A Clinically Viable Medial Olivocochlear Reflex Assay Using Transient-Evoked Otoacoustic Emissions.

OBJECTIVES: The contralateral medial olivocochlear reflex (MOCR) strength may indicate various auditory conditions in humans, but a clinically viable assay and equipment are needed for quick, accurate, and reliable measurements. The first experiment compared an earlier version of the assay, which used a nonlinear-mode chirp stimulus, with a new assay using a linear-mode click stimulus, designed to give reliable MOCR measurements in most normal-hearing ears. The second experiment extended the improved assay on a purpose-built binaural hardware platform that used forward-pressure level (FPL) calibration for both the stimulus and the contralateral MOCR elicitor. DESIGN: Transient-evoked otoacoustic emission (TEOAE) tests were measured with and without a 60-dB SPL MOCR-evoking contralateral broadband noise. The normalized MOCR strength (MOCR%) was derived from the TEOAE responses for each trial pair using the complex pressure difference weighted by the TEOAE magnitude. Experiment 1 compared MOCR% within-subject and across-day using two TEOAE stimuli: nonlinear-mode chirps (50 dB SPL, bandpass 1-5 kHz, 14 ms window delayed by 2 ms) and linear-mode clicks (50 dB SPL, bandpass 0.5-2.5 kHz, 13 ms window delayed by 5 ms). TEOAE responses were analyzed in the 0.5 to 2.5 kHz band. Thirty adult participants with normal hearing (30 ears) completed the study. The TEOAE stimulus was calibrated in situ using spectral flattening, and the contralateral noise was calibrated in a coupler. Twelve TEOAE trial pairs were collected for each participant and condition. Experiment 2 used a purpose-built binaural system. The TEOAE stimuli were linear-mode clicks (50 dB SPL, bandpass 1-3 kHz, 13 ms window delayed by 5 ms), analyzed in the 1 to 3 kHz band over ~12 trial pairs. After a probe refit, an additional trial pair was collected for the two early-stopping signal-to-noise ratio criteria (15 and 20 dB). They were evaluated for single-trial reliability and test time. Nineteen adult participants with normal hearing (38 ears) completed the study. The TEOAE clicks and contralateral elicitor noise were calibrated in situ using FPL and delivered with automated timing. RESULTS: MOCR% for linear-mode clicks was distinguishable from measurement variability in 98% to 100% of participants' ears (both experiments), compared with only 73% for the nonlinear-mode chirp (experiment 1). MOCR detectability was assessed using the MOCR% across-subject/within-subject variance ratio. The ratio in experiment 1 for linear-mode clicks was higher (8.0) than for nonlinear-mode chirps (6.4). The ratio for linear-mode clicks (8.9) in experiment 2 was slightly higher than for the comparable linear-mode stimulus (8.0) in experiment 1. TEOAEs showed excellent reliability with high signal-to-noise ratios in both experiments, but reliability was higher for linear-mode clicks than nonlinear-mode chirps. MOCR reliability for the two stimuli was comparable. The FPL pressure response retest reliability derived from the SPL at the microphone was higher than the SPL retest reliability across 0.4 to 8 kHz. Stable results required 2 to 3 trial pairs for the linear-mode click (experiments 1 and 2) and three for the nonlinear-mode chirp (experiment 1), taking around 2 min on average. CONCLUSIONS: The linear-mode click assay produced measurable, reliable, and stable TEOAE and MOCR results on both hardware platforms in around 2 min per ear. The stimulus design and response window ensured that any stimulus artifact in linear mode was unlikely to confound the results. The refined assay is ready to produce high-quality data quickly for clinical and field studies to develop population norms, recognize diagnostic patterns, and determine risk profiles.

Kiss1 expression in the hypothalamic arcuate nucleus is lower in dairy cows of reduced fertility†.

