Envelope Research Articles

Shouting affects temporal properties of the speech amplitude envelope.

Distinguishing shouted from non-shouted speech is crucial in communication. We examined how shouting affects temporal properties of the amplitude envelope (ENV) in a total of 720 sentences read by 18 Swiss German speakers in normal and shouted modes; shouting was characterised by maintaining sound pressure levels of ≥80 dB sound pressure level (dB-SPL) (C-weighted) at a 1-meter distance from the mouth. Generalized additive models revealed significant temporal alterations of ENV in shouted speech, marked by steeper ascent, delayed peak, and extended high levels. These findings offer potential cues for identifying shouting, particularly useful when fine-structure and dynamic range cues are absent, for example, in cochlear implant users.

Identification of Cartilaginous Fish Endogenous Foamy Virus Rooting to Vertebrate Counterparts.

Foamy viruses (FVs) are ideal models for studying the long-term evolutionary history between viruses and their hosts. Currently, FVs have been documented in nearly all major taxa of vertebrates, but evidence is lacking for true FV infiltration in cartilaginous fish, the most basal living vertebrates with jaws. Here, we screened 11 available genomes and 10 transcriptome sequence assemblies of cartilaginous fish and revealed a novel endogenous foamy virus, termed cartilaginous fish endogenous foamy virus (CFEFV), in the genomes of sharks and rays. Genomic analysis of CFEFVs revealed feature motifs that were retained among canonical FVs. Phylogenetic analysis using polymerase sequences revealed the rooting nature of CFEFVs to vertebrate FVs, indicating their deep origin. Interestingly, three viral lineages were found in a shark (Scyliorhinus torazame), one of which was clustered with ray-finned fish foamy-like viruses, indicating that multiple episodes of viral infiltrations had occurred in this species. These findings fill a major gap in the Spumaretrovirinae taxon and reveal the aquatic origin of FVs found in terrestrial vertebrates. IMPORTANCE Although foamy viruses (FVs) have been found in major branches of vertebrates, the presence of these viruses in cartilaginous fish, the most basal living vertebrates with jaws, remains to be explored. This study revealed a collection of cartilaginous endogenous FVs in sharks and rays through in silico genomic mining. These viruses were rooted in the polymerase (POL) phylogeny, indicating the ancient aquatic origin of FVs. However, their envelope (ENV) protein grouped with those of amphibian FVs, suggesting different evolutionary histories of different FV genes. Overall, we provide the last missing gap for the taxonomic investigation of Spumaretrovirinae and provide concrete support for the aquatic origin of FVs.

Modeling temporal information encoding by the population of fibers in the healthy and synaptopathic auditory nerve

We report a theoretical study aimed at investigating the impact of cochlear synapse loss (synaptopathy) on the encoding of the envelope (ENV) and temporal fine structure (TFS) of sounds by the population of auditory nerve fibers. A computational model was used to simulate auditory-nerve spike trains evoked by sinusoidally amplitude-modulated (AM) tones at 10 Hz with various carrier frequencies and levels. The model included 16 cochlear channels with characteristic frequencies (CFs) from 250 Hz to 8 kHz. Each channel was innervated by 3, 4 and 10 fibers with low (LSR), medium (MSR), and high spontaneous rates (HSR), respectively. For each channel, spike trains were collapsed into three separate ‘population’ post-stimulus time histograms (PSTHs), one per fiber type. Information theory was applied to reconstruct the stimulus waveform, ENV, and TFS from one or more PSTHs in a mathematically optimal way. The quality of the reconstruction was regarded as an estimate of the information present in the used PSTHs. Various synaptopathy scenarios were simulated by removing fibers of specific types and/or cochlear regions before stimulus reconstruction. We found that the TFS was predominantly encoded by HSR fibers at all stimulus carrier frequencies and levels. The encoding of the ENV was more complex. At lower levels, the ENV was predominantly encoded by HSR fibers with CFs near the stimulus carrier frequency. At higher levels, the ENV was equally well or better encoded by HSR fibers with CFs different from the AM carrier frequency as by LSR fibers with CFs at the carrier frequency. Altogether, findings suggest that a healthy population of HSR fibers (i.e., including fibers with CFs around and remote from the AM carrier frequency) might be sufficient to encode the ENV and TFS over a wide range of stimulus levels. Findings are discussed regarding their relevance for diagnosing synaptopathy using non-invasive ENV- and TFS-based measures.

