Discrete tissue microenvironments instruct diversity in resident memory T cell function and plasticity.

Tissue-resident memory T (TRM) cells are non-recirculating cells that exist throughout the body. Although TRM cells in various organs rely on common transcriptional networks to establish tissue residency, location-specific factors adapt these cells to their tissue of lodgment. Here we analyze TRM cell heterogeneity between organs and find that the different environments in which these cells differentiate dictate TRM cell function, durability and malleability. We find that unequal responsiveness to TGFß is a major driver of this diversity. Notably, dampened TGFß signaling results in CD103- TRM cells with increased proliferative potential, enhanced function and reduced longevity compared with their TGFß-responsive CD103+ TRM counterparts. Furthermore, whereas CD103- TRM cells readily modified their phenotype upon relocation, CD103+ TRM cells were comparatively resistant to transdifferentiation. Thus, despite common requirements for TRM cell development, tissue adaptation of these cells confers discrete functional properties such that TRM cells exist along a spectrum of differentiation potential that is governed by their local tissue microenvironment.

Dinoflagellate vertical migration fuels an intense red tide.

Harmful algal blooms (HABs) are increasing globally, causing economic, human health, and ecosystem harm. In spite of the frequent occurrence of HABs, the mechanisms responsible for their exceptionally high biomass remain imperfectly understood. A 50-y-old hypothesis posits that some dense blooms derive from dinoflagellate motility: organisms swim upward during the day to photosynthesize and downward at night to access deep nutrients. This allows dinoflagellates to outgrow their nonmotile competitors. We tested this hypothesis with in situ data from an autonomous, ocean-wave-powered vertical profiling system. We showed that the dinoflagellate Lingulodinium polyedra's vertical migration led to depletion of deep nitrate during a 2020 red tide HAB event. Downward migration began at dusk, with the maximum migration depth determined by local nitrate concentrations. Losses of nitrate at depth were balanced by proportional increases in phytoplankton chlorophyll concentrations and suspended particle load, conclusively linking vertical migration to the access and assimilation of deep nitrate in the ocean environment. Vertical migration during the red tide created anomalous biogeochemical conditions compared to 70 y of climatological data, demonstrating the capacity of these events to temporarily reshape the coastal ocean's ecosystem and biogeochemistry. Advances in the understanding of the physiological, behavioral, and metabolic dynamics of HAB-forming organisms from cutting-edge observational techniques will improve our ability to forecast HABs and mitigate their consequences in the future.

Nonequilibrium phase transitions in competitive markets caused by network effects.

Network effects are the added value derived solely from the popularity of a product in an economic market. Using agent-based models inspired by statistical physics, we propose a minimal theory of a competitive market for (nearly) indistinguishable goods with demand-side network effects, sold by statistically identical sellers. With weak network effects, the model reproduces conventional microeconomics: there is a statistical steady state of (nearly) perfect competition. Increasing network effects, we find a phase transition to a robust nonequilibrium phase driven by the spontaneous formation and collapse of fads in the market. When sellers update prices sufficiently quickly, an emergent monopolist can capture the market and undercut competition, leading to a symmetry- and ergodicity-breaking transition. The nonequilibrium phase simultaneously exhibits three empirically established phenomena not contained in the standard theory of competitive markets: spontaneous price fluctuations, persistent seller profits, and broad distributions of firm market shares.

Integrated Genomic and Social Network Analyses of SARS-CoV-2 Transmission in the Healthcare Setting.

