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At least 1,531 records · Page 85Linked to original sources
PubMed2000

Frequency selectivity as a function of level and frequency measured with uniformly exciting notched noise.

Thresholds for detecting sinusoidal signals were measured as a function of the spectral width of a notch in a noise masker. The notch was positioned both symmetrically and asymmetrically around the signal frequency. The noise was designed to create equal excitation per ERB within its passbands (uniformly exciting noise), after allowing for the transfer function of the headphone and the middle ear. For a signal frequency of 250 Hz, the level per ERB ranged from 35 to 80 dB in 15-dB steps. For signal frequencies of 500, 1,000, 2,000, and 4,000 Hz, the level per ERB ranged from 40 to 70 dB per ERB in 15-dB steps. Auditory filter shapes were derived from the data by modeling the auditory filter as the sum of a sharply tuned tip filter and a broader tail filter. The gain of the tip filter was assumed to be a function of level. The shape of the tip filter and the gain and shape of the tail filter were assumed to be level independent. The data for all levels were fitted simultaneously. The data were fitted best when the gain of the tip filter was assumed to be a function of the signal level (as opposed to the masker level per ERB). The filter shapes showed a level dependence that qualitatively resembled the level dependence of filtering on the basilar membrane. The maximum gain of the tip filter tended to increase with increasing center frequency up to 1 kHz, but to remain roughly constant for higher frequencies.

Adult↗
PubMed2002

Auditory filter shapes for the bottlenose dolphin (Tursiops truncatus) and the white whale (Delphinapterus leucas) derived with notched noise.

Auditory filter shapes were estimated in two bottlenose dolphins (Tursiops truncatus) and one white whale (Delphinapterus leucas) using a behavioral response paradigm and notched noise. Masked thresholds were measured at 20 and 30 kHz. Masking noise was centered at the test tone and had a bandwidth of 1.5 times the tone frequency. Half-notch width to center frequency ratios were 0, 0.125, 0.25, 0.375, and 0.5. Noise spectral density levels were 90 and 105 dB re: 1 microPa2/Hz. Filter shapes were approximated using a roex(p,r) function; the parameters p and r were found by fitting the integral of the roex(p,r) function to the measured threshold data. Mean equivalent rectangular bandwidths (ERBs) calculated from the filter shapes were 11.8 and 17.1% of the center frequency at 20 and 30 kHz, respectively, for the dolphins and 9.1 and 15.3% of the center frequency at 20 and 30 kHz, respectively, for the white whale. Filter shapes were broader at 30 kHz and 105 dB re: 1 microPa2/Hz masking noise. The results are in general agreement with previous estimates of ERBs in Tursiops obtained with a behavioral response paradigm.

Animals↗
PubMed2006

Auditory filter nonlinearity across frequency using simultaneous notched-noise masking.

Psychoacoustic masking experiments have been widely used to investigate cochlear function in human listeners. Here we use simultaneous notched-noise masking experiments in normal hearing listeners to characterize the changes in auditory filter shape with stimulus level over the frequency range 0.25-6 kHz. At each frequency a range of fixed signal levels (30-70 dB SPL) and fixed masker levels (20-50 dB SPL spectrum level) are used in order to obtain accurate descriptions of the filter shapes in individual listeners. The notched-noise data for individual listeners are fitted with two filter shape models: a rounded exponential (roex) shape in which the filter skirt changes as a linear function of probe-tone level and the other, in which the gain of the tip filter relative to the filter tail changes as a function of signal level [Glasberg and Moore, J. Acoust. Soc. Am. 108, 2318-2328 (2000)]. The parameters for these fitted models are then described with a simple set of equations that quantify the changes in auditory filter shape across level and frequency. Both these models fitted the data equally well and both demonstrated increasing tip-tail gain as frequency increased.

Adult↗
PubMed1997

Relations between notched-noise suppressed TEOAE and the psychoacoustical critical bandwidth.

