Cooling microwave fields into general multimode Gaussian states

Nahid Yazdi, Juan José García-Ripoll, Diego Porras, Carlos Navarrete-Benlloch

We show that a collection of lossy multi-chromatically modulated qubits can be used to dissipa- tively engineer arbitrary Gaussian states of a set of bosonic modes. Our ideas are especially suited to superconducting-circuit architectures, where all the required ingredients are experimentally avail- able. The generation of such multimode Gaussian states is necessary for many applications, most notably measurement-based quantum computation. We build upon some of our previous proposals, where we showed how to generate single-mode and two-mode squeezed states through cooling and lasing. Special care must be taken when extending these ideas to many bosonic modes, and we discuss here how to overcome all the limitations and hurdles that naturally appear. We illustrate our ideas with a fully worked out example consisting of GHZ states, but have also tested several other examples such as cluster states. All these examples allow us to show that it is possible to use a set of N lossy qubits to cool down a bosonic chain of N modes to any desired Gaussian state.

Protection of all nondefective twofold degeneracies by antiunitary symmetries in non-Hermitian systems

Sharareh Sayyad

Non-Hermitian degeneracies are classified as defective exceptional points (EPs) and nondefective de- generacies. While in defective EPs, both eigenvalues and eigenvectors coalesce, nondefective degeneracies are characterized merely by the emergence of degenerate eigenvalues. It is also known that all degeneracies are either symmetryprotected or accidental. In this paper, I prove that antiunitary symmetries protect all nondefective twofold degeneracies. By developing a 2D non-Hermitian tight-binding model, I have demonstrated that these symmetries comprise various symmetry operations, such as discrete or spatial point-group symmetries and Wick’s rotation in the non-Hermitian parameter space. Introducing these composite symmetries, I present the protection of nondefective degeneracies in various parameter regimes of my model. This work paves the way to stabilizing nondefective degeneracies and offers a new perspective on understanding non-Hermitian band crossings.

Evolutionary rescue of resistant mutants is governed by a balance between radial expansion and selection in compact populations

Serhii Aif, Nico Appold, Lucas Kampman, Oskar Hallatschek, Jona Kayser

Mutation-mediated treatment resistance is one of the primary challenges for modern antibiotic and anti-cancer therapy. Yet, many resistance mutations have a substantial fitness cost and are subject to purifying selection. How emerging resistant lineages may escape purifying selection via subsequent compensatory mutations is still unclear due to the difficulty of tracking such evolutionary rescue dynamics in space and time. Here, we introduce a system of fluorescence-coupled synthetic mutations to show that the probability of evolutionary rescue, and the resulting long-term persistence of drug resistant mutant lineages, is dramatically increased in dense microbial populations. By tracking the entire evolutionary trajectory of thousands of resistant lineages in expanding yeast colonies we uncover an underlying quasi-stable equilibrium between the opposing forces of radial expansion and natural selection, a phenomenon we term inflation-selection balance. Tailored computational models and agent-based simulations corroborate the fundamental nature of the observed effects and demonstrate the potential impact on drug resistance evolution in cancer. The described phenomena should be considered when predicting multi-step evolutionary dynamics in any mechanically compact cellular population, including pathogenic microbial biofilms and solid tumors. The insights gained will be especially valuable for the quantitative understanding of response to treatment, including emerging evolution-based therapy strategies.

Caveolin-1 dolines form a distinct and rapid caveolae-independent mechanoadaptation system

Fidel-Nicolás Lolo, Nikhil Walani, Eric Seemann, Dobryna Zalvidea, Dácil María Pavón, Gheorghe Cojoc, Moreno Zamai, Christine Varis de Lesegno, Fernando Martínez de Benito, et al.

In response to different types and intensities of mechanical force, cells modulate their physical properties and adapt their plasma membrane (PM). Caveolae are PM nano-invaginations that contribute to mechanoadaptation, buffering tension changes. However, whether core caveolar proteins contribute to PM tension accommodation independently from the caveolar assembly is unknown. Here we provide experimental and computational evidence supporting that caveolin-1 confers deformability and mechanoprotection independently from caveolae, through modulation of PM curvature. Freeze-fracture electron microscopy reveals that caveolin-1 stabilizes non-caveolar invaginations—dolines—capable of responding to low-medium mechanical forces, impacting downstream mechanotransduction and conferring mechanoprotection to cells devoid of caveolae. Upon cavin-1/PTRF binding, doline size is restricted and membrane buffering is limited to relatively high forces, capable of flattening caveolae. Thus, caveolae and dolines constitute two distinct albeit complementary components of a buffering system that allows cells to adapt efficiently to a broad range of mechanical stimuli.

Spectral theorem for dummies: A pedagogical discussion on quantum probability and random variable theory

Andrea Aiello

John von Neumann's spectral theorem for self-adjoint operators is a cornerstone of quantum mechanics. Among other things, it also provides a connection between expectation values of self-adjoint operators and expected values of real-valued random variables. This paper presents a plain-spoken formulation of this theorem in terms of Dirac's bra and ket notation, which is based on physical intuition and provides techniques that are important for performing actual calculations. The goal is to engage students in a constructive discussion about similarities and differences in the use of random variables in classical and quantum mechanics. Special emphasis is given on operators that are simple functions of noncommuting self-adjoint operators. The presentation is self-contained and includes detailed calculations for the most relevant results.

Deep learning of spatial densities in inhomogeneous correlated quantum systems

Alex Blania, Sandro Herbig, Fabian Dechent, Evert van Nieuwenburg, Florian Marquardt

Machine learning has made important headway in helping to improve the treatment of quantum many-body systems. A domain of particular relevance are correlated inhomogeneous systems. What has been missing so far is a general, scalable deep-learning approach that would enable the rapid prediction of spatial densities for strongly correlated systems in arbitrary potentials. In this work, we present a straightforward scheme, where we learn to predict densities using convolutional neural networks trained on random potentials. While we demonstrate this approach in 1D and 2D lattice models using data from numerical techniques like Quantum Monte Carlo, it is directly applicable as well to training data obtained from experimental quantum simulators. We train networks that can predict the densities of multiple observables simultaneously and that can predict for a whole class of many-body lattice models, for arbitrary system sizes. We show that our approach can handle well the interplay of interference and interactions and the behaviour of models with phase transitions in inhomogeneous situations, and we also illustrate the ability to solve inverse problems, finding a potential for a desired density.

Interferometric nanoparticle tracking analysis enables label-free discrimination of extracellular vesicles from large lipoproteins

Anna D. Kashkanova, Martin Blessing, Marie Reischke, Andreas S. Baur, Vahid Sandoghdar, Jan Van Deun

Complex decoherence-free interactions between giant atoms

Lei Du, Lingzhen Guo, Yong Li

Giant atoms provide a promising platform for engineering decoherence-free interactions which <br><br><br>is a major task in modern quantum technologies. Here we study systematically how to implement <br><br><br>complex decoherence-free interactions among giant atoms resorting to periodic coupling modulations and suitable arrangements of coupling points. We demonstrate that the phase of the modulation, which is tunable in experiments, can be encoded into the decoherence-free interactions, and thus <br><br><br>enables the Aharonov-Bohm effect of photons when the giant atoms constitute an effective closed loop. In particular, we consider the influence of non-Markovian retardation effect arising from large separations of the coupling points and study its dependence on the modulation parameters.

Realizing a deep reinforcement learning agent discovering real-time feedback control strategies for a quantum system

Kevin Reuer, Jonas Landgraf, Thomas Fösel, James O'Sullivan, Liberto Beltrán, Abdulkadir Akin, Graham J. Norris, Ants Remm, Michael Kerschbaum, et al.

To realize the full potential of quantum technologies, finding good strategies to control quantum information processing devices in real time becomes increasingly important. Usually these strategies require a precise understanding of the device itself, which is generally not available. Model-free reinforcement learning circumvents this need by discovering control strategies from scratch without relying on an accurate description of the quantum system. Furthermore, important tasks like state <br><br>preparation, gate teleportation and error correction need feedback at time scales much shorter than the coherence time, which for superconducting circuits is in the microsecond range. Developing and training a deep reinforcement learning agent able to operate in this real-time feedback regime has been an open challenge. Here, we have implemented such an agent in the form of a latency-optimized deep neural network on a field-programmable gate array (FPGA). We demonstrate its use to efficiently initialize a superconducting qubit into a target state. To train the agent, we use <br><br>model-free reinforcement learning that is based solely on measurement data. We study the agent’s performance for strong and weak measurements, and for three-level readout, and compare with simple strategies based on thresholding. This demonstration motivates further research towards adoption of <br><br>reinforcement learning for real-time feedback control of quantum devices and more generally any physical system requiring learnable low-latency feedback control.

Helicity, chirality, and spin of optical fields without vector potentials

Andrea Aiello

Helicity H, chirality C, and spin angular momentum S are three physical observables that play an important role in the study of optical fields. These quantities are closely related, but their connection is hidden by the use of four different vector fields for their representation, namely, the electric and magnetic fields E and B, and the two transverse potential vectors C⊥ and A⊥. Helmholtz's decomposition theorem restricted to solenoidal vector fields entails the introduction of a bona fide inverse curl operator, which permits one to express the above three quantities in terms of the observable electric and magnetic fields only. This yields clear expressions for H,C, and S, which are automatically gauge invariant and display electric-magnetic democracy.

Identification of a Distinct Monocyte-Driven Signature in Systemic Sclerosis Using Biophysical Phenotyping of Circulating Immune Cells

Alexandru-Emil Matei, Markéta Kubánková, Liyan Xu, Andrea-Hermina Györfi, Evgenia Boxberger, Despina Soteriou, Maria Papava, Julia Prater, Xuezhi Hong, et al.

Objective<br>Pathologically activated circulating immune cells, including monocytes, play major roles in systemic sclerosis (SSc). Their functional characterization can provide crucial information with direct clinical relevance. However, tools for the evaluation of pathologic immune cell activation and, in general, of clinical outcomes in SSc are scarce. Biophysical phenotyping (including characterization of cell mechanics and morphology) provides access to a novel, mostly unexplored layer of information regarding pathophysiologic immune cell activation. We hypothesized that the biophysical phenotyping of circulating immune cells, reflecting their pathologic activation, can be used as a clinical tool for the evaluation and risk stratification of patients with SSc.<br><br>Methods<br>We performed biophysical phenotyping of circulating immune cells by real-time fluorescence and deformability cytometry (RT-FDC) in 63 SSc patients, 59 rheumatoid arthritis (RA) patients, 28 antineutrophil cytoplasmic antibody–associated vasculitis (AAV) patients, and 22 age- and sex-matched healthy donors.<br><br>Results<br>We identified a specific signature of biophysical properties of circulating immune cells in SSc patients that was mainly driven by monocytes. Since it is absent in RA and AAV, this signature reflects an SSc-specific monocyte activation rather than general inflammation. The biophysical properties of monocytes indicate current disease activity, the extent of skin or lung fibrosis, and the severity of manifestations of microvascular damage, as well as the risk of disease progression in SSc patients.<br><br>Conclusion<br>Changes in the biophysical properties of circulating immune cells reflect their pathologic activation in SSc patients and are associated with clinical outcomes. As a high-throughput approach that requires minimal preparations, RT-FDC–based biophysical phenotyping of monocytes can serve as a tool for the evaluation and risk stratification of patients with SSc.

Nonreciprocal vortex isolator via topology-selective stimulated Brillouin scattering

Xinglin Zeng, Philip Russell, Christian Wolff , Michael Frosz, Gordon Wong, Birgit Stiller

Optical nonreciprocity, which breaks the symmetry between forward and backward propagating optical waves, has become vital in photonic systems and enables many key applications. So far, all the existing nonreciprocal systems are implemented for linearly or randomly polarized fundamental modes. Optical vortex modes, with wavefronts that spiral around the central axis of propagation, have been extensively studied over the past decades and offer an additional degree of freedom useful in many applications. Here, we report a light-driven nonreciprocal isolation system for optical vortex modes based on topology-selective stimulated Brillouin scattering (SBS) in chiral photonic crystal fiber. The device can be reconfigured as an amplifier or an isolator by adjusting the frequency of the control signal. The experimental results show vortex isolation of 22 decibels (dB), which is at the state of the art in fundamental mode isolators using SBS. This device may find applications in optical communications, fiber lasers, quantum information processing, and optical tweezers.

Digital Discovery of a Scientific Concept at the Core of Experimental Quantum Optics

Sören Arlt, Carlos Ruiz-Gonzalez, Mario Krenn

Entanglement is a crucial resource for quantum technologies ranging from quantum communication to quantum-enhanced measurements and computation. Finding experimental setups for these tasks is a conceptual challenge for human scientists due to the counterintuitive behavior of multiparticle interference and the enormously large combinatorial search space. Recently, new possibilities have been opened by artificial discovery where artificial intelligence proposes experimental setups for the creation and manipulation of high-dimensional multi-particle entanglement. While digitally discovered experiments go beyond what has been conceived by human experts, a crucial goal is to understand the underlying concepts which enable these new useful experimental blueprints. Here, we present Halo (Hyperedge Assembly by Linear Optics), a new form of multiphoton quantum interference with surprising properties. Halos were used by our digital discovery framework to solve previously open questions. We -- the human part of this collaboration -- were then able to conceptualize the idea behind the computer discovery and describe them in terms of effective probabilistic multi-photon emitters. We then demonstrate its usefulness as a core of new experiments for highly entangled states, communication in quantum networks, and photonic quantum gates. Our manuscript has two conclusions. First, we introduce and explain the physics of a new practically useful multi-photon interference phenomenon that can readily be realized in advanced setups such as integrated photonic circuits. Second, our manuscript demonstrates how artificial intelligence can act as a source of inspiration for the scientific discoveries of new actionable concepts in physics.

Digital Discovery of 100 diverse Quantum Experiments with PyTheus

Carlos Ruiz-Gonzalez, Sören Arlt, Jan Petermann, Sharareh Sayyad, Tareq Jaouni, Ebrahim Karimi, Nora Tischler, Xuemei Gu, Mario Krenn

Photons are the physical system of choice for performing experimental tests of the foundations of quantum mechanics. Furthermore, photonic quantum technology is a main player in the second quantum revolution, promising the development of better sensors, secure communications, and quantum-enhanced computation. These endeavors require generating specific quantum states or efficiently performing quantum tasks. The design of the corresponding optical experiments was historically powered by human creativity but is recently being automated with advanced computer algorithms and artificial intelligence. While several computer-designed experiments have been experimentally realized, this approach has not yet been widely adopted by the broader photonic quantum optics community. The main roadblocks consist of most systems being closed-source, inefficient, or targeted to very specific use-cases that are difficult to generalize. Here, we overcome these problems with a highly-efficient, open-source digital discovery framework PyTheus, which can employ a wide range of experimental devices from modern quantum labs to solve various tasks. This includes the discovery of highly entangled quantum states, quantum measurement schemes, quantum communication protocols, multi-particle quantum gates, as well as the optimization of continuous and discrete properties of quantum experiments or quantum states. PyTheus produces interpretable designs for complex experimental problems which human researchers can often readily conceptualize. PyTheus is an example of a powerful framework that can lead to scientific discoveries -- one of the core goals of artificial intelligence in science. We hope it will help accelerate the development of quantum optics and provide new ideas in quantum hardware and technology.

Theory of Laser-Assisted Nuclear Excitation by Electron Capture

Pavlo Bilous

The interplay of x-ray ionization and atomic and nuclear degrees of freedom is investigated theoretically in the process of laser-assisted nuclear excitation by electron capture. In the resonant process of nuclear excitation by electron capture, an incident electron recombines into a vacancy in the atomic shell with simultaneous nuclear excitation. Here we investigate the specific scenario in which the free electron and the required atomic shell hole<br>are generated by an x-ray free electron laser pulse. We develop a theoretical description based on the Feshbach projection operator formalism and consider numerically experimental scenarios at the SACLA x-ray free electron laser. Our numerical results for excitation of the 29.2 keV nuclear state in<br>$^{229}\text{Th}$ and the 14.4 keV M\"ossbauer transition in $^{57}\text{Fe}$<br>show low excitation rates but strong enhancement with respect to direct two<br>photon nuclear excitation.<br>

SELFIES and the future of molecular string representations

Mario Krenn, Qianxiang Ai, Senja Barthel, Nessa Carson, Angelo Frei, Nathan C. Frey, Pascal Friederich, Théophile Gaudin, Alberto Alexander Gayle, et al.

Artificial intelligence (AI) and machine learning (ML) are expanding in popularity for broad applications to challenging tasks in chemistry and materials science. Examples include the prediction of properties, the discovery of new reaction pathways, or the design of new molecules. The machine needs to read and write fluently in a chemical language for each of these tasks. Strings are a common tool to represent molecular graphs, and the most popular molecular string representation, SMILES, has powered cheminformatics since the late 1980s. However, in the context of AI and ML in chemistry, SMILES has several shortcomings -- most pertinently, most combinations of symbols lead to invalid results with no valid chemical interpretation. To overcome this issue, a new language for molecules was introduced in 2020 that guarantees 100\% robustness: SELFIES (SELF-referencIng Embedded Strings). SELFIES has since simplified and enabled numerous new applications in chemistry. In this manuscript, we look to the future and discuss molecular string representations, along with their respective opportunities and challenges. We propose 16 concrete Future Projects for robust molecular representations. These involve the extension toward new chemical domains, exciting questions at the interface of AI and robust languages and interpretability for both humans and machines. We hope that these proposals will inspire several follow-up works exploiting the full potential of molecular string representations for the future of AI in chemistry and materials science.

Design of quantum optical experiments with logic artificial intelligence

Alba Cervera-Lierta, Mario Krenn, Alán Aspuru-Guzik

Logic Artificial Intelligence (AI) is a subfield of AI where variables can take two defined arguments, True or False, and are arranged in clauses that follow the rules of formal logic. Several problems that span from physical systems to mathematical conjectures can be encoded into these clauses and solved by checking their satisfiability (SAT). In contrast to machine learning approaches where the results can be approximations or local minima, Logic AI delivers formal and mathematically exact solutions to those problems. In this work, we propose the use of logic AI for the design of optical quantum experiments. We show how to map into a SAT problem the experimental preparation of an arbitrary quantum state and propose a logic-based algorithm, called Klaus, to find an interpretable representation of the photonic setup that generates it. We compare the performance of Klaus with the state-of-the-art algorithm for this purpose based on continuous optimization. We also combine both logic and numeric strategies to find that the use of logic AI significantly improves the resolution of this problem, paving the path to developing more formal-based approaches in the context of quantum physics experiments.

Ultralong Imaging Range Chromatic Confocal Microscopy

Gargi Sharma, Kanwarpal Singh

Confocal microscopy is regularly used in cellular research but unfortunately, the imaging is restricted to a single plane. Chromatic confocal microscopy (CCM) offers the possibility to image multiple planes simultaneously, thus providing a manifold increase in the imaging speed, whereas eliminating the need for z-axis scanning. Standard chromatic confocal systems have a limited imaging range of the order of a few hundreds of micrometers which limits their applications. Herein, using a single zinc selenide lens, a CCM system that has an imaging range of 18 mm (±68 nm) with an average spatial resolution of 2.46 μm (±44 nm) and another system with a 1.55 mm (±14 nm) imaging range with 0.86 μm (±30 nm) average lateral spatial resolution is demonstrated. In doing so, sevenfold increase in the imaging range for the system with 1.55 mm imaging when compared with previously reported systems with similar lateral spatial resolution is achieved. The proposed approach can be a powerful tool for confocal imaging of biological samples or surface profiling of industrial samples.

On scientific understanding with artificial intelligence

Mario Krenn, Robert Pollice, Si Yue Guo, Matteo Aldeghi, Alba Cervera-Lierta, Pascal Friederich, Gabriel dos Passos Gomes, Florian Häse, Adrian Jinich, et al.

An oracle that correctly predicts the outcome of every particle physics experiment, the products of every possible chemical reaction or the function of every protein would revolutionize science and technology. However, scientists would not be entirely satisfied because they would want to comprehend how the oracle made these predictions. This is scientific understanding, one of the main aims of science. With the increase in the available computational power and advances in artificial intelligence, a natural question arises: how can advanced computational systems, and specifically artificial intelligence, contribute to new scientific understanding or gain it autonomously? Trying to answer this question, we adopted a definition of ‘scientific understanding’ from the philosophy of science that enabled us to overview the scattered literature on the topic and, combined with dozens of anecdotes from scientists, map out three dimensions of computer-assisted scientific understanding. For each dimension, we review the existing state of the art and discuss future developments. We hope that this Perspective will inspire and focus research directions in this multidisciplinary emerging field.<br><br><br><br>

Two-photon-absorption measurements in the presence of single-photon losses

Shahram Panahiyan, Carlos Sánchez Muñoz, Maria V. Chekhova, Frank Schlawin

We discuss how two-photon absorption (TPA) of squeezed and coherent states of light can be detected in measurements of the transmitted light fields. Such measurements typically suffer from competing loss mechanisms such as experimental imperfections (i.e., imperfect photodetectors) and other linear scattering losses inside the sample itself, which can lead to incorrect assessments of the two-photon-absorption cross section. We evaluate the sensitivity with which TPA can be detected and find that at sufficiently large photon numbers TPA sensitivity of squeezed vacua or squeezed coherent states can become independent of linear losses that occur after the TPA event has taken place. In particular, this happens for measurements of the photon number or of the antisqueezed field quadrature, where large fluctuations counteract and exactly cancel the degradation caused by single-photon losses.

Investigation of inverse design of multilayer thin-films with conditional invertible Neural Networks

Alexander Luce, Ali Mahdavi, Heribert Wankerl, Florian Marquardt

The task of designing optical multilayer thin-films regarding a given target is currently solved using gradient-based optimization in conjunction with methods that can introduce additional thin-film layers. Recently, Deep Learning and Reinforcement Learning have been been introduced to the task of designing thin-films with great success, however a trained network is usually only able to become proficient for a single target and must be retrained if the optical<br>targets are varied. In this work, we apply conditional Invertible Neural Networks (cINN) to inversely designing multilayer thin-films given an optical target. Since the cINN learns the energy landscape of all thin-film configurations within the training dataset, we show that cINNs can generate a stochastic ensemble of proposals for thin-film configurations that that are reasonably close to the desired target depending only on random variables. By refining the proposed configurations further by a local optimization, we show that the generated thin-films reach the target with significantly greater precision than comparable state-of-the art approaches. Furthermore, we tested the generative capabilities on samples which are outside the training data distribution and found that the cINN was able to predict thin-films for<br>out-of-distribution targets, too. The results suggest that in order to improve the generative design of thin-films, it is instructive to use established and new machine learning methods in conjunction in order to obtain the most<br>favorable results.

Predicting the Future of AI with AI: High-quality link prediction in an exponentially growing knowledge network

Mario Krenn, Lorenzo Buffoni, Bruno Coutinho, Sagi Eppel, Jacob Gates Foster, Andrew Gritsevskiy, Harlin Lee, Yichao Lu, Joao P. Moutinho, et al.

A tool that could suggest new personalized research directions and ideas by taking insights from the scientific literature could significantly accelerate the progress of science. A field that might benefit from such an approach is artificial intelligence (AI) research, where the number of scientific publications has been growing exponentially over the last years, making it challenging for human researchers to keep track of the progress. Here, we use AI techniques to predict the future research directions of AI itself. We develop a new graph-based benchmark based on real-world data -- the Science4Cast benchmark, which aims to predict the future state of an evolving semantic network of AI. For that, we use more than 100,000 research papers and build up a knowledge network with more than 64,000 concept nodes. We then present ten diverse methods to tackle this task, ranging from pure statistical to pure learning methods. Surprisingly, the most powerful methods use a<br>carefully curated set of network features, rather than an end-to-end AI approach. It indicates a great potential that can be unleashed for purely ML approaches without human knowledge. Ultimately, better predictions of new future research directions will be a crucial component of more advanced research suggestion tools.

Label-free monitoring of proteins in optofluidic hollow-core photonic crystal fibres

Jan R. Heck , Ermanno Miele, Ralf Mouthaan, Michael Frosz, Tuomas P J Knowles, Tijmen G Euser

The fluorescent detection of proteins without labels or stains, which affect their behaviour and require additional genetic or chemical preparation, has broad applications to biological research. However, standard approaches require large sample volumes or analyse only a small fraction of the sample. Here we use optofluidic hollow-core photonic crystal fibres to detect and quantify sub-microlitre volumes of unmodified bovine serum albumin (BSA) protein down to 100 nM concentrations. The optofluidic fibre's waveguiding properties are optimised for guidance at the (auto)fluorescence emission wavelength, enabling fluorescence collection from a 10 cm long excitation region, increasing sensitivity. The observed spectra agree with spectra taken from a conventional cuvette-based fluorimeter, corrected for the guidance properties of the fibre. The BSA fluorescence depended linearly on BSA concentration, while only a small hysteresis effect was observed, suggesting limited biofouling of the fibre sensor. Finally, we briefly discuss how this method could be used to study aggregation kinetics. With small sample volumes, the ability to use unlabelled proteins, and continuous flow, the method will be of interest to a broad range of protein-related research.

