Spectroscopic characterization of carbon monoxide activation by neutral chromium carbides.

Spectroscopic characterization of carbon monoxide activation by neutral metal carbides is of essential importance for understanding the structure-reactivity relationships of catalytic sites, but has been proven to be very challenging owing to the difficulty in size selection. Here, we report a size-specific infrared-vacuum ultraviolet spectroscopic study of the reactions between carbon monoxide with neutral chromium carbides. Quantum chemical calculations were carried out to identify the low-lying structures and to interpret the experimental features. The results reveal that the most stable structure of CrC3(CO)2 consists of a CCO ketenylidene unit and that of CrC4(CO)2 has a semi-bridging CO with a very low CO stretching vibrational frequency at 1821 cm-1. The electron structure analyses show that this semi-bridging CO is highly activated through the delocalized Cr-C-C three-center two-electron (3c-2e) interaction between the antibonding orbitals of CO and the metal carbide skeleton. The formation of these metal carbide carbonyls is found to be both thermodynamically exothermic and kinetically facile in the gas phase. The present findings have important implications for the mechanical understanding of the catalytic processes with isolated metal atoms/clusters dispersed on supports.

Spectroscopic Characterization of Highly Excited Neutral Chromium Tricarbonyl.

Spectroscopic characterization of highly excited neutral transition-metal complexes is important for understanding the multifaceted reaction mechanisms between metals and ligands. In this work, the reactions of neutral chromium atoms with carbon monoxide were probed by size-specific infrared spectroscopy. Interestingly, Cr(CO)3 was found to have an unprecedented 7A2″ septet excited state rather than the singlet ground state. A combination of experiment and theory shows that the gas-phase formation of this highly excited Cr(CO)3 is facile both thermodynamically and kinetically. Electronic structure and bonding analyses indicate that the valence electrons of Cr atoms in the septet Cr(CO)3 are in a relatively stable configuration, which facilitate the highly excited structure and the planar geometric shape (D3h symmetry). The observed septet Cr(CO)3 affords a paradigm for exploring the structure, properties, and formation mechanism of a large variety of excited neutral compounds.

Register transitions in an in vivo canine model as a function of intrinsic laryngeal muscle stimulation, fundamental frequency, and sound pressure level.

Phonatory instabilities and involuntary register transitions can occur during singing. However, little is known regarding the mechanisms which govern such transitions. To investigate this phenomenon, we systematically varied laryngeal muscle activation and airflow in an in vivo canine larynx model during phonation. We calculated voice range profiles showing average nerve activations for all combinations of fundamental frequency (F0) and sound pressure level (SPL). Further, we determined closed-quotient (CQ) and minimum-posterior-area (MPA) based on high-speed video recordings. While different combinations of muscle activation favored different combinations of F0 and SPL, in the investigated larynx there was a consistent region of instability at about 400 Hz which essentially precluded phonation. An explanation for this region may be a larynx specific coupling between sound source and subglottal tract or an effect based purely on larynx morphology. Register transitions crossed this region, with different combinations of cricothyroid and thyroarytenoid muscle (TA) activation stabilizing higher or lower neighboring frequencies. Observed patterns in CQ and MPA dependent on TA activation reproduced patterns found in singers in previous work. Lack of control of TA stimulation may result in phonation instabilities, and enhanced control of TA stimulation may help to avoid involuntary register transitions, especially in the singing voice.

Autoxidation Mechanism and Kinetics of Methacrolein in the Atmosphere.

Elucidating the autoxidation of volatile organic compounds (VOCs) is crucial to understanding the formation mechanism of secondary organic aerosols, but it has been proven to be challenging due to the complexity of reactions under atmospheric conditions. Here, we report a comprehensive theoretical study of atmospheric autoxidation in VOCs exemplified by the atmospherically important methacrolein (MACR), a major oxidation product of isoprene. The results indicate that the Cl-adducts and H-abstraction products of MACR readily react with O2 and undergo subsequent isomerizations via H-shift and cyclization, forming a large variety of lowly and highly oxygenated organic molecules. In particular, the first- and third-generation oxidation products derived from the Cl-adducts and the methyl-H-abstraction complexes are dominated in the atmospheric autoxidation, for which the fractional yields are remarkably affected by the NO concentration. The present findings have important implications for a systematical understanding of the oxidation processes of isoprene-derived compounds in the atmospheric environments.

