recent research topics in optics

• Cryogenic Lasers at 1 and 2 micron

We develop novel high average power and high energy laser systems at both 1 mciron wavelength such as Yb:YAG and Yb:YLF as well as in the 2 micron region with Tm:YLF and Ho:YLF. Cryogenic cooling results in a significant advantage in the thermo-optical and thermo-mechanical properties of laser materials resulting in significant advantages in power and energy handling. The lasers are applied to drive optical parametric sources, high energy THz generation and direct laser acceleration in the MID-IR within the international accelerator on chip program (ACHIP). Direct laser acceleration of relativistic electron beams with dielectric structures or pursued jointly with DESY’s accelerator division.

Nanophotonics ↓ (Click to see Ph.D. topics) Fellows: Dr. Falk Eilenberger | Prof. Rainer Heintzmann | Prof. Stefan Hell | Prof. David Hunger | Prof. Franz Kärtner | Prof. Matthias Kling | Prof. Uli Lemmer | Prof. Peter Loosen | Prof. Ulrich Nienhaus | Prof. Stefan Nolte | Prof. Thomas Pertsch | Prof. Carsten Rockstuhl | Prof. Ralf Röhlsberger | Prof. Claus Ropers | Dr. Steffen Sahl | Dr. Birgit Stiller | Prof. Martin Wegener | Prof. Uwe Zeitner

• Functionalization of Photonic Nanocircuits with 2D-Materials

Semiconducting 2D-Materials are a new and exciting material for Photonics. They exhibit unusually strong light matter interaction, including nonlinear effects, single photon emitters, and collective quantum behaviour. Moreover, they can be grown on as crystals structured substrates and can be used to functionalize optical nanostructures and circuits. Possible research topics include the growth of 2D-Materials on nanowaveguides and inside photonic crystal fibers, the characterization of light matter interaction therein and the development of applications in optical sensing and quantum technology.

• Femtosecond Laser on a Chip

We explore and advance nonlinear optical technologies for realizing an integrated femtosecond laser in a silicon photonics process. The laser should provide optical pulse trains with quantum limited timing jitter on the single femtosecond range and below. The nonlinear processes enable sub-shot noise photon statistics, which shall be modelled and characterized experimentally. The project can be theoretical and/and experimental depending on preference.

• Design, realization, and characterization of metaoptics in the VIS to NIR-spectrum

Metaoptics are evolving as a competitor to conventional optics by offering more design freedom and new resulting functionalities. One remaining obstacle still is the cost-efficient fabrication of these nanostructured surfaces that is so far mainly realized by time-expensive electron beam lithography. Within this thesis, the lab-based interference lithography with extreme-ultraviolet radiation which has been developed at the chair TOS shall be extended from periodic structures to quasi-periodic and even aperiodic structures. Main tasks are the design of compatible metaatom arrangements, the creation and functionalization of those structures and the subsequent characterization of the metaoptics’ performance at visible (VIS) and near-infrared (NIR) wavelengths serving as a basis for an industrial evolution in optics.

• Design of EUV-systems for processing and characterization of nanostructures

In the course of the industrial implementation of extreme-ultraviolet (EUV) radiation for the realization of next-gen microchips, we are developing compact lab-based EUV-systems. These unique systems are used to support industrial applications like photoresist characterization or critical dimension metrology both on the nanoscale. Within this thesis, existing and new experimental systems shall be (re-) designed and upgraded to keep up the pace with the industrial developments. The tasks also include the development and evaluation of efficient algorithms to predict intensity distributions or reconstruct nanoscale structures by the analysis of their diffraction pattern for inline process control.

• Spin-orbit photonics in inhomogeneous anisotropic media

In standard photonics light propagation is dictated by the refractive index gradient: photons behave as massive quantum particles under the action of a potential equal to the refractive index. Nonetheless, the behavior of photons can be far more complex, especially in the presence of exotic light-matter interaction. Here we aim to investigate the strong interaction between the spin (i.e., the light polarization) and the orbital (i.e., the wave vector) occurring when photons propagate in inhomogeneous anisotropic materials. In this regime light evolution recalls the propagation of charged particles in a magnetic field, and new effects are observed due to the gradients in the Pancharatnam-Berry phase. The fundamental nature and possible applications of spin-orbit phenomena will be both pursued, in the linear and nonlinear regime, including materials such as liquid crystals, light-written nanogratings in glass, two-photon polymerized structures and biased nanoguides in Lithium Niobate.

Nanosized quantum emitters are the basis of many quantum photonic circuits. However due to the size mismatch between the nanosized emitters and the micron scale radiation fields, their coupling to propagating electro-magnetic waves is weak and difficult to control. Therefore, exploiting strongly localized nearfields of nano-resonators or plasmonic elements is considered to be a key element for the realization of strong coupling. Scanning near-field optical microscopy (SNOM) is a powerful technique to measure and study simultaneously the architecture of nanostructures and their electromagnetic near fields. Among the different types of SNOMs, the scattering pseudo-heterodyne SNOM (ps-het SNOM) offers two main advantages: high resolution in topographical and optical images by employing sharp cantilever tips and simultaneous detection of field intensity and phase by exploiting lock-in detection methods and interferometry. In this PhD project, we aim to take the performance of ps-het SNOM-based near-field detection and control to the next level with the vision to realize strong coupling to quantum emitters, as e.g. vacancy centers, quantum dots, quantum dots, lanthanide nanoparticles, and emission centers in atomically thin membranes of MoS2. To achieve this goal we study a new generation of high-performance plasmonic tips, which promise to provide unprecedented performance parameters. As a first step, the SNOM tips' performance parameters are to be evaluated by exploring the tip's interaction with different quantum systems. To explore the spectral and temporal characteristics of the quantum systems, a superfocusing SNOM setup will be combined with a time correlated single photon counting system and a single photon sensitive optical spectrometer. After establishing stable measurement methods and skills, we want to apply this tool to the in depths investigation of the interaction of the nano-sized quantum systems with plasmonic and dielectric nano-antennas. Besides experimental characterization, analytical and computational modeling shall be carried out to understand the complex behavior of the quantum emitters and their interaction with the tips.

• Spatiotemporal dynamics of nano-scale light-matter interactions in metasurfaces and atomic membranes

The control and characterization of light on length scales shorter than the diffraction limit (~500 nm) requires shaping or probing of the photonic states by nano-scale matter. Therefore, basically all nanooptical effects are coupled states of light and excited matter. Hence, the exploration of optics down to the nanoscale requires detailed knowledge about strong light-matter interaction at these ultrashort length scales. This interaction typically concerns the electronic states and happens on ultrashort time scales of a few femtoseconds. The experimental observation of such effects hence requires tools probing simultaneously the electronic matter states and the photonic states with nanometer spatial and femtosecond temporal resolution. The aim of this PhD project is to study such ultrafast nanoscale dynamics in semiconductor metasurfaces, which are hybridized with plasmonic antennas, nanowires, and atomic membranes like graphene or MoS2. To achieve this goal new experimental techniques with unprecedented temporal and spatial have to developed. Besides scanning nearfield optical microscopy (SNOM), laser driven photoemission electron microscopy (PEEM) is such a technique, which probes directly the electronic excitation of matter with the spatial resolution of an electron microscope. Temporal resolution is obtained by triggering the photoemission by few-cycle laser pulses. These ultra-short laser pulses give access to dynamical processes, inaccessible to electronic measurement systems. Laser driven PEEM is thus an ideal probe to study the photo-induced electron dynamics in the building blocks of photonic nanosystems. A typical PhD project will combine advanced instrumentation of fs lasers and ultra-high vacuum systems for electron microscopy with the physics of several novel quantum systems and metasurfaces.

• Machine learning based design of nanostructured photonic metamaterials

Photonic metamaterials are a novel class of artificial matter consisting of building blocks, which are derived from sophisticated nanotechnologies and which have a mesoscopic size smaller than the wavelength of light. Metamaterials promise to obtain complete control over all classical, nonlinear, and quantum-optical properties characterizing light propagation. By designing the metamaterials´ unit cells one can tailor the linear and nonlinear light propagation in such media beyond the limits given by natural occurring materials. A focus of the PhD topic will lie in machine learning based algorithms for inverse design processes of novel nanomaterials. The project will evolve along the lines of simulation-based design of metamaterials, their practical realization using state-of-the-art lithography-based nanotechnologies, as well as their experimental characterization to close the loop for application-oriented optimization of resulting electromagnetic parameters.

• Theoretical and Numerical Nanooptics

We study by analytical and numerical means the interaction of light in the linear, nonlinear, and quantum regime with nanostructured materials such as metals, semiconductors, dielectrics, or also molecular materials and explore applications thereof with different partners. Referential examples for such applications are, e.g., in the field of wave front shaping in integrated optical systems or for quantum sensing devices. We have activities in the field of plasmonics, optical nanoantannas, metamaterials and metasurfaces, computational material design (also known as solving the inverse problem), and quantum optics at the nanoscale in place and are currently seeking a PhD student to reinforce our team.

