Local fractal dimension of collagen detects increased spatial complexity in fibrosis.

Increase of collagen content and reorganization characterizes fibrosis but quantifying the latter remains challenging. Spatially complex structures are often analyzed via the fractal dimension; however, established methods for calculating this quantity either provide a single dimension for an entire object or a spatially distributed dimension that only considers binary images. These neglect valuable information related to collagen density in images of fibrotic tissue. We sought to develop a fractal analysis that can be applied to 3-dimensional (3D) images of fibrotic tissue. A fractal dimension map for each image was calculated by determining a single fractal dimension for a small area surrounding each image pixel, using fiber thickness as the third dimension. We found that this local fractal dimension increased with age and with progression of fibrosis regardless of collagen content. Our new method of distributed 3D fractal analysis can thus distinguish between changes in collagen content and organization induced by fibrosis.

Patterns and effects of gene flow on adaptation across spatial scales: implications for management.

Gene flow can have rapid effects on adaptation and is an important evolutionary tool available when undertaking biological conservation and restoration. This tool is underused partly because of the perceived risk of outbreeding depression and loss of mean fitness when different populations are crossed. In this article, we briefly review some theory and empirical findings on how genetic variation is distributed across species ranges, describe known patterns of gene flow in nature with respect to environmental gradients, and highlight the effects of gene flow on adaptation in small or stressed populations in challenging environments (e.g., at species range limits). We then present a case study involving crosses at varying spatial scales among mountain populations of a trigger plant (Stylidium armeria: Stylidiaceae) in the Australian Alps to highlight how some issues around gene flow effects can be evaluated. We found evidence of outbreeding depression in seed production at greater geographic distances. Nevertheless, we found no evidence of maladaptive gene flow effects in likelihood of germination, plant performance (size), and performance variance, suggesting that gene flow at all spatial scales produces offspring with high adaptive potential. This case study demonstrates a path to evaluating how increasing sources of gene flow in managed wild and restored populations could identify some offspring with high fitness that could bolster the ability of populations to adapt to future environmental changes. We suggest further ways in which managers and researchers can act to understand and consider adaptive gene flow in natural and conservation contexts under rapidly changing conditions.

Semiclassical Husimi Distributions of Schur Vectors in Non-Hermitian Quantum Systems.

We construct a semiclassical phase-space density of Schur vectors in non-Hermitian quantum systems. Each Schur vector is associated to a single Planck cell. The Schur states are organized according to a classical norm landscape on phase space-a classical manifestation of the lifetimes which are characteristic of non-Hermitian systems. To demonstrate the generality of this construction we apply it to a highly nontrivial example: a PT-symmetric kicked rotor in the regimes of mixed and chaotic classical dynamics.

Effects of Self-Generated Noise on Estimates of Detection Threshold in Quiet for School-Age Children and Adults.

OBJECTIVES: Detection thresholds in quiet become adult-like earlier in childhood for high than low frequencies. When adults listen for sounds near threshold, they tend to engage in behaviors that reduce physiologic noise (e.g., quiet breathing), which is predominantly low frequency. Children may not suppress self-generated noise to the same extent as adults, such that low-frequency self-generated noise elevates thresholds in the associated frequency regions. This possibility was evaluated by measuring noise levels in the ear canal simultaneous with adaptive threshold estimation. DESIGN: Listeners were normal-hearing children (4.3 to 16.0 years) and adults. Detection thresholds were measured adaptively for 250-, 1000-, and 4000-Hz pure tones using a three-alternative forced-choice procedure. Recordings of noise in the ear canal were made while the listeners performed this task, with the earphone and microphone routed through a single foam insert. Levels of self-generated noise were computed in octave-wide bands. Age effects were evaluated for four groups: 4- to 6-year olds, 7- to 10-year olds, 11- to 16-year olds, and adults. RESULTS: Consistent with previous data, the effect of child age on thresholds was robust at 250 Hz and fell off at higher frequencies; thresholds of even the youngest listeners were similar to adults' at 4000 Hz. Self-generated noise had a similar low-pass spectral shape for all age groups, although the magnitude of self-generated noise was higher in younger listeners. If self-generated noise impairs detection, then noise levels should be higher for trials associated with the wrong answer than the right answer. This association was observed for all listener groups at the 250-Hz signal frequency. For adults and older children, this association was limited to the noise band centered on the 250-Hz signal. For the two younger groups of children, this association was strongest at the signal frequency, but extended to bands spectrally remote from the 250-Hz signal. For the 1000-Hz signal frequency, there was a broadly tuned association between noise and response only for the two younger groups of children. For the 4000-Hz signal frequency, only the youngest group of children demonstrated an association between responses and noise levels, and this association was particularly pronounced for bands below the signal frequency. CONCLUSIONS: These results provide evidence that self-generated noise plays a role in the prolonged development of low-frequency detection thresholds in quiet. Some aspects of the results are consistent with the possibility that self-generated noise elevates thresholds via energetic masking, particularly at 250 Hz. The association between behavioral responses and noise spectrally remote from the signal frequency is also consistent with the idea that self-generated noise may also reflect contributions of more central factors (e.g., inattention to the task). Evaluation of self-generated noise could improve diagnosis of minimal or mild hearing loss.

