

PubMed Central

Hasson, Christopher J.; Sternad, Dagmar

2014-01-01

Older adults face decreasing motor capabilities due to pervasive neuromuscular degradations. As a consequence, errors in movement control increase. Thus, older individuals should maintain larger safety margins than younger adults. While this has been shown for object manipulation tasks, several reports on whole-body activities, such as posture and locomotion, demonstrate age-related reductions in safety margins. This is despite increased costs for control errors, such as a fall. We posit that this paradox could be explained by the dynamic challenge presented by the body or also an external object, and that age-related reductions in safety margins are in part due to a decreased ability to control dynamics. To test this conjecture we used a virtual ball-in-cup task that had challenging dynamics, yet afforded an explicit rendering of the physics and safety margin. The hypotheses were: (1) When manipulating an object with challenging dynamics, older adults have smaller safety margins than younger adults. (2) Older adults increase their safety margins with practice. Nine young and 10 healthy older adults practiced moving the virtual ball-in-cup to a target location in exactly 2 s. The accuracy and precision of the timing error quantified skill, and the ball energy relative to an escape threshold quantified the safety margin. Compared to the young adults, older adults had increased timing errors, greater variability, and decreased safety margins. With practice, both young and older adults improved their ability to control the object with decreased timing errors and variability, and increased their safety margins. These results suggest that safety margins are related to the ability to control dynamics, and may explain why in tasks with simple dynamics older adults use adequate safety margins, but in more complex tasks, safety margins may be inadequate. Further, the results indicate that task-specific training may improve safety margins in older adults. PMID:25071566

Does attention play a role in dynamic receptive field adaptation to changing acoustic salience in A1?

PubMed

Fritz, Jonathan B; Elhilali, Mounya; David, Stephen V; Shamma, Shihab A

2007-07-01

Acoustic filter properties of A1 neurons can dynamically adapt to stimulus statistics, classical conditioning, instrumental learning and the changing auditory attentional focus. We have recently developed an experimental paradigm that allows us to view cortical receptive field plasticity on-line as the animal meets different behavioral challenges by attending to salient acoustic cues and changing its cortical filters to enhance performance. We propose that attention is the key trigger that initiates a cascade of events leading to the dynamic receptive field changes that we observe. In our paradigm, ferrets were initially trained, using conditioned avoidance training techniques, to discriminate between background noise stimuli (temporally orthogonal ripple combinations) and foreground tonal target stimuli. They learned to generalize the task for a wide variety of distinct background and foreground target stimuli. We recorded cortical activity in the awake behaving animal and computed on-line spectrotemporal receptive fields (STRFs) of single neurons in A1. We observed clear, predictable task-related changes in STRF shape while the animal performed spectral tasks (including single tone and multi-tone detection, and two-tone discrimination) with different tonal targets. A different set of task-related changes occurred when the animal performed temporal tasks (including gap detection and click-rate discrimination). Distinctive cortical STRF changes may constitute a "task-specific signature". These spectral and temporal changes in cortical filters occur quite rapidly, within 2min of task onset, and fade just as quickly after task completion, or in some cases, persisted for hours. The same cell could multiplex by differentially changing its receptive field in different task conditions. On-line dynamic task-related changes, as well as persistent plastic changes, were observed at a single-unit, multi-unit and population level. Auditory attention is likely to be pivotal in mediating these task-related changes since the magnitude of STRF changes correlated with behavioral performance on tasks with novel targets. Overall, these results suggest the presence of an attention-triggered plasticity algorithm in A1 that can swiftly change STRF shape by transforming receptive fields to enhance figure/ground separation, by using a contrast matched filter to filter out the background, while simultaneously enhancing the salient acoustic target in the foreground. These results favor the view of a nimble, dynamic, attentive and adaptive brain that can quickly reshape its sensory filter properties and sensori-motor links on a moment-to-moment basis, depending upon the current challenges the animal faces. In this review, we summarize our results in the context of a broader survey of the field of auditory attention, and then consider neuronal networks that could give rise to this phenomenon of attention-driven receptive field plasticity in A1.

Applying Cognitive Work Analysis to Time Critical Targeting Functionality

DTIC Science & Technology

2004-10-01

Cognitive Task Analysis , CTA, Cognitive Task Analysis , Human Factors, GUI, Graphical User Interface, Heuristic Evaluation... Cognitive Task Analysis MITRE Briefing January 2000 Dynamic Battle Management Functional Architecture 3-1 Section 3 Human Factors...clear distinction between Cognitive Work Analysis (CWA) and Cognitive Task Analysis (CTA), therefore this document will refer to these

A new task scheduling algorithm based on value and time for cloud platform

NASA Astrophysics Data System (ADS)

Kuang, Ling; Zhang, Lichen

2017-08-01

Tasks scheduling, a key part of increasing resource utilization and enhancing system performance, is a never outdated problem especially in cloud platforms. Based on the value density algorithm of the real-time task scheduling system and the character of the distributed system, the paper present a new task scheduling algorithm by further studying the cloud technology and the real-time system: Least Level Value Density First (LLVDF). The algorithm not only introduces some attributes of time and value for tasks, it also can describe weighting relationships between these properties mathematically. As this feature of the algorithm, it can gain some advantages to distinguish between different tasks more dynamically and more reasonably. When the scheme was used in the priority calculation of the dynamic task scheduling on cloud platform, relying on its advantage, it can schedule and distinguish tasks with large amounts and many kinds more efficiently. The paper designs some experiments, some distributed server simulation models based on M/M/C model of queuing theory and negative arrivals, to compare the algorithm against traditional algorithm to observe and show its characters and advantages.

On-the-fly scheduling as a manifestation of partial-order planning and dynamic task values.