Deep-learning approach for large atomic structure calculations

Pavlo Bilous, Adriana Pálffy, Florian Marquardt

High-precision atomic structure calculations require accurate modelling of<br>electronic correlations involving large multiconfiguration wave function<br>expansions. Here we develop a deep-learning approach which allows to preselect<br>the most relevant configurations out of large basis sets until the targeted<br>precision is achieved. Our method replaces a large multiconfiguration<br>Dirac-Hartree-Fock computation by a series of smaller ones performed on an<br>iteratively expanding basis subset managed by a convolutional neural network.<br>The results for several examples with many-electron atoms show that deep<br>learning can significantly reduce the required computational memory and running<br>time and renders possible large-scale computations on otherwise unaccessible<br>basis sets.<br>

Tunneling-induced fractal transmission in Valley Hall waveguides

Tirth Shah, Florian Marquardt, Vittorio Peano

The Valley Hall effect provides a popular route to engineer robust waveguides<br>for bosonic excitations such a photons and phonons. The almost complete absence<br>of backscattering in many experiments has its theoretical underpinning in a<br>smooth-envelope approximation that neglects large momentum transfer and is<br>accurate only for small bulk band gaps and/or smooth domain walls. For larger<br>bulk band gaps and hard domain walls backscattering is expected to become<br>significant. Here, we show that in this experimentally relevant regime, the<br>reflection of a wave at a sharp corner becomes highly sensitive on the<br>orientation of the outgoing waveguide relative to the underlying lattice.<br>Enhanced backscattering can be understood as being triggered by resonant<br>tunneling transitions in quasimomentum space. Tracking the resonant tunneling<br>energies as a function of the waveguide orientation reveals a self-repeating<br>fractal pattern that is also imprinted in the density of states and the<br>backscattering rate at a sharp corner.<br>

Analysis of the signal measured in spectral-domain optical coherence tomography based on nonlinear interferometers

Arturo Rojas-Santana, Gerard J. Machado, Maria V. Chekhova, Dorilian Lopez-Mago, Juan P. Torres

We analyze and compare the output signals obtained in three different configurations of optical coherence tomography (OCT). After appropriate processing, these signals are used to retrieve an image of the sample under investigation. One of the configurations considered is the common choice in most OCT applications and is based on the use of a Michelson interferometer. For brevity, here we refer to it as standard OCT. The other two configurations are two types of optical coherence tomography based on the use of so-called nonlinear interferometers, interferometers that contain optical parametric amplifiers inside. The goal is to highlight the differences and similarities between the output signals measured in standard OCT and in these two OCT schemes, with the aim of evaluating if retrieval of information about the sample can be better done in one case over the others. We consider schemes where the optical sectioning of the sample is obtained by measuring the output signal spectrum (spectral or Fourier-domain OCT), since it shows better performance in terms of speed and sensitivity than the counterpart time-domain OCT.

Strong circular dichroism for the HE11 mode in twisted single-ring hollow-core photonic crystal fiber: erratum

Paul Roth, Yang Chen, Mehmet Can Günendi, Ramin Beravat, Nitin Edavalath, Michael Frosz, Goran Ahmed, Gordon Wong, Philip Russell

Recent work has revealed that the dispersion relation, given inOptica 5, 1315 (2018), for helicalBloch modes in a ring of capillaries surrounding a central hollowcore, is incorrect.Herewe correct this error and provide a revised version of Fig. 2. The overall conclusions of the original paper are unaffected.

Viscoelastic properties of suspended cells measured with shear flow deformation cytometry

Richard Gerum, Elham Mirzahossein, Mar Eroles, Jennifer Elsterer, Astrid Mainka, Andreas Bauer, Selina Sonntag, Alexander Winterl, Johannes Bartl, et al.

Numerous cell functions are accompanied by phenotypic changes in viscoelastic properties, and measuring them can help elucidate higher level cellular functions in health and disease. We present a high-throughput, simple and low-cost microfluidic method for quantitatively measuring the elastic (storage) and viscous (loss) modulus of individual cells. Cells are suspended in a high-viscosity fluid and are pumped with high pressure through a 5.8 cm long and 200 µm wide microfluidic channel. The fluid shear stress induces large, ear ellipsoidal cell deformations. In addition, the flow profile in the channel causes the cells to rotate in a tank-treading manner. From the cell deformation and tank treading frequency, we extract the frequency-dependent viscoelastic cell properties based on a theoretical framework developed by R. Roscoe [1] that describes the deformation of a viscoelastic sphere in a viscous fluid under steady laminar flow. We confirm the accuracy of the method using atomic force microscopy-calibrated polyacrylamide beads and cells. Our measurements demonstrate that suspended cells exhibit power-law, soft glassy rheological behavior that is cell-cycle-dependent and mediated by the physical interplay between the actin filament and intermediate filament networks.

Erratum to “Bragg Reflection and Conversion Between Helical Bloch Modes in Chiral Three-Core Photonic Crystal Fiber”

Sébastien Loranger, Yang Chen, Paul Roth, Michael Frosz, Gordon Wong, Philip Russell

The dispersion relation for the helical Bloch modes in this paper contains an error, which affects Equation (3) in the original manuscript, as well as Fig. 2. Otherwise the conclusions of the paper are unaffected.

Stern–Volmer analysis of photocatalyst fluorescence quenching within hollow-core photonic crystal fibre microreactors

Alexander S. Gentleman, Takashi Lawson, Matthew G. Ellis, Molly Davis, Jacob Turner-Dore, Alison S. H. Ryder, Michael Frosz, Maria Ciaccia, Erwin Reisner, et al.

We report the use of optofluidic hollow-core photonic crystal fibres as microreactors for Stern–Volmer (SV) luminescence quenching analysis of visible-light photocatalytic reactions. This technology enables measurements on nanolitre volumes and paves the way for automated SV analyses in continuous flow that minimise catalyst and reagent usage. The method is showcased using a recently developed photoredox-catalysed α-C–H alkylation reaction of unprotected primary alkylamines.

Resonant metasurfaces for generating complex quantum states

Tomas Santiago-Cruz, Sylvain D. Gennaro, Oleg Mitrofanov, Sadhvikas Addamane, John Reno, Igal Brener, Maria V. Chekhova

Quantum state engineering, the cornerstone of quantum photonic technologies, mainly relies on spontaneous parametric downconversion and four-wave mixing, where one or two pump photons spontaneously decay into a photon pair. Both of these nonlinear effects require momentum conservation for the participating photons, which strongly limits the versatility of the resulting quantum states. Nonlinear metasurfaces have subwavelength thickness and allow the relaxation of this constraint; when combined with resonances, they greatly expand the possibilities of quantum state engineering. Here, we generated entangled photons via spontaneous parametric downconversion in semiconductor metasurfaces with high–quality factor, quasi-bound state in the continuum resonances. By enhancing the quantum vacuum field, our metasurfaces boost the emission of nondegenerate entangled photons within multiple narrow resonance bands and over a wide spectral range. A single resonance or several resonances in the same sample, pumped at multiple wavelengths, can generate multifrequency quantum states, including cluster states. These features reveal metasurfaces as versatile sources of complex states for quantum information.

Cooperative subwavelength molecular quantum emitter arrays

Raphael Holzinger, Sue Ann Oh, Michael Reitz, Helmut Ritsch, Claudiu Genes

Dipole-coupled subwavelength quantum emitter arrays respond cooperatively to<br>external light fields as they may host collective delocalized excitations (a<br>form of excitons) with super- or subradiant character. Deeply subwavelength<br>separations typically occur in molecular ensembles, where in addition to<br>photon-electron interactions, electron-vibron couplings and vibrational<br>relaxation processes play an important role. We provide analytical and<br>numerical results on the modification of super- and subradiance in molecular<br>rings of dipoles including excitations of the vibrational degrees of freedom.<br>While vibrations are typically considered detrimental to coherent dynamics, we<br>show that molecular dimers or rings can be operated as platforms for the<br>preparation of long-lived dark superposition states aided by vibrational<br>relaxation. In closed ring configurations, we extend previous predictions for<br>the generation of coherent light from ideal quantum emitters to molecular<br>emitters, quantifying the role of vibronic coupling onto the output intensity<br>and coherence.<br>

Recent advances in petahertz electric field sampling

Andreas Herbst, Kilian Scheffter, M.M. Bidhendi, M. Kieker, Anchit Srivastava, Hanieh Fattahi

The ability to resolve the complete electric field of laser pulses from terahertz to mid-infrared spectral ranges has enriched time-domain spectroscopy for decades. Field-resolved measurements in this range have been performed routinely in ambient air by various techniques like electro-optic sampling, photoconductive switching, field-induced second harmonic generation, and time stretch photonics. On the contrary, resolving the electric field of light at the near-infrared spectral range has been limited to attosecond streaking and other techniques that require operation in vacuum. Recent advances are circumventing these<br>shortcomings and extending the direct, ambient air field detection of light to petahertz frequencies. In the first part of this letter, recent field-resolved techniques are reviewed. In the second part, different approaches for temporal scanning are discussed, as the temporal resolution of the time-domain methods is prone to temporal jitter. The review concludes by discussing technological obstacles and emerging applications of such advancements.

Robust Tipless Positioning Device for Near-Field Investigations: Press and Roll Scan (PROscan)

Hsuan-Wei Liu, Michael A. Becker, Korenobu Matsuzaki, Randhir Kumar, Stephan Götzinger, Vahid Sandoghdar

Scanning probe microscopes scan and manipulate a sharp tip in the immediate vicinity of a sample surface. The limited bandwidth of the feedback mechanism used for stabilizing the separation between the tip and the sample makes the fragile nanoscopic tip very susceptible to mechanical instabilities. We propose, demonstrate, and characterize an alternative device based on bulging a thin substrate against a second substrate and rolling them with respect to each other. We showcase the power of this method by placing gold nanoparticles and semiconductor quantum dots on the two opposite substrates and positioning them with nanometer precision to enhance the fluorescence intensity and emission rate. Furthermore, we exhibit the passive mechanical stability of the system over more than 1 h. Our design concept finds applications in a variety of other scientific and technological contexts, where nanoscopic features have to be positioned and kept near contact with each other.<br>a thin substrate against a second substrate and rolling them with respect each other. We showcase the power of this method by placing gold nanoparticles and semiconductor quantum dots on the<br>two opposite substrates and positioning them with nanometer precision to enhance the fluorescence intensity and emission rate. We exhibit the passive mechanical stability of the system over more than<br>one hour. The design concept presented in this work holds promise in a variety of other contexts, where nanoscopic features have to be positioned and kept near contact with each other.

Classical model of spontaneous parametric down-conversion

Girish Kulkarni, Jeremy Rioux, Boris Braverman, Maria V. Chekhova, Robert W. Boyd

We model spontaneous parametric down-conversion (SPDC) as classical difference frequency generation (DFG) of the pump field and a hypothetical stochastic “vacuum” seed field. We analytically show that the second-order spatiotemporal correlations of the field generated from the DFG process replicate those of the signal field from SPDC. Specifically, for low gain, the model is consistent with the quantum calculation of the signal photon’s reduced density matrix; and for high gain, the model’s predictions are in good agreement with our experimental measurements of the far-field intensity profile, orbital angular momentum spectrum, and wavelength spectrum of the SPDC field for increasing pump strengths. We further theoretically show that the model successfully captures second-order SU(1,1) interference and induced coherence effects in both gain regimes. Intriguingly, the model also correctly predicts the linear scaling of the interference visibility with object transmittance in the low-gain regime—a feature that is often regarded as a quintessential signature of the nonclassicality of induced coherence. Our model may not only lead to fundamental insights into the classical-quantum divide in the context of SPDC and induced coherence, but can also be a useful theoretical tool for numerous experiments and applications based on SPDC.

Metasurfaces for quantum technologies

Kai Wang, Maria V. Chekhova, Yuri S. Kivshar

Subwavelength planar structures can generate, reshape, and entangle photons in a compact and stable device.

Control of Yu-Shiba-Rusinov States through a Bosonic Mode

Helene Müller, Martin Eckstein, Silvia Viola-Kusminskiy

We investigate the impact of a bosonic degree of freedom on Yu-Shiba-Rusinov (YSR) states emerging from a magnetic impurity in a conventional superconductor. Starting from the Anderson impurity model, we predict that an additional p-wave conduction band channel opens up if a bosonic mode is coupled to the tunnelling between impurity and host, which implies an additional pair of odd-parity YSR states. The bosonic mode can be a vibrational mode or the electromagnetic field in a cavity. The exchange couplings in the two channels depend sensitively on the state of the bosonic mode (ground state, few quanta or classically driven Floquet state), which opens possibilities for phononics or photonics control of such systems, with a rich variety of ground and excited states.

Protocol for generating an arbitrary quantum state of the magnetization in cavity magnonics

Sanchar Sharma, Victor A. S. V. Bittencourt, Silvia Viola-Kusminskiy

We propose and numerically evaluate a protocol to generate an arbitrary quantum state of the magnetization in a magnet. The protocol involves repeatedly exciting a frequency-tunable superconducting transmon and transferring the excitations to the magnet via a microwave cavity. To avoid decay, the protocol must be much shorter than magnon lifetime. Speeding up the protocol by simply shortening the pulses leads to non-resonant leakage of excitations to higher levels of the transmon accompanied by higher decoherence. We discuss how to correct for such leakages by applying counter pulses to de-excite these higher levels. In our protocol, states with a maximum magnon occupation of up to ∼9 and average magnon number up to ∼4 can be generated with fidelity >0.75.

Curiosity in exploring chemical spaces: Intrinsic rewards for deep molecular reinforcement learning

Luca A. Thiede, Mario Krenn, AkshatKumar Nigam, Alán Aspuru-Guzik

Computer-aided design of molecules has the potential to disrupt the field of drug and material discovery. Machine learning, and deep learning, in particular, have been topics where the field has been developing at a rapid pace. Reinforcement learning is a particularly promising approach since it allows for molecular design without prior knowledge. However, the search space is vast and efficient exploration is desirable when using reinforcement learning agents. In this study, we propose an algorithm to aid efficient exploration. The algorithm is inspired by a concept known in the literature as curiosity. We show on three benchmarks that a curious agent finds better performing molecules. This indicates an exciting new research direction for reinforcement learning agents that can explore the chemical space out of their own motivation. This has the potential to eventually lead to unexpected new molecules that no human has thought about so far.

Direct optical probe of magnon topology in two-dimensional quantum magnets

Emil Viñas Boström, Tahereh S. Parvini, James W. McIver, Angel Rubio, Silvia Viola-Kusminskiy, Michael A. Sentef

Controlling edge states of topological magnon insulators is a promising route to stable spintronics devices. However, to experimentally ascertain the topology of magnon bands is a challenging task. Here we derive a fundamental relation between the light-matter coupling and the quantum geometry of magnon states. This allows to establish the two-magnon Raman circular dichroism as an optical probe of magnon topology in honeycomb magnets, in particular of the Chern number and the topological gap. Our results pave the way for interfacing light and topological magnons in functional quantum devices.

Flat-optics generation of broadband photon pairs with tunable polarization entanglement

Vitaliy Sultanov, José Tomás Santiago-Cruz, Maria V. Chekhova

The concept of “flat optics” is quickly conquering different fields of photonics, but its implementation in quantum optics is still in its infancy. In particular, polarization entanglement, strongly required in quantum photonics, is so far not realized on “flat” platforms. Meanwhile, relaxed phase matching of “flat” nonlinear optical sources enables enormous freedom in tailoring their polarization properties. Here we use this freedom to generate photon pairs with tunable polarization entanglement via spontaneous parametric downconversion (SPDC) in a 400 nm GaP film. By changing the pump polarization, we tune the polarization state of photon pairs from maximally entangled to almost disentangled, which is impossible in a single bulk SPDC source. Polarization entanglement, together with the broadband frequency spectrum, results in an ultranarrow (12 fs) Hong–Ou–Mandel effect and promises extensions to hyperentanglement.

Quantitative phase imaging through an ultra-thin lensless fiber endoscope

Jiawei Sun, Jiachen Wu, Ruchi Goswami, Salvatore Girardo, Liangcai Cao, Jochen Guck, Nektarios Koukourakis, Jürgen W. Czarske

Quantitative phase imaging (QPI) is a label-free technique providing both morphology and quantitative biophysical information in biomedicine. However, applying such a powerful technique to in vivo pathological diagnosis remains challenging. Multi-core fiber bundles (MCFs) enable ultra-thin probes for in vivo imaging, but current MCF imaging techniques are limited to amplitude imaging modalities. We demonstrate a computational lensless microendoscope that uses an ultra-thin bare MCF to perform quantitative phase imaging with microscale lateral resolution and nanoscale axial sensitivity of the optical path length. The incident complex light field at the measurement side is precisely reconstructed from the far-field speckle pattern at the detection side, enabling digital refocusing in a multi-layer sample without any mechanical movement. The accuracy of the quantitative phase reconstruction is validated by imaging the phase target and hydrogel beads through the MCF. With the proposed imaging modality, three-dimensional imaging of human cancer cells is achieved through the ultra-thin fiber endoscope, promising widespread clinical applications.

PNIPAAm microgels with defined network architecture as temperature sensors in optical stretchers

Nicolas Hauck, Timon Beck, Gheorghe Cojoc, Raimund Schlüßler, Saeed Ahmed, Ivan Raguzin, Martin Mayer, Jonas Schubert, Paul Müller, et al.

Stretching individual living cells with light is a standard method to assess their mechanical properties. Yet, heat introduced by the laser light of optical stretchers may unwittingly change the mechanical properties of cells therein. To estimate the temperature induced by an optical trap, we introduce cell-sized, elastic poly(N-isopropylacrylamide) (PNIPAAm) microgels that relate temperature changes to hydrogel swelling. For their usage as a standardized calibration tool, we analyze the effect of free-radical chain-growth gelation (FCG) and polymer-analogous photogelation (PAG) on hydrogel network heterogeneity, micromechanics, and temperature response by Brillouin microscopy and optical diffraction tomography. Using a combination of tailor-made PNIPAAm macromers, PAG, and microfluidic processing, we obtain microgels with homogeneous network architecture. With that, we expand the capability of standardized microgels in calibrating and validating cell mechanics analysis, not only considering cell and microgel elasticity but also providing stimuli-responsiveness to consider dynamic changes that cells may undergo during characterization.

Topologically Protected Transport in Engineered Mechanical Systems

Tirth Shah, Christian Brendel, Vittorio Peano, Florian Marquardt

Mechanical vibrations are being harnessed for a variety of purposes and at many length scales, from the macroscopic world down to the nanoscale. The considerable design freedom in mechanical structures allows to engineer new<br>functionalities. In recent years, this has been exploited to generate setups that offer topologically protected transport of vibrational waves, both in the solid state and in fluids. Borrowing concepts from electronic physics and being cross-fertilized by concurrent studies for cold atoms and electromagnetic waves, this field of topological transport in engineered mechanical systems offers a rich variety of phenomena and platforms. In this review, we provide a unifying overview of the various ideas employed in this area, summarize the different approaches and experimental implementations, and comment on the challenges as well as the prospects.

Long COVID: Association of Functional Autoantibodies against G-Protein-Coupled Receptors with an Impaired Retinal Microcirculation

Charlotte Szewczykowski, Christian Mardin, Marianna Lucio, Gerd Wallukat, Jakob Hoffmanns, Thora Schröder, Franziska Raith, Lennart Rogge, Felix Heltmann, et al.

Long COVID (LC) describes the clinical phenotype of symptoms after infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Diagnostic and therapeutic options are limited, as the pathomechanism of LC is elusive. As the number of acute SARS-CoV-2 infections was and is large, LC will be a challenge for the healthcare system. Previous studies revealed an impaired blood flow, the formation of microclots, and autoimmune mechanisms as potential factors in this complex interplay. Since functionally active autoantibodies against G-protein-coupled receptors (GPCR-AAbs) were observed in patients after SARS-CoV-2 infection, this study aimed to correlate the appearance of GPCR-AAbs with capillary microcirculation. The seropositivity of GPCR-AAbs was measured by an established cardiomyocyte bioassay in 42 patients with LC and 6 controls. Retinal microcirculation was measured by OCT–angiography and quantified as macula and peripapillary vessel density (VD) by the Erlangen-Angio Tool. A statistical analysis yielded impaired VD in patients with LC compared to the controls, which was accentuated in female persons. A significant decrease in macula and peripapillary VD for AAbs targeting adrenergic β2-receptor, MAS-receptor angiotensin-II-type-1 receptor, and adrenergic α1-receptor were observed. The present study might suggest that a seropositivity of GPCR-AAbs can be linked to an impaired retinal capillary microcirculation, potentially mirroring the systemic microcirculation with consecutive clinical symptoms.

A non-separability measure for spatially disjoint vectorial fields

Andrea Aiello, Xiao-Bo Hu, Valeria Rodríguez-Fajardo, Andrew Forbes, Raul I. Hernandez-Aranda, Benjamin Perez-Garcia, Carmelo Rosales-Guzmán

Vectorial forms of structured light that are non-separable in their spatial and polarisation degrees of freedom have become topical of late, with an extensive toolkit for their creation and control. In contrast, the toolkit for quantifying their non-separability, the inhomogeneity of the polarisation structure, is less developed and in some cases fails altogether. To overcome this, here we introduce a new measure for vectorial light, which we demonstrate both theoretically and experimentally. We consider the general case where the local polarisation homogeneity can vary spatially across the field, from scalar to vector, a condition that can arise naturally if the composite scalar fields are path separable during propagation, leading to spatially disjoint vectorial light. We show how the new measure correctly accounts for the local path-like separability of the individual scalar beams, which can have varying degrees of disjointness, even though the global vectorial field remains intact. Our work attempts to address a pressing issue in the analysis of such complex light fields, and raises important questions on spatial coherence in the context of vectorially polarised light.

Deep Reinforcement Learning for Quantum State Preparation with Weak Nonlinear Measurements

Riccardo Porotti, Antoine Essig, Benjamin Huard, Florian Marquardt

Quantum control has been of increasing interest in recent years, e.g. for tasks like state initialization and stabilization. Feedback-based strategies are particularly powerful, but also hard to find, due to the exponentially increased search space. Deep reinforcement learning holds great promise in this regard. It may provide new answers to difficult questions, such as whether nonlinear measurements can compensate for linear, constrained control. Here we show that reinforcement learning can successfully discover such feedback strategies, without prior knowledge. We illustrate this for state reparation in a cavity subject to quantum-non-demolition detection of photon number, with a simple linear drive as control. Fock states can be produced and stabilized at very high fidelity. It is even possible to reach superposition states, provided the measurement rates for different Fock states can be controlled as well.

In vivo assessment of mechanical properties during axolotl development and regeneration using confocal Brillouin microscopy

Camilo Riquelme-Guzmán, Timon Beck, Sandra Edwards-Jorquera, Raimund Schlüßler, Paul Müller, Jochen Guck, Stephanie Möllmert, Tatiana Sandoval-Guzmán

In processes such as development and regeneration, where large cellular and tissue rearrangements occur, cell fate and behaviour are strongly influenced by tissue mechanics. While most well-established tools probing mechanical properties require an invasive sample preparation, confocal Brillouin microscopy captures mechanical parameters optically with high resolution in a contact-free and label-free fashion. In this work, we took advantage of this tool and the transparency of the highly regenerative axolotl to probe its mechanical properties in vivo for the first time. We mapped the Brillouin frequency shift with high resolution in developing limbs and regenerating digits, the most studied structures in the axolotl. We detected a gradual increase in the cartilage Brillouin frequency shift, suggesting decreasing tissue compressibility during both development and regeneration. Moreover, we were able to correlate such an increase with the regeneration stage, which was undetected with fluorescence microscopy imaging. The present work evidences the potential of Brillouin microscopy to unravel the mechanical changes occurring in vivo in axolotls, setting the basis to apply this technique in the growing field of epimorphic regeneration.

Quantum indistinguishability by path identity and with undetected photons

Armin Hochrainer, Mayukh Lahiri, Manuel Erhard, Mario Krenn, Anton Zeilinger

Two processes of photon-pair creation can be arranged such that the paths of the emitted photons are identical. The path information is thereby not erased but rather never born in the first place due to this path identity. In addition to its implications for fundamental physics, this concept has recently led to a series of impactful discoveries in the fields of imaging, spectroscopy, and quantum information science. Here the idea of path identity is presented and a comprehensive review of recent developments is provided. Specifically, the concept of path identity is introduced based on three defining experimental ideas from the early 1990s. The three experiments have in common that they contain two photon-pair sources. The paths of one or both photons from the different sources overlap such that no measurement can recognize from which source they originate. A wide range of noteworthy quantum interference effects (at the single- or two-photon level), such as induced coherence, destructive interference of photon pairs, and entanglement generation, are subsequently described. Progress in the exploration of these ideas has stagnated and has gained momentum again only in the last few years. The focus of the review is the new development in the last few years that modified and generalized the ideas from the early 1990s. These developments are overviewed and explained under the same conceptual umbrella, which will help the community develop new applications and realize the foundational implications of this sleeping beauty.