Factors affecting the development of speech recognition in steady and modulated noise.

This study used a checkerboard-masking paradigm to investigate the development of the speech reception threshold (SRT) for monosyllabic words in synchronously and asynchronously modulated noise. In asynchronous modulation, masker frequencies below 1300 Hz were gated off when frequencies above 1300 Hz were gated on, and vice versa. The goals of the study were to examine development of the ability to use asynchronous spectro-temporal cues for speech recognition and to assess factors related to speech frequency region and audible speech bandwidth. A speech-shaped noise masker was steady or was modulated synchronously or asynchronously across frequency. Target words were presented to 5-7 year old children or to adults. Overall, children showed higher SRTs and smaller masking release than adults. Consideration of the present results along with previous findings supports the idea that children can have particularly poor masked SRTs when the speech and masker spectra differ substantially, and that this may arise due to children requiring a wider speech bandwidth than adults for speech recognition. The results were also consistent with the idea that children are relatively poor in integrating speech cues when the frequency regions with the best signal-to-noise ratios vary across frequency as a function of time.

Effect of response context and masker type on word recognition in school-age children and adults.

In adults, masked speech recognition improves with the provision of a closed set of response alternatives. The present study evaluated whether school-age children (5-13 years) benefit to the same extent as adults from a forced-choice context, and whether this effect depends on masker type. Experiment 1 compared masked speech reception thresholds for disyllabic words in either an open-set or a four-alternative forced-choice (4AFC) task. Maskers were speech-shaped noise or two-talker speech. Experiment 2 compared masked speech reception thresholds for monosyllabic words in two 4AFC tasks, one in which the target and foils were phonetically similar and one in which they were dissimilar. Maskers were speech-shaped noise, amplitude-modulated noise, or two-talker speech. For both experiments, it was predicted that children would not benefit from the information provided by the 4AFC context to the same degree as adults, particularly when the masker was complex (two-talker) or when audible speech cues were temporally sparse (modulated-noise). Results indicate that young children do benefit from a 4AFC context to the same extent as adults in speech-shaped noise and amplitude-modulated noise, but the benefit of context increases with listener age for the two-talker speech masker.

The effect of noise fluctuation and spectral bandwidth on gap detection.

Experiment 1 investigated gap detection for random and low-fluctuation noise (LFN) markers as a function of bandwidth (25-1600 Hz), level [40 or 75 dB sound pressure level (SPL)], and center frequency (500-4000 Hz). Gap thresholds for random noise improved as bandwidth increased from 25 to 1600 Hz, but there were only minor effects related to center frequency and level. For narrow bandwidths, thresholds were lower for LFN than random markers; this difference extended to higher bandwidths at the higher center frequencies and was particularly large at high stimulus level. Effects of frequency and level were broadly consistent with the idea that peripheral filtering can increase fluctuation in the encoded LFN stimulus. Experiment 2 tested gap detection for 200-Hz-wide noise bands centered on 2000 Hz, using high-pass maskers to examine spread of excitation effects. Such effects were absent or minor for random noise markers and the 40-dB-SPL LFN markers. In contrast, some high-pass maskers substantially worsened performance for the 75-dB-SPL LFN markers. These results were consistent with an interpretation that relatively acute gap detection for the high-level LFN gap markers resulted from spread of excitation to higher-frequency auditory filters where the magnitude and phase characteristics of the LFN stimuli are better preserved.

Cochlear hearing loss and the detection of sinusoidal versus random amplitude modulation.

This study assessed the effect of cochlear hearing loss on detection of random and sinusoidal amplitude modulation. Listeners with hearing loss and normal-hearing listeners (eight per group) generated temporal modulation transfer functions (TMTFs) for envelope fluctuations carried by a 2000-Hz pure tone. TMTFs for the two groups were similar at low modulation rates but diverged at higher rates presumably because of differences in frequency selectivity. For both groups, detection of random modulation was poorer than for sinusoidal modulation at lower rates but the reverse occurred at higher rates. No evidence was found that cochlear hearing loss, per se, affects modulation detection.