PubMed

Hannah, Samuel D; Neal, Andrew

2014-09-01

The aim of this study was to develop a computational account of the spontaneous task ordering that occurs within jobs as work unfolds ("on-the-fly task scheduling"). Air traffic control is an example of work in which operators have to schedule their tasks as a partially predictable work flow emerges. To date, little attention has been paid to such on-the-fly scheduling situations. We present a series of discrete-event models fit to conflict resolution decision data collected from experienced controllers operating in a high-fidelity simulation. Our simulations reveal air traffic controllers' scheduling decisions as examples of the partial-order planning approach of Hayes-Roth and Hayes-Roth. The most successful model uses opportunistic first-come-first-served scheduling to select tasks from a queue. Tasks with short deadlines are executed immediately. Tasks with long deadlines are evaluated to assess whether they need to be executed immediately or deferred. On-the-fly task scheduling is computationally tractable despite its surface complexity and understandable as an example of both the partial-order planning strategy and the dynamic-value approach to prioritization.

An involuntary stereotypical grasp tendency pervades voluntary dynamic multifinger manipulation

PubMed Central

Rácz, Kornelius; Brown, Daniel

2012-01-01

We used a novel apparatus with three hinged finger pads to characterize collaborative multifinger interactions during dynamic manipulation requiring individuated control of fingertip motions and forces. Subjects placed the thumb, index, and middle fingertips on each hinged finger pad and held it—unsupported—with constant total grasp force while voluntarily oscillating the thumb's pad. This task combines the need to 1) hold the object against gravity while 2) dynamically reconfiguring the grasp. Fingertip force variability in this combined motion and force task exhibited strong synchrony among normal (i.e., grasp) forces. Mechanical analysis and simulation show that such synchronous variability is unnecessary and cannot be explained solely by signal-dependent noise. Surprisingly, such variability also pervaded control tasks requiring different individuated fingertip motions and forces, but not tasks without finger individuation such as static grasp. These results critically extend notions of finger force variability by exposing and quantifying a pervasive challenge to dynamic multifinger manipulation: the need for the neural controller to carefully and continuously overlay individuated finger actions over mechanically unnecessary synchronous interactions. This is compatible with—and may explain—the phenomenology of strong coupling of hand muscles when this delicate balance is not yet developed, as in early childhood, or when disrupted, as in brain injury. We conclude that the control of healthy multifinger dynamic manipulation has barely enough neuromechanical degrees of freedom to meet the multiple demands of ecological tasks and critically depends on the continuous inhibition of synchronous grasp tendencies, which we speculate may be of vestigial evolutionary origin. PMID:22956798

Laboratory Investigation of Expansion and Venting and Plug Response in the MX Trench.

DTIC Science & Technology

1979-02-01

twnch is it hotoi. [’i’-t lb) W~ls t’olld(itd I-r il no0111a I 1rLt I I ,C tLit prl( SIrt OL’f 2 1 1 )S pi. SOil Irf1oil thi IL\\V 1 11051 F5S1 to Ua W...hloc ks bn,;ian to opc -n 111) . SCVCla Il add i tL/Io;il I .r [1ks Ircl :11 OSt immc!Ld 1;ltc lV. (The", (’[ll 1wscl cilsil :Vit t - i IhLc roof I

Evaluation of an Impedance Threshold Device as a VIIP Countermeasure

NASA Technical Reports Server (NTRS)

Ebert, Douglas; Macias, Brandon; Sargsyan, Ashot; Garcia, Kathleen; Stenger, Michael; Hargens, Alan; Johnston, Smith; Kemp, David; Danielson, Richard

2017-01-01

Visual Impairment/Intracranial Pressure (VIIP) is a top human spaceflight risk for which NASA does not currently have a proven mitigation strategy. Thigh cuffs and lower body negative pressure (LBNP) devices have been or are currently being evaluated as a means to reduce VIIP signs and symptoms, but these methods alone may not provide sufficient relief of cephalic venous congestion and VIIP symptoms. Additionally, current LBNP devices are too large and cumbersome for their systematic use as a countermeasure. Therefore, a novel approach is needed that is easy to implement and provides specific relief of symptoms. This investigation will evaluate an impedance threshold device (ITD) as a VIIP countermeasure.

Instantaneous brain dynamics mapped to a continuous state space.

PubMed

Billings, Jacob C W; Medda, Alessio; Shakil, Sadia; Shen, Xiaohong; Kashyap, Amrit; Chen, Shiyang; Abbas, Anzar; Zhang, Xiaodi; Nezafati, Maysam; Pan, Wen-Ju; Berman, Gordon J; Keilholz, Shella D

2017-11-15

Measures of whole-brain activity, from techniques such as functional Magnetic Resonance Imaging, provide a means to observe the brain's dynamical operations. However, interpretation of whole-brain dynamics has been stymied by the inherently high-dimensional structure of brain activity. The present research addresses this challenge through a series of scale transformations in the spectral, spatial, and relational domains. Instantaneous multispectral dynamics are first developed from input data via a wavelet filter bank. Voxel-level signals are then projected onto a representative set of spatially independent components. The correlation distance over the instantaneous wavelet-ICA state vectors is a graph that may be embedded onto a lower-dimensional space to assist the interpretation of state-space dynamics. Applying this procedure to a large sample of resting-state and task-active data (acquired through the Human Connectome Project), we segment the empirical state space into a continuum of stimulus-dependent brain states. Upon observing the local neighborhood of brain-states adopted subsequent to each stimulus, we may conclude that resting brain activity includes brain states that are, at times, similar to those adopted during tasks, but that are at other times distinct from task-active brain states. As task-active brain states often populate a local neighborhood, back-projection of segments of the dynamical state space onto the brain's surface reveals the patterns of brain activity that support many experimentally-defined states. Copyright © 2017 Elsevier Inc. All rights reserved.

Intelligent robot control using an adaptive critic with a task control center and dynamic database

NASA Astrophysics Data System (ADS)

Hall, E. L.; Ghaffari, M.; Liao, X.; Alhaj Ali, S. M.