Narrow-band transitory evoked otoacoustic emissions (TEOAE) were recorded for nine normal hearing subjects in the presence of a broadband tone complex suppressor. Introducing a spectral notch at the frequency of the narrow-band stimulus causes the suppression effect to decrease, the more so the wider the notch. This decrease in suppression permits an estimate of the size of one critical band. One advantage of this approach is that no active participation of the subjects is required. The estimated critical bandwidth is then compared with independent estimates based on a simultaneous masking experiment, using the same stimuli. The two measures of the critical bandwidth coincide well for those six subjects with spontaneous otoacoustic emissions. However, the bandwidth estimate based on the OAE measurements is too large for the other three subjects without spontaneous emissions. Simulations of the suppression effect with a driven van der Pol oscillator with moderate undamping produce critical bandwidth estimates consistent with those observed in the psychoacoustical experiments. This allows an estimate of the "effective" amount of undamping on the basilar membrane that is required to produce the critical bandwidth observable in psychoacoustic experiments.

Acoustic Stimulation↗
PubMed2005

Kaposi's sarcoma-associated herpesvirus reactivation is regulated by interaction of latency-associated nuclear antigen with recombination signal sequence-binding protein Jkappa, the major downstream effector of the Notch signaling pathway.

Kaposi's sarcoma-associated herpesvirus (KSHV) is the major biological cofactor contributing to development of Kaposi's sarcoma. KSHV establishes a latent infection in human B cells expressing the latency-associated nuclear antigen (LANA), a critical factor in the regulation of viral latency. LANA controls KSHV latent infection through repression of RTA, an activator of many lytic promoters. RTA activates the expression of several lytic viral genes by interacting with recombination signal sequence-binding protein Jkappa (RBP-Jkappa), a transcriptional repressor and the target of the Notch signaling pathway. The recognition that a number of KSHV lytic gene promoters, including RTA, contain RBP-Jkappa binding sites raised the possibility that RBP-Jkappa-mediated repression may be central to the establishment of latency. Here, we tested this hypothesis by examining the regulation of RTA by LANA through binding to RBP-Jkappa. This study demonstrates that LANA physically associates with RBP-Jkappa in vitro and in KSHV-infected cells, with the complex formed capable of binding to RBP-Jkappa cognate sequences. RBP-Jkappa binding sites within the RTA promoter have been found to be critical for LANA-mediated repression. Our study describes a novel mechanism through which LANA maintains KSHV latency by targeting a major downstream effector of the Notch signaling pathway.

Antigens, Viral↗
PubMed1987

Restriction of P-element insertions at the Notch locus of Drosophila melanogaster.

P elements move about the Drosophila melanogaster genome in a nonrandom fashion, preferring some chromosomal targets for insertion over others (J. C. J. Eeken, F. H. Sobels, V. Hyland, and A. P. Schalet, Mutat. Res. 150:261-275, 1985; W. R. Engels, Annu. Rev. Genet. 17:315-344, 1983; M. D. Golubovsky, Y. N. Ivanov, and M. M. Green, Proc. Natl. Acad. Sci. USA 74:2973-2975, 1977; M. J. Simmons and J. K. Lim, Proc. Natl. Acad. Sci. USA 77:6042-6046, 1980). Some of this specificity may be due to recognition of a particular DNA sequence in the target DNA; derivatives of an 8-base-pair consensus sequence are occupied by these transposable elements at many different chromosomal locations (K. O'Hare and G. M. Rubin, Cell 34:25-36, 1983). An additional level of specificity of P-element insertions is described in this paper. Of 14 mutations induced in the complex locus Notch by hybrid dysgenesis, 13 involved P-element insertions at or near the transcription start site of the gene. This clustering was not seen in other transposable element-induced mutations of Notch. DNA sequences homologous to the previously described consensus target for P-element insertion are not preferentially located in this region of the locus. The choice of a chromosomal site for integration appears to be based on more subtle variations in chromosome structure that are probably associated with activation or expression of the target gene.

Animals↗
PubMed1999

Decreased amplitude of left ventricular posterior wall motion with notch movement to determine the left posterior septal accessory pathway in Wolff-Parkinson-White syndrome.