Objective speech intelligibility prediction using a deep learning model with continuous speech-evoked cortical auditory responses.

Auditory prostheses provide an opportunity for rehabilitation of hearing-impaired patients. Speech intelligibility can be used to estimate the extent to which the auditory prosthesis improves the user’s speech comprehension. Although behavior-based speech intelligibility is the gold standard, precise evaluation is limited due to its subjectiveness. Here, we used a convolutional neural network to predict speech intelligibility from electroencephalography (EEG). Sixty-four–channel EEGs were recorded from 87 adult participants with normal hearing. Sentences spectrally degraded by a 2-, 3-, 4-, 5-, and 8-channel vocoder were used to set relatively low speech intelligibility conditions. A Korean sentence recognition test was used. The speech intelligibility scores were divided into 41 discrete levels ranging from 0 to 100%, with a step of 2.5%. Three scores, namely 30.0, 37.5, and 40.0%, were not collected. The speech features, i.e., the speech temporal envelope (ENV) and phoneme (PH) onset, were used to extract continuous-speech EEGs for speech intelligibility prediction. The deep learning model was trained by a dataset of event-related potentials (ERP), correlation coefficients between the ERPs and ENVs, between the ERPs and PH onset, or between ERPs and the product of the multiplication of PH and ENV (PHENV). The speech intelligibility prediction accuracies were 97.33% (ERP), 99.42% (ENV), 99.55% (PH), and 99.91% (PHENV). The models were interpreted using the occlusion sensitivity approach. While the ENV models’ informative electrodes were located in the occipital area, the informative electrodes of the phoneme models, i.e., PH and PHENV, were based on the occlusion sensitivity map located in the language processing area. Of the models tested, the PHENV model obtained the best speech intelligibility prediction accuracy. This model may promote clinical prediction of speech intelligibility with a comfort speech intelligibility test.

Cross-Frequency Coupling in Cortical Processing of Speech.

This study examines power-power cross-frequency coupling (CFC) between different frequency bands of cortical activity in normal-hearing (NH) listeners and its association to the processing temporal envelope (ENV) and temporal fine structure (TFS) of speech. CFC between alpha and theta bands and between gamma and theta bands was investigated when only ENV or TFS or the original speech itself were processed. Comparing the cortical activity in response to ENV and original speech, there was an increase in alpha-theta CFC and in gamma-theta CFC when listening to ENV alone. However, when comparing the response when to listening TFS alone, there was a reduction in gamma-theta CFC compared to the original speech and the alpha-theta CFC was comparable to the equivalent observed with original speech. The increase in CFC may suggest that there is more synchrony across different bands of cortical activity in processing ENV than TFS. These measures can serve as indicators when either ENV or TFS is perceived.

TLR4 Associated Signaling Disrupters as a New Means to Overcome HERV-W Envelope-Mediated Myelination Deficits.

Myelin repair in the adult central nervous system (CNS) is driven by successful differentiation of resident oligodendroglial precursor cells (OPCs) and thus constitutes a neurodegenerative process capable to compensate for functional deficits upon loss of oligodendrocytes and myelin sheaths as it is observed in multiple sclerosis (MS). The human endogenous retrovirus type W (HERV-W) represents an MS-specific pathogenic entity, and its envelope (ENV) protein was previously identified as a negative regulator of OPC maturation—hence, it is of relevance in the context of diminished myelin repair. We here focused on the activity of the ENV protein and investigated how it can be neutralized for improved remyelination. ENV-mediated activation of toll like receptor 4 (TLR4) increases inducible nitric oxide synthase (iNOS) expression, prompts nitrosative stress, and results in myelin-associated deficits, such as decreased levels of oligodendroglial maturation marker expression and morphological alterations. The intervention of TLR4 surface expression represents a potential means to rescue such ENV-dependent deficits. To this end, the rescue capacity of specific substances, either modulating V-ATPase activity or myeloid differentiation 2 (MD2)-mediated TLR4 glycosylation status, such as compound 20 (C20), L48H437, or folimycin, was analyzed, as these processes were demonstrated to be relevant for TLR4 surface expression. We found that pharmacological treatment can rescue the maturation arrest of oligodendroglial cells and their myelination capacity and can prevent iNOS induction in the presence of the ENV protein. In addition, downregulation of TLR4 surface expression was observed. Furthermore, mitochondrial integrity crucial for oligodendroglial cell differentiation was affected in the presence of ENV and ameliorated upon pharmacological treatment. Our study, therefore, provides novel insights into possible means to overcome myelination deficits associated with HERV-W ENV-mediated myelin deficits.

