Signal processing approaches on otoacoustic emissions

The recent achievement on the measurement of otoacoustic emissions (OAEs) is based on a novel technical development of digital signal processing. OAEs measured in the external ear canal are normal by-products of the active process in hearing, which was discovered by Kemp (1978). Outer hair cells (OHCs) are thought to be the active source in the generation of this energy. Signal processing methods play a crucial role in the detection of OAEs in noise and artifacts, and in the extraction of information from OAE recordings.The present thesis is focused on the signal processing methods used in the recording, data representation, and information extraction of OAEs:(1) A time-frequency method for analysis of transient evoked OAEs (TEOAEs) via smoothed pseudo Wigner distribution has been developed. TEOAEs can be transformed into the time-frequency plane to give a three-dimensional pattern. The analysis of shape and localization of TEOAE pattern and the comparison of pattern differences establish a method to extract more information from TEOAEs.(2) An optimal recording protocol based on time-frequency analysis of TEOAEs has been proposed for neonatal hearing screening. A better signal-to-noise ratio (SNR) and a lower noise level of TEOAEs have been achieved by shortening the recording window and by using a linear recording protocol. The method has been applied in three audiological clinics in Europe. Time-frequency analysis of TEOAEs indicates a significantly reduced energy in the mid to high frequency bands for subjects with sensorineural hearing loss (SNHL) compared to normal-hearing subjects.(3) TEOAEs, spontaneous OAEs (SOAEs) and distortion-product OAEs (DPOAEs) are related. The contribution from synchronized SOAEs to TEOAEs was demonstrated. The female and right ear advantages on OAEs were observed.(4) Spectral estimation of SOAEs was performed by an average periodogram, a reduced variance estimate, and a model based high-order autoregressive (AR) estimate. Different spectral estimation methods can give more information on the spectral pattern of SOAEs.(5) Active cochlear nonlinearity was estimated by multi-component DPOAEs and by introducing generating models of DPOAEs. The input-output function of the active cochlear nonlinearity was calculated from the multi-component DPOAEs. The results show that the generating mechanism of DPOAEs is dependent on stimulus level.(6) The "bounce" phenomenon on basilar membrane nonlinearity was observed after exposure to a loud, but not traumatic low-frequency tone. This may give objective information on an individual's ability to recover from a temporal threshold shift (TTS).In summary, the importance of these results relies mainly on the refinements of the measurement tools created, which can be used to investigate the function of the inner ear, especially the outer hair cells (OHCs).List of scientific papersI. Cheng J (1995). "Time-frequency analysis of transient evoked otoacoustic emissions via smoothed pseudo Wigner distribution" Scand Audiol 24(2): 91-96 https://pubmed.ncbi.nlm.nih.gov/95389095II. Hatzopoulos S, Cheng J, Grzanka A, Morlet T, Martini A (2000). "Optimization of TEOAE recording protocols: a linear protocol derived from parameters of a time-frequency analysis: a pilot study on neonatal subjects" Scand Audiol 29(1): 21-27 https://pubmed.ncbi.nlm.nih.gov/20181601III. Hatzopoulos S, Cheng J, Grzanka A, Martini A (2000). "Time-frequency analyses of TEOAE recordings from normals and SNHL patients" Audiology 39(1): 1-12 https://pubmed.ncbi.nlm.nih.gov/20210623IV. Cheng, J (1998). "Otoacoustic emissions: Measurement, data and interrelations" Acustica - acta acustica 84: 320-328V. Cheng, J (1998). "Spectral estimation of spontaneous otoacoustic emissions" Acustica - acta acustica 84: 712-719VI. Cheng, J (1999). "Estimation of active cochlear nonlinearity by multi-component distortion-product otoacoustic emissions" Acustica - acta acustica 85: 721-727VII. Cheng, J (2000). "Quantifying basilar membrane nonlinearity and the "bounce" phenomenon on the nonlinearity estimated by multi-component DPOAEs" (Manuscript)</p

Table1_Rivaroxaban plus aspirin vs. dual antiplatelet therapy in endovascular treatment in peripheral artery disease and analysis of medication utilization of different lesioned vascular regions.docx

