Spectral Cues Research Articles

Effect of Sound Coding Strategies on Music Perception with a Cochlear Implant.

The goal of this study was to evaluate the music perception of cochlear implantees with two different sound processing strategies. Methods: Twenty-one patients with unilateral or bilateral cochlear implants (Oticon Medical®) were included. A music trial evaluated emotions (sad versus happy based on tempo and/or minor versus major modes) with three tests of increasing difficulty. This was followed by a test evaluating the perception of musical dissonances (marked out of 10). A novel sound processing strategy reducing spectral distortions (CrystalisXDP, Oticon Medical) was compared to the standard strategy (main peak interleaved sampling). Each strategy was used one week before the music trial. Results: Total music score was higher with CrystalisXDP than with the standard strategy. Nine patients (21%) categorized music above the random level (>5) on test 3 only based on mode with either of the strategies. In this group, CrystalisXDP improved the performances. For dissonance detection, 17 patients (40%) scored above random level with either of the strategies. In this group, CrystalisXDP did not improve the performances. Conclusions: CrystalisXDP, which enhances spectral cues, seemed to improve the categorization of happy versus sad music. Spectral cues could participate in musical emotions in cochlear implantees and improve the quality of musical perception.

Cochlear tuning and the peripheral representation of harmonic sounds in mammals.

Albert Feng was a prominent comparative neurophysiologist whose research provided numerous contributions towards understanding how the spectral and temporal characteristics of vocalizations underlie sound communication in frogs and bats. The present study is dedicated to Al's memory and compares the spectral and temporal representations of stochastic, complex sounds which underlie the perception of pitch strength in humans and chinchillas. Specifically, the pitch strengths of these stochastic sounds differ between humans and chinchillas, suggesting that humans and chinchillas may be using different cues. Outputs of auditory filterbank models based on human and chinchilla cochlear tuning were examined. Excitation patterns of harmonics are enhanced in humans as compared with chinchillas. In contrast, summary correlograms are degraded in humans as compared with chinchillas. Comparing summary correlograms and excitation patterns with corresponding behavioral data on pitch strength suggests that the dominant cue for pitch strength in humans is spectral (i.e., harmonic) structure, whereas the dominant cue for chinchillas is temporal (i.e., envelope) structure. The results support arguments that the broader cochlear tuning in non-human mammals emphasizes temporal cues for pitch perception, whereas the sharper cochlear tuning in humans emphasizes spectral cues.

Immediate Integration of Coarticulatory Cues for /s/-Retraction in American English

Coarticulatory “noise” has long been presumed to benefit the speaker at the expense of the listener. However, recent work has found that listeners make use of that variation in real time to aid speech processing, immediately integrating coarticulatory cues as soon as they become available. Yet sibilants, sounds notable for their high degree of context-dependent variability, have been presumed to be unavailable for immediate integration, requiring that listeners hold all cues in a buffer until all relevant cues are available. The present study examines the cue integration strategies that listeners employ in the perception of prevocalic and pre-consonantal sibilants. In particular, this study examines the perception of /s/-retraction, an ongoing sound change whereby /s/ is realized approaching /ʃ/ as a result of long distance coarticulation from /r/. The study uses eye tracking in the Visual World Paradigm in order to determine precisely when listeners are able to utilize the spectral cues in sibilants in different phonological environments. Results demonstrate that while in most instances listeners wait until more cues are available before considering the correct candidate, fixation accuracy increases significantly throughout the sibilant interval alone. In the pre-consonantal environment, immediate integration strategies were strengthened when the coarticulatory cues of retraction were stronger and when they were more predictable. These findings provide further evidence that context-dependent variation can be helpful to listeners, even on the most variable of sounds.

High-Frequency Hearing Is Required to Compute a Topographic Map of Auditory Space in the Mouse Superior Colliculus.

