Kevin Kit Parker

The long-standing role of fibers as basic structural components has given way to a new paradigm of smart fibers that integrate environmental sensing with programmable responses. Despite recent progress in materials chemistry and device engineering, fabrication choices are often guided by cost and convenience at the expense of advanced capabilities. This review reframes manufacturing as a central design axis that governs not only morphological properties but also molecular orientation, hierarchical organization, and interfacial properties, all of which determine performance. In this review, we first discuss the design principles of activation triggers and response mechanisms, highlighting how they interplay with the unique geometry of fibers. We then provide a detailed comparison of manufacturing strategies, including continuous single fiber spinning, non-woven deposition, and direct synthesis, emphasizing their distinct trade-offs in scalability, resolution, and material compatibility. We further examine post-processing and multiscale integration as steps that preserve, refine, and extend fiber-level properties into system-level functions. Finally, we discuss emerging directions toward fiber electronics and intelligent systems that merge physical in-fiber processing with data-driven interpretation. Together, these principles establish a task-dependent framework that aligns design, manufacturing, and function, advancing smart fibers from isolated demonstrations to integrated next-generation devices.

Diastolic dysfunction, defined by impaired relaxation and increased ventricular stiffness, is central to heart failure with preserved ejection fraction, yet cardiomyocyte-intrinsic mechanisms remain incompletely understood. Here, we show that SORBS2 is a vital component of murine cardiomyocyte adhesion complexes. Its genetic ablation in mice causes progressive diastolic dysfunction with preserved systolic function, accompanied by atrial enlargement and reduced survival. Postnatal cardiomyocyte-directed re-expression of SORBS2 restores diastolic indices and significantly improves longevity. Mechanistically, SORBS2 functions as an integrative scaffold linking adhesome integrity, cytoskeletal remodeling, and calcium homeostasis. SORBS2 deficiency increases microtubule detyrosination, reduces SERCA2 abundance, disrupts dyad-associated organization, which collectively impair active cardiomyocyte relaxation. Concurrently, this deficiency promotes extracellular matrix remodeling and myocardial fibrosis, driving passive ventricular stiffness. Pharmacological inhibition of microtubule detyrosination partially rescues relaxation defects. These findings establish SORBS2 as a key regulator of diastolic function and define a structural axis governing myocardial mechanics, offering potential therapeutic targets.

Abstract Large-scale clinical genome sequencing yields vast numbers of variants of unknown significance (VUSs). The high frequency of VUSs and the paucity of platforms to characterize their functional impact pose significant challenges for clinical decision making. Here, we present an integrated end-to-end platform, REVi-SCOPE (Rapid evaluation of variants in single cells by optogenetics and prime editing), for characterization of the impact of VUSs on cardiac physiology. Our strategy consists of (1) introduction of variants directly into wild-type (WT) human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) via prime editing; (2) optogenetic assessment of calcium and membrane voltage dynamics in single hiPSC-CMs within the pool of edited and unedited cells; and (3) in situ single-cell genotyping of the phenotyped hiPSC-CMs with single-allele resolution. By optimizing and integrating each of these steps, we created a platform that enables VUS characterization in 10 days. We validated the REVi-SCOPE’s capabilities by analyzing the properties of established arrhythmogenic variants. We then used REVi-SCOPE to reveal the functional impact of a VUS, TRPM4 A320V , identified in a child with a conduction block. Together, our results show that REVi-SCOPE enables functional characterization of VUSs linked to cardiac arrhythmias with unprecedented throughput.

Vascular trauma demands rapid intervention to avert severe outcomes, yet current surgical treatments, including invasive autologous grafts and limited, potentially degrading synthetic prostheses, often fail to accommodate the requirements of variable vessel dimensions and shapes. To address these limitations, we present an additive manufacturing strategy for rapid, point-of-care fabrication of customizable vascular grafts using Focused Rotary Jet Spinning (FRJS). This technique enables the rapid, point-of-care fabrication of customizable small-caliber vascular grafts within minutes. FRJS facilitates independent control over nanofiber alignment and centimeter-scale vessel dimensions, yielding grafts with appropriate mechanical properties and flow characteristics. Four-week in vivo evaluation in a rat femoral vasculature replacement model demonstrated sustained vascular patency and early tissue remodeling, supporting the potential for intraoperative generation of tailored vascular conduits.