2006-10-01

The purpose of this paper is to describe the design, development and simulation of a real time controller for an intelligent, vision guided robot. The use of a creative controller that can select its own tasks is demonstrated. This creative controller uses a task control center and dynamic database. The dynamic database stores both global environmental information and local information including the kinematic and dynamic models of the intelligent robot. The kinematic model is very useful for position control and simulations. However, models of the dynamics of the manipulators are needed for tracking control of the robot's motions. Such models are also necessary for sizing the actuators, tuning the controller, and achieving superior performance. Simulations of various control designs are shown. Also, much of the model has also been used for the actual prototype Bearcat Cub mobile robot. This vision guided robot was designed for the Intelligent Ground Vehicle Contest. A novel feature of the proposed approach is that the method is applicable to both robot arm manipulators and robot bases such as wheeled mobile robots. This generality should encourage the development of more mobile robots with manipulator capability since both models can be easily stored in the dynamic database. The multi task controller also permits wide applications. The use of manipulators and mobile bases with a high-level control are potentially useful for space exploration, certain rescue robots, defense robots, and medical robotics aids.

A Dynamic Connectome Supports the Emergence of Stable Computational Function of Neural Circuits through Reward-Based Learning.

PubMed

Kappel, David; Legenstein, Robert; Habenschuss, Stefan; Hsieh, Michael; Maass, Wolfgang

2018-01-01

Synaptic connections between neurons in the brain are dynamic because of continuously ongoing spine dynamics, axonal sprouting, and other processes. In fact, it was recently shown that the spontaneous synapse-autonomous component of spine dynamics is at least as large as the component that depends on the history of pre- and postsynaptic neural activity. These data are inconsistent with common models for network plasticity and raise the following questions: how can neural circuits maintain a stable computational function in spite of these continuously ongoing processes, and what could be functional uses of these ongoing processes? Here, we present a rigorous theoretical framework for these seemingly stochastic spine dynamics and rewiring processes in the context of reward-based learning tasks. We show that spontaneous synapse-autonomous processes, in combination with reward signals such as dopamine, can explain the capability of networks of neurons in the brain to configure themselves for specific computational tasks, and to compensate automatically for later changes in the network or task. Furthermore, we show theoretically and through computer simulations that stable computational performance is compatible with continuously ongoing synapse-autonomous changes. After reaching good computational performance it causes primarily a slow drift of network architecture and dynamics in task-irrelevant dimensions, as observed for neural activity in motor cortex and other areas. On the more abstract level of reinforcement learning the resulting model gives rise to an understanding of reward-driven network plasticity as continuous sampling of network configurations.

A Dynamic Connectome Supports the Emergence of Stable Computational Function of Neural Circuits through Reward-Based Learning

PubMed Central

Habenschuss, Stefan; Hsieh, Michael

2018-01-01

Synaptic connections between neurons in the brain are dynamic because of continuously ongoing spine dynamics, axonal sprouting, and other processes. In fact, it was recently shown that the spontaneous synapse-autonomous component of spine dynamics is at least as large as the component that depends on the history of pre- and postsynaptic neural activity. These data are inconsistent with common models for network plasticity and raise the following questions: how can neural circuits maintain a stable computational function in spite of these continuously ongoing processes, and what could be functional uses of these ongoing processes? Here, we present a rigorous theoretical framework for these seemingly stochastic spine dynamics and rewiring processes in the context of reward-based learning tasks. We show that spontaneous synapse-autonomous processes, in combination with reward signals such as dopamine, can explain the capability of networks of neurons in the brain to configure themselves for specific computational tasks, and to compensate automatically for later changes in the network or task. Furthermore, we show theoretically and through computer simulations that stable computational performance is compatible with continuously ongoing synapse-autonomous changes. After reaching good computational performance it causes primarily a slow drift of network architecture and dynamics in task-irrelevant dimensions, as observed for neural activity in motor cortex and other areas. On the more abstract level of reinforcement learning the resulting model gives rise to an understanding of reward-driven network plasticity as continuous sampling of network configurations. PMID:29696150

The Role of Dynamic Geometry Software in High School Geometry Curricula: An Analysis of Proof Tasks

ERIC Educational Resources Information Center

Oner, Diler

2009-01-01

In this study, I examine the role of dynamic geometry software (DGS) in curricular proof tasks. I investigated seven US high school geometry textbooks that were categorised into three groups: technology-intensive, standards-based, and traditional curricula. I looked at the frequency and purpose of DGS use in these textbooks. In addition, I…

Can Robots Help the Learning of Skilled Actions?

PubMed Central

Reinkensmeyer, David J.; Patton, James L.

2010-01-01

Learning to move skillfully requires that the motor system adjusts muscle commands based on ongoing performance errors, a process influenced by the dynamics of the task being practiced. Recent experiments from our laboratories show how robotic devices can temporarily alter task dynamics in ways that contribute to the motor learning experience, suggesting possible applications in rehabilitation and sports training. PMID:19098524

I. WORKING MEMORY CAPACITY IN CONTEXT: MODELING DYNAMIC PROCESSES OF BEHAVIOR, MEMORY, AND DEVELOPMENT.

PubMed

Simmering, Vanessa R

2016-09-01

Working memory is a vital cognitive skill that underlies a broad range of behaviors. Higher cognitive functions are reliably predicted by working memory measures from two domains: children's performance on complex span tasks, and infants' performance in looking paradigms. Despite the similar predictive power across these research areas, theories of working memory development have not connected these different task types and developmental periods. The current project takes a first step toward bridging this gap by presenting a process-oriented theory, focusing on two tasks designed to assess visual working memory capacity in infants (the change-preference task) versus children and adults (the change detection task). Previous studies have shown inconsistent results, with capacity estimates increasing from one to four items during infancy, but only two to three items during early childhood. A probable source of this discrepancy is the different task structures used with each age group, but prior theories were not sufficiently specific to explain how performance relates across tasks. The current theory focuses on cognitive dynamics, that is, how memory representations are formed, maintained, and used within specific task contexts over development. This theory was formalized in a computational model to generate three predictions: 1) capacity estimates in the change-preference task should continue to increase beyond infancy; 2) capacity estimates should be higher in the change-preference versus change detection task when tested within individuals; and 3) performance should correlate across tasks because both rely on the same underlying memory system. I also tested a fourth prediction, that development across tasks could be explained through increasing real-time stability, realized computationally as strengthening connectivity within the model. Results confirmed these predictions, supporting the cognitive dynamics account of performance and developmental changes in real-time stability. The monograph concludes with implications for understanding memory, behavior, and development in a broader range of cognitive development. © 2016 The Society for Research in Child Development, Inc.