We tested the hypothesis that divergent genetic merit for fertility of dairy cows is due to aberrant reproductive neuroendocrine function. The kisspeptin status of non-pregnant cows of either positive (POS) or negative (NEG) breeding values (BVs) for fertility was studied in three groups (n = 8), based on their previous post-partum period: POS cows, which had spontaneous ovarian cycles (POS-CYC) and NEG cows, which either cycled (NEG-CYC) or did not cycle (NEG-NONCYC). Ovarian cycles were synchronized, blood samples were taken to define endocrine status, and the animals were slaughtered in an artificial follicular phase. The brains and the pituitary glands were collected for quantitative polymerase chain reaction (qPCR) and in situ hybridization of hypothalamic GNRH1, Kiss1, TAC3, and PDYN and pituitary expression of LHB and FSHB. Gonadotropin releasing hormone (GnRH) and kisspeptin levels were quantified in snap frozen median eminence (ME). GNRH1 expression and GnRH levels in the ME were similar across groups. Kiss1 expression in the preoptic area of the hypothalamus was also similar across groups, but Kiss1 in the arcuate nucleus was almost 2-fold higher in POS-CYC cows than in NEG groups. TAC3 expression was higher in POS-CYC cows. The number of pituitary gonadotropes and the level of expression of LHB and FSHB were similar across groups. We conclude that the lower levels of Kiss1 and TAC3 in NEG cows with low fertility status and may lead to deficient GnRH and gonadotropin secretion.

Changes in tree drought sensitivity provided early warning signals to the California drought and forest mortality event.

Climate warming in recent decades has negatively impacted forest health in the western United States. Here, we report on potential early warning signals (EWS) for drought-related mortality derived from measurements of tree-ring growth (ring width index; RWI) and carbon isotope discrimination (∆13 C), primarily focused on ponderosa pine (Pinus ponderosa). Sampling was conducted in the southern Sierra Nevada Mountains, near the epicenter of drought severity and mortality associated with the 2012-2015 California drought and concurrent outbreak of western pine beetle (Dendroctonus brevicomis). At this site, we found that widespread mortality was presaged by five decades of increasing sensitivity (i.e., increased explained variation) of both tree growth and ∆13 C to Palmer Drought Severity Index (PDSI). We hypothesized that increasing sensitivity of tree growth and ∆13 C to hydroclimate constitute EWS that indicate an increased likelihood of widespread forest mortality caused by direct and indirect effects of drought. We then tested these EWS in additional ponderosa pine-dominated forests that experienced varying mortality rates associated with the same California drought event. In general, drier sites showed increasing sensitivity of RWI to PDSI over the last century, as well as higher mortality following the California drought event compared to wetter sites. Two sites displayed evidence that thinning or fire events that reduced stand basal area effectively reversed the trend of increasing hydroclimate sensitivity. These comparisons indicate that reducing competition for soil water and/or decreasing bark beetle host tree density via forest management-particularly in drier regions-may buffer these forests against drought stress and associated mortality risk. EWS such as these could provide land managers more time to mitigate the extent or severity of forest mortality in advance of droughts. Substantial efforts at deploying additional dendrochronological research in concert with remote sensing and forest modeling will aid in forecasting of forest responses to continued climate warming.

Limited evidence for CO2 -related growth enhancement in northern Rocky Mountain lodgepole pine populations across climate gradients.

Forests sequester large amounts of carbon annually and are integral in buffering against effects of global change. Increasing atmospheric CO2 may enhance photosynthesis and/or decrease stomatal conductance (gs ) thereby enhancing intrinsic water-use efficiency (iWUE), having potential indirect and direct benefits to tree growth. While increasing iWUE has been observed in most trees globally, enhanced growth is not ubiquitous, possibly due to concurrent climatic constraints on growth. To investigate our incomplete understanding of interactions between climate and CO2 and their impacts on tree physiology and growth, we used an environmental gradient approach. We combined dendrochronology with carbon isotope analysis (δ13 C) to assess the covariation of basal area increment (BAI) and iWUE over time in lodgepole pine. Trees were sampled at 18 sites spanning two climatically distinct elevation transects on the lee and windward sides of the Continental Divide, encompassing the majority of lodgepole pine's northern Rocky Mountain elevational range. We analyzed BAI and iWUE from 1950 to 2015, and explored correlations with monthly climate variables. As expected, iWUE increased at all sites. However, concurrent growth trends depended on site climatic water deficit (CWD). Significant growth increases occurred only at the driest sites, where increases in iWUE were strongest, while growth decreases were greatest at sites where CWD has been historically lowest. Late summer drought of the previous year negatively affected growth across sites. These results suggest that increasing iWUE, if strong enough, may indirectly benefit growth at drier sites by effectively extending the growing season via reductions in gs . Strong growth decreases at high elevation windward sites may reflect increasing water stress as a result of decreasing snowpack, which was not offset by greater iWUE. Our results imply that increasing iWUE driven by decreasing gs may benefit tree growth in limited scenarios, having implications for future carbon uptake potential of semiarid ecosystems.

