TY - JOUR AB - Adeno-associated viruses (AAVs) are widely used to deliver genetic material in vivo to distinct cell types such as neurons or glial cells, allowing for targeted manipulation. Transduction of microglia is mostly excluded from this strategy, likely due to the cells’ heterogeneous state upon environmental changes, which makes AAV design challenging. Here, we established the retina as a model system for microglial AAV validation and optimization. First, we show that AAV2/6 transduced microglia in both synaptic layers, where layer preference corresponds to the intravitreal or subretinal delivery method. Surprisingly, we observed significantly enhanced microglial transduction during photoreceptor degeneration. Thus, we modified the AAV6 capsid to reduce heparin binding by introducing four point mutations (K531E, R576Q, K493S, and K459S), resulting in increased microglial transduction in the outer plexiform layer. Finally, to improve microglial-specific transduction, we validated a Cre-dependent transgene delivery cassette for use in combination with the Cx3cr1CreERT2 mouse line. Together, our results provide a foundation for future studies optimizing AAV-mediated microglia transduction and highlight that environmental conditions influence microglial transduction efficiency. AU - Maes, Margaret E AU - Wögenstein, Gabriele M. AU - Colombo, Gloria AU - Casado Polanco, Raquel AU - Siegert, Sandra ID - 10655 JF - Molecular Therapy - Methods and Clinical Development TI - Optimizing AAV2/6 microglial targeting identified enhanced efficiency in the photoreceptor degenerative environment VL - 23 ER - TY - JOUR AB - Enzymatic digestion of the extracellular matrix with chondroitinase-ABC reinstates juvenile-like plasticity in the adult cortex as it also disassembles the perineuronal nets (PNNs). The disadvantage of the enzyme is that it must be applied intracerebrally and it degrades the ECM for several weeks. Here, we provide two minimally invasive and transient protocols for microglia-enabled PNN disassembly in mouse cortex: repeated treatment with ketamine-xylazine-acepromazine (KXA) anesthesia and 60-Hz light entrainment. We also discuss how to analyze PNNs within microglial endosomes-lysosomes. For complete details on the use and execution of this protocol, please refer to Venturino et al. (2021). AU - Venturino, Alessandro AU - Siegert, Sandra ID - 10565 IS - 4 JF - STAR Protocols TI - Minimally invasive protocols and quantification for microglia-mediated perineuronal net disassembly in mouse brain VL - 2 ER - TY - JOUR AB - Mosaic analysis with double markers (MADM) technology enables the generation of genetic mosaic tissue in mice. MADM enables concomitant fluorescent cell labeling and introduction of a mutation of a gene of interest with single-cell resolution. This protocol highlights major steps for the generation of genetic mosaic tissue and the isolation and processing of respective tissues for downstream histological analysis. For complete details on the use and execution of this protocol, please refer to Contreras et al. (2021). AU - Amberg, Nicole AU - Hippenmeyer, Simon ID - 10321 IS - 4 JF - STAR Protocols TI - Genetic mosaic dissection of candidate genes in mice using mosaic analysis with double markers VL - 2 ER - TY - JOUR AB - A precise quantitative description of the ultrastructural characteristics underlying biological mechanisms is often key to their understanding. This is particularly true for dynamic extra- and intracellular filamentous assemblies, playing a role in cell motility, cell integrity, cytokinesis, tissue formation and maintenance. For example, genetic manipulation or modulation of actin regulatory proteins frequently manifests in changes of the morphology, dynamics, and ultrastructural architecture of actin filament-rich cell peripheral structures, such as lamellipodia or filopodia. However, the observed ultrastructural effects often remain subtle and require sufficiently large datasets for appropriate quantitative analysis. The acquisition of such large datasets has been enabled by recent advances in high-throughput cryo-electron tomography (cryo-ET) methods. This also necessitates the development of complementary approaches to maximize the extraction of relevant biological information. We have developed a computational toolbox for the semi-automatic quantification of segmented and vectorized filamentous networks from pre-processed cryo-electron tomograms, facilitating the analysis and cross-comparison of multiple experimental conditions. GUI-based