A topographic map of auditory space is a feature found in the superior colliculus (SC) of many species, including CBA/CaJ mice. In this genetic background, high-frequency monaural spectral cues and interaural level differences (ILDs) are used to compute spatial receptive fields (RFs) that form a topographic map along the azimuth. Unfortunately, C57BL/6 mice, a strain widely used for transgenic manipulation, display age-related hearing loss (AHL) because of an inbred mutation in the Cadherin 23 gene (Cdh23) that affects hair cell mechanotransduction. To overcome this problem, researchers have used young C57BL/6 mice in their studies, as they have been shown to have normal hearing thresholds. However, important details of the auditory response characteristics of the SC such as spectral responses and spatial localization, have not been characterized in young C57BL/6 mice. Here, we show that two- to four-month C57BL/6 mice lack neurons with frontal auditory RFs and therefore lack a topographic representation of auditory space in the SC. Analysis of the spectrotemporal RFs (STRFs) of the SC auditory neurons shows that C57BL/6 mouse SC neurons lack the ability to detect the high-frequency (>40 kHz) spectral cues that are needed to compute frontal RFs. We also show that crossing C57BL/6 mice with CBA/CaJ mice or introducing one copy of the wild-type Cdh23 to C57BL/6 mice rescues the high-frequency hearing deficit and improves the topographic map of auditory space. Taken together, these results demonstrate the importance of high-frequency hearing in computing a topographic map of auditory space.

Amplification of input differences by dynamic heterogeneity in the spiral ganglion.

A defining feature of type I primary auditory afferents that compose ∼95% of the spiral ganglion is their intrinsic electrophysiological heterogeneity. This diversity is evident both between and within unitary, rapid, and slow adaptation (UA, RA, and SA) classes indicative of specializations designed to shape sensory receptor input. But to what end? Our initial impulse is to expect the opposite: that auditory afferents fire uniformly to represent acoustic stimuli with accuracy and high fidelity. Yet this is clearly not the case. One explanation for this neural signaling strategy is to coordinate a system in which differences between input stimuli are amplified. If this is correct, then stimulus disparity enhancements within the primary afferents should be transmitted seamlessly into auditory processing pathways that utilize population coding for difference detection. Using sound localization as an example, one would expect to observe separately regulated differences in intensity level compared with timing or spectral cues within a graded tonotopic distribution. This possibility was evaluated by examining the neuromodulatory effects of cAMP on immature neurons with high excitability and slow membrane kinetics. We found that electrophysiological correlates of intensity and timing were indeed independently regulated and tonotopically distributed, depending on intracellular cAMP signaling level. These observations, therefore, are indicative of a system in which differences between signaling elements of individual stimulus attributes are systematically amplified according to auditory processing constraints. Thus, dynamic heterogeneity mediated by cAMP in the spiral ganglion has the potential to enhance the representations of stimulus input disparities transmitted into higher level difference detection circuitry.NEW & NOTEWORTHY Can changes in intracellular second messenger signaling within primary auditory afferents shift our perception of sound? Results presented herein lead to this conclusion. We found that intracellular cAMP signaling level systematically altered the kinetics and excitability of primary auditory afferents, exemplifying how dynamic heterogeneity can enhance differences between electrophysiological correlates of timing and intensity.

Cue selection in the perception of pitch in music and speech

Spectral shape affects pitch perception; sounds with more high energy harmonics sound higher than sounds with low energy in higher harmonics. Flatter spectral slope corresponds to "tenser" voices while steeper spectral slope correlates to "breathier" voices in speech. In string instruments, the spectral slope differentiates sul ponticello and sul tasto. Listeners were found to integrate spectral slope cues in pitch perception in speech; however, work on music focused on cross-instrument differences, glossing over cue integration within instruments with fixed-formant frequencies. Furthermore, spectral cues and F0 co-vary in human pitch production, but are largely independent in instrumental music. It remains unclear whether music processing is as integrative as speech processing. In this study, listeners were given either speech or violin stimuli with identical pitch contour pairs, and were asked to decide whether the second contour was higher or lower in pitch compared to the first. The spectral slope of each sound was manipulated to include all combinations of “breathier”/“sul tasto” and “tenser”/“sul ponticello” sounding pairs. Results show that listeners integrate spectral slope cues in pitch perception in speech and violin stimuli similarly, with similar categoricity and shift. Overall, listeners with higher musicality have more categorical responses but no differences in shift.

