Emergent order in hydrodynamic spin lattices.

Macroscale analogues1-3 of microscopic spin systems offer direct insights into fundamental physical principles, thereby advancing our understanding of synchronization phenomena4 and informing the design of novel classes of chiral metamaterials5-7. Here we introduce hydrodynamic spin lattices (HSLs) of 'walking' droplets as a class of active spin systems with particle-wave coupling. HSLs reveal various non-equilibrium symmetry-breaking phenomena, including transitions from antiferromagnetic to ferromagnetic order that can be controlled by varying the lattice geometry and system rotation8. Theoretical predictions based on a generalized Kuramoto model4 derived from first principles rationalize our experimental observations, establishing HSLs as a versatile platform for exploring active phase oscillator dynamics. The tunability of HSLs suggests exciting directions for future research, from active spin-wave dynamics to hydrodynamic analogue computation and droplet-based topological insulators.

A guideline to limit indoor airborne transmission of COVID-19.

The current revival of the American economy is being predicated on social distancing, specifically the Six-Foot Rule, a guideline that offers little protection from pathogen-bearing aerosol droplets sufficiently small to be continuously mixed through an indoor space. The importance of airborne transmission of COVID-19 is now widely recognized. While tools for risk assessment have recently been developed, no safety guideline has been proposed to protect against it. We here build on models of airborne disease transmission in order to derive an indoor safety guideline that would impose an upper bound on the "cumulative exposure time," the product of the number of occupants and their time in an enclosed space. We demonstrate how this bound depends on the rates of ventilation and air filtration, dimensions of the room, breathing rate, respiratory activity and face mask use of its occupants, and infectiousness of the respiratory aerosols. By synthesizing available data from the best-characterized indoor spreading events with respiratory drop size distributions, we estimate an infectious dose on the order of 10 aerosol-borne virions. The new virus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) is thus inferred to be an order of magnitude more infectious than its forerunner (SARS-CoV), consistent with the pandemic status achieved by COVID-19. Case studies are presented for classrooms and nursing homes, and a spreadsheet and online app are provided to facilitate use of our guideline. Implications for contact tracing and quarantining are considered, and appropriate caveats enumerated. Particular consideration is given to respiratory jets, which may substantially elevate risk when face masks are not worn.

Superradiant Droplet Emission from Parametrically Excited Cavities.

Superradiance occurs when a collection of atoms exhibits a cooperative, spontaneous emission of photons at a rate that exceeds that of its component parts. Here, we reveal a similar phenomenon in a hydrodynamic system consisting of a pair of vibrationally excited cavities, coupled through their common wave field, that spontaneously emit droplets via interfacial fracture. We show that the droplet emission rate of two coupled cavities is higher than the emission rate of two isolated cavities. Moreover, the amplified emission rate varies sinusoidally with distance between the cavities, as is characteristic of superradiance. We thus present a hydrodynamic phenomenon that captures several essential features of superradiance in optical systems.

Injection of Cultured Cells with a ROCK Inhibitor for Bullous Keratopathy.

BACKGROUND: Corneal endothelial cell (CEC) disorders, such as Fuchs's endothelial corneal dystrophy, induce abnormal corneal hydration and result in corneal haziness and vision loss known as bullous keratopathy. We investigated whether injection of cultured human CECs supplemented with a rho-associated protein kinase (ROCK) inhibitor into the anterior chamber could increase CEC density. METHODS: We performed an uncontrolled, single-group study involving 11 persons who had received a diagnosis of bullous keratopathy and had no detectable CECs. Human CECs were cultured from a donor cornea; a total of 1×106 passaged cells were supplemented with a ROCK inhibitor (final volume, 300 µl) and injected into the anterior chamber of the eye that was selected for treatment. After the procedure, patients were placed in a prone position for 3 hours. The primary outcome was restoration of corneal transparency, with a CEC density of more than 500 cells per square millimeter at the central cornea at 24 weeks after cell injection. Secondary outcomes were a corneal thickness of less than 630 µm and an improvement in best corrected visual acuity equivalent to two lines or more on a Landolt C eye chart at 24 weeks after cell injection. RESULTS: At 24 weeks after cell injection, we recorded a CEC density of more than 500 cells per square millimeter (range, 947 to 2833) in 11 of the 11 treated eyes (100%; 95% confidence interval [CI], 72 to 100), of which 10 had a CEC density exceeding 1000 cells per square millimeter. A corneal thickness of less than 630 µm (range, 489 to 640) was attained in 10 of the 11 treated eyes (91%; 95% CI, 59 to 100), and an improvement in best corrected visual acuity of two lines or more was recorded in 9 of the 11 treated eyes (82%; 95% CI, 48 to 98). CONCLUSIONS: Injection of human CECs supplemented with a ROCK inhibitor was followed by an increase in CEC density after 24 weeks in 11 persons with bullous keratopathy. (Funded by the Japan Agency for Medical Research and Development and others; UMIN number, UMIN000012534 .).

