Assembly of the hair bundle, the sensory organelle of the inner ear, depends on differential growth of actin-based stereocilia. Separate rows of stereocilia, labeled 1 through 3 from tallest to ...shortest, lengthen or shorten during discrete time intervals during development. We used lattice structured illumination microscopy and surface rendering to measure dimensions of stereocilia from mouse apical inner hair cells during early postnatal development; these measurements revealed a sharp transition at postnatal day 8 between stage III (row 1 and 2 widening; row 2 shortening) and stage IV (final row 1 lengthening and widening). Tip proteins that determine row 1 lengthening did not accumulate simultaneously during stages III and IV; while the actin-bundling protein EPS8 peaked at the end of stage III, GNAI3 peaked several days later-in early stage IV-and GPSM2 peaked near the end of stage IV. To establish the contributions of key macromolecular assemblies to bundle structure, we examined mouse mutants that eliminated tip links (Cdh23v2J or Pcdh15av3J), transduction channels (TmieKO), or the row 1 tip complex (Myo15ash2). Cdh23v2J/v2J and Pcdh15av3J/av3J bundles had adjacent stereocilia in the same row that were not matched in length, revealing that a major role of these cadherins is to synchronize lengths of side-by-side stereocilia. Use of the tip-link mutants also allowed us to distinguish the role of transduction from effects of transduction proteins themselves. While levels of GNAI3 and GPSM2, which stimulate stereocilia elongation, were greatly attenuated at the tips of TmieKO/KO row 1 stereocilia, they accumulated normally in Cdh23v2J/v2J and Pcdh15av3J/av3J stereocilia. These results reinforced the suggestion that the transduction proteins themselves facilitate localization of proteins in the row 1 complex. By contrast, EPS8 concentrates at tips of all TmieKO/KO, Cdh23v2J/v2J, and Pcdh15av3J/av3J stereocilia, correlating with the less polarized distribution of stereocilia lengths in these bundles. These latter results indicated that in wild-type hair cells, the transduction complex prevents accumulation of EPS8 at the tips of shorter stereocilia, causing them to shrink (rows 2 and 3) or disappear (row 4 and microvilli). Reduced rhodamine-actin labeling at row 2 stereocilia tips of tip-link and transduction mutants suggests that transduction's role is to destabilize actin filaments there. These results suggest that regulation of stereocilia length occurs through EPS8 and that CDH23 and PCDH15 regulate stereocilia lengthening beyond their role in gating mechanotransduction channels.
To ensure the sustainability of the future power grid, the rate of expansion of distributed energy resources (DERs) has introduced operational challenges. These include managing transmission ...constraints with DER power injection, dispatching DERs efficiently, managing system frequency, and ensuring sufficient reactive power for voltage support. Coupled with the intensification of wildfires, power infrastructures across the United States face challenges to minimize the impact of these factors and maintain system reliability and resiliency. This research embarked on a comprehensive evaluation, beginning with an in-depth historical analysis to delineate regions most susceptible to wildfires. Utilizing a multidimensional approach, the study assessed wildfire-induced risks to power grids by integrating historical wildfire occurrences, real-time wildfire proximities, Moderate-Resolution Imaging Spectroradiometer (MODIS)-derived vegetation metrics, and system parameters. Principal component analysis (PCA)-based optimal weights were then used, leading to the formulation of a novel risk factor model. This risk factor model has the potential to be the key to ensuring the resilience of a renewable-rich smart grid when faced with a severe weather event. Our model’s applicability was further verified through an empirical assessment, selecting representative networks from diverse regions, providing insights into the geographical variability of risk factors. Ultimately, this study offers stakeholders and policymakers a comprehensive toolset, empowering decisions regarding infrastructure investments, grid reinforcements, and strategic power rerouting to ensure consistent energy delivery during wildfires.
Sensory hair cells of the inner ear rely on the hair bundle, a cluster of actin-filled stereocilia, to transduce auditory and vestibular stimuli into electrical impulses. Because they are long and ...thin projections, stereocilia are most prone to damage at the point where they insert into the hair cell's soma. Moreover, this is the site of stereocilia pivoting, the mechanical movement that induces transduction, which additionally weakens this area mechanically. To bolster this fragile area, hair cells construct a dense core called the rootlet at the base of each stereocilium, which extends down into the actin meshwork of the cuticular plate and firmly anchors the stereocilium. Rootlets are constructed with tightly packed actin filaments that extend from stereocilia actin filaments which are wrapped with TRIOBP; in addition, many other proteins contribute to the rootlet and its associated structures. Rootlets allow stereocilia to sustain innumerable deflections over their lifetimes and exemplify the unique manner in which sensory hair cells exploit actin and its associated proteins to carry out the function of mechanotransduction.