Optical Design | Communication ↓ (Click to see Ph.D. topics) Fellows: Prof. Peter Loosen | Prof. Bernhard Schmauß | Prof. Dr. Christine Silberhorn | Prof. Andreas Tünnermann

• Novel concepts for high-power digital laser beam shaping

Numerous approaches for dynamic beam shaping of laser radiation already exist, such as spatial light modulators (SLMs). A common problem is that the optical elements for beam shaping are not applicable for the high-power range (> 500 W). Especially in the field of laser material processing like laser hardening or laser powder bed fusion (LPBF), high laser powers are needed with a simultaneous increasing demand for individual beam shaping to optimize the process result. For this reason, we are exploring possibilities to make highly dynamic beam shaping accessible for high power applications. We are working on the optimization of existing optical elements as well as on fundamentally new approaches.

• Computational methods for application adapted intensity distributions

In many application areas such as automotive or architectural lighting, freeform optics with many degrees of freedom enable complex illumination. The surfaces of these optics are shaped to specifically redirect the light so that in total a prescribed pattern of dark and bright areas on a target surface is obtained that might e.g. be completely homogeneous within a given area or form an image (of a person, a place of interest etc.). As the surfaces and their mathematical descriptions are complex, numerical freeform optics design strategies are required. We developed several algorithms for the design of freeform optics for various optimization goals. In the next years, research will focus on increasing the robustness of freeform optics, on using coherent light sources (lasers) and on enhancing the flexibility regarding wavelength as well as thermal loads.

• Multi-physics modelling of metaoptics

Flat metaoptics consist of geometries with extents in the size of the wavelength that are arranged in a two-dimensional array on a substrate. By employing wave optical effects that cannot be achieved with classical optical elements, completely new functional behavior is obtained, e.g. a high numerical aperture (NA) or so-called anomalous reflection or refraction which goes beyond Snell’s law and the law of reflection, respectively. We develop methods that simulate the behavior of metaoptics and other small-size components using wave optical approaches. To analyze the functionality of metaoptics in macroscale setups and in combination with classical optical elements, wave optical models are combined with raytracing and rendering techniques. Within the planned project, computational methods are developed to design metaoptics for various applications such as augmented reality, laser beam shaping, and general lighting.

• Multi-outcome quantum pulse gate for time-frequency high-dimensional quantum key distribution

High-dimensional quantum key distribution (HDQKD) promises an increase in both the security and secret key rates by going beyond a traditional qubit encoding. This excludes the use of polarization and - if we additionally require compatibility with integrated optics - spatial encodings. Information can be encoded in the time-frequency domain. Our group has shown that a quantum pulse gate (QPG) implements projective measurements onto arbitrary time-frequency bases. Yet, the current device design is limited to only one single measurement outcome; a limitation that makes it unsuitable for HDQKD. The goal of this project is to implement a multi-outcome QPG for time-frequency HDQKD with more than 10 dimensions. The research strategy will combine nonlinearity engineering, resonant structures, and temporal multiplexing, and will yield a high-performing plug-and-play device that is compatible with single-mode fibre.

• High-dimensional quantum communication in tailored optical fibers

Path-encoded quantum bits have provided the basis for a myriad of proof-of-concept experiments in photonic quantum computing in the laboratory. As applications of quantum computers venture into the realm of distributed quantum information processing, a key challenge is the transmission of such states over long distances. Recent developments in multi-core fibers and tailored few-mode fibers would allow vast amounts of quantum information to be transmitted between distributed parties in a manner that is compatible with photonic quantum computing platforms.

• High-dimensional quantum communication in long-distance free-space and fiber links

Increasing the throughput of quantum communication links is a key technological challenge on the way to a global quantum internet. Research topics include the development of field- and space-ready quantum hardware, broadband quantum key distribution systems based on time- and frequency-encoded quantum states, and the integration of quantum communication systems into a long-haul optical fiber link between Jena and Erfurt and/or a local free-space optical link.

Quantum Optics ↓ (Click to see Ph.D. topics) Fellows: Dr. Maria Chekhova | Dr. Falk Eilenberger | Prof. David Hunger | Prof. Nicolas Joly | Prof. Gerd Leuchs | Prof. Ulrich Nienhaus | Prof. Dr. Ferenc Krausz | Dr. Christoph Marquart | Prof. Thomas Pertsch | Prof. Dr. Christine Silberhorn | Dr. Birgit Stiller | Prof. Andreas Tünnermann

• Single Photon Sources for Quantum Communication and Quantum Computing

Single Photon Sources are among the key elements in Quantum Communication networks and will play a major role in the interconnection of quantum computers. We investigate single photon source in 2D-Materials: such sources have supreme photon quality, are very robust and have the potential to be integrated in photonic appliances. Possible research topics include the development of a quantum payload for a cube satellite mission, experimental investigations of theories in quantum gravity and the integration of 2D materials in advanced optical systems.

• Photonic crystal fibres under pressure, one, two, three photons sources for quantum optics
• Interaction of light with single atoms/ions, optically trapped nano-particles and gaseous nonlinear optical media

The dynamics of the interaction of light and matter depends sensitively on the properties of the light field. When focusing light, the electric field in the focus is maximized by sending in linear-dipole radiation from the full solid angle, optimizing the efficiency of the interaction with dipole-like matter. We offer topics for PhD theses centered around this scenario, in particular (1) the interaction of light with single atoms/ions, (2) optically trapped nano-particles as well as (3) gaseous nonlinear optical media. The topics relate to fundamental questions in classical and quantum optics and to the development of optical quantum technologies.

• Nanoscale integrated quantum photonics

Nanoscale waveguides in lithium niobate on insulator systems are an emerging platform for integrated optics that offers unrivalled properties like small absorption losses in a wide spectral range, high optical nonlinearities, and the ability for ultrafast modulation of material properties. Based on these exceptional properties, a number of basic elements for integrated optics, e.g. low-loss waveguides, fast modulators, and nonlinear frequency converters have been demonstrated. All these demonstrations used waveguides with cross-sections in the range of a few hundred nm, showing the large potential of this platform for high-performance integrated optics that can realize complex photonic functionalities in very small devices. We aim to use this platform to move quantum optics to the nanoscale by implementing sources for photonic quantum states, optical elements to modify and control these quantum states as well as single-photon detectors in a single optical chip. This will enable to realize different quantum functionalities in lithium niobate nano-waveguides, e.g. quantum-enhanced sensing devices, sources, and receivers for quantum communication, or circuits that implement optical quantum computing. The project comprises the development, optimization, and test of individual quantum elements in such circuits, the implementation of basic quantum interference experiments to gauge the performance of complex lithium niobate quantum circuits and the design and realization of large-scale circuits that perform applicable functionalities.

• Development of integrated nonlinear optical and electro-optical devices exploiting counter-propagating interactions in periodically poled waveguides with ultra-short poling periods

Future progress in the development in the emerging field of optical quantum technologies requires compact and miniaturized solutions for quantum circuits. Lithium niobate is proven to be a well-established material platform for numerous integrated quantum optical circuits. Recent progress in the technology for the fabrication of specifically tailored domain patterns with ultra-short poling periods will complement the portfolio of integrated functional elements in LiNbO3 for quantum applications. This project aims on the development of integrated nonlinear optical and electro-optical devices exploiting counter-propagating interactions in periodically poled waveguides with ultra-short poling periods. Among them can be photon-pair sources for the generation of decorrelated quantum states and electro-optically tuneable mirrors and polarization converters.

• High-dimensional quantum Comb Entanglement

High-dimensional quantum states (known as qudits, with dimension d>2) allow storing and processing more information than the 2-dimensional qubits, and have proven to make quantum information processing more resistant to noise. Encoding such states in discrete frequency modes has key advantages, such as huge parallelization, the possibility to implement universal quantum gates, as well as compatibility with standard telecommunication components. Possible research topics include the development of frequency-entangled and squeezed light sources, novel methods to detect and manipulate frequency-entangled states using electrooptic modulators and dispersive elements, and the application of frequency-entanglement in quantum sensing and information processing.

• Quantum information processing with spatially structured photons

The structuring of the wavefront of photons allows complex entangled quantum states to be generated and promises quantum information processing with improved capacity. Research topics include engineering quantum states using diffractive optical elements and metamaterials, the propagation of spatial modes through atmospheric free-space links, mode correction of photons using machine learning, and the application of spatial quantum states in quantum information processing.

• Development of squeezed light sources for photonic quantum simulation and sensing applications

Squeezed states of light are a key resource in photonic quantum computing and quantum sensing. Possible research topics include tailoring the spectral properties of squeezed states of light, manipulation and generation of complex continuously-variable quantum states (Schrödinger cat states, Entangled Coherent States, NOON States), and the application of non-classical light sources in quantum ranging or photonic quantum computing.

• Development of quantum spectroscopy based on non-linear interferometers

Similar to microscopy, the spectroscopic analysis of substances is a crucial process in life and material sciences. One of the main obstacles in application is the lack of high-efficient detectors in vital spectral ranges. For instance, molecular fingerprint spectroscopy in the MIR suffers from poor detection efficiencies provided by InGaAs cameras. The utilization of correlated photon pairs and interferometric settings allows the achievement of spectroscopy in extreme spectral ranges while efficiently detecting visible light only. In addition, multi-photon spectroscopy of photosensitive substances becomes more efficient when harnessing photon pairs. In this project, you will develop and implement novel approaches for quantum spectroscopy. The work will involve the theoretical modelling, experimental proof-of-concept realization, and transfer into applicable devices. Particular interest should be spent on benchmarking and comparison with standard spectroscopy techniques and demonstrating the feasibility and advantage for extreme wavelengths applications.