Native listeners rely on rhythmic cues when deciding on the nativeness of speech.

Foreign-accented speech typically deviates segmentally and suprasegmentally from native-accented speech. Two experiments were conducted to investigate the role of amplitude envelope (ENV), segment duration (DUR), and speech rate (SR) on Italian listeners' ability to identify native-accented Italian in utterances produced by Zurich German speakers. In experiment 1, listeners judged in a two-alternative forced-choice perception task which of the two stimuli in a trial they perceived as more native-like. Stimuli in each trial only varied in ENV and DUR, which were retrieved either from a native Italian speaker [first language (L1) donor] or from a German speaker of Italian [second language (L2) donor]. Results revealed that listeners make use of both DUR and ENV to identify the more native-like stimuli, but the effect of ENV was more subtle. In experiment 2, SR differences (resulting from native and non-native segment duration differences in experiment 1) were normalized for. It was found that this drastically reduced the effect of segment durations in terms of perceived nativeness; however, the ENV effect still remained. This was not the case in a control group of listeners without competence in Italian. Though effects were subtle, the study shows that ENV cues contribute to the percept of nativeness in L2 speech.

Different binaural processing of the envelope component and the temporal fine structure component of a narrowband noise in rat inferior colliculus

Complex broadband sounds are decomposed by peripheral auditory filters into a series of relatively narrowband signals, each with a slowly varying envelope (ENV) and a rapidly fluctuating temporal fine structure (TFS). ENV and TFS information at the bilateral ears contribute differentially to auditory perception. However, whether the difference could attribute to mechanisms of binaural integration remains an open question. As a potential neural correlate, subsets of neurons in the central nucleus of the inferior colliculus (ICC) are known to integrate binaural information with binaural inhibition or binaural summation. Therefore, we recorded the frequency-following responses (FFRs) to the ENV and TFS components of narrowband noises in the ICC of anesthetized rats and examined changes in FFR amplitude and stimulus-response coherence under various sound-delivery settings. We showed that binaural FFRENV was predominantly elicited by contralateral inputs and inhibited by ipsilateral inputs, exhibiting a “binaural-inhibition” like property. On the other hand, binaural FFRTFS received a balanced contribution from both sides, echoing the “binaural-summation” mechanism. What is more, binaural FFRENV was significantly correlated with contralateral-evoked but not ipsilateral-evoked FFRENV, while binaural FFRTFS correlated with both contralateral- and ipsilateral-evoked FFRTFS. Overall, these results suggest distinct binaural processing of ENV and TFS information at the midbrain level.

Signal envelope and speech intelligibility differentially impact auditory motion perception

Our acoustic environment contains a plethora of complex sounds that are often in motion. To gauge approaching danger and communicate effectively, listeners need to localize and identify sounds, which includes determining sound motion. This study addresses which acoustic cues impact listeners’ ability to determine sound motion. Signal envelope (ENV) cues are implicated in both sound motion tracking and stimulus intelligibility, suggesting that these processes could be competing for sound processing resources. We created auditory chimaera from speech and noise stimuli and varied the number of frequency bands, effectively manipulating speech intelligibility. Normal-hearing adults were presented with stationary or moving chimaeras and reported perceived sound motion and content. Results show that sensitivity to sound motion is not affected by speech intelligibility, but shows a clear difference for original noise and speech stimuli. Further, acoustic chimaera with speech-like ENVs which had intelligible content induced a strong bias in listeners to report sounds as stationary. Increasing stimulus intelligibility systematically increased that bias and removing intelligible content reduced it, suggesting that sound content may be prioritized over sound motion. These findings suggest that sound motion processing in the auditory system can be biased by acoustic parameters related to speech intelligibility.