OBJECTIVE: To determine preoperatively, by analysing asynchronous left ventricular wall motion, whether to approach through the right ventricle or the left ventricle when carrying out catheter ablation of the accessory pathway in Wolff-Parkinson-White syndrome, especially in patients with the pathway located on the septum. METHODS: 73 patients with manifest Wolff-Parkinson-White syndrome who underwent successful catheter ablation were studied. Location of accessory pathway was classified as right ventricular side: right anterior paraseptum, right anterior, right lateral, right posterior, anterior septum, midseptum, right posterior septum; left ventricular side: left posterior septum, left posterior, left lateral, left anterior. Asynchronous systolic wall motion was analysed by cross sectional echocardiography. RESULTS: Echocardiography showed that the amplitude of left ventricular posterior systolic wall motion was reduced when the pathway was located on the left ventricular side as opposed to the right ventricular side (mean (SD), 11.1 (1.7) v 12.9 (1.1) mm, p < 0.001), especially in patients with left posterior septal accessory pathway (9.7 (0.8) mm). There were no overlapping values between the left posterior septal accessory pathway and the right ventricular side accessory pathway. Posterior wall notch motion was observed in all patients with a left posterior septal accessory pathway (9/9), but not at all in patients with pathways located on the right ventricular side of the septum. In patients with a septal accessory pathway, an ECG algorithm provided poor information (relatively low sensitivity, specificity, and predictive value) for determining whether the subsite faced either the left (left posterior septum) or the right ventricle (anterior septum, midseptum, right posterior septum). CONCLUSIONS: Decreased amplitude of left ventricular posterior wall motion with notch movement is an important finding for accessory pathways located on the left posterior septum. These findings provided clinically useful information for determining whether to approach catheter ablation from the right or the left ventricle.

Adolescent↗
PubMed2000

Delta-Notch lateral inhibitory patterning in the emergence of ciliated cells in Xenopus: experimental observations and a gene network model.

In diverse vertebrate and invertebrate systems, lateral inhibition through the Delta-Notch signaling pathway can lead to cells in initially uniform epithelial tissues differentiating in "salt-and-pepper", regular spacing patterns. In this paper we examine lateral inhibition during the emergence of ciliated cells in Xenopus embryonic skin, using experimental manipulations of the Delta-Notch pathway and a connectionist gene-network model of the process. The results of our model are in agreement with previous models of regular patterning through lateral inhibition and reproduce the observations of our experimental assays. Moreover, the model provides an account for the variability of embryonic responses to the experimental assays, points to a component of lateral inhibition that may be the chief source of this variability, and suggests ways to control it. Our model could thus serve as a tool to generate predictions about this and other regular patterning systems governed by lateral inhibition.

Animals↗
PubMed1979

Exaggerated anterior vertebral notching.

Three children with marrow-packing disorders demonstrated exaggerated anterior vertebral notches with poorly defined cortical margins. One child had thalassemia major, another had Gaucher disease, and a third had metastatic neuroblastoma. A discussion of each case and the etiology of the notches is presented.

Bone Neoplasms↗
PubMed2001

First-pass myocardial perfusion MR imaging with interleaved notched saturation: feasibility study.

The authors evaluated a magnetization preparation scheme with a "notched" section profile for T1-weighted first-pass myocardial perfusion magnetic resonance (MR) imaging at 1.5 T. The pulse sequence consisted of a preparation sequence followed by an interleaved gradient-echo echo-planar sequence. Image contrast was evaluated in a feasibility study in 12 adult patients. The notched saturation pulse allowed long magnetization recovery times without sacrificing section coverage. Image contrast between normal and ischemic myocardium was excellent.

Adenosine↗
PubMed1996

I(to) and action potential notch are smaller in left vs. right canine ventricular epicardium.