Amoeboid-like migration ensures correct horizontal cell layer formation in the developing vertebrate retina

Rana Amini, Archit Bhatnagar, Raimund Schlüßler, Stephanie Möllmert, Jochen Guck, Caren Norden

Migration of cells in the developing brain is integral for the establishment of neural circuits and function of the central nervous system. While migration modes during which neurons employ predetermined directional guidance of either preexisting neuronal processes or underlying cells have been well explored, less is known about how cells featuring multipolar morphology migrate in the dense environment of the developing brain. To address this, we here investigated multipolar migration of horizontal cells in the zebrafish retina. We found that these cells feature several hallmarks of amoeboid-like migration that enable them to tailor their movements to the spatial constraints of the crowded retina. These hallmarks include cell and nuclear shape changes, as well as persistent rearward polarization of stable F-actin. Interference with the organization of the developing retina by changing nuclear properties or overall tissue architecture hampers efficient horizontal cell migration and layer formation showing that cell-tissue interplay is crucial for this process. In view of the high proportion of multipolar migration phenomena observed in brain development, the here uncovered amoeboid-like migration mode might be conserved in other areas of the developing nervous system.

Adipose cells and tissues soften with lipid accumulation while in diabetes adipose tissue stiffens

Shada Abuhattum, Petra Kotzbeck, Raimund Schlüßler, Alexandra Harger, Angela Ariza de Schellenberger, Kyoohyun Kim, Joan-Carles Escolano, Torsten Müller, Jürgen Braun, et al.

Adipose tissue expansion involves both differentiation of new precursors and size increase of mature adipocytes. While the two processes are well balanced in healthy tissues, obesity and diabetes type II are associated with abnormally enlarged adipocytes and excess lipid accumulation. Previous studies suggested a link between cell stiffness, volume and stem cell differentiation, although in the context of preadipocytes, there have been contradictory results regarding stiffness changes with differentiation. Thus, we set out to quantitatively monitor adipocyte shape and size changes with differentiation and lipid accumulation. We quantified by optical diffraction tomography that differentiating preadipocytes increased their volumes drastically. Atomic force microscopy (AFM)-indentation and -microrheology revealed that during the early phase of differentiation, human preadipocytes became more compliant and more fluid-like, concomitant with ROCK-mediated F-actin remodelling. Adipocytes that had accumulated large lipid droplets were more compliant, and further promoting lipid accumulation led to an even more compliant phenotype. In line with that, high fat diet-induced obesity was associated with more compliant adipose tissue compared to lean animals, both for drosophila fat bodies and murine gonadal adipose tissue. In contrast, adipose tissue of diabetic mice became significantly stiffer as shown not only by AFM but also magnetic resonance elastography. Altogether, we dissect relative contributions of the cytoskeleton and lipid droplets to cell and tissue mechanical changes across different functional states, such as differentiation, nutritional state and disease. Our work therefore sets the basis for future explorations on how tissue mechanical changes influence the behaviour of mechanosensitive tissue-resident cells in metabolic disorders.

Topological phonon transport in an optomechanical system

Hengjiang Ren, Tirth Shah, Hannes Pfeifer, Christian Brendel, Vittorio Peano, Florian Marquardt, Oskar Painter

Recent advances in cavity-optomechanics have now made it possible to use light not just as a passive measuring device of mechanical motion, but also to manipulate the motion of mechanical objects down to the level of individual quanta of vibrations (phonons). At the same time, microfabrication techniques have enabled small-scale optomechanical circuits capable of on-chip manipulation of mechanical and optical signals. Building on these developments, theoretical proposals have shown that larger scale optomechanical arrays can be used to modify the propagation of phonons, realizing a form of topologically protected phonon transport. Here, we report the observation of topological phonon transport within a multiscale optomechanical crystal structure consisting of an array of over 800 cavity-optomechanical elements. Using sensitive, spatially resolved optical read-out we detect thermal phonons in a 0.325−0.34GHz band traveling along a topological edge channel, with substantial reduction in backscattering. This represents an important step from the pioneering macroscopic mechanical systems work towards topological phononic systems at the nanoscale, where hypersonic frequency (≳GHz) acoustic wave circuits consisting of robust delay lines and non-reciprocal elements may be implemented. Owing to the broadband character of the topological channels, the control of the flow of heat-carrying phonons, albeit at cryogenic temperatures, may also be envisioned.

Learning Interpretable Representations of Entanglement in Quantum Optics Experiments using Deep Generative Models

Daniel Flam-Shepherd, Tony Wu, Xuemei Gu, Alba Cervera-Lierta, M. Krenn, Alan Aspuru-Guzik

Quantum physics experiments produce interesting phenomena such as interference or entanglement, which is a core property of numerous future quantum technologies. The complex relationship between a quantum experiment's structure and its entanglement properties is essential to fundamental research in quantum optics but is difficult to intuitively understand. We present the first deep generative model of quantum optics experiments where a variational autoencoder (QOVAE) is trained on a dataset of experimental setups. In a series of computational experiments, we investigate the learned representation of the QOVAE and its internal understanding of the quantum optics world. We demonstrate that the QOVAE learns an intrepretable representation of quantum optics experiments and the relationship between experiment structure and entanglement. We show the QOVAE is able to generate novel experiments for highly entangled quantum states with specific distributions that match its training data. Importantly, we are able to fully interpret how the QOVAE structures its latent space, finding curious patterns that we can entirely explain in terms of quantum physics. The results demonstrate how we can successfully use and understand the internal representations of deep generative models in a complex scientific domain. The QOVAE and the insights from our investigations can be immediately applied to other physical systems throughout fundamental scientific research.

Learning Quantum Systems

Valentin Gebhart, Raffaele Santagati, Antonio Andrea Gentile, Erik Gauger, David Craig, Natalia Ares, Leonardo Banchi, Florian Marquardt, Luca Pezzè, et al.

Quantum technologies hold the promise to revolutionise our society with<br>ground-breaking applications in secure communication, high-performance<br>computing and ultra-precise sensing. One of the main features in scaling up<br>quantum technologies is that the complexity of quantum systems scales<br>exponentially with their size. This poses severe challenges in the efficient<br>calibration, benchmarking and validation of quantum states and their dynamical<br>control. While the complete simulation of large-scale quantum systems may only<br>be possible with a quantum computer, classical characterisation and<br>optimisation methods (supported by cutting edge numerical techniques) can still<br>play an important role.<br> Here, we review classical approaches to learning quantum systems, their<br>correlation properties, their dynamics and their interaction with the<br>environment. We discuss theoretical proposals and successful implementations in<br>different physical platforms such as spin qubits, trapped ions, photonic and<br>atomic systems, and superconducting circuits. This review provides a brief<br>background for key concepts recurring across many of these approaches, such as<br>the Bayesian formalism or Neural Networks, and outlines open questions.<br>

Deciphering a hexameric protein complex with Angstrom optical resolution

Hisham Mazal, Franz Wieser, Vahid Sandoghdar

Cryogenic optical localization in three dimensions (COLD) was recently shown to resolve up to four binding sites on a single protein. However, because COLD relies on intensity fluctuations that result from the blinking behavior of fluorophores, it is limited to cases, where individual emitters show different brightness. This significantly lowers the measurement yield. To extend the number of resolved sites as well as the measurement yield, we employ partial labeling and combine it with polarization encoding in order to identify single fluorophores during their stochastic blinking. We then use a particle classification scheme to identify and resolve heterogenous subsets and combine them to reconstruct the three-dimensional arrangement of large molecular complexes. We showcase this method (polarCOLD) by resolving the trimer arrangement of proliferating cell nuclear antigen (PCNA) and the hexamer geometry of Caseinolytic Peptidase B (ClpB) of Thermus thermophilus in its quaternary structure, both with Angstrom resolution. The combination of polarCOLD and single-particle cryogenic electron microscopy (cryoEM) promises to provide crucial insight into intrinsic, environmental and dynamic heterogeneities of biomolecular structures. Furthermore, our approach is fully compatible with fluorescent protein labeling and can, thus, be used in a wide range of studies in cell and membrane biology.<br><br>Significance statement Fluorescence super-resolution microscopy has witnessed many clever innovations in the last two decades. Here, we advance the frontiers of this field of research by combining partial labeling and 2D image classification schemes with polarization-encoded single-molecule localization at liquid helium temperature to reach Angstrom resolution in three dimensions. We demonstrate the performance of the method by applying it to trimer and hexamer protein complexes. Our approach holds great promise for examining membrane protein structural assemblies and conformations in challenging native environments. The methodology closes the gap between electron and optical microscopy and offers an ideal ground for correlating the two modalities at the single-particle level. Indeed, correlative light and electron microscopy is an emerging technique that will provide new insight into cell biology.

Theory of phase-adaptive parametric cooling

Alekhya Ghosh, Pardeep Kumar, Fidel Jimenez, Vivishek Sudhir, Claudiu Genes

We propose an adaptive phase technique for the parametric cooling of<br>mechanical resonances. This involves the detection of the mechanical<br>quadratures, followed by a sequence of periodic controllable adjustments of the<br>phase of a parametric modulation. The technique allows the preparation of the<br>quantum ground state with an exponential loss of thermal energy, similarly to<br>the case of cold-damping or cavity self-cooling. Analytical derivations are<br>presented for the cooling rate and final occupancies both in the classical and<br>quantum regimes.<br>

One more time on the helicity decomposition of spin and orbital optical currents

Andrea Aiello

The helicity representation of the linear momentum density of a light wave is well understood for monochromatic optical fields in both paraxial and non-paraxial regimes of propagation. In this note we generalize such representation to nonmonochromatic optical fields. We find that, differently from the monochromatic case, the linear momentum density, aka the Poynting vector divided by c2, does not separate into the sum of right-handed and left-handed terms, even when the so-called electric–magnetic democracy in enforced by averaging the electric and magnetic contributions. However, for quasimonochromatic light, such a separation is approximately restored after time-averaging. This paper is dedicated to Sir Michael Berry on the occasion of his 80th birthday.

Realizing exceptional points of any order in the presence of symmetry

Sharareh Sayyad, Flore K. Kunst

Exceptional points~(EPs) appear as degeneracies in the spectrum of non-Hermitian matrices at which the eigenvectors coalesce. In general, an EP of order n may find room to emerge if 2(n−1) real constraints are imposed. Our results show that these constraints can be expressed in terms of the determinant and traces of the non-Hermitian matrix. Our findings further reveal that the total number of constraints may reduce in the presence of unitary and antiunitary symmetries. Additionally, we draw generic conclusions for the low-energy dispersion of the EPs. Based on our calculations, we show that in odd dimensions the presence of sublattice or pseudo-chiral symmetry enforces nth order EPs to disperse with the (n−1)th root. For two-, three- and four-band systems, we explicitly present the constraints needed for the occurrence of EPs in terms of system parameters and classify EPs based on their low-energy dispersion relations.

Deep Learning of Quantum Many-Body Dynamics via Random Driving

Naeimeh Mohseni, Thomas Fösel, Lingzhen Guo, Carlos Navarrete-Benlloch, Florian Marquardt

Neural networks have emerged as a powerful way to approach many practical problems in quantumphysics. In this work, we illustrate the power of deep learning to predict the dynamics of a quantummany-body system, where the training is based purely on monitoring expectation values of observables under random driving. The trained recurrent network is able to produce accurate predictions for driving trajectories entirely different than those observed during training. As a proof of principle, here we train the network on numerical data generated from spin models, showing that it can learn the dynamics of observables of interest without needing information about the full quantum state.This allows our approach to be applied eventually to actual experimental data generated from aquantum many-body system that might be open, noisy, or disordered, without any need for a detailedunderstanding of the system. This scheme provides considerable speedup for rapid explorations andpulse optimization. Remarkably, we show the network is able to extrapolate the dynamics to times longer than those it has been trained on, as well as to the infinite-system-size limit.

Depth of focus extension in optical coherence tomography using ultrahigh chromatic dispersion of zinc selenide

Maria N. Romodina, Kanwarpal Singh

We report a novel technique to overcome<br>the depth-of-focus limitation in optical coherence tomography (OCT) using chromatic<br>dispersion of zinc selenide lens.<br>OCT is an established method of optical<br>imaging, which found numerous biomedical<br>applications. However, the depth scanning range of high-resolution OCT is limited by its depth of focus. Chromatic dispersion of zinc selenide lens allows to get high lateral resolution along extended depth of focus, because the different spectral components are focused at a different position along axes of light propagation. Test measurements with nanoparticle phantom show 2.8 times extension of the depth of focus compare to the system with a standard achromatic lens. The feasibility of biomedical applications was demonstrated by ex vivo imaging of the pig cornea and chicken fat tissue.

Optimal broad-band frequency conversion via a magnetomechanical transducer

Fabian Engelhardt, Victor A. S. V. Bittencourt, Hans Huebl, Olivier Klein , Silvia Viola-Kusminskiy

Developing schemes for efficient and broad-band frequency conversion of quantum signals is an ongoing challenge in the field of modern quantum information. Especially the coherent conversion between microwave and optical signals is an important milestone towards long-distance quantum communication. In this work, we propose a two-stage conversion protocol, employing a resonant interaction between magnetic and mechanical excitations as a mediator between microwave and optical photons. Based on estimates for the coupling strengths under optimized conditions for yttrium iron garnet, we predict close to unity conversion efficiency without the requirement of matching cooperativities. We predict a conversion bandwidth in the regions of largest efficiency on the order of magnitude of the coupling strengths which can be further increased at the expense of reduced conversion efficiency.

Anomalous Behaviors of Quantum Emitters in Non-Hermitian Baths

Zongping Gong, Miguel Bello, Daniel Malz, Flore K. Kunst

Both non-Hermitian systems and the behaviour of emitters coupled to structured baths have been studied intensely in recent years. Here we study the interplay of these paradigmatic settings. In a series of examples, we show that a single quantum emitter coupled to a non-Hermitian bath displays a number of unconventional behaviours, many without Hermitian counterpart. We first consider a unidirectional hopping lattice whose complex dispersion forms a loop. We identify peculiar bound states inside the loop as a manifestation of the non-Hermitian skin effect. In the same setting, emitted photons may display spatial amplification markedly distinct from free propagation, which can be understood with the help of the generalized Brillouin zone. We then consider a nearest-neighbor lattice with alternating loss. We find that the long-time emitter decay always follows a power law, which is usually invisible for Hermitian baths. Our work points toward a rich landscape of anomalous quantum emitter dynamics induced by non-Hermitian baths.

Bound states and photon emission in non-Hermitian nanophotonics

Zongping Gong, Miguel Bello, Daniel Malz, Flore K. Kunst

We establish a general framework for studying the bound states and the photon-emission dynamics of quantum emitters coupled to structured nanophotonic lattices with engineered dissipation (loss). In the single-excitation sector, the system can be described exactly by a non-Hermitian formalism. We have pointed out in the accompanying letter [Gong \emph{et al}., arXiv:2205.05479] that a single emitter coupled to a one-dimensional non-Hermitian lattice may already exhibit anomalous behaviors without Hermitian counterparts. Here we provide further detail on these observations. We also present several additional examples on the cases with multiple quantum emitters or in higher dimensions. Our work unveils the tip of the iceberg of the rich non-Hermitian phenomena in dissipative nanophotonic systems.

TMM-Fast: A Transfer Matrix Computation Package for Multilayer Thin-Film Optimization: tutorial

Alexander Luce, Ali Mahdavi, Florian Marquardt, Heribert Wankerl

Achieving the desired optical response from a multilayer thin-film structure over a broad range of wavelengths and angles of incidence can be challenging. An advanced thin-film structure can consist of multiple materials with different thicknesses and numerous layers. Design and optimization of complex thin-film structures with multiple variables is a computationally heavy problem that is still under active research. To enable fast and easy experimentation with new optimization techniques, we propose the Python package TMM-Fast which enables parallelized computation of reflection and transmission of light at different angles of incidence and wavelengths through the multilayer thin-film.<br>By decreasing computational time, generating datasets for machine learning becomes feasible and evolutionary optimization can be used effectively. Additionally, the sub-package TMM-Torch allows to directly compute analytical<br>gradients for local optimization by using PyTorch Autograd functionality. Finally, an OpenAi Gym environment is presented which allows the user to train reinforcement learning agents on the problem of finding multilayer thin-film configurations.

Topological interface of light

Flore K. Kunst

Upon combining dissipative and nonlinear effects in a bipartite lattice of cavity polaritons, dissipatively stabilized bulk gap solitons emerge, which create a topological interface.

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Precision size and refractive index analysis of weakly scattering nanoparticles in polydispersions

Anna D. Kashkanova, Martin Blessing, André Gemeinhardt, Didier Soulat, Vahid Sandoghdar

Characterization of the size and material properties of particles in liquid suspensions is in very high demand, for example, in the analysis of colloidal samples or of bodily fluids such as urine or blood plasma. However, existing methods are limited in their ability to decipher the constituents of realistic samples. Here we introduce iNTA as a new method that combines interferometric detection of scattering with nanoparticle tracking analysis to reach unprecedented sensitivity and precision in determining the size and refractive index distributions of nanoparticles in suspensions. After benchmarking iNTA with samples of colloidal gold, we present its remarkable ability to resolve the constituents of various multicomponent and polydisperse samples of known origin. Furthermore, we showcase the method by elucidating the refractive index and size distributions of extracellular vesicles from Leishmania parasites and human urine. The current performance of iNTA already enables advances in several important applications, but we also discuss possible improvements.

Optomagnonics in Dispersive Media: Magnon-Photon Coupling Enhancement at the Epsilon-near-Zero Frequency

V. A. S. V. Bittencourt, I. Liberal, S. Viola-Kusminskiy

Reaching strong light-matter coupling in solid-state systems has long been pursued for the implementation of scalable quantum devices. Here, we put forward a system based on a magnetized epsilon-near-zero (ENZ) medium, and we show that strong coupling between magnetic excitations (magnons) and light can be achieved close to the ENZ frequency due to a drastic enhancement of the magneto-optical response. We adopt a phenomenological approach to quantize the electromagnetic field inside a dispersive magnetic medium in order to obtain the frequency-dependent coupling between magnons and photons. We predict that, in the epsilon-near-zero regime, the single-magnon single-photon coupling can be comparable to the magnon frequency for a small magnetic volume and perfect mode overlap. For state-of-the-art illustrative values, this would correspond to achieving the single-magnon strong coupling regime, where the coupling rate is larger than all the decay rates. Finally, we show that the nonlinear energy spectrum intrinsic to this coupling regime can be probed via the characteristic multiple magnon sidebands in the photon power spectrum.

Tunable and state-preserving frequency conversion of single photons in hydrogen

Rinat Tyumenev, Jonas Hammer, Nicolas Joly, Philip St.J. Russell, David Novoa

In modern quantum technologies, preservation of the photon statistics of quantum optical states upon frequency conversion holds the key to the viable implementation of quantum networks, which often require interfacing of several subsystems operating in widely different spectral regions. Most current approaches offer only very small frequency shifts and limited tunability, while suffering from high insertion loss and Raman noise originating in the materials used. We introduce a route to quantum-correlation–preserving frequency conversion using hydrogen-filled antiresonant-reflecting photonic crystal fibers. Transient optical phonons generated by stimulated Raman scattering enable selective frequency up-conversion by 125 terahertz of the idler photon of an entangled pair, with efficiencies up to 70%. This threshold-less molecular modulation process preserves quantum correlations, making it ideal for applications in quantum information.<br><br>https://www.science.org/stoken/author-tokens/ST-474/full

Observing polarization patterns in the collective motion of nanomechanical arrays

Juliane Doster, Tirth Shah, Thomas Fösel, Philipp Paulitschke, Florian Marquardt, Eva Weig

In recent years, nanomechanics has evolved into a mature field, with wide-ranging impact from sensing applications to fundamental physics, and it has now reached a stage which enables the fabrication and study of ever more elaborate devices. This has led to the emergence of arrays of coupled nanomechanical resonators as a promising field of research, serving as model systems to study collective dynamical phenomena such as synchronization or topological transport. From a general point of view, the arrays investigated so far represent scalar fields on a lattice. Moving to a scenario where these could be extended to vector fields would unlock a whole host of conceptually interesting additional phenomena, including the physics of polarization patterns in wave fields and their associated topology. Here we introduce a new platform, a two-dimensional array of coupled nanomechanical pillar resonators, whose orthogonal vibration directions encode a mechanical polarization degree of freedom. We demonstrate direct optical imaging of the collective dynamics, enabling us to analyze the emerging polarization patterns and follow their evolution with drive frequency.

Ising machines: Hardware solvers for combinatorial optimization problems

Naeimeh Mohseni, Peter McMahon, Tim Byrnes

Ising machines are hardware solvers which aim to find the absolute or approximate ground states of the Ising model. The Ising model is of fundamental computational interest because it is possible to formulate any problem in the complexity class NP as an Ising problem with only polynomial overhead. A scalable Ising machine that outperforms existing standard digital computers could have a huge impact for practical applications for a wide variety of optimization problems. In this review, we survey the current status of various approaches to constructing Ising machines and explain their underlying operational principles. The types of Ising machines considered here include classical thermal annealers based on technologies such as<br>spintronics, optics, memristors, and digital hardware accelerators; dynamical-systems solvers implemented with optics and electronics; and superconducting-circuit quantum annealers. We compare and contrast their performance using standard metrics such as the ground-state success probability and time-to-solution, give their scaling relations with problem size, and<br>discuss their strengths and weaknesses.

Best practices for reporting throughput in biomedical research

Maik Herbig, Akihiro Isozaki, Dino Di Carlo, Jochen Guck, Nao Nitta, Robert Damoiseaux, Shogo Kamikawaji, Eigo Suyama, Hirofumi Shintaku, et al.

mRNA Subtype of Cancer-Associated Fibroblasts Significantly Affects Key Characteristics of Head and Neck Cancer Cells

Barbora Peltanová, Hana Holcová Polanská, Martina Raudenská, Jan Balvan, Jiri Navrátil, Tomás Vicar, Jaromir Gumulec, Barbora Cechová, Martin Kräter, et al.

Head and neck squamous cell carcinomas (HNSCC) belong among severe and highly complex malignant diseases showing a high level of heterogeneity and consequently also a variance in therapeutic response, regardless of clinical stage. Our study implies that the progression of HNSCC may be supported by cancer-associated fibroblasts (CAFs) in the tumour microenvironment (TME) and the heterogeneity of this disease may lie in the level of cooperation between CAFs and epithelial cancer cells, as communication between CAFs and epithelial cancer cells seems to be a key factor for the sustained growth of the tumour mass. In this study, we investigated how CAFs derived from tumours of different mRNA subtypes influence the proliferation of cancer cells and their metabolic and biomechanical reprogramming. We also investigated the clinicopathological significance of the expression of these metabolism-related genes in tissue samples of HNSCC patients to identify a possible gene signature typical for HNSCC progression. We found that the right kind of cooperation between cancer cells and CAFs is needed for tumour growth and progression, and only specific mRNA subtypes can support the growth of primary cancer cells or metastases. Specifically, during coculture, cancer cell colony supporting effect and effect of CAFs on cell stiffness of cancer cells are driven by the mRNA subtype of the tumour from which the CAFs are derived. The degree of colony-forming support is reflected in cancer cell glycolysis levels and lactate shuttle-related transporters.

Symmetry-protected exceptional and nodal points in non-Hermitian systems

Sharareh Sayyad, Marcus Stålhammar, Lukas Rødland, Flore K. Kunst

One of the unique features of non-Hermitian (NH) systems is the appearance of non-Hermitian degeneracies known as exceptional points~(EPs). The occurrence of EPs in NH systems requires satisfying constraints whose number can be reduced in the presence of some symmetries. This results in stabilizing the appearance of EPs. Even though two different types of EPs, namely defective and non-defective EPs, may emerge in NH systems, exploring the possibilities of stabilizing EPs has been only addressed for defective EPs, at which the Hamiltonian becomes non-diagonalizable. In this letter, we show that certain discrete symmetries, namely parity-time, parity-particle-hole, and pseudo-Hermitian symmetry, may guarantee the occurrence of both defective and non-defective EPs. We extend this list of symmetries by including the non-Hermitian time-reversal symmetry in the two-band systems. <br>We further show that the non-defective EPs manifest themselves by i) the diagonalizability of non-Hermitian Hamiltonian at these points and ii) the non-diagonalizability of the Hamiltonian along certain intersections of non-defective EPs. Two-band and four-band models exemplify our findings. Through an example, we further reveal that ordinary (Hermitian) nodal points may coexist with defective EPs in non-Hermitian models when the above symmetries are relaxed.

A Proposal to Perform High Contrast Imaging of Human Palatine Tonsil with Cross Polarized Optical Coherence Tomography

Gargi Sharma, Asha Parmar, Franziska Hoffmann, Katharina Geißler, Ferdinand von Eggeling, Orlando Guntinas-Lichius, Kanwarpal Singh

The palatine tonsils provide the first line of immune defense against foreign pathogens<br>inhaled or ingested. However, a disruption in the epithelial layer within the tonsil crypts can lead to recurrent acute tonsillitis (RAT). Current imaging techniques suffer from poor resolution and contrast and do not allow a classification of the severity of RAT. We have developed a cross-polarized optical coherence tomography system. The system can detect a change in the polarization of the light after the light-tissue interaction. We demonstrate improved resolution and contrast in tonsil imaging with the developed method. Intensity, as well as retardance images of the excised tonsil tissue, were acquired. Features such as crypt epithelium, lymphoid follicles, and dense connective tissue were observed with improved contrast. Cross polarized optical coherence tomography can be a valuable tool in the clinic to evaluate palatine tonsils as it would allow visualizing common tonsil features without the need for any external contrast agent.

