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.

Temporal Self-Compression and Self-Frequency Shift of Submicrojoule Pulses at a Repetition Rate of 8 MHz

Francesco Tani, Jacob Lampen, Martin Butryn, Michael Frosz, Jie Jiang, Martin E. Fermann, Philip Russell

We combine soliton dynamics in gas-filled hollow-core photonic crystal fibers with a state-of-the-art fiber laser to realize a turnkey system producing few-femtosecond pulses at 8-MHz repetition rate at pump energies as low as 220 nJ. Furthermore, by exploiting the soliton self-frequency shift in a second hydrogen-filled hollow-core fiber, we efficiently generate pulses as short as 22 fs, continuously tunable from 1100 to 1474 nm.

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.

Small molecule inhibitors of mammalian glycosylation

Karim Almahayni, Malte Spiekermann, Antonio Fiore, Guoqiang Yu, Kayvon Pedram, Leonhard Möckl

Glycans are one of the fundamental biopolymers encountered in living systems. Compared to polynucleotide and polypeptide biosynthesis, polysaccharide biosynthesis is a uniquely combinatorial process to which interdependent enzymes with seemingly broad specificities contribute. The resulting intracellular, cell surface, and secreted glycans play key roles in health and disease, from embryogenesis to cancer progression. The study and modulation of glycans in cell and organismal biology is aided by small molecule inhibitors of the enzymes involved in glycan biosynthesis. In this review, we survey the arsenal of currently available inhibitors, focusing on agents which have been independently validated in diverse<br>systems. We highlight the utility of these inhibitors and drawbacks to their use, emphasizing the need for innovation for basic research as well as for therapeutic applications.

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.

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.

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.

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.

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.

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.

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.

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>

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.

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.

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.

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>

Counterpropagating light in ring resonators: Switching fronts, plateaus, and oscillations

Graeme N. Campbell, Shuangyou Zhang, Leonardo Del Bino, Pascal Del'Haye, Gian-Luca Oppo

We characterize the formation of robust stationary states formed by light plateaus separated by two local switching fronts in only one of two counterpropagating fields in ring resonators with normal dispersion. Such states are due to global cross coupling and allow for frequency combs to switch from one field to the other by simply tuning the input laser frequency. Exact expressions for the distance between fronts and for plateau powers are provided in excellent agreement with simulations. These demonstrate an unusual high degree of control over pulse and plateau duration in one of the fields upon changes of one of the input laser frequencies. We identify a wide parameter region in which light plateaus are self-starting and are the only stable solution. For certain values of the detunings we find multistable states of plateaus with switching fronts, slowly oscillating homogeneous states and nonoscillating homogeneous states of the counterpropagating fields. Robustness and multistability of these unusual single-field front solutions are provided in parameter ranges that are experimentally achievable in a wide variety of ring resonators.

The deep space quantum link: prospective fundamental physics experiments using long-baseline quantum optics

Makan Mohageg, Luca Mazzarella, Charis Anastopoulos, Jason Gallicchio, Bei-Lok Hu, Thomas Jennewein, Spencer Johnson, Shih-Yuin Lin, Alexander Ling, et al.

The National Aeronautics and Space Administration’s Deep Space Quantum Link mission concept enables a unique set of science experiments by establishing robust quantum optical links across extremely long baselines. Potential mission configurations include establishing a quantum link between the Lunar Gateway moon-orbiting space station and nodes on or near the Earth. This publication summarizes the principal experimental goals of the Deep Space Quantum Link. These goals, identified through a multi-year design study conducted by the authors, include long-range teleportation, tests of gravitational coupling to quantum states, and advanced tests of quantum nonlocality.

Immune Cell Deformability in Depressive Disorders: Longitudinal Associations Between Depression, Glucocorticoids and Cell Deformabilit

Andreas Walter, Martin Kräter, Clemens Kirschbaum, Wei Gao, Magdalena Wekenborg, Marlene Penz, Nicole Rothe, Jochen Guck, Lukas Daniel Wittwer, et al.