Interactions between chronic ethanol consumption and thiamine deficiency on neural plasticity, spatial memory, and cognitive flexibility.

BACKGROUND: Many alcoholics display moderate to severe cognitive dysfunction accompanied by brain pathology. A factor confounded with prolonged heavy alcohol consumption is poor nutrition, and many alcoholics are thiamine deficient. Thus, thiamine deficiency (TD) has emerged as a key factor underlying alcohol-related brain damage (ARBD). TD in humans can lead to Wernicke Encephalitis that can progress into Wernicke-Korsakoff syndrome and these disorders have a high prevalence among alcoholics. Animal models are critical for determining the exact contributions of ethanol (EtOH)- and TD-induced neurotoxicity, as well as the interactions of those factors to brain and cognitive dysfunction. METHODS: Adult rats were randomly assigned to 1 of 6 treatment conditions: chronic EtOH treatment (CET) where rats consumed a 20% v/v solution of EtOH over 6 months; severe pyrithiamine-induced TD (PTD-moderate acute stage); moderate PTD (PTD-early acute stage); moderate PTD followed by CET (PTD-CET); moderate PTD during CET (CET-PTD); and pair-fed (PF) control. After recovery from treatment, all rats were tested on spontaneous alternation and attentional set-shifting. After behavioral testing, brains were harvested for determination of mature brain-derived neurotrophic factor (BDNF) and thalamic pathology. RESULTS: Moderate TD combined with CET, regardless of treatment order, produced significant impairments in spatial memory, cognitive flexibility, and reductions in brain plasticity as measured by BDNF levels in the frontal cortex and hippocampus. These alterations are greater than those seen in moderate TD alone, and the synergistic effects of moderate TD with CET lead to a unique cognitive profile. However, CET did not exacerbate thalamic pathology seen after moderate TD. CONCLUSIONS: These data support the emerging theory that subclinical TD during chronic heavy alcohol consumption is critical for the development of significant cognitive impairment associated with ARBD.

Masked sentence recognition assessed at ascending target-to-masker ratios: modest effects of repeating stimuli.

OBJECTIVES: Masked sentence recognition is typically evaluated by presenting a novel stimulus on each trial. As a consequence, experiments calling for replicate estimates in multiple conditions require large corpora of stimuli. The present study evaluated the consequences of repeating sentence-plus-masker pairs at ascending target-to-masker ratios (TMRs). The hypothesis was that performance on each trial would be consistent with the cues available to the listener at the associated TMR, resulting in similar estimates of threshold and slope for procedures using novel versus repeated sentences within an ascending-TMR block of trials. DESIGN: A group of 37 normal-hearing young adults participated. Each listener was tested in the presence of one of three maskers: a multitalker babble, a speech-shaped noise, or an amplitude-modulated speech-shaped noise. There were two data collection procedures, both proceeding in blocks of trials with ascending TMRs. The novel-stimulus procedure used five lists of AzBio sentences, one presented at each of five TMRs, with a novel sentence and masker sample on each trial. The repeated-stimulus procedure used a single list of AzBio sentences, with each sentence presented at multiple TMRs, progressing from low to high; each sentence was paired with a single masker sample, such that only the TMR changed within blocks of repeated stimuli. Listeners completed one run with the novel-stimulus procedure and five runs with the repeated-stimulus procedure. The resulting values of percent correct at each TMR were fitted with a logit function to estimate threshold and psychometric function slope. RESULTS: The novel- and repeated-stimulus procedures resulted in generally similar data patterns. After controlling for effects related to the order in which listeners completed the six data collection runs, mean thresholds were slightly higher (<0.5 dB) for the repeated-stimulus procedure than the novel-stimulus procedure in all three maskers. Function slopes for the multitalker babble and amplitude-modulated noise maskers were slightly shallower using the repeated-stimulus than the novel-stimulus procedure, but slopes were comparable for the speech-shaped noise. The quality of psychometric function fits was significantly better for the repeated-stimulus than the novel-stimulus procedure, even when comparing a single run of the repeated-stimulus procedure (using one list) to a run of the novel-stimulus procedure (using five lists). CONCLUSIONS: Repeating sentences at ascending TMRs is an efficient method for estimating thresholds and psychometric function slopes, both in terms of the number of sentences and the number of trials.

Toxicity of Raw and Purified Single-Walled Carbon Nanotubes in Rat's Lung Epithelial and Cervical Cancer Cells.