A novel CDK8 inhibitor with poly-substituted pyridine core: Discovery and anti-inflammatory activity evaluation in vivo.

As an ideal anti-inflammatory target, cyclin-dependent kinase 8 (CDK8) has gradually attracted the attention of researchers. CDK8 inhibition up-regulates Interleukin-10 (IL-10) expression by enhancing the transcriptional activity of activator protein-1 (AP-1), and augmenting IL-10 abundance is a viable strategy for the treatment of inflammatory bowel disease (IBD). In this research, through structure-based drug design and dominant fragment hybridization, a series of poly-substituted pyridine derivatives were designed and synthesized as CDK8 inhibitors. Ultimately, compound CR16 was identified as the best one, which exhibited good inhibitory activity against CDK8 (IC50 = 74.4 nM). In vitro and in vivo studies indicated that CR16 could enhance the transcriptional activity of AP-1, augment the abundance of IL-10, and affect CDK8-related signaling pathways including TLR7/NF-κB/MAPK and IL-10-JAK1-STAT3 pathways. In addition, CR16 showed potent therapeutic effect in an animal model of IBD.

The influence of source-filter interaction on the voice source in a three-dimensional computational model of voice production.

The goal of this computational study is to quantify global effects of vocal tract constriction at various locations (false vocal folds, aryepiglottic folds, pharynx, oral cavity, and lips) on the voice source across a large range of vocal fold conditions. The results showed that while inclusion of a uniform vocal tract had notable effects on the voice source, further constricting the vocal tract only had small effects except for conditions of extreme constriction, at which constrictions at any location along the vocal tract decreased the mean and peak-to-peak amplitude of the glottal flow waveform. Although narrowing in the epilarynx increased the normalized maximum flow declination rate, vocal tract constriction in general slightly reduced the source strength and high-frequency harmonic production at the glottis, except for a limited set of vocal fold conditions (e.g., soft, long vocal folds subject to relatively high pressure). This suggests that simultaneous laryngeal and vocal tract adjustments are required to maximize source-filter interaction. While vocal tract adjustments are often assumed to improve voice production, our results indicate that such improvements are mainly due to changes in vocal tract acoustic response rather than improved voice production at the glottis.

Neural Adaptive H∞ Sliding-Mode Control for Uncertain Nonlinear Systems with Disturbances Using Adaptive Dynamic Programming.

This paper focuses on a neural adaptive H∞ sliding-mode control scheme for a class of uncertain nonlinear systems subject to external disturbances by the aid of adaptive dynamic programming (ADP). First, by combining the neural network (NN) approximation method with a nonlinear disturbance observer, an enhanced observer framework is developed for estimating the system uncertainties and observing the external disturbances simultaneously. Then, based on the reliable estimations provided by the enhanced observer, an adaptive sliding-mode controller is meticulously designed, which can effectively counteract the effects of the system uncertainties and the separated matched disturbances, even in the absence of prior knowledge regarding their upper bounds. While the remaining unmatched disturbances are attenuated by means of H∞ control performance on the sliding surface. Moreover, a single critic network-based ADP algorithm is employed to learn the cost function related to the Hamilton-Jacobi-Isaacs equation, and thus, the H∞ optimal control is obtained. An updated law for the critic NN is proposed not only to make the Nash equilibrium achieved, but also to stabilize the sliding-mode dynamics without the need for an initial stabilizing control. In addition, we analyze the uniform ultimate boundedness stability of the resultant closed-loop system via Lyapunov's method. Finally, the effectiveness of the proposed scheme is verified through simulations of a single-link robot arm and a power system.

Versatile DIY Route for Incorporation of a Wide Range of Electrode Materials into Rotating Ring Disk Electrodes.

Rotating ring disk electrodes (RRDEs) are a powerful and versatile tool for mechanistically investigating electrochemical reactions at electrode surfaces, particularly in the area of electroanalysis and catalysis. Despite their importance, only limited electrode materials (typically glassy carbon, platinum, and gold) and combinations thereof are available commercially. In this work, we present a method employing three-dimensional (3D) printing in conjunction with machined brass components to produce housing, which can accommodate any electrode material in, e.g., pressed powdered pellet, wafer, rod, foil, or vapor deposited onto a conductive substrate form. In this way, the range and usability of RRDEs is extended. This custom do-it-yourself (DIY) approach to fabricating RRDEs also enables RRDEs to be produced at a significant fraction of the cost of commercial RRDEs. To illustrate the versatility of our approach, coplanar boron-doped diamond (BDD) RRDEs are fabricated for the first time using the approach described. Experimental collection efficiencies for the redox couple FcTMA+/FcTMA2+ are found to be very close to those predicted theoretically. BDD electrodes serve as an ideal electrocatalyst support due to their low background currents, wide solvent potential window in aqueous solution, and chemical and electrochemical stability in acid and alkali solutions. The BDD RRDE configuration is employed to investigate the importance of surface-incorporated nondiamond carbon in BDD on hydrogen peroxide generation via the oxygen reduction reaction in acid solutions.

