Sequence modeling and design from molecular to genome scale with Evo.

The genome is a sequence that encodes the DNA, RNA, and proteins that orchestrate an organism's function. We present Evo, a long-context genomic foundation model with a frontier architecture trained on millions of prokaryotic and phage genomes, and report scaling laws on DNA to complement observations in language and vision. Evo generalizes across DNA, RNA, and proteins, enabling zero-shot function prediction competitive with domain-specific language models and the generation of functional CRISPR-Cas and transposon systems, representing the first examples of protein-RNA and protein-DNA codesign with a language model.

Design and Validation of Soft Sliding Structure with Adjustable Stiffness for Ankle Sprain Prevention.

This study presents the design and validation of a soft sliding stiffness structure with a soft-rigid layer sliding mechanism. It aims to mitigate ankle sprains and address the progression of chronic ankle instability by providing stiffness support. The soft-rigid layer sliding mechanism of the structure is designed to achieve a wide range of stiffness while maintaining a compact form factor.

TNFR2 signaling in oligodendrocyte precursor cells suppresses their immune-inflammatory function and detrimental microglia activation in CNS demyelinating disease.

Multiple Sclerosis (MS) is a chronic degenerative disease of the central nervous system (CNS) characterized by inflammation, demyelination, and progressive neurodegeneration. These processes, combined with the failure of reparative remyelination initiated by oligodendrocyte precursor cells (OPCs), lead to irreversible neurological impairment. The cytokine tumor necrosis factor (TNF) has been implicated in CNS repair via activation of its cognate receptor TNFR2 in glia.

The Obesity Epidemic Is Not the Victims' Fault.

The Centers for Disease Control and Prevention recently issued two statements that 1) maintain that obesity causes diabetes and other expressions of the metabolic syndrome and 2) that imply obesity is the victim's fault. Both statements are incorrect and potentially harmful.

PI3K signaling promotes formation of lipid-laden foamy macrophages at the spinal cord injury site.

After spinal cord injury (SCI), infiltrating macrophages undergo excessive phagocytosis of myelin and cellular debris, forming lipid-laden foamy macrophages. To understand their role in the cellular pathology of SCI, investigation of the foamy macrophage phenotype in vitro revealed a pro-inflammatory profile, increased reactive oxygen species (ROS) production, and mitochondrial dysfunction. Bioinformatic analysis identified PI3K as a regulator of inflammation in foamy macrophages, and inhibition of this pathway decreased their lipid content, inflammatory cytokines, and ROS production.

Single-Step 3D Printing of Bio-Inspired Printable Joints Applied to a Prosthetic Hand.

Single-step 3D printing, which can manufacture complicated designs without assembly, has the potential to completely change our design perspective, and how 3D printing products, rather than printing static components, ready-to-use movable mechanisms become a reality. Existing 3D printing solutions are challenged by precision limitations, and cannot directly produce tightly mated moving surfaces. Therefore, joints must be designed with a sufficient gap between the components, resulting in joints and other mechanisms with imprecise motion.

Highly multiplexed mRNA quantitation with CRISPR-Cas13.

RNA quantitation tools are often either high-throughput or cost-effective, but rarely are they both. Existing methods can profile the transcriptome at great expense or are limited to quantifying a handful of genes by labor constraints. A technique that permits more throughput at a reduced cost could enable multi-gene kinetic studies, gene regulatory network analysis, and combinatorial genetic screens.

Multiplexed CRISPR-based Methods for Pathogen Nucleic Acid Detection.

Bacterial and viral pathogens are devastating to human health and well-being. In many regions, dozens of pathogen species and variants co-circulate. Thus, it is important to detect many different species and variants of pathogens in a given sample through multiplexed detection methods.

Specified-duration shapers for suppressing residual vibrations.

Input-shaping control has received considerable research attention for suppressing residual vibrations. Although numerous studies have been conducted on designing input shapers with arbitrary robustness to modeling errors, no studies have focused on the design of input shapers with arbitrarily specified shaping times. In this study, a specified-duration (SD) shaper, which is an input shaper with an arbitrarily specified shaping time, and a systematic method to design an SD shaper using impulse vectors are proposed.

Cytostatic hypothermia and its impact on glioblastoma and survival.

Patients with glioblastoma (GBM) have limited options and require novel approaches to treatment. Here, we studied and deployed nonfreezing "cytostatic" hypothermia to stunt GBM growth. This growth-halting method contrasts with ablative, cryogenic hypothermia that kills both neoplastic and infiltrated healthy tissue.

Review of machine learning methods in soft robotics.

Soft robots have been extensively researched due to their flexible, deformable, and adaptive characteristics. However, compared to rigid robots, soft robots have issues in modeling, calibration, and control in that the innate characteristics of the soft materials can cause complex behaviors due to non-linearity and hysteresis. To overcome these limitations, recent studies have applied various approaches based on machine learning.

Psychometric properties of measures of substance use: a systematic review and meta-analysis of reliability, validity and diagnostic test accuracy.

Background: Synthesis of psychometric properties of substance use measures to identify patterns of use and substance use disorders remains limited. To address this gap, we sought to systematically evaluate the psychometric properties of measures to detect substance use and misuse.