The increased applications of carbon nanotubes in the field of drug delivery, bioimaging and biosensors demand nanotubes to be of highest purity, free from metallic impurities and amorphous carbon. All of these sectors require a profound investigation about the toxic effects on human and the environment. Many attempts have been made to purify and surface modify the carbon nanotubes, however a detailed study on the raw and purified material has yet to be conducted. Here we present the toxicity studies of raw and the purified single-walled carbon nanotubes in rat's lung epithelial cell and cervical cancer cells (HeLa). These cells were treated with increasing concentration of 0.5 µg/mL to 50 µg/mL and the various biocompatibility assays were performed. The results showed an increased cell death with purified single-walled carbon nanotubes followed by the depletion of antioxidant levels and activation of the caspase cascade at a rapid rate compared to raw single-walled carbon nanotubes. This suggests that purified single walled carbon nanotubes are more toxic to the cells and exhibit ultra-fine particulate matter like toxicity.

Effect of stimulus bandwidth and duration on monaural envelope correlation perception.

Monaural envelope correlation perception is the ability to discriminate between stimuli composed of two or more bands of noise based on envelope correlation. Sensitivity decreases as stimulus bandwidth is reduced below 100 Hz. The present study manipulated stimulus bandwidth (25-100 Hz) and duration (25-800 ms) to evaluate whether performance of highly trained listeners is limited by the number of inherent modulation periods in each presentation. Stimuli were two bands of noise, separated by a 500-Hz gap centered on 2250 Hz. Performance improved reliably with increasing numbers of envelope modulation periods, although there were substantial individual differences.

Agarose gel tailored calcium carbonate nanoparticles-synthesis and biocompatibility evaluation.

In this study, a novel approach to tailor the calcium carbonate nanoparticles was exploited based on agarose gel as polymer medium. The size of nanoparticles formed was governed by ionic diffusion and affected by weight percent of agarose and reaction temperature. The size, shape, purity, composition and allotropy of the synthesized nanoparticles were analyzed by different characterization techniques. Purity of nanoparticles as small as 37 nm demonstrates their suitability for broad range of industrial applications. The exposure of rat lung epithelial cells to these nanoparticles even at a higher concentration (50 microg/ml) did not induce considerable oxidative stress or cell death authenticating their fidelity to potential applications in the field of biotechnology and medicine. Through the simple and economic method of synthesis adopted in this study, separation of nanoparticles from the gel was easy, and process parameters could be optimized to control the particle size.

Effects of linguistic experience on the ability to benefit from temporal and spectral masker modulation.

Masked speech perception can often be improved by modulating the masker temporally and/or spectrally. These effects tend to be larger in normal-hearing listeners than hearing-impaired listeners, and effects of temporal modulation are larger in adults than young children [Hall et al. (2012). Ear Hear. 33, 340-348]. Initial reports indicate non-native adult speakers of the target language also have a reduced ability to benefit from temporal masker modulation [Stuart et al. (2010). J. Am. Acad. Aud. 21, 239-248]. The present study further investigated the effect of masker modulation on English speech recognition in normal-hearing adults who are non-native speakers of English. Sentence recognition was assessed in a steady-state baseline masker condition and in three modulated masker conditions, characterized by spectral, temporal, or spectro-temporal modulation. Thresholds for non-natives were poorer than those of native English speakers in all conditions, particularly in the presence of a modulated masker. The group differences were consistent across maskers when assessed in percent correct, suggesting that a single factor may limit the performance of non-native listeners similarly in all conditions.

Development of speech glimpsing in synchronously and asynchronously modulated noise.

This study investigated development of the ability to integrate glimpses of speech in modulated noise. Noise was modulated synchronously across frequency or asynchronously such that when noise below 1300 Hz was "off," noise above 1300 Hz was "on," and vice versa. Asynchronous masking was used to examine the ability of listeners to integrate speech glimpses separated across time and frequency. The study used the Word Intelligibility by Picture Identification (WIPI) test and included adults, older children (age 8-10 yr) and younger children (5-7 yr). Results showed poorer masking release for the children than the adults for synchronous modulation but not for asynchronous modulation. It is possible that children can integrate cues relatively well when all intervals provide at least partial speech information (asynchronous modulation) but less well when some intervals provide little or no information (synchronous modulation). Control conditions indicated that children appeared to derive less benefit than adults from speech cues below 1300 Hz. This frequency effect was supported by supplementary conditions where the noise was unmodulated and the speech was low- or high-pass filtered. Possible sources of the developmental frequency effect include differences in frequency weighting, effective speech bandwidth, and the signal-to-noise ratio in the unmodulated noise condition.

Elucidating the interaction between stretch and stiffness using an agent-based spring network model of progressive pulmonary fibrosis.