Background: Cell deformability of all major blood cell types is increased in depressive disorders (DD).<br>Furthermore, impaired glucocorticoid secretion is causally related to DD. Nevertheless, there are no longitudinal studies examining changes in glucocorticoid output and depressive symptoms regarding cell deformability in DD.<br>Aim: To investigate, whether changes in depressive symptoms or hair glucocorticoids predict cell deformability in DD.<br>Methods: In 136 individuals, depressive symptoms (PHQ-9) and hair glucocorticoids (cortisol and cortisone) were measured at timepoint one (T1), while one year later (T2) depressive symptoms and hair glucocorticoids were remeasured and additionally cell deformability of peripheral blood cells was assessed and DD status was determined by clinical interview.<br>Results: Depression severity at T1 predicted higher cell deformability in monocytes and lymphocytes over the entire sample. Subjects with continuously high depressive symptoms at T1 and T2 showed elevated monocyte<br>deformability as compared to subjects with low depressive symptoms. Depression severity at T1 of subjects with a lifetime persistent depressive disorder (PDD) was associated with elevated monocyte, neutrophil, and granulo-<br>monocyte deformability. Depression severity at T1 of subjects with a 12-month PDD was positively associated with monocyte deformability. Furthermore, increases in glucocorticoid concentrations from T1 to T2 tended to be associated with higher immune cell deformability, while strongest associations emerged for the increase in cortisone with elevated neutrophil and granulo-monocyte deformability in the 12-month PDD group.<br>Conclusion: Continuously elevated depressive symptomatology as well as an increase in glucocorticoid levels over one year are associated with higher immune cell deformability, particularly in PDD. These findings suggest, that persistent depressive symptomatology associated with increased glucocorticoid secretion may lead to<br>increased immune cell deformability thereby compromising immune cell function and likely contributing to the perpetuation of PDD.

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.

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.

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.

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.

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.

Fluorophores’ talk turns them dark

Karim Almahayni, Malte Spiekermann, Leonhard Möckl

Dipole–dipole crosstalk between fluorophores separated by a distance of less than 10 nm induces changes in their photophysics, which adds a challenge to localization microscopy in the sub-10-nm regime.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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>

Kerr frequency combs: a million ways to fit light pulses into tiny rings

Aurélien Coillet, Shuangyou Zhang, Pascal Del'Haye

Frequency combs can be generated in millimeter-sized optical resonators thanks to their ability to store extremely high light intensities and the nonlinearity of their materials. New frequencies are generated through a cascaded parametric amplification process which can result in various optical waveforms, from ultrastable pulse patterns to optical chaos. These Kerr frequency combs have been studied extensively, with a wealth of fascinating nonlinear dynamics reported, and myriads of applications being developed, ranging from precision spectroscopy and Lidars to telecom channel generators.

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.

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.

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.

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.

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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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.

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

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.

Wie mikrobielle Modellsysteme helfen, Tumorevolution zu entschlüsseln

Maximilian Eiche, Jona Kayser

While cellular evolution is one of the most fundamental concepts of<br>life, its consequences are among the most pressing issues of modern<br>health care, including cancer and the emergence of therapy resistance.<br>We currently still lack the ability to accurately predict evolutionary trajectories,<br>especially in spatially dense, pathogenic cellular populations<br>such as microbial biofi lms or solid tumors. Here, we discuss the conceptual<br>framework of evolution in dense populations and the potential<br>of tailored microbial model systems to systematically study the underlying<br>mechanisms.

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.

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.

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>

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.

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.

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.

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.

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.