Modern applications of machine learning in quantum sciences

Anna Dawid, Julian Arnold, Borja Requena, Alexander Gresch, Marcin Płodzień, Kaelan Donatella, Kim Nicoli, Paolo Stornati, Rouven Koch, et al.

In these Lecture Notes, we provide a comprehensive introduction to the most<br>recent advances in the application of machine learning methods in quantum<br>sciences. We cover the use of deep learning and kernel methods in supervised,<br>unsupervised, and reinforcement learning algorithms for phase classification,<br>representation of many-body quantum states, quantum feedback control, and<br>quantum circuits optimization. Moreover, we introduce and discuss more<br>specialized topics such as differentiable programming, generative models,<br>statistical approach to machine learning, and quantum machine learning.<br>

Depressive disorders are associated with increased peripheral blood cell deformability: a cross-sectional case-control study (Mood-Morph)

Andreas Walther, Anne Mackens-Kiani, Julian Eder, Maik Herbig, Christoph Herold, Clemens Kirschbaum, Jochen Guck, Lucas Wittwer, Katja Beesdo-Baum, et al.

Pathophysiological landmarks of depressive disorders are chronic low-grade inflammation and elevated glucocorticoid output. Both can potentially interfere with cytoskeleton organization, cell membrane bending and cell function, suggesting altered cell morpho-rheological properties like cell deformability and other cell mechanical features in depressive disorders. We performed a cross-sectional case-control study using the image-based morpho-rheological characterization of unmanipulated blood samples facilitating real-time deformability cytometry (RT-DC). Sixty-nine pre-screened individuals at high risk for depressive disorders and 70 matched healthy controls were included and clinically evaluated by Composite International Diagnostic Interview leading to lifetime and 12-month diagnoses. Facilitating deep learning on blood cell images, major blood cell types were classified and morpho-rheological parameters such as cell size and cell deformability of every individual cell was quantified. We found peripheral blood cells to be more deformable in patients with depressive disorders compared to controls, while cell size was not affected. Lifetime persistent depressive disorder was associated with increased cell deformability in monocytes and neutrophils, while in 12-month persistent depressive disorder erythrocytes deformed more. Lymphocytes were more deformable in 12-month major depressive disorder, while for lifetime major depressive disorder no differences could be identified. After correction for multiple testing, only associations for lifetime persistent depressive disorder remained significant. This is the first study analyzing morpho-rheological properties of entire blood cells and highlighting depressive disorders and in particular persistent depressive disorders to be associated with increased blood cell deformability. While all major blood cells tend to be more deformable, lymphocytes, monocytes, and neutrophils are mostly affected. This indicates that immune cell mechanical changes occur in depressive disorders, which might be predictive of persistent immune response.

Changes in Blood Cell Deformability in Chorea-Acanthocytosis and Effects of Treatment With Dasatinib or Lithium

Felix Reichel, Martin Kräter, Kevin Peikert, Hannes Glaß, Philipp Rosendahl, Maik Herbig, Alejandro Rivera Prieto, Alexander Kihm, Giel Bosman, et al.

Misshaped red blood cells (RBCs), characterized by thorn-like protrusions known as acanthocytes, are a key diagnostic feature in Chorea-Acanthocytosis (ChAc), a rare neurodegenerative disorder. The altered RBC morphology likely influences their biomechanical properties which are crucial for the cells to pass the microvasculature. Here, we investigated blood cell deformability of five ChAc patients compared to healthy controls during up to 1-year individual off-label treatment with the tyrosine kinase inhibitor dasatinib or several weeks with lithium. Measurements with two microfluidic techniques allowed us to assess RBC deformability under different shear stresses. Furthermore, we characterized leukocyte stiffness at high shear stresses. The results showed that blood cell deformability–including both RBCs and leukocytes - in general was altered in ChAc patients compared to healthy donors. Therefore, this study shows for the first time an impairment of leukocyte properties in ChAc. During treatment with dasatinib or lithium, we observed alterations in RBC deformability and a stiffness increase for leukocytes. The hematological phenotype of ChAc patients hinted at a reorganization of the cytoskeleton in blood cells which partly explains the altered mechanical properties observed here. These findings highlight the need for a systematic assessment of the contribution of impaired blood cell mechanics to the clinical manifestation of ChAc.

Unbiased retrieval of frequency-dependent mechanical properties from noisy time-dependent signals

Shada Abuhattum, Hui-Shun Kuan, Paul Mueller, Jochen Guck, Vasily Zaburdaev

The mechanical response of materials to dynamic loading is often quantified by the frequency-dependent complex modulus. Probing materials directly in the frequency domain faces technical challenges such as a limited range of frequencies, long measurement times, or small sample sizes. Furthermore, many biological samples, such as cells or tissues, can change their properties upon repetitive probing at different frequencies. Therefore, it is common practice to extract the material properties by fitting predefined mechanical models to measurements performed in the time domain. This practice, however, precludes the probing of unique and yet unexplored material properties. In this report, we demonstrate that the frequency-dependent complex modulus can be robustly retrieved in a model-independent manner directly from time-dependent stress-strain measurements. While applying a rolling average eliminates random noise and leads to a reliable complex modulus in the lower frequency range, a Fourier transform with a complex frequency helps to recover the material properties at high frequencies. Finally, by properly designing the probing procedure, the recovery of reliable mechanical properties can be extended to an even wider frequency range. Our approach can be used with many state-of-the-art experimental methods to interrogate the mechanical properties of biological and other complex materials.

Hollow-core optical fibre sensors for operando Raman spectroscopy investigation of Li-ion battery liquid electrolytes

Ermanno Miele, Wesley M. Dose, Ilya Manyakin, Michael Frosz, Zachary Ruff, Michael F. L. De Volder, Clare P. Grey, Jeremy J. Baumberg, Tijmen G. Euser

Improved analytical tools are urgently required to identify degradation and failure mechanisms in Li-ion batteries. However, understanding and ultimately avoiding these detrimental mechanisms requires continuous tracking of complex electrochemical processes in different battery components. Here, we report an operando spectroscopy method that enables monitoring the chemistry of a carbonate-based liquid electrolyte during electrochemical cycling in Li-ion batteries with a graphite anode and a LiNi0.8Mn0.1Co0.1O2 cathode. By embedding a hollow-core optical fibre probe inside a lab-scale pouch cell, we demonstrate the effective evolution of the liquid electrolyte species by background-free Raman spectroscopy. The analysis of the spectroscopy measurements reveals changes in the ratio of carbonate solvents and electrolyte additives as a function of the cell voltage and show the potential to track the lithium-ion solvation dynamics. The proposed operando methodology contributes to understanding better the current Li-ion battery limitations and paves the way for studies of the degradation mechanisms in different electrochemical energy storage systems.

PiSCAT: A Python Package for Interferometric Scattering Microscopy

Houman Mirzaalian Dastjerdi, Reza Gholami Mahmoodabadi, Matthias Bär, Vahid Sandoghdar, Harald Köstler

Interferometric scattering (iSCAT) microscopy allows one to image and track nano-objects with a nanometer spatial and microsecond temporal resolution over arbitrarily long measurement times (Lindfors et al., 2004; Taylor & Sandoghdar, 2019b, 2019a). A key advantage of this technique over the well-established fluorescence methods is the indefinite photostability of the scattering phenomenon in contrast to the photobleaching of fluorophores. This means that one can perform very long measurements. Moreover, scattering processes are linear and thus do not saturate. This leads to larger signals than is possible from a single fluorophore. As a result, one can image at a much faster rate than in fluorescence microscopy. Furthermore, the higher signal makes it possible to localize a nano-object with much better spatial precision.<br>The remarkable sensitivity of iSCAT, however, also brings about the drawback that one obtains a rich speckle-like background from other nano-objects in the field of view.

Introduction to quantum optics

Carlos Navarrete-Benlloch

These are the lecture notes for a course that I am teaching at Zhiyuan College of Shanghai Jiao<br>Tong University (available at www.youtube.com/derekkorg), though the first draft was created for a previous course I taught at the University of Erlangen-Nuremberg in Germany. It has been designed for students who have only had basic training on quantum mechanics, and hence, the course is suited<br>for people at all levels (say, from the end of the bachelor all the way into the PhD). The notes are<br>a work in progress, meaning that some proofs and many figures are still missing. However, I’ve<br>tried my best to write everything in such a way that a reader can follow naturally all arguments<br>and derivations even with these missing bits. Also a few chapters are left to add, including one<br>on mathematical methods to analyze the dynamics of open systems, and another introducing the plethora of current experimental platforms where the tools and ideas developed in these notes are being currently implemented.

Quantum physics in space

Alessio Belenchia, Matteo Carlesso, Ömer Bayraktar, Daniele Dequal, Ivan Derkach, Giulio Gasbarri, Waldemar Herr, Ying Lia Li, Markus Rademacher, et al.

Advances in quantum technologies are giving rise to a revolution in the way fundamental physics questions are explored at the empirical level. At the same time, they are the seeds for future disruptive technological applications of quantum physics. Remarkably, a space-based environment may open many new avenues for exploring and employing quantum physics and technologies. Recently, space missions employing quantum technologies for fundamental or applied studies have been proposed and implemented with stunning results. The combination of quantum physics and its space application is the focus of this review: we cover both the fundamental scientific questions that can be tackled with quantum technologies in space and the possible implementation of these technologies for a variety of academic and commercial purposes.

High-resolution vibronic spectroscopy of a single molecule embedded in a crystal

Johannes Zirkelbach, Masoud Mirzaei, Irena Deperasińska, Boleslaw Kozankiewicz, Burak Gürlek, Alexey Shkarin, Tobias Utikal, Stephan Götzinger, Vahid Sandoghdar

Vibrational levels of the electronic ground states in dye molecules have not been previously explored at high resolution<br>in solid matrices. We present new spectroscopic measurements on single polycyclic aromatic molecules of dibenzoter-<br>rylene embedded in an organic crystal made of para-dichlorobenzene. To do this, we use narrow-band continuous-wave<br>lasers and combine spectroscopy methods based on fluorescence excitation and stimulated emission depletion (STED)<br>to select individual vibronic transitions at a resolution of ∼30 MHz dictated by the linewidth of the electronic ex-<br>cited state. In this fashion, we identify several exceptionally narrow vibronic levels in the electronic ground state with<br>linewidths down to values around 2 GHz. Additionally, we sample the distribution of vibronic wavenumbers, relax-<br>ation rates, and Franck-Condon factors, both in the electronic ground and excited states for a handful of individual<br>molecules. We discuss various noteworthy experimental findings and compare them with the outcome of DFT cal-<br>culations. The highly detailed vibronic spectra obtained in our work pave the way for studying the nanoscopic local<br>environment of single molecules. The approach also provides an improved understanding of the vibrational relaxation<br>mechanisms in the electronic ground state, which may help to create long-lived vibrational states for applications in<br>quantum technology.

Gradient Ascent Pulse Engineering with Feedback

Riccardo Porotti, Vittorio Peano, Florian Marquardt

Efficient approaches to quantum control and feedback are essential for quantum technologies, from sensing to quantum computation. Pure control tasks have been successfully solved using optimization techniques, including methods like gradient-ascent pulse engineering (GRAPE) , relying on a differentiable model of the quantum dynamics. For feedback tasks, such methods are not directly applicable, since the aim is to discover strategies conditioned on measurement outcomes. There, model-free reinforcement learning (RL) has recently proven a powerful new ansatz. What is missing is a way to combine the best of both approaches for scenarios that go beyond weak measurements. In this work, we introduce feedback-GRAPE, which borrows concepts from model-free RL to incorporate the response to strong stochastic (discrete or continuous) measurements, while still performing direct gradient ascent through the quantum dynamics. We illustrate its power on a Jaynes-Cummings model with feedback, where it yields interpretable feedback strategies for state preparation and stabilization in the presence of noise. This approach could be employed for discovering strategies in a wide range of feedback tasks, from calibration of multi-qubit devices to linear-optics quantum computation strategies, quantum-enhanced sensing with adaptive measurements, and quantum error correction.

An explicit model to extract viscoelastic properties of cells from AFM force-indentation curves

Shada Abuhattum Hofemeier, Dominic Mokbel, Paul Müller, Despina Soteriou, Jochen Guck, Sebastian Aland

Atomic force microscopy (AFM) is widely used for quantifying the mechanical properties of soft materials such as cells. AFM force-indentation curves are conventionally fitted with a Hertzian model to extract elastic properties. These properties solely are, however, insufficient to describe the mechanical properties of cells. Here, we expand the analysis capabilities to describe the viscoelastic behavior while using the same force-indentation curves. Our model gives an explicit relation of force and indentation and extracts physically meaningful mechanical parameters. We first validated the model on simulated force-indentation curves. Then, we applied the fitting model to the force-indentation curves of two hydrogels with different crosslinking mechanisms. Finally, we characterized HeLa cells in two cell cycle phases, interphase and mitosis, and showed that mitotic cells have a higher apparent elasticity and a lower apparent viscosity. Our study provides a simple method, which can be directly integrated into the standard AFM framework for extracting the viscoelastic properties of materials.

Polarization Independent Optical Coherence Tomography

Asha Parmar, Gargi Sharma, Kanwarpal Singh

Optical coherence tomography (OCT) is a well established imaging modality for high-resolution three-dimensional imaging in clinical settings. While imaging, care must be taken to minimize the imaging artifacts related to the polarization differences between the sample and the reference signals. Current OCT systems adopt complicated mechanisms, such as the use of multiple detectors, polarization-maintaining fibers, polarization controllers to achieve polarization artifacts free sample images.<br>Often the polarization controllers need readjustment which is not suitable for clinical settings. In this work, we demonstrate a simple approach that can minimize the polarization-related artifacts in the OCT systems. Polarization artifact-free images are acquired using two orthogonally polarized reference signals where the orthogonal polarization is achieved using a Faraday mirror. In the current approach, only a single detector is required which makes the current approach compatiblewith swept-source or camera-basedOCT systems. Furthermore, no polarization controllers are used in the system which increases the system stability while minimizing the artifacts related to the sample birefringence, polarization change due to the sample scattering, and polarization change due to the optical fiber movements present in the system.

Nonreciprocal and chiral single-photon scattering for giant atoms

Yao-Tong Chen, Lei Du, Lingzhen Guo, Zhihai Wang, Yan Zhang, Yong Li, Jin-Hui Wu

In this work, we investigate the nontrivial single-photon scattering properties of giant atoms cou-<br>pled to waveguides that can be an effective platform for realising nonreciprocal and chiral quantum optics. For the two-level giant-atom setup, we identify the condition for nonreciprocal transmission: the external atomic dissipation is further required other than the breaking of time-reversal symmetry by local coupling phases. Especially, in the non-Markovian regime, unconventional revival peaks periodically appear in the reflection spectrum of such a two-level giant-atom system. To explore more interesting scattering behaviours, we further extend the two-level giant-atom system to ∆-type and<br>∇-type three-level giant atoms coupled to double waveguides without external atomic dissipation.<br>We analyse the different physical mechanisms for the nonreciprocal and chiral scattering properties of the ∆-type and ∇-type giant atoms. Our proposed giant-atom structures have potential applications of high-efficient single-photon targeted router and circulator for quantum information precessing.

Phase Space Crystal Vibrations: Chiral Edge States with Preserved Time-reversal Symmetry

Lingzhen Guo, Vittorio Peano, Florian Marquardt

Chiral transport along edge channels in Chern insulators represents the most robust version of topological transport, but it usually requires breaking of the physical time-reversal symmetry. In this work, we introduce a different mechanism that foregoes this requirement, based on the combination of the symplectic geometry of phase space and interactions. Starting from a honeycomb phase-space crystal of atoms, which can be generated by periodic driving of a one-dimensional interacting quantum gas, we show that the resulting vibrational lattice waves have topological properties. Our work provides a new platform to study topological many-body physics in dynamical systems.

suggested by editors

An exception to the rule? Regeneration of the injured spinal cord in the spiny mouse

Daniel Wehner, Catherina G. Becker

The capacity for long-distance axon regeneration and functional recovery after spinal cord injury in the adult has long been thought to be a unique feature of certain non-mammalian vertebrates. However, in this issue of Developmental Cell, Nogueira-Rodrigues et al. report an astonishingly high regenerative ability in the spiny mouse.

Experimental high-dimensional Greenberger-Horne-Zeilinger entanglement with superconducting transmon qutrits

Alba Cervera-Lierta, Mario Krenn, Alan Aspuru-Guzik, Alexey Galda

Multipartite entanglement is one of the core concepts in quantum information science with broad applications that span from condensed matter physics to quantum physics foundations tests. Although its most studied and tested forms encompass two-dimensional systems, current quantum platforms technically allow the manipulation of additional quantum levels. We report the first experimental demonstration of a high-dimensional multipartite entangled state in a superconducting quantum processor. We generate the three-qutrit Greenberger-Horne-Zeilinger state by designing the necessary pulses to perform high-dimensional quantum operations. We obtain the fidelity of 76 ±1%, proving the generation of a genuine three-partite and three-dimensional entangled state.<br>To this date, only photonic devices have been able to create and manipulate these high-dimensional states. Our work demonstrates that another platform, superconducting systems, is ready to exploit<br>high-dimensional physics phenomena and that a programmable quantum device accessed on the<br>cloud can be used to design and execute experiments beyond binary quantum computation.

Stimulated Brillouin scattering in chiral photonic crystal fiber

Xinglin Zeng, Wenbin He, Michael Frosz, Andreas Geilen, Paul Roth, Gordon Wong, Philip Russell, Birgit Stiller

Stimulated Brillouin scattering (SBS) has many applications; for example, in sensing, microwave photonics, and signal processing. Here, we report the first experimental study of SBS in chiral photonic crystal fiber (PCF), which displays optical activity and robustly maintains circular polarization states against external perturbations. As a result, circularly polarized pump light is cleanly backscattered into a Stokes signal with the orthogonal circular polarization state, as is required by angular momentum conservation. By comparison, untwisted PCF generates a Stokes signal with an unpredictable polarization state, owing to its high sensitivity to external perturbations. We use chiral PCF to realize a circularly polarized continuous-wave Brillouin laser. The results pave the way for a new generation of stable circularly polarized SBS systems with applications in quantum manipulation, optical tweezers, optical gyroscopes, and fiber sensors.

Quantitative imaging of Caenorhabditis elegans dauer larvae during cryptobiotic transition

Kyoohyun Kim, Vamshidhar Gade, Teymuras V. Kurzchalia, Jochen Guck

Upon starvation or overcrowding, the nematode Caenorhabditis elegans enters diapause by forming a dauer larva, which can then further survive harsh desiccation in an anhydrobiotic state. We have previously identified the genetic and biochemical pathways essential for survival—but without detailed knowledge of their material properties, the mechanistic understanding of this intriguing phenomenon remains incomplete. Here we employed optical diffraction tomography (ODT) to quantitatively assess the internal mass density distribution of living larvae in the reproductive and diapause stages. ODT revealed that the properties of the dauer larvae undergo a dramatic transition upon harsh desiccation. Moreover, mutants that are sensitive to desiccation displayed structural abnormalities in the anhydrobiotic stage that could not be observed by conventional microscopy. Our advance opens a door to quantitatively assessing the transitions in material properties and structure necessary to fully understand an organism on the verge of life and death.

Efficient Excitation of High-Purity Modes in Arbitrary Waveguide Geometries

Ralf Mouthaan, Peter J. Christopher, Jonathan Pinnell, Michael Frosz, George Gordon, Timothy D. Wilkinson, Tijmen G. Euser

A general method is presented for exciting discrete modes in waveguides of arbitrary geometry. Guided modes supported by the waveguide are first calculated using a finite difference frequency domain model. High efficiency holograms to excite these discrete modes are then generated using the Direct Search hologram generation algorithm. The Direct Search algorithm is optimised such that the inherent properties of waveguide modes are exploited to give faster execution times. A nodeless antiresonant photonic crystal fibre is considered as a test geometry, in which high-purity modes are experimentally excited and in-coupling efficiencies of up to 32.8% are obtained.

Advances in Magnetics Roadmap on Spin-Wave Computing

A. V. Chumak, P. Kabos, M. Wu, C. Abert, C. Adelmann, A. Adeyeye, J. Åkerman, F. G. Aliev, A. Anane, et al.

Magnonics addresses the physical properties of spin waves and utilizes them for data processing. Scalability down to atomic dimensions, operation in the GHz-to-THz frequency range, utilization of nonlinear and nonreciprocal phenomena, and compatibility with CMOS are just a few of many advantages offered by magnons. Although magnonics is still primarily positioned in the academic domain, the scientific and technological challenges of the field are being extensively investigated, and many proof-of-concept prototypes have already been realized in laboratories. This roadmap is a product of the collective work of many authors, which covers versatile spin-wave computing approaches, conceptual building blocks, and underlying physical phenomena. In particular, the roadmap discusses the computation operations with the Boolean digital data, unconventional approaches, such as neuromorphic computing, and the progress toward magnon-based quantum computing. This article is organized as a collection of sub-sections grouped into seven large thematic sections. Each sub-section is prepared by one or a group of authors and concludes with a brief description of current challenges and the outlook of further development for each research direction.

Cascaded frequency up-conversion of bright squeezed vacuum: spectral and correlation properties

Andrei V. Rasputnyi, Denis A. Kopylov, Tatiana V. Murzina, Maria V. Chekhova

High-gain parametric down-conversion (PDC) is inevitably accompanied by cascaded up-conversion (CUpC) of PDC radiation in a nonlinear crystal even if CUpC is nonphase matched. Here we study experimentally and theoretically the spectral properties of broadband phase-matched and nonphase-matched CUpC radiation in a beta barium borate (BBO) crystal. Our calculations of the normalized second- order correlation function predict the super-bunching of CUpC radiation.

Nonlinear microscopy using impulsive stimulated Brillouin scattering for high-speed elastography

Benedikt Krug, Nektarios Koukourakis, Jochen Guck, Jürgen Czarske

The impulsive stimulated Brillouin microscopy promises fast, non-contact measurements of the elastic properties of biological samples. The used pump-probe approach employs an ultra-short pulse laser and a cw laser to generate Brillouin signals. Modeling of the microscopy technique has already been carried out partially, but not for biomedical applications. The nonlinear relationship between pulse energy and Brillouin signal amplitude is proven with both simulations and experiments. Tayloring of the excitation parameters on the biologically relevant polyacrylamide hydrogels outline sub-ms temporal resolutions at a relative precision of <1%. Brillouin microscopy using the impulsive stimulated scattering therefore exhibits high potential for the measurements of viscoelastic properties of cells and tissues.

Cross-Polarized Optical Coherence Tomography System with Unpolarized Light

Georg R. Hartl, Asha Parmar, Gargi Sharma, Kanwarpal Singh

Cross-polarized optical coherence tomography offers improved contrast for samples which<br>can alter the polarization of light when it interacts with the sample. This property has been utilized to screen pathological conditions in several organs. Existing cross-polarized optical coherence tomography systems require several polarization-controlling elements to minimize the optical fiber movement-related image artifacts. In this work, we demonstrate a cross-polarized optical coherence tomography system using unpolarized light and only two quarter-wave plates, which is free from fiber-induced image artifacts. The simplicity of the approach will find many applications in clinical settings.

Single photon sources for quantum radiometry: a brief review about the current state‑of‑the‑art

Stefan Kück, Marco López, Helmuth Hofer, Hristina Georgieva, Justus Christinck, Beatrice Rodiek, Geiland Porrovecchio, Marek Smid, Stephan Götzinger, et al.

Single-photon sources have a variety of applications. One of these is quantum radiometry, which is reported on in this<br>paper in the form of an overview, specifically of the current state of the art in the application of deterministic single photon<br>sources to the calibration of single photon detectors. To optimize single-photon sources for this purpose, extensive research<br>is currently carried out at the European National Metrology Institutes (NMIs), in collaboration with partners from universi-<br>ties. Single-photon sources of different types are currently under investigation, including sources based on defect centres in<br>(nano-)diamonds, on molecules and on semiconductor quantum dots. We will present, summarise, and compare the current<br>results obtained at European NMIs for single-photon sources in terms of photon flux, single-photon purity, and spectral<br>power distribution as well as the results of single-photon detector calibrations carried out with this type of light sources.