Methods: We conducted a systematic review and meta-analysis of literature on measures of substance classes associated with HIV risk (heroin, methamphetamine, cocaine, ecstasy, alcohol) that were published in English before June 2016 that reported at least one of the following psychometric outcomes of interest: internal consistency (alpha), test-retest/inter-rater reliability (kappa), sensitivity, specificity, positive predictive value, and negative predictive value.

Eyes are faster than hands: A soft wearable robot learns user intention from the egocentric view.

To perceive user intentions for wearable robots, we present a learning-based intention detection methodology using a first-person-view camera.

Exo-Glove Poly II: A Polymer-Based Soft Wearable Robot for the Hand with a Tendon-Driven Actuation System.

This article presents Exo-Glove Poly (EGP) II, a soft wearable robot for the hand with a glove that is completely constructed of polymer materials and that operates through tendon-driven actuation for use in spinal cord injury (SCI). EGP II can restore the ability to pinch and grasp any object for people with SCI in daily life. The design of the glove allows it to be compact and extends the range of hand sizes that can fit.

Re-sensitizing Multidrug Resistant Bacteria to Antibiotics by Targeting Bacterial Response Regulators: Characterization and Comparison of Interactions between 2-Aminoimidazoles and the Response Regulators BfmR from and QseB from spp.

2-aminoimidazole (2-AI) compounds inhibit the formation of bacterial biofilms, disperse preformed biofilms, and re-sensitize multidrug resistant bacteria to antibiotics. 2-AIs have previously been shown to interact with bacterial response regulators, but the mechanism of interaction is still unknown. Response regulators are one part of two-component systems (TCS).

Fish Oil Contaminated with Persistent Organic Pollutants Induces Colonic Aberrant Crypt Foci Formation and Reduces Antioxidant Enzyme Gene Expression in Rats.

Epidemiologic, clinical, and experimental studies have suggested that fish oil (FO), a rich source of n-3 (ω-3) polyunsaturated fatty acids, protects against colon cancer. However, this message is confounded by the FDA's warning that the consumption of certain types of fish should be restricted because of contamination with persistent organic pollutants (POPs), such as polychlorinated biphenyls (PCBs) and organochlorine pesticides. We examined FO contaminated with POPs (PCBs, dichlorodiphenyltrichloroethane, and chlordane) compared with unmodified FO on the risk factors of colon cancer development.

Proposed clinical internal carotid artery classification system.

Introduction: Numerical classification systems for the internal carotid artery (ICA) are available, but modifications have added confusion to the numerical systems. Furthermore, previous classifications may not be applicable uniformly to microsurgical and endoscopic procedures. The purpose of this study was to develop a clinically useful classification system.

Directed evolution of a pyruvate aldolase to recognize a long chain acyl substrate.

The use of biological catalysts for industrial scale synthetic chemistry is highly attractive, given their cost effectiveness, high specificity that obviates the need for protecting group chemistry, and the environmentally benign nature of enzymatic procedures. Here we evolve the naturally occurring 2-keto-3-deoxy-6-phosphogluconate (KDPG) aldolases from Thermatoga maritima and Escherichia coli, into enzymes that recognize a nonfunctionalized electrophilic substrate, 2-keto-4-hydroxyoctonoate (KHO). Using an in vivo selection based on pyruvate auxotrophy, mutations were identified that lower the K(M) value up to 100-fold in E.

CCR2-antagonist prophylaxis reduces pulmonary immune pathology and markedly improves survival during influenza infection.

Infection with influenza virus induces severe pulmonary immune pathology that leads to substantial human mortality. Although antiviral therapy is effective in preventing infection, no current therapy can prevent or treat influenza-induced lung injury. Previously, we reported that influenza-induced pulmonary immune pathology is mediated by inflammatory monocytes trafficking to virus-infected lungs via CCR2 and that influenza-induced morbidity and mortality are reduced in CCR2-deficient mice.

Bacteria-induced static batch fungal fermentation of the diterpenoid cyathin A(3), a small-molecule inducer of nerve growth factor.

Cyathin A(3), produced by the fungus Cyathus helenae, is a member of the cyathane family of diterpene natural products. While many of the cyathanes display antibacterial/antimicrobial activity or have cytotoxic activity against human cancer cell lines, their most exciting therapeutic potential is derived from their ability to induce nerve growth factor (NGF) release from glial cells, making the cyathanes attractive lead molecules for the development of neuroprotective therapeutics to prevent/treat Alzheimer's disease. To investigate if cyathin A(3) has NGF-inducing activity, we set out to obtain it using published C.

Assessing spinal axon regeneration and sprouting in Nogo-, MAG-, and OMgp-deficient mice.

A central hypothesis for the limited capacity for adult central nervous system (CNS) axons to regenerate is the presence of myelin-derived axon growth inhibitors, the role of which, however, remains poorly understood. We have conducted a comprehensive genetic analysis of the three major myelin inhibitors, Nogo, MAG, and OMgp, in injury-induced axonal growth, including compensatory sprouting of uninjured axons and regeneration of injured axons. While deleting any one inhibitor in mice enhanced sprouting of corticospinal or raphespinal serotonergic axons, there was neither associated behavioral improvement nor a synergistic effect of deleting all three inhibitors.