Advancements in digital automation for smart grids have led to the installation of measurement devices like phasor measurement units (PMUs), micro-PMUs (μ-PMUs), and smart meters. However, large ...amount of data collected by these devices bring several challenges as control room operators need to use this data with models to make confident decisions for reliable and resilient operation of the cyber-power systems. Machine-learning (ML) based tools can provide a reliable interpretation of the deluge of data obtained from the field. For the decision-makers to ensure reliable network operation under all operating conditions, these tools need to identify solutions that are feasible and satisfy the system constraints, while being efficient, trustworthy and interpretable. This resulted in the increasing popularity of physics-informed machine learning (PIML) approaches, as these methods overcome challenges that model-based or data-driven ML methods face in silos. This work aims at the following: a) review existing strategies and techniques for incorporating underlying physical principles of the power grid into different types of ML approaches (supervised/semi-supervised learning, unsupervised learning, and reinforcement learning (RL)); b) explore the existing works on PIML methods for anomaly detection, classification, localization, and mitigation in power transmission and distribution systems, c) discuss improvements in existing methods through consideration of potential challenges while also addressing the limitations to make them suitable for real-world applications.
The stereocilia rootlet is a key structure in vertebrate hair cells, anchoring stereocilia firmly into the cell's cuticular plate and protecting them from overstimulation. Using superresolution ...microscopy, we show that the ankyrin-repeat protein ANKRD24 concentrates at the stereocilia insertion point, forming a ring at the junction between the lower and upper rootlets. Annular ANKRD24 continues into the lower rootlet, where it surrounds and binds TRIOBP-5, which itself bundles rootlet F-actin. TRIOBP-5 is mislocalized in Ankrd24KO/KO hair cells, and ANKRD24 no longer localizes with rootlets in mice lacking TRIOBP-5; exogenous DsRed-TRIOBP-5 restores endogenous ANKRD24 to rootlets in these mice. Ankrd24KO/KO mice show progressive hearing loss and diminished recovery of auditory function after noise damage, as well as increased susceptibility to overstimulation of the hair bundle. We propose that ANKRD24 bridges the apical plasma membrane with the lower rootlet, maintaining a normal distribution of TRIOBP-5. Together with TRIOBP-5, ANKRD24 organizes rootlets to enable hearing with long-term resilience.
The protein otoferlin plays an essential role at the sensory hair cell synapse. Mutations in otoferlin result in deafness and depending on the species, mild to strong vestibular deficits. While ...studies in mouse models suggest a role for otoferlin in synaptic vesicle exocytosis and endocytosis, it is unclear whether these functions are conserved across species. To address this question, we characterized the impact of otoferlin depletion in zebrafish larvae and found defects in synaptic vesicle recycling, abnormal synaptic ribbons, and higher resting calcium concentrations in hair cells. We also observed abnormal expression of the calcium binding hair cell genes s100s and parvalbumin, as well as the nogo related proteins rtn4rl2a and rtn4rl2b. Exogenous otoferlin partially restored expression of genes affected by endogenous otoferlin depletion. Our results suggest that in addition to vesicle recycling, depletion of otoferlin disrupts resting calcium levels, alters synaptic ribbon architecture, and perturbs transcription of hair cells specific genes during zebrafish development.
This is the first book to explore the emergence and function of a novel pictorial format in the Middle Ages, the vita icon, which displayed the magnified portrait of a saint framed by scenes from his ...or her life. The vita icon was used for depicting the most popular figures in the Orthodox calendar and, in the Latin West, was deployed most vigorously in the service of Francis of Assisi. This book offers a compelling account of how this type of image embodied and challenged the prevailing structures of vision, representation and sanctity in Byzantium and among the Franciscans in Italy between the eleventh and thirteenth centuries. Paroma Chatterjee uncovers the complexities of the philosophical and theological issues that had long engaged both the medieval East and West, such as the fraught relations between words and images, relics and icons, a representation and its subject, and the very nature of holy presence.
This article looks closely at the report of a miracle that occurred in eleventh-century Constantinople in which the veil covering an icon of the Theotokos (Virgin) at the Blachernae church lifted ...itself miraculously. The report, scripted by the Byzantine polymath Michael Psellos, focuses in intriguing ways on the actions and nonactions of the veil when the icon presided over a judicial trial. The article contends that Psellos insists on the theme of timing (with regard to the lifting and otherwise of the veil) and the Blachernae icon's role in determining a critical, decisive moment in the arbitration of human affairs. This emphasis, in turn, bespeaks a broader concern over the timing of sacred icons during significant moments in Byzantine history as understood by contemporary chroniclers: namely, their failure to act in appropriate ways at critical moments when the empire itself was at stake.
The Trier ivory depicts the translation of an unseen relic into an unnamed city, welcomed by an unidentified Byzantine imperial couple. Scholarship so far has concentrated on deciphering the ...identities of the characters portrayed on it. A close look at the image itself reveals that the composition juxtaposes icons and relics in deliberate antitheses to evoke pressing questions regarding manufacture and veneration in the tenth century. Thus, the ivory can be regarded as a provocative statement on the intellectual legacy of the image debates in Byzantium.
Aim of the volume is the analysis of the entanglement of religious communication and city life during an arc of time that is characterised by dramatic and even contradicting developments. Bringing ...together textual analyses and archaelogical case studies in a comparative perspective, the volume zooms in on the historical context of the advanced imperial and late antique Mediterranean space (2nd–8th centuries CE).
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