Ligand-Induced Tuning of the Electronic Structure of Rhombus Tetraboron Cluster.

A neutral boron carbonyl complex B4 (CO)3 is generated in the gas phase and is characterized by infrared plus vacuum ultraviolet (IR+VUV) two-color ionization spectroscopy and quantum chemical calculations. The complex is identified to have a planar C2v structure with three CO ligands terminally coordinated to a rhombus B4 core. It has a closed-shell singlet ground state that correlates to an excited state of B4 . Bonding analyses on B4 (CO)3 as well as the previously reported B4 and B4 (CO)2 indicate that the electronic structure of rhombus tetraboron cluster changes from a close-shell singlet to an open-shell singlet in B4 (CO)2 and to a close-shell singlet in B4 (CO)3 , demonstrating that the electronic structures of boron clusters can be effectively tuned via sequential CO ligand coordination.

Aerosol mass spectrometry of neutral species based on a tunable vacuum ultraviolet free electron laser.

A vacuum ultraviolet free electron laser (VUV-FEL) photoionization aerosol mass spectrometer (AMS) has been developed for online measurement of neutral compounds in laboratory environments. The aerosol apparatus is mainly composed of a smog chamber and a reflectron time-of-flight mass spectrometer (TOF-MS). The indoor smog chamber had a 2 m3 fluorinated ethylene propylene film reactor placed in a temperature- and humidity-controlled room, which was used to generate the aerosols. The aerosols were sampled via an inlet system consisting of a 100 µm orifice nozzle and aerodynamic lenses. The application of this VUV-FEL AMS to the α-pinene ozonolysis under different concentrations reveals two new compounds, for which the formation mechanisms are proposed. The present findings contribute to the mechanistic understanding of the α-pinene ozonolysis in the neighborhood of emission origins of α-pinene. The VUV-FEL AMS method has the potential for chemical analysis of neutral aerosol species during the new particle formation processes.

Estimating subglottal pressure and vocal fold adduction from the produced voice in a single-subject study (L).

We previously reported a simulation-based neural network for estimating vocal fold properties and subglottal pressure from the produced voice. This study aims to validate this neural network in a single-human subject study. The results showed reasonable accuracy of the neural network in estimating the subglottal pressure in this particular human subject. The neural network was also able to qualitatively differentiate soft and loud speech conditions regarding differences in the subglottal pressure and degree of vocal fold adduction. This simulation-based neural network has potential applications in identifying unhealthy vocal behavior and monitoring progress of voice therapy or vocal training.

Oral vibratory sensations during voice production at different laryngeal and semi-occluded vocal tract configurations.

Voice therapy often emphasizes vibratory sensations in the front part of the vocal tract during phonation to improve vocal efficiency. It remains unclear what laryngeal and vocal tract adjustments are elicited in speakers by this emphasis on oral vibratory sensations. Using a three-dimensional phonation model, this study aims to identify laryngeal and epilaryngeal adjustments that might produce maximal oral vibratory sensations during phonation, as quantified by the oral sound pressure level (SPL), and thus are likely to be elicited in voice therapy at different semi-occluded vocal tract configurations. Results show that maximum oral SPL occurs at intermediate vocal fold adduction configurations characterized by a trade-off between glottal gap and vocal fold vertical thickness. Epilaryngeal tube narrowing further increases the oral SPL in an open vocal tract, but has little effect on oral SPL in semi-occluded vocal tracts. Laryngeal and epilaryngeal configurations producing the maximum oral SPL generally have lower peak vocal fold contact pressure when producing a target output SPL. These favorable configurations are more easily identified in open vocal tracts than semi-occluded vocal tracts. However, semi-occlusion increases both the mean and dynamic oral pressure, which may familiarize speakers with oral vibratory sensations and facilitate adoption of favorable laryngeal configurations.