Pulmonary fibrosis is a deadly disease that involves the dysregulation of fibroblasts and myofibroblasts, which are mechanosensitive. Previous computational models have succeeded in modeling stiffness-mediated fibroblasts behaviors; however, these models have neglected to consider stretch-mediated behaviors, especially stretch-sensitive channels and the stretch-mediated release of latent TGF-ß. Here, we develop and explore an agent-based model and spring network model hybrid that is capable of recapitulating both stiffness and stretch. Using the model, we evaluate the role of mechanical signaling in homeostasis and disease progression during self-healing and fibrosis, respectively. We develop the model such that there is a fibrotic threshold near which the network tends towards instability and fibrosis or below which the network tends to heal. The healing response is due to the stretch signal, whereas the fibrotic response occurs when the stiffness signal overpowers the stretch signal, creating a positive feedback loop. We also find that by changing the proportional weights of the stretch and stiffness signals, we observe heterogeneity in pathological network structure similar to that seen in human IPF tissue. The system also shows emergent behavior and bifurcations: whether the network will heal or turn fibrotic depends on the initial network organization of the damage, clearly demonstrating structure's pivotal role in healing or fibrosis of the overall network. In summary, these results strongly suggest that the mechanical signaling present in the lungs combined with network effects contribute to both homeostasis and disease progression.

Wideband monaural envelope correlation perception.

This study investigated monaural envelope correlation perception (Richards 1987) for noise bandwidths ranging from 25 to 1,600 Hz. The high-frequency side of the low band was fixed at 3,000 Hz and the low-frequency side of the high band was fixed at 3,500 Hz. When comodulated, the magnitude spectra of the pair of noise bands were either identical or reflected around the midpoint. Six listeners with normal hearing participated. Listeners showed similar performance for identical and reflected-spectrum conditions, with best performance usually occurring for bandwidths between 200 and 800 Hz. Results were considered in terms of envelope comparisons of waveforms at the outputs of multiple peripheral filters or envelope comparisons of waveforms at the outputs of central filters set to the bandwidths of the noise stimuli. Some aspects of the results were incompatible with the account based on multiple peripheral filters. However, the results of a supplementary condition involving the gating of band subregions indicated that this incompatibility could be accounted for by nonoptimal weighting of peripheral filter outputs.

Monaural envelope correlation perception for bands narrower or wider than a critical band.

Monaural envelope correlation perception concerns the ability of listeners to discriminate stimuli based on the degree of correlation between the temporal envelopes of two or more frequency-separated bands of noise [Richards, J. Acoust. Soc. Am. 82, 1621-1630 (1987)]. Previous work has examined this ability for relatively narrow bandwidths, generally 100 Hz or less. The present experiment explored a wide range of bandwidths, from 25 to 1600 Hz, which included bands narrower and wider than a critical bandwidth. Stimuli were pairs of noise bands separated by a 500-Hz-wide spectral gap centered on 2250 Hz. The magnitude spectra of the pair of comodulated bands were either identical or reflected around the midpoint of the band, and performance was assessed with and without a low-pass noise masker. Although discrimination was best for intermediate bandwidths, mean performance was above chance for all bandwidths tested. Data were similar for stimuli with identical and reflected magnitude spectra, and for stimuli with and without the low-pass masker. The one exception was particularly good performance for intermediate-bandwidth stimuli with identical spectra, for which some listeners reported hearing a tonal cue. Results indicate that listeners are flexible in selecting spectral regions upon which to base across-frequency comparisons.

The monaural temporal window based on masking period pattern data in school-aged children and adults.

Several lines of evidence indicate that auditory temporal resolution improves over childhood, whereas other data implicate the development of processing efficiency. The present study used the masking period pattern paradigm to examine the maturation of temporal processing in normal-hearing children (4.8 to 10.7 yrs) compared to adults. Thresholds for a brief tone were measured at 6 temporal positions relative to the period of a 5-Hz quasi-square-wave masker envelope, with a 20-dB modulation depth, as well as in 2 steady maskers. The signal was a pure tone at either 1000 or 6500 Hz, and the masker was a band of noise, either spectrally wide or narrow (21.3 and 1.4 equivalent rectangular bandwidths, respectively). Masker modulation improved thresholds more for wide than narrow bandwidths, and adults tended to receive more benefit from modulation than young children. Fits to data for the wide maskers indicated a change in window symmetry with development, reflecting relatively greater backward masking for the youngest listeners. Data for children >6.5 yrs of age appeared more adult-like for the 6500- than the 1000-Hz signal. Differences in temporal window asymmetry with listener age cannot be entirely explained as a consequence of a higher criterion for detection in children, a form of inefficiency.