Continuously Adaptive vs. Discrete Changes of Task Difficulty in the Training of a Complex Perceptual-Motor Task.

ERIC Educational Resources Information Center

Wood, Milton E.

The purpose of the effort was to determine the benefits to be derived from the adaptive training technique of automatically adjusting task difficulty as a function of a student skill during early learning of a complex perceptual motor task. A digital computer provided the task dynamics, scoring, and adaptive control of a second-order, two-axis,…

Human Guidance Behavior Decomposition and Modeling

NASA Astrophysics Data System (ADS)

Feit, Andrew James

Trained humans are capable of high performance, adaptable, and robust first-person dynamic motion guidance behavior. This behavior is exhibited in a wide variety of activities such as driving, piloting aircraft, skiing, biking, and many others. Human performance in such activities far exceeds the current capability of autonomous systems in terms of adaptability to new tasks, real-time motion planning, robustness, and trading safety for performance. The present work investigates the structure of human dynamic motion guidance that enables these performance qualities. This work uses a first-person experimental framework that presents a driving task to the subject, measuring control inputs, vehicle motion, and operator visual gaze movement. The resulting data is decomposed into subspace segment clusters that form primitive elements of action-perception interactive behavior. Subspace clusters are defined by both agent-environment system dynamic constraints and operator control strategies. A key contribution of this work is to define transitions between subspace cluster segments, or subgoals, as points where the set of active constraints, either system or operator defined, changes. This definition provides necessary conditions to determine transition points for a given task-environment scenario that allow a solution trajectory to be planned from known behavior elements. In addition, human gaze behavior during this task contains predictive behavior elements, indicating that the identified control modes are internally modeled. Based on these ideas, a generative, autonomous guidance framework is introduced that efficiently generates optimal dynamic motion behavior in new tasks. The new subgoal planning algorithm is shown to generate solutions to certain tasks more quickly than existing approaches currently used in robotics.

Functional coordination of muscles underlying changes in behavioural dynamics.

PubMed

Vernooij, Carlijn A; Rao, Guillaume; Perdikis, Dionysios; Huys, Raoul; Jirsa, Viktor K; Temprado, Jean-Jacques

2016-06-10

The dynamical systems approach addresses Bernstein's degrees of freedom problem by assuming that the neuro-musculo-skeletal system transiently assembles and dismantles its components into functional units (or synergies) to meet task demands. Strikingly, little is known from a dynamical point of view about the functioning of the muscular sub-system in this process. To investigate the interaction between the dynamical organisation at muscular and behavioural levels, we searched for specific signatures of a phase transition in muscular coordination when a transition is displayed at the behavioural level. Our results provide evidence that, during Fitts' task when behaviour switches to a different dynamical regime, muscular activation displays typical signatures of a phase transition; a reorganisation in muscular coordination patterns accompanied by a peak in the variability of muscle activation. This suggests that consistent changes occur in coordination processes across the different levels of description (i.e., behaviour and muscles). Specifically, in Fitts' task, target size acts as a control parameter that induces a destabilisation and a reorganisation of coordination patterns at different levels of the neuro-musculo-skeletal system.

Identification of Time-Varying Pilot Control Behavior in Multi-Axis Control Tasks

NASA Technical Reports Server (NTRS)

Zaal, Peter M. T.; Sweet, Barbara T.

2012-01-01

Recent developments in fly-by-wire control architectures for rotorcraft have introduced new interest in the identification of time-varying pilot control behavior in multi-axis control tasks. In this paper a maximum likelihood estimation method is used to estimate the parameters of a pilot model with time-dependent sigmoid functions to characterize time-varying human control behavior. An experiment was performed by 9 general aviation pilots who had to perform a simultaneous roll and pitch control task with time-varying aircraft dynamics. In 8 different conditions, the axis containing the time-varying dynamics and the growth factor of the dynamics were varied, allowing for an analysis of the performance of the estimation method when estimating time-dependent parameter functions. In addition, a detailed analysis of pilots adaptation to the time-varying aircraft dynamics in both the roll and pitch axes could be performed. Pilot control behavior in both axes was significantly affected by the time-varying aircraft dynamics in roll and pitch, and by the growth factor. The main effect was found in the axis that contained the time-varying dynamics. However, pilot control behavior also changed over time in the axis not containing the time-varying aircraft dynamics. This indicates that some cross coupling exists in the perception and control processes between the roll and pitch axes.