BACKGROUND: Infection prevention (IP) measures are designed to mitigate the transmission of pathogens in healthcare. Using large-scale viral genomic and social network analyses, we determined if IP measures used during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic were adequate in protecting healthcare workers (HCWs) and patients from acquiring SARS-CoV-2. METHODS: We performed retrospective cross-sectional analyses of viral genomics from all available SARS-CoV-2 viral samples collected at UC San Diego Health and social network analysis using the electronic medical record to derive temporospatial overlap of infections among related viromes and supplemented with contact tracing data. The outcome measure was any instance of healthcare transmission, defined as cases with closely related viral genomes and epidemiological connection within the healthcare setting during the infection window. Between November 2020 through January 2022, 12 933 viral genomes were obtained from 35 666 patients and HCWs. RESULTS: Among 5112 SARS-CoV-2 viral samples sequenced from the second and third waves of SARS-CoV-2 (pre-Omicron), 291 pairs were derived from persons with a plausible healthcare overlap. Of these, 34 pairs (12%) were phylogenetically linked: 19 attributable to household and 14 to healthcare transmission. During the Omicron wave, 2106 contact pairs among 7821 sequences resulted in 120 (6%) related pairs among 32 clusters, of which 10 were consistent with healthcare transmission. Transmission was more likely to occur in shared spaces in the older hospital compared with the newer hospital (2.54 vs 0.63 transmission events per 1000 admissions, P < .001). CONCLUSIONS: IP strategies were effective at identifying and preventing healthcare SARS-CoV-2 transmission.

Patient perspectives on the unwanted effects of multidisciplinary pain management programmes: A qualitative study.

OBJECTIVE: This study aimed to understand the impact of pain management programmes, focusing on the unwanted effects and their influence on patients' long-term use of self-management strategies. DESIGN: Qualitative study. SETTING: Specialist musculoskeletal hospital in North London, England. PARTICIPANTS: Patients with chronic musculoskeletal pain that have completed a pain management programme. INTERVENTION: Multidisciplinary pain management programmes. MAIN MEASURES: Data were collected regarding patients' experiences and unwanted effects from the pain management programme using semi-structured interviews. Data were analysed using thematic analysis. RESULTS: Fourteen participant interviews were included in the analysis (median age 54 years, 12 females). Four themes were generated from the data: Benefits and burdens, Pain management programme and real life, Social support and Healthcare interventions. Unwanted effects included heightened anxiety related to negative interactions with peers, being in a new environment, worries about ability to cope with the programme, social anxiety from being in a group, the strain on families due to participants being away from home and a sense of abandonment at end of the programme. Burdens associated with implementing pain management strategies were identified, including the emotional burden of imposing their self-management on close family and competing demands with time and energy spent on self-management at the expense of work or home commitments. CONCLUSIONS: Pain management programmes have an important role in helping patients to learn how to self-manage chronic pain. Their unwanted effects and the treatment burdens associated with long-term self-management may be an important consideration in improving the longevity of their beneficial effects.

Investigation of the pharmacokinetic properties of synthetic heparan sulfate oligosaccharides.

Heparan sulfate (HS) is a sulfated polysaccharide with a wide range of biological activities. There is an increasing interest in the development of structurally homogeneous HS oligosaccharides as therapeutics. However, the factors influencing the pharmacokinetic properties of HS-based therapeutics remain unknown. Here, we report the pharmacokinetic properties of a panel of dodecasaccharides (12-mers) with varying sulfation patterns in healthy mice and uncover the pharmacokinetic properties of an octadecasaccharide (18-mer) in acutely injured mice. In the 12-mer panel, 1 12-mer, known as dekaparin, is anticoagulant, and 3 12-mers are nonanticoagulant. The concentrations of 12-mers in plasma and urine were determined by the disaccharide analysis using liquid chromatography coupled with tandem mass spectrometry. We observed a striking difference between anticoagulant and nonanticoagulant oligosaccharides in the 12-mer panel, showing that anticoagulant dekaparin had a 4.6-fold to 8.6-fold slower clearance and 4.4-fold to 8-fold higher plasma exposure compared to nonanticoagulant 12-mers. We also observed that the clearance of HS oligosaccharides is impacted by disease. Using an antiinflammatory 18-mer, we discovered that the clearance of 18-mer is reduced 2.8-fold in a liver failure mouse model compared to healthy mice. Our results suggest that oligosaccharides are rapidly cleared renally if they have low interaction with circulating proteins. We observed that the clearance rate of oligosaccharides is inversely associated with the degree of binding to target proteins, which can vary in response to pathophysiological conditions. Our findings uncover a contributing factor for the plasma and renal clearance of oligosaccharides which will aid the development of HS-based therapeutics.