Insights from the interfaces of HIV-1 envelope (ENV) trimer viral protein GP160 (GP120-GP41)

The Human Immunodeficiency Virus (HIV-1) type 1 viral protein is a life threatening virus causing HIV/AIDS in infected humans. The HIV-1 envelope (ENV) trimer glycoprotein GP160 (GP120-GP41) is gaining attention in recent years as a potential vaccine candidate for HIV-1/AIDS. However, the sequence variation and charge polarity at the interacting sites across clades is a shortcoming faced in the development of an effective HIV-1 vaccine. We analyzed the interfaces in terms of its interface area, interface size, and interface energies (van der Waals, hydrogen bonds, and electrostatics). The interfaces were divided as dominant (≥60%) and subdominant (<60%) based on van der Waals contribution to total energies. 88% of GP120 and 74% of GP41 interfaces are highly pronounced with van der Waals energy having large interfaces with interface size (98±65 (GP120) and 73±65 (GP41)) and interface area (882±1166Å2 (GP120) and 921±1288Å2 (GP41)). Nevertheless, 12% of GP120 and 26% of GP41 interfaces have subdominant van der Waals energies having small interfaces with interface size (58±20 (GP120) and 27±9 (GP41)) and interface area (581±1605Å2 (GP120) and 483±896Å2 (GP41)). It was interesting to observe GP41 small interfaces with subdominant van der Waals are stabilized by electrostatics (r2=0.63) without hydrogen bonds (r2=0). However, GP120 small interfaces were found to have two fold more hydrogen bonds (r2=0.59) than electrostatics (r2=0.20). Therefore, our previous finding stating that small protein-protein interfaces rich in electrostatics holds true in case of GP41 whereas not with GP120 protein interfaces.

Effectiveness Analysis of Rolling Bearing Fault Detectors Based On Self-Organising Kohonen Neural Network – A Case Study of PMSM Drive

Abstract Due to their many advantages, permanent magnet synchronous motors (PMSMs) are increasingly used in not only industrial drive systems but also electric and hybrid vehicle drives, aviation and other applications. Unfortunately, PMSMs are not free from damage that occurs during their operation. It is assumed that about 40% of the damage that occurs is related to rolling bearing damage. This article focuses on the use of Kohonen neural network (KNN) for rolling bearing damage detection in a PMSM drive system. The symptoms from the fast Fourier transform (FFT) and Envelope (ENV) Analysis of the mechanical vibration acceleration signal were analysed. The signal ENV was obtained by applying the Hilbert transform (HT). Two neural network functions are discussed: a detector and a classifier. The detector detected the damage and the classifier determined the type of damage to the rolling bearing (undamaged bearing, damaged rolling element, outer or inner race). The effectiveness of the analysed networks from the point of view of the applied signal processing method, map size, type of neighbourhood radius, distance function and the influence of input data normalisation are presented. The results are presented in the form of a confusion matrix, together with 2D and 3D maps of active neurons.

Characterizing speech rhythm using spectral coherence between jaw displacement and speech temporal envelope

Lower modulation rates in the temporal envelope (ENV) of the acoustic signal are believed to be the rhythmic backbone in speech, facilitating speech comprehension in terms of neuronal entrainments at δ- and θ-rates (these rates are comparable to the foot- and syllable-rates phonetically). The jaw plays the role of a carrier articulator regulating mouth opening in a quasi-cyclical way, which correspond to the low-frequency modulations as a physical consequence. This paper describes a method to examine the joint roles of jaw oscillation and ENV in realizing speech rhythm using spectral coherence. Relative powers in the frequency bands corresponding to the δ-and θ-oscillations in the coherence (respectively notated as %δ and %θ) were quantified as one possible way of revealing the amount of concomitant foot- and syllable-level rhythmicities carried by both acoustic and articulatory domains. Two English corpora (mngu0 and MOCHA-TIMIT) were used for the proof of concept. %δ and %θ were regressed on utterance duration for an initial analysis. Results showed that the degrees of foot- and syllable-sized rhythmicities are different and are contingent upon the utterance length.

The impact of temporal fine structure and signal envelope on auditory motion perception.

The majority of psychoacoustic research investigating sound localization has utilized stationary sources, yet most naturally occurring sounds are in motion, either because the sound source itself moves, or the listener does. In normal hearing (NH) listeners, previous research showed the extent to which sound duration and velocity impact the ability of listeners to detect sound movement. By contrast, little is known about how listeners with hearing impairments perceive moving sounds; the only study to date comparing the performance of NH and bilateral cochlear implant (BiCI) listeners has demonstrated significantly poorer performance on motion detection tasks in BiCI listeners. Cochlear implants, auditory protheses offered to profoundly deaf individuals for access to spoken language, retain the signal envelope (ENV), while discarding temporal fine structure (TFS) of the original acoustic input. As a result, BiCI users do not have access to low-frequency TFS cues, which have previously been shown to be crucial for sound localization in NH listeners. Instead, BiCI listeners seem to rely on ENV cues for sound localization, especially level cues. Given that NH and BiCI listeners differentially utilize ENV and TFS information, the present study aimed to investigate the usefulness of these cues for auditory motion perception. We created acoustic chimaera stimuli, which allowed us to test the relative contributions of ENV and TFS to auditory motion perception. Stimuli were either moving or stationary, presented to NH listeners in free field. The task was to track the perceived sound location. We found that removing low-frequency TFS reduces sensitivity to sound motion, and fluctuating speech envelopes strongly biased the judgment of sounds to be stationary. Our findings yield a possible explanation as to why BiCI users struggle to identify sound motion, and provide a first account of cues important to the functional aspect of auditory motion perception.

