Dysregulation of N-terminal acetylation causes cardiac arrhythmia and cardiomyopathy.

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.

Single-cell image-based genetic screens systematically identify regulators of Ebola virus subcellular infection dynamics.

Ebola virus (EBOV) is a high-consequence filovirus that gives rise to frequent epidemics with high case fatality rates and few therapeutic options. Here, we applied image-based screening of a genome-wide CRISPR library to systematically identify host cell regulators of Ebola virus infection in 39,085,093 million single cells. Measuring viral RNA and protein levels together with their localization in cells identified over 998 related host factors and provided detailed information about the role of each gene across the virus replication cycle.

Mechanism for feature learning in neural networks and backpropagation-free machine learning models.

Understanding how neural networks learn features, or relevant patterns in data, for prediction is necessary for their reliable use in technological and scientific applications. In this work, we presented a unifying mathematical mechanism, known as average gradient outer product (AGOP), that characterized feature learning in neural networks. We provided empirical evidence that AGOP captured features learned by various neural network architectures, including transformer-based language models, convolutional networks, multilayer perceptrons, and recurrent neural networks.

BlastAssist: a deep learning pipeline to measure interpretable features of human embryos.

Study Question: Can the BlastAssist deep learning pipeline perform comparably to or outperform human experts and embryologists at measuring interpretable, clinically relevant features of human embryos in IVF?

Summary Answer: The BlastAssist pipeline can measure a comprehensive set of interpretable features of human embryos and either outperform or perform comparably to embryologists and human experts in measuring these features.

What Is Known Already: Some studies have applied deep learning and developed 'black-box' algorithms to predict embryo viability directly from microscope images and videos but these lack interpretability and generalizability. Other studies have developed deep learning networks to measure individual features of embryos but fail to conduct careful comparisons to embryologists' performance, which are fundamental to demonstrate the network's effectiveness.

Report of the Assay Guidance Workshop on 3-Dimensional Tissue Models for Antiviral Drug Development.

The National Center for Advancing Translational Sciences (NCATS) Assay Guidance Manual (AGM) Workshop on 3D Tissue Models for Antiviral Drug Development, held virtually on 7-8 June 2022, provided comprehensive coverage of critical concepts intended to help scientists establish robust, reproducible, and scalable 3D tissue models to study viruses with pandemic potential. This workshop was organized by NCATS, the National Institute of Allergy and Infectious Diseases, and the Bill and Melinda Gates Foundation. During the workshop, scientific experts from academia, industry, and government provided an overview of 3D tissue models' utility and limitations, use of existing 3D tissue models for antiviral drug development, practical advice, best practices, and case studies about the application of available 3D tissue models to infectious disease modeling.

Dry Deposition Methods Based on Turbulence Kinetic Energy: Part 1. Evaluation of Various Resistances and Sensitivity Studies Using a Single-Point Model.

Different functions are used to account for turbulence strength in the atmospheric boundary layer for different stability regimes. These functions are one of the sources for differences among different atmospheric models' predictions and associated biases. Also, turbulence strength is underrepresented in some of the resistance formulations.

Importance of Preserved Tricuspid Valve Function for Effective Soft Robotic Augmentation of the Right Ventricle in Cases of Elevated Pulmonary Artery Pressure.

Purpose: In clinical practice, many patients with right heart failure (RHF) have elevated pulmonary artery pressures and increased afterload on the right ventricle (RV). In this study, we evaluated the feasibility of RV augmentation using a soft robotic right ventricular assist device (SRVAD), in cases of increased RV afterload.

Methods: In nine Yorkshire swine of 65-80 kg, a pulmonary artery band was placed to cause RHF and maintained in place to simulate an ongoing elevated afterload on the RV.

Automatic extraction of the mitral valve chordae geometry for biomechanical simulation.

Purpose: Mitral valve computational models are widely studied in the literature. They can be used for preoperative planning or anatomical understanding. Manual extraction of the valve geometry on medical images is tedious and requires special training, while automatic segmentation is still an open problem.

Clocks without "Time" in Entangled-State Experiments.