BackgroundIn the management of Peripheral Arterial Disease (PAD), the administration of anticoagulant or antiplatelet agents is imperative. The use of Dual Antiplatelet Therapy (DAPT) in conjunction with rivaroxaban has shown potential in mitigating adverse outcomes. Given the heterogeneity in the pathology of lower limb arteries, there is a compelling case for individualized treatment strategies.MethodsIn a single-center retrospective study on pharmacotherapy for peripheral artery disease, patients were treated with either aspirin combined with rivaroxaban or aspirin coupled with clopidogrel. The primary efficacy outcome encompassed a composite of increases in the Rutherford classification, acute limb ischemia, amputations due to vascular causes, target lesion revascularization, myocardial infarction, ischemic stroke, and cardiovascular death. The primary safety outcome was major bleeding, as defined by the Thrombolysis in Myocardial Infarction (TIMI) criteria; meanwhile, major bleeding as categorized by the International Society on Thrombosis and Haemostasis (ISTH) served as a secondary safety outcome. The study differentiated between two subgroups: patients with only above-the-knee and below-the-knee arterial lesions.ResultsFrom January 2016 to December 2021, 455 patients received either clopidogrel plus aspirin or rivaroxaban plus aspirin following endovascular treatment (EVT). The rivaroxaban group (n = 220) exhibited a lower incidence of primary efficacy outcomes [49.1% vs. 60.4%, hazard ratio (HR) 0.77, P = 0.006] but had more TIMI major bleeding events (5.9% vs. 2.1%, HR 2.6, P = 0.04). ISTH major bleeding events did not show a significant difference, though a higher percentage of rivaroxaban patients discontinued medication due to bleeding (10% vs. 4.7%, HR 2.2, P = 0.03). In the above-the-knee arterial disease subgroup, the rivaroxaban group demonstrated a lower incidence of primary efficacy outcomes (28.2% vs. 45.2%, HR 0.55, P = 0.02). In the below-the-knee arterial disease subgroup, no significant difference was observed in the occurrence of primary efficacy events between the two groups (58.7% vs. 64.8%, HR 0.76, P = 0.14).ConclusionRivaroxaban plus aspirin improved outcomes compared to DAPT in patients with lower extremity artery disease. Similar findings were observed in the above-the-knee artery lesion-only group. However, in the below-the-knee artery lesion-only group, rivaroxaban plus aspirin did not surpass DAPT in efficacy. Regarding safety, rivaroxaban plus aspirin exhibited higher bleeding risks and more frequent treatment discontinuation than aspirin combined with clopidogrel.</p

Utilization of the Three-Dimensional Volcano Surface To Understand the Chemistry of Multiphase Systems in Heterogeneous Catalysis

Utilization of the Three-Dimensional Volcano Surface To Understand the Chemistry of Multiphase Systems in Heterogeneous Catalysi

Spectrosome material is transferred via ring canal in GSCs.

<p>Spectrosome (Short Adducin-GFP) in wild type GSC is located in the basal position (0 min: interphase and 24min: metaphase). At 1hr 12min, spectrosome is co-localized with the ring canal structure. Spectrosome, together with ring canal structure, grows into the stem cell daughter at 6hr 16min, segregates into both daughter cells and form spectrosome-like structure again at 15hr 20 min. At 20hr 40 min, spectrosomes in both GSC and gonialblast further develop, and the gonialblast separates from GSC. Cellular boundaries and mitotic spindle are visualized with α-tub-GFP. Black arrow: spectrosome. White dash-arrow: spectrosome and/or ring canal tail. *: hub cells. Yellow dash-line: GSC or gonialblast boundary. Solid white arrow: mitotic spindle.</p

Dynamic Interplay of Spectrosome and Centrosome Organelles in Asymmetric Stem Cell Divisions

<div><p>Stem cells have remarkable self-renewal ability and differentiation potency, which are critical for tissue repair and tissue homeostasis. Recently it has been found, in many systems (e.g. gut, neurons, and hematopoietic stem cells), that the self-renewal and differentiation balance is maintained when the stem cells divide asymmetrically. <i>Drosophila</i> male germline stem cells (GSCs), one of the best characterized model systems with well-defined stem cell niches, were reported to divide asymmetrically, where centrosome plays an important role. Utilizing time-lapse live cell imaging, customized tracking, and image processing programs, we found that most acentrosomal GSCs have the spectrosomes reposition from the basal end (wild type) to the apical end close to hub-GSC interface (acentrosomal GSCs). In addition, these apically positioned spectrosomes were mostly stationary while the basally positioned spectrosomes were mobile. For acentrosomal GSCs, their mitotic spindles were still highly oriented and divided asymmetrically with longer mitosis duration, resulting in asymmetric divisions. Moreover, when the spectrosome was knocked out, the centrosomes velocity decreased and centrosomes located closer to hub-GSC interface. We propose that in male GSCs, the spectrosome recruited to the apical end plays a complimentary role in ensuring proper spindle orientation when centrosome function is compromised.</p></div

Acidity of the Aqueous Rutile TiO₂(110) Surface from Density Functional Theory Based Molecular Dynamics