Front Cover The artwork depicts extracellular matrix–coated giant unilamellar vesicles as synthetic cell boundaries. The left vesicle illustrates collagen forming a fibrous, network-like architecture, while the right highlights fibronectin creating isolated island-like domains on pure phospholipid membranes. These contrasting assemblies reveal a biomimetic platform that captures membrane–matrix interplay and protein-specific mechanical regulation reminiscent of living cell membranes. More in article number e01785, Kwanwoo Shin and co-workers.

Optostimulation is rapidly emerging as a promising approach to control cardiac bioelectricity, combining minimal invasiveness with unparalleled spatiotemporal precision and reversibility. Building on previous findings demonstrating that Ziapin2, a membrane-targeted molecular photoswitch, can modulate cardiomyocyte electrophysiology upon visible light stimulation, we evaluated its potential to precisely terminate reentry-based arrhythmias. Reentrant activity was induced in aligned laminar cardiac microtissues from human-induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs), using an S1S2 electrical pacing protocol in wild-type tissues and rapid pacing combined with catecholamine exposure in gene-edited microtissues harboring the CPVT-associated S404R variant in the RYR2 gene. Photostimulation disrupted spiral wave dynamics in Ziapin2-loaded tissues, whereas it had no effect on vehicle-treated controls. These results provide proof of principle for Ziapin2-mediated optotermination of arrhythmias and highlight its potential as a precise, non-genetic, and minimally invasive strategy for arrhythmia modulation.

RecommendationsF or more than 250 years, the United States Army has served as an engine of materials innovation, catalyzing advances across metallurgy, ceramics, polymers, composites, electronic materials, energetics, computational design, and more.To commemorate the Army turning 250 years old this year, this perspective examines the Army's synergistic role in driving materials science and engineering innovation and leadership development, from early armories that pioneered interchangeable parts and precision steelmaking to today's U.S. Army Combat Capabilities Development Command (

We demonstrate the use of muscular thin films (MTFs) as a hydrodynamic assay to measure cardiac stroke volume on a chip, and quantify changes in response to ionotropic dosing; helping bridge the gap between in vitro and in vivo measurements.

Artificial membrane systems have enabled powerful studies of lipid dynamics and bilayer mechanics, yet they lack the structural complexity of living cells, where membranes are embedded within an extracellular matrix (ECM). Here, a biomimetic platform is presented that integrates fibronectin (FN) and collagen type I (COL) onto the surface of giant unilamellar vesicles (GUVs) to investigate ECM-induced modulation of membrane properties. ECM coating imparts distinct, protein-specific effects on vesicle curvature, mechanical resilience, and lipid diffusivity. FN promotes vesicle budding and membrane softening, while COL induces rugged membrane topographies and mechanical stiffening. Furthermore, ECM proteins reshape the geometry and stability of phase-separated lipid domains, mimicking curvature heterogeneity observed in cell membranes. Strikingly, vesicle budding events observed in FN-coated GUVs resemble exosome-like release, suggesting that ECM identity not only dictates membrane mechanics but may also regulate vesicle biogenesis. This system captures essential mechanobiological interactions between the ECM and the plasma membrane in the absence of transmembrane linkers. The findings provide a tunable platform for studying ECM-membrane coupling and ECM-vesicle interplay with relevance to exosome modeling, offering new directions for engineering responsive synthetic cells and advancing extracellular vesicle biology.