The frequency-following response to assess the neural representation of spectral speech cues in older adults

Older adults often present difficulties understanding speech that cannot be explained by age-related changes in sound audibility. Psychoacoustic and electrophysiologic studies have linked these suprathreshold difficulties to age-related deficits in the auditory processing of temporal and spectral sound information. These studies suggest the existence of an age-related temporal processing deficit in the central auditory system, but the existence of such deficit in the spectral domain remains understudied. The FFR is an electrophysiological evoked response that assesses the ability of the neural auditory system to reproduce the spectral and temporal patterns of a sound. The main goal of this short review is to investigate if the FFR can identify and measure spectral processing deficits in the elderly compared to younger adults (for both, without hearing loss or competing noise). Furthermore, we want to determine what stimuli and analyses have been used in the literature to assess the neural encoding of spectral cues in older adults. Almost all reviewed articles showed an age-related decline in the auditory processing of spectral acoustic information. Even when using different speech and non-speech stimuli, studies reported an age-related decline at the fundamental frequency, at the first formant, and at other harmonic components using different metrics, such as the response's amplitude, inter-trial phase coherence, signal-to-response correlation, and signal-to-noise ratio. These results suggest that older adults may present age-related spectral processing difficulties, but further FFR studies are needed to clarify the effect of advancing age on the neural encoding of spectral speech cues. Spectral processing research on aging would benefit from using a broader variety of stimuli and from rigorously controlling for hearing thresholds even in the absence of disabling hearing loss. Advances in the understanding of the effect of age on FFR measures of spectral encoding could lead to the development of new clinical tools, with possible applications in the field of hearing aid fitting.

Unified Coding of Spectral and Temporal Phonetic Cues: Electrophysiological Evidence for Abstract Phonological Features.

Spoken word recognition models and phonological theory propose that abstract features play a central role in speech processing. It remains unknown, however, whether auditory cortex encodes linguistic features in a manner beyond the phonetic properties of the speech sounds themselves. We took advantage of the fact that English phonology functionally codes stops and fricatives as voiced or voiceless with two distinct phonetic cues: Fricatives use a spectral cue, whereas stops use a temporal cue. Evidence that these cues can be grouped together would indicate the disjunctive coding of distinct phonetic cues into a functionally defined abstract phonological feature. In English, the voicing feature, which distinguishes the consonants [s] and [t] from [z] and [d], respectively, is hypothesized to be specified only for voiceless consonants (e.g., [s t]). Here, participants listened to syllables in a many-to-one oddball design, while their EEG was recorded. In one block, both voiceless stops and fricatives were the standards. In the other block, both voiced stops and fricatives were the standards. A critical design element was the presence of intercategory variation within the standards. Therefore, a many-to-one relationship, which is necessary to elicit an MMN, existed only if the stop and fricative standards were grouped together. In addition to the ERPs, event-related spectral power was also analyzed. Results showed an MMN effect in the voiceless standards block-an asymmetric MMN-in a time window consistent with processing in auditory cortex, as well as increased prestimulus beta-band oscillatory power to voiceless standards. These findings suggest that (i) there is an auditory memory trace of the standards based on the shared [voiceless] feature, which is only functionally defined; (ii) voiced consonants are underspecified; and (iii) features can serve as a basis for predictive processing. Taken together, these results point toward auditory cortex's ability to functionally code distinct phonetic cues together and suggest that abstract features can be used to parse the continuous acoustic signal.

Musicality and Age Interaction in Tone Development.

Vocal pitch, which involves not only F0 but also multiple covarying acoustic cues is central to linguistic perception and production at various levels of prosodic structure. Recent studies on language development have shown that differences in learners' musicality affect the F0 cue development in perception of sentence-level intonation or in prosodic realization of focus. This study aims to contribute toward a fuller understanding of the effect of musicality on linguistic pitch development via a close investigation of the relationship between musicality, age, and lexical tone production covering both F0 and spectral cues in children. Forty-three native Mandarin-speaking children between the ages of 4 and 6 years are recruited to participate in both a semi-spontaneous tone production task and a musicality test. For each age (4, 5, and 6 years) and musicality (below or above the median score of each age group) group, the contrastivity of the four tones is evaluated by performing automatic tone classification using three sets of acoustic cues (F0, spectral cues, and both). It has been found that higher musicality is associated with higher contrastivity of the tones produced at the age of 4 and 5 years, but not at the age of 6 years. These results suggest that musicality promotes earlier development of tone production only in earlier stages of prosodic development; by the age of 6 years, the musicality advantage in tone production subsides.