The Dynamic Multiprocess Framework: Evidence from Prospective Memory with Contextual Variability

PubMed Central

Scullin, Michael K.; McDaniel, Mark A.; Shelton, Jill Talley

2013-01-01

The ability to remember to execute delayed intentions is referred to as prospective memory. Previous theoretical and empirical work has focused on isolating whether a particular prospective memory task is supported either by effortful monitoring processes or by cue-driven spontaneous processes. In the present work, we advance the Dynamic Multiprocess Framework, which contends that both monitoring and spontaneous retrieval may be utilized dynamically to support prospective remembering. To capture the dynamic interplay between monitoring and spontaneous retrieval we had participants perform many ongoing tasks and told them that their prospective memory cue may occur in any context. Following either a 20-min or a 12-hr retention interval, the prospective memory cues were presented infrequently across three separate ongoing tasks. The monitoring patterns (measured as ongoing task cost relative to a between-subjects control condition) were consistent and robust across the three contexts. There was no evidence for monitoring prior to the initial prospective memory cue; however, individuals who successfully spontaneously retrieved the prospective memory intention, thereby realizing that prospective memory cues could be expected within that context, subsequently monitored. These data support the Dynamic Multiprocess Framework, which contends that individuals will engage monitoring when prospective memory cues are expected, disengage monitoring when cues are not expected, and that when monitoring is disengaged, a probabilistic spontaneous retrieval mechanism can support prospective remembering. PMID:23916951

High degree-of-freedom dynamic manipulation

NASA Astrophysics Data System (ADS)

Murphy, Michael P.; Stephens, Benjamin; Abe, Yeuhi; Rizzi, Alfred A.

2012-06-01

The creation of high degree of freedom dynamic mobile manipulation techniques and behaviors will allow robots to accomplish difficult tasks in the field. We are investigating the use of the body and legs of legged robots to improve the strength, velocity, and workspace of an integrated manipulator to accomplish dynamic manipulation. This is an especially challenging task, as all of the degrees of freedom are active at all times, the dynamic forces generated are high, and the legged system must maintain robust balance throughout the duration of the tasks. To accomplish this goal, we are utilizing trajectory optimization techniques to generate feasible open-loop behaviors for our 28 dof quadruped robot (BigDog) by planning the trajectories in a 13 dimensional space. Covariance Matrix Adaptation techniques are utilized to optimize for several criteria such as payload capability and task completion speed while also obeying constraints such as torque and velocity limits, kinematic limits, and center of pressure location. These open-loop behaviors are then used to generate feed-forward terms, which are subsequently used online to improve tracking and maintain low controller gains. Some initial results on one of our existing balancing quadruped robots with an additional human-arm-like manipulator are demonstrated on robot hardware, including dynamic lifting and throwing of heavy objects 16.5kg cinder blocks, using motions that resemble a human athlete more than typical robotic motions. Increased payload capacity is accomplished through coordinated body motion.

The Question Shapes the Answer: The Neural Correlates of Task Differences Reveal Dynamic Semantic Processing

ERIC Educational Resources Information Center

Hargreaves, Ian S.; White, Michelle; Pexman, Penny M.; Pittman, Dan; Goodyear, Brad G.

2012-01-01

Task effects in semantic processing were investigated by contrasting the neural activation associated with two semantic categorization tasks (SCT) using event-related fMRI. The two SCTs involved different decision categories: "is it an animal?" vs. "is it a concrete thing?" Participants completed both tasks and, across participants, the same core…

Development and validation of methods for man-made machine interface evaluation. [for shuttles and shuttle payloads

NASA Technical Reports Server (NTRS)

Malone, T. B.; Micocci, A.

1975-01-01

The alternate methods of conducting a man-machine interface evaluation are classified as static and dynamic, and are evaluated. A dynamic evaluation tool is presented to provide for a determination of the effectiveness of the man-machine interface in terms of the sequence of operations (task and task sequences) and in terms of the physical characteristics of the interface. This dynamic checklist approach is recommended for shuttle and shuttle payload man-machine interface evaluations based on reduced preparation time, reduced data, and increased sensitivity of critical problems.

Dynamic Task Allocation in Multi-Hop Multimedia Wireless Sensor Networks with Low Mobility

PubMed Central

Jin, Yichao; Vural, Serdar; Gluhak, Alexander; Moessner, Klaus

2013-01-01

This paper presents a task allocation-oriented framework to enable efficient in-network processing and cost-effective multi-hop resource sharing for dynamic multi-hop multimedia wireless sensor networks with low node mobility, e.g., pedestrian speeds. The proposed system incorporates a fast task reallocation algorithm to quickly recover from possible network service disruptions, such as node or link failures. An evolutional self-learning mechanism based on a genetic algorithm continuously adapts the system parameters in order to meet the desired application delay requirements, while also achieving a sufficiently long network lifetime. Since the algorithm runtime incurs considerable time delay while updating task assignments, we introduce an adaptive window size to limit the delay periods and ensure an up-to-date solution based on node mobility patterns and device processing capabilities. To the best of our knowledge, this is the first study that yields multi-objective task allocation in a mobile multi-hop wireless environment under dynamic conditions. Simulations are performed in various settings, and the results show considerable performance improvement in extending network lifetime compared to heuristic mechanisms. Furthermore, the proposed framework provides noticeable reduction in the frequency of missing application deadlines. PMID:24135992

Effect of pencil grasp on the speed and legibility of handwriting after a 10-minute copy task in Grade 4 children.

PubMed

Schwellnus, Heidi; Carnahan, Heather; Kushki, Azadeh; Polatajko, Helene; Missiuna, Cheryl; Chau, Tom

2012-06-01

To investigate the impact of common pencil grasp patterns on the speed and legibility of handwriting after a 10-minute copy task, intended to induce muscle fatigue, in typically developing children and in those non-proficient in handwriting. A total of 120 Grade 4 students completed a standardised handwriting assessment before and after a 10-minute copy task. The students indicated the perceived difficulty of the handwriting task at baseline and after 10 minutes. The students also completed a self-report questionnaire regarding their handwriting proficiency upon completion. The majority of the students rated higher effort after the 10-minute copy task than at baseline (rank sum: P = 0.00001). The effort ratings were similar for the different grasp patterns (multiple linear regression: F = 0.37, P = 0.895). For both typically developing children and those with handwriting issues, the legibility of the writing samples decreased after the 10-minute copy task but the speed of writing increased. CONCLUSIONS AND SIGNIFICANCE OF THE STUDY: The quality of the handwriting decreased after the 10-minute copy task; however, there was no difference in the quality or speed scores among the different pencil grasps before and after the copy task. The dynamic tripod pencil grasp did not offer any advantage over the lateral tripod or the dynamic or lateral quadrupod pencil grasps in terms of quality of handwriting after a 10-minute copy task. These four pencil grasp patterns performed equivalently. Our findings question the practice of having students adopt the dynamic tripod pencil grasp. © 2012 The Authors Australian Occupational Therapy Journal © 2012 Occupational Therapy Australia.