The upcycling of protein materials has long been hindered by the difficulty in restructuring them to usable forms. In contrast to proteins extracted using conventional organic denaturants, keratin treated with concentrated inorganic lithium bromide (LiBr) solution undergoes spontaneous aggregation into a stable gel with rapid phase-transition capability. We hypothesize that this distinct behaviour arises from an alternative denaturation mechanism that does not rely on direct interactions between proteins and concentrated ions. To investigate this, we study the denaturation effects of concentrated inorganic ion pairs using thermodynamic and spectroscopic analyses combined with atomistic molecular simulations. Through the isolation of indirect solute effects, our findings suggest a universal mechanism of salt-induced denaturation driven by entropy instead of enthalpy. We find that concentrated ion pairs like LiBr disrupt the water network structure rather than directly interacting with proteins. The mechanistic insight enables us to refine our previous extraction process of keratin materials, allowing for the spontaneous separation of denatured keratin into a condensed gel phase without additional chemicals and achieve closed-loop recycling of the LiBr denaturant. This simple, effective strategy can repurpose protein resources into versatile biomaterials in a simple, effective way without the need to separate organic denaturants from bulk proteins. The upcycling of protein materials has been hindered by the difficulty in restructuring them to usable forms. Here, the authors reveal that concentrated ion pairs like LiBr disrupt the water network structure rather than directly interacting with proteins, and develop a sustainable keratin regeneration method with closed-loop recycling of ionic denaturant and rapid solidification of protein gels.

N-terminal acetyltransferases including NAA10 catalyze N-terminal acetylation, an evolutionarily conserved co- and post-translational modification. However, little is known about the role of N-terminal acetylation in cardiac homeostasis. To gain insight into cardiac-dependent NAA10 function, we studied a previously unidentified NAA10 variant p.(Arg4Ser) segregating with QT-prolongation, cardiomyopathy, and developmental delay in a large kindred. Here, we show that the NAA10R4S variant reduced enzymatic activity, decreased NAA10-NAA15 complex formation, and destabilized the enzymatic complex N-terminal acetyltransferase A. In NAA10R4S/Y-induced pluripotent stem-cell-derived cardiomyocytes (iPSC-CMs), dysregulation of the late sodium and slow delayed rectifier potassium currents caused severe repolarization abnormalities, consistent with clinical QT prolongation. Engineered heart tissues generated from NAA10R4S/Y-iPSC-CMs had significantly decreased contractile force and sarcomeric disorganization, consistent with the pedigree’s cardiomyopathic phenotype. Proteomic studies revealed dysregulation of metabolic pathways and cardiac structural proteins. We identified small molecule and genetic therapies that normalized the phenotype of NAA10R4S/Y-iPSC-CMs. Our study defines the roles of N-terminal acetylation in cardiac regulation and delineates mechanisms underlying QT prolongation, arrhythmia, and cardiomyopathy caused by NAA10 dysfunction. N-terminal acetylation dysregulation in the heart causes severe arrhythmia and cardiomyopathy. The authors show that stem cell models demonstrate ion channel trafficking defects and sarcomeric disarray as the underlying mechanisms, with gene therapy reversing both phenotypes

In vitro cardiac microphysiological models are highly reliable for scientific research, drug development, and medical applications. Although widely accepted by the scientific community, these systems are still limited in longevity due to the absence of non-invasive stimulation techniques. Phototransducers provide an efficient stimulation method, offering a wireless approach with high temporal and spatial resolution while minimizing invasiveness in stimulation processes. In this manuscript, we present a fully optical method for stimulating and detecting the activity of an in vitro cardiac microphysiological model. Specifically, we fabricated engineered laminar anisotropic tissues by seeding human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) generated in a 3D bioreactor suspension culture. We employed a phototransducer, an amphiphilic azobenzene derivative, named Ziapin2, for stimulation and a Ca2+ dye (X-Rhod 1) for monitoring the system's response. The results demonstrate that Ziapin2 can photomodulate Ca2+ responses in the employed system without compromising tissue integrity, viability, or behavior. Furthermore, we showed that the light-based stimulation approach offers a similar resolution compared to electrical stimulation, the current gold standard. Overall, this protocol opens promising perspectives for the application of Ziapin2 and material-based photostimulation in cardiac research.

In biomimetic design, researchers recreate existing biological structures to form functional devices. For biohybrid robotic swimmers assembled with tissue engineering, this is problematic because most devices operate at different length scales than their naturally occurring counterparts, resulting in reduced performance. To overcome these challenges, here, we demonstrate how machine learning-directed optimization (ML-DO) can be used to inform the design of a biohybrid robot, outperforming other nonlinear optimization techniques, such as Bayesian optimization, in the selection of high-performance geometries. We show how this approach can be used to maximize the thrust generated by a tissue-engineered mobuliform miniray. This results in devices that can swim at the millimeter scale while more closely preserving natural locomotive scaling laws. Overall, this work provides a quantitatively rigorous approach for the engineering design of muscular structure-function relationships in an automated fashion.

Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) lack nanoscale structures essential for efficient excitation–contraction coupling. Such nanostructures, known as dyads, are frequently disrupted in heart failure. Here we show that the reduced expression of cardiomyopathy-associated 5 (CMYA5), a master protein that establishes dyads, contributes to dyad disorganization in heart failure and to impaired dyad assembly in hiPSC-CMs, and that a miniaturized form of CMYA5 suitable for delivery via an adeno-associated virus substantially improved dyad architecture and normalized cardiac function under pressure overload. In hiPSC-CMs, the miniaturized form of CMYA5 increased contractile forces, improved Ca2+ handling and enhanced the alignment of sarcomere Z-lines with ryanodine receptor 2, a protein that mediates the sarcoplasmic release of stored Ca2+. Our findings clarify the mechanisms responsible for impaired dyad structure in diseased cardiomyocytes, and suggest strategies for promoting dyad assembly and stability in heart disease and during the derivation of hiPSC-CMs. The viral delivery of a miniaturized form of a master protein that establishes dyads (nanostructures involved in excitation–contraction coupling in cardiomyocytes) improved dyad architecture and normalized cardiac function under pressure overload.

N-terminal-acetyltransferases including NAA10 catalyze N-terminal acetylation (Nt-acetylation), an evolutionarily conserved co-translational modification. Little is known about the role of Nt-acetylation in cardiac homeostasis. To gain insights, we studied a novel NAA10 variant (p.R4S) segregating with QT-prolongation, cardiomyopathy and developmental delay in a large kindred. Here we show that the NAA10-R4S mutation reduced enzymatic activity, decreased expression levels of NAA10/NAA15 proteins, and destabilized the enzymatic complex NatA. In NAA10R4S/Y-iPSC-CMs, dysregulation of the late sodium and slow rectifying potassium currents caused severe repolarization abnormalities, consistent with clinical QT prolongation. Engineered heart tissues generated from NAA10R4S/Y-iPSC-CMs had significantly decreased contractile force and sarcomeric disorganization, consistent with the pedigree’s cardiomyopathic phenotype. We identified small molecule and genetic therapies that normalized the phenotype of NAA10R4S/Y-iPSC-CMs. Our study defines novel roles of Nt-acetylation in cardiac regulation and delineates mechanisms underlying QT prolongation, arrhythmia, and cardiomyopathy caused by NAA10 dysfunction.

Human iPSC-derived cardiomyocytes (hiPSC-CMs) have proven invaluable for cardiac disease modeling and regeneration. Challenges with quality, inter-batch consistency, cryopreservation and scale remain, reducing experimental reproducibility and clinical translation. Here, we report a robust stirred suspension cardiac differentiation protocol, and we perform extensive morphological and functional characterization of the resulting bioreactor-differentiated iPSC-CMs (bCMs). Across multiple different iPSC lines, the protocol produces 1.2E6/mL bCMs with ~94% purity. bCMs have high viability after cryo-recovery (>90%) and predominantly ventricular identity. Compared to standard monolayer-differentiated CMs, bCMs are more reproducible across batches and have more mature functional properties. The protocol also works with magnetically stirred spinner flasks, which are more economical and scalable than bioreactors. Minor protocol modifications generate cardiac organoids fully in suspension culture. These reproducible, scalable, and resource-efficient approaches to generate iPSC-CMs and organoids will expand their applications, and our benchmark data will enable comparison to cells produced by other cardiac differentiation protocols.