Contribution of Vocal Tract and Glottal Source Spectral Cues in the Generation of Acted Happy and Aggressive Spanish Vowels

The source-filter model is one of the main techniques applied to speech analysis and synthesis. Recent advances in voice production by means of three-dimensional (3D) source-filter models have overcome several limitations of classic one-dimensional techniques. Despite the development of preliminary attempts to improve the expressiveness of 3D-generated voices, they are still far from achieving realistic results. Towards this goal, this work analyses the contribution of both the the vocal tract (VT) and the glottal source spectral (GSS) cues in the generation of happy and aggressive speech through a GlottDNN-based analysis-by-synthesis methodology. Paired neutral expressive utterances are parameterised to generate different combinations of expressive vowels, applying the target expressive GSS and/or VT cues on the neutral vowels after transplanting the expressive prosody on these utterances. The conducted objective tests focused on Spanish [a], [i] and [u] vowels show that both GSS and VT cues significantly reduce the spectral distance to the expressive target. The results from the perceptual test show that VT cues make a statistically significant contribution in the expression of happy and aggressive emotions for [a] vowels, while the GSS contribution is significant in [i] and [u] vowels.

Learning Spectral Cues for Multispectral and Panchromatic Image Fusion.

Recently, deep learning based multispectral (MS) and panchromatic (PAN) image fusion methods have been proposed, which extracted features automatically and hierarchically by a series of non-linear transformations to model the complicated imaging discrepancy. But they always pay more attention to the extraction and compensation of spatial details and use the mean squared error or mean absolute error as a loss function, regardless of the preservation of spectral information contained in multispectral images. For the sake of the improvements in both spatial and spectral resolution, this paper presents a novel fusion model that takes the spectral preservation into consideration, and learns the spectral cues from the process of generating a spectrally refined multispectral image, which is constrained by a spectral loss between the generated image and the reference image. Then these spectral cues are used to modulate the PAN features to obtain final fusion result. Experimental results on reduced-resolution and full-resolution datasets demonstrate that the proposed method can obtain a better fusion result in terms of visual inspection and evaluation indices when compared with current state-of-the-art methods.

The Influence of Dialect on the Perception and Production of Lax-Tense Vowel Distinction in English Learning

This acoustic experimental study investigates the influence of dialectal background on the perception and production of lax-tense vowel distinction in English learning from the theoretical standpoint of language transfer. Previous studies usually regard the first language as a source of transfer, with few considering the influence of dialect in the process of transfer, while this study has taken account of participants’ dialects and biological genders and look at whether and how Chinese dialectal knowledge is transferred in English learning. A perception and a production experiment are conducted with two groups of participants -- Cantonese Chinese speakers and Mandarin Chinese speakers -- to respectively analyze their perception and production strategy for English lax-tense vowel pairs [I]/[i:] and [ʊ]/[u:]. The study finds out that dialect and gender cause statistically significant difference. The result shows that Cantonese speakers can effectively leverage spectral cues to differentiate English tense vowels from lax vowels, while Mandarin speakers rely heavily on durational cues. The two lingual groups have disparate production result, but no one group is overall better than the other in producing lax-tense vowels. Mandarin and Cantonese participants only differ in the F2 of the [u:] production. Moreover, when gender is considered, Mandarin females can produce native-like [ʊ]; Cantonese males and females can produce native-like [I], Cantonese females native-like [i:] and Cantonese males native-like [u:]. This study confirms that dialect should be considered in transfer study, and further points out that both dialect and gender are significant variables of the transfer mechanism in foreign language acquisition.

Deep neural network models of sound localization reveal how perception is adapted to real-world environments

Mammals localize sounds using information from their two ears. Localization in real-world conditions is challenging, as echoes provide erroneous information, and noises mask parts of target sounds. To better understand real-world localization we equipped a deep neural network with human ears and trained it to localize sounds in a virtual environment. The resulting model localized accurately in realistic conditions with noise and reverberation. In simulated experiments, the model exhibited many features of human spatial hearing: sensitivity to monaural spectral cues and interaural time and level differences, integration across frequency, biases for sound onsets, and limits on localization of concurrent sources. But when trained in unnatural environments without either reverberation, noise, or natural sounds, these performance characteristics deviated from those of humans. The results show how biological hearing is adapted to the challenges of real-world environments and illustrate how artificial neural networks can reveal the real-world constraints that shape perception.