Pure-Tone Audiometry With Forward Pressure Level Calibration Leads to Clinically-Relevant Improvements in Test-Retest Reliability.

OBJECTIVES: Clinical pure-tone audiometry is conducted using stimuli delivered through supra-aural headphones or insert earphones. The stimuli are calibrated in an acoustic (average ear) coupler. Deviations in individual-ear acoustics from the coupler acoustics affect test validity, and variations in probe insertion and headphone placement affect both test validity and test-retest reliability. Using an insert earphone designed for otoacoustic emission testing, which contains a microphone and loudspeaker, an individualized in-the-ear calibration can be calculated from the ear-canal sound pressure measured at the microphone. However, the total sound pressure level (SPL) measured at the microphone may be affected by standing-wave nulls at higher frequencies, producing errors in stimulus level of up to 20 dB. An alternative is to calibrate using the forward pressure level (FPL) component, which is derived from the total SPL using a wideband acoustic immittance measurement, and represents the pressure wave incident on the eardrum. The objective of this study is to establish test-retest reliability for FPL calibration of pure-tone audiometry stimuli, compared with in-the-ear and coupler sound pressure calibrations. DESIGN: The authors compared standard audiometry using a modern clinical audiometer with TDH-39P supra-aural headphones calibrated in a coupler to a prototype audiometer with an ER10C earphone calibrated three ways: (1) in-the-ear using the total SPL at the microphone, (2) in-the-ear using the FPL at the microphone, and (3) in a coupler (all three are derived from the same measurement). The test procedure was similar to that commonly used in hearing-conservation programs, using pulsed-tone test frequencies at 0.5, 1, 2, 3, 4, 6, and 8 kHz, and an automated modified Hughson-Westlake audiometric procedure. Fifteen adult human participants with normal to mildly-impaired hearing were selected, and one ear from each was tested. Participants completed 10 audiograms on each system, with test-order randomly varied and with headphones and earphones refitted by the tester between tests. RESULTS: Fourteen of 15 ears had standing-wave nulls present between 4 and 8 kHz. The mean intrasubject SD at 6 and 8 kHz was lowest for the FPL calibration, and was comparable with the low-frequency reliability across calibration methods. This decrease in variability translates to statistically-derived significant threshold shift criteria indicating that 15 dB shifts in hearing can be reliably detected at 6 and 8 kHz using FPL-calibrated ER10C earphones, compared with 20 to 25 dB shifts using standard TDH-39P headphones with a coupler calibration. CONCLUSIONS: These results indicate that reliability is better with insert earphones, especially with in-the-ear FPL calibration, compared with a standard clinical audiometer with supra-aural headphones. However, in-the-ear SPL calibration should not be used due to its sensitivity to standing waves. The improvement in reliability is clinically meaningful, potentially allowing hearing-conservation programs to more confidently determine significant threshold shifts at 6 kHz-a key frequency for the early detection of noise-induced hearing loss.

Proteome profiling of exosomes derived from plasma of heifers with divergent genetic merit for fertility.

The current study evaluated exosomes isolated from plasma of heifers bred to have high or low fertility through developing extreme diversity in fertility breeding values, however, key animal traits (e.g., body weight, milk production, and percentage of North American genetics) remained similar between the 2 groups. The exosomes were isolated by a combined ultracentrifugation and size exclusion chromatography approach and characterized by their size distribution (nanoparticle tracking analysis), morphology (transmission electron microscopy), and presence of exosomal markers (immunoblotting). In addition, a targeted mass spectrometry approach was used to confirm the presence of 2 exosomal markers, tumor susceptibility gene 101 and flotillin 1. The number of exosomes from plasma of high fertility heifers was greater compared with low fertility heifers. Interestingly, the exosomal proteomic profile, evaluated using mass spectrometry, identified 89 and 116 proteins in the high and low fertility heifers respectively, of which 4 and 31 were unique, respectively. These include proteins associated with specific biological processes and molecular functions of fertility. Most notably, the tetratricopeptide repeat protein 41-related, glycodelin, and kelch-like protein 8 were identified in plasma exosomes unique to the low fertility heifers. These proteins are suggested to play a role in reproduction; however, the role of these proteins in dairy cow reproduction remains to be elucidated. Their identification underscores the potential for proteins within exosomes to provide information on the fertility status and physiological condition of the cow. This may potentially lead to the development of prognostic tools and interventions to improving dairy cow fertility.