• Investigation of higher-order events and higher-order correlations in non-linear interferometers

Microscopy is a versatile tool without which modern life science and material analysis could not exist. However, there are intrinsic limitations in the interplay of the wavelength for investigation, the available detection efficiency in that spectral range and the acceptable photon dose for the specimen. Based on quantum optical effects in non-linear interferometers one can overcome some of these restrictions by allowing the imaging in extreme wavelength ranges while detecting visible light only. So far, all implementations relied on two-photon events and two-photon correlations. Your task will be to investigate the impact of high-order photon events and high-order correlations in order to increase spatial resolution, sensitivity, and precision. Moreover, your work will include the analyze the transition from the quantum regime towards the classical regime, where stimulated rather than spontaneous conversion processes are dominating.

• Interaction of non-classical states of light with matter within the framework of entangled two-photon absorption and fluorescence microscopy

Two-photon microscopy is a special form of laser scanning microscopy that uses the non-linear effects of two-photon absorption. Since both photons are correlated (in energy, impulse, time and room), the fluorescence depends only linearly on the excitation intensity. Furthermore, the phototoxicity is minimized due to the single photon level. However, proof-of-principle experiments and fundamental questions regarding light matter interaction in a quantum mechanical description are still open. Your tasks include to address the fundamental modelling of non-classical light interaction with molecular structures to deduct strategies for enhancement of entangled two-photon absorption processes as well as the experimental implementation.

Strongfield Physics ↓ (Click to see Ph.D. topics) Fellows: Dr. Hanieh Fattahi | Prof. Stefanie Gräfe | Prof. Peter Hommelhoff | Prof. Franz Kärtner | Prof. Matthias Kling | Prof. Stefan Nolte | Prof. Gerhard Paulus | Prof. Nina Rohringer | Dr. Vladislav Yakovlev

• Particle acceleration on a nanophotonic chip

Before particle acceleration comes transport. Transport through an accelerator structure means that a particle beam can be actively steered through the required elements needed to build a particle accelerator. This is what we have achieved through a nanophotonic channel (Nature 2021). Based on this, we are now ready to build the particle accelerator on a chip. Various topics have to be tackled for this, ranging from electron beam simulation driven with the optical nearfields, via structure optimization to the integration of the optics to power the structure. * Building the accelerator on a naonphotonic chip * Next to acceleration, these structures also allow generation of attosecond electron bunches, which we will use for various laser pump--electron probe experiments.

• Efficient THz generation

We explore different ways to overcome the Manley-Rowe limit for THz generation with lasers through optical rectification through cascading in periodically poled nonlinear materials. Students will get familiar with the use of high energy short pulse lasers in driving strongly nonlinear processes. Eventually conversion beyond several percent from optical to THz is realized. The high energy THz pulses are used ifor THz acceleration.

• Photocatalysis for the synthesis of fuels and sustainable resources

The world faces tremendous challenges in environmental technology, as the emission of greenhouse gases has to be reduced rapidly and significantly to achieve climate goals. One of the main unsolved problems is the lack of technology for energy storage. A promising approach is the conversion of exhaust gases (CH4, CO, CO2, H2) to storable and transportable resources. Catalytic processes are the method of choice for this purpose, but it is difficult to trigger these reactions with thermal activation energy only. The present project should investigate the control of chemical reactions to produce fuels and sustainable resources using innovative laser technologies. Among these, coherent control using few-cycle pulses and pulse shaping will be applied to drive chemical reactions in the desired direction.

• Tailored Light-induced molecular potentials

The structure and dynamics of a molecule are governed by the forces between its nuclei and electrons. These forces give rise to the molecular potentials, on which nuclear motion and chemical reactions occur. Intense femtosecond laser fields can exert external forces comparable to the intermolecular ones. Thus, they can be used to manipulate molecular potentials on the timescales on the time scale of the nuclear dynamics. In this project, we will explore such routes to manipulate chemical reactions by means of tailored laser light.

Laser-Driven Particle Acceleration ↓ (Click to see Ph.D. topics) Fellows: Prof. Peter Hommelhoff | Prof. Stefan Karsch

• Development of ultralow-emittance electron beams for driving high-brilliance X-ray sources

Photonic Production and System Design ↓ (Click to see Ph.D. topics) Fellows: Prof. Nicolas Joly | Prof. Uli Lemmer | Prof. Peter Loosen | Prof. Heinrich Schleifenbaum | Prof. Martin Wegener | Prof. Uwe Zeitner

• Systems integration and realization of high-power digital laser beam shaping

The use of process-adapted intensity distributions and the design of optical systems for the realization of these intensity distributions is essential for digital photonics production. We are investigating new ways to generate flexible and highly dynamic intensity profiles. With the help of so-called Spatial Light Modulators (SLMs), among other devices, the phase front of the laser radiation can be manipulated digitally with high resolution which enables the dynamic control of the intensity distribution in the processing plane. Commercially available SLMs are already capable of shaping the phase front of a laser beam. However, there are significant limitations to this. For example, neighboring pixels influence each other in their phase deviation (crosstalk). For the efficient use of SLMs, a method has to be developed to circumvent, compensate or at least take into account the existing limitations in phase matching. In this project, optical systems with integrated SLMs will be developed and validated for selected applications in laser material processing.

• Application adapted intensity distributions

In laser materials processing, the intensity distribution of the laser beam significantly influences the temperature profile that is induced in the workpiece. As this temperature profile on the other hand accounts for the obtained material modifications, the processing quality and efficiency can be influenced by adapting the intensity distribution to the respective process. However, the computation of such an application adapted intensity distribution is not straightforward as an inverse heat conduction problem must be solved. In our group, we develop numerical solution methods which combine FEM and FDM solutions of the heat conduction equation with state-of-the-art optimization strategies. Up to date, these methods have been applied to laser heat treatment. In the research project, the algorithms will be extended to more complex materials, geometries, and especially processes such as laser powder bed fusion, laser welding or laser structuring with ultra-short pulsed radiation.

• Digitalization and digital twins in optical technologies

The increasing digitization of products and production processes not only changes our everyday life and creates new possibilities almost daily, but also impacts the design process and operation of optical systems. The use of sensor technology during assembly (wavefront sensor) and the integration of miniaturized sensor technology in optical systems enables the feedback of the acquired data into the digital (optical) models. It becomes possible to create a digital optical twin (DOT), which accompanies an optical system over its entire life cycle. This makes it possible to generate service life forecasts, enable targeted adjustments and plan adapted maintenance intervals at an early stage. In addition, improvements for future product design upgrades can be derived from the obtained data. Another research topic in the context of digitization is the use of artificial intelligence and the exploration of quantum computing for optics design and multi-physics optimization problems. One aim of using AI algorithms is the acceleration and automation of the design process of optical systems. Currently, the use of reinforcement learning to automate the design process of optical systems is being investigated.

• Interaction of laser radiation and polymers in Laser Sintering

Laser Sintering (LS) is a powder bed based Additive Manufacturing (AM) technology for the processing of polymer powders. To generate polymer parts with LS, CO2 lasers with a wavelength of 10.6 µm are used as standard, as the CO2 laser radiation is strongly absorbed by the polymer powders. In contrast, polymers hardly absorb any radiation in the near infrared (IR) at about 1 µm wavelength (e.g. fiber and diode laser radiation). In order to deepen research in this field, a fundamental understanding of the interaction of the laser radiation with different wavelengths and polymer materials must be developed. For this purpose, both the material itself as well as the interaction with the laser source have to be fundamentally investigated. Material combinations of polymers and absorber materials increase the absorption capacity at wavelengths of approximately 1 µm and offer the possibility to process polymers, but at the same time affect the resulting component properties. In addition, the fragile heat balance in LS (maximum variations of ±2-4°C) is to be analyzed with improved heating concepts in order to extend the knowledge gained on the processing of e.g. high-performance polymers such as PEEK with different radiation sources.

• Simulation of the correlation between laser radiation and the polymer melting process in Laser Sintering

Nowadays, laser technology is used in many cases to melt materials. Especially in the field of Additive Manufacturing (AM) this is one of the most common processes (e.g. in Laser Sintering – LS). However, the exact interaction between the laser radiation and the molten material particles is not yet well understood. In view of the research into the processing of polymers by LS using laser beam sources with wavelengths that are insufficiently absorbed by the polymers, the sintering process must be analyzed in detail. The wavelength absorption as well as the conversion of the introduced energy to form sintered and molten polymer particles have not been sufficiently investigated so far. As a result, the formation of the molten material in correlation with the laser radiation, the formation of macro- and microscopic defects and the thermal behavior in x-, y- and z-direction must be studied. Therefore, different simulation methods (e.g. DEM, FEM) and monitoring equipment (e.g. pyrometers) will be further developed and applied to gain a fundamental understanding of the interaction between laser radiation and melting behavior, which will be calibrated and validated by iterative experiments.

• Adaption of the chemical material composition for cross-layer crystallization in Laser Sintering

Laser sintering (LS) is a powder bed based additive manufacturing (AM) technology for the processing of polymers. Since LS is a layer-by-layer process in which the material is sintered and melted, the interconnection between the individual layers is of utmost importance to achieve the required stability of the component in the build-up direction. This could be achieved by increased crystallization of the material across the layers, requiring research into the adaption of the chemical composition of the polymer. Furthermore, to produce high-performance polymer components with LS, additives such as carbon or glass fibers are often added to the base material itself. During the melting process of the layers to each other, these fibers are interference bodies and reduce the layer bonding. Accordingly, the matrix material (base polymer) must achieve the required crystallization across the layers and therefore requires material adaptation which has to be investigated.