Single-Channel Focused Thresholds Relate to Vowel Identification in Pediatric and Adult Cochlear Implant Listeners.

Speech recognition outcomes are highly variable among pediatric and adult cochlear implant (CI) listeners. Although there is some evidence that the quality of the electrode-neuron interface (ENI) contributes to this large variability in auditory perception, its relationship with speech outcomes is not well understood. Single-channel auditory detection thresholds measured in response to focused electrical fields (i.e., focused thresholds) are sensitive to properties of ENI quality, including electrode-neuron distance, intracochlear resistance, and neural health. In the present study, focused thresholds and speech perception abilities were assessed in 15 children and 21 adult CI listeners. Focused thresholds were measured for all active electrodes using a fast sweep procedure. Speech perception performance was evaluated by assessing listeners’ ability to identify vowels presented in /h-vowel-d/ context. Consistent with prior literature, focused thresholds were lower for children than for adults, but vowel identification did not differ significantly across age groups. Higher across-array average focused thresholds, which may indicate a relatively poor ENI quality, were associated with poorer vowel identification scores in both children and adults. Adult CI listeners with longer durations of deafness had higher focused thresholds. Findings from this study demonstrate that poor-quality ENIs may contribute to reduced speech outcomes for pediatric and adult CI listeners. Estimates of ENI quality (e.g., focused thresholds) may assist in developing customized programming interventions that serve to improve the transmission of spectral cues that are important in vowel identification.

Temporal Versus Spectral Cues in L2 Perception of Vowels: A Study with Polish and Croatian Learners of English

Temporal Versus Spectral Cues in L2 Perception of Vowels: A Study with Polish and Croatian Learners of English

Rabbits use both spectral and temporal cues to discriminate the fundamental frequency of harmonic complexes with missing fundamentals.

The pitch of harmonic complex tones (HCTs) common in speech, music, and animal vocalizations plays a key role in the perceptual organization of sound. Unraveling the neural mechanisms of pitch perception requires animal models, but little is known about complex pitch perception by animals, and some species appear to use different pitch mechanisms than humans. Here, we tested rabbits' ability to discriminate the fundamental frequency (F0) of HCTs with missing fundamentals, using a behavioral paradigm inspired by foraging behavior in which rabbits learned to harness a spatial gradient in F0 to find the location of a virtual target within a room for a food reward. Rabbits were initially trained to discriminate HCTs with F0s in the range 400-800 Hz and with harmonics covering a wide frequency range (800-16,000 Hz) and then tested with stimuli differing in spectral composition to test the role of harmonic resolvability (experiment 1) or in F0 range (experiment 2) or in both F0 and spectral content (experiment 3). Together, these experiments show that rabbits can discriminate HCTs over a wide F0 range (200-1,600 Hz) encompassing the range of conspecific vocalizations and can use either the spectral pattern of harmonics resolved by the cochlea for higher F0s or temporal envelope cues resulting from interaction between unresolved harmonics for lower F0s. The qualitative similarity of these results to human performance supports the use of rabbits as an animal model for studies of pitch mechanisms, providing species differences in cochlear frequency selectivity and F0 range of vocalizations are taken into account.NEW & NOTEWORTHY Understanding the neural mechanisms of pitch perception requires experiments in animal models, but little is known about pitch perception by animals. Here we show that rabbits, a popular animal in auditory neuroscience, can discriminate complex sounds differing in pitch using either spectral cues or temporal cues. The results suggest that the role of spectral cues in pitch perception by animals may have been underestimated by predominantly testing low frequencies in the range of human voice.

LightCue: An Innovative Far-Red Light Emitter for Locally Modifying the Spectral Cue in Outdoor Conditions with Global Consequences on Plant Architecture.

Plasticity of plant architecture is a promising lever to increase crop resilience to biotic and abiotic damage. Among the main drivers of its regulation are the spectral signals which occur via photomorphogenesis processes. In particular, branching, one of the yield components, is responsive to photosynthetic photon flux density (PPFD) and to red to far-red ratio (R:FR), both signals whose effects are tricky to decorrelate in the field. Here, we developed a device consisting of far-red light emitting diode (LED) rings. It can reduce the R:FR ratio to 0.14 in the vicinity of an organ without changing the PPFD in outdoor high irradiance fluctuating conditions, which is a breakthrough as LEDs have been mostly used in non-fluctuant controlled conditions at low irradiance over short periods of time. Applied at the base of rapeseed stems during the whole bolting-reproductive phase, LightCue induced an expected significant inhibitory effect on two basal targeted axillary buds and a strong unexpected stimulatory effect on the overall plant aerial architecture. It increased shoot/root ratio while not modifying the carbon balance. LightCue therefore represents a promising device for progress in the understanding of light signal regulation in the field.