Label-free imaging flow cytometry for analysis and sorting of enzymatically dissociated tissues

Maik Herbig, Karen Tessmer, Martin Nötzel, Ahmad Ahsan Nawaz, Tiago Santos-Ferreira, Oliver Borsch, Sylvia J. Gasparini, Jochen Guck, Marius Ader

Biomedical research relies on identification and isolation of specific cell types using molecular biomarkers and sorting methods such as fluorescence or magnetic activated cell sorting. Labelling processes potentially alter the cells’ properties and should be avoided, especially when purifying cells for clinical applications. A promising alternative is the label-free identification of cells based on physical properties. Sorting real-time deformability cytometry (soRT-DC) is a microfluidic technique for label-free analysis and sorting of single cells. In soRT-FDC, bright-field images of cells are analyzed by a deep neural net (DNN) to obtain a sorting decision, but sorting was so far only demonstrated for blood cells which show clear morphological differences and are naturally in suspension. Most cells, however, grow in tissues, requiring dissociation before cell sorting which is associated with challenges including changes in morphology, or presence of aggregates. Here, we introduce methods to improve robustness of analysis and sorting of single cells from nervous tissue and provide DNNs which can distinguish visually similar cells. We employ the DNN for image-based sorting to enrich photoreceptor cells from dissociated retina for transplantation into the mouse eye.

Machine learning assisted real-time deformability cytometry of CD34+ cells allows to identify patients with myelodysplastic syndromes

Maik Herbig, Angela Jacobi, Manja Wobus, Heike Weidner, Anna Mies, Martin Kräter, Oliver Otto, Christian Thiede, Marie-Theresa Weickert, et al.

Diagnosis of myelodysplastic syndrome (MDS) mainly relies on a manual assessment of the peripheral blood and bone marrow cell morphology. The WHO guidelines suggest a visual screening of 200 to 500 cells which inevitably turns the assessor blind to rare cell populations and leads to low reproducibility. Moreover, the human eye is not suited to detect shifts of cellular properties of entire populations. Hence, quantitative image analysis could improve the accuracy and reproducibility of MDS diagnosis. We used real-time deformability cytometry (RT-DC) to measure bone marrow biopsy samples of MDS patients and age-matched healthy individuals. RT-DC is a high-throughput (1000 cells/s) imaging flow cytometer capable of recording morphological and mechanical properties of single cells. Properties of single cells were quantified using automated image analysis, and machine learning was employed to discover morpho-mechanical patterns in thousands of individual cells that allow to distinguish healthy vs. MDS samples. We found that distribution properties of cell sizes differ between healthy and MDS, with MDS showing a narrower distribution of cell sizes. Furthermore, we found a strong correlation between the mechanical properties of cells and the number of disease-determining mutations, inaccessible with current diagnostic approaches. Hence, machine-learning assisted RT-DC could be a promising tool to automate sample analysis to assist experts during diagnosis or provide a scalable solution for MDS diagnosis to regions lacking sufficient medical experts.

Mechanical spinal cord transection in larval zebrafish and subsequent whole-mount histological processing

Nora John, Julia Kolb, Daniel Wehner

Zebrafish regenerate their spinal cord after injury, both at larval and adult stages. Larval zebrafish have emerged as a powerful model system to study spinal cord injury and regeneration due to their high optical transparency for in vivo imaging, amenability to high-throughput analysis, and rapid regeneration time. Here, we describe a protocol for the mechanical transection of the larval zebrafish spinal cord, followed by whole-mount tissue processing for in situ hybridization and immunohistochemistry to elucidate principles of regeneration.

Bright squeezed vacuum for two-photon spectroscopy: simultaneously high resolution in time and frequency, space and wavevector

Paula Cutipa, Maria V. Chekhova

Entangled photons offer two advantages for two-photon absorption spectroscopy. One of them, the linear scaling of two-photon absorption rate with the input photon flux, is valid only at very low photon fluxes and is therefore impractical. The other is the overcoming of the classical constraints for simultaneous resolution in time–frequency and in space–wavevector. Here we consider bright squeezed vacuum (BSV) as an alternative to entangled photons. The efficiency increase it offers in comparison with coherent light is modest, but it does not depend on the photon flux. Moreover, and this is what we show in this work, BSV also provides simultaneously high resolution in time and frequency, and in space and wavevector. In our experiment, we measure the widths of the second-order correlation functions in space, time, frequency, and angle and demonstrate the violation of the constraint given by the Fourier transformation, in the case of photon pairs, known as the Mancini criterion of entanglement.

Light propagation and magnon-photon coupling in optically dispersive magnetic media

V. A. S. V. Bittencourt, I. Liberal, S. Viola-Kusminskiy

Achieving strong coupling between light and matter excitations in hybrid systems is a benchmark for the implementation of quantum technologies. We recently proposed (Bittencourt, Liberal, and Viola-Kusminskiy, arXiv:2110.02984) that strong single-particle coupling between magnons and light can be realized in a magnetized epsilon-near-zero (ENZ) medium, in which magneto-optical effects are enhanced. Here we present a detailed derivation of the magnon-photon coupling Hamiltonian in dispersive media both for degenerate and nondegenerate optical modes, and show the enhancement of the coupling near the ENZ frequency. Moreover, we show that the coupling of magnons to plane-wave nondegenerate Voigt modes vanishes at specific frequencies due to polarization selection rules tuned by dispersion. Finally, we present specific results using a Lorentz dispersion model. Our results pave the way for the design of dispersive optomagnonic systems, providing a general theoretical framework for describing and engineering ENZ-based optomagnonic systems.

Correlative all-optical quantification of mass density and mechanics of subcellular compartments with fluorescence specificity

Raimund Schlüßler, Kyoohyun Kim, Martin Nötzel, Anna Taubenberger, Shada Abuhattum, Timon Beck, Paul Müller, Shovamaye Maharana, Gheorghe Cojoc, et al.

Quantitative measurements of physical parameters become increasingly important for understanding biological processes. Brillouin microscopy (BM) has recently emerged as one technique providing the 3D distribution of viscoelastic properties inside biological samples − so far relying on the implicit assumption that refractive index (RI) and density can be neglected. Here, we present a novel method (FOB microscopy) combining BM with optical diffraction tomography and epifluorescence imaging for explicitly measuring the Brillouin shift, RI, and absolute density with specificity to fluorescently labeled structures. We show that neglecting the RI and density might lead to erroneous conclusions. Investigating the nucleoplasm of wild-type HeLa cells, we find that it has lower density but higher longitudinal modulus than the cytoplasm. Thus, the longitudinal modulus is not merely sensitive to the water content of the sample − a postulate vividly discussed in the field. We demonstrate the further utility of FOB on various biological systems including adipocytes and intracellular membraneless compartments. FOB microscopy can provide unexpected scientific discoveries and shed quantitative light on processes such as phase separation and transition inside living cells.

Cooperative quantum phenomena in light-matter platforms

Michael Reitz, Christian Sommer, Claudiu Genes

Quantum cooperativity is evident in light-matter platforms where quantum-emitter ensembles are interfaced<br>with confined optical modes and are coupled via the ubiquitous electromagnetic quantum vacuum.<br>Cooperative effects can find applications, among other areas, in topological quantum optics, in quantum<br>metrology, or in quantum information. This tutorial provides a set of theoretical tools to tackle the behavior<br>responsible for the onset of cooperativity by extending open quantum system dynamics methods, such as<br>the master equation and quantum Langevin equations, to electron-photon interactions in strongly coupled<br>and correlated quantum-emitter ensembles. The methods are illustrated on a wide range of current research<br>topics such as the design of nanoscale coherent-light sources, highly reflective quantum metasurfaces, or<br>low intracavity power superradiant lasers.

Comparison of back focal plane imaging of nitrogen vacancy centers in nanodiamond and core-shell CdSe/CdS quantum dots

Justus Christinck, Beatrice Rodiek, Marco Lopez , Hristina Georgieva, Stephan Götzinger, Stefan Kück

We report on the characterization of the angular-dependent emission of two different <br>single-photon emitters based on nitrogen-vacancy centers in nanodiamond and on core-shell CdSe/CdS quantum dot nanoparticles. The emitters were characterized in a confocal microscope <br>setup by spectroscopy and Hanbury-Brown and Twiss interferometry. The angular-dependent emission is measured using a back focal plane imaging technique. A theoretical model of the angular emission patterns of the 2D dipoles of the emitters is developed to determine their orientation. Experiment and model agree well with each other.

Tunneling in the Brillouin Zone: Theory of Backscattering in Valley Hall Edge Channels

Tirth Shah, Florian Marquardt, Vittorio Peano

A large set of recent experiments has been exploring topological transport in bosonic systems,e.g. of photons or phonons. In the vast majority, time-reversal symmetry is preserved, and bandstructures are engineered by a suitable choice of geometry, to produce topologically nontrivialbandgaps in the vicinity of high-symmetry points. However, this leaves open the possibility oflarge-quasimomentum backscattering, destroying the topological protection. Up to now, it has beenunclear what precisely are the conditions where this effect can be sufficiently suppressed. In thepresent work, we introduce a comprehensive semiclassical theory of tunneling transitions in momen-tum space, describing backscattering for one of the most important system classes, based on thevalley Hall effect. We predict that even for a smooth domain wall effective scattering centres developat locations determined by both the local slope of the wall and the energy. Moreover, our theoryprovides a quantitative analysis of the exponential suppression of the overall reflection amplitudewith increasing domain wall smoothness.

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Synchronization of gigahertz core resonances in multiple photonic crystal fiber cores by timing-modulated harmonic mode locking

Dung-Han Yeh, Wenbin He, Meng Pang, Xin Jiang, Philip St.J. Russell

Synchronization of mechanical oscillators by optical forces is a topic that has been much explored in recent years, for example, in the context of SiN microdisk resonators. Here we report stable long-term synchronization of the core vibrations of three different photonic crystal fibers, driven intra-cavity by a 2 GHz train of timing-modulated pulses in a high harmonic opto-acoustically mode-locked fiber laser. The core resonances are equally spaced in frequency and are coupled purely by the optical field. Under the correct conditions, they become stably synchronized, being simultaneously driven by the timing-modulated pulse train. Floquet–Bloch theory, in which the pulses are treated as particles trapped in potential wells and coupled by optomechanical back-action, describes the complex temporal dynamics observed in the experiments. This unique system provides a novel means of modifying the temporal structure of pulse trains running at few-gigahertz repetition rates.

Real-Time Deformability Cytometry Detects Leukocyte Stiffening After Gadolinium-Based Contrast Agent Exposure

Angela Jacobi, Angela Ariza de Schellenberger, Yavuz Oguz Uca, Maik Herbig, Jochen Guck, Ingolf Sack

Objectives <br>Reports on gadolinium (Gd) retention in soft tissues after administration of Gd-based contrast agents (GBCAs) raise concerns about Gd-induced changes in the biophysical properties of cells and tissues. Here, we investigate if clinical GBCAs of both classes of linear and macrocyclic structure cause changes in the mechanical properties of leukocytes in human blood samples.<br><br>Material and Methods <br>Real-time deformability cytometry was applied to human blood samples from 6 donors. The samples were treated with 1 mM gadoteric acid (Dotarem), gadopentetic acid (Magnevist), gadobutrol (Gadovist), or Gd trichloride at 37°C for 1 hour to mimic clinical doses of GBCAs and exposure times. Leukocyte subtypes—lymphocytes, monocytes, and neutrophils—were identified based on their size and brightness and analyzed for deformability, which is inversely correlated with cellular stiffness.<br><br>Results <br>We observed significant stiffening (3%–13%, P < 0.01) of all investigated leukocyte subtypes, which was most pronounced for lymphocytes, followed by neutrophils and monocytes, and the effects were independent of the charge and steric structure of the GBCA applied. In contrast, no changes in cell size and brightness were observed, suggesting that deformability and cell stiffness measured by real-time deformability cytometry are sensitive to changes in the physical phenotypes of leukocytes after GBCA exposure.<br><br>Conclusions <br>Real-time deformability cytometry might provide a quantitative blood marker for critical changes in the physical properties of blood cells in patients undergoing GBCA-enhanced magnetic resonance imaging.

Phase Space Crystals: Condensed matter in dynamical systems

Lingzhen Guo

This book aims to develop a general framework of condensed matter theory in phase space, instead of configuration space, of a dynamical system. Different from Euclidean real space, phase space is embedded with symplectic geometry in classical mechanics or noncommutative geometry in quantum mechanics. Arbitrary lattice Hamiltonians and crystalline many-body states in phase space can be created with the Floquet approach. The book covers topics ranging from dynamical systems, Floquet theory, topological physics to quantum many-body physics and time crystals. The book fills in the blanks in the study of dynamical systems by considering many-body physics in the phase space.

Playing Ping Pong with Light: Directional Emission of White Light

Heribert Wankerl, Christopher Wiesmann, Laura Kreiner, Rainer Butendeich, Alexander Luce, Sandra Sobczyk, Maike Lorena Stern, Elmar Wolfgang Lang

Over the last decades, light-emitting diodes (LED) have replaced common light bulbs in almost every application, from flashlights in smartphones to automotive headlights. Illuminating nightly streets requires LEDs to emit a light spectrum that is perceived as pure white by the human eye. The power associated with such a white light spectrum is not only distributed over the contributing wavelengths but also over the angles of vision. For many applications, the usable light rays are required to exit the LED in forward direction, namely under small angles to the perpendicular. In this work, we demonstrate that a specifically designed multi-layer thin film on top of a white LED increases the power of pure white light emitted in forward direction. Therefore, the deduced multi-objective optimization problem is reformulated via a real-valued physics-guided objective function that represents the<br>hierarchical structure of our engineering problem. Variants of Bayesian optimization are employed to maximize this non-deterministic objective function based on ray tracing simulations. Eventually, the investigation of optical properties of suitable multi-layer thin films allowed to identify the mechanism behind the increased directionality of white light: angle and wavelength selective filtering causes the multi-layer thin film to play ping pong with<br>rays of light.

Accelerated Non-Reciprocal Transfer of Energy Around an Exceptional Point

Hugo Ribeiro, Florian Marquardt

We develop perturbative methods to study and control dynamical phenomena related to exceptional points in Non-Hermitian systems. In particular, we show how to find perturbative solutions based on the Magnus expansion that accurately describe the evolution of non-Hermitian systems when encircling an exceptional point. This allows us to use the recently proposed Magnus-based strategy for control to design fast non-reciprocal, topological operations whose fidelity error is orders of magnitude smaller than their much slower adiabatic counterparts.

Passive coupling of membrane tension and cell volume during active response of cells to osmosis

Chloé Roffay, Guillaume Molinard, Kyoohyun Kim, Marta Urbanska, Virginia Andrade, Victoria Barbarasa, Paulina Nowak, Vincent Mercier, José García-Calvo, et al.

During osmotic changes of their environment, cells actively regulate their volume and plasma membrane tension that can passively change through osmosis. How tension and volume are coupled during osmotic adaptation remains unknown, as their quantitative characterization is lacking. Here, we performed dynamic membrane tension and cell volume measurements during osmotic shocks. During the first few seconds following the shock, cell volume varied to equilibrate osmotic pressures inside and outside the cell, and membrane tension dynamically followed these changes. A theoretical model based on the passive, reversible unfolding of the membrane as it detaches from the actin cortex during volume increase quantitatively describes our data. After the initial response, tension and volume recovered from hypoosmotic shocks but not from hyperosmotic shocks. Using a fluorescent membrane tension probe (fluorescent lipid tension reporter [Flipper-TR]), we investigated the coupling between tension and volume during these asymmetric recoveries. Caveolae depletion and pharmacological inhibition of ion transporters and channels, mTORCs, and the cytoskeleton all affected tension and volume responses. Treatments targeting mTORC2 and specific downstream effectors caused identical changes to both tension and volume responses, their coupling remaining the same. This supports that the coupling of tension and volume responses to osmotic shocks is primarily regulated by mTORC2.

Mapping Tumor Spheroid Mechanics in Dependence of 3D Microenvironment Stiffness and Degradability by Brillouin Microscopy

Vaibhav Mahajan, Timon Beck, Paulina Gregorczyk, André Ruland, Simon Alberti, Jochen Guck, Carsten Werner, Raimund Schlüßler, Anna V. Taubenberger

Altered biophysical properties of cancer cells and of their microenvironment contribute to cancer progression. While the relationship between microenvironmental stiffness and cancer cell mechanical properties and responses has been previously studied using two-dimensional (2D) systems, much less is known about it in a physiologically more relevant 3D context and in particular for multicellular systems. To investigate the influence of microenvironment stiffness on tumor spheroid mechanics, we first generated MCF-7 tumor spheroids within matrix metalloproteinase (MMP)-degradable 3D polyethylene glycol (PEG)-heparin hydrogels, where spheroids showed reduced growth in stiffer hydrogels. We then quantitatively mapped the mechanical properties of tumor spheroids in situ using Brillouin microscopy. Maps acquired for tumor spheroids grown within stiff hydrogels showed elevated Brillouin frequency shifts (hence increased longitudinal elastic moduli) with increasing hydrogel stiffness. Maps furthermore revealed spatial variations of the mechanical properties across the spheroids’ cross-sections. When hydrogel degradability was blocked, comparable Brillouin frequency shifts of the MCF-7 spheroids were found in both compliant and stiff hydrogels, along with similar levels of growth-induced compressive stress. Under low compressive stress, single cells or free multicellular aggregates showed consistently lower Brillouin frequency shifts compared to spheroids growing within hydrogels. Thus, the spheroids’ mechanical properties were modulated by matrix stiffness and degradability as well as multicellularity, and also to the associated level of compressive stress felt by tumor spheroids. Spheroids generated from a panel of invasive breast, prostate and pancreatic cancer cell lines within degradable stiff hydrogels, showed higher Brillouin frequency shifts and less cell invasion compared to those in compliant hydrogels. Taken together, our findings contribute to a better understanding of the interplay between cancer cells and microenvironment mechanics and degradability, which is relevant to better understand cancer progression.

Arbitrary optical wave evolution with Fourier transforms and phase masks

Victor Lopéz-Pastor, Jeff S. Lundeen, Florian Marquardt

A large number of applications in classical and quantum photonics require the capability of implementing arbitrary linear unitary transformations on a set of optical modes. In a seminal work by Reck et al. it was shown how to build such multiport universal interferometers with a mesh of beam splitters and phase shifters, and this design became the basis for most experimental implementations in the last decades. However, the design of Reck et al. is difficult to scale up to a large number of modes, which would be required for many applications. Here we present a constructive proof that it is possible to realize a multiport universal interferometer on N modes with a succession of 6N Fourier transforms and 6N+1 phase masks, for any even integer N. Furthermore, we provide an algorithm to find the correct succesion of Fourier transforms and phase masks to realize a given arbitrary unitary transformation. Since Fourier transforms and phase masks are routinely implemented in several optical setups and they do not suffer from the scalability issues associated with building extensive meshes of beam splitters, we believe that our design can be useful for many applications in photonics.

Efficient nonlinear compression of a thin-disk oscillator to 8.5 fs at 55 W average power

Gaia Barbiero, Haochuang Wang, Martin Grassl, Sebastian Groebmeyer, Dziugas Kimbaras, Marcel Neuhaus, Vladimir Pervak, Thomas Nubbemeyer, Hanieh Fattahi, et al.

We demonstrate an efficient hybrid-scheme for nonlinear pulse compression of high-power thin-disk oscillator pulses to the sub-10 fs regime. The output of a home-built, 16 MHz, 84 W, 220 fs Yb:YAG thin-disk oscillator at 1030 nm is first compressed to 17 fs in two nonlinear multipass cells. In a third stage, based on multiple thin sapphire plates, further compression to 8.5 fs with 55 W output power and an overall optical efficiency of 65% is achieved. Ultrabroadband mid-infrared pulses covering the spectral range 2.4-8 μm were generated from these compressed pulses by intra-pulse difference frequency generation.

Optimized analysis for sensitive detection and analysis of single proteins via interferometric scattering microscopy

Houman Mirzaalian Dastjerdi, Mahyar Dahmardeh, André Gemeinhardt, Reza Gholami Mahmoodabadi, Harald Köstler, Vahid Sandoghdar

It has been shown that interferometric detection of Rayleigh scattering (iSCAT) can reach an exquisite sensitivity for label-free detection of nano-matter, down to single proteins. The sensitivity of iSCAT detection is intrinsically limited by shot noise, which can be indefinitely improved by employing higher illumination power or longer integration times. In practice, however, a large speckle-like background and technical issues in the experimental setup limit the attainable signal-to-noise ratio. Strategies and algorithms in data analysis are, thus, crucial for extracting quantitative results from weak signals, e.g. regarding the mass (size) of the detected nano-objects or their positions. In this article, we elaborate on some algorithms for processing iSCAT data and identify some key technical as well as conceptual issues that have to be considered when recording and interpreting the data. The discussed methods and analyses are made available in the extensive python-based platform, PiSCAT.

Critical dynamics of an asymmetrically bidirectionally pumped optical microresonator

Jonathan M. Silver, Kenneth T. V. Grattan, Pascal Del'Haye

An optical ring resonator with third-order, or Kerr, nonlinearity will exhibit symmetry breaking between the two counterpropagating circulating powers when pumped with sufficient power in both the clockwise and counterclockwise directions. This is due to the effects of self- and cross-phase modulation on the resonance frequencies in the two directions. The critical point of this symmetry breaking exhibits universal behaviors including divergent responsivity to external perturbations, critical slowing down, and scaling invariance. Here we derive a model for the critical dynamics of this system, first for a symmetrically pumped resonator and then for the general case of asymmetric pumping conditions and self- and cross-phase modulation coefficients. This theory not only provides a detailed understanding of the dynamical response of critical-point-enhanced optical gyroscopes and near-field sensors, but is also applicable to nonlinear critical points in a wide range of systems.

Design of quantum optical experiments with logic artificial intelligence

Alba Cervera-Lierta, M. Krenn, Alan Aspuru-Guzik

Logic artificial intelligence (AI) is a subfield of AI where variables can take two defined arguments, True or False, and are arranged in clauses that follow the rules of formal logic. Several problems that span from physical systems to mathematical conjectures can be encoded into these clauses and be solved by checking their satisfiability (SAT). Recently, SAT solvers have become a sophisticated and powerful computational tool capable, among other things, of solving long-standing mathematical conjectures. In this work, we propose the use of logic AI for the design of optical quantum experiments. We show how to map into a SAT problem the experimental preparation of an arbitrary quantum state and propose a logic-based algorithm, called Klaus, to find an interpretable representation of the photonic setup that generates it. We compare the performance of Klaus with the state-of-the-art algorithm for this purpose based on continuous optimization. We also combine both logic and numeric strategies to find that the use of logic AI improves significantly the resolution of this problem, paving the path to develop more formal-based approaches in the context of quantum physics experiments.

Single-molecule vacuum Rabi splitting: four-wave mixing and optical switching at the single-photon level

André Pscherer, Manuel Meierhofer, Daqing Wang, Hrishikesh Kelkar, Diego-Martin Cano, Tobias Utikal, Stephan Götzinger, Vahid Sandoghdar

A single quantum emitter can possess a very strong intrinsic nonlinearity, but its overall promise for nonlinear effects is hampered by the challenge of efficient coupling to incident photons. Common nonlinear optical materials, on the other hand, are easy to couple to but are bulky, imposing a severe limitation on the miniaturization of photonic systems. In this work, we show that a single organic molecule acts as an extremely efficient nonlinear optical element in the strong coupling regime of cavity quantum electrodynamics. We report on single-photon sensitivity in nonlinear signal generation and all-optical switching. Our work promotes the use of molecules for applications such as integrated photonic circuits, operating at very low powers.

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Nonlinear enhanced microresonator gyroscope

Jonathan M. Silver, Leonardo Del Bino, Michael T. M. Woodley, George N. Ghalanos, Andreas O. Svela, Niall Moroney, Shuangyou Zhang, Kenneth T. V. Grattan, Pascal Del'Haye

Optical gyroscopes based on the Sagnac effect have been the mainstay of inertial navigation in aerospace and shipping for decades. These gyroscopes are typically realized either as ring-laser gyroscopes (RLGs) or fiber-optic gyroscopes (FOGs). With the recent rapid progress in the field of ultrahigh-quality optical whispering-gallery mode and ring microresonators, attention has been focused on the development of microresonator-based Sagnac gyroscopes as a more compact alternative to RLGs and FOGs. One avenue that has been explored is the use of exceptional points in non-Hermitian systems to enhance the responsivity to rotation. We use a similar phenomenon, namely, the critical point of a spontaneous symmetry-breaking transition between counterpropagating light, to demonstrate a microresonator gyroscope with a responsivity enhanced by a factor of around 10(4). We present a proof-of-principle rotation measurement as well as a characterization of the system's dynamical response, which shows the universal critical behaviors of responsivity enhancement and critical slowing down, both of which are beneficial in an optical gyroscope. We believe that this concept could be used to realize simple and cheap chip-based gyroscopes with sensitivities approaching those of today's RLGs and FOGs. (C) 2021 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

Deep recurrent networks predicting the gap evolution in adiabatic quantum computing

Naeimeh Mohseni, Carlos Navarrete-Benlloch, Tim Byrnes, Florian Marquardt

One of the main challenges in quantum physics is predicting efficiently the dynamics of observables in many-body problems out of equilibrium. A particular example occurs in adiabatic quantum computing, where finding the structure of the instantaneous gap of the Hamiltonian is crucial in order to optimize the speed of the computation. Inspired by this challenge, in this work we explore the potential of deep learning for discovering a mapping from the parameters that fully identify a problem Hamiltonian to the full evolution of the gap during an adiabatic sweep applying different network architectures. Through this example, we find that a limiting factor for the learnability of the dynamics is the size of the input, that is, how the number of parameters needed to identify the Hamiltonian scales with the system size. We demonstrate that a long short-term memory network succeeds in predicting the gap when the parameter space scales linearly with system size. Remarkably, we show that once this architecture is combined with a convolutional neural network to deal with the spatial structure of the model, the gap evolution can even be predicted for system sizes larger than the ones seen by the neural network during training. This provides a significant speedup in comparison with the existing exact and approximate algorithms in calculating the gap.