components simplify the processing of data and allow users to obtain a large number of ultrastructural parameters describing filamentous assemblies. We demonstrate the feasibility of this workflow by analyzing cryo-ET data of untreated and chemically perturbed branched actin filament networks and that of parallel actin filament arrays. In principle, the computational toolbox presented here is applicable for data analysis comprising any type of filaments in regular (i.e. parallel) or random arrangement. We show that it can ease the identification of key differences between experimental groups and facilitate the in-depth analysis of ultrastructural data in a time-efficient manner. AU - Dimchev, Georgi A AU - Amiri, Behnam AU - Fäßler, Florian AU - Falcke, Martin AU - Schur, Florian KM ID - 10290 IS - 4 JF - Journal of Structural Biology KW - Structural Biology SN - 1047-8477 TI - Computational toolbox for ultrastructural quantitative analysis of filament networks in cryo-ET data VL - 213 ER - TY - CONF AB - Payment channel networks are a promising approach to improve the scalability of cryptocurrencies: they allow to perform transactions in a peer-to-peer fashion, along multihop routes in the network, without requiring consensus on the blockchain. However, during the discovery of cost-efficient routes for the transaction, critical information may be revealed about the transacting entities. This paper initiates the study of privacy-preserving route discovery mechanisms for payment channel networks. In particular, we present LightPIR, an approach which allows a client to learn the shortest (or cheapest in terms of fees) path between two nodes without revealing any information about the endpoints of the transaction to the servers. The two main observations which allow for an efficient solution in LightPIR are that: (1) surprisingly, hub labelling algorithms – which were developed to preprocess “street network like” graphs so one can later efficiently compute shortest paths – also perform well for the graphs underlying payment channel networks, and that (2) hub labelling algorithms can be conveniently combined with private information retrieval. LightPIR relies on a simple hub labeling heuristic on top of existing hub labeling algorithms which leverages the specific topological features of cryptocurrency networks to further minimize storage and bandwidth overheads. In a case study considering the Lightning network, we show that our approach is an order of magnitude more efficient compared to a privacy-preserving baseline based on using private information retrieval on a database that stores all pairs shortest paths. AU - Pietrzak, Krzysztof Z AU - Salem, Iosif AU - Schmid, Stefan AU - Yeo, Michelle X ID - 9969 SN - 978-1-6654-4501-6 TI - LightPIR: Privacy-preserving route discovery for payment channel networks ER - TY - CONF AB - We present a new approach to proving non-termination of non-deterministic integer programs. Our technique is rather simple but efficient. It relies on a purely syntactic reversal of the program's transition system followed by a constraint-based invariant synthesis with constraints coming from both the original and the reversed transition system. The latter task is performed by a simple call to an off-the-shelf SMT-solver, which allows us to leverage the latest advances in SMT-solving. Moreover, our method offers a combination of features not present (as a whole) in previous approaches: it handles programs with non-determinism, provides relative completeness guarantees and supports programs with polynomial arithmetic. The experiments performed with our prototype tool RevTerm show that our approach, despite its simplicity and stronger theoretical guarantees, is at least on par with the state-of-the-art tools, often achieving a non-trivial improvement under a proper configuration of its parameters. AU - Chatterjee, Krishnendu AU - Goharshady, Ehsan Kafshdar AU - Novotný, Petr AU - Zikelic, Dorde ID - 9644 SN - 9781450383912 T2 - Proceedings of the 42nd ACM SIGPLAN International Conference on Programming Language Design and Implementation TI - Proving non-termination by program reversal ER - TY - JOUR AB - The quantum approximate optimization algorithm (QAOA) is a prospective near-term quantum algorithm due to its modest circuit depth and promising benchmarks. However, an external parameter optimization required in the QAOA could become a performance bottleneck. This motivates studies of the optimization landscape and search for heuristic ways of parameter