The thermodynamics of protonation and deprotonation of the rutile TiO2(110) water interface is studied using a combination of density functional theory based molecular dynamics (DFTMD) and free energy perturbation methods. Acidity constants are computed from the free energy for chaperone assisted insertion/removal of protons in fully atomistic periodic model systems treating the solid and solvent at the same level of theory. The pKa values we find for the two active surface hydroxyl groups on TiO2(110), the bridge OH (Ti2OH+), and terminal H2O adsorbed on a 5-fold Ti site (TiOH2) are −1 and 9, leading to a point of zero proton charge of 4, well within the computational error margin (2 pKa units) from the experimental value (4.5−5.5). The computed intrinsic surface acidities have also been used to estimate the dissociation free energy of adsorbed water giving 0.6 eV, suggesting that water dissociation is unlikely on a perfect aqueous TiO2(110) surface. For further analysis, we compare to the predictions of the MUltiSIte Complexation (MUSIC) and Solvation, Bond strength, and Electrostatic (SBE) models. The conclusion regarding the MUSIC model is that, while there is good agreement for the acidity of an adsorbed water molecule, the proton affinity of the bridging oxygen obtained in the DFTMD calculation is significantly lower (more than 5 pKa units) than the MUSIC model value. Structural analysis shows that there are significant differences in hydrogen bonding, in particular to a bridging oxygen which is assumed to be stronger in the MUSIC model compared to what we find using DFTMD. Using DFTMD coordination numbers as input for the MUSIC model, however, led to a pKa prediction which is inconsistent with the estimates obtained from the DFTMD free energy calculation

Dynamic migration patterns of spectrosomes are quantified utilizing time-lapse live-imaging.

<p><b>(A)</b> Spectrosome localization in <i>DSas4-mut</i> becomes predominantly apical compared to wild type. #: p<0.05. <b>(B)</b> Live image sequences shows apically (to the hub cells) migrating spectrosome in a dividing <i>DSas4-mut</i> GSC. Arrowhead: spectrosome. *: hub cells. Yellow dash-line: GSC. <b>(C)</b> In wild type GSCs, large majority of spectrosomes were mobile and located basally (39%) during interphase. In <i>DSas4-mut</i> GSCs, majority of spectrosomes were stationary and located apically (54%). Wild type: n = 23, DSas4-mut: n = 24. <b>(D)</b><i>DSas4-mut</i> GSCs had higher percentage of spectrosomes migrating from apical to the basal side prior to mitosis. Spectrosome switches are categorized as such if they migrate within 30 mins prior to mitosis (identified by nuclear envelope breakdown).</p

Deciphering the Anomalous Acidic Tendency of Terminal Water at Rutile(110)–Water Interfaces

Understanding the mechanism of the oxygen evolution reaction (OER) is essential to improve the efficiency of photocatalysis for TiO2. Previous studies have highlighted the importance of terminal hydroxide radical (TiOH•) in the OER. Ab initio molecular dynamics simulations (AIMD) with hybrid functional have revealed that this radical readily loses its proton, creating the key intermediate, oxygen radical anion (Ti5cO•–). Herein, we combine machine-learning-accelerated molecular dynamics with density functional theory calculations to demonstrate that the Ti5cO•– can alternatively be generated through the trapping of a hole in a terminal oxygen anion (Ti5cO2–) at rutile(110)–water interfaces. Further examination reveals that the Ti5cO2– results from the deprotonation of Ti5cOH– and remains stable at the charge-neutral interfaces for a transient time period of ca. 100 ps. The AIMD-based free energy perturbation method predicts that the acidity constant of Ti5cOH– is even smaller than that of Ti5cOH2, thereby rationalizing the stability of Ti5cO2–. Structural analyses show that this anomalous acidic tendency of terminal water originates from the decrease of Ti–O bond length and the transition of Titanium’s coordination from octahedral to pyramidal in Ti5cO2–. Our findings provide valuable insights into the surface acid–base chemistry and a potential explanation for the pH-dependent behavior of photogenerated holes for TiO2

Spectrosome Knockout minimally affects centrosome orientation, spindle orientation, mitosis duration, and stem cell numbers in male GSCs.

<p><b>(A)</b> Centrosome misorientation during interphase was analyzed from time lapse image sequences, and there is no significant difference between the <i>hts-mut</i> and the wild type. <b>(B)</b> There is minimal change in the spindle orientation between the <i>hts-mut</i> and the wild type. <b>(C)</b> Mitosis duration is not affected in <i>hts-mut</i> compared to the wild type when measured from nuclear envelope breakdown time to anaphase. <b>(D)</b> There is no significant difference for GSC number per testis in hts-mut and wild type flies.</p

Centrosome velocity and distance to hub-GSC interface change in <i>hts-mut</i> GSCs.

<p>Based on the centrosome tracking analysis of live-image sequences, the <b>A)</b> Interphase centrosome velocities are shown for both <i>hts-mut</i> GSCs and wild type GSCs (p<0.01 between <i>hts-mut</i> and wild type for both GSC-inherited and GB-inherited centrosomes), and the <b>B)</b> GSC-inherited centrosome distance to the hub-GSC interphase histograms are shown for both <i>hts-mut</i> and wild type GSCs (p<0.01).</p