Entangled states of light exhibit measurable correlations between light detections at separated locations. These correlations are exploited in entangled-state quantum key distribution. To do so involves setting up and maintaining a rhythm of communication among clocks at separated locations.

The extension of internal humidity levels beyond the soil surface facilitates mound expansion in .

Termites in the genus construct large-scale soil mounds above their nests. The classic explanation for how termites coordinate their labour to build the mound, based on a putative cement pheromone, has recently been called into question. Here, we present evidence for an alternate interpretation based on sensing humidity.

Local rotation invariance in 3D CNNs.

Locally Rotation Invariant (LRI) image analysis was shown to be fundamental in many applications and in particular in medical imaging where local structures of tissues occur at arbitrary rotations. LRI constituted the cornerstone of several breakthroughs in texture analysis, including Local Binary Patterns (LBP), Maximum Response 8 (MR8) and steerable filterbanks. Whereas globally rotation invariant Convolutional Neural Networks (CNN) were recently proposed, LRI was very little investigated in the context of deep learning.

Chemically Coupled Interfacial Adhesion in Multimaterial Printing of Hydrogels and Elastomers.

Functional devices that use hydrogels as ionic conductors and elastomers as dielectrics have the advantage of being soft, stretchable, transparent, and biocompatible, making them ideal for biomedical applications. These devices are typically fabricated by manual assembly. Techniques for the manufacturing of soft materials have generally not looked at integrating multiple dissimilar materials.

Peax: Interactive Visual Pattern Search in Sequential Data Using Unsupervised Deep Representation Learning.

We present Peax, a novel feature-based technique for interactive visual pattern search in sequential data, like time series or data mapped to a genome sequence. Visually searching for patterns by similarity is often challenging because of the large search space, the visual complexity of patterns, and the user's perception of similarity. For example, in genomics, researchers try to link patterns in multivariate sequential data to cellular or pathogenic processes, but a lack of ground truth and high variance makes automatic pattern detection unreliable.

Dynamic Augmentation of Left Ventricle and Mitral Valve Function With an Implantable Soft Robotic Device.

Left ventricular failure is strongly associated with secondary mitral valve regurgitation. Implantable soft robotic devices are an emerging technology that enables augmentation of a native function of a target tissue. We demonstrate the ability of a novel soft robotic ventricular assist device to dynamically augment left ventricular contraction, provide native pulsatile flow, simultaneously reshape the mitral valve apparatus, and eliminate the associated regurgitation in an Short-term large animal model of acute left ventricular systolic dysfunction.

Reconstruction of Large Skeletal Defects: Current Clinical Therapeutic Strategies and Future Directions Using 3D Printing.

The healing of bone fractures is a well-orchestrated physiological process involving multiple cell types and signaling molecules interacting at the fracture site to replace and repair bone tissue without scar formation. However, when the lesion is too large, normal healing is compromised. These so-called non-union bone fractures, mostly arising due to trauma, tumor resection or disease, represent a major therapeutic challenge for orthopedic and reconstructive surgeons.

Electrolyte Lifetime in Aqueous Organic Redox Flow Batteries: A Critical Review.

Aqueous organic redox flow batteries (RFBs) could enable widespread integration of renewable energy, but only if costs are sufficiently low. Because the levelized cost of storage for an RFB is a function of electrolyte lifetime, understanding and improving the chemical stability of active reactants in RFBs is a critical research challenge. We review known or hypothesized molecular decomposition mechanisms for all five classes of aqueous redox-active organics and organometallics for which cycling lifetime results have been reported: quinones, viologens, aza-aromatics, iron coordination complexes, and nitroxide radicals.

Atmospheric Acetaldehyde: Importance of Air-Sea Exchange and a Missing Source in the Remote Troposphere.

We report airborne measurements of acetaldehyde (CHCHO) during the first and second deployments of the National Aeronautics and Space Administration (NASA) Atmospheric Tomography Mission (ATom). The budget of CHCHO is examined using the Community Atmospheric Model with chemistry (CAM-chem), with a newly-developed online air-sea exchange module. The upper limit of the global ocean net emission of CHCHO is estimated to be 34 Tg a (42 Tg a if considering bubble-mediated transfer), and the ocean impacts on tropospheric CHCHO are mostly confined to the marine boundary layer.