Effects of rehabilitation training on an elderly population with mild to moderate hearing loss: study protocol for a randomised clinical trial

Background: Age-related hearing loss (presbycusis) is a form of hearing loss in over 60-years-olds and has a negative impact on quality of life. Presbycusis is multifactorial and is predominately characterised with a loss of speech perception in noise. In the cochlea, auditory filters decompose broadband sound into a series of narrowband output signals, which contains two kinds of temporal information: slow changes in overall amplitude envelope (ENV) and faster variations in temporal fine structure (TFS). TFS is important for recognition of target speech in noise. The main aim of the study is to evaluate the effect of TFS rehabilitation training in participants over the age of 60 years with mild to moderate hearing loss. Methods: A randomised clinical trial conducted on 30 participants with mild (loss of 20-39dB HL) to moderate (40-69dB HL) hearing loss, aged between 60 and 75 years old. Participants with conductive hearing loss, abnormal middle ear pathology and central nervous system disease were excluded. Participants were selected randomly to an intervention and control group with a 1:1 ratio. Rehabilitation for the intervention Group are 30-minute sessions three times a week for a total five weeks of vowel consonant vowel words that are used to eliminate ENV and keep only TFS. Word in noise test, binaural TFS test, and Speech, Spatial and Qualities of Hearing Scale scores are performed at the beginning and end of study to evaluate the effect of rehabilitation training. Conclusion: Life expectancy in the elderly has improved, leading to an increased prevalence of age-related diseases including presbycusis. A literature review highlighted that TFS damage is permanent; however, in this study we will attempt to prove that TFS training may lead to speech in noise perception improvement. Trial registration: Registry of Clinical Trials, IRCT2019625044006N1 (7 th August 2019).

T-cells producing multiple combinations of IFNγ, TNF and IL10 are associated with mild forms of dengue infection.

Multifunctional interleukin 10 (IL10)+ Th1 cells have been implicated in favorable evolution of many infectious diseases, promoting an efficacious immune response while limiting immunopathology. Here, we investigated the presence of multifunctional CD4+ and CD8+ T-cells that expressed interferon gamma (IFNγ), IL10 and tumor necrosis factor (TNF), or its combinations during dengue infection. Peripheral blood mononuclear cells (PBMCs) from outpatients with dengue (mild dengue forms) and hospitalized patients (or patients with dengue with warning signs and severe dengue) were cultured in the presence of envelope (ENV) or NS3 peptide libraries of DENV during critical (hospitalization period) and convalescence phases. The production of IFNγ, IL10 and TNF by CD4+ and CD8+ T-cells was assessed by flow cytometry. Our data show that patients with mild dengue, when compared with patients with dengue with warning signs and severe dengue, presented higher frequencies of multifunctional T-cells like NS3-specific IFNγ/IL10-producing CD4+ T-cells in critical phase and NS3- and ENV-specific CD8+ T-cells producing IFNγ/IL10. In addition, NS3-specific CD8+ T-cells producing high levels of IFNγ/TNF and IFNγ/TNF/IL10 were also observed in the mild dengue group. We observed that multifunctional T-cells produced higher levels of cytokines as measured by intracellular content when compared with single producer T-cells. Importantly, multifunctional CD4+ and CD8+ T-cells producing IFNγ, TNF and IL10 simultaneously displayed positive correlation with platelet levels, suggesting a protective role of this population. The presence of IL10+ Th1 and IL10+ Tc1 multifunctional cells was associated with mild dengue presentation, suggesting that these cells play a role in clinical evolution of dengue infection.