Dynamical phase transitions in quantum spin models with antiferromagnetic long-range interactions

Jad C. Halimeh, Maarten Van Damme, Lingzhen Guo, Johannes Lang, Philipp Hauke

In recent years, dynamical phase transitions and out-of-equilibrium criticality have been at the forefront of ultracold gases and condensed matter research. Whereas universality and scaling are established topics in equilibrium quantum many-body physics, out-of-equilibrium extensions of such concepts still leave much to be desired. Using exact diagonalization and the time-dependent variational principle in uniform matrix product states, we calculate the time evolution of the local order parameter and Loschmidt return rate in transverse-field Ising chains with antiferromagnetic power law-decaying interactions, and map out the corresponding rich dynamical phase diagram. Anomalous cusps in the return rate, which are ubiquitous at small quenches within the ordered phase in the case of ferromagnetic long-range interactions, are absent within the accessible timescales of our simulations in the antiferromagnetic case, showing that long-range interactions are not a sufficient condition for their appearance. We attribute this to much weaker domain-wall binding in the antiferromagnetic case. For quenches across the quantum critical point, regular cusps appear in the return rate and connect to the local order parameter changing sign, indicating the concurrence of two major concepts of dynamical phase transitions. Our results consolidate conclusions of previous works that a necessary condition for the appearance of anomalous cusps in the return rate after quenches within the ordered phase is for topologically trivial local spin flips to be the energetically dominant excitations in the spectrum of the quench Hamiltonian. Our findings are readily accessible in modern trapped-ion setups and we outline the associated experimental considerations.

Engineering long-lived vibrational states for an organic molecule

Burak Gürlek, Vahid Sandoghdar, Diego-Martin Cano

The optomechanical character of molecules was discovered by Raman about one century ago. Today, molecules are promising contenders for high-performance quantum optomechanical platforms because their small size and large energy-level separations make them intrinsically robust against thermal agitations. Moreover, the precision and throughput of chemical synthesis can ensure a viable route to quantum technological applications. The challenge, however, is that the coupling of molecular vibrations to environmental phonons limits their coherence to picosecond time scales. Here, we improve the optomechanical quality of a molecule by several orders of magnitude through phononic engineering of its surrounding. By dressing a molecule with long-lived high-frequency phonon modes of its nanoscopic environment, we achieve storage and retrieval of photons at millisecond time scales and allow for the emergence of single-photon strong coupling in optomechanics. Our strategy can be extended to the realization of molecular optomechanical networks.

Matrix stiffness mechanosensing modulates the expression and distribution of transcription factors in Schwann cells

Gonzalo Rosso, Daniel Wehner, Christine Schweitzer, Stephanie Möllmert, Elisabeth Sock, Jochen Guck, Victor Shahin

After peripheral nerve injury, mature Schwann cells (SCs) de-differentiate and undergo cell reprogramming to convert into a specialized cell repair phenotype that promotes nerve regeneration. Reprogramming of SCs into the repair phenotype is tightly controlled at the genome level and includes downregulation of pro-myelinating genes and activation of nerve repair-associated genes. Nerve injuries induce not only biochemical but also mechanical changes in the tissue architecture which impact SCs. Recently, we showed that SCs mechanically sense the stiffness of the extracellular matrix and that SC mechanosensitivity modulates their morphology and migratory behavior. Here, we explore the expression levels of key transcription factors and myelin-associated genes in SCs, and the outgrowth of primary dorsal root ganglion (DRG) neurites, in response to changes in the stiffness of generated matrices. The selected stiffness range matches the physiological conditions of both utilized cell types as determined in our previous investigations. We find that stiffer matrices induce upregulation of the expression of transcription factors Sox2, Oct6, and Krox20, and concomitantly reduce the expression of the repair-associated transcription factor c-Jun, suggesting a link between SC substrate mechanosensing and gene expression regulation. Likewise, DRG neurite outgrowth correlates with substrate stiffness. The remarkable intrinsic physiological plasticity of SCs, and the mechanosensitivity of SCs and neurites, may be exploited in the design of bioengineered scaffolds that promote nerve regeneration upon injury.

Dynamical Backaction Magnomechanics

Clinton A. Potts, Emil Varga, Victor A. S. V. Bittencourt, Silvia Viola-Kusminskiy, John P. Davis

Dynamical backaction resulting from radiation pressure forces in optomechanical systems has proven to be a versatile tool for manipulating mechanical vibrations. Notably, dynamical backaction has resulted in the cooling of a mechanical resonator to its ground state, driving phonon lasing, the generation of entangled states, and observation of the optical-spring effect. In certain magnetic materials, mechanical vibrations can interact with magnetic excitations (magnons) via the magnetostrictive interaction, resulting in an analogous magnon-induced dynamical backaction. In this article, we directly observe the impact of magnon-induced dynamical backaction on a spherical magnetic sample’s mechanical vibrations. Moreover, dynamical backaction effects play a crucial role in many recent theoretical proposals; thus, our work provides the foundation for future experimental work pursuing many of these theoretical proposals.

All-Optical Generation of Antiferromagnetic Magnon Currents via the Magnon Circular Photogalvanic Effect

Emil Viñas Boström, Tahereh S. Parvini, James W. McIver, Angel Rubio, Silvia Viola-Kusminskiy, Michael A. Sentef

We introduce the magnon circular photogalvanic effect enabled by two-magnon Raman scattering. This provides an all-optical pathway to the generation of directed magnon currents with circularly polarized light in honeycomb antiferromagnetic insulators. The effect is the leading order contribution to magnon photocurrent generation via optical fields. Control of the magnon current by the polarization and angle of incidence of the laser is demonstrated. Experimental detection by sizable inverse spin Hall voltages in platinum contacts is proposed.

Certification of Genuine Multipartite Entanglement with General and Robust Device-independent Witnesses

Chao Zhang, Wen-Hao Zhang, Pavel Sekatski, Jean-Daniel Bancal, Michael Zwerger, Peng Yin, Gong-Chu Li, Xing-Xiang Peng, Lei Chen, et al.

Genuine multipartite entanglement represents the strongest type of entanglement, which is an essential resource for quantum information<br>processing. Standard methods to detect genuine multipartite entanglement, e.g., entanglement witnesses, state tomography, or quantum state verification, require full knowledge of the Hilbert space dimension and precise calibration of measurement devices, which are usually difficult to acquire in an experiment. The most radical way to overcome these problems is to detect<br>entanglement solely based on the Bell-like correlations of measurement outcomes collected in the experiment, namely, device-independently (DI). However, it is difficult to certify genuine entanglement of practical multipartite states in<br>this way, and even more difficult to quantify it, due to the difficulty to identify optimal multipartite Bell inequalities and protocols tolerant to state impurity. In this work, we explore a general and robust DI method which can be applied to various realistic multipartite quantum state in arbitrary finite dimension, while merely relying on bipartite Bell inequalities. Our method allows us both to certify the presence of genuine multipartite entanglement and to quantify it. Several important classes of entangled states are tested with this method, leading to the detection of genuinely entangled states. We also certify genuine multipartite entanglement in weakly-entangled GHZ states, thus showing that the method applies equally well to less standard states.

Channel discord and distortion

Wei-Wei Zhang, Yuval R. Sanders, Barry C. Sanders

Discord, originally notable as a signature of bipartite quantum correlation, in fact can be nonzero<br>classically, i.e. arising from noisy measurements by one of the two parties. Here we redefine<br>classical discord to quantify channel distortion, in contrast to the previous restriction of classical<br>discord to a state, and we then show a monotonic relationship between classical (channel) discord<br>and channel distortion. We show that classical discord is equivalent to (doubly stochastic) channel<br>distortion by numerically discovering a monotonic relation between discord and total-variation<br>distance for a bipartite protocol with one party having a noiseless channel and the other party<br>having a noisy channel. Our numerical method includes randomly generating doubly stochastic<br>matrices for noisy channels and averaging over a uniform measure of input messages. Connecting<br>discord with distortion establishes discord as a signature of classical, not quantum, channel<br>distortion.

Perturbation theory of nearly spherical dielectric optical resonators

Julius Gohsrich, Tirth Shah, Andrea Aiello

Dielectric spheres of various sizes may sustain electromagnetic whispering-gallery modes resonating at optical frequencies with very narrow linewidths. Arbitrary small deviations from the spherical shape typically shift and broaden such resonances. Our goal is to determine these shifted and broadened resonances. A boundary-condition perturbation theory for the acoustic vibrations of nearly circular membranes was developed by Rayleigh more than a century ago. We extend this theory to describe the electromagnetic excitations of nearly spherical dielectric cavities. This approach permits us to avoid dealing with decaying quasinormal modes. We explicitly find the frequencies and the linewidths of the optical resonances for arbitrarily deformed nearly spherical dielectric cavities, as power series expansions by a small parameter, up to and including second-order terms. We thoroughly discuss the physical conditions for the applicability of perturbation theory.

Optical signatures of the coupled spin-mechanics of a levitated magnetic microparticle

Vanessa Wachter, Victor A. S. V. Bittencourt, Shangran Xie, Sanchar Sharma, Nicolas Joly, Philip Russell, Florian Marquardt, Silvia Viola-Kusminskiy

We propose a platform that combines the fields of cavity optomagnonics and levitated optome-<br>chanics in order to control and probe the coupled spin-mechanics of magnetic dielectric particles. We theoretically study the dynamics of a levitated Faraday-active dielectric microsphere serving as an optomagnonic cavity, placed in an external magnetic field and driven by an external laser. We find that the optically driven magnetization dynamics induces angular oscillations of the particle with low associated damping. Further, we show that the magnetization and angular motion dynamics<br>can be probed via the power spectrum of the outgoing light. Namely, the characteristic frequencies attributed to the angular oscillations and the spin dynamics are imprinted in the light spectrum by two main resonance peaks. Additionally, we demonstrate that a ferromagnetic resonance setup with an oscillatory perpendicular magnetic field can enhance the resonance peak corresponding to<br>the spin oscillations and induce fast rotations of the particle around its anisotropy axis.

Fiber-based biphoton source with ultrabroad frequency tunability

Santiago López-Huidrobro, Markus Lippl, Nicolas Joly, Maria Chekhova

Tunable biphotons are highly important for a wide range of quantum applications. For some applications, especially interesting are cases where two photons of a pair are far apart in frequency. Here, we report a tunable biphoton source based on a xenon-filled hollow-core photonic crystal fiber. Tunability is achieved by adjusting the pressure of the gas inside the fiber. This allows us to tailor the dispersion landscape of the fiber, overcoming the principal limitations of solid-core fiber-based biphoton sources. We report a maximum tunability of 120 THz for a pressure range of 4 bar with a continuous shift of 30 THz/bar. At 21 bar, the photons of a pair are separated by more than one octave. Despite the large separation, both photons have large bandwidths. At 17 bar, they form a very broad (110 THz) band around the frequency of the pump.

Molecular polaritonics in dense mesoscopic disordered ensembles

Christian Sommer, Michael Reitz, Francesca Mineo, Claudiu Genes

We study the dependence of the vacuum Rabi splitting (VRS) on frequency disorder, vibrations, near-field effects, and density in molecular polaritonics. In the mesoscopic limit, static frequency disorder alone can already introduce a loss mechanism from polaritonic states into a dark state reservoir, which we quantitatively describe, providing an analytical scaling of the VRS with the level of disorder. Disorder additionally can split a molecular ensemble into donor-type and acceptor-type molecules and the combination of vibronic coupling, dipole-dipole interactions, and vibrational relaxation induces an incoherent FRET (Förster resonance energy transfer) migration of excitations within the collective molecular state. This is equivalent to a dissipative disorder and has the effect of saturating and even reducing the VRS in the mesoscopic, high-density limit. Overall, this analysis allows to quantify the crucial role played by dark states in cavity quantum electrodynamics with mesoscopic, disordered ensembles.

Physical phenotype of blood cells is altered in COVID-19

Markéta Kubánková, Bettina Hohberger, Jakob Hoffmanns, Julia Fürst, Martin Herrmann, Jochen Guck, Martin Kräter

Clinical syndrome coronavirus disease 2019 (COVID-19) induced by severe acute respiratory syndrome coronavirus 2 is characterized by rapid spreading and high mortality worldwide. Although the pathology is not yet fully understood, hyperinflammatory response and coagulation disorders leading to congestions of microvessels are considered to be key drivers of the still-increasing death toll. Until now, physical changes of blood cells have not been considered to play a role in COVID-19 related vascular occlusion and organ damage. Here, we report an evaluation of multiple physical parameters including the mechanical features of five frequent blood cell types, namely erythrocytes, lymphocytes, monocytes, neutrophils, and eosinophils. More than four million blood cells of 17 COVID-19 patients at different levels of severity, 24 volunteers free from infectious or inflammatory diseases, and 14 recovered COVID-19 patients were analyzed. We found significant changes in lymphocyte stiffness, monocyte size, neutrophil size and deformability, and heterogeneity of erythrocyte deformation and size. Although some of these changes recovered to normal values after hospitalization, others persisted for months after hospital discharge, evidencing the long-term imprint of COVID-19 on the body.

Analytic Design of Accelerated Adiabatic Gates in Realistic Qubits: General Theory and Applications to Superconducting Circuits

F Setiawan, Peter Groszkowski, Hugo Ribeiro, Aashish A Clerk

Shortcuts to adiabaticity (STA) is a general methodology for speeding up adiabatic quantumprotocols, and has many potential applications in quantum information processing. Unfortunately,analytically constructing STAs for systems having complex interactions and more than a few levelsis a challenging task. This is usually overcome by assuming an idealized Hamiltonian (e.g., only alimited subset of energy levels are retained, and the rotating-wave approximation (RWA) is made).Here, we develop ananalyticapproach that allows one to go beyond these limitations. Our methodis general and results in analytically-derived pulse shapes that correct both non-adiabatic errorsas well as non-RWA errors. We also show that our approach can yield pulses requiring a smallerdriving power than conventional non-adiabatic protocols. We show in detail how our ideas can beused to analytically design high-fidelity single-qubit “tripod” gates in a realistic superconductingfluxonium qubit.

suggested by editors

Specialty Photonic Crystal Fibers and Their Applications

David Novoa, Nicolas Joly

This year not only commemorates the 60th anniversary of nonlinear optics with the seminal experiment of second harmonic generation, but it is also the 30th anniversary of the invention of the photonic crystal fiber (PCF). Following their first practical demonstration in 1996, PCFs have rapidly evolved into an established platform for applications in both academic and industrial environments. Their unique ability to confine light in a far more versatile way than possible with conventional optical fibers facilitated the expansion of the multifaceted world of PCF to cover not only nonlinear optics, but also many other disparate fields such as interferometry, beam delivery, laser science, telecommunications, quantum optics, sensing, microscopy, and many others.

Quantum technologies in space

Rainer Kaltenbaek, Antonio Acin, Laszlo Bacsardi, Paolo Bianco, Philippe Bouyer, Eleni Diamanti, Christoph Marquardt, Yasser Omar, Valerio Pruneri, et al.

Recently, the European Commission supported by many European countries has announced large investments towards the commercialization of quantum technology (QT) to address and mitigate some of the biggest challenges facing today’s digital era – e.g. secure communication and computing power. For more than two decades the QT community has been working on the development of QTs, which promise landmark breakthroughs leading to commercialization in various areas. The ambitious goals of the QT community and expectations of EU authorities cannot be met solely by individual initiatives of single countries, and therefore, require a combined European effort of large and unprecedented dimensions comparable only to the Galileo or Copernicus programs. Strong international competition calls for a coordinated European effort towards the development of QT in and for space, including research and development of technology in the areas of communication and sensing. Here, we aim at summarizing the state of the art in the development of quantum technologies which have an impact in the field of space applications. Our goal is to outline a complete framework for the design, development, implementation, and exploitation of quantum technology in space.

HIF2α is a Direct Regulator of Neutrophil Motility

Sundary Sormendi, Mathieu Deygas, Anupam Sinha, Anja Krüger, Ioannis Kourtzelis, Gregoire Le Lay, Mathilde Bernard, Pablo J. Sáez, Michael Gerlach, et al.

Orchestrated recruitment of neutrophils to inflamed tissue is essential during initiation of inflammation. Inflamed areas are usually hypoxic, and adaptation to reduced oxygen pressure is typically mediated by hypoxia pathway proteins. However, it is still unclear how these factors influence the migration of neutrophils to and at the site of inflammation either during their transmigration through the blood-endothelial cell barrier, or their motility in the interstitial space. Here, we reveal that activation of the Hypoxia Inducible Factor-2 (HIF2α) due to deficiency of HIF-prolyl hydroxylase domain protein-2 (PHD2) boosts neutrophil migration specifically through highly confined microenvironments. In vivo, the increased migratory capacity of PHD2-deficient neutrophils resulted in massive tissue accumulation in models of acute local inflammation. Using systematic RNAseq analyses and mechanistic approaches, we identified RhoA, a cytoskeleton organizer, as the central downstream factor that mediates HIF2α-dependent neutrophil motility. Thus, we propose that the here identified novel PHD2-HIF2α-RhoA axis is vital to the initial stages of inflammation as it promotes neutrophil movement through highly confined tissue landscapes.

Picosecond acoustic dynamics in stimulated Brillouin scattering

Johannes Piotrowski, Mikołaj K Schmidt, Birgit Stiller, Christopher G. Poulton, Michael Steel

Recent experiments demonstrating storage of optical pulses in acoustic phonons via stimulated Brillouin scattering raise questions about the spectral and temporal capacities of such protocols and the limitations of the theoretical frameworks routinely used to describe them. We consider the dynamics of photon-phonon scattering induced by optical pulses with temporal widths comparable to the period of acoustic oscillations. We revisit the widely adopted classical formalism of coupled modes and demonstrate its breakdown. We use a simple extension to the formulation and find potentially measurable consequences in the dynamics of Brillouin experiments involving ultrashort pulses. (C) 2021 Optical Society of America

Rapid Exploration of Topological Band Structures using Deep Learning

Vittorio Peano, Florian Sapper, Florian Marquardt

The design of periodic nanostructures allows to tailor the transport of photons, phonons, and matter waves for specific applications. Recent years have seen a further expansion of this field by engineering topological properties. However, what is missing currently are efficient ways to rapidly explore and optimize band structures and to classify their topological characteristics for arbitrary unit-cell geometries. In this work, we show how deep learning can address this challenge. We introduce an approach where a neural network first maps the geometry to a tight-binding model. The tight-binding model encodes not only the band structure but also the symmetry properties of the Bloch waves. This allows us to rapidly categorize a large set of geometries in terms of their band representations, identifying designs for fragile topologies. We demonstrate that our method is also suitable to calculate strong topological invariants, even when (like the Chern number) they are not symmetry indicated. Engineering of domain walls and optimization are accelerated by orders of magnitude. Our method directly applies to any passive linear material, irrespective of the symmetry class and space group. It is general enough to be extended to active and nonlinear metamaterials.

A unique macrophage subpopulation signals directly to progenitor cells to promote regenerative neurogenesis in the zebrafish spinal cord

Leonardo Cavone, Tess McCann, Louisa K. Drake, Erika A. Aguzzi, Ana-Maria Oprisoreanu, Elisa Pedersen, Soe Sandi, Jathurshan Selvarajah, Themistoklis M. Tsarouchas, et al.

Central nervous system injury re-initiates neurogenesis in anamniotes (amphibians and fishes), but not in mammals. Activation of the innate immune system promotes regenerative neurogenesis, but it is fundamentally unknown whether this is indirect through the activation of known developmental signaling pathways or whether immune cells directly signal to progenitor cells using mechanisms that are unique to regeneration. Using single-cell RNA-seq of progenitor cells and macrophages, as well as cell-type-specific manipulations, we provide evidence for a direct signaling axis from specific lesion-activated macrophages to spinal progenitor cells to promote regenerative neurogenesis in zebrafish. Mechanistically, TNFa from pro-regenerative macrophages induces Tnfrsf1a-mediated AP-1 activity in progenitors to increase regeneration-promoting expression of hdac1 and neurogenesis. This establishes the principle that macrophages directly communicate to spinal progenitor cells via non-developmental signals after injury, providing potential targets for future interventions in the regeneration-deficient spinal cord of mammals.

Synthesis and dissociation of soliton molecules in parallel optical-soliton reactors

W He, M Pang, D.-H. Yeh, J Huang, Philip St. J. Russell

Mode-locked lasers have been widely used to explore interactions between optical solitons, including bound-soliton<br>states that may be regarded as “photonic molecules”. Conventional mode-locked lasers normally, however, host at<br>most only a few solitons, which means that stochastic behaviours involving large numbers of solitons cannot easily be<br>studied under controlled experimental conditions. Here we report the use of an optoacoustically mode-locked fibre<br>laser to create hundreds of temporal traps or “reactors” in parallel, within each of which multiple solitons can be<br>isolated and controlled both globally and individually using all-optical methods. We achieve on-demand synthesis and<br>dissociation of soliton molecules within these reactors, in this way unfolding a novel panorama of diverse dynamics in<br>which the statistics of multi-soliton interactions can be studied. The results are of crucial importance in understanding<br>dynamical soliton interactions and may motivate potential applications for all-optical control of ultrafast light fields in<br>optical resonators.

Scaling rules for high quality soliton self-compression in hollow-core fibers

Daniel Schade, Felix Köttig, Johannes Köhler, Michael H. Frosz, Philip St.J. Russell, Francesco Tani

Soliton dynamics can be used to temporally compress laser pulses to few fs durations in many different spectral regions. Here we study analytically, numerically and experimentally the scaling of soliton dynamics in noble gas-filled hollow-core fibers. We identify an optimal parameter region, taking account of higher-order dispersion, photoionization, self-focusing, and modulational instability. Although for single-shots the effects of photoionization can be reduced by using lighter noble gases, they become increasingly important as the repetition rate rises. For the same optical nonlinearity, the higher pressure and longer diffusion times of the lighter gases can considerably enhance the long-term effects of ionization, as a result of pulse-by-pulse buildup of refractive index changes. To illustrate the counter-intuitive nature of these predictions, we compressed 250 fs pulses at 1030 nm in an 80-cm-long hollow-core photonic crystal fiber (core radius 15 µm) to ∼5 fs duration in argon and neon, and found that, although neon performed better at a repetition rate of 1 MHz, stable compression in argon was still possible up to 10 MHz.

Online Monitoring of Microscale Liquid-Phase Catalysis Using in-Fiber Raman Spectroscopy

Florian Schorn, Manfred Aubermann, Richard Zeltner, Marco Haumann, Nicolas Y. Joly

We report on the use of hollow-core photonic crystal fibers to monitor the evolution of chemical reactions. The combination of tight confinement and long interaction length allows single-pass spectroscopic measurements using less than a microliter volume of chemicals with good accuracy. As a proof of principle, we used here nonlinear Raman spectroscopy for a reaction screening of the acidic catalyzed esterification of methanol and acetic acid.

Know How to Regrow-Axon Regeneration in the Zebrafish Spinal Cord

Vasiliki Tsata, Daniel Wehner

The capacity for long-distance axon regeneration and functional recovery after spinal cord injury is poor in mammals but remarkable in some vertebrates, including fish and salamanders. The cellular and molecular basis of this interspecies difference is beginning to emerge. This includes the identification of target cells that react to the injury and the cues directing their pro-regenerative responses. Among existing models of successful spinal cord regeneration, the zebrafish is arguably the most understood at a mechanistic level to date. Here, we review the spinal cord injury paradigms used in zebrafish, and summarize the breadth of neuron-intrinsic and -extrinsic factors that have been identified to play pivotal roles in the ability of zebrafish to regenerate central nervous system axons and recover function.

Machine Learning and Quantum Devices

Florian Marquardt

These brief lecture notes cover the basics of neural networks and deep learning as well as their applications in the quantum domain, for physicists without prior knowledge. In the first part, we describe training using back-propagation, image classification, convolutional networks and autoencoders.The second part is about advanced techniques like reinforcement learning (for discovering control strategies), recurrent neural networks (for analyzing timetraces), and Boltzmann machines (for learning probability distributions). In the third lecture, we discuss first recent applications to quantum physics, with an emphasis on quantum information processing machines. Finally, the fourth lecture is devoted to the promise of using quantum effects to accelerate machine learning.