Proficiency in Using Level Cue for Sound Localization Is Related to the Auditory Cortical Structure in Patients With Single-Sided Deafness.

Spatial hearing, which largely relies on binaural time/level cues, is a challenge for patients with asymmetric hearing. The degree of the deficit is largely variable, and better sound localization performance is frequently reported. Studies on the compensatory mechanism revealed that monaural level cues and monoaural spectral cues contribute to variable behavior in those patients who lack binaural spatial cues. However, changes in the monaural level cues have not yet been separately investigated. In this study, the use of the level cue in sound localization was measured using stimuli of 1 kHz at a fixed level in patients with single-sided deafness (SSD), the most severe form of asymmetric hearing. The mean absolute error (MAE) was calculated and related to the duration/age onset of SSD. To elucidate the biological correlate of this variable behavior, sound localization ability was compared with the cortical volume of the parcellated auditory cortex. In both SSD patients (n = 26) and normal controls with one ear acutely plugged (n = 23), localization performance was best on the intact ear side; otherwise, there was wide interindividual variability. In the SSD group, the MAE on the intact ear side was worse than that of the acutely plugged controls, and it deteriorated with longer duration/younger age at SSD onset. On the impaired ear side, MAE improved with longer duration/younger age at SSD onset. Performance asymmetry across lateral hemifields decreased in the SSD group, and the maximum decrease was observed with the most extended duration/youngest age at SSD onset. The decreased functional asymmetry in patients with right SSD was related to greater cortical volumes in the right posterior superior temporal gyrus and the left planum temporale, which are typically involved in auditory spatial processing. The study results suggest that structural plasticity in the auditory cortex is related to behavioral changes in sound localization when utilizing monaural level cues in patients with SSD.

Hemispheric lateralization during spectral envelope perception is dynamic and individualized

The spectral envelope is an important acoustic cue for vowel and consonant perception. Sensitivity to the spectral envelope is commonly studied with a spectral modulation detection task in which two co-occurring spectral cues (spectral modulation—SM, carrier frequency—CF) may be available. Neuroimaging studies indicate that spectral cues are often processed asymmetrically in the cortex, but it is unknown if such lateralization depends on perceptual weighting of the available cues. Here we simultaneously measured SM discrimination and electroencephalography (EEG) in young adult listeners in a single-interval, two-alternative task during passive and active attention conditions as well as in a separate perceptual decision-weights task. Using condition-on-a-single-stimulus (COSS) analyses, individual differences in perceptual weights of spectral cues (SM, CF) were obtained for each listener. EEG source localized results showed that hemispheric lateralization was dynamically modulated over time between left and right auditory cortices and that lateralization was dependent on individual perceptual weighting patterns for SM and CF. [Work supported by NIH/NIA P01-AG09524 (ACE) and NIH/NIDCD R01- DC001262 (RL, ACE).]

Sound-source localization when listeners and/or sound sources move

In the dynamic everyday world, sound sources and/or listeners move when animals attempt to localize sound sources. Determining sound-source locations in these dynamic scenarios requires several computations by the brain. The auditory-spatial cues (Interaural Time Differences, ITDs; Interaural Level Differences, ITDS; and spectral cues associated with the head-related transfer function, HRTF) indicate the location of sound sources relative to the head. When the source and/or listener move, these cues change and by knowing the position of the head, the brain could determine which moved and where it moved based on the auditory-spatial cue changes. If interaural cues (ITDs or ILDs) are used for sound-source localization, cone-of-confusion errors occur, and head motion can resolve front-back, cone of-confusion errors. The elevation of a sound source, not effected by cone-of-confusion errors, might be able to be determined when both the source and listener move. This presentation will describe work in the Spatial Hearing Lab at ASU related to how sound source and listener motion affect sound source-location judgements in these scenarios. [Research supported by grants from NIDCD, WAY: R01-DC015214 and MTP: F32-DC016808.]