Effect of inter-aural modulation depth difference on interaural time difference thresholds for speech: An observational study

Background: The temporal envelope (ENV) plays a vital role in conveying inter-aural time difference (ITD) in many clinical populations. However, the presence of background noise and electronic features, such as compression, reduces the modulation depth of ENV to a different degree in both ears. The effect of ENV modulation depth differences between the ears on ITD thresholds is unknown; therefore, this was the aim of the current study’s investigation. Methods: Six normally hearing young adults (age range 20-30 years) participated in the current study. Six vowel-consonant-vowel (VCV) (/aka/, /aga/, /apa/, /aba/, /ata/, /ada/) tokens were used as the probe stimuli. ENV depth of VCV tokens was smeared by 0%, 29%, and 50%, which results in 100%, 71%, and 50% of the original modulation depth. ITD thresholds were estimated as a function of the difference in temporal ENV depth between the ears, wherein in one ear the modulation depth was retained at 100% and in the other ear, the modulation depth was changed to 100%, 71%, and 50%. Results: Repeated measures of ANOVA revealed a significant main effect of interaural modulation depth differences on the ITD threshold (F(2,10)= 9.04, p= 0.006). ITD thresholds increased with an increase in the inter-aural modulation depth difference. Conclusion: Inter-aural ENV depth is critical for ITD perception.

PORÓWNANIE SYLABICZNIE I PODWÓJNIE SKOMPRESOWANYCH MALAJSKICH ZDAŃ CHIMERYCZNYCH PRZETWORZONYCH PRZEZ APARAT SŁUCHOWY

ObjectivesThe human auditory system perceives any speech sound through the inherent temporal cues i.e., the temporal fine structure (TFS) and envelope (ENV) cues which has its own predominance for perception across languages. Research in English and Mandarin Chinese language showed the difference between these cues with tonal language employ more of TFS cues and non-tonal language employ ENV cues for perception. Earlier studies on Indian language (Kannada and Malayalam) revealed ENV cues predominance for perception. Based on this, the aim of this study was to compare stimuli in which the TFS and ENV cues had been interchanged (so-called auditory chimeras). The stimuli were Malayalam language sentences delivered through a hearing aid using two compression schemes – syllabic compression and dual compres-sion – and processed by a nonlinear 8-channel and 16-channel system.MethodThirty-five normal hearing individuals were assessed for the perception of chimeric sentences across eight sets of frequency bands (1, 4, 6, 8, 16, 24, 32, and 64 bands). Before the administration of the chimeric sentences all the individuals were assessed for normal hearing abilities through routine audiological evaluations.ResultsThe results of the present study reveal there is a significant difference across frequency bands on both the syllabic and dual compression processed stimuli using either 8 or 16 channels. The ENV cues were better perceived whether 4, 6, 8, or 16 frequency bands were used, with dual compression being marginally better than syllabic compression for both 8 and 16 channels. However, 16 channels gave overall better perception than 8 channels.ConclusionsThe results of the study revealed a better processing of envelope (ENV) cues, which are most important for understanding speech through a hearing aid.

Effect of inter-aural modulation depth difference on interaural time difference thresholds for speech: An observational study.

Background: The temporal envelope (ENV) plays a vital role in conveying inter-aural time difference (ITD) in many clinical populations. However, the presence of background noise and electronic features, such as compression, reduces the modulation depth of ENV to a different degree in both ears. The effect of ENV modulation depth differences between the ears on ITD thresholds is unknown; therefore, this was the aim of the current study's investigation. Methods: Six normally hearing young adults (age range 20-30 years) participated in the current study. Six vowel-consonant-vowel (VCV) (/aka/, /aga/, /apa/, /aba/, /ata/, /ada/) tokens were used as the probe stimuli. ENV depth of VCV tokens was smeared by 0%, 29%, and 50%, which results in 100%, 71%, and 50% of the original modulation depth. ITD thresholds were estimated as a function of the difference in temporal ENV depth between the ears, wherein in one ear the modulation depth was retained at 100% and in the other ear, the modulation depth was changed to 100%, 71%, and 50%. Results: Repeated measures of ANOVA revealed a significant main effect of interaural modulation depth differences on the ITD threshold (F(2,10)= 9.04, p= 0.006). ITD thresholds increased with an increase in the inter-aural modulation depth difference. Conclusion: Inter-aural ENV depth is critical for ITD perception.

Identifying cues for tone-in-noise detection using decision variable correlation in the budgerigar (Melopsittacus undulatus).