Masking release for hearing-impaired listeners: The effect of increased audibility through reduction of amplitude variability.

The masking release (i.e., better speech recognition in fluctuating compared to continuous noise backgrounds) observed for normal-hearing (NH) listeners is generally reduced or absent in hearing-impaired (HI) listeners. One explanation for this lies in the effects of reduced audibility: elevated thresholds may prevent HI listeners from taking advantage of signals available to NH listeners during the dips of temporally fluctuating noise where the interference is relatively weak. This hypothesis was addressed through the development of a signal-processing technique designed to increase the audibility of speech during dips in interrupted noise. This technique acts to (i) compare short-term and long-term estimates of energy, (ii) increase the level of short-term segments whose energy is below the average energy, and (iii) normalize the overall energy of the processed signal to be equivalent to that of the original long-term estimate. Evaluations of this energy-equalizing (EEQ) technique included consonant identification and sentence reception in backgrounds of continuous and regularly interrupted noise. For HI listeners, performance was generally similar for processed and unprocessed signals in continuous noise; however, superior performance for EEQ processing was observed in certain regularly interrupted noise backgrounds.

Water relations and photosynthesis along an elevation gradient for Artemisia tridentata during an historic drought.

Quantifying the variation in plant-water relations and photosynthesis over environmental gradients and during unique events can provide a better understanding of vegetation patterns in a future climate. We evaluated the hypotheses that photosynthesis and plant water potential would correspond to gradients in precipitation and soil moisture during a lengthy drought, and that experimental water additions would increase photosynthesis for the widespread evergreen shrub Artemisia tridentata ssp. vaseyana. We quantified abiotic conditions and physiological characteristics for control and watered plants at 2135, 2315, and 2835 m near Mammoth Lakes, CA, USA, at the ecotone of the Sierra Nevada and Great Basin ecoregions. Snowfall, total precipitation, and soil moisture increased with elevation, but air temperature and soil N content did not. Plant water potential (Ψ), stomatal conductance (g s), maximum photosynthetic rate (A max), carboxylation rate (V cmax), and electron transport rate (J max) all significantly increased with elevations. Addition of water increased Ψ, g s, J max, and A max only at the lowest elevation; g s contributed about 30 % of the constraints on photosynthesis at the lowest elevation and 23 % at the other two elevations. The physiology of this foundational shrub species was quite resilient to this 1-in-1200 year drought. However, plant water potential and photosynthesis corresponded to differences in soil moisture across the gradient. Soil re-wetting in early summer increased water potential and photosynthesis at the lowest elevation. Effects on water relations and photosynthesis of this widespread, cold desert shrub species may be disproportionate at lower elevations as drought length increases in a future climate.

Level variations in speech: Effect on masking release in hearing-impaired listeners.

Acoustic speech is marked by time-varying changes in the amplitude envelope that may pose difficulties for hearing-impaired listeners. Removal of these variations (e.g., by the Hilbert transform) could improve speech reception for such listeners, particularly in fluctuating interference. Léger, Reed, Desloge, Swaminathan, and Braida [(2015b). J. Acoust. Soc. Am. 138, 389-403] observed that a normalized measure of masking release obtained for hearing-impaired listeners using speech processed to preserve temporal fine-structure (TFS) cues was larger than that for unprocessed or envelope-based speech. This study measured masking release for two other speech signals in which level variations were minimal: peak clipping and TFS processing of an envelope signal. Consonant identification was measured for hearing-impaired listeners in backgrounds of continuous and fluctuating speech-shaped noise. The normalized masking release obtained using speech with normal variations in overall level was substantially less than that observed using speech processed to achieve highly restricted level variations. These results suggest that the performance of hearing-impaired listeners in fluctuating noise may be improved by signal processing that leads to a decrease in stimulus level variations.