X-ray Science ↓ (Click to see Ph.D. topics) Fellows: Prof. Henry Chapman | Prof. Stefan Karsch | Prof. Matthias Kling | Prof. Ralf Röhlsberger | Prof. Tim Salditt

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Future Vision 2020 and Beyond—5 Critical Trends in Eye Research

Suber s. huang.

∗ Retina Center of Ohio, Cleveland, OH

† National Eye Health Education Program Steering Committee, National Eye Institute, National Institutes of Health, USA

‡ Bascom Palmer Eye Institute, University of Miami, Miami, FL.

Ophthalmology has been at the forefront of many innovations in basic science and clinical research. The randomized prospective multicenter clinical trial, comparative clinical trials, the bench to beside development of diagnostic and therapeutic devices, the powerful combination of biostatistics and epidemiology, gene therapy, cell-based therapy, stem cell therapy, regenerative medicine, artificial intelligence, and the development of personalized molecular medicine continue to propel us forward. This article summarizes several critical trends in eye research.

Innovative translational research continues to bring new solutions to blinding retinal diseases. The discovery of the genetic code presaged a day when the development of molecular tools and understanding of the basis of disease would lead not only to disease management but potentially lifelong cure. After decades of investigation, gene therapy is now a reality for a single autosomal recessive bi-allelic disease, Lebers Congenital Amaurosis. Its success has paved the way for a myriad of conditions once thought to be untreatable. In parallel, the progress to utilize pluripotential stem cells, immunomodulation, computational biology, and continued investigation into the fundamental mechanisms of cell and molecular biology is breathtaking in its rapidity. The next decade is likely to be the most exciting in the history of medicine. It will be essential that research progresses in a meticulously thoughtful, ethical, and collaborative process that safeguards the trust of our work and that of the society we serve.

Presented as the International Award Lecture, Asia-Pacific Vitreoretinal Society meeting, November 2019, Shanghai China.

GENE THERAPY

Hereditary diseases of the retina represent a group of diseases with several heterogeneous mutations that have the common result of progressive photoreceptor death leading to blindness. Retinal degenerations include multifactorial diseases such as age-related macular degeneration, Lebers congenital amaurosis type 2, Stargardt disease, and retinitis pigmentosa. There is currently no cure for degenerative retinal diseases; ophthalmology has been at the forefront of the development of gene therapy, which offers hope for the treatment of these conditions. Clinical trials for achromatopsia, choroideremia, MERKT, Leber congenital amaurosis 2, Leber hereditary optic neuropathy, neovascular age-related macular degeneration, retinitis pigmentosa, Stargardt disease, Usher syndrome 1B, X-linked retinitis pigmentosa, and X-linked retinoschisis are underway ( www.ClinicalTrials.gov )

The first successful gene therapy product for an inherited disease was approved by the US Food and Drug Administration (FDA) in December 2017. Of note, indication statement was not for a specific disease but “for the treatment of patients with confirmed biallelic RPE65 mutation-associated retinal dystrophy.” 1 , 2 This seminal observation highlights a key difference between traditional pharmacologic therapy and that of gene therapy where clinical phenotypes may have a common genetic basis. Approval followed 20 years of research to identify the mutation causing Lebers congenital amaurosis type 2 (LCA2), development of an animal model, 3 techniques for viral transfection, and establishment of biomarkers to evaluate efficacy. 2 , 4 – 7 The capability to develop animal models for testing of gene therapy is a critical precursor to human clinical trials.

The eye is well-suited for target organ gene therapy. Its uniqueness as an immune-privileged organ that is isolated from much of the systemic host immune response is that retinal cells do not divide after birth, and its small size confers singular advantages over other areas of human gene therapy. These advantages are key factors for gene therapy success, an isolated target organ/tissue with little opportunity for spillover effect, that transfected retinal cells are likely to maintain transgene production for life, and that the volume of distribution is also small. All are critical factors for transfection efficiency and clinical success.

CHALLENGES AND STRATEGIES

Despite the success and approval of gene therapy for bi-allelic RPRE65 mutation-associated retinal dystrophy, many challenges remain. Identification of a causative gene for retinal and ocular disease is difficult and elusive. Although treatment of single gene mutations is most likely to have positive clinical results, the treatment of common causes of blinding retinal disease [diabetic retinopathy (DR), age-related macular degeneration, and retinopathy of prematurity] are likely to be polygenic in nature. These conditions may require different approaches targeting neurotrophic factors that preserve function, by blocking apoptotic or degenerative pathway, or through expression of a blocking anti-vascular endothelial growth factor protein. 8

A second major challenge is the size of genetic payload. Adeno-associated virus (AAV) has emerged has an efficient method of gene delivery with low levels of immunogenicity and side effects as compared with lentivirus, adenovirus, or nonviral transfection systems. 9 – 11 AAV-2 and AAV-8 are among many possibilities for naturally occurring viral vectors but have an effective payload of only 5 kb of DNA. 12 Most genes encoding for major structural or regulatory functions are significantly larger. Strategies to address this include a double vector approach where each vector carries a unique fragment into the cell. Host mechanisms anneal each transgene via intermolecular recombination to form a product nearly twice the size of a single vector. Protein expression was noted to be lower but was sufficient to improve the retinal phenotype in mouse models of Stargardt disease and Usher IB. 10 , 11

Assessment of clinical response and efficiency of transgene expression is a third area of study. The use of promotors and directed evolution of high efficiency mutant AAV has been shown to transfect the outer retina in small animal models but failed to reproduce similar levels of expression in dogs and nonhuman primates. 13 , 14 It is unknown whether the anatomy of humans, volume of distribution, the level of transgene production needed to ameliorate the gene defect, or other mechanisms contribute to these disappointing results. Measurement of transfection efficiency in human clinical trials is also a challenge. Measurement of aqueous/vitreous transgene protein levels is a useful biomarker for production but does not necessarily reflect whether these are enough to produce similar physiologic changes noted in preclinical studies. Subjective measurement of function including visual acuity, microperimetry, and visual field assessment remains the primary outcome measures in studies of inherited retinal disease but is severely limited in assessing functional changes for the entire retina. Objective testing such as electrophysiology combined with increasingly detailed anatomic assessment holds promise. A unique test of visual function was created to test patients receiving gene therapy for patients with RPE65-mediated Leber congenital amaurosis type 2. A new quantitative for visual function and mobility was created in collaboration of the FDA, the multiluminance mobility test. Twelve different mazes were created for the subject to navigate with arrows to guide the subject around and over a variety of obstacles under light conditions ranging from dim to bright. The subjects were filmed and scored via a masked independent reading center. 2 , 15 To date, this is the standard for testing visual function in patient with inherited retinal disease who have progressive night blindness. Optimization of delivery systems, viral vectors, and improved functional testing are needed.

To date, immunogenicity of AAV vectors and adverse events are low in early-phase studies for a variety of conditions. On December 16, 2017, the US FDA approved Luxturna (voretigene neparvovec-rzyl) to treat children and adult patients with bi-allelic RPE-65 mutation-associated retinal dystrophy. Luxturna is the first directly administered gene therapy approved in the United States that targets a disease caused by mutations in a specific gene. However, many questions remain unanswered. Will every gene therapy have an acceptable profile of safety and efficacy? What is the durability of effect? Will transgene production remain constant over a lifetime? Will promotors and other enhancements to drive gene production have adverse effects? Could there be unanticipated effects if additional gene therapy is desired in the same eye/fellow eye? What are the financial and economic implications of cure? This milestone is but a first step in the treatment of our most intractable blinding diseases.

Presaged by the discovery of the genetic code, 25 years of gene therapy research has culminated in the first successful gene therapy for inherited disease in the US. Gene-targeted mutations have determined the functions of genes, their functional domains, and the mechanisms underlying the dysfunction of their disease alleles. Ongoing discovery will provide new molecular targets and will form the basis for clinical trials for many blinding inherited retinal dystrophies. Viral vector-mediated pronuclear transgenesis for retinal disease has promise but polygenic and multifactorial diseases such as age-related macular degeneration (AMD) are likely to require different approaches. 8 , 16 – 18 Whole gene editing or gene silencing using CRISPR/Cas9 technology can be used to directly treat target tissues and to develop target-specific strategies using iPSC (induced pluripotential stem cells). Other strategies of inducing mechanisms which promote neuroprotection or retard cell damage are likely pathways to pursue. For eye diseases which have a genetic determinant, we begin a decade where the goal is not just management, but cure.

Immunomodulation

There is increasing recognition of the role of host immunity in disease. Immunotherapy, immunomodulation, tumor targeting, and chimeric antigen receptor T-cell immunosensitization techniques have emerged as another strategy for clinical treatment. Public confusion exists over the term stem cells. Human embryonic stem cells and induced pleuripotential stem cells (iPSCs) can be manipulated in a wide variety of ways in the treatment of retinal disease. These will be discussed in the section on Regenerative Medicine to follow.