Transmural heterogeneities of repolarizing currents underlie prominent differences in the electrophysiology and pharmacology of ventricular epicardial, endocardial, and M cells in a number of species. The degree to which heterogeneities exist between the right and left ventricles is not well appreciated. The present study uses standard microelectrode and whole cell patch-clamp techniques to contrast the electrophysiological characteristics and pharmacological responsiveness of tissues and myocytes isolated from right (RVE) and left canine ventricular epicardium (LVE). RVE and LVE studied under nearly identical conditions displayed major differences in the early repolarizing phases of the action potential. The magnitude of phase 1 in RVE was nearly threefold that in LVE: 28.7 +/- 6.2 vs. 10.6 +/- 4.1 mV (basic cycle length = 2,000 ms). Phase 1 in RVE was also more sensitive to alterations of the stimulation rate and to 4-aminopyridine (4-AP), suggesting a much greater contribution of the transient outward current (I(to) 1) in RVE than in LVE. The combination of 4-AP plus ryanodine, low chloride, or 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (chloride channel blocker) completely eliminated the notch and all rate dependence of the early phases of the action potential, making RVE and LVE indistinguishable. At +70 mV, RVE myocytes displayed peak I(to) 1 densities between 28 and 37 pA/pF. LVE myocytes included cells with similar I(to) 1 densities (thought to represent subsurface cells) but also cells with much smaller current levels (thought to represent surface cells). Average peak I(to) 1 density was significantly smaller in LVE than in RVE at voltages more than or equal to +10 mV. Our data point to prominent differences in the magnitude of the I(to) 1-mediated action potential notch in cells at the surface of RVE compared with the LVE and suggest that important distinctions may exist in the response of these two tissues to pharmacological agents and pathophysiological states, as previously demonstrated for epicardium and endocardium. Our findings also suggest that a calcium-activated outward current contributes to the early repolarization phase in RVE and LVE and that the influence of this current, although small, is more important in the left ventricle.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed2006

Notch signaling in astrocytes and neuroblasts of the adult subventricular zone in health and after cortical injury.

The postnatal subventricular zone (SVZ) is a niche for continuous neurogenesis in the adult brain and likely plays a fundamental role in self-repair responses in neurodegenerative conditions. Maintenance of the pool of neural stem cells within this area depends on cell-cell communication such as that provided by the Notch signaling pathway. Notch1 receptor mRNA has been found distributed in different areas of the postnatal brain including the SVZ. Although the identity of Notch1-expressing cells has been established in the majority of these areas, it is still unclear what cell types within the SVZ are expressing components of this pathway. Here we demonstrate that most of expression of Notch1 in the adult SVZ occurs in polysialylated neural cell adhesion molecule (PSA-NCAM)-positive neural precursors and in glial fibrillary acidic protein-positive SVZ astrocytes. Notch1 was also found in PSA-NCAM-positive neuroblasts located within the rostral migratory stream (RMS) but much less in those that have reached the olfactory bulb. We show that two of the naturally occurring Notch1 activators, Jagged1 and Delta1, are also expressed in the SVZ and within the RMS in the adult mouse brain. Finally, using a model of cortical stab wound, we show that the astrogliogenic response of the SVZ to injury is accompanied by activation of the Notch pathway.

Animals↗
PubMed1995

Locational relationship of the supraorbital notch or foramen and infraorbital and mental foramina in Koreans.

The morphology and locational relationship of the supraorbital notch/foramen, infraorbital foramen, and mental foramen were studied from photographs of 124 Korean skulls (male 35, female 18, unknown sex 71). The infraorbital foramen was on the sagittal plane passing through the supraorbital notch/foramen (36.4%), or lateral to the plane (63.6%). The mental foramen was either on the plane (69.3%), lateral to the plane (21.8%), or medial to the plane (9.0%). The supraorbital notch/foramen, infraorbital foramen, and mental foramen were on the same sagittal plane in 38.1% of the cases. The supraorbital notch (69.9%) was found more frequently than the supraorbital foramen (28.9%). The average distance from the median plane to the center of the supraorbital notch/foramen, infraorbital foramen, and mental foramen was 22.7, 27.2 and 24.4 mm, respectively. The average length of the line from the center of the supraorbital notch/foramen to the center of the infraorbital foramen was 45.6 mm, and the angle of this line to the sagittal plane was 5.8 degrees. The average distance from the infraorbital margin to the center of the infraorbital foramen was 8.6 mm, and that from the inferior margin of mandible to the center of the mental foramen was 15.5 mm in males and 14.0 mm in females. The average horizontal width of the supraorbital notch/foramen, infraorbital foramen, and mental foramen was 4.7, 4.8 and 2.4 mm, respectively. Most commonly, the infraorbital foramen was lateral to the sagittal plane of the supraorbital notch/foramen, and the mental foramen was on that plane. This locational relationship would be helpful clinically to determine the location of the infraorbital and mental foramina, by palpation of the supraorbital notch.