Consonant identification in noise using Hilbert-transform temporal fine-structure speech and recovered-envelope speech for listeners with normal and impaired hearing.

Consonant-identification ability was examined in normal-hearing (NH) and hearing-impaired (HI) listeners in the presence of steady-state and 10-Hz square-wave interrupted speech-shaped noise. The Hilbert transform was used to process speech stimuli (16 consonants in a-C-a syllables) to present envelope cues, temporal fine-structure (TFS) cues, or envelope cues recovered from TFS speech. The performance of the HI listeners was inferior to that of the NH listeners both in terms of lower levels of performance in the baseline condition and in the need for higher signal-to-noise ratio to yield a given level of performance. For NH listeners, scores were higher in interrupted noise than in steady-state noise for all speech types (indicating substantial masking release). For HI listeners, masking release was typically observed for TFS and recovered-envelope speech but not for unprocessed and envelope speech. For both groups of listeners, TFS and recovered-envelope speech yielded similar levels of performance and consonant confusion patterns. The masking release observed for TFS and recovered-envelope speech may be related to level effects associated with the manner in which the TFS processing interacts with the interrupted noise signal, rather than to the contributions of TFS cues per se.

Consonant identification using temporal fine structure and recovered envelope cues.

The contribution of recovered envelopes (RENVs) to the utilization of temporal-fine structure (TFS) speech cues was examined in normal-hearing listeners. Consonant identification experiments used speech stimuli processed to present TFS or RENV cues. Experiment 1 examined the effects of exposure and presentation order using 16-band TFS speech and 40-band RENV speech recovered from 16-band TFS speech. Prior exposure to TFS speech aided in the reception of RENV speech. Performance on the two conditions was similar (∼50%-correct) for experienced listeners as was the pattern of consonant confusions. Experiment 2 examined the effect of varying the number of RENV bands recovered from 16-band TFS speech. Mean identification scores decreased as the number of RENV bands decreased from 40 to 8 and were only slightly above chance levels for 16 and 8 bands. Experiment 3 examined the effect of varying the number of bands in the TFS speech from which 40-band RENV speech was constructed. Performance fell from 85%- to 31%-correct as the number of TFS bands increased from 1 to 32. Overall, these results suggest that the interpretation of previous studies that have used TFS speech may have been confounded with the presence of RENVs.

Otoacoustic-emission-based medial-olivocochlear reflex assays for humans.

Otoacoustic emission (OAE) tests of the medial-olivocochlear reflex (MOCR) in humans were assessed for viability as clinical assays. Two reflection-source OAEs [TEOAEs: transient-evoked otoacoustic emissions evoked by a 47 dB sound pressure level (SPL) chirp; and discrete-tone SFOAEs: stimulus-frequency otoacoustic emissions evoked by 40 dB SPL tones, and assessed with a 60 dB SPL suppressor] were compared in 27 normal-hearing adults. The MOCR elicitor was a 60 dB SPL contralateral broadband noise. An estimate of MOCR strength, MOCR%, was defined as the vector difference between OAEs measured with and without the elicitor, normalized by OAE magnitude (without elicitor). An MOCR was reliably detected in most ears. Within subjects, MOCR strength was correlated across frequency bands and across OAE type. The ratio of across-subject variability to within-subject variability ranged from 2 to 15, with wideband TEOAEs and averaged SFOAEs giving the highest ratios. MOCR strength in individual ears was reliably classified into low, normal, and high groups. SFOAEs using 1.5 to 2 kHz tones and TEOAEs in the 0.5 to 2.5 kHz band gave the best statistical results. TEOAEs had more clinical advantages. Both assays could be made faster for clinical applications, such as screening for individual susceptibility to acoustic trauma in a hearing-conservation program.

Auditory and tactile gap discrimination by observers with normal and impaired hearing.