Speed limits and locality in many-body quantum dynamics.

We review the mathematical speed limits on quantum information processing in many-body systems. After the proof of the Lieb-Robinson Theorem in 1972, the past two decades have seen substantial developments in its application to other questions, such as the simulatability of quantum systems on classical or quantum computers, the generation of entanglement, and even the properties of ground states of gapped systems. Moreover, Lieb-Robinson bounds have been extended in non-trivial ways, to demonstrate speed limits in systems with power-law interactions or interacting bosons, and even to prove notions of locality that arise in cartoon models for quantum gravity with all-to-all interactions. We overview the progress which has occurred, highlight the most promising results and techniques, and discuss some central outstanding questions which remain open. To help bring newcomers to the field up to speed, we provide self-contained proofs of the field's most essential results.

Prethermalization and the Local Robustness of Gapped Systems.

We prove that prethermalization is a generic property of gapped local many-body quantum systems, subjected to small perturbations, in any spatial dimension. More precisely, let H_{0} be a Hamiltonian, spatially local in d spatial dimensions, with a gap Δ in the many-body spectrum; let V be a spatially local Hamiltonian consisting of a sum of local terms, each of which is bounded by ε≪Δ. Then, the approximation that quantum dynamics is restricted to the low-energy subspace of H_{0} is accurate, in the correlation functions of local operators, for stretched exponential timescale τ∼exp[(Δ/ε)^{a}] for any a<1/(2d-1). This result does not depend on whether the perturbation closes the gap. It significantly extends previous rigorous results on prethermalization in models where H_{0} was frustration-free. We infer the robustness of quantum simulation in low-energy subspaces, the existence of athermal "scarred" correlation functions in gapped systems subject to generic perturbations, the long lifetime of false vacua in symmetry broken systems, and the robustness of quantum information in non-frustration-free gapped phases with topological order.

Disordered Quantum Critical Fixed Points from Holography.

Using holographic duality, we present an analytically controlled theory of quantum critical points without quasiparticles, at finite disorder and finite charge density. These fixed points are obtained by perturbing a disorder-free quantum critical point with relevant disorder whose operator dimension is perturbatively close to Harris marginal. We analyze these fixed points both using field theoretic arguments, and by solving the bulk equations of motion in holography. We calculate the critical exponents of the IR theory, together with thermoelectric transport coefficients. Our predictions for the critical exponents of the disordered fixed point are consistent with previous work, both in holographic and nonholograpic models.

Out-of-plane arrivals recorded by drifting hydrophones during the Northern Ocean Rapid Surface Evolution Experiment.

This paper reports on an observation of three-dimensional (3D) arrivals for which the change in the direction of horizontally refracted sound is nearly 180°. The experimental site is Jan Mayen Channel (JMCh), which connects the Greenland and Norwegian Seas. During the experiment, signals from a moored source transmitting a 500-1500 Hz sweep every 4 h were recorded by three surface drifters equipped with hydrophone arrays. Over a 3-day period, the drifters moved north across JMCh toward the moored source. In each recording, an in-plane arrival is identified. In a subset of these recordings, a second arrival is observed, having travel time consistent with propagation from the moored source, turning at the ridge on the south side of the channel, and arriving at the drifters. In a smaller subset of recordings, a third arrival is also observed having travel time consistent with a turning point on the face of the bathymetric rise on the west end of the channel that forms the Jan Mayen volcano. A 3D ray trace is employed to show the change in direction results from repeated reflections from the seafloor such that it is classified as horizontal refraction and not a single-bounce reflection.

Observations and simulations of caustic formation due to oceanographic fine structure.