Managing Multiple Tasks in Complex, Dynamic Environments

NASA Technical Reports Server (NTRS)

Freed, Michael; Null, Cynthia H. (Technical Monitor)

1998-01-01

Sketchy planners are designed to achieve goals in realistically complex, time-pressured, and uncertain task environments. However, the ability to manage multiple, potentially interacting tasks in such environments requires extensions to the functionality these systems typically provide. This paper identifies a number of factors affecting how interacting tasks should be prioritized, interrupted, and resumed, and then describes a sketchy planner called APEX that takes account of these factors when managing multiple tasks.

Inter-subject phase synchronization for exploratory analysis of task-fMRI.

PubMed

Bolt, Taylor; Nomi, Jason S; Vij, Shruti G; Chang, Catie; Uddin, Lucina Q

2018-08-01

Analysis of task-based fMRI data is conventionally carried out using a hypothesis-driven approach, where blood-oxygen-level dependent (BOLD) time courses are correlated with a hypothesized temporal structure. In some experimental designs, this temporal structure can be difficult to define. In other cases, experimenters may wish to take a more exploratory, data-driven approach to detecting task-driven BOLD activity. In this study, we demonstrate the efficiency and power of an inter-subject synchronization approach for exploratory analysis of task-based fMRI data. Combining the tools of instantaneous phase synchronization and independent component analysis, we characterize whole-brain task-driven responses in terms of group-wise similarity in temporal signal dynamics of brain networks. We applied this framework to fMRI data collected during performance of a simple motor task and a social cognitive task. Analyses using an inter-subject phase synchronization approach revealed a large number of brain networks that dynamically synchronized to various features of the task, often not predicted by the hypothesized temporal structure of the task. We suggest that this methodological framework, along with readily available tools in the fMRI community, provides a powerful exploratory, data-driven approach for analysis of task-driven BOLD activity. Copyright © 2018 Elsevier Inc. All rights reserved.

Optimal dynamic voltage scaling for wireless sensor nodes with real-time constraints

NASA Astrophysics Data System (ADS)

Cassandras, Christos G.; Zhuang, Shixin

2005-11-01

Sensors are increasingly embedded in manufacturing systems and wirelessly networked to monitor and manage operations ranging from process and inventory control to tracking equipment and even post-manufacturing product monitoring. In building such sensor networks, a critical issue is the limited and hard to replenish energy in the devices involved. Dynamic voltage scaling is a technique that controls the operating voltage of a processor to provide desired performance while conserving energy and prolonging the overall network's lifetime. We consider such power-limited devices processing time-critical tasks which are non-preemptive, aperiodic and have uncertain arrival times. We treat voltage scaling as a dynamic optimization problem whose objective is to minimize energy consumption subject to hard or soft real-time execution constraints. In the case of hard constraints, we build on prior work (which engages a voltage scaling controller at task completion times) by developing an intra-task controller that acts at all arrival times of incoming tasks. We show that this optimization problem can be decomposed into two simpler ones whose solution leads to an algorithm that does not actually require solving any nonlinear programming problems. In the case of soft constraints, this decomposition must be partly relaxed, but it still leads to a scalable (linear in the number of tasks) algorithm. Simulation results are provided to illustrate performance improvements in systems with intra-task controllers compared to uncontrolled systems or those using inter-task control.

Static and dynamic posture control in postlingual cochlear implanted patients: effects of dual-tasking, visual and auditory inputs suppression

PubMed Central

Bernard-Demanze, Laurence; Léonard, Jacques; Dumitrescu, Michel; Meller, Renaud; Magnan, Jacques; Lacour, Michel

2014-01-01

Posture control is based on central integration of multisensory inputs, and on internal representation of body orientation in space. This multisensory feedback regulates posture control and continuously updates the internal model of body's position which in turn forwards motor commands adapted to the environmental context and constraints. The peripheral localization of the vestibular system, close to the cochlea, makes vestibular damage possible following cochlear implant (CI) surgery. Impaired vestibular function in CI patients, if any, may have a strong impact on posture stability. The simple postural task of quiet standing is generally paired with cognitive activity in most day life conditions, leading therefore to competition for attentional resources in dual-tasking, and increased risk of fall particularly in patients with impaired vestibular function. This study was aimed at evaluating the effects of postlingual cochlear implantation on posture control in adult deaf patients. Possible impairment of vestibular function was assessed by comparing the postural performance of patients to that of age-matched healthy subjects during a simple postural task performed in static (stable platform) and dynamic (platform in translation) conditions, and during dual-tasking with a visual or auditory memory task. Postural tests were done in eyes open (EO) and eyes closed (EC) conditions, with the CI activated (ON) or not (OFF). Results showed that the postural performance of the CI patients strongly differed from the controls, mainly in the EC condition. The CI patients showed significantly reduced limits of stability and increased postural instability in static conditions. In dynamic conditions, they spent considerably more energy to maintain equilibrium, and their head was stabilized neither in space nor on trunk: they behaved dynamically without vision like an inverted pendulum while the controls showed a whole body rigidification strategy. Hearing (prosthesis on) as well as dual-tasking did not really improve the dynamic postural performance of the CI patients. We conclude that CI patients become strongly visual dependent mainly in challenging postural conditions, a result they have to be awarded of particularly when getting older. PMID:24474907

Static and dynamic posture control in postlingual cochlear implanted patients: effects of dual-tasking, visual and auditory inputs suppression.