Studying the behavior of electroactive cells, such as firing dynamics and chemical secretion, is crucial for developing human disease models and therapeutics. Following the recent advances in cell culture technology, traditional monolayers are optimized to resemble more 3D, organ‐like structures. The biological and electrochemical complexity of these structures requires devices with adaptive shapes and novel features, such as precise electrophysiological mapping and stimulation in the case of brain‐ and heart‐derived tissues. However, conventional organ‐on‐chip platforms often fall short, as they do not recreate the native environment of the cells and lack the functional interfaces necessary for long‐term monitoring. Origami‐on‐a‐chip platforms offer a solution for this problem, as they can flexibly adapt to the structure of the desired biological sample and can be integrated with functional components enabled by chosen materials. In this review, the evolution of origami‐on‐a‐chip biointerfaces is discussed, emphasizing folding stimuli, materials, and critical findings. In the prospects, microfluidic integration, functional tissue engineering scaffolds, and multi‐organoid networks are included, allowing patient‐specific diagnoses and therapies through computational and in vitro disease modeling.

For over a century, an explanation for how concentrated ions denature proteins has proven elusive. Here, we report a novel mechanism of protein denaturation driven by entropy changes in water networks. Experiments and simulations show that ion pairs like LiBr and LiCl localize water molecules and disrupt the water network's structure, while others exert a more global effect without compromising network integrity. This disruption reduces the entropy penalty when proteins sequester water molecules during unfolding, resulting in a peculiar yet universal "inverse hydrophobic effect" that potentiates protein denaturation. Through successful isolation and systematic study of indirect solute effects, our findings offer a universal approach to salt induced protein denaturation and provide a unified framework for the decoding of the protein-water-solute nexus.

In the last decade human iPSC-derived cardiomyocytes (hiPSC-CMs) proved to be valuable for cardiac disease modeling and cardiac regeneration, yet challenges with scale, quality, inter-batch consistency, and cryopreservation remain, reducing experimental reproducibility and limiting clinical translation. Here, we report a robust cardiac differentiation protocol that uses Wnt modulation and a stirred suspension bioreactor to produce on average 124 million hiPSC-CMs with >90% purity using a variety of hiPSC lines (19 differentiations; 10 iPSC lines). After controlled freeze and thaw, bioreactor-derived CMs (bCMs) showed high viability (>90%), interbatch reproducibility in cellular morphology, function, drug response and ventricular identity, which was further supported by single cell transcriptomes. bCMs on microcontact printed substrates revealed a higher degree of sarcomere maturation and viability during long-term culture compared to monolayer-derived CMs (mCMs). Moreover, functional investigation of bCMs in 3D engineered heart tissues showed earlier and stronger force production during long-term culture, and robust pacing capture up to 4 Hz when compared to mCMs. bCMs derived from this differentiation protocol will expand the applications of hiPSC-CMs by providing a reproducible, scalable, and resource efficient method to generate cardiac cells with well-characterized structural and functional properties superior to standard mCMs.

In tissues and organs, the extracellular matrix (ECM) helps maintain inter- and intracellular architectures that sustain the structure-function relationships defining physiological homeostasis. Combining fiber scaffolds and cells to form engineered tissues is a means of replicating these relationships. Engineered tissues' fiber scaffolds are designed to mimic the topology and chemical composition of the ECM network. Here, we asked how cells found in the heart compare in their propensity to align their cytoskeleton and self-organize in response to topological cues in fibrous scaffolds. We studied cardiomyocytes, valvular interstitial cells, and vascular endothelial cells as they adapted their inter- and intracellular architectures to the extracellular space. We used focused rotary jet spinning to manufacture aligned fibrous scaffolds to mimic the length scale and three-dimensional (3D) nature of the native ECM in the muscular, valvular, and vascular tissues of the heart. The representative cardiovascular cell types were seeded onto fiber scaffolds and infiltrated the fibrous network. We measured different cell types' propensity for cytoskeletal alignment in response to fiber scaffolds with differing levels of anisotropy. The results indicated that valvular interstitial cells on moderately anisotropic substrates have a higher propensity for cytoskeletal alignment than cardiomyocytes and vascular endothelial cells. However, all cell types displayed similar levels of alignment on more extreme (isotropic and highly anisotropic) fiber scaffold organizations. These data suggest that in the hierarchy of signals that dictate the spatiotemporal organization of a tissue, geometric cues within the ECM and cellular networks may homogenize behaviors across cell populations and demographics.