Five-Year Follow-up of First 11 Patients Undergoing Injection of Cultured Corneal Endothelial Cells for Corneal Endothelial Failure.

PURPOSE: To report the safety and efficacy of a novel cell injection therapy using cultured human corneal endothelial cells (hCECs) for endothelial failure conditions via the report of the long-term 5-year postoperative clinical data from a first-in-humans clinical trial group. DESIGN: Prospective observational study. PARTICIPANTS: This study involved 11 eyes of 11 patients with pseudophakic endothelial failure conditions who underwent hCEC injection therapy between December 2013 and December 2014. METHODS: All patients underwent follow-up examinations at 1 week, 4 weeks, 12 weeks, and 24 weeks and 1 year, 2 years, 3 years, 4 years, and 5 years after surgery. Specific corneal endothelial cell parameters (i.e., corneal endothelial cell density [ECD], coefficient of variation of area, and percentage of hexagonal cells) and central corneal thickness, best-corrected visual acuity (BCVA) on a Landolt C eye chart, and intraocular pressure (IOP) were recorded. MAIN OUTCOME MEASURES: The primary outcome was the change in central ECD after cell injection therapy, and the secondary outcome was corneal thickness, BCVA, and IOP during the 5-year-postoperative follow-up period. RESULTS: At 5 years after surgery, normal corneal endothelial function was restored in 10 of the 11 eyes, the mean ± standard deviation central corneal ECD was 1257 ± 467 cells/mm2 (range, 601-2067 cells/mm2), BCVA improved significantly in 10 treated eyes, the mean visual acuity changed from 0.876 logarithm of the minimum angle of resolution before surgery to 0.046 logarithm of the minimum angle of resolution after surgery, and no major adverse reactions directly related to the hCEC injection therapy were observed. CONCLUSIONS: The findings in this study confirmed the safety and efficacy of cultured hCEC injection therapy for up to 5 years after surgery.

Antigen Priming with Enantiospecific Cationic Lipid Nanoparticles Induces Potent Antitumor CTL Responses through Novel Induction of a Type I IFN Response.

Certain types of cationic lipids have shown promise in cancer immunotherapy, but their mechanism of action is poorly understood. In this study, we describe the properties of an immunotherapeutic consisting of the pure cationic lipid enantiomer R-1,2-dioleoyl-3-trimethyl-ammonium-propane (R-DOTAP) formulated with modified viral or self-peptide Ags. R-DOTAP formulations with peptide Ags stimulate strong cross-presentation and potent CD8 T cell responses associated with a high frequency of polyfunctional CD8 T cells. In a human papillomavirus tumor model system, a single s.c. injection of tumor-bearing mice with R-DOTAP plus human papillomavirus Ags induces complete regression of large tumors associated with an influx of Ag-specific CD8 T cells and a reduction of the ratio of regulatory/Ag-specific CD8 T cells. R-DOTAP also synergizes with an anti-PD1 checkpoint inhibitor, resulting in a significant inhibition of B16 melanoma tumor growth. We found that R-DOTAP stimulates type I IFN production by dendritic cells in vivo and in vitro. s.c. injection of R-DOTAP results in an IFN-dependent increase in draining lymph node size and a concomitant increase in CD69 expression. Using knockout mice, we show that type I IFN is required for the induction of CD8 T cell activity following administration of R-DOTAP plus Ag. This response requires Myd88 but not TRIF or STING. We also show that R-DOTAP stimulates both TLR7 and 9. Collectively, these studies reveal that R-DOTAP stimulates endosomal TLRs, resulting in a Myd88-dependent production of type I IFN. When administered with Ag, this results in potent Ag-specific CD8 T cell responses and antitumor activity.

Classical pilot-wave dynamics: The free particle.

We present the results of a theoretical investigation into the dynamics of a vibrating particle propelled by its self-induced wave field. Inspired by the hydrodynamic pilot-wave system discovered by Yves Couder and Emmanuel Fort, the idealized pilot-wave system considered here consists of a particle guided by the slope of its quasi-monochromatic "pilot" wave, which encodes the history of the particle motion. We characterize this idealized pilot-wave system in terms of two dimensionless groups that prescribe the relative importance of particle inertia, drag and wave forcing. Prior work has delineated regimes in which self-propulsion of the free particle leads to steady or oscillatory rectilinear motion; it has further revealed parameter regimes in which the particle executes a stable circular orbit, confined by its pilot wave. We here report a number of new dynamical states in which the free particle executes self-induced wobbling and precessing orbital motion. We also explore the statistics of the chaotic regime arising when the time scale of the wave decay is long relative to that of particle motion and characterize the diffusive and rotational nature of the resultant particle dynamics. We thus present a detailed characterization of free-particle motion in this rich two-parameter family of dynamical systems.