Temporal processing ability for the senses of hearing and touch was examined through the measurement of gap-duration discrimination thresholds (GDDTs) employing the same low-frequency sinusoidal stimuli in both modalities. GDDTs were measured in three groups of observers (normal-hearing, hearing-impaired, and normal-hearing with simulated hearing loss) covering an age range of 21-69 yr. GDDTs for a baseline gap of 6 ms were measured for four different combinations of 100-ms leading and trailing markers (250-250, 250-400, 400-250, and 400-400 Hz). Auditory measurements were obtained for monaural presentation over headphones and tactile measurements were obtained using sinusoidal vibrations presented to the left middle finger. The auditory GDDTs of the hearing-impaired listeners, which were larger than those of the normal-hearing observers, were well-reproduced in the listeners with simulated loss. The magnitude of the GDDT was generally independent of modality and showed effects of age in both modalities. The use of different-frequency compared to same-frequency markers led to a greater deterioration in auditory GDDTs compared to tactile GDDTs and may reflect differences in bandwidth properties between the two sensory systems.

Nonstructural carbohydrates explain post-fire tree mortality and recovery patterns.

Trees use nonstructural carbohydrates (NSCs) to support many functions, including recovery from disturbances. However, NSC's importance for recovery following fire and whether NSC depletion contributes to post-fire delayed mortality are largely unknown. We investigated how fire affects NSCs based on fire-caused injury from a prescribed fire in a young Pinus ponderosa (Lawson & C. Lawson) stand. We assessed crown injury (needle scorch and bud kill) and measured NSCs of needles and inner bark (i.e., secondary phloem) of branches and main stems of trees subject to fire and at an adjacent unburned site. We measured NSCs pre-fire and at six timesteps post-fire (4 days-16 months). While all trees initially survived the fire, NSC concentrations declined quickly in burned trees relative to unburned controls over the same post-fire period. This decline was strongest for trees that eventually died, but those that survived recovered to unburned levels within 14 months post-fire. Two months post-fire, the relationship between crown scorch and NSCs of the main stem inner bark was strongly negative (Adj-R2 = 0.83). Our results support the importance of NSCs for tree survival and recovery post-fire and suggest that post-fire NSC depletion is in part related to reduced photosynthetic leaf area that subsequently limits carbohydrate availability for maintaining tree function. Crown scorch is a commonly measured metric of tree-level fire severity and is often linked to post-fire tree outcome (i.e., recovery or mortality). Thus, our finding that NSC depletion may be the mechanistic link between the fire-caused injury and tree outcome will help improve models of post-fire tree mortality and forest recovery.

Exploring the Efficacy of Selected Allografts in Chronic Wound Healing: Evidence from Murine Models and Clinical Data for a Proposed Treatment Algorithm.

SIGNIFICANCE: Chronic wounds can lead to poor outcomes for patients, with risks including amputation and death. In the United States, chronic wounds affect 2.5% of the population and cost up to $28 billion per year in primary healthcare costs. RECENT ADVANCES: Allograft tissues (dermal, amnion, and amnion/chorion) have shown efficacy in improving healing of chronic, recalcitrant wounds in human patients, as evidenced by multiple clinical trials. Their mechanisms of actions have been relatively understudied, until recently. Research in murine models has shown dermal allografts promote re-epithelialization, amnion allografts promote granulation tissue formation and angiogenesis, and amnion/chorion allografts support all stages of wound healing. These findings not only confirm effectiveness, but they shed light on mechanisms of action responsible for their therapeutic utility in patients. CRITICAL ISSUES: Despite the promise of allografts in chronic wound care, a gap exists in understanding which allografts are most effective during each wound healing stage. The variable efficacy among each type of allograft suggests a mechanistic approach towards a proposed clinical treatment algorithm, based on wound characteristics and patient's needs, may be beneficial. FUTURE DIRECTIONS: Recent advances in allografts provide a framework for further investigations on how allograft selection can be based on specific needs of individual patients. This requires additional research to identify which allografts support the best outcomes during each stage of the wound healing process as well as utility in specific wound types. Longitudinal human studies investigating the long-term impacts of allografts, particularly in the remodeling phase, are also essential to developing a deeper understanding of their role in sustained wound repair and recovery.

Exploring a targeted approach for public health capacity restrictions during COVID-19 using a new computational model.

This work introduces the Queen's University Agent-Based Outbreak Outcome Model (QUABOOM). This tool is an agent-based Monte Carlo simulation for modelling epidemics and informing public health policy. We illustrate the use of the model by examining capacity restrictions during a lockdown. We find that public health measures should focus on the few locations where many people interact, such as grocery stores, rather than the many locations where few people interact, such as small businesses. We also discuss a case where the results of the simulation can be scaled to larger population sizes, thereby improving computational efficiency.