PubMed

Bernard-Demanze, Laurence; Léonard, Jacques; Dumitrescu, Michel; Meller, Renaud; Magnan, Jacques; Lacour, Michel

2013-01-01

Posture control is based on central integration of multisensory inputs, and on internal representation of body orientation in space. This multisensory feedback regulates posture control and continuously updates the internal model of body's position which in turn forwards motor commands adapted to the environmental context and constraints. The peripheral localization of the vestibular system, close to the cochlea, makes vestibular damage possible following cochlear implant (CI) surgery. Impaired vestibular function in CI patients, if any, may have a strong impact on posture stability. The simple postural task of quiet standing is generally paired with cognitive activity in most day life conditions, leading therefore to competition for attentional resources in dual-tasking, and increased risk of fall particularly in patients with impaired vestibular function. This study was aimed at evaluating the effects of postlingual cochlear implantation on posture control in adult deaf patients. Possible impairment of vestibular function was assessed by comparing the postural performance of patients to that of age-matched healthy subjects during a simple postural task performed in static (stable platform) and dynamic (platform in translation) conditions, and during dual-tasking with a visual or auditory memory task. Postural tests were done in eyes open (EO) and eyes closed (EC) conditions, with the CI activated (ON) or not (OFF). Results showed that the postural performance of the CI patients strongly differed from the controls, mainly in the EC condition. The CI patients showed significantly reduced limits of stability and increased postural instability in static conditions. In dynamic conditions, they spent considerably more energy to maintain equilibrium, and their head was stabilized neither in space nor on trunk: they behaved dynamically without vision like an inverted pendulum while the controls showed a whole body rigidification strategy. Hearing (prosthesis on) as well as dual-tasking did not really improve the dynamic postural performance of the CI patients. We conclude that CI patients become strongly visual dependent mainly in challenging postural conditions, a result they have to be awarded of particularly when getting older.

Flexible establishment of functional brain networks supports attentional modulation of unconscious cognition.

PubMed

Ulrich, Martin; Adams, Sarah C; Kiefer, Markus

2014-11-01

In classical theories of attention, unconscious automatic processes are thought to be independent of higher-level attentional influences. Here, we propose that unconscious processing depends on attentional enhancement of task-congruent processing pathways implemented by a dynamic modulation of the functional communication between brain regions. Using functional magnetic resonance imaging, we tested our model with a subliminally primed lexical decision task preceded by an induction task preparing either a semantic or a perceptual task set. Subliminal semantic priming was significantly greater after semantic compared to perceptual induction in ventral occipito-temporal (vOT) and inferior frontal cortex, brain areas known to be involved in semantic processing. The functional connectivity pattern of vOT varied depending on the induction task and successfully predicted the magnitude of behavioral and neural priming. Together, these findings support the proposal that dynamic establishment of functional networks by task sets is an important mechanism in the attentional control of unconscious processing. © 2014 Wiley Periodicals, Inc.

Degradation of learned skills. Effectiveness of practice methods on simulated space flight skill retention

NASA Technical Reports Server (NTRS)

Sitterley, T. E.; Berge, W. A.

1972-01-01

Manual flight control and emergency procedure task skill degradation was evaluated after time intervals of from 1 to 6 months. The tasks were associated with a simulated launch through the orbit insertion flight phase of a space vehicle. The results showed that acceptable flight control performance was retained for 2 months, rapidly deteriorating thereafter by a factor of 1.7 to 3.1 depending on the performance measure used. Procedural task performance showed unacceptable degradation after only 1 month, and exceeded an order of magnitude after 4 months. The effectiveness of static rehearsal (checklists and briefings) and dynamic warmup (simulator practice) retraining methods were compared for the two tasks. Static rehearsal effectively countered procedural skill degradation, while some combination of dynamic warmup appeared necessary for flight control skill retention. It was apparent that these differences between methods were not solely a function of task type or retraining method, but were a function of the performance measures used for each task.

SRM Internal Flow Test and Computational Fluid Dynamic Analysis. Volume 1; Major Task Summaries

NASA Technical Reports Server (NTRS)

Whitesides, R. Harold; Dill, Richard A.; Purinton, David C.

1995-01-01

During the four year period of performance for NASA contract, NASB-39095, ERC has performed a wide variety of tasks to support the design and continued development of new and existing solid rocket motors and the resolution of operational problems associated with existing solid rocket motor's at NASA MSFC. This report summarizes the support provided to NASA MSFC during the contractual period of performance. The report is divided into three main sections. The first section presents summaries for the major tasks performed. These tasks are grouped into three major categories: full scale motor analysis, subscale motor analysis and cold flow analysis. The second section includes summaries describing the computational fluid dynamics (CFD) tasks performed. The third section, the appendices of the report, presents detailed descriptions of the analysis efforts as well as published papers, memoranda and final reports associated with specific tasks. These appendices are referenced in the summaries. The subsection numbers for the three sections correspond to the same topics for direct cross referencing.

Augmented Go/No-Go Task: Mouse Cursor Motion Measures Improve ADHD Symptom Assessment in Healthy College Students

PubMed Central

Leontyev, Anton; Sun, Stanley; Wolfe, Mary; Yamauchi, Takashi

2018-01-01

Attention deficit/hyperactivity disorder (ADHD) is frequently characterized as a disorder of executive function (EF). However, behavioral tests of EF, such as go/No-go tasks, often fail to grasp the deficiency in EF revealed by questionnaire-based measures. This inability is usually attributed to questionnaires and behavioral tasks assessing different constructs of EFs. We propose an additional explanation for this discrepancy. We hypothesize that this problem stems from the lack of dynamic assessment of decision-making (e.g., continuous monitoring of motor behavior such as velocity and acceleration in choice reaching) in classical versions of behavioral tasks. We test this hypothesis by introducing dynamic assessment in the form of mouse motion in a go/No-go task. Our results indicate that, among healthy college students, self-report measures of ADHD symptoms become strongly associated with performance in behavioral tasks when continuous assessment (e.g., acceleration in the mouse-cursor motion) is introduced. PMID:29695985

Augmented Go/No-Go Task: Mouse Cursor Motion Measures Improve ADHD Symptom Assessment in Healthy College Students.

