Enhancing Genomic Prediction Accuracy for Body Conformation Traits in Korean Holstein Cattle.

The Holstein breed is the mainstay of dairy production in Korea. In this study, we evaluated the genomic prediction accuracy for body conformation traits in Korean Holstein cattle, using a range of π levels (0.75, 0.90, 0.99, and 0.995) in Bayesian methods (BayesB and BayesC). Focusing on 24 traits, we analyzed the impact of different π levels on prediction accuracy. We observed a general increase in accuracy at higher levels for specific traits, with variations depending on the Bayesian method applied. Notably, the highest accuracy was achieved for rear teat angle when using deregressed estimated breeding values including parent average as a response variable. We further demonstrated that incorporating parent average into deregressed estimated breeding values enhances genomic prediction accuracy, showcasing the effectiveness of the model in integrating both offspring and parental genetic information. Additionally, we identified 18 significant window regions through genome-wide association studies, which are crucial for future fine mapping and discovery of causal mutations. These findings provide valuable insights into the efficiency of genomic selection for body conformation traits in Korean Holstein cattle and highlight the potential for advancements in the prediction accuracy using larger datasets and more sophisticated genomic models.

Evaluation of a novel, low-cost, 3D printed video laryngoscope with borescope in anesthetized Beagle dogs.

OBJECTIVE: To develop and evaluate a low-cost three-dimensional (3D)-printed video laryngoscope (VLVET) for use with a commercial borescope. STUDY DESIGN: Instrument development and pilot study. ANIMALS: A total of six adult male Beagle dogs. METHODS: The VLVET consisted of a laryngoscope handle and a Miller-type blade, and a detachable camera holder that attached to various locations along the blade. The laryngoscope and camera holder were 3D-printed using black polylactic acid filament. Dogs were premedicated with intravenous (IV) medetomidine (15 µg kg-1) and anesthesia induced with IV alfaxalone (1.5 mg kg-1). The VLVET, combined with a borescope, was used for laryngeal visualization and intubation. Performance was evaluated by comparing direct and video-assisted views in sternal recumbency. The borescope camera was sequentially positioned at 2, 4, 6, 8 and 10 cm from the blade tip (distanceLARYNX-CAM), which was placed on the epiglottis during intubation or laryngoscopy. At the 10 cm distanceLARYNX-CAM, laryngeal visualization was sequentially scored at inter-incisor gaps of 10, 8, 6, 4 and 2 cm. Laryngeal visualization scores (0-3 range, with 0 = obstructed and 3 = unobstructed views) were statistically analyzed using the Friedman's test. RESULTS: Under direct visualization, the 2 cm distanceLARYNX-CAM had a significantly lower score compared with all other distanceLARYNX-CAM (all p = 0.014) because the view was obstructed by the camera holder and borescope camera. With both direct and camera-assisted views, visualization scores were higher at inter-incisor gaps ≥ 4 cm compared with 2 cm (all p < 0.05). CONCLUSIONS AND CLINICAL RELEVANCE: During laryngoscopy and intubation, the VLVET and borescope facilitated both direct and video laryngoscopy at distanceLARYNX-CAM in Beagle dogs when inter-incisor gaps were ≥ 4 cm.

3D spatiotemporally scalable in vivo neural probes based on fluorinated elastomers.

Electronic devices for recording neural activity in the nervous system need to be scalable across large spatial and temporal scales while also providing millisecond and single-cell spatiotemporal resolution. However, existing high-resolution neural recording devices cannot achieve simultaneous scalability on both spatial and temporal levels due to a trade-off between sensor density and mechanical flexibility. Here we introduce a three-dimensional (3D) stacking implantable electronic platform, based on perfluorinated dielectric elastomers and tissue-level soft multilayer electrodes, that enables spatiotemporally scalable single-cell neural electrophysiology in the nervous system. Our elastomers exhibit stable dielectric performance for over a year in physiological solutions and are 10,000 times softer than conventional plastic dielectrics. By leveraging these unique characteristics we develop the packaging of lithographed nanometre-thick electrode arrays in a 3D configuration with a cross-sectional density of 7.6 electrodes per 100 µm2. The resulting 3D integrated multilayer soft electrode array retains tissue-level flexibility, reducing chronic immune responses in mouse neural tissues, and demonstrates the ability to reliably track electrical activity in the mouse brain or spinal cord over months without disrupting animal behaviour.