Efficient and gentle delivery of molecules into cells with different elasticity via Progressive Mechanoporation

Alena Uvizl, Ruchi Goswami, Shanil Durgeshkumar Gandhi, Martina Augsburg, Frank Buchholz, Jochen Guck, Jörg Mansfeld, Salvatore Girardo

On Quantum Efficiency Measurements and Plasmonic Nano-Antennas

Korenobu Matsuzaki, Hsuan-Wei Liu, Stephan Götzinger, Vahid Sandoghdar

Quantum efficiency is a key quantity that describes the performance of light-emitting materials and is, thus, an important metric for assessing novel nanophotonic systems. This Perspective provides a concise discussion of the difficulties encountered in the characterization of quantum efficiencies, especially for studies that involve single emitters. In particular, we review various approaches that have been recently used for determining quantum efficiencies of emitters coupled to plasmonic antennas and highlight the subtleties and challenges that hinder precise measurements.

Renormalized Mutual Information for Artificial Scientific Discovery

Leopoldo Sarra, Andrea Aiello, Florian Marquardt

We derive a well-defined renormalized version of mutual information that allows to estimate the dependence between continuous random variables in the important case when one is deterministically dependent on the other. This is the situation relevant for feature extraction, where the goal is to produce a low-dimensional effective description of a high-dimensional system. Our approach enables the discovery of collective variables in physical systems, thus adding to the toolbox of artificial scientific discovery, while also aiding the analysis of information flow in artificial neural networks.

Rapid computational cell-rotation around arbitrary axes in 3D with multi-core fiber

Jiawei Sun, Nektarios Koukourakis, Jochen Guck, Jürgen W. Czarske

Optical trapping is a vital tool in biology, allowing precise optical manipulation of nanoparticles, micro-robots, and cells. Due to the low risk of photodamage and high trap stiffness, fiber-based dual-beam traps are widely used for optical manipulation of large cells. Besides trapping, advanced applications like 3D refractive index tomography need a rotation of cells, which requires precise control of the forces, for example, the acting-point of the forces and the intensities in the region of interest (ROI). A precise rotation of large cells in 3D about arbitrary axes has not been reported yet in dual-beam traps. We introduce a novel dual-beam optical trap in which a multi-core fiber (MCF) is transformed to a phased array, using wavefront shaping and computationally programmable light. The light-field distribution in the trapping region is holographically controlled within 0.1 s, which determines the orientation and the rotation axis of the cell with small retardation. We demonstrate real-time controlled rotation of HL60 cells about all 3D axes with a very high degree of freedom by holographic controlled light through an MCF with a resolution close to the diffraction limit. For the first time, the orientation of the cell can be precisely controlled about all 3D axes in a dual-beam trap. MCFs provide much higher flexibility beyond the bulky optics, enabling lab-on-a-chip applications and can be easily integrated for applications like contactless cell surgery, refractive index tomography, cell-elasticity measurement, which require precise 3D manipulation of cells.

Overcoming detection loss and noise in squeezing-based optical sensing

Gaetano Frascella, Sascha Agne, Farid Ya. Khalili, Maria V. Chekhova

Among the known resources of quantum metrology, one of the most practical and efficient is squeezing. Squeezed states of atoms and light improve the sensing of the phase, magnetic field, polarization, mechanical displacement. They promise to considerably increase signal-to-noise ratio in imaging and spectroscopy, and are already used in real-life gravitational-wave detectors. But despite being more robust than other states, they are still very fragile, which narrows the scope of their application. In particular, squeezed states are useless in measurements where the detection is inefficient or the noise is high. Here, we experimentally demonstrate a remedy against loss and noise: strong noiseless amplification before detection. This way, we achieve loss-tolerant operation of an interferometer fed with squeezed and coherent light. With only 50% detection efficiency and with noise exceeding the level of squeezed light more than 50 times, we overcome the shot-noise limit by 6 dB. Sub-shot-noise phase sensitivity survives up to 87% loss. Application of this technique to other types of optical sensing and imaging promises a full use of quantum resources in these fields.

Intrinsic Sensitivity Limits for Multiparameter Quantum Metrology

Aaron Z. Goldberg, Luis Sanchez-Soto, Hugo Ferretti

The quantum Cramér-Rao bound is a cornerstone of modern quantum metrology, as it provides the ultimate precision in parameter estimation. In the multiparameter scenario, this bound becomes a matrix inequality, which can be cast to a scalar form with a properly chosen weight matrix. Multiparameter estimation thus elicits tradeoffs in the precision with which each parameter<br>can be estimated. We show that, if the information is encoded in a unitary transformation, we can naturally choose the weight matrix as the metric tensor<br>linked to the geometry of the underlying algebra su(n). This ensures an intrinsic bound that is independent of the choice of parametrization.<br>

Error suppression in adiabatic quantum computing with qubit ensembles

Naeimeh Mohseni, Marek Narozniak, Alexey N Pyrkov, Valentin Ivannikov, Jonathan P Dowling

Incorporating protection against quantum errors into adiabatic quantum computing (AQC) is an important task due to the inevitable presence of decoherence. Here, we investigate an error-protected encoding of the AQC Hamiltonian, where qubit ensembles are used in place of qubits. Our Hamiltonian only involves total spin operators of the ensembles, offering a simpler route towards error-corrected quantum computing. Our scheme is particularly suited to neutral atomic gases where it is possible to realize large ensemble sizes and produce ensemble-ensemble entanglement. We identify a critical ensemble size Nc where the nature of the first excited state becomes a single particle perturbation of the ground state, and the gap energy is predictable by mean-field theory. For ensemble sizes larger than Nc, the ground state becomes protected due to the presence of logically equivalent states and the AQC performance improves with N, as long as the decoherence rate is sufficiently low.

Single organic molecules for photonic quantum technologies

C. Toninelli, I. Gerhardt, A.S. Clark, A. Reserbat-Plantey, Stephan Götzinger, Z. Ristanovic, M. Colautti, P. Lombardi, K.D. Major, et al.

Isolating single molecules in the solid state has allowed fundamental experiments in basic and applied sciences. When cooled down to liquid helium temperature, certain molecules show transition lines, that are tens of megahertz wide, limited only by the excited state lifetime. The extreme flexibility in the synthesis of organic materials provides, at low costs, a wide palette of emission wavelengths and supporting matrices for such single chromophores. In the last decades, the controlled coupling to photonic structures has led to an optimized interaction efficiency with light. Molecules can hence be operated as single photon sources and as non-linear elements with competitive performance in terms of coherence, scalability and compatibility with diverse integrated platforms. Moreover, they can be used as transducers for the optical read-out of fields and material properties, with the promise of single-quanta resolution in the sensing of charges and motion. We show that quantum emitters based on single molecules hold promise to play a key role in the development of quantum science and technologies.

Photon Pairs from Resonant Metasurfaces

Tomas Santiago-Cruz, Anna Fedotova, Vitaliy Sultanov, Maximilian A. Weissflog, Dennis Arslan, Mohammadreza Younesi, Thomas Pertsch, Isabelle Staude, Frank Setzpfandt, et al.

All-dielectric optical metasurfaces are a workhorse in nano-optics, because of both their ability to manipulate light in different degrees of freedom and their excellent performance at light frequency conversion. Here, we demonstrate first-time generation of photon pairs via spontaneous parametric-down conversion in lithium niobate quantum optical metasurfaces with electric and magnetic Mie-like resonances at various wavelengths. By engineering the quantum optical metasurface, we tailor the photon-pair spectrum in a controlled way. Within a narrow bandwidth around the resonance, the rate of pair production is enhanced up to 2 orders of magnitude, compared to an unpatterned film of the same thickness and material. These results enable flat-optics sources of entangled photons—a new promising platform for quantum optics experiments.

Multimode optical parametric amplification in the phase-sensitive regime

Gaetano Frascella, R. V. Zakharov, O. V. Tikhonova, Maria V. Chekhova

Phase-sensitive optical parametric amplification of squeezed states helps to overcome detection loss and noise and thus increases the robustness of sub-shot-noise sensing. Because such techniques, e.g., imaging and spectroscopy, operate with multimode light, multimode amplification is required. Here we find the optimal methods for multimode phase-sensitive amplification and verify them in an experiment where a pumped second-order nonlinear crystal is seeded with a Gaussian coherent beam. Phase-sensitive amplification is obtained by tightly focusing the seed into the crystal, rather than seeding with close-to-plane waves. This suggests that phase-sensitive amplification of sub-shot-noise images should be performed in the near field. A similar recipe can be formulated for the time and frequency, which makes this work relevant for quantum-enhanced spectroscopy.

Doppler optical frequency domain reflectometry for remote fiber sensing

Max Koeppel, Abhinav Sharma, Jasper Podschus, Sanju Sundaramahalingam, Nicolas Y. Joly, Shangran Xie, Philip Russell, Bernhard Schmauss

Coherent optical frequency domain reflectometry has been widely used to locate static reflectors with high spatial resolution. Here, we present a new type of Doppler optical frequency domain reflectometry that offers simultaneous measurement of the position and speed of moving objects. The system is exploited to track optically levitated "flying" particles inside a hollow-core photonic crystal fiber. As an example, we demonstrate distributed temperature sensing with sub-mm-scale spatial resolution and a standard deviation of similar to 10 degrees C up to 200 degrees C. (C) 2021 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

Depth encoded input polarisation independent swept source cross-polarised optical coherence tomography probe

Katharina Blessing, Judith Schirmer, Asha Parmar, Kanwarpal Singh

Within the last decades, several studies have been published that prove the benefit of polarisation sensitive optical coherence (psOCT) tomography for the field of biomedical diagnostics. However, polarisation sensitive imaging typically requires careful control of the polarisation state of the input illumination, which leads to bulky and delicate systems. While psOCT provides quantitative information, it is mostly sufficient to analyse the images qualitatively in the field of biomedical diagnostics. Therefore, a reduced form of this technique, cross-polarised optical coherence tomography (cpOCT), moves into the focus of interest that serves to visualise the birefringence properties of a sample. Despite the low requirements for the illumination's polarisation, most of the proposed systems still include complex illumination control mechanisms. Here, we propose a common path probe based endoscopic system with an lateral resolution of 30 µm and a sensitivity of 103 dB comprising a commercially available swept-source OCT system and a free-space module which does not require any polarisation controlling elements. A Faraday mirror substitutes the complex polarisation control apparatus. We demonstrate the independence of the approach from the polarisation state of the light source by monitoring the illumination power in the orthogonal channels while varying the source polarisation. Furthermore, we validate the ability of the system to reveal the birefringence properties of different samples, starting from a quarter-wave plate, since its properties are fully characterised. Additionally, we present imaging results from several tissues to demonstrate its feasibility for the field of biomedical diagnostics.

Toward deep biophysical cytometry: prospects and challenges

Kelvin C.M. Lee, Jochen Guck, Keisuke Goda, Kevin K. Tsia

The biophysical properties of cells reflect their identities, underpin their homeostatic<br>state in health, and define the pathogenesis of disease. Recent leapfrogging<br>advances in biophysical cytometry now give access to this information,<br>which is obscured in molecular assays, with a discriminative power that was<br>once inconceivable. However, biophysical cytometry should go 'deeper' in<br>terms of exploiting the information-rich cellular biophysical content, generating<br>a molecular knowledge base of cellular biophysical properties, and standardizing<br>the protocols for wider dissemination. Overcoming these barriers, which<br>requires concurrent innovations in microfluidics, optical imaging, and computer<br>vision, could unleash the enormous potential of biophysical cytometry not only<br>for gaining a new mechanistic understanding of biological systems but also for<br>identifying new cost-effective biomarkers of disease.

Efficient self-compression of ultrashort near-UV pulses in air-filled hollow-core photonic crystal fibers

Jie Luan, Philip St. J. Russell, David Novoa

We report generation of ultrashort near-UV pulses by soliton self-compression in kagomé-style hollow-core photonic crystal fibers filled with ambient air. Pump pulses with the energy of 2.6 µJ and duration of 54 fs at 400 nm were compressed temporally by a factor of 5, to a duration of ∼11 fs. The experimental results are supported by numerical simulations, showing that both Raman and Kerr effects play a role in the compression dynamics. The convenience of using ambient air and the absence of glass windows that would distort the compressed pulses makes the setup highly attractive as the basis of an efficient table-top UV pulse compressor.

Microsphere kinematics from the polarization of tightly focused nonseparable light

Stefan Berg-Johansen, Martin Neugebauer, Andrea Aiello, Gerd Leuchs, Peter Banzer, Christoph Marquardt

Recently, it was shown that vector beams can be utilized for fast kinematic sensing via measurements of their global polarization state [Optica 2, 864 (2015)]. The method relies on correlations between the spatial and polarization degrees of freedom of the illuminating field which result from its nonseparable mode structure. Here, we extend the method to the nonparaxial regime. We study experimentally and theoretically the far-field polarization state generated by the scattering of a dielectric microsphere in a tightly focused vector beam as a function of the particle position. Using polarization measurements only, we demonstrate position sensing of a Mie particle in three dimensions. Our work extends the concept of back focal plane interferometry and highlights the potential of polarization analysis in optical tweezers employing structured light.

Microsphere kinematics from the polarization of tightly focused nonseparable light

Stefan Berg-Johansen, Martin Neugebauer, Andrea Aiello, Gerd Leuchs, Peter Banzer, Christoph Marquardt

Recently, it was shown that vector beams can be utilized for fast kinematic sensing via measurements of their global polarization state [Optica 2(10), 864 (2015)]. The method relies on correlations between the spatial and polarization degrees of freedom of the illuminating field which result from its nonseparable mode structure. Here, we extend the method to the nonparaxial regime. We study experimentally and theoretically the far-field polarization state generated by the scattering of a dielectric microsphere in a tightly focused vector beam as a function of the particle position. Using polarization measurements only, we<br>demonstrate position sensing of a Mie particle in three dimensions. Our work extends the concept of back focal plane interferometry and highlights the potential of polarization analysis in optical tweezers employing structured light.<br>

Portable Optical Coherence Elastography System With Flexible and Phase Stable Common Path Optical Fiber Probe

Asha Parmar, Gargi Sharma, Shivani Sharma, Kanwarpal Singh

Biomechanical properties drive the functioning of cells and tissue. Measurement of such properties in the clinic is quite challenging, however. Optical coherence elastography is an emerging technique in this field that can measure the biomechanical properties of the tissue. Unfortunately, such systems have been limited to benchtop configuration with limited clinical applications. A truly portable system with a flexible probe that could probe different sample sites with ease is still missing. In this work, we report a portable optical coherence elastography system based on a flexible common path optical fiber probe. The common path approach allows us to reduce the undesired phase noise in the system by an order of magnitude less than the standard non-common path systems. The flexible catheter makes it possible to probe different parts of the body with ease. Being portable, our system can be easily transported to and from the clinic. We tested the efficacy of the system by measuring the mechanical properties of the agar-based tissue phantoms. We also measured the mechanical properties (Young’s Modulus) of the human skin at different sites. The measured values for the agar phantom and the skin were found to be comparable with the previously reported studies. Ultra-high phase stability and flexibility of the probe along with the portability of the whole system makes an ideal combination for the faster clinical adoption of the optical coherence elastography technique.

The Xenopus spindle is as dense as the surrounding cytoplasm

Abin Biswas, Kyoohyun Kim, Gheorghe Cojoc, Jochen Guck, Simone Reber

The mitotic spindle is a self-organizing molecular machine, where hundreds of different molecules continuously interact to maintain a dynamic steady state. While our understanding of key molecular players in spindle assembly is significant, it is still largely unknown how the spindle’s material properties emerge from molecular interactions. Here, we use correlative fluorescence imaging and label-free three-dimensional optical diffraction tomography (ODT) to measure the Xenopus spindle’s mass density distribution. While the spindle has been commonly referred to as a denser phase of the cytoplasm, we find that it has the same density as its surrounding, which makes it neutrally buoyant. Molecular perturbations suggest that spindle mass density can be modulated by tuning microtubule nucleation and dynamics. Together, ODT provides direct, unbiased, and quantitative information of the spindle’s emergent physical properties—essential to advance predictive frameworks of spindle assembly and function.

Nanoscopic charge fluctuations in a gallium phosphide waveguide measured by single molecules

Alexey Shkarin, Dominik Rattenbacher, Jan Renger, Simon Hönl, Tobias Utikal, Paul Seidler, Stephan Götzinger, Vahid Sandoghdar

We present efficient coupling of single organic molecules to a gallium phosphide subwavelengthwaveguide (nanoguide). By examining and correlating the temporal dynamics of various single-molecule resonances at different locations along the nanoguide, we reveal light-induced fluctuationsof their Stark shifts. Our observations are consistent with the predictions of a simple model basedon the optical activation of a small number of charges in the GaP nanostructure.

Comment on “An encryption protocol for NEQR images based on one-particle quantum walks on a circle”

Markus Grassl

Rotation sensing at the ultimate limit

Aaron Z. Goldberg, Andrei B. Klimov, Gerd Leuchs, Luis Sanchez-Soto

Conventional classical sensors are approaching their maximum sensitivity<br>levels in many areas. Yet these levels still are far from the ultimate limits<br>dictated by quantum mechanics. Quantum sensors promise a substantial step ahead<br>by taking advantage of the salient sensitivity of quantum states to the<br>environment. Here, we focus on sensing rotations, a topic of broad application.<br>By resorting to the basic tools of estimation theory, we derive states that<br>achieve the ultimate sensitivities in estimating both the orientation of an<br>unknown rotation axis and the angle rotated about it. The critical enhancement<br>obtained with these optimal states should make of them an indispensable<br>ingredient in the next generation of rotation sensors that is now blossoming.<br>

Brillouin scattering - theory and experiment: tutorial

C. Wolff, M.J.A. Smith, Birgit Stiller, C. G. Poulton

Brillouin scattering is an important and interesting nonlinear effect involving the interaction between optical and acoustic fields in optical waveguides. It is increasingly useful in the field of photonics, where it supplies a tunable ultra-narrow linewidth response that can be used for applications including sensing, filtering, and lasing, as well as the acoustic storage of optical pulses. This tutorial gives an overview of the fundamentals of Brillouin scattering aimed at newcomers to the field, and covers the physics underlying the interaction, the mathematical theory, and setup details of foundational Brillouin experiments. (C) 2021 Optical Society of America

Axial superlocalization with vortex beams

D. Koutny, Z. Hradil, J. Rehacek, Luis Sanchez-Soto

Improving axial resolution is of paramount importance for three-dimensional optical imaging systems. Here, we investigate the ultimate precision in axial<br>localization using vortex beams. For Laguerre-Gauss beams, this limit can be achieved with just an intensity scan. The same is not true for superpositions<br>of Laguerre-Gauss beams, in particular for those with intensity profiles that rotate on defocusing. Microscopy methods based on rotating vortex beams may thus benefit from replacing traditional intensity sensors with advanced mode-sorting techniques.

Compliant Substrates Enhance Macrophage Cytokine Release and NLRP3 Inflammasome Formation During Their Pro-Inflammatory Response

Joan-Carles Escolano, Anna V. Taubenberger, Shada Abuhattum, Christine Schweitzer, Aleeza Farrukh, Aránzazu del Campo, Clare E. Bryant, Jochen Guck

Immune cells process a myriad of biochemical signals but their function and behavior are also determined by mechanical cues. Macrophages are no exception to this. Being present in all types of tissues, macrophages are exposed to environments of varying stiffness, which can be further altered under pathological conditions. While it is becoming increasingly clear that macrophages are mechanosensitive, it remains poorly understood how mechanical cues modulate their inflammatory response. Here we report that substrate stiffness influences the expression of pro-inflammatory genes and the formation of the NLRP3 inflammasome, leading to changes in the secreted protein levels of the cytokines IL-1β and IL-6. Using polyacrylamide hydrogels of tunable elastic moduli between 0.2 and 33.1 kPa, we found that bone marrow-derived macrophages adopted a less spread and rounder morphology on compliant compared to stiff substrates. Upon LPS priming, the expression levels of the gene encoding for TNF-α were higher on more compliant hydrogels. When additionally stimulating macrophages with the ionophore nigericin, we observed an enhanced formation of the NLRP3 inflammasome, increased levels of cell death, and higher secreted protein levels of IL-1β and IL-6 on compliant substrates. The upregulation of inflammasome formation on compliant substrates was not primarily attributed to the decreased cell spreading, since spatially confining cells on micropatterns led to a reduction of inflammasome-positive cells compared to well-spread cells. Finally, interfering with actomyosin contractility diminished the differences in inflammasome formation between compliant and stiff substrates. In summary, we show that substrate stiffness modulates the pro-inflammatory response of macrophages, that the NLRP3 inflammasome is one of the components affected by macrophage mechanosensing, and a role for actomyosin contractility in this mechanosensory response. Thus, our results contribute to a better understanding of how microenvironment stiffness affects macrophage behavior, which might be relevant in diseases where tissue stiffness is altered and might potentially provide a basis for new strategies to modulate inflammatory responses.

Precision single-particle localization using radial variance transform

Anna Kashkanova, Alexey Shkarin, Reza Gholami Mahmoodabadi, Martin Blessing, Yazgan Tuna, André Gemeinhardt, Vahid Sandoghdar

We introduce an image transform designed to highlight features with high degree of radial symmetry for identification and subpixel localization of particles in microscopy images. The transform is based on analyzing pixel value variations in radial and angular directions. We compare the subpixel localization performance of this algorithm to other common methods based on radial or mirror symmetry (such as fast radial symmetry transform, orientation alignment transform, XCorr, and quadrant interpolation), using both synthetic and experimentally obtained data. We find that in all cases it achieves the same or lower localization error, frequently reaching the theoretical limit.

Design of an optomagnonic crystal: Towards optimal magnon-photon mode matching at the microscale

Jasmin Graf, Sanchar Sharma, Hans Hübl, Silvia Viola-Kusminskiy

We put forward the concept of an optomagnonic crystal: a periodically patterned structure at the microscale based on a magnetic dielectric, which can co-localize magnon and photon modes. The co-localization in small volumes can result in large values of the photon-magnon coupling at the single quanta level, which opens perspectives for quantum information processing and quantum conversion schemes with these systems. We study theoretically a simple geometry consisting of a one-dimensional array of holes with an abrupt defect, considering the ferrimagnet yttrium iron garnet (YIG) as the basis material. We show that both magnon and photon modes can be localized at the defect, and use symmetry arguments to select an optimal pair of modes in order to maximize the coupling. We show that an optomagnonic coupling in the kHz range is achievable in this geometry, and discuss possible optimization routes in order to improve both coupling strengths and optical losses.

Chromatic Dispersion Based Wide-Band, Fiber-Coupled, Tunable Light Source for Hyperspectral Imaging

Gargi Sharma, Sheeza Kainat Naveed, Asha Parmar, Kanwarpal Singh

Hyperspectral imaging is a powerful label-free imaging technique that provides topological and spectral information at once. In this work, we have designed and characterized a hyperspectral source based on the chromatic dispersion property of off-the-shelf lenses and converted a supercontinuum laser light source into a hyperspectral imaging light source for 490 nm to 900 nm wavelength range with a spectral resolution of 3.5 nm to 18 nm respectively. The potential of the source was demonstrated by imaging two color dots with different absorption bands. Further, we generated the hypercube of the lily ovary and dense connective tissue and measured their spectral signature as a function of wavelength. We also imaged the lower tongue of a healthy volunteer at 540 nm, 630 nm, and white light. Our simple hyperspectral light source design can easily be incorporated in a standard endoscope or microscope to perform hyperspectral imaging.

Polarization of Light: In Classical, Quantum, and Nonlinear Optics

Maria V. Chekhova, Peter Banzer

This book starts with the description of polarization in classical optics, including also a chapter on crystal optics, which is necessary to understand the use of nonlinear crystals. In addition, spatially non-uniform polarization states are introduced and described. Further, the role of polarization in nonlinear optics is discussed. The final chapters are devoted to the description and applications of polarization in quantum optics and quantum technologies.

Broadband mid-infrared supercontinuum generation in dispersion-engineered As2S3-silica nanospike waveguides pumped by 2.8 μm femtosecond laser

Pan Wang, Jiapeng Huang, Shangran Xie, Johann Troles, Philip St. J. Russell

Broadband mid-infrared (IR) supercontinuum laser sources are essential for spectroscopy in the molecular fingerprint region. Here, we report generation of octave-spanning and coherent mid-IR supercontinua in As2S3-silica nanospike hybrid waveguides pumped by a custom-built 2.8 μm femtosecond fiber laser. The waveguides are formed by pressure-assisted melt-filling of molten As2S3 into silica capillaries, allowing the dispersion and nonlinearity to be precisely tailored. Continuous coherent spectra spanning from 1.1 μm to 4.8 μm (30 dB level) are observed when the waveguide is designed so that 2.8 μm lies in the anomalous dispersion regime. Moreover, linearly tapered millimeter-scale As2S3-silica waveguides are fabricated and investigated for the first time, to the best of our knowledge, showing much broader supercontinua than uniform waveguides, with improved spectral coherence. The waveguides are demonstrated to be long-term stable and water-resistant due to the shielding of the As2S3 by the fused silica sheath. They offer an alternative route to generating broadband mid-IR supercontinua, with applications in frequency metrology and molecular spectroscopy, especially in humid and aqueous environments.