Adolescent↗
PubMedDate not supplied

Correlation of anthropometric measurements, strength, anterior cruciate ligament size, and intercondylar notch characteristics to sex differences in anterior cruciate ligament tear rates.

We performed a prospective study based on the hypothesis that physiologic differences exist between men and women in strength after adjustments for body weight; that the size of the anterior cruciate ligament is proportionate to the strength of its antagonists, the quadriceps muscles; and that women have a relatively small anterior cruciate ligament, thus predisposing them to a disproportionate number of anterior cruciate ligament injuries. One hundred matched high school basketball players, 50 male and 50 female, were evaluated with anthropometric measurements, body fat analysis, muscle strength evaluation, and magnetic resonance imaging measurements of the intercondylar notch and cross-sectional area of the anterior cruciate ligament at the outlet. The male players were taller and heavier than their female counterparts, although they had 11% less body fat. Male players had statistically greater quadriceps and hamstring muscle strength than female players, even when adjustments were made for body weight. With adjustments for body weight, the size of the anterior cruciate ligament in girls was found to be statistically smaller than in boys. There was no statistically significant difference in the notch width index between the sexes. The study data support our hypothesis that sex differences in anterior cruciate ligament tear rates are caused primarily by several interrelated intrinsic factors. Most importantly, stiffness and muscular strength increase stress on the anterior cruciate ligament in female athletes. The anterior cruciate ligament, when adjustments have been made for body weight, is smaller in female athletes, and therefore, probably does not compensate for the lack of stiffness and strength.

Adolescent↗
PubMed2001

A novel Notch ligand, Dll4, induces T-cell leukemia/lymphoma when overexpressed in mice by retroviral-mediated gene transfer.

Notch receptors mediate cell-fate decisions through interaction with specific ligands during development. The biological role of a novel Notch ligand, Dll4, in mice was explored by reconstituting lethally irradiated mice with bone marrow (BM) cells transduced with Dll4 retroviral vector. White blood cell and lymphocyte counts in Dll4-overexpressing mice were reduced at the early stage of reconstitution but increased significantly at approximately 10 weeks after BM transplantation. BM, spleen, lymph nodes, and peripheral blood of Dll4-overexpressing mice contained predominantly CD4(+)CD8(+) T cells and virtually lacked B cells. The Dll4-overexpressing mice eventually developed a lethal phenotype that was characterized by the progression of a T-cell lymphoproliferative disease (restricted to BM and lymphoid tissues) to transplantable monoclonal T-cell leukemia/lymphoma scattered to multiple organs. Results suggest that the interaction of Dll4 with Notch1 may provide key signals for T-cell development.

Animals↗
PubMed2005

A novel role for Notch ligand Delta-1 as a regulator of human Langerhans cell development from blood monocytes.

Human Langerhans cells (LCs) are of hematopoietic origin, but cytokine regulation of their development is not fully understood. Notch ligand Delta-1 is expressed in a proportion of the skin. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and transforming growth factor-beta1 (TGF-beta1) are also secreted in the skin. We report here that Delta-1, in concert with GM-CSF and TGF-beta1, induces the differentiation of human CD14(+) blood monocytes into cells that express LC markers: CD1a, Langerin, cutaneous lymphocyte-associated antigen, CC chemokine receptor 6, E-cadherin, and Birbeck granules. The resulting cells display phagocytic activity and chemotaxis to macrophage inflammatory protein-1alpha (MIP-1alpha). In response to CD40 ligand and tumor necrosis factor alpha, the cells acquire a mature phenotype of dendritic cells that is characterized by up-regulation of human leukocyte antigen (HLA)-ABC, HLA-DR, CD80, CD86, CD40, and CD54 and appearance of CD83. These cells in turn show chemotaxis toward MIP-1beta and elicit activation of CD8(+) T cells and T helper cell type 1 polarization of CD4(+) T cells. Thus, blood monocytes can give rise to LCs upon exposure to the skin cytokine environment consisting of Delta-1, GM-CSF, and TGF-beta1, which may be, in part, relevant to the development of human epidermal LCs. Our results extend the functional scope of Notch ligand delta-1 in human hematopoiesis.

Amyloid Precursor Protein Secretases↗