Hydrodynamic quantum analogs.

The walking droplet system discovered by Yves Couder and Emmanuel Fort presents an example of a vibrating particle self-propelling through a resonant interaction with its own wave field. It provides a means of visualizing a particle as an excitation of a field, a common notion in quantum field theory. Moreover, it represents the first macroscopic realization of a form of dynamics proposed for quantum particles by Louis de Broglie in the 1920s. The fact that this hydrodynamic pilot-wave system exhibits many features typically associated with the microscopic, quantum realm raises a number of intriguing questions. At a minimum, it extends the range of classical systems to include quantum-like statistics in a number of settings. A more optimistic stance is that it suggests the manner in which quantum mechanics might be completed through a theoretical description of particle trajectories. We here review the experimental studies of the walker system, and the hierarchy of theoretical models developed to rationalize its behavior. Particular attention is given to enumerating the dynamical mechanisms responsible for the emergence of robust, structured statistical behavior. Another focus is demonstrating how the temporal nonlocality of the droplet dynamics, as results from the persistence of its pilot wave field, may give rise to behavior that appears to be spatially nonlocal. Finally, we describe recent explorations of a generalized theoretical framework that provides a mathematical bridge between the hydrodynamic pilot-wave system and various realist models of quantum dynamics.

Enzymatic analysis of glucuronidation of synthetic cannabinoid 1-naphthyl 1-(4-fluorobenzyl)-1H-indole-3-carboxylate (FDU-PB-22).

Recently, there has been a rise in abuse of synthetic cannabinoids (SCBs). The consumption of SCBs results in various effects and can induce toxic reactions, including paranoia, seizures, tachycardia and even death. 1-Naphthyl 1-(4-fluorobenzyl)-1H-indole-3-carboxylate (FDU-PB-22) is a third generation SCB whose metabolic pathway has not been fully characterized. In this study, we conducted in vitro pharmacokinetic analysis of FDU-PB-22 metabolism. Metabolic reactions containing FDU-PB-22 and human liver microsomes (HLMs) were independent of NADPH but not UDP-glucuronic acid (UDPGA), suggesting that UDP-glucuronosyltransferases (UGTs) are the primary enzymes involved in this metabolism. It was further determined that the metabolite extensively formed after incubating FDU-PB-22 with UDPGA in HLMs was the glucuronide of FDU-PB-22 3-carboxyindole (FBI-COOH). Various hepatic UGTs showed enzymatic activity for FBI-COOH. A series of UGT inhibitors showed moderate to strong inhibition of FBI-COOH-glucuronidation in HLMs, suggesting that multiple UGT isoforms are involved in FBI-COOH-glucuronidation in the liver. Interestingly, an extra-hepatic isoform, UGT1A10, exhibited the highest activity with a Km value of 38 µM and a Vmax value of 5.90 nmol/min/mg. Collectively, these results suggest that both genetic mutations of and the co-administration of inhibitors for FDU-PB-22-metabolizing UGTs will likely increase the risk of FDU-PB-22-induced toxicity.

Role of inositol polyphosphates in programed cell death in Dictyostelium discoideum and its developmental life cycle.

Programed cell death or apoptosis is a key developmental process that maintains tissue homeostasis in multicellular organisms. Inositol polyphosphates (InsPs) are key signaling molecules known to regulate a variety of cellular processes including apoptosis in such organisms. The signaling role of InsPs in unicellular organisms such as Dictyostelium discoideum (D. discoideum) is not well understood. We investigated whether InsPs also play any role in apoptosis in D. discoideum and whether InsPs-mediated apoptosis follows a mechanism similar to that present in higher multicellular eukaryotes. We measured known apoptotic markers in response to exogenously administered InsP6, the major InsPs in the cell. We found that InsP6 was able to cause cell death in D. discoideum cell culture in a dose- and time-dependent manner as determined by cytotoxicity assays. Fluorescence staining with acridine orange/ethidium bromide and flow cytometry results confirmed that the cell death in D. discoideum by InsP6 was due to apoptotic changes. Poly(ADP-ribose) expression, a known apoptotic marker used in D. discoideum, was also increased following InsP6 treatment suggesting a role for InsP6-mediated apoptosis in this organism. InsP6-mediated cell death was accompanied by production of reactive oxygen species and a decrease in mitochondrial membrane potential. Additionally, we studied the effects of InsP6 on the developmental life cycle of D. discoideum, the process likely affected by apoptosis. In conclusion, our studies provide evidence that InsP6-mediated cell death process is conserved in D. discoideum and plays an important signaling role in its developmental life cycle.