Previous studies evaluated cues for masked tone detection using reproducible noise waveforms. Human results founded on this approach suggest that tone detection is based on combined energy and envelope (ENV) cues, but detection cues in nonhuman species are less clear. Decision variable correlation (DVC) was used to evaluate tone-in-noise detection cues in the budgerigar, an avian species with human-like behavioral sensitivity to many complex sounds. DVC quantifies a model's ability to predict trial-by-trial variance in behavioral responses. Budgerigars were behaviorally conditioned to detect 500-Hz tones in wideband (WB; 100-3000 Hz) and narrowband (NB; 452-552 Hz) noise. Behavioral responses were obtained using a single-interval, two-alternative discrimination task and two-down, one-up adaptive tracking procedures. Tone-detection thresholds in WB noise were higher than human thresholds, putatively due to broader peripheral frequency tuning, whereas NB thresholds were within ∼1 dB of human results. Budgerigar average hit and false-alarm rates across noise waveforms were consistent, highly correlated across subjects, and correlated to human results. Trial-by-trial behavioral results in NB noise were best explained by a model combining energy and ENV cues. In contrast, WB results were better predicted by ENV-based or multiple-channel energy detector models. These results suggest that budgerigars and humans use similar cues for tone-in-noise detection.

Abstract 1623: Autoantibodies to human endogenous retrovirus K envelope protein (HERV-K ENV) are associated with features of prostate cancer aggressiveness in African American men

Abstract Prostate cancer (PCa) is the most commonly diagnosed cancer and the second leading cause of cancer-related deaths in American men. African-American (AA) men are more likely to develop PCa at a younger age and are twice as likely to die from the disease compared to men from other ethnic/racial backgrounds. Even when normalized with equal access to healthcare, socioeconomic status and familial PCa history, AA men still die disproportionately from PCa. Thus, it is paramount to improve the early detection of aggressive PCa. A cancer patient’s humoral immune response to a tumor offers us a minimally invasive opportunity to detect aggressive cancers before a symptomatic tumor emerges. Previous studies indicate that genes associated with immunity and inflammation are significantly upregulated in prostate tumors from AA men compared to European-American (EA) men, suggesting that there are racial differences in the anti-tumor immune response in patients with PCa. This has prompted our laboratory to evaluate the autoantibody repertoire to tumor-associated antigens (TAA) in ethnically diverse patients. Previous studies showed a higher frequency of autoantibodies to the human endogenous retrovirus K (HERV-K) GAG protein in men with late stage PCa. In addition, investigators in this team reported previously an elevated expression of the envelope (ENV) protein in PCa tumors from AA men compared to PCa tumors from EA men. Given the emerging role of HERV-K in human cancers and the potential use of autoantibodies to the ENV and GAG viral proteins as cancer serum biomarkers and immunotherapeutic tools, we investigated the antibody response to the HERV-K ENV in AA and EA men with and without PCa. Using an enzyme-linked immunosorbent assay (ELISA), we detected a significant increase in the frequency of autoantibodies to HERV-K ENV in AA men with PCa compared to EA men with PCa (N=100, p<0.05) and AA men without PCa (N=100, p<0.0001). The frequency of autoantibodies to ENV was also significantly higher in AA men with stage IV (29%, p<0.0001) and AA men with PCa metastasis (40%, p<0.0001) compared to AA men without PCa or EA men with and without PCa. The immunoreactivity of the sera against ENV was confirmed by immunoblotting. To our knowledge this is the first report of an increased autoantibody frequency to HERV-K ENV in PCa patients and the first report of autoantibodies associated with racial differences in PCa. The observation that these autoantibodies are significantly linked to a more aggressive PCa in AA men is also consistent with previous observation of increased upregulation of HERV-K ENV in prostate tumors from AA men. The biological and clinical significance of anti-HERV-K ENV and GAG autoantibodies in PCa, and the racial differences in their frequency and clinical associations, warrant further investigation. Citation Format: Tino W. Sanchez, Shannalee R. Martinez, Greisha Ortiz-Hernandez, Evelyn Sanchez-Hernandez, Christopher Montgomery, Benjamin Becerra, Tiffany Dorsey, Feng Wang-Johanning, Stefan Ambs, Carlos A. Casiano. Autoantibodies to human endogenous retrovirus K envelope protein (HERV-K ENV) are associated with features of prostate cancer aggressiveness in African American men [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1623.