Gap junction and ion channel remodeling occur early in arrhythmogenic cardiomyopathy (ACM), but their pathogenic consequences have not been elucidated. Here, we identified the arrhythmogenic substrate, consisting of propagation slowing and conduction block, in ACM models expressing two different desmosomal gene variants. Neonatal rat ventricular myocytes were transduced to express variants in genes encoding desmosomal proteins plakoglobin or plakophilin-2. Studies were performed in engineered cells and anisotropic tissues to quantify changes in conduction velocity, formation of unidirectional propagation, cell-cell electrical coupling, and ion currents. Conduction velocity decreased by 71% and 63% in the two ACM models. SB216763, an inhibitor of glycogen synthase kinase-3 beta, restored conduction velocity to near normal levels. Compared to control, both ACM models showed greater propensity for unidirectional conduction block, which increased further at greater stimulation frequencies. Cell-cell electrical conductance measured in cell pairs was reduced by 86% and 87% in the two ACM models. Computer modeling showed close correspondence between simulated and experimentally determined changes in conduction velocity. The simulation identified that reduced cell-cell electrical coupling was the dominant factor leading to slow conduction, while the combination of reduced cell-cell electrical coupling, reduced sodium current and inward rectifier potassium current explained the development of unidirectional block. Expression of two different ACM variants markedly reduced cell-cell electrical coupling and conduction velocity, and greatly increased the likelihood of developing unidirectional block – both key features of arrhythmogenesis. This study provides the first quantitative analysis of cellular electrophysiological changes leading to the substrate of reentrant arrhythmias in early stage ACM.

Combat helmets are designed to protect against ballistic threats and fragments of explosive devices. There are numerous types of helmet comfort foams available. However, pad systems have not been evaluated in combat helmets to understand to what extent they mitigate head accelerations. In this work, different pad systems are studied to analyze the ballistic performance of combat helmets using a Hybrid III dummy equipped with longitudinal accelerometers at the head and a neck simulator. The tests are conducted with 9 mm Full Metal Jacket (FMJ) projectiles according to the performance requirements III-A of the NIJ 0106.01 standard. This experimental methodology allows the evaluation of brain and neck injuries. The thicker bicomponent polyurethane foams and the honeycomb configuration provided the best results in terms of mitigating brain damage due to accelerations applying different criteria (PLA, WSTC, HIC). However, it was concluded that there is no cervical injury or cranial fracture risk for any of the cases studied.

Arrhythmogenic cardiomyopathy (ACM) is an inherited cardiac disorder that causes life-threatening arrhythmias and myocardial dysfunction. Pathogenic variants in Plakophilin-2 ( PKP2 ), a desmosome component within specialized cardiac cell junctions, cause the majority of ACM cases. However, the molecular mechanisms by which PKP2 variants induce disease phenotypes remain unclear. Here we built bioengineered platforms using genetically modified human induced pluripotent stem cell-derived cardiomyocytes to model the early spatiotemporal process of cardiomyocyte junction assembly in vitro . Heterozygosity for truncating variant PKP2 R413X reduced Wnt/β-catenin signaling, impaired myofibrillogenesis, delayed mechanical coupling, and reduced calcium wave velocity in engineered tissues. These abnormalities were ameliorated by SB216763, which activated Wnt/β-catenin signaling, improved cytoskeletal organization, restored cell junction integrity in cell pairs, and improved calcium wave velocity in engineered tissues. Together, these findings highlight the therapeutic potential of modulating Wnt/β-catenin signaling in a human model of ACM.

Hydrogels are attractive materials for tissue engineering, but efforts to date have shown limited ability to produce the microstructural features necessary to promote cellular self-organization into hierarchical three-dimensional (3D) organ models. Here we develop a hydrogel ink containing prefabricated gelatin fibres to print 3D organ-level scaffolds that recapitulate the intra- and intercellular organization of the heart. The addition of prefabricated gelatin fibres to hydrogels enables the tailoring of the ink rheology, allowing for a controlled sol–gel transition to achieve precise printing of free-standing 3D structures without additional supporting materials. Shear-induced alignment of fibres during ink extrusion provides microscale geometric cues that promote the self-organization of cultured human cardiomyocytes into anisotropic muscular tissues in vitro. The resulting 3D-printed ventricle in vitro model exhibited biomimetic anisotropic electrophysiological and contractile properties. A gelatin–alginate hydrogel ink incorporating short gelatin fibres guides the self-organization of human cardiomyocytes into contractile tissues that can be 3D-printed into structures mimicking human organs.