Exploring orbital dynamics and trapping with a generalized pilot-wave framework.

We explore the effects of an imposed potential with both oscillatory and quadratic components on the dynamics of walking droplets. We first conduct an experimental investigation of droplets walking on a bath with a central circular well. The well acts as a source of Faraday waves, which may trap walking droplets on circular orbits. The observed orbits are stable and quantized, with preferred radii aligning with the extrema of the well-induced Faraday wave pattern. We use the stroboscopic model of Oza et al. [J. Fluid Mech. 737, 552-570 (2013)] with an added potential to examine the interaction of the droplet with the underlying well-induced wavefield. We show that all quantized orbits are stable for low vibrational accelerations. Smaller orbits may become unstable at higher forcing accelerations and transition to chaos through a path reminiscent of the Ruelle-Takens-Newhouse scenario. We proceed by considering a generalized pilot-wave system in which the relative magnitudes of the pilot-wave force and drop inertia may be tuned. When the drop inertia is dominated by the pilot-wave force, all circular orbits may become unstable, with the drop chaotically switching between them. In this chaotic regime, the statistically stationary probability distribution of the drop's position reflects the relative instability of the unstable circular orbits. We compute the mean wavefield from a chaotic trajectory and confirm its predicted relationship with the particle's probability density function.

Hydrodynamic spin states.

We present the results of a theoretical investigation of hydrodynamic spin states, wherein a droplet walking on a vertically vibrating fluid bath executes orbital motion despite the absence of an applied external field. In this regime, the walker's self-generated wave force is sufficiently strong to confine the walker to a circular orbit. We use an integro-differential trajectory equation for the droplet's horizontal motion to specify the parameter regimes for which the innermost spin state can be stabilized. Stable spin states are shown to exhibit an analog of the Zeeman effect from quantum mechanics when they are placed in a rotating frame.

Walking droplets in a circular corral: Quantisation and chaos.

A millimetric liquid droplet may walk across the surface of a vibrating liquid bath through a resonant interaction with its self-generated wavefield. Such walking droplets, or "walkers," have attracted considerable recent interest because they exhibit certain features previously believed to be exclusive to the microscopic, quantum realm. In particular, the intricate motion of a walker confined to a closed geometry is known to give rise to a coherent wave-like statistical behavior similar to that of electrons confined to quantum corrals. Here, we examine experimentally the dynamics of a walker inside a circular corral. We first illustrate the emergence of a variety of stable dynamical states for relatively low vibrational accelerations, which lead to a double quantisation in angular momentum and orbital radius. We then characterise the system's transition to chaos for increasing vibrational acceleration and illustrate the resulting breakdown of the double quantisation. Finally, we discuss the similarities and differences between the dynamics and statistics of a walker inside a circular corral and that of a walker subject to a simple harmonic potential.

Dynamics, emergent statistics, and the mean-pilot-wave potential of walking droplets.

A millimetric droplet may bounce and self-propel on the surface of a vertically vibrating bath, where its horizontal "walking" motion is induced by repeated impacts with its accompanying Faraday wave field. For ergodic long-time dynamics, we derive the relationship between the droplet's stationary statistical distribution and its mean wave field in a very general setting. We then focus on the case of a droplet subjected to a harmonic potential with its motion confined to a line. By analyzing the system's periodic states, we reveal a number of dynamical regimes, including those characterized by stationary bouncing droplets trapped by the harmonic potential, periodic quantized oscillations, chaotic motion and wavelike statistics, and periodic wave-trapped droplet motion that may persist even in the absence of a central force. We demonstrate that as the vibrational forcing is increased progressively, the periodic oscillations become chaotic via the Ruelle-Takens-Newhouse route. We rationalize the role of the local pilot-wave structure on the resulting droplet motion, which is akin to a random walk. We characterize the emergence of wavelike statistics influenced by the effective potential that is induced by the mean Faraday wave field.

Introduction to focus issue on hydrodynamic quantum analogs.