Multiscale stress deconcentration amplifies fatigue resistance of rubber.

Rubbers reinforced with rigid particles are used in high-volume applications, including tyres, dampers, belts and hoses1. Many applications require high modulus to resist excessive deformation and high fatigue threshold to resist crack growth under cyclic load. The particles are known to greatly increase modulus but not fatigue threshold. For example, adding carbon particles to natural rubber increases its modulus by one to two orders of magnitude1-3, but its fatigue threshold, reinforced or not, has remained approximately 100 J m-2 for decades4-7. Here we amplify the fatigue threshold of particle-reinforced rubbers by multiscale stress deconcentration. We synthesize a rubber in which highly entangled long polymers strongly adhere with rigid particles. At a crack tip, stress deconcentrates across two length scales: first through polymers and then through particles. This rubber achieves a fatigue threshold of approximately 1,000 J m-2. Mounts and grippers made of this rubber bear high loads and resist crack growth over repeated operation. Multiscale stress deconcentration expands the space of materials properties, opening doors to curtailing polymer pollution and building high-performance soft machines.

SARS-CoV-2 infection engenders heterogeneous ribonucleoprotein interactions to impede translation elongation in the lungs.

Translational regulation in tissue environments during in vivo viral pathogenesis has rarely been studied due to the lack of translatomes from virus-infected tissues, although a series of translatome studies using in vitro cultured cells with viral infection have been reported. In this study, we exploited tissue-optimized ribosome profiling (Ribo-seq) and severe-COVID-19 model mice to establish the first temporal translation profiles of virus and host genes in the lungs during SARS-CoV-2 pathogenesis. Our datasets revealed not only previously unknown targets of translation regulation in infected tissues but also hitherto unreported molecular signatures that contribute to tissue pathology after SARS-CoV-2 infection. Specifically, we observed gradual increases in pseudoribosomal ribonucleoprotein (RNP) interactions that partially overlapped the trails of ribosomes, being likely involved in impeding translation elongation. Contemporaneously developed ribosome heterogeneity with predominantly dysregulated 5 S rRNP association supported the malfunction of elongating ribosomes. Analyses of canonical Ribo-seq reads (ribosome footprints) highlighted two obstructive characteristics to host gene expression: ribosome stalling on codons within transmembrane domain-coding regions and compromised translation of immunity- and metabolism-related genes with upregulated transcription. Our findings collectively demonstrate that the abrogation of translation integrity may be one of the most critical factors contributing to pathogenesis after SARS-CoV-2 infection of tissues.

A soft, self-sensing tensile valve for perceptive soft robots.

Soft inflatable robots are a promising paradigm for applications that benefit from their inherent safety and adaptability. However, for perception, complex connections of rigid electronics both in hardware and software remain the mainstay. Although recent efforts have created soft analogs of individual rigid components, the integration of sensing and control systems is challenging to achieve without compromising the complete softness, form factor, or capabilities. Here, we report a soft self-sensing tensile valve that integrates the functional capabilities of sensors and control valves to directly transform applied tensile strain into distinctive steady-state output pressure states using only a single, constant pressure source. By harnessing a unique mechanism, "helical pinching", we derive physical sharing of both sensing and control valve structures, achieving all-in-one integration in a compact form factor. We demonstrate programmability and applicability of our platform, illustrating a pathway towards fully soft, electronics-free, untethered, and autonomous robotic systems.

Low-intensity mixing process of high molecular weight polymer chains leads to elastomers of long network strands and high fatigue threshold.

Many polymer networks are prepared by crosslinking polymer chains. The polymer chains and crosslinkers are commonly mixed in internal mixers or roll mills. These intense processes break the polymer chains, lower viscosity, and ease mixing. The resulting polymer networks have short chains and a fatigue threshold of ∼100 J m-2. Here, we show that a low-intensity process, a combination of kneading and annealing, preserves long chains, leading to a network of polybutadiene to achieve a fatigue threshold of 440 J m-2. In a network, each chain has multiple crosslinks, which divides the chain into multiple strands. At the ends of the chain are two dangling strands that do not bear the load. The larger the number of crosslinks per chain, the lower the fraction of dangling strands. High fatigue threshold requires long strands, as well as a low fraction of dangling strands. Once intense mixing cuts chains short, each short chain can only have a few crosslinks; the strands are short and the fraction of dangling strands is high-both lower the fatigue threshold. By contrast, a low-intensity mixing process preserves long chains, which can have many crosslinks; the strands are long and the fraction of dangling strands is low-both increase the fatigue threshold. It is hoped that this work will aid the development of fatigue-resistant elastomers.