Advances in therapeutic applications of extracellular vesicles.

Extracellular vesicles (EVs) are nanometer-sized, lipid membrane-enclosed vesicles secreted by most, if not all, cells and contain lipids, proteins, and various nucleic acid species of the source cell. EVs act as important mediators of intercellular communication that influence both physiological and pathological conditions. Given their ability to transfer bioactive components and surmount biological barriers, EVs are increasingly being explored as potential therapeutic agents.

Reprogramming the microenvironment with tumor-selective angiotensin blockers enhances cancer immunotherapy.

Cancer-associated fibroblasts (CAFs) can either suppress or support T lymphocyte activity, suggesting that CAFs may be reprogrammable to an immunosupportive state. Angiotensin receptor blockers (ARBs) convert myofibroblast CAFs to a quiescent state, but whether ARBs can reprogram CAFs to promote T lymphocyte activity and enhance immunotherapy is unknown. Moreover, ARB doses are limited by systemic adverse effects such as hypotension due to the importance of angiotensin signaling outside tumors.

Surface curvature guides early construction activity in mound-building termites.

Termite colonies construct towering, complex mounds, in a classic example of distributed agents coordinating their activity via interaction with a shared environment. The traditional explanation for how this coordination occurs focuses on the idea of a 'cement pheromone', a chemical signal left with deposited soil that triggers further deposition. Recent research has called this idea into question, pointing to a more complicated behavioural response to cues perceived with multiple senses.

Immune Modulation by Transplanted Calcium Phosphate Biomaterials and Human Mesenchymal Stromal Cells in Bone Regeneration.

A wide variety of biomaterials have been developed as both stabilizing structures for the injured bone and inducers of bone neoformation. They differ in chemical composition, shape, porosity, and mechanical properties. The most extensively employed and studied subset of bioceramics are calcium phosphate materials (CaPs).

Blocking CXCR4 alleviates desmoplasia, increases T-lymphocyte infiltration, and improves immunotherapy in metastatic breast cancer.

Metastatic breast cancers (mBCs) are largely resistant to immune checkpoint blockade, but the mechanisms remain unclear. Primary breast cancers are characterized by a dense fibrotic stroma, which is considered immunosuppressive in multiple malignancies, but the stromal composition of breast cancer metastases and its role in immunosuppression are largely unknown. Here we show that liver and lung metastases of human breast cancers tend to be highly fibrotic, and unlike primary breast tumors, they exclude cytotoxic T lymphocytes (CTLs).

Comparison of Tumor- and Bone Marrow-Derived Mesenchymal Stromal/Stem Cells from Patients with High-Grade Osteosarcoma.

Osteosarcoma (OS) is suspected to originate from dysfunctional mesenchymal stromal/stem cells (MSC). We sought to identify OS-derived cells (OSDC) with potential cancer stem cell (CSC) properties by comparing OSDC to MSC derived from bone marrow of patients. This study included in vitro characterization with sphere forming assays, differentiation assays, cytogenetic analysis, and in vivo investigations of their tumorigenicity and tumor supportive capacities.

Fast image-based mitral valve simulation from individualized geometry.

Background: Common surgical procedures on the mitral valve of the heart include modifications to the chordae tendineae. Such interventions are used when there is extensive leaflet prolapse caused by chordae rupture or elongation. Understanding the role of individual chordae tendineae before operating could be helpful to predict whether the mitral valve will be competent at peak systole.

Leveraging advances in biology to design biomaterials.

Biomaterials have dramatically increased in functionality and complexity, allowing unprecedented control over the cells that interact with them. From these engineering advances arises the prospect of improved biomaterial-based therapies, yet practical constraints favour simplicity. Tools from the biology community are enabling high-resolution and high-throughput bioassays that, if incorporated into a biomaterial design framework, could help achieve unprecedented functionality while minimizing the complexity of designs by identifying the most important material parameters and biological outputs.