Hydrodynamic quantum analogs is a nascent field initiated in 2005 by the discovery of a hydrodynamic pilot-wave system [Y. Couder, S. Protière, E. Fort, and A. Boudaoud, Nature 437, 208 (2005)]. The system consists of a millimetric droplet self-propeling along the surface of a vibrating bath through a resonant interaction with its own wave field [J. W. M. Bush, Annu. Rev. Fluid Mech. 47, 269-292 (2015)]. There are three critical ingredients for the quantum like-behavior. The first is "path memory" [A. Eddi, E. Sultan, J. Moukhtar, E. Fort, M. Rossi, and Y. Couder, J. Fluid Mech. 675, 433-463 (2011)], which renders the system non-Markovian: the instantaneous wave force acting on the droplet depends explicitly on its past. The second is the resonance condition between droplet and wave that ensures a highly structured monochromatic pilot wave field that imposes an effective potential on the walking droplet, resulting in preferred, quantized states. The third ingredient is chaos, which in several systems is characterized by unpredictable switching between unstable periodic orbits. This focus issue is devoted to recent studies of and relating to pilot-wave hydrodynamics, a field that attempts to answer the following simple but provocative question: Might deterministic chaotic pilot-wave dynamics underlie quantum statistics?

The interaction of a walking droplet and a submerged pillar: From scattering to the logarithmic spiral.

Millimetric droplets may walk across the surface of a vibrating fluid bath, propelled forward by their own guiding or "pilot" wave field. We here consider the interaction of such walking droplets with a submerged circular pillar. While simple scattering events are the norm, as the waves become more pronounced, the drop departs the pillar along a path corresponding to a logarithmic spiral. The system behavior is explored both experimentally and theoretically, using a reduced numerical model in which the pillar is simply treated as a region of decreased wave speed. A trajectory equation valid in the limit of weak droplet acceleration is used to infer an effective force due to the presence of the pillar, which is found to be a lift force proportional to the product of the drop's walking speed and its instantaneous angular speed around the post. This system presents a macroscopic example of pilot-wave-mediated forces giving rise to apparent action at a distance.

Drop impact and capture on a thin flexible fiber.

When a drop impacts a thin fiber, a critical impact speed can be defined, below which the drop is entirely captured by the fiber, and above which the drop pinches-off and fractures. We discuss here the capture dynamics of both inviscid and viscous drops on flexible fibers free to deform following impact. We characterize the impact-induced elongation of the drop thread for both high and low viscosity drops, and show that the capture dynamics depends on the relative magnitudes of the bending time of the fiber and deformation time of the drop. In particular, when these two timescales are comparable, drop capture is less prevalent, since the fiber rebounds when the drop deformation is maximal. Conversely, larger elasticity and slower bending time favor drop capture, as fiber rebound happens only after the drop has started to recoil. Finally, in the limit of highly flexible fibers, drop capture depends solely on the relative speed between the drop and the fiber directly after impact, as is prescribed by the momentum transferred during impact. Because the fiber speed directly after impact decreases with increasing fiber length and fiber mass, our study identifies an optimal fiber length for maximizing the efficiency of droplet capture.

The onset of chaos in orbital pilot-wave dynamics.

We present the results of a numerical investigation of the emergence of chaos in the orbital dynamics of droplets walking on a vertically vibrating fluid bath and acted upon by one of the three different external forces, specifically, Coriolis, Coulomb, or linear spring forces. As the vibrational forcing of the bath is increased progressively, circular orbits destabilize into wobbling orbits and eventually chaotic trajectories. We demonstrate that the route to chaos depends on the form of the external force. When acted upon by Coriolis or Coulomb forces, the droplet's orbital motion becomes chaotic through a period-doubling cascade. In the presence of a central harmonic potential, the transition to chaos follows a path reminiscent of the Ruelle-Takens-Newhouse scenario.

Capillary instability on an elastic helix.

We present the results of a combined experimental and theoretical investigation of the capillary instability of an elastic helical thread bound within a fluid. The influence of the thread's elastic energy on the classic Rayleigh-Plateau instability is elucidated. The most unstable wavelength can be substantially increased by the influence of the helical coil. The relation between our system and the capture thread of the orb-spider is discussed.

Optimal concentrations in nectar feeding.

Nectar drinkers must feed quickly and efficiently due to the threat of predation. While the sweetest nectar offers the greatest energetic rewards, the sharp increase of viscosity with sugar concentration makes it the most difficult to transport. We here demonstrate that the sugar concentration that optimizes energy transport depends exclusively on the drinking technique employed. We identify three nectar drinking techniques: active suction, capillary suction, and viscous dipping. For each, we deduce the dependence of the volume intake rate on the nectar viscosity and thus infer an optimal sugar concentration consistent with laboratory measurements. Our results provide the first rationale for why suction feeders typically pollinate flowers with lower sugar concentration nectar than their counterparts that use viscous dipping.