The 1.06 frequency ratio in the cochlea: evidence and outlook for a natural musical semitone

A frequency ratio of about 1.06 often appears in cochlear mechanics, and the question naturally arises, why? The ratio is close to that of the semitone (1.059) in music, giving reason to think that this aspect of musical perception might have a cochlear basis. Here, data on synchronised spontaneous otoacoustic emissions is presented, and a clustering of ratios between 1.05 and 1.07 is found with a peak at 1.063 +/- 0.005. These findings reinforce what has been found from previous sources, which are reviewed and placed alongside the present work. The review establishes that a peak in the vicinity of 1.06 has often been found in human cochlear data. Several possible cochlear models for explaining the findings are described. Irrespective of which model is selected, the fact remains that the cochlea itself appears to be the origin of a ratio remarkably close to an equal-tempered musical semitone, and this close coincidence leads to the suggestion that the inner ear may play a role in constructing a natural theory of music. The outlook for such an enterprise is surveyed.Andrew Bell received funding from the Institute of Physiology and Pathology of Hearing, Warsaw, under contracts 132/IFPS/2015 and 109/IFPS/2017

The Dimerization Domain in DapE Enzymes Is Required for Catalysis

The emergence of antibiotic-resistant bacterial strains underscores the importance of identifying new drug targets and developing new antimicrobial compounds. Lysine and meso-diaminopimelic acid are essential for protein production and bacterial peptidoglycan cell wall remodeling and are synthesized in bacteria by enzymes encoded within dap operon. Therefore dap enzymes may serve as excellent targets for developing a new class of antimicrobial agents. The dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase (DapE) converts N-succinyl-L,L-diaminopimelic acid to L,Ldiaminopimelic acid and succinate. The enzyme is composed of catalytic and dimerization domains, and belongs to the M20 peptidase family. To understand the specific role of each domain of the enzyme we engineered dimerization domain deletion mutants of DapEs from Haemophilus influenzae and Vibrio cholerae, and characterized these proteins structurally and biochemically. No activity was observed for all deletion mutants. Structural comparisons of wild-type, inactive monomeric DapE enzymes with other M20 peptidases suggest that the dimerization domain is essential for DapE enzymatic activity. Structural analysis and molecular dynamics simulations indicate that removal of the dimerization domain increased the flexibility of a conserved active site loop that may provide critical interactions with the substrate

Otoacoustic Emissions in Smoking and Nonsmoking Young Adults

ObjectivesThe present study investigates the usefulness of transiently evoked otoacoustic emissions (TEOAEs) and distortion product OAEs (DPOAEs) in detecting small changes in the hearing of young smoking adults.MethodsOtoacoustic emissions were acquired from the ears of 48 young adults (age, 20 to 27 years). The dataset was divided into two groups, smoking (24 persons/48 ears) and nonsmoking (24 persons/48 ears). The level of smoking was relatively small in comparison to previous studies, an average of 3.8 years and 8.7 cigarettes per day. In each ear three OAE measurements were made: TEOAEs, DPOAEs, and spontaneous OAEs (SOAEs). Pure tone audiometry and tympanometry were also conducted. Audiometric thresholds did not differ significantly between the datasets. Half-octave-band values of OAE signal to noise ratios and response levels were used to assess statistical differences.ResultsAveraged data initially revealed that differences between the two study groups occurred only for TEOAEs at 1 kHz. However when the datasets were divided into ears with and without SOAEs more differences became apparent, both for TEOAEs and DPOAEs. In ears that exhibited SOAEs, both smokers and nonsmokers, there were no statistically significant differences between evoked OAEs; however in all ears without SOAEs, evoked OAEs were higher in the ears of nonsmokers, by as much as 5 dB. These differences were most prominent in the 1-2 kHz range.ConclusionA general decrease in OAE levels was found in the group of smokers. However, in ears which exhibited SOAEs, there was no difference between the evoked OAEs of smokers and nonsmokers. We conclude that smoking had not yet measurably affected the ears of those with acute hearing (i.e., those who exhibit SOAEs). However, in ears without SOAEs, smokers exhibited smaller evoked OAE amplitudes than nonsmokers, even though their audiometric thresholds were within the norm

Musical Ratios in Sounds from the Human Cochlea

The physiological roots of music perception are a matter of long-lasting debate. Recently light on this problem has been shed by the study of otoacoustic emissions (OAEs), which are weak sounds generated by the inner ear following acoustic stimulation and, sometimes, even spontaneously. In the present study, a high-resolution time–frequency method called matching pursuit was applied to the OAEs recorded from the ears of 45 normal volunteers so that the component frequencies, amplitudes, latencies, and time-spans could be accurately determined. The method allowed us to find that, for each ear, the OAEs consisted of characteristic frequency patterns that we call resonant modes. Here we demonstrate that, on average, the frequency ratios of the resonant modes from all the cochleas studied possessed small integer ratios. The ratios are the same as those found by Pythagoras as being most musically pleasant and which form the basis of the Just tuning system. The statistical significance of the results was verified against a random distribution of ratios. As an explanatory model, there are attractive features in a recent theory that represents the cochlea as a surface acoustic wave resonator; in this situation the spacing between the rows of hearing receptors can create resonant cavities of defined lengths. By adjusting the geometry and the lengths of the resonant cavities, it is possible to generate the preferred frequency ratios we have found here. We conclude that musical perception might be related to specific geometrical and physiological properties of the cochlea

Biosimilar G-CSF versus filgrastim and lenograstim in healthy unrelated volunteer hematopoietic stem cell donors