Another cell type is the mesenchymal stem cell (MSC). Neither derived from mesenchyme nor a true progenitor cell, the MSC is traditionally defined as a bone marrow stromal cell which may develop into chondrocytes, adipocytes, myocytes, and osteoblasts. They are found in enriched populations in the bone marrow, umbilical cord, adipose tissue, molar teeth, and in amniotic fluid. They do not have the ability to differentiate to produce hematopoietic cells. Long thought to be a structural connective cell, our laboratory in 2012 demonstrated elimination of corneal scarring in a murine model of bacterial keratitis and reduction in the neovascular response in a laser injury model in the rodent retina. 19 , 20 Numerous other studies have confirmed that MSCs exert strong immunomodulatory effects through a variety of mechanisms including those that “cloak” the MSC surface rendering it invisible to host immune response, that modulates lymphokine and cytokine response, and placing erythropoietin gene modified MSC in the subretinal space for the treatment of retinal degeneration. 21 – 23 Dubbed “nature's natural healers,” these cells have chemotactic attraction to sites of inflammation and exert immunomodulation of scarring in multiple studies of microbial infection. 24 MSCs have been shown to improve corneal regeneration, further supporting the integrated role of limbal and MSC therapy. 25

In 2011 and 2012, we described a new mechanism for the pathogenesis of DR. 26 – 28 We found convincing evidence that there was pericyte autoimmunity in the retinal capillaries of deceased patients with DR. An autoimmune mechanism may explain how retinal microvascular disease might progress even with good glycemic control. With time and immune attack on capillary pericytes, endothelial dysfunction leads to loss of endothelial cell integrity, macular edema, and eventually nonperfusion. These findings suggest that therapeutic immunomodulation may be a pathway to retard or ameliorate diabetic microvascular disease throughout the body. Although there is growing recognition for a therapeutic effect of MSCs in ocular degenerative disorders, problems of precision targeting of tissues and survivability remain practical issues of concern. 29 , 30 The role of systemic or periocular MSC infusion for DR disease requires additional investigation.

Chimeric antigen receptor T-cell therapy is the latest immunomodulatory therapy to use host immune mechanisms to specifically identify target cells. Primarily used in the treatment of cancer, this technique uses T-cells modified by chimeric antigen receptors to selective target tumor surface antigens. 31 , 32 This approach has not been used in the eye but is an example of a novel approach for targeted immune therapy.

Regenerative Medicine

Strategies for tissue replacement or regenerative therapies have been building momentum as understanding of stem cell biology, substrates, delivery systems, nanomaterials, and 3-D machined structures converge. Investigations using structures which combine cells and/or substrates include preclinical investigations of corneal disease, glaucoma, cataract, age-related macular degeneration, and retinitis pigmentosa. The use of 3-D and microengineering of bionic interfaces is being tried in many areas. Phase I studies include: implantation of ex vivo cultured corneal stroma stem cells to reverse stromal scarring, and replacement of glaucomatous trabecular meshwork with stem cell-derived trabecular meshwork cells for intraocular pressure regulation. Phase II studies include cell suspension and cells on matrix subretinal implantation of stem-cell derived retinal pigment epithelium (RPE), subretinal RPC (retinal progenitor cell) transplant, and trophic support to retard or prevent the progression of retinal cell death. 33

Retinal stem cell transplantation and tissue engineering have largely focused on replacement or regeneration of photoreceptors (PRs) and retinal pigment epithelial cells (RPEs). 34 , 35 Retinitis pigmentosa is a heterogeneous genetic mix of diseases which may affect PRs, RPEs, or both. Similarly, age-related macular degeneration is also characterized by PR loss. Whether PR loss is primary or a secondary effect due to RPE dysfunction, the ability to regenerate normal function of the PR and RPE is an attractive therapeutic option. For patients in advanced stage of outer retinal degeneration, gene therapy is unlikely to restore function and, at best, may only preserve the integrity of remaining tissues. Whether tissue replacement techniques ultimately improve vision has yet to be conclusively determined. 35

Sources for RPE transplantation include human fetal RPE cells, allogenic human cadavers, alternative cell sources, and human pluripotential stem cells (hPSCs) (including human embryonic stem cells, and human iPSCs). Each has demonstrated the ability to assume some of the functions of native tissue without conclusive improvement in vision. The need to provide large numbers of clinical grade replacement cells has tipped the process toward the use of human pluripotential stem cells. hPSCs are induced to undergo embryologic differentiation into immature PR cells or RPE cells. For conditions primarily characterized by PR loss such as some forms of RP, a suspension of immature PR cells may be placed in the subretinal space. For patients with RP or atrophic AMD characterized by absent PR and RPE, both tissues may be required. For RPE dystrophic changes with preservation of PR, an RPE cell suspension alone might be used. 33 – 35 Successful implantation of a bioengineered RPE cell on a monolayer has been successfully performed and demonstrates proof of principle in patients with advanced, dry age-related macular degeneration, and macular atrophy. 36 Ultimately, success of this technology will be defined by sustained viability of host and transplanted tissue, restoration of physiologic function, and stabilization or improvement in visual function. 33 – 35

Rescue strategies that seek to induce positive trophic effects from implanted tissue are being investigated. The subretinal space is believed to have moderate immune privilege. However, inflammation was noted in studies of subretinal injection of transplanted allogenic iPSC-RPE cells in rhesus macaques and minipig models. 37 , 38 It is becoming apparent that transfer of cytoplasmic materials between transplanted cells and the host cells occurs when enough viable host cells are present but does not occur when disease is advanced, and PRs are in low number. 36 These findings suggest that the timing of tissue transplantation is important to rescue existing PR function and maximize transplantation effect. Numerous Phase 1/2 studies are underway and explore intravitreal cell suspension, subretinal cell suspension, stem cell on scaffold, and suprachoroidal subretinal techniques. Designed primarily as proof of principle studies, these human trials have demonstrated broad tolerability and evidence of cell integration. 35 Whether retinal stem cell transplantation for retinal dystrophy or advanced dry AMD can retard disease progression or to improve retinal function is unknown and awaits further investigation.

Regenerative medicine holds significant promise for those for whom replacement of tissue is the best approach to restore neuroretinal function. An intriguing recent study of in vitro cortical brain organoids demonstrated oscillatory potentials at a level equal to the visual potentials noted in a 12-week-old premature infant. This extraordinary finding demonstrates the potential of regenerative medicine strategies to repair or replace neural tissue. Because the eye is an extension of the central nervous system, guiding eye precursor cells to full development may be a future approach to inherited and degenerative eye disease. 39

Artificial Intelligence

Perhaps no technological advance is as widely anticipated as the introduction of artificial intelligence (AI) into the medical biome. Alternately feared and hailed as a paradigm shift in clinical care, AI engenders deep feelings that accompany transition into civilization's fourth industrial revolution. 40 Each medical specialty will have areas where AI will help analyze massive data sets, identify clinically relevant patterns of disease, anticipate disease progression, guide clinical care, and optimize operations and resources. Electrocardiography, dermatology, radiology, and breast cancer screening all utilize image recognition. 40

In ophthalmology, the data generated from increasingly sophisticated imaging modalities are surpassing the ability to synthesize the clinical dataset. The rapidly expanding number of tests and the amount of data gathered are overwhelming the clinician's capacity to perform detailed analysis. AI will have the ability to identify patterns, progression, and most importantly, new markers that guide management. 41 – 43 It is worthwhile goal of AI programs to enhance the clinician's ability to practice more efficiently, more effectively, and to intervene before function is lost.

DEFINING AI

AI broadly refers to computer programs with the ability to learn and reason like humans. After training extensively on fundus images of patients with known grades and severity of DR, AI independently provides diagnostic recommendation. In the example of DR, AI might perform screening of patients with known diabetes and provide a simple output: DR present, DR absent, or needs triage for additional testing.

Machine Learning algorithms feature programing that instills the ability to learn without being explicitly programed. Machine learning is a subset of AI that permits independent review of datasets with previously known DR to “learn” what DR looks like, identify key features, and assign a diagnosis and stage. Much more sophisticated than “simple” AI, most current AI is at or near this level of sophistication. Ten thousand known imaging data sets are needed to begin to acquire this more sophisticated level of analysis.

Deep Learning subset of machine learning is the most powerful of the 3 modalities. Deep learning utilizes artificial neural networks that can learn and adapt from vast amount of data. Deep learning requires large curated data sets. One hundred thousand image sets were used in the National Institutes of Health chest x-ray studies and for dermatology deep learning projects. 44 , 45 Deep learning for DR would be able to identify and assign classification of DR from unknown retinal images. Over time, continuous learning on millions of images would permit searches for new patterns, biomarkers, and prognostic factors for disease progression. The ability to predict progression and the optimal time for intervention would forever change the paradigm for management, selection of subjects for clinical trials, and the efficiency of clinical care.

It is estimated that Deep Learning on 3D reconstructed images combining multimodal imaging would require training on 500,000 stereo paired images. Image sharpening using adaptive optics and image synthesis that sharpen weak imaging will be critical to avoid imprecise interpretation to default to human imaging. 46 , 47 , 42 Other challenges include the identification of training data sets, validation testing of data sets, sensitivity testing for heterogeneous populations, generalizability, display of analyzed data, algorithms for clinical care, deployment of systems, and financial impact. 41

Opportunities for AI in Medicine

Diagnostics.