PubMed

Leontyev, Anton; Sun, Stanley; Wolfe, Mary; Yamauchi, Takashi

2018-01-01

Attention deficit/hyperactivity disorder (ADHD) is frequently characterized as a disorder of executive function (EF). However, behavioral tests of EF, such as go/No-go tasks, often fail to grasp the deficiency in EF revealed by questionnaire-based measures. This inability is usually attributed to questionnaires and behavioral tasks assessing different constructs of EFs. We propose an additional explanation for this discrepancy. We hypothesize that this problem stems from the lack of dynamic assessment of decision-making (e.g., continuous monitoring of motor behavior such as velocity and acceleration in choice reaching) in classical versions of behavioral tasks. We test this hypothesis by introducing dynamic assessment in the form of mouse motion in a go/No-go task. Our results indicate that, among healthy college students, self-report measures of ADHD symptoms become strongly associated with performance in behavioral tasks when continuous assessment (e.g., acceleration in the mouse-cursor motion) is introduced.

Visual-motor response of crewmen during a simulated 90-day space mission as measured by the critical task battery

NASA Technical Reports Server (NTRS)

Allen, R. W.; Jex, H. R.

1973-01-01

In order to test various components of a regenerative life support system and to obtain data on the physiological and psychological effects of long duration exposure to confinement in a space station atmosphere, four carefully screened young men were sealed in a space station simulator for 90 days and administered a tracking test battery. The battery included a clinical test (Critical Instability Task) designed to measure a subject's dynamic time delay, and a more conventional steady tracking task, during which dynamic response (describing functions) and performance measures were obtained. Good correlation was noted between the clinical critical instability scores and more detailed tracking parameters such as dynamic time delay and gain-crossover frequency. The levels of each parameter span the range observed with professional pilots and astronaut candidates tested previously. The chamber environment caused no significant decrement on the average crewman's dynamic response behavior, and the subjects continued to improve slightly in their tracking skills during the 90-day confinement period.

Functional split brain in a driving/listening paradigm

PubMed Central

Boly, Melanie; Mensen, Armand; Tononi, Giulio

2016-01-01

We often engage in two concurrent but unrelated activities, such as driving on a quiet road while listening to the radio. When we do so, does our brain split into functionally distinct entities? To address this question, we imaged brain activity with fMRI in experienced drivers engaged in a driving simulator while listening either to global positioning system instructions (integrated task) or to a radio show (split task). We found that, compared with the integrated task, the split task was characterized by reduced multivariate functional connectivity between the driving and listening networks. Furthermore, the integrated information content of the two networks, predicting their joint dynamics above and beyond their independent dynamics, was high in the integrated task and zero in the split task. Finally, individual subjects’ ability to switch between high and low information integration predicted their driving performance across integrated and split tasks. This study raises the possibility that under certain conditions of daily life, a single brain may support two independent functional streams, a “functional split brain” similar to what is observed in patients with an anatomical split. PMID:27911805

Functional split brain in a driving/listening paradigm.

PubMed

Sasai, Shuntaro; Boly, Melanie; Mensen, Armand; Tononi, Giulio

2016-12-13

We often engage in two concurrent but unrelated activities, such as driving on a quiet road while listening to the radio. When we do so, does our brain split into functionally distinct entities? To address this question, we imaged brain activity with fMRI in experienced drivers engaged in a driving simulator while listening either to global positioning system instructions (integrated task) or to a radio show (split task). We found that, compared with the integrated task, the split task was characterized by reduced multivariate functional connectivity between the driving and listening networks. Furthermore, the integrated information content of the two networks, predicting their joint dynamics above and beyond their independent dynamics, was high in the integrated task and zero in the split task. Finally, individual subjects' ability to switch between high and low information integration predicted their driving performance across integrated and split tasks. This study raises the possibility that under certain conditions of daily life, a single brain may support two independent functional streams, a "functional split brain" similar to what is observed in patients with an anatomical split.

Dynamic inverse models in human-cyber-physical systems

NASA Astrophysics Data System (ADS)

Robinson, Ryan M.; Scobee, Dexter R. R.; Burden, Samuel A.; Sastry, S. Shankar

2016-05-01

Human interaction with the physical world is increasingly mediated by automation. This interaction is characterized by dynamic coupling between robotic (i.e. cyber) and neuromechanical (i.e. human) decision-making agents. Guaranteeing performance of such human-cyber-physical systems will require predictive mathematical models of this dynamic coupling. Toward this end, we propose a rapprochement between robotics and neuromechanics premised on the existence of internal forward and inverse models in the human agent. We hypothesize that, in tele-robotic applications of interest, a human operator learns to invert automation dynamics, directly translating from desired task to required control input. By formulating the model inversion problem in the context of a tracking task for a nonlinear control system in control-a_ne form, we derive criteria for exponential tracking and show that the resulting dynamic inverse model generally renders a portion of the physical system state (i.e., the internal dynamics) unobservable from the human operator's perspective. Under stability conditions, we show that the human can achieve exponential tracking without formulating an estimate of the system's state so long as they possess an accurate model of the system's dynamics. These theoretical results are illustrated using a planar quadrotor example. We then demonstrate that the automation can intervene to improve performance of the tracking task by solving an optimal control problem. Performance is guaranteed to improve under the assumption that the human learns and inverts the dynamic model of the altered system. We conclude with a discussion of practical limitations that may hinder exact dynamic model inversion.