Comparison of one-dimensional and three-dimensional glottal flow models in left-right asymmetric vocal fold conditions.

While the glottal flow is often simplified as one-dimensional (1D) in computational models of phonation to reduce computational costs, the 1D flow model has not been validated in left-right asymmetric vocal fold conditions, as often occur in both normal and pathological voice production. In this study, we performed three-dimensional (3D) and 1D flow simulations coupled to a two-mass model of adult male vocal folds and compared voice production at different degrees of left-right stiffness asymmetry. The flow and acoustic fields in 3D were obtained by solving the compressible Navier-Stokes equations using the volume penalization method with the moving vocal fold wall as an immersed boundary. Despite differences in the predicted flow pressure on vocal fold surface between the 1D and 3D flow models, the results showed reasonable agreement in vocal fold vibration patterns and selected voice outcome measures between the 1D and 3D models for the range of left-right asymmetric conditions investigated. This indicates that vocal fold properties play a larger role than the glottal flow in determining the overall pattern of vocal fold vibration and the produced voice, and the 1D flow simplification is sufficient in modeling phonation, at least for the simplified glottal geometry of this study.

Contribution of laryngeal size to differences between male and female voice production.

In this study we investigated the effect of sex- and age-related differences in vocal fold length, thickness, and depth on voice production in a three-dimensional vocal fold model. The results showed that the cause-effect relationships between vocal fold physiology and voice production previously identified in an adult male-like vocal fold geometry remained qualitatively the same in vocal folds with geometry representative of adult females and children. We further showed that the often-observed differences in voice production between adult males, adult females, and children can be explained by differences in length and thickness. The lower F0, higher flow rate, larger vocal fold vibration amplitude, and higher sound pressure level (SPL) in adult males as compared to adult females and children can be explained by differences in vocal fold length. In contrast, the thickness effect dominated and contributed to the larger closed quotient of vocal fold vibration, larger normalized maximum flow declination rate, and lower H1-H2 in adult males as compared to adult females and children. The effect of differences in vocal fold depth was generally small. When targeting a specific SPL, adult males experienced a lower peak vocal fold contact pressure during phonation than adult females and children.

Vocal tract adjustments to minimize vocal fold contact pressure during phonation.

This computational study aims to identify vocal tract adjustments that minimize the peak vocal fold contact pressure during phonation and thus should be targeted in voice therapy treating phonotraumatic vocal hyperfunction. The results showed that for a given subglottal pressure, the effect of vocal tract adjustments on the peak vocal fold contact pressure was generally small except when such adjustments caused noticeable changes in the glottal flow amplitude. In this study, this occurred mainly when the lip opening was reduced and at conditions of large initial glottal angles or high subglottal pressures, which decreased the peak contact pressure but also significantly reduced the output sound pressure level (SPL). On the other hand, increasing lip opening significantly increased sound radiation efficiency from the mouth and reduced the subglottal pressure required to produce a target SPL. Because of the large effect of the subglottal pressure on the peak contact pressure, increasing lip opening thus was able to significantly reduce the peak contact pressure in voice tasks targeting a specific SPL. In contrast, the effect of pharyngeal expansion alone had only a small effect on the peak contact pressure, whether controlling for the subglottal pressure or targeting a specific SPL.

Computational simulations of respiratory-laryngeal interactions and their effects on lung volume termination during phonation: Considerations for hyperfunctional voice disorders.

Glottal resistance plays an important role in airflow conservation, especially in the context of high vocal demands. However, it remains unclear if laryngeal strategies most effective in controlling airflow during phonation are consistent with clinical manifestations of vocal hyperfunction. This study used a previously validated three-dimensional computational model of the vocal folds coupled with a respiratory model to investigate which laryngeal strategies were the best predictors of lung volume termination (LVT) and how these strategies' effects were modulated by respiratory parameters. Results indicated that the initial glottal angle and vertical thickness of the vocal folds were the best predictors of LVT regardless of subglottal pressure, lung volume initiation, and breath group duration. The effect of vertical thickness on LVT increased with the subglottal pressure-highlighting the importance of monitoring loudness during voice therapy to avoid laryngeal compensation-and decreased with increasing vocal fold stiffness. A positive initial glottal angle required an increase in vertical thickness to complete a target utterance, especially when the respiratory system was taxed. Overall, findings support the hypothesis that laryngeal strategies consistent with hyperfunctional voice disorders are effective in increasing LVT, and that conservation of airflow and respiratory effort may represent underlying mechanisms in those disorders.