Hydrogels of arrested phase separation simultaneously achieve high strength and low hysteresis.

Hydrogels are being developed to bear loads. Applications include artificial tendons and muscles, which require high strength to bear loads and low hysteresis to reduce energy loss. However, simultaneously achieving high strength and low hysteresis has been challenging. This challenge is met here by synthesizing hydrogels of arrested phase separation. Such a hydrogel has interpenetrating hydrophilic and hydrophobic networks, which separate into a water-rich phase and a water-poor phase. The two phases arrest at the microscale. The soft hydrophilic phase deconcentrates stress in the strong hydrophobic phase, leading to high strength. The two phases are elastic and adhere through topological entanglements, leading to low hysteresis. For example, a hydrogel of 76 weight % water, made of poly(ethyl acrylate) and poly(acrylic acid), achieves a tensile strength of 6.9 megapascals and a hysteresis of 16.6%. This combination of properties has not been realized among previously existing hydrogels.

Clozapine-Induced Chemogenetic Neuromodulation Rescues Post-Stroke Deficits After Chronic Capsular Infarct.

Long-term disabilities induced by stroke impose a heavy burden on patients, families, caregivers, and public health systems. Extensive studies have demonstrated the therapeutic value of neuromodulation in enhancing post-stroke recovery. Among them, chemogenetic neuromodulation activated by clozapine-N-oxide (CNO) has been proposed as the potential tool of neuromodulation. However, recent evidence showed that CNO does not cross the blood - brain barrier and may in fact have low binding affinity for chemogenetic tool. Thus, clozapine (CLZ) has been suggested for use in chemogenetic neuromodulation, in place of CNO, because it readily crosses the blood-brain barrier. Previously we reported that low doses of CLZ (0.1 mg/kg) successfully induced neural responses without off-target effects. Here, we show that low-dose clozapine (0.1 mg/kg) can induce prolonged chemogenetic activation while avoiding permeability issues and minimizing off-target effects. In addition, clozapine-induced excitatory chemogenetic neuromodulation (CLZ-ChemoNM) of sensory-parietal cortex with hsyn-hM3Dq-YFP-enhanced motor recovery in a chronic capsular infarct model of stroke in rats, improving post-stroke behavioral scores to 56% of pre-infarct levels. Longitudinal 2-deoxy-2-[18F]-fluoro-D-glucose microPET (FDG-microPET) scans showed that a reduction in diaschisis volume and activation of corticostriatal circuits were both correlated with post-stroke recovery. We also found c-Fos increases in bilateral cortices and BDNF increases in the cortices and striatum after CLZ-ChemoNM, indicating an increase in neural plasticity. These findings suggest the translational feasibility of CLZ-ChemoNM for augmenting recovery in chronic stroke.

Making Highly Elastic and Tough Hydrogels from Doughs.

A hydrogel is often fabricated from preexisting polymer chains by covalently crosslinking them into a polymer network. The crosslinks make the hydrogel swell-resistant but brittle. This conflict is resolved here by making a hydrogel from a dough. The dough is formed by mixing long polymer chains with a small amount of water and photoinitiator. The dough is then homogenized by kneading and annealing at elevated temperatures, during which the crowded polymer chains densely entangle. The polymer chains are then sparsely crosslinked into a polymer network under an ultraviolet lamp, and submerged in water to swell to equilibrium. The resulting hydrogel is both swell-resistant and tough. The hydrogel also has near-perfect elasticity, high strength, high fatigue resistance, and low friction. The method is demonstrated with two widely used polymers, poly(ethylene glycol) and cellulose. These hydrogels have never been made swell-resistant, elastic, and tough before. The method is generally applicable to synthetic and natural polymers, and is compatible with industrial processing technologies, opening doors to the development of sustainable, high-performance hydrogels.