Multi-color super-resolution imaging to study human coronavirus RNA during cellular infection

Jiarui Wang, Mengting Han, Anish R. Roy, Haifeng Wang, Leonhard Möckl, Leiping Zeng, W.E. Moerner, Lei S. Qi

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the third human coronavirus within 20 years that gave rise to a life-threatening disease and the first to reach pandemic spread. To make therapeutic headway against current and future coronaviruses, the biology of coronavirus RNA during infection must be<br>precisely understood. Here, we present a robust and generalizable framework combining high-throughput confocal and super-resolution microscopy imaging to study coronavirus infection at the nanoscale. Using<br>the model human coronavirus HCoV-229E, we specifically labeled coronavirus genomic RNA (gRNA) and double-stranded RNA (dsRNA) via multi-color RNA immunoFISH and visualized their localization patterns within the cell. The 10-nm resolution achieved by our approach uncovers a striking spatial organization of<br>gRNA and dsRNA into three distinct structures and enables quantitative characterization of the status of the infection after antiviral drug treatment. Our approach provides a comprehensive imaging framework that will enable future investigations of coronavirus fundamental biology and therapeutic effects.

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.

Generalized Theory of Optical Resonator and Waveguide Modes and their Linear and Kerr Nonlinear Coupling

Jonathan M. Silver, Pascal Del'Haye

We derive a general theory of linear coupling and Kerr nonlinear coupling between modes of dielectric optical resonators from first principles. The treatment is not specific to a particular geometry or choice of mode basis, and can therefore be used as a foundation for describing any phenomenon resulting from any combination of linear coupling, scattering and Kerr nonlinearity, such as bending and surface roughness losses, geometric backscattering, self- and cross-phase modulation, four-wave mixing, third-harmonic generation and Kerr frequency comb generation. The theory is then applied to a translationally symmetric waveguide in order to calculate the evanescent coupling strength to the modes of a microresonator placed nearby, as well as the Kerr self- and cross-phase modulation terms between the modes of the resonator. This is then used to derive a dimensionless equation describing the symmetry-breaking dynamics of two counterpropagating modes of a loop resonator and prove that cross-phase modulation is exactly twice as strong as self-phase modulation only in the case that the two counterpropagating modes are otherwise identical.

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.

A Kerr Polarization Controller

Niall Moroney, Leonardo Del Bino, Shuangyou Zhang, Michael T. M. Woodley, Lewis Hill, Thibault Wildi, Valentin J. Wittwer, Thomas Südmeyer, Gian-Luca Oppo, et al.

Kerr-effect-induced changes of the polarization state of light are well known in pulsed laser systems. An example is nonlinear polarization rotation, which is critical to the operation of many types of mode-locked lasers. Here, we demonstrate that the Kerr effect in a high-finesse Fabry-Pérot resonator can be utilized to control the polarization of a continuous wave laser. It is shown that a linearly-polarized input field is converted into a left- or right-circularly-polarized field, controlled via the optical power. The observations are explained by Kerr-nonlinearity induced symmetry breaking, which splits the resonance frequencies of degenerate modes with opposite polarization handedness in an otherwise symmetric resonator. The all-optical polarization control is demonstrated at threshold powers down to 7 mW. The physical principle of such Kerr effect-based polarization controllers is generic to high-Q Kerr-nonlinear resonators and could also be implemented in photonic integrated circuits. Beyond polarization control, the spontaneous symmetry breaking of polarization states could be used for polarization filters or highly sensitive polarization sensors when operated close to the symmetry-breaking point.

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.

Dark-Bright Soliton Bound States in a Microresonator

Shuangyou Zhang, Toby Bi, George N. Ghalanos, Niall P. Moroney, Leonardo Del Bino, Pascal Del'Haye

Dissipative Kerr solitons in microresonators have facilitated the development of fully coherent, chip-scale frequency combs. In addition, dark soliton pulses have been observed in microresonators in the normal dispersion regime. Here, we report bound states of mutually trapped dark-bright soliton pairs in a microresonator. The soliton pairs are generated seeding two modes with opposite dispersion but with similar group velocities. One laser operating in the anomalous dispersion regime generates a bright soliton microcomb, while the other laser in the normal dispersion regime creates a dark soliton via Kerr-induced cross-phase modulation with the bright soliton. Numerical simulations agree well with experimental results and reveal a novel mechanism to generate dark soliton pulses. The trapping of dark and bright solitons can lead to light states with the intriguing property of constant output power while spectrally resembling a frequency comb. These results can be of interest for telecommunication systems, frequency comb applications, and ultrafast optics.

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.

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.

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.

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.