A Serum Metabolomic Study on Rats Induced by Polygoni Multiflori Radix and Polygoni Multiflori Radix Preparata by Pattern Recognition and Pathways Analysis.

This study focused on the differential metabolomic effects between water extracts of Polygoni Multiflori Radix and Polygoni Multiflori Radix Preparata in rats. The extracts were subsequently administered for 28 d. Serum biochemical indicators were tested, hematoxylin-eosin staining and immunohistochemistry staining were used to detect histopathological changes in the livers. Ultra-performance LC/quadrupole time-of-flight mass spectrometry was used to detect the changes in endogenous metabolites. Finally, we performed detailed analysis of the changes in metabolic pathways. Hematoxylin-eosin staining and immunohistochemistry staining results indicated that the water extracts of Polygoni Multiflori Radix and Polygoni Multiflori Radix Preparata had mild liver injury effect. Fifty-two differential endogenous biomarkers were confirmed as potential biomarkers between Polygoni Multiflori Radix and Polygoni Multiflori Radix Preparata groups. In the positive ion mode, the biomarkers included 31 Phosphatidyl cholines (PCs), six lysoPCs, and ceramide. In the negative ion mode, 12 biomarkers were confirmed, including glycodeoxycholic acid, chenodeoxycholic acid, and deoxycholic acid, etc. In Hydrophilic Interaction Liquid Chromatography (HILIC) mode, nine biomarkers were confirmed, including niacinamide, L-palmitoylcarnitine, and butyrylcarnitine, etc. Using MetaboAnalyst 4.0, six related metabolic pathways, including taurine and hypotaurine metabolism, sphingolipid metabolism, glycerophospholipid metabolism, nicotinate and nicotinamide metabolism, arginine and proline metabolism, and tryptophan metabolism and primary bile synthesis, were confirmed as the most differential pathways between the Polygoni Multiflori Radix and Polygoni Multiflori Radix Preparata groups.

Laryngeal strategies to minimize vocal fold contact pressure and their effect on voice production.

The goal of this study is to identify laryngeal strategies that minimize vocal fold contact pressure while producing a target sound pressure level (SPL) using a three-dimensional voice production model. The results show that while the subglottal pressure and transverse stiffness can be manipulated to reduce the peak contact pressure, such manipulations also reduce the SPL, and are thus less effective in reducing contact pressure in voice tasks targeting a specific SPL level. In contrast, changes in the initial glottal angle and vocal fold vertical thickness that reduce the contact pressure also increase the SPL. Thus, in voice tasks targeting a specific SPL, such changes in the initial glottal angle and vertical thickness also lower the subglottal pressure, which further reduces the peak contact pressure. Overall the results show that for voice tasks with a target SPL level, vocal fold contact pressure can be significantly reduced by adopting a barely abducted glottal configuration or reducing the vocal fold vertical thickness. Aerodynamic measures are effective in identifying voice production with large initial glottal angles, but by themselves alone are not useful in differentiating hyperadducted vocal folds from barely abducted vocal folds, which may be better differentiated by closed quotient and voice type measures.

Estimation of vocal fold physiology from voice acoustics using machine learning.

The goal of this study is to estimate vocal fold geometry, stiffness, position, and subglottal pressure from voice acoustics, toward clinical and other voice technology applications. Unlike previous voice inversion research that often uses lumped-element models of phonation, this study explores the feasibility of voice inversion using data generated from a three-dimensional voice production model. Neural networks are trained to estimate vocal fold properties and subglottal pressure from voice features extracted from the simulation data. Results show reasonably good estimation accuracy, particularly for vocal fold properties with a consistent global effect on voice production, and reasonable agreement with excised human larynx experiment.

Structural constitutive modeling of the anisotropic mechanical properties of human vocal fold lamina propria.

The anisotropic mechanical properties of the vocal fold lamina propria play an important role in voice production and control. The goal of this study is to develop a constitutive model capable of predicting lamina propria elastic moduli along both the longitudinal and transverse directions under different conditions of vocal fold elongation, which can be used as input to reduced-order phonation models based on linear elasticity. A structurally-based constitutive model that links microstructural characteristics of the lamina propria to its macromechanical properties is proposed. The model prediction has been shown to agree reasonably well with recent biaxial tensile testing results.