Haptic Communication of Language.

In this review, the development of communication systems and devices that convey language tactually is examined, first from an historical perspective focusing on the communities who use the tactile modality to substitute for impairments in vision and/or hearing. Then, the more recent developments in wearable tactile communication systems for conveying text and speech to those without sensory impairments are reviewed. The performance of tactile display technology developed for these user communities is discussed in the context of the proficiency achieved by skilled users of natural methods of tactile communication. In tracing the history of tactile devices used to convey language, it is evident that technological advances in other domains, such as screen readers and speech synthesizers for the visually impaired and cochlear implants for those with hearing loss, have had a profound impact on the requirements for effective tactile language systems. For some communities, such as the Deafblind, it is essential that the tactile communication platform is bi-directional so that the user can both send and receive language. Devices developed to address such needs have yet to achieve commercial success. Recent research on wearable tactile displays has highlighted the importance of extensive training for learning and retaining languages presented tactually.

Anti-fibrotic effects of statin drugs: A review of evidence and mechanisms.

Fibrosis is a pathological repair process common among organs, that responds to tissue damage by replacement with non-functional connective tissue. Despite the widespread prevalence of tissue fibrosis, manifesting in numerous disease states across myriad organs, therapeutic modalities to prevent or alleviate fibrosis are severely lacking in quantity and efficacy. Alongside development of new drugs, repurposing of existing drugs may be a complementary strategy to elect anti-fibrotic compounds for pharmacologic treatment of tissue fibrosis. Drug repurposing can provide key advantages to de novo drug discovery, harnessing the benefits of previously elucidated mechanisms of action and already existing pharmacokinetic profiles. One class of drugs with a wealth of clinical data and extensively studied safety profiles is the statins, a class of antilipidemic drugs widely prescribed for hypercholesterolemia. In addition to these widely utilized lipid-lowering effects, increasing data from cellular, pre-clinical mammalian, and clinical human studies have also demonstrated that statins are able to alleviate tissue fibrosis originating from a variety of pathological insults via lesser-studied, pleiotropic effects of these drugs. Here we review literature demonstrating evidence for direct effects of statins antagonistic to fibrosis, as well as much of the available mechanistic data underlying these effects. A more complete understanding of the anti-fibrotic effects of statins may paint a clearer picture of their anti-fibrotic potential for various clinical indications. Additionally, more lucid comprehension of the mechanisms by which statins exert anti-fibrotic effects may aid in development of novel therapeutic agents that target similar pathways but with greater specificity or efficacy.

A set of Saccharomyces cerevisiae integration vectors for fluorescent dye labeling of proteins.

Protein fusions are frequently used for fluorescence imaging of individual molecules, both in vivo and in vitro. The SNAP, CLIP, HALO (aka HaloTag7), and DHFR protein tags can be linked to small molecule dyes that provide brightness and photo-stability superior to fluorescent proteins. To facilitate fluorescent dye tagging of proteins in the yeast Saccharomyces cerevisiae, we constructed a modular set of vectors with various combinations of labeling protein tags and selectable markers. These vectors can be used in combination to create strains where multiple proteins labeled with different colored dyes can be simultaneously observed.

Performance of a convolutional autoencoder designed to remove electronic noise from p-type point contact germanium detector signals.

We present a convolutional autoencoder to denoise pulses from a p-type point contact high-purity germanium detector similar to those used in several rare event searches. While we focus on training procedures that rely on detailed detector physics simulations, we also present implementations requiring only noisy detector pulses to train the model. We validate our autoencoder on both simulated data and calibration data from an 241 Am source, the latter of which is used to show that the denoised pulses are statistically compatible with data pulses. We demonstrate that our denoising method is able to preserve the underlying shapes of the pulses well, offering improvement over traditional denoising methods. We also show that the shaping time used to calculate energy with a trapezoidal filter can be significantly reduced while maintaining a comparable energy resolution. Under certain circumstances, our denoising method can improve the overall energy resolution. The methods we developed to remove electronic noise are straightforward to extend to other detector technologies. Furthermore, the latent representation from the encoder is also of use in quantifying shape-based characteristics of the signals. Our work has great potential to be used in particle physics experiments and beyond.