An at-sea experiment in deep water was conducted to explore the impact of small-scale sound-speed variability on mid-frequency (1-10 kHz) acoustic propagation. Short-range (1-5 km) acoustic transmissions were sent through the upper ocean (0-200 m) while oceanographic instruments simultaneously measured the ocean environment within 2 km of the single upper turning points of the acoustic transmissions. During these transmissions, acoustic receptions over a 7.875 m vertical line array show closely spaced, sometimes interfering arrivals. Ray and full-wave simulations of the transmissions using nearby sound-speed profiles are compared deterministically to the received acoustic signals. The sensitivity of the acoustic arrivals to the vertical scales of ocean sound speed is tested by comparing the observed and simulated arrival intensity where the sound-speed profile used by the simulation is smoothed to varying scales. Observations and modeling both suggest that vertical fine-scale structures (1-10 m) embedded in the sound-speed profile have strong second derivatives which allow for the formation of acoustic caustics as well as potentially interfering acoustic propagation multipaths.

Plasma cell but not CD20-mediated B-cell depletion protects from bleomycin-induced lung fibrosis.

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease associated with chronic inflammation and tissue remodelling leading to fibrosis, reduced pulmonary function, respiratory failure and death. Bleomycin (Blm)-induced lung fibrosis in mice replicates several clinical features of human IPF, including prominent lymphoid aggregates of predominantly B-cells that accumulate in the lung adjacent to areas of active fibrosis. We have shown previously a requirement for B-cells in the development of Blm-induced lung fibrosis in mice. To determine the therapeutic potential of inhibiting B-cell function in pulmonary fibrosis, we examined the effects of anti-CD20 B-cell ablation therapy to selectively remove mature B-cells from the immune system and inhibit Blm-induced lung fibrosis. Anti-CD20 B-cell ablation did not reduce fibrosis in this model; however, immune phenotyping of peripheral blood and lung resident cells revealed that anti-CD20-treated mice retained a high frequency of CD19+ CD138+ plasma cells. Interestingly, high levels of CD138+ cells were also identified in the lung tissue of patients with IPF, consistent with the mouse model. Treatment of mice with bortezomib, which depletes plasma cells, reduced the level of Blm-induced lung fibrosis, implicating plasma cells as important effector cells in the development and progression of pulmonary fibrosis.

Fracton Hydrodynamics without Time-Reversal Symmetry.

We present an effective field theory for the nonlinear fluctuating hydrodynamics of a single conserved charge with or without time-reversal symmetry, based on the Martin-Siggia-Rose formalism. Applying this formalism to fluids with only charge and multipole conservation, and with broken time-reversal symmetry, we predict infinitely many new dynamical universality classes, including some with arbitrarily large upper critical dimensions. Using large scale simulations of classical Markov chains, we find numerical evidence for a breakdown of hydrodynamics in quadrupole-conserving models with broken time-reversal symmetry in one spatial dimension. Our framework can be applied to the hydrodynamics around stationary states of open systems, broadening the applicability of previously developed ideas and methods to a wide range of systems in driven and active matter.

Imaging the Breakdown of Ohmic Transport in Graphene.

Ohm's law describes the proportionality of the current density and electric field. In solid-state conductors, Ohm's law emerges due to electron scattering processes that relax the electrical current. Here, we use nitrogen-vacancy center magnetometry to directly image the local breakdown of Ohm's law in a narrow constriction fabricated in a high mobility graphene monolayer. Ohmic flow is visible at room temperature as current concentration on the constriction edges, with flow profiles entirely determined by sample geometry. However, as the temperature is lowered below 200 K, the current concentrates near the constriction center. The change in the flow pattern is consistent with a crossover from diffusive to viscous electron transport dominated by electron-electron scattering processes that do not relax current.

Fast scrambling on sparse graphs.

Given a quantum many-body system with few-body interactions, how rapidly can quantum information be hidden during time evolution? The fast-scrambling conjecture is that the time to thoroughly mix information among N degrees of freedom grows at least logarithmically in N. We derive this inequality for generic quantum systems at infinite temperature, bounding the scrambling time by a finite decay time of local quantum correlations at late times. Using Lieb-Robinson bounds, generalized Sachdev-Ye-Kitaev models, and random unitary circuits, we propose that a logarithmic scrambling time can be achieved in most quantum systems with sparse connectivity. These models also elucidate how quantum chaos is not universally related to scrambling: We construct random few-body circuits with infinite Lyapunov exponent but logarithmic scrambling time. We discuss analogies between quantum models on graphs and quantum black holes and suggest methods to experimentally study scrambling with as many as 100 sparsely connected quantum degrees of freedom.