ABSTRACT BACKGROUND N-terminal-acetyltransferases catalyze N-terminal acetylation (Nt-acetylation), an evolutionarily conserved co-translational modification. Nt-acetylation regulates diverse signaling pathways, yet little is known about its effects in the heart. To gain insights, we studied NAA10-related syndrome, in which mutations in NAA10, which catalyzes Nt-acetylation, causes severe QT prolongation, hypotonia, and neurodevelopmental delay. METHODS We identified a missense variant in NAA10 (c.10C>A; p.R4S) that segregated with severe QT prolongation, arrhythmia, cardiomyopathy, and sudden death in a large kindred. We developed patient-derived and genome-edited human induced pluripotent stem cell (iPSC) models and deeply phenotyped iPSC-derived cardiomyocytes (iPSC-CMs) to dissect the mechanisms underlying NAA10-mediated cardiomyocyte dysfunction. RESULTS The NAA10-R4S mutation reduced enzymatic activity, decreased expression levels of NAA10/NAA15 proteins, and destabilized the NatA complex. In iPSC-CM models of NAA10 dysfunction, dysregulation of the late sodium and slow rectifying potassium currents caused severe repolarization abnormalities, consistent with clinical QT prolongation and increased risk for arrhythmogenesis. Engineered heart tissues generated from mutant NAA10 cell lines had significantly decreased contractile force and sarcomeric disorganization, consistent with the cardiomyopathic phenotype in the identified family members. Diastolic calcium levels were increased with corresponding alterations in calcium handling pathways. We identified small molecule and genetic therapies that reversed the effects of NAA10 dysregulation of iPSC-CMs. CONCLUSIONS Our study defines novel roles of Nt-acetylation in cardiac ion channel regulation and delineates mechanisms underlying QT prolongation, arrhythmia, and cardiomyopathy caused by NAA10 dysfunction.

Combat helmets are the primary system for protecting the head against ballistic impacts. Generally, combat helmets have been evaluated using a ballistic plasticine head surrogate based on international standards. More realistic human head models have recently been introduced to assess combat helmet performance considering biomechanical requirements. In this work, the Hybrid III dummy head and neck has been introduced to evaluate the performance of the combat helmet against the ballistic impact of live ammunition at different impact locations, considering two different thicknesses of the padding system. A numerical model including a helmet and a Hybrid III head and neck, is developed and validated with our experimental data. The results reveal the influence of the location, where the rear impact leads to the highest risk of brain damage. The effect of pad thickness is closely related to the energy absorbed by the helmet, the backface deformation (BFD), the contact force and the acceleration measured on the head.

Light is recognized as an accurate and noninvasive tool for stimulating excitable cells. Here, we report on a non-genetic approach based on organic molecular phototransducers that allows wiring- and electrode-free tissue modulation. As a proof of concept, we show photostimulation of an in vitro cardiac microphysiological model mediated by an amphiphilic azobenzene compound that preferentially dwells in the cell membrane. Exploiting this optical based stimulation technology could be a disruptive approach for highly resolved cardiac tissue stimulation.

The present invention provides tissue-engineered pumps and valves, methods of fabricating such pumps and valves, and methods of use of such pumps and valves.

Fully integrated low power 200Gb/s DSP based optical transmitter and receiver ICs with transmitter chip incorporating fully integrated laser drivers and receiver chip with fully integrated Transimpedance amplifier (TIA) in 16nm FinFet using wirebond technology

Fully integrated low power 200Gb/s DSP based optical transmitter and receiver ICs with transmitter chip incorporating fully integrated laser drivers and receiver chip with fully integrated Transimpedance amplifier (TIA) in 16nm FinFet using wirebond technology.

Image files used in the figures and numeric data source in the supplementary information