Effects of coherence on temporal resolution

Syamsundar De, Jano Gil-Lopez, Benjamin Brecht, Christine Silberhorn, Luis Sanchez-Soto, Z. Hradil, J. Rehacek

Measuring small separations between two optical sources, either in space or in time, constitute an important metrological challenge as standard<br>intensity-only measurements fail for vanishing separations. Contrarily, it has been established that appropriate coherent mode projections can appraise<br>arbitrarily small separations with quantum-limited precision. However, the question of whether the optical coherence brings any metrological advantage to<br>mode projections is still a point of debate. Here, we elucidate this problem by experimentally investigating the effect of varying coherence on estimating the<br>temporal separation between two single-photon pulses. We show that, for an accurate interpretation, special attention must be paid to properly normalize<br>the quantum Fisher information to account for the strength of the signal. Our experiment demonstrates that coherent mode projections are optimal for any<br>degree of coherence.<br>

AIDeveloper: deep learning image classification in life science and beyond

Martin Kräter, Shada Abuhattum Hofemeier, Despina Soteriou, Angela Jacobi, Thomas Krüger, Jochen Guck, Maik Herbig

Artificial intelligence (AI)‐based image analysis has increased drastically in recent years. However, all applications use individual solutions, highly specialized for a particular task. Here, an easy‐to‐use, adaptable, and open source software, called AIDeveloper (AID) to train neural nets (NN) for image classification without the need for programming is presented. AID provides a variety of NN‐architectures, allowing to apply trained models on new data, obtain performance metrics, and export final models to different formats. AID is benchmarked on large image datasets (CIFAR‐10 and Fashion‐MNIST). Furthermore, models are trained to distinguish areas of differentiated stem cells in images of cell culture. A conventional blood cell count and a blood count obtained using an NN are compared, trained on >1.2 million images, and demonstrated how AID can be used for label‐free classification of B‐ and T‐cells. All models are generated by non‐programmers on generic computers, allowing for an interdisciplinary use.

Frenet–Serret analysis of helical Bloch modes in N-fold rotationally symmetric rings of coupled spiraling optical waveguides

Yang Chen, Philip St.J. Russell

The behavior of electromagnetic waves in chirally twisted structures is a topic of enduring interest, dating back at least to the 1940s invention of the microwave travelling-wave-tube amplifier and culminating in contemporary studies of chiral metamaterials, metasurfaces, and photonic crystal fibers (PCFs). Optical fibers with chiral microstructures, drawn from a spinning preform, have many useful properties, exhibiting, for example, circular birefringence and circular dichroism. It has recently been shown that chiral fibers with N-fold rotationally symmetric (symmetry group CN) transverse microstructures support families of helical Bloch modes (HBMs), each of which consists of a superposition of azimuthal Bloch harmonics (or optical vortices). An example is a fiber with N coupled cores arranged in a ring around its central axis (N-core single-ring fiber). Although this type of fiber can be readily modeled using scalar coupled-mode theory, a full description of its optical properties requires a vectorial analysis that takes account of the polarization state of the light, which is particularly important in studies of circular and vortical birefringence. In this paper, we develop, using an orthogonal 2D helicoidal coordinate system embedded in a cylindrical surface at constant radius, a rigorous vector coupled-mode description of the fields using local Frenet–Serret frames that rotate and twist with each of the N cores. The analysis places on a firm theoretical footing a previous HBM theory in which a heuristic approach was taken, based on physical intuition of the properties of Bloch waves. After a detailed review of the polarization evolution in a single spiraling core, analysis of the N-core single-ring system is carefully developed step by step. Accuracy limits of the analysis are assessed by comparison with the results of finite element modeling, focusing in particular on the dispersion, polarization states, and transverse field profiles of the HBMs. We believe this study provides clarity into what can sometimes be a rather difficult field and will facilitate further exploration of real-world applications of these fascinating waveguiding systems.

Quantum circuit optimization with deep reinforcement learning

Thomas Fösel, Murphy Yuezhen Niu, Florian Marquardt, Li Li (李力)

A central aspect for operating future quantum computers is quantum circuit optimization, i.e., the search for efficient realizations of quantum algorithms given the device capabilities. In recent years, powerful approaches have been developed which focus on optimizing the high-level circuit structure. However, these approaches do not consider and thus cannot optimize for the hardware details of the quantum architecture, which is especially important for near-term devices. To address this point, we present an approach to quantum circuit optimization based on reinforcement learning. We demonstrate how an agent, realized by a deep convolutional neural network, can autonomously learn generic strategies to optimize arbitrary circuits on a specific architecture, where the optimization target can be chosen freely by the user. We demonstrate the feasibility of this approach by training agents on 12-qubit random circuits, where we find on average a depth reduction by 27% and a gate count reduction by 15%. We examine the extrapolation to larger circuits than used for training, and envision how this approach can be utilized for near-term quantum devices.

Self-learning Machines based on Hamiltonian Echo Backpropagation

Victor Lopez-Pastor, Florian Marquardt

A physical self-learning machine can be defined as a nonlinear dynamical system that can be trained on data (similar to artificial neural networks), but where the update of the internal degrees of freedom that serve as learnable parameters happens autonomously. In this way, neither external processing and feedback nor knowledge of (and control of) these internal degrees of freedom is required. We introduce a general scheme for self-learning in any time-reversible Hamiltonian system. We illustrate the training of such a self-learning machine numerically for the case of coupled nonlinear wave fields.

Mechanical properties of cell- and microgel bead-laden oxidized alginate-gelatin hydrogels

Thomas Distler, Lena Kretzschmar, Dominik Schneidereit, Salvatore Girardo, Ruchi Goswami, Oliver Friedrich, Rainer Detsch, Jochen Guck, Aldo R. Boccaccini, et al.

3D-printing technologies, such as biofabrication, capitalize on the homogeneous distribution and growth of cells inside biomaterial hydrogels, ultimately aiming to allow for cell differentiation, matrix remodeling, and functional tissue analogues. However, commonly, only the mechanical properties of the bioinks or matrix materials are assessed, while the detailed influence of cells on the resulting mechanical properties of hydrogels remains insufficiently understood. Here, we investigate the properties of hydrogels containing cells and spherical PAAm microgel beads through multi-modal complex mechanical analyses in the small- and large-strain regimes. We evaluate the individual contributions of different filler concentrations and a non-fibrous oxidized alginate-gelatin hydrogel matrix on the overall mechanical behavior in compression, tension, and shear. Through material modeling, we quantify parameters that describe the highly nonlinear mechanical response of soft composite materials. Our results show that the stiffness significantly drops for cell- and bead concentrations exceeding four million per milliliter hydrogel. In addition, hydrogels with high cell concentrations (≥6 mio ml−1) show more pronounced material nonlinearity for larger strains and faster stress relaxation. Our findings highlight cell concentration as a crucial parameter influencing the final hydrogel mechanics, with implications for microgel bead drug carrier-laden hydrogels, biofabrication, and tissue engineering.

Spin cat states in ferromagnetic insulators

Sanchar Sharma, V. A. S. V. Bittencourt, Alexy D. Karenowska, Silvia Viola-Kusminskiy

Generating nonclassical states in macroscopic systems is a long-standing challenge. A promising platform in the context of this quest are novel hybrid systems based on magnetic dielectrics, where photons can couple strongly and coherently to magnetic excitations, although a nonclassical state therein is yet to be observed. We propose a scheme to generate a magnetization cat state, i.e., a quantum superposition of two distinct magnetization directions, using a conventional setup of a macroscopic ferromagnet in a microwave cavity. Our scheme uses the ground state of an ellipsoid shaped magnet, which displays anisotropic quantum fluctuations akin to a squeezed vacuum. The magnetization collapses to a cat state by either a single photon or a parity measurement of the microwave cavity state. We find that a cat state with two components separated by ∼5ℏ is feasible and briefly discuss potential experimental setups that can achieve it.

Benchmarking quantum tomography completeness and fidelity with machine learning

Yong Siah Teo, Seongwook Shin, Hyunseok Jeong, Yosep Kim, Yoon-Ho Kim, Gleb I. Struchalin, Egor V. Kovlakov, Stanislav S. Straupe, Sergei P. Kulik, et al.

We train convolutional neural networks to predict whether or not a set of measurements is informationally complete to uniquely reconstruct any given quantum state with no prior information. In addition, we perform fidelity benchmarking based on this measurement set without explicitly carrying out state tomography. The networks are trained to recognize the fidelity and a<br>reliable measure for informational completeness through collective encoding of quantum measurements, data and target states into grayscale images. By<br>gradually accumulating measurements and data, these convolutional networks can efficiently certify a low-measurement-cost quantum-state characterization<br>scheme. We confirm the potential of this machine-learning approach by presenting experimental results for both spatial-mode and multiphoton systems<br>of large dimensions. These predictions are further shown to improve with noise recognition when the networks are trained with additional bootstrapped training sets from real experimental data.<br>

Entanglement-assisted quantum communication beating the quantum Singleton bound

Markus Grassl

Brun, Devetak, and Hsieh [Science 314, 436 (2006)] demonstrated that preshared entanglement between the sender and receiver enables quantum communication protocols that have better parameters than schemes without the assistance of entanglement. Subsequently, the same authors derived a version of the so-called quantum Singleton bound that relates the parameters of the entanglement-assisted quantum-error-correcting codes proposed by them. We present an entanglement-assisted quantum communication scheme with parameters violating this bound in certain ranges. For a fixed transmission rate, our scheme allows one to correct a larger fraction of errors.

Agile and versatile quantum communication: Signatures and secrets

Stefan Richter, Matthew Thornton, Imran Khan, Hamish Scott, Kevin Jaksch, Ulrich Vogl, Birgit Stiller, Gerd Leuchs, Christoph Marquardt, et al.

Agile cryptography allows for a resource-efficient swap of a cryptographic core in case the security of an underlying classical cryptographic algorithm becomes compromised. Conversely, versatile cryptography allows the user to switch the cryptographic task without requiring any knowledge of its inner workings.<br>In this paper, we suggest how these related principles can be applied to the field of quantum cryptography by explicitly demonstrating two quantum cryptographic protocols, quantum digital signatures (QDS) and quantum secret sharing (QSS), on the same hardware sender and receiver platform. Crucially, the protocols differ only in their classical postprocessing. The system is also suitable for quantum key distribution (QKD) and is highly compatible with deployed telecommunication infrastructures, since it uses standard quadrature phase-shift keying encoding and heterodyne detection. For the first time, QDS protocols are modified to allow for postselection at the receiver, enhancing protocol performance. The cryptographic primitives QDS and QSS are inherently multipartite, and we prove that they are secure not only when a player internal to the task is dishonest, but also when (external) eavesdropping on the quantum channel is allowed. In our first proof-of-principle demonstration of an agile and versatile quantum communication system, the quantum states are distributed at GHz rates. A 1-bit message may be securely signed using our QDS protocols in less than 0.05 ms over a 2-km fiber link and in less than 0.2 s over a 20-km fiber link. To our knowledge, this also marks the first demonstration of a continuous-variable direct QSS protocol.

Floquet theory for temporal correlations and spectra in time-periodic open quantum systems: Application to squeezed parametric oscillation beyond the rotating-wave approximation

Carlos Navarrete-Benlloch, Rafael Garcés, Naeimeh Mohseni, German J. de Valcarcel

Open quantum systems can display periodic dynamics at the classical level either due to external periodic modulations or to self-pulsing phenomena typically following a Hopf bifurcation. In both cases, the quantum fluctuations around classical solutions do not reach a quantum-statistical stationary state, which prevents adopting the simple and reliable methods used for stationary quantum systems. Here we put forward a general and efficient method to compute two-time correlations and corresponding spectral densities of time-periodic open quantum systems within the usual linearized (Gaussian) approximation for their dynamics. Using Floquet theory, we show how the quantum Langevin equations for the fluctuations can be efficiently integrated by partitioning the time domain into one-period duration intervals, and relating the properties of each period to the first one. Spectral densities, like squeezing spectra, are computed similarly, now in a two-dimensional temporal domain that is treated as a chessboard with one-period × one-period cells. This technique avoids cumulative numerical errors as well as efficiently saving computational time. As an illustration of the method, we analyze the quantum fluctuations of a damped parametrically driven oscillator (degenerate parametric oscillator) below threshold and far away from rotating-wave approximation conditions, which is a relevant scenario for modern low-frequency quantum oscillators. Our method reveals that the squeezing properties of such devices are quite robust against the amplitude of the modulation or the low quality of the oscillator, although optimal squeezing can appear for parameters that are far from the ones predicted within the rotating-wave approximation.

suggested by editors

Excitation transport with collective radiative decay

Francesca Mineo, Claudiu Genes

We investigate a one-dimensional quantum emitter chain where transport of excitations and correlations takes place via nearest neighbor, dipole-dipole interactions. In the presence of collective radiative emission, we show that a phase imprinting wavepacket initialization procedure can lead to subradiant transport and can preserve quantum correlations. In the context of cavity mediated transport, where emitters are coupled to a common delocalized optical mode, we analyze the effect of frequency disorder and nonidentical photon-emitter couplings on excitation transport.

Special Topic: Quantum sensing with correlated light sources

Alex S. Clark, Maria V. Chekhova, Jonathan C F Matthews, John G. Rarity, Rupert F. Oulton

Engineering Fast High-Fidelity Quantum Operations With Constrained Interactions

Thales Figueiredo Roque, Aashish A Clerk, Hugo Ribeiro

Understanding how to tailor quantum dynamics to achieve a desired evolution is a crucial problemin almost all quantum technologies. We present a very general method for designing high-efficiencycontrol sequences that are always fully compatible with experimental constraints on available inter-actions and their tunability. Our approach reduces in the end to finding control fields by solvinga set of time-independent linear equations. We illustrate our method by applying it to a numberof physically-relevant problems: the strong-driving limit of a two-level system, fast squeezing in aparametrically driven cavity, the leakage problem in transmon qubit gates, and the acceleration ofSNAP gates in a qubit-cavity system.

Analytical model of the deformation-induced inertial dynamics of a magnetic vortex

Myoung-Woo Yoo, Francesca Mineo, Joo-Von Kim

We present an analytical model to account for the deformation-induced inertial dynamics of a magnetic vortex. The model is based on a deformation of the vortex core profile based on the Döring kinetic field, whereby the deformation amplitudes are promoted to dynamical variables in a collective-coordinate approach that provides a natural extension to the Thiele model. This extended model describes complex transients due to inertial effects and the variation of the effective mass with velocity. The model also provides a quantitative description of the inertial dynamics leading up to vortex core reversal, which is analogous to the Walker transition in domain wall dynamics. Our work paves the way for a standard prescription for describing the inertial effects of topological magnetic solitons

Genome-wide CRISPR screens reveal a specific ligand for the glycan-binding immune checkpoint receptor Siglec-7

Simon Wisnovsky, Leonhard Möckl, Stacy A. Malaker, Kayvon Pedram, Gaelen T. Hess, Nicholas M. Riley, Melissa A. Gray, Benjamin A. H. Smith, Michael C. Bassik, et al.

Glyco-immune checkpoint receptors, molecules that inhibit immune cell activity following binding to glycosylated cell-surface<br>antigens, are emerging as attractive targets for cancer immunotherapy.<br>Defining biologically relevant ligands that bind and activate such receptors, however, has historically been a significant challenge. Here, we present a CRISPRi genomic screening strategy that allowed unbiased identification of the key genes required for<br>cell-surface presentation of glycan ligands on leukemia cells that bind the glyco-immune checkpoint receptors Siglec-7 and Siglec-9.<br>This approach revealed a selective interaction between Siglec-7 and the mucin-type glycoprotein CD43. Further work identified a specific N-terminal glycopeptide region of CD43 containing clusters of disialylated O-glycan tetrasaccharides that form specific Siglec-7 binding motifs. Knockout or blockade of CD43 in leukemia<br>cells relieves Siglec-7-mediated inhibition of immune killing activity.<br>This work identifies a potential target for immune checkpoint blockade therapy and represents a generalizable approach to dissection of glycan–receptor interactions in living cells.

Entangled photons from subwavelength nonlinear films

Tomas Santiago-Cruz, Vitaliy Sultanov, Haizhong Zhang, Leonid A. Krivitsky, Maria V. Chekhova

Miniaturized entangled photon sources, in particular based on subwavelength metasurfaces, are highly demanded for the development of integrated quantum photonics. Here, as a first step towards the development of quantum optical metasurfaces (QOMs), we demonstrate generation of entangled photons via spontaneous parametric down-conversion (SPDC) from subwavelength films. We achieve photon pair generation with a high coincidence-to-accidental ratio in lithium niobate and gallium phosphide nanofilms. By implementing the fiber spectroscopy of SPDC in nanofilms, we measure a spectrum with a bandwidth of 500 nm, limited only by the overall detection efficiency. The spectrum reveals vacuum field enhancement due to a Fabry–Perot resonance inside the nonlinear films. It also suggests a strategy for observing SPDC from QOM. Our experiments lay the groundwork for future development of flat SPDC sources, including QOM.

Self-Switching Kerr Oscillations of Counterpropagating Light in Microresonators

Michael T. M. Woodley, Lewis Hill, Leonardo Del Bino, Gian-Luca Oppo, Pascal Del'Haye

We report the experimental and numerical observation of oscillatory antiphase switching between counterpropagating light beams in Kerr ring microresonators, where dominance between the intensities of the two beams is periodically or chaotically exchanged. Self-switching occurs in balanced regimes of operation and is well captured by a simple coupled dynamical system featuring only the self- and crossphase Kerr nonlinearities. Switching phenomena are due to temporal instabilities of symmetry-broken states combined with attractor merging, which restores the broken symmetry on average. Self-switching of counterpropagating light is robust for realizing controllable, all-optical generation of waveforms, signal encoding, and chaotic cryptography.

suggested by editors

Optofluidic photonic crystal fiber microreactors for in-situ studies of carbon nanodot-driven photoreduction

Philipp Koehler, Takashi Lawson, Julian Neises, Janina Willkomm, Benjamin C. M. Martindale , Georgina A. M. Hutton, Daniel Antón-García, Ava Lage, Alexander S. Gentleman, et al.

Performing quantitative in situ spectroscopic analysis on minuscule sample volumes is a common difficulty in photochemistry. To address this challenge, we use a hollow-core photonic crystal fiber (HC-PCF) that guides light at the center of a microscale liquid channel and acts as an optofluidic microreactor with a reaction volume of less than 35 nL. The system was used to demonstrate in situ optical detection of photoreduction processes that are key components of many photocatalytic reaction schemes. The photoreduction of viologens (XV2+) to the radical XV•+ in a homogeneous mixture with carbon nanodot (CND) light absorbers is studied for a range of different carbon dots and viologens. Time-resolved absorption spectra, measured over several UV irradiation cycles, are interpreted with a quantitative kinetic model to determine photoreduction and photobleaching rate constants. The powerful combination of time-resolved, low-volume absorption spectroscopy and kinetic modeling highlights the potential of optofluidic microreactors as a highly sensitive, quantitative, and rapid screening platform for novel photocatalysts and flow chemistry in general.

Optical memories and switching dynamics of counterpropagating light states in microresonators

Leonardo Del Bino, Niall Moroney, Pascal Del'Haye

The Kerr nonlinearity can be a key enabler for many digital photonic circuits as it allows access to bistable states needed for all-optical memories and switches. A common technique is to use the Kerr shift to control the resonance frequency of a resonator and use it as a bistable, optically-tunable filter. However, this approach works only in a narrow power and frequency range or requires the use of an auxiliary laser. An alternative approach is to use the asymmetric bistability between counterpropagating light states resulting from the interplay between self- and cross-phase modulation, which allows light to enter a ring resonator in just one direction. Logical HIGH and Low states can be represented and stored as the direction of circulation of light, and controlled by modulating the input power. Here we study the switching speed, operating laser frequency and power range, and contrast ratio of such a device. We reach a bitrate of 2 Mbps in our proof-of-principle device over an optical frequency range of 1 GHz and an operating power range covering more than one order of magnitude. We also calculate that integrated photonic circuits could exhibit bitrates of the order of Gbps, paving the way for the realization of robust and simple all-optical memories, switches, routers and logic gates that can operate at a single laser frequency with no additional electrical power. Published by The Optical Society under the terms of the Creative Commons Attribution 4.0 License

SU(1, 1) covariant s-parametrized maps

Andrei B. Klimov, Ulrich Seyfarth, Hubert de Guise, Luis Sanchez-Soto

We propose a practical recipe to compute the s-parametrized maps for systems with SU(1, 1) symmetry using a connection between the Q- and P-symbols through the action of an operator invariant under the group. This establishes equivalence relations between s-parametrized SU(1, 1)-covariant maps. The particular case of the self-dual (Wigner) phase-space functions, defined on the upper sheet of the two-sheet hyperboloid (or, equivalently, inside the Poincaré disc) are analysed.

Squeezed comb states

Namrata Shukla, Stefan Nimmrichter, Barry C. Sanders

Continuous-variable codes are an expedient solution for quantum information processing and quantum communication involving optical networks. Here we characterize the squeezed comb, a finite superposition of equidistant squeezed coherent states on a line, and its properties as a continuous-variable encoding choice for a logical qubit. The squeezed comb is a realistic approximation to the ideal code proposed by Gottesman et al. [D. Gottesman, A. Kitaev, and J. Preskill, Phys. Rev. A 64, 012310 (2001)], which is fully protected against errors caused by the paradigmatic types of quantum noise in continuous-variable systems: damping and diffusion. This is no longer the case for the code space of finite squeezed combs, and noise robustness depends crucially on the encoding parameters. We analyze finite squeezed comb states in phase space, highlighting their complicated interference features and characterizing their dynamics when exposed to amplitude damping and Gaussian diffusion noise processes. We find that squeezed comb states are more suitable and less error prone when exposed to damping, which speaks against standard error-correction strategies that employ linear amplification to convert damping into easier-to-describe isotropic diffusion noise.

A switch in pdgfrb+ cell-derived ECM composition prevents inhibitory scarring and promotes axon regeneration in the zebrafish spinal cord

Vasiliki Tsata, Stephanie Möllmert, Christine Schweitzer, Julia Kolb, Conrad Möckel, Benjamin Böhm, Gonzalo Rosso, Christian Lange, Mathias Lesche, et al.

In mammals, perivascular cell-derived scarring after spinal cord injury impedes axonal regrowth. In contrast, the extracellular matrix (ECM) in the spinal lesion site of zebrafish is permissive and required for axon regeneration. However, the cellular mechanisms underlying this interspecies difference have not been investigated. Here, we show that an injury to the zebrafish spinal cord triggers recruitment of pdgfrb+ myoseptal and perivascular cells in a PDGFR signaling-dependent manner. Interference with pdgfrb+ cell recruitment or depletion of pdgfrb+ cells inhibits axonal regrowth and recovery of locomotor function. Transcriptional profiling and functional experiments reveal that pdgfrb+ cells upregulate expression of axon growth-promoting ECM genes (cthrc1a and col12a1a/b) and concomitantly reduce synthesis of matrix molecules that are detrimental to regeneration (lum and mfap2). Our data demonstrate that a switch in ECM composition is critical for axon regeneration after spinal cord injury and identify the cellular source and components of the growth-promoting lesion ECM.

Achieving the ultimate quantum timing resolution

Vahid Ansari, Benjamin Brecht, Jano Gil-López, John M. Donohue, Jaroslav Řeháček, Zdeněk Hradil, Luis Sanchez-Soto, Christine Silberhorn

Accurate time-delay measurement is at the core of many modern technologies.<br>Here, we present a temporal-mode demultiplexing scheme that achieves the<br>ultimate quantum precision for the simultaneous estimation of the temporal<br>centroid, the time offset, and the relative intensities of an incoherent<br>mixture of ultrashort pulses at the single-photon level. We experimentally<br>resolve temporal separations ten times smaller than the pulse duration, as well<br>as imbalanced intensities differing by a factor of 10^2. This represents an<br>improvement of more than an order of magnitude over the best standard methods<br>based on intensity detection.<br>

Cross-phase modulational instability of circularly polarized helical Bloch modes carrying optical vortices in a chiral three-core photonic crystal fiber

Paul Roth, Michael Frosz, Linda Weise, Philip Russell, Gordon Wong

We report the first, to the best of our knowledge, observation of cross-phase modulational instability (XPMI) of circularly polarized helical Bloch modes carrying optical vortices in a twisted photonic crystal fiber with a three-fold symmetric core, formed by spinning the fiber preform during the draw. When the fiber is pumped by a superposition of left-circular polarization (LCP) and right-circular polarization (RCP) modes, a pair of orthogonal circularly polarized sidebands of opposite topological charge is generated. When, on the other hand, a pure LCP (or RCP) mode is launched, the XPMI gain is zero, and no sidebands are seen. This observation has not been seen before in any system and is unique to chiral structures with N-fold rotational symmetry. The polarization state and topological charge of the generated sidebands are measured. By decomposing the helical Bloch modes into their azimuthal harmonics, we are able to deduce the selection rules for the appearance of modulational instability sidebands. We showed that the four waves in the nonlinear mixing process must exhibit the same set of azimuthal harmonic orders.