Viscometry of Electron Fluids from Symmetry.

When electrons flow as a viscous fluid in anisotropic metals, the reduced symmetry can lead to exotic viscosity tensors with many additional, nonstandard components. We present a viscometry technique that can, in principle, measure the multiple dissipative viscosities allowed in isotropic and anisotropic fluids alike. By applying representation theory to exploit the intrinsic symmetry of the fluid, our viscometry is also exceptionally robust to both boundary complications and ballistic effects. We present the technique via the illustrative example of dihedral symmetry, relevant in this context as the point symmetry of 2D crystals. Finally, we propose a present-day realizable experiment for detecting, in a metal, a novel hydrodynamic phenomenon: the presence of rotational dissipation in an otherwise isotropic fluid.

Lieb-Robinson Light Cone for Power-Law Interactions.

The Lieb-Robinson theorem states that information propagates with a finite velocity in quantum systems on a lattice with nearest-neighbor interactions. What are the speed limits on information propagation in quantum systems with power-law interactions, which decay as 1/r^{α} at distance r? Here, we present a definitive answer to this question for all exponents α>2d and all spatial dimensions d. Schematically, information takes time at least r^{min{1,α-2d}} to propagate a distance r. As recent state transfer protocols saturate this bound, our work closes a decades-long hunt for optimal Lieb-Robinson bounds on quantum information dynamics with power-law interactions.

Resistivity bound for hydrodynamic bad metals.

We obtain a rigorous upper bound on the resistivity [Formula: see text] of an electron fluid whose electronic mean free path is short compared with the scale of spatial inhomogeneities. When such a hydrodynamic electron fluid supports a nonthermal diffusion process-such as an imbalance mode between different bands-we show that the resistivity bound becomes [Formula: see text] The coefficient [Formula: see text] is independent of temperature and inhomogeneity lengthscale, and [Formula: see text] is a microscopic momentum-preserving scattering rate. In this way, we obtain a unified mechanism-without umklapp-for [Formula: see text] in a Fermi liquid and the crossover to [Formula: see text] in quantum critical regimes. This behavior is widely observed in transition metal oxides, organic metals, pnictides, and heavy fermion compounds and has presented a long-standing challenge to transport theory. Our hydrodynamic bound allows phonon contributions to diffusion constants, including thermal diffusion, to directly affect the electrical resistivity.

Operator Size at Finite Temperature and Planckian Bounds on Quantum Dynamics.

It has long been believed that dissipative timescales τ obey a "Planckian" bound τ≳(ℏ/k_{B}T) in strongly coupled quantum systems. Despite much circumstantial evidence, however, there is no known τ for which this bound is universal. Here we define operator size at a finite temperature, and conjecture such a τ: the timescale over which small operators become large. All known many-body theories are consistent with this conjecture. This proposed bound explains why previously conjectured Planckian bounds do not always apply to weakly coupled theories, and how Planckian timescales can be relevant to both transport and chaos.

Finite Speed of Quantum Scrambling with Long Range Interactions.

In a locally interacting many-body system, two isolated qubits, separated by a large distance r, become correlated and entangled with each other at a time t≥r/v. This finite speed v of quantum information scrambling limits quantum information processing, thermalization, and even equilibrium correlations. Yet most experimental systems contain long range power-law interactions-qubits separated by r have potential energy V(r)∝r^{-α}. Examples include the long range Coulomb interactions in plasma (α=1) and dipolar interactions between spins (α=3). In one spatial dimension, we prove that the speed of quantum scrambling remains finite for sufficiently large α. This result parametrically improves previous bounds, compares favorably with recent numerical simulations, and can be realized in quantum simulators with dipolar interactions. Our new mathematical methods lead to improved algorithms for classically simulating quantum systems, and improve bounds on environmental decoherence in experimental quantum information processors.