• Reading imaging scans such as x-Rays, magnetic resonance imagings, ultrasounds, and so on, with increased accuracy
• Conduct virtual biopsies and assist in screening for cancer

Administrative

• Automate routine tasks for hospital staff
• Monitor member interactions with call center staff to ensure that calls are compliant
• Utilize Electronic Health Records as a predictor of patient risk

Patient Monitoring

• Integrate with smart devices to alert and to aid in the prevention of complications such as sepsis
• Leverage data provided by patient devices such as smart watches and mobile pictures to scan for risk factors while the patient is not at the site of care

Clinical Research

• Collapse data set to eliminate patients who are unlikely to progress or to respond to treatment
• Will help direct patient management by making recommendations on follow-up

This daunting challenge would seem to be on a distant horizon but consider the story of Stockfish and AlphaZero. 48 From its earliest inception, computer programming had its roots in game theory. The race to surpass the human mind in games of multidimensional thinking like Go, Shogi, and Chess were felt to be forever beyond the grasp of nascent computer programming. In 2018, Stockfish version 9 was the undisputed king of the chessboard. With every move of every game in recorded history in its database and computational speed of 60 million moves per second, Stockfish was lightyears ahead of the programs than first conquered the best human players in the world. Pitted against an upstart program in a 1000 match challenge was AlphaZero. The program could calculate a mere 60,000 moves per second and had not one game in its database. With no match experience and armed only with the instructions of play, AlphaZero was armed only with Deep Learning and a novel neural network. The rest is history. After 3 hours of self-study, AlphaZero registers its first win against the most powerful chess program in history. After 9 hours of play at a limit of 15 minutes a move (a lifetime in computer chess), AlphaZero never lost again.

The power and speed of deep learning programs will improve our ability to care for patients and accelerate every aspect of our journey to molecular medicine and individualized care. The future is now.

CONCLUSIONS

This review of critical trends in retinal research has touched on some of the vast efforts of clinician scientists around the world. The last critical trend is the need for collaboration. The randomized clinical trial, the Diabetic Retinopathy Clinical Research network, the Human Genome Project, and virtually every area and strata of civilization will depend on the ability of people to work together toward a common goal. Opportunities for misconduct, misuse, or worse may intensify. The ability to alter the human genome through gene editing and somatic gene rearrangement provides limitless chances for unintended consequences.

And yet, we are living in the most hopeful time in our history. We have limitless chances to improve the human condition and the opportunity to do so together. “If you want to go fast, go alone. If you want to go far, go together.”

The authors have no conflicts of interest to disclose.

Financial Disclosure: American Academy of Ophthalmology—C; American Society of Retina Specialists—C; Asia Pacific Academy of Ophthalmology—C; Asia Pacific Vitreoretinal Society—C; Diopsys—C, L, S; i2i Innovative Ideas, Inc. —C, O; Lumoptik—C, O; NEHEP/National Eye Institute/NIH—C; RegenXbio—C; Regenerative Patch Technologies—C; Second Sight—C; Spark Therapeutics—C; Volk Optical—C, L; Washington University, St. Louis—C. Category Code Legend: C indicates Consultant/Advisor; E, Employee; L, Lecture Fees; O, Equity Owner; P, Patents / Royalty; S, Grant Support.

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Researchers unveil unique tidal disruption event with pronounced early optical bump

by Chen Na, Chinese Academy of Sciences

A research team from the University of Science and Technology of China (USTC) of the Chinese Academy of Sciences (CAS) presented a detailed analysis of a tidal disruption event (TDE) with unique characteristics, providing new insights into the behavior of TDEs and their multiwavelength emissions. The study was published online in The Astrophysical Journal Letters .

When a star ventures too close to a supermassive black hole at the center of a galaxy, it gets torn apart by the black hole's immense tidal forces, resulting in a phenomenon known as a TDE.

The researchers found that the AT2023lli event observed by various ground and space telescopes including the newly constructed Wide Field Survey Telescope (WFST) jointly operated by the USTC and the Purple Mountain Observatory of CAS exhibited unique features unlike previous TDEs. Traditionally, TDE light curves display a smooth "rapid rise, slow decline" trend. However, AT2023lli deviated from this pattern significantly.

Optical monitoring revealed a strong "bump" in its early light curve, lasting nearly a month and separated by two months from the main peak. This extended and pronounced "bump" was unprecedented in TDE observations. The researchers proposed that the "bump" could be the result of the self-intersection of the stream debris, while the primary peak was likely generated by the reprocessed emission from the accretion process.

Moreover, the researchers observed delayed and intermittent X-ray emissions compared to optical/ultraviolet (UV) radiation, which they attributed to the obscuration of the accretion disk by outflowing material, resulting in the absorption and reprocessing of soft X-rays into optical/UV radiation. The intermittent nature of the X-ray emission was suggested to be due to the presence of an inhomogeneous reprocessing layer around the accretion disk , which could be associated with the obscuring material's patchy distribution.

This study underscores the importance of high-cadence, multiwavelength sampling in understanding the physics of TDEs. The sensitivity of WFST is highlighted in providing high-quality multicolor photometric data during the late evolution of AT2023lli.

The unique survey design of WFST's high-cadence deep fields, coupled with the recently launched Einstein Probe, holds promise for discoveries in transient source research including TDEs.

Journal information: Astrophysical Journal Letters

Provided by Chinese Academy of Sciences

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New findings on pancreatic anatomy may affect diabetes research and treatment

by Claes Björnberg, Umea University

Researchers at Umeå University have succeeded in imaging an entire human organ, a pancreas, in microscopic resolution. By staining different cell-types with antibodies and then using optical 3D imaging techniques to study the entire organ, their data provides a partially new picture of the pancreas.

The results may be of great importance for diabetes research , especially when developing various new forms of treatment. The study is published in Nature Communications .

The pancreas is a key organ for the development of diabetes, a disease that today affects over half a billion people. It contains millions of small cell clusters, the so-called islets of Langerhans, which function to regulate blood sugar levels in the body.

The islets chiefly contain beta- and alpha-cells that produce the hormones insulin and glucagon, respectively. Insulin is secreted into the bloodstream and acts much like a key to unlock the body's cells so that they can take up sugar (glucose) after a meal, the main form of energy used by the body. Glucagon in turn releases glucose stores when we need a supply of energy. These two cell-types also communicate directly with each other to optimize the correct glucose level in the body.

"Both insulin and glucagon cells were discovered over a hundred years ago, and it has long been believed that the islets should contain both cell types to form a fully functioning unit," says Ulf Ahlgren, professor at the Department of Medical and Translational Biology.

Since the islets of Langerhans make up only a small percentage of the pancreas, even though they occur in such large numbers, they have historically been very difficult to study directly within the pancreas. In most cases, researchers have had to study tissue sections that only provide a 2D image of a very small part of the organ. Now, Umeå researchers have used optical 3D techniques in which different cell-types can be marked with fluorescently colored antibodies.

Entire organ at microscopic resolution

"By dividing the entire organ into smaller parts, we enable the antibodies to get where they need to go. Since we know where each piece comes from, we can then, after scanning the different parts individually, 'reassemble' the entire pancreas again using computer software. This allows us to perform a plethora of calculations and study which cell-types are present, as well as where they are located in 3D space, as we know the 3D coordinates, their volume, shape and other parameters for each and every stained object in the entire organ," says Ahlgren.

In addition to new data on how insulin-producing cells are distributed in the pancreas, the researchers now show that glucagon-producing cells are not present in as many as 50% of the islets of Langerhans that do contain insulin cells. This is contrary to what was previously thought, where islets were believed to contain both insulin- and glucagon-expressing cell-types with the same islet.

"This was a surprise to us, and I believe that these results may be of great importance for diabetes research. First, it shows that the islets have a much more uneven composition, or cellularity, than previously thought. This could mean that islets of different composition might be specifically specialized to respond to different signals and/or operate in different metabolic environments. Of course, we really want to find this out," says Ahlgren.

"Second, a great deal of research in the diabetes field is carried out on isolated islets of Langerhans from deceased donors. Since we also show that this uneven composition is largely linked to islet size, it means that results from such experiments may not fully reflect how the islets are structured and function in the living pancreas. This could potentially be important for everything from islet transplants in type 1 diabetes to studies trying to produce islets of Langerhans from stem cells."

Basis for future studies

The research team will now continue to work to see if their methods can be used to determine whether other cell types in the pancreas also contribute to the formation of the islets in a way that has not previously been known. In addition, they will study whether it looks similar in mouse models, which could affect the use of mice for preclinical diabetes research.

"The methods and data we are now publishing will be able to form an important basis for future studies of human material in order to better understand what happens in the pancreas in the development of type 1 and type 2 diabetes, but also for diseases such as pancreatic cancer," says Ahlgren.