An Electret-Powered Skin-Attachable Auditory Sensor that Functions in Harsh Acoustic Environments.

Auditory sensors have shortcomings with respect to not only personalization with wearability and portability but also detecting a human voice clearly in a noisy environment or when a mask covers the mouth. In this work, an electret-powered and hole-patterned polymer diaphragm is exploited into a skin-attachable auditory sensor. The optimized charged electret diaphragm induces a voltage bias of >400 V against the counter electrode, which reduces the necessity of a bulky power source and enables the capacitive sensor to show high sensitivity (2.2 V Pa-1 ) with incorporation of an elastomer nanodroplet seismic mass. The sophisticated capacitive structure with low mechanical damping enables a flat frequency response (80-3000 Hz) and good linearity (50-80 dBSPL ). The hole-patterned electret diaphragms help the skin-attachable sensor detect only neck-skin vibration rather than dynamic air pressure, enabling a person's voice to be detected in a harsh acoustic environment. The sensor operates reliably even in the presence of surrounding noise and when the user is wearing a gas mask. Therefore, the sensor shows strong potential of a communication tool for disaster response and quarantine activities, and of diagnosis tool for vocal healthcare applications such as cough monitoring and voice dosimetry.

Self-assembled nanocomposites of high water content and load-bearing capacity.

Biological tissues, such as cartilage, tendon, ligament, skin, and plant cell wall, simultaneously achieve high water content and high load-bearing capacity. The high water content enables the transport of nutrients and wastes, and the high load-bearing capacity provides structural support for the organisms. These functions are achieved through nanostructures. This biological fact has inspired synthetic mimics, but simultaneously achieving both functions has been challenging. The main difficulty is to construct nanostructures of high load-bearing capacity, characterized by multiple properties, including elastic modulus, strength, toughness, and fatigue threshold. Here we develop a process that self-assembles a nanocomposite using a hydrogel-forming polymer and a glass-forming polymer. The process separates the polymers into a hydrogel phase and a glass phase. The two phases arrest at the nanoscale and are bicontinuous. Submerged in water, the nanocomposite maintains the structure and resists further swelling. We demonstrate the process using commercial polymers, achieving high water content, as well as load-bearing capacity comparable to that of polyethylene. During the process, a rubbery stage exists, enabling us to fabricate objects of complex shapes and fine features. We conduct further experiments to discuss likely molecular origins of arrested phase separation, swell resistance, and ductility. Potential applications of the nanocomposites include artificial tissues, high-pressure filters, low-friction coatings, and solid electrolytes.

A High-Fidelity Skin-Attachable Acoustic Sensor for Realizing Auditory Electronic Skin.

Wearable auditory sensors are critical in user-friendly sound-recognition systems for smart human-machine interaction and the Internet of Things. However, previously reported wearable sensors have limited sound-sensing quality as a consequence of a poor frequency response and a narrow acoustic-pressure range. Here, a skin-attachable acoustic sensor is presented that has higher sensing accuracy in wider auditory field than human ears, with flat frequency response (15-10 000 Hz) and a good range of linearity (29-134 dBSPL ) as well as high conformality to flexible surfaces and human skin. This high sound-sensing quality is achieved by exploiting the low residual stress and high processability of polymer materials in a diaphragm structure designed using acousto-mechano-electric modeling. Thus, this acoustic sensor shows high acoustic fidelity by sensing human-audible sounds, even loud sounds and low-frequency sounds that human ears cannot detect without distorting them. The polymer-based ultrasmall (<9 mm2 ) and thin sensor maintains sound-detection quality on flexible substrates and in a wide temperature range (25 to 90 °C). The acoustic sensor shows a significant potential of auditory electronic skin, by recognizing voice successfully when the sensor attached on human skin is connected to a commercial mobile device running the latest artificial intelligence assistant.

Design Rule for Constructing Buckling-Free Polymeric Stencil with Microdot Apertures.