The World Marrow Donor Organization recommends original granulocyte-colony stimulating factor (G-CSF) for the mobilization of stem cells in healthy unrelated hematopoietic stem cell donors. We report the comparison of a biosimilar G-CSF (Zarzio) with two original G-CSFs (filgrastim and lenograstim) in mobilization in unrelated donors. We included data of 313 consecutive donors who were mobilized during the period from October 2014 to March 2016 at the Medical University of Warsaw. The primary endpoints of this study were the efficiency of CD34+ cell mobilization to the circulation and results of the first apheresis. The mean daily dose of G-CSF was 9.1 μg/kg for lenograstim, 9.8 μg/kg for biosimilar filgrastim, and 9.3 μg/kg for filgrastim (p < 0.001). The mean CD34+ cell number per microliter in the blood before the first apheresis was 111 for lenograstim, 119 for biosimilar filgrastim, and 124 for filgrastim (p = 0.354); the mean difference was even less significant when comparing CD34+ number per dose of G-CSF per kilogram (p = 0.787). Target doses of CD34+ cells were reached with one apheresis in 87% donors mobilized with lenograstim and in 93% donors mobilized with original and biosimilar filgrastim (p = 0.005). The mobilized apheresis outcomes (mean number of CD34+ cells/kg of donor collected during the first apheresis) was similar with lenograstim, biosimilar filgrastim, and filgrastim: 6.2 × 10⁶, 7.6 × 10⁶, and 7.3 × 10⁶, respectively, p = 0.06. There was no mobilization failure in any of the donors. Biosimilar G-CSF is as effective in the mobilization of hematopoietic stem cells in unrelated donors as original G-CSFs. Small and clinically irrelevant differences seen in the study can be attributed to differences in G-CSF dose and collection-related factors. Active safety surveillance concurrent to clinical use and reporting to donor outcome registry (e.g., EBMT donor outcome registry or WMDA SEAR/SPEAR) might help to evaluate the possible short- and long-term complications of biosimilar G-CSF

DM-like anomalies in neutron multiplicity spectra

Publisher Copyright: © 2022 Institute of Physics Publishing. All rights reserved.A new experiment collects data, since November 2019, at a depth of 210 m.w.e. in the Callio Lab in the Pyhasalmi mine in Finland. The setup, called NEMESIS (New Emma MEasurementS Including neutronS), incorporates infrastructure from the EMMA experiment with neutron and large-area plastic scintillator detectors. The experiment's primary aim is to combine muon tracking with position-sensitive neutron detection to measure precision yields, multiplicities, and lateral distributions of high-multiplicity neutron events induced by cosmic muons in various materials. The data are relevant for background evaluation of the deep-underground searches for Dark Matter (DM), neutrino-less double beta decay, etc. Preliminary analysis revealed anomalies in muon-suppressed neutron multiplicity spectra collected during a 344-day run (live time) with a 565 kg Pb target. The spectra, otherwise well described by an exponential fit, show three peaks at high multiplicities. Although still at a low statistical significance, these small excesses match the outcome of an earlier measurement. The nature of the anomalies remains unclear, but, in principle, they may be a signature of self-annihilation of a WIMP with a mass close to 13 GeV/c2. With that assumption, the expected cross-section would be around 10-42 cm2 for Spin-Dependent or 10-46 cm2 for Spin Independent interactions. We propose verifying this hypothesis with an upgraded NEMESIS experiment, able to collect an order of magnitude more data than this measurement. Based on the statistical uncertainty, analysis of the event rate indicates that cross-section limits for DM mass range of approximately 3-40 GeV/c2 can be investigated with such a setup.Peer reviewe

New NEMESIS Results

Funding Information: This work has been supported in part by the EU INTERREG for the Baltic Sea programme within the BSUIN project, and by the Polish Ministry of Science and Higher Education (Grant no. Funding Information: This work has been supported in part by the EU INTERREG for the Baltic Sea programme within the BSUIN project, and by the Polish Ministry of Science and Higher Education (Grant no. 3988/INTERREG BSR/2018/2). Publisher Copyright: © Copyright owned by the author(s) under the terms of the Creative Commons.Preliminary results from a 349-day run (live time) with a 565 kg Pb target and a 166-day background measurement are presented. Three minor anomalies were detected in muon-suppressed neutron multiplicity spectra. The multiplicities of these small excesses match the outcome of an earlier, similar but independent measurement. The nature of the anomalies remains unclear, but, in principle, they may be a signature of self-annihilation of a Weakly Interacting Massive Particle (WIMP) with a mass around 10 GeV/c2. If our interpretation is correct, the expected cross section would be of the order of 10-42 cm2 for Spin Dependent and 10-46 cm2 for Spin Independent interactions. Analysis of the event rate, based on the statistical uncertainty, indicates that cross-section limits for Dark Matter (DM) mass range of approximately 3-40 GeV/c2 can be investigated with an upgraded NEMESIS setup.Peer reviewe

NEMESIS setup for Indirect Detection of WIMPs

We summarize the evidence for DM-like anomalies in neutron multiplicity spectra collected underground with Pb targets by three independent experiments: NEMESIS (at 210 m.w.e.) NMDS (at 583 m.w.e.), and ZEPLIN-II (at 2850 m.w.e.). A new analysis shows small but persistent anomalies at high neutron multiplicities. Adjusted for differences in detection efficiencies, the positions of the anomalies are consistent between the three systems. Also, the intensities match when corrected for the acquisition time and estimated detection efficiency. While the three measurements are inconclusive when analyzed separately, together, they exclude a statistical fluke to better than one in a million. To prove the existence of the anomalies above the 5-sigma discovery threshold, we propose to upgrade the current NEMESIS setup. The upgrade concept and the critical components of the new experiment are described. The upgraded setup would already acquire the needed data sample during the first year of operation. Additional information, vital for the physics interpretation of the analysis, will be obtained with a Cu target.Peer reviewe