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Apr 15, 2024

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Apr 11, 2024

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Optical physics articles within Scientific Reports

Article 20 April 2024 | Open Access

Photoresponse of new azo pyridine functionalized poly(2-hydroxyethyl methacrylate- co -methyl methacrylate)

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Article 18 April 2024 | Open Access

Modulation instability in nonlinear media with sine-oscillatory nonlocal response function and pure quartic diffraction

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Measurement of mass force field driving water refilling of cuttage

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Large enhancement of red upconversion luminescence in beta Ba 2 Sc 0.67 Yb 0.3 Er 0.03 AlO 5 phosphor via Mn 2+ ions doping for thermometry

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Enhancing the color gamut of waveguide displays for augmented reality head-mounted displays through spatially modulated diffraction grating

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Link budget analysis of bi-directional LEO and GEO optical feeder links advancing the beam wander model’s accuracy

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Article 09 April 2024 | Open Access

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Effect of acidic polymers on the morphology of non-photochemical laser-induced nucleation of potassium bromide

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Optimizing PCF-SPR sensor design through Taguchi approach, machine learning, and genetic algorithms

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Light squeezing enhancement by coupling nonlinear optical cavities

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Speeding up the classical simulation of Gaussian boson sampling with limited connectivity

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Complete electromagnetic consideration of plasmon mode excitation in graphene rectangles by incident terahertz wave

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Analytical formulation of spatiotemporal modulated graphene-based waveguides using Floquet-Bloch theory

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Surface potential-adjusted surface states in 3D topological photonic crystals

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Quantum scissor from exact generalized photon number statistics

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Physics-assisted machine learning for THz time-domain spectroscopy: sensing leaf wetness

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Hybridization of graphene-gold plasmons for active control of mid-infrared radiation

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From instable directional switching to controlled unidirectional operation in a nonlinear fiber ring laser

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Voltage-controlled two-dimensional Fresnel diffraction pattern in quantum dot molecules

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Quantum measurement enables single biomarker sensitivity in flow cytometry

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New research defines specific genomic changes associated with the transmissibility of the monkeypox virus

Mount Sinai scientists, in collaboration with researchers from the Carlos III Health Institute (ISCIII) in Madrid, Spain, have located and identified alterations in the monkeypox virus genome that potentially correlate with changes in the virus's transmissibility observed in the 2022 outbreak. The findings were published April 18 in Nature Communications.

Monkeypox virus (MPXV) is a double-stranded DNA virus that can infect animals and humans. MPXV causes a disease known as mpox, with symptoms that include fever, swollen lymph nodes, and a rash. Most cases are mild and tend to get better on their own; however, mpox can be very painful and may lead to permanent scarring. First encountered in 1958 in crab-eating macaque monkeys imported to Belgium, MPXV has caused sporadic human disease outbreaks since the 1970s in Central and Western Africa. In May 2022, multiple countries, including the United States, reported an increasing number of MPXV infections and associated disease, including clusters in cases potentially linked to super-spreading events in Belgium, Spain, and the United Kingdom. While the number of new cases associated with the 2022 spillover has decreased over time, cases of the disease are still occurring among unvaccinated individuals, including a current increase in Central Africa due to a new spillover. As the virus's circulation in humans increases, the risk of emergence of a more transmissible variant capable of becoming endemic in the human population increases.

"Biopreparedness and virological surveillance involves studying the causes that favor zoonotic spillover and facilitates human-to-human transmission. When we observe significant changes in basic epidemiological features of a viral agent like monkeypox, it should reinvigorate our interest in understanding those transmission conditions. The increasing number of cases currently happening in Africa, and the 2022 epidemic, should be clear alert signals," says Gustavo Palacios, PhD, Professor of Microbiology at the Icahn School of Medicine at Mount Sinai and a senior author of the study.

To carry out the study, researchers analyzed samples from 46 patients infected with MPXV whose diagnosis and sequencing were carried out at the ISCIII at the beginning of the 2022 mpox outbreak. The team performed high-quality sequencing of each study participant's complete monkeypox virus genome to determine possible correlations between genomic variations in the different groups of sequences and epidemiological links associated with the virus's ability to evolve, transmit, and infect.

According to the research team, recurrent observed genomic changes were located in areas of the genome that could be related to viral adaptation. Those specific locations would contribute to modulating the viral replication cycle, adaptability, and path of entry and egress. These alterations appear in areas known as low complexity genomic regions, which are particularly difficult to sequence and analyze, explaining why they were overlooked before. This highly sophisticated complete genome sequencing was made possible through the use of two advanced sequencing technologies: single-molecule long-read sequencing (to cover highly repetitive regions) and deep short sequencing reads (to provide accuracy and depth).

By detailing the genomic alterations within these repetitive genomic sequences and linking them to critical viral functions, researchers provide a plausible explanation for the heightened transmissibility observed during the 2022 mpox outbreak.

"These findings might be offering the first hints to help us understand the unique features of the strains associated with sustained human-to-human transmission, which has not ever been observed in these agents," says Dr. Palacios. "Better understanding of the doors that facilitate transmission of viral agents and impact their clinical presentations will enable us to develop more effective prevention and treatment strategies."

• HIV and AIDS
• Infectious Diseases
• Microbes and More
• Bird Flu Research
• Microbiology
• Epstein-Barr virus
• Flu vaccine
• Hepatitis E
• West Nile virus

Story Source:

Materials provided by The Mount Sinai Hospital / Mount Sinai School of Medicine . Note: Content may be edited for style and length.

Journal Reference :

• Sara Monzón, Sarai Varona, Anabel Negredo, Santiago Vidal-Freire, Juan Angel Patiño-Galindo, Natalia Ferressini-Gerpe, Angel Zaballos, Eva Orviz, Oskar Ayerdi, Ana Muñoz-Gómez, Alberto Delgado-Iribarren, Vicente Estrada, Cristina García, Francisca Molero, Patricia Sánchez-Mora, Montserrat Torres, Ana Vázquez, Juan-Carlos Galán, Ignacio Torres, Manuel Causse del Río, Laura Merino-Diaz, Marcos López, Alicia Galar, Laura Cardeñoso, Almudena Gutiérrez, Cristina Loras, Isabel Escribano, Marta E. Alvarez-Argüelles, Leticia del Río, María Simón, María Angeles Meléndez, Juan Camacho, Laura Herrero, Pilar Jiménez, María Luisa Navarro-Rico, Isabel Jado, Elaina Giannetti, Jens H. Kuhn, Mariano Sanchez-Lockhart, Nicholas Di Paola, Jeffrey R. Kugelman, Susana Guerra, Adolfo García-Sastre, Isabel Cuesta, Maripaz P. Sánchez-Seco, Gustavo Palacios. Monkeypox virus genomic accordion strategies . Nature Communications , 2024; 15 (1) DOI: 10.1038/s41467-024-46949-7

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Research: More People Use Mental Health Benefits When They Hear That Colleagues Use Them Too

• Laura M. Giurge,
• Lauren C. Howe,
• Zsofia Belovai,
• Guusje Lindemann,
• Sharon O’Connor

A study of 2,400 Novartis employees around the world found that simply hearing about others’ struggles can normalize accessing support at work.

Novartis has trained more than 1,000 employees as Mental Health First Aiders to offer peer-to-peer support for their colleagues. While employees were eager for the training, uptake of the program remains low. To understand why, a team of researchers conducted a randomized controlled trial with 2,400 Novartis employees who worked in the UK, Ireland, India, and Malaysia. Employees were shown one of six framings that were designed to overcome two key barriers: privacy concerns and usage concerns. They found that employees who read a story about their colleague using the service were more likely to sign up to learn more about the program, and that emphasizing the anonymity of the program did not seem to have an impact. Their findings suggest that one way to encourage employees to make use of existing mental health resources is by creating a supportive culture that embraces sharing about mental health challenges at work.

“I almost scheduled an appointment about a dozen times. But no, in the end I never went. I just wasn’t sure if my problems were big enough to warrant help and I didn’t want to take up someone else’s time unnecessarily.”

• Laura M. Giurge is an assistant professor at the London School of Economics, and a faculty affiliate at London Business School. Her research focuses on time and boundaries in organizations, workplace well-being, and the future of work. She is also passionate about translating research to the broader public through interactive and creative keynote talks, workshops, and coaching. Follow her on LinkedIn  here .
• Lauren C. Howe is an assistant professor in management at the University of Zurich. As head of research at the Center for Leadership in the Future of Work , she focuses on how human aspects, such as mindsets, socioemotional skills, and leadership, play a role in the changing world of work.
• Zsofia Belovai is a behavioral science lead for the organizational performance research practice at MoreThanNow, focusing on exploring how employee welfare can drive KPIs.
• Guusje Lindemann is a senior behavioral scientist at MoreThanNow, in the social impact and organizational performance practices, working on making the workplace better for all.
• Sharon O’Connor is the global employee wellbeing lead at Novartis. She is a founding member of the Wellbeing Executives Council of The Conference Board, and a guest lecturer on the Workplace Wellness postgraduate certificate at Trinity College Dublin.

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Striking findings from 2023

Pew Research Center has gathered data around some of this year’s defining news stories, from the rise of artificial intelligence to the debate over affirmative action in college admissions . Here’s a look back at 2023 through some of our most striking research findings.

These findings only scratch the surface of the Center’s research from this past year .

A record-high share of 40-year-olds in the U.S. have never been married, according to a Center analysis of the most recent U.S. Census Bureau data . As of 2021, a quarter of 40-year-olds had never been married – up from 6% in 1980.

In 2021, the demographic groups most likely not to have ever been married by age 40 include men, Black Americans and those without a four-year college degree.

A Center survey conducted in April found that relatively few Americans see marriage as essential for people to live a fulfilling life compared with factors like job satisfaction and friendship. While majorities say that having a job or career they enjoy (71%) and having close friends (61%) are extremely or very important for living a fulfilling life, far fewer say this about having children (26%) or being married (23%). Larger shares, in fact, say having children (42%) or being married (44%) are not too or not at all important.

About half of Americans say the increased use of artificial intelligence in daily life makes them feel more concerned than excited – up 14 percentage points from last year, according to an August survey . Overall, 52% of Americans say they feel this way, an increase from 38% in December 2022.