A polymeric stencil with microdot apertures made by using polydimethylsiloxane (PDMS) molds with pillar patterns has many advantages, including conformal contact, easy processability, flexibility, and low cost compared to conventional silicon-based membranes. However, due to the inherent deformability of PDMS materials in response to external pressure, it is challenging to construct structurally stable stencils with high structural fidelity. Here, we propose a design rule on the buckling pressure for constructing polymeric stencils without process failure. To investigate the critical buckling pressure (Pcr), stencils are fabricated by using different PDMS molds with aspect ratio variations (AR: 1.6, 2.0, 4.0, and 5.3). By observing the buckled morphology of apertures, the structures can be classified into two groups: low (AR 1.6 and 2.0) and high (AR 4.0 and 5.3) AR groups, and Pcr decreases as AR increases in each group. To investigate the results theoretically, the analysis based on Euler's buckling theory and slenderness ratio is conducted, indicating that the theory is only valid for the high-AR group herein. Besides, considering the correction factor, Pcr agrees well with the experimental results.

Improving the Performance of the ToGoFET Probe: Advances in Design, Fabrication, and Signal Processing.

We report recent improvements of the tip-on-gate of field-effect-transistor (ToGoFET) probe used for capacitive measurement. Probe structure, fabrication, and signal processing were modified. The inbuilt metal-oxide-semiconductor field-effect-transistor (MOSFET) was redesigned to ensure reliable probe operation. Fabrication was based on the standard complementary metal-oxide-semiconductor (CMOS) process, and trench formation and the channel definition were modified. Demodulation of the amplitude-modulated drain current was varied, enhancing the signal-to-noise ratio. The I-V characteristics of the inbuilt MOSFET reflect the design and fabrication modifications, and measurement of a buried electrode revealed improved ToGoFET imaging performance. The minimum measurable value was enhanced 20-fold.

Capillary-Induced Clustering of Thermoresponsive Micropillars.

In this study, we demonstrate the controllable clustering of thermoresponsive high-aspect-ratio hydrogel pillars by modulating the elastic modulus of the materials. Generally, high-aspect-ratio polymeric pillars readily cluster owing to the effect of capillary force and adhesion. However, this unstable behavior hinders the implementation of various functionalities such as wetting, adhesion, and energy harvesting on surfaces with such pillars. Conversely, clustering behavior may be required in the case of digital microfluidic platforms that grip tiny particles or perform biological and chemical analyses. Therefore, it is necessary to develop a reliable method for controlling the clustering behavior. To this end, we fabricate high-aspect-ratio pillars that exhibit capillary-induced clustering behavior based on the cross-linker density of the thermoresponsive hydrogel and the temperature of the surrounding environment. Through experimental and theoretical analyses, a criterion for controlling the clustering and recovery behavior of the fabricated pillars is determined. The established criterion is employed to fabricate a smart mobile camera lens cover that can produce blurred and deblurred images based on optical variations resulting from the clustering and recovery of the pillars. The results of this study can be used to fabricate high-aspect-ratio polymeric pillars for use in diverse applications.

Fracture, fatigue, and friction of polymers in which entanglements greatly outnumber cross-links.

In gels and elastomers, the role of entanglements on deformation has been studied, but their effects on fracture, fatigue, and friction are less well understood. In this study, we synthesized polymers in which entanglements greatly outnumber cross-links. The dense entanglements enable transmission of tension in a polymer chain along its length and to many other chains. The sparse cross-links prevent the polymer chains from disentangling. These polymers have high toughness, strength, and fatigue resistance. After submersion in water, the polymers swell to equilibrium, and the resulting hydrogels have low hysteresis, low friction, and high wear resistance.

A piezoelectric micro-cantilever acoustic vector sensor designed considering fluid-structure interaction.

We developed a piezoelectric micromachined cantilever acoustic vector (PEMCAV) sensor. We modeled the device using a "lumped" approach that considers fluid-structure interaction, the piezoelectric effect, and the mechanical impedance of the cantilever. Due to the high flexibility, the influence of the medium is significant, so fluid-structure interaction must be considered in theoretical modeling. We compared the model data to experimental results. The design parameters optimized using the derived analytical open-circuit sensitivity equation are presented, and the physical characteristics of the sensor are discussed. We used a micromachining technique to fabricate the sensor, added a preamplifier, and tested it using a reference hydrophone under a frequency range of 100 Hz-1 kHz. The analytical predictions and experimental results were in good agreement with respect to frequency response and the directivity of the sensor. Even when the sensor was much smaller than the wavelength ( ka≪1), the proposed sensor exhibited a typical cosine directivity pattern, and the measured sensitivity at 100 Hz was -194 dBV/µPa.