Just 10% of adults say they are more excited than concerned about the increased use of AI, while 36% say they feel an equal mix of these emotions.

The rise in concern about AI has taken place alongside growing public awareness of the technology. Nine-in-ten adults say they have heard either a lot (33%) or a little (56%) about artificial intelligence. The share of those who have heard  a lot  is up 7 points since December 2022.

For the first time in over 30 years of public opinion polling, Americans’ views of the U.S. Supreme Court are more negative than positive, a July survey found . A narrow majority (54%) have an unfavorable view of the high court, while fewer than half (44%) express a favorable one.

The court’s favorable rating has declined 26 percentage points since 2020, following a series of high-profile rulings on issues including affirmative action in college admissions, LGBTQ+ rights and student loans. The drop in favorability is primarily due to a decline among Democrats and Democratic-leaning independents, just 24% of whom express a favorable opinion of the court.

A growing share of U.S. adults say the federal government should take steps to restrict false information online, even if it limits freedom of information, a June survey found . The share of U.S. adults with this view has risen from 39% in 2018 to 55% in 2023.

In the most recent survey, 42% of adults took the opposite view, saying the government should protect freedom of information, even if it means false information can be published.

Still, Americans remain more likely to say that tech companies – rather than the U.S. government – should be responsible for restricting false information online. About two-thirds (65%) said this in June.

The number of U.S. children and teens killed by gunfire rose 50% in just two years, according to a 2023 analysis of data from the Centers for Disease Control and Prevention (CDC). In 2019, there were 1,732 gun deaths among U.S. children and teens under 18. By 2021, that figure had increased to 2,590.

The gun death  rate  among children and teens – a measure that adjusts for changes in the nation’s population – rose 46% during that span.

Both the number and rate of children and teens killed by gunfire in 2021 were the highest since at least 1999, the earliest year for which this information is available in the CDC’s mortality database.

Most Asian Americans view their ancestral homelands favorably – but not Chinese Americans, according to a multilingual, nationally representative survey of Asian American adults .

Only about four-in-ten Chinese Americans (41%) have a favorable opinion of China, while 35% have an unfavorable one. Another 22% say they have a neither favorable nor unfavorable view. This stands in contrast to how other Asian Americans view their ancestral homelands. For instance, about nine-in-ten Taiwanese and Japanese Americans have a very or somewhat favorable opinion of their place of origin, as do large majorities of Korean, Indian and Filipino Americans.

While Chinese Americans’ views of China are more mixed, they still have a more favorable opinion of the country than other Asian adults do. Just 14% of other Asian Americans view China favorably.

Even before the Israel-Hamas war, Israelis had grown more skeptical of a two-state solution. In a survey conducted in March and April , prior to the war, just 35% of Israelis thought “a way can be found for Israel and an independent Palestinian state to coexist peacefully.” This share had declined by 9 percentage points since 2017 and 15 points since 2013.

Among both Arabs and Jews living in Israel, there have been declines over the past decade in the share of people who believe that a peaceful coexistence between Israel and an independent Palestinian state is possible.

A majority of Americans say they would tip 15% or less for an average restaurant dining experience, including 2% who wouldn’t leave a tip at all, an August survey shows . The survey presented respondents with a hypothetical scenario in which they went to a sit-down restaurant and had average – but not exceptional – food and service. About six-in-ten (57%) say they would leave a tip of 15% or less in this situation. Another 12% say they would leave a tip of 18%, and a quarter of people say they’d tip 20% or more.

Adults in lower-income households and those ages 65 and older are more likely than their counterparts to say they would tip 15% or less in a situation like this.

Partisan views of Twitter – the social media platform now called X – have shifted over the last two years, with Republican users’ views of the site growing more positive and those of Democratic users becoming more negative, according to a March survey . The share of Republican and GOP-leaning users who said the site is mostly bad for American democracy fell from 60% in 2021 to 21% earlier this year. At the same time, the share of Republican users who said the site is mostly good for democracy rose from 17% to 43% during the same span.

Democrats’ views moved in the opposite direction during that time frame. The percentage of Democratic and Democratic-leaning Twitter users who said the platform is good for American democracy decreased from 47% to 24%, while the share who said it is bad for democracy increased – though more modestly – from 28% to 35%.

These changes in views follow Elon Musk’s takeover of the platform in fall 2022.

Nearly half of U.S. workers who get paid time off don’t take all the time off their employer offers, according to a February survey of employed Americans . Among those who say their employer offers paid time off for vacation, doctors’ appointments or to deal with minor illnesses, 46% say they take less time off than they are allowed. A similar share (48%) say they typically take all the time off they are offered.

Among those who don’t take all their paid time off, the most common reasons cited are not feeling the need to take more time off (52% say this), worrying they might fall behind at work (49%), and feeling badly about their co-workers taking on additional work (43%).

Smaller shares cite other concerns, including the feeling that taking more time off might hurt their chances for job advancement (19%) or that they might risk losing their job (16%). Some 12% say their manager or supervisor discourages them from taking time off.

An overwhelming majority of Americans (79%) express a negative sentiment when asked to describe politics in the United States these days, a July survey found . Just 2% offer a positive word or phrase, while 10% say something neutral.

Among those who volunteered an answer, 8% use the word “ divisive” or variations of it, while 2% cite the related term “polarized.” “Corrupt” is the second-most frequent answer, given by 6% of respondents.

The top 15 most cited words also include “messy,” “chaos,” “broken” and “dysfunctional.” Many respondents are even more negative in their views: “terrible,” “disgusting,” “disgrace” and the phrase “dumpster fire” are each offered by at least 1% of respondents.

Around half of Americans (53%) say they have ever been visited by a dead family member in a dream or in another form, according to a spring survey . Overall, 46% of Americans report that they’ve been visited by a dead family member in a dream, while 31% report having been visited by dead relatives in some other form.

Women are more likely than men to report these experiences.

While the survey asked whether people have had interactions with dead relatives, it did not ask for explanations. So, we don’t know whether people view these experiences as mysterious or supernatural, whether they see them as having natural or scientific causes, or some of both.

For example, the survey did not ask what respondents meant when they said they had been visited in a dream by a dead relative. Some might have meant that relatives were trying to send them messages or information from beyond the grave. Others might have had something more commonplace in mind, such as dreaming about a favorite memory of a family member.

More Americans disapprove than approve of selective colleges and universities taking race and ethnicity into account when making admissions decisions, according to another spring survey , fielded before the Supreme Court ruled on the practice in June. Half of U.S. adults disapprove of colleges considering race and ethnicity to increase diversity at the schools, while a third approve and 16% are not sure.

Views differ widely by party, as well as by race and ethnicity. Around three-quarters of Republicans and Republican leaners (74%) disapprove of the practice, while 54% of Democrats and Democratic leaners approve of it.

Nearly half of Black Americans (47%) say they approve of colleges and universities considering race and ethnicity in admissions, while smaller shares of Hispanic (39%), Asian (37%) and White (29%) Americans say the same.

The share of Americans who say science has had a mostly positive effect on society has declined since 2019, before the coronavirus outbreak, a fall survey shows : 57% say science has had a mostly positive effect on society, down from 73% in 2019.

About a third of adults (34%) now say the impact of science on society has been equally positive and negative. And 8% say science has had a mostly negative impact on society.

Democrats have become much more likely than Republicans to say science has had a mostly positive impact on society (69% vs. 47%). This gap is the result of steeper declines in positive ratings among Republicans than among Democrats since 2019 (down 23 points and 8 points, respectively).

Nearly three-in-ten Americans express an unfavorable opinion of both major political parties – the highest share in at least three decades, according to a July survey . Overall, 28% of Americans have an unfavorable opinion of both the Republican and Democratic parties. This is more than quadruple the share in 1994, when just 6% of Americans viewed both parties negatively.

A majority of Americans say TikTok is a threat to national security, according to a survey conducted in May . About six-in-ten adults (59%) see the social media platform as a major or minor threat to national security in the United States. Just 17% say it is  not  a threat to national security and another 23% aren’t sure.

Views vary by partisanship and age. Seven-in-ten Republicans and GOP leaners say TikTok is at least a minor threat to national security, compared with 53% of Democrats and Democratic leaners. Conservative Republicans are more likely than moderate or liberal Republicans – or Democrats of any ideology – to say the view the app as a major threat.

Nearly half of those ages 65 and older (46%) see TikTok as a major threat to national security, compared with a much smaller share (13%) of adults ages 18 to 29.

Read the other posts in our striking findings series:

• Striking findings from 2022
• Striking findings from 2021
• 20 striking findings from 2020
• 19 striking findings from 2019
• 18 striking findings from 2018
• 17 striking findings from 2017
• 16 striking findings from 2016
• 15 striking findings from 2015
• 14 striking findings from 2014
• Affirmative Action
• Artificial Intelligence
• Asian Americans
• Business & Workplace
• Death & Dying
• Defense & National Security
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Private, selective colleges are most likely to use race, ethnicity as a factor in admissions decisions

Americans and affirmative action: how the public sees the consideration of race in college admissions, hiring, asian americans hold mixed views around affirmative action, more americans disapprove than approve of colleges considering race, ethnicity in admissions decisions, hispanic enrollment reaches new high at four-year colleges in the u.s., but affordability remains an obstacle, most popular.

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