initialization. In this work we visualize the optimization landscape of the QAOA applied to the MaxCut problem on random graphs, demonstrating that random initialization of the QAOA is prone to converging to local minima with suboptimal performance. We introduce the initialization of QAOA parameters based on the Trotterized quantum annealing (TQA) protocol, parameterized by the Trotter time step. We find that the TQA initialization allows to circumvent the issue of false minima for a broad range of time steps, yielding the same performance as the best result out of an exponentially scaling number of random initializations. Moreover, we demonstrate that the optimal value of the time step coincides with the point of proliferation of Trotter errors in quantum annealing. Our results suggest practical ways of initializing QAOA protocols on near-term quantum devices and reveal new connections between QAOA and quantum annealing. AU - Sack, Stefan AU - Serbyn, Maksym ID - 9760 JF - Quantum TI - Quantum annealing initialization of the quantum approximate optimization algorithm VL - 5 ER - TY - CONF AB - We consider the almost-sure (a.s.) termination problem for probabilistic programs, which are a stochastic extension of classical imperative programs. Lexicographic ranking functions provide a sound and practical approach for termination of non-probabilistic programs, and their extension to probabilistic programs is achieved via lexicographic ranking supermartingales (LexRSMs). However, LexRSMs introduced in the previous work have a limitation that impedes their automation: all of their components have to be non-negative in all reachable states. This might result in LexRSM not existing even for simple terminating programs. Our contributions are twofold: First, we introduce a generalization of LexRSMs which allows for some components to be negative. This standard feature of non-probabilistic termination proofs was hitherto not known to be sound in the probabilistic setting, as the soundness proof requires a careful analysis of the underlying stochastic process. Second, we present polynomial-time algorithms using our generalized LexRSMs for proving a.s. termination in broad classes of linear-arithmetic programs. AU - Chatterjee, Krishnendu AU - Goharshady, Ehsan Kafshdar AU - Novotný, Petr AU - Zárevúcky, Jiří AU - Zikelic, Dorde ID - 10414 SN - 0302-9743 T2 - 24th International Symposium on Formal Methods TI - On lexicographic proof rules for probabilistic termination VL - 13047 ER - TY - JOUR AB - Research on two-dimensional (2D) materials has been explosively increasing in last seventeen years in varying subjects including condensed matter physics, electronic engineering, materials science, and chemistry since the mechanical exfoliation of graphene in 2004. Starting from graphene, 2D materials now have become a big family with numerous members and diverse categories. The unique structural features and physicochemical properties of 2D materials make them one class of the most appealing candidates for a wide range of potential applications. In particular, we have seen some major breakthroughs made in the field of 2D materials in last five years not only in developing novel synthetic methods and exploring new structures/properties but also in identifying innovative applications and pushing forward commercialisation. In this review, we provide a critical summary on the recent progress made in the field of 2D materials with a particular focus on last five years. After a brief background introduction, we first discuss the major synthetic methods for 2D materials, including the mechanical exfoliation, liquid exfoliation, vapor phase deposition, and wet-chemical synthesis as well as phase engineering of 2D materials belonging to the field of phase engineering of nanomaterials (PEN). We then introduce the superconducting/optical/magnetic properties and chirality of 2D materials along with newly emerging magic angle 2D superlattices. Following that, the promising applications of 2D materials in electronics, optoelectronics, catalysis, energy storage, solar cells, biomedicine, sensors, environments, etc. are described sequentially. Thereafter, we present the theoretic calculations and simulations of 2D materials. Finally, after concluding the current progress, we provide some personal discussions on the existing challenges and future outlooks in this rapidly developing field. AU - Chang, Cheng AU - Chen, Wei AU - Chen, Ye AU - Chen, Yonghua AU - Chen, Yu AU - Ding, Feng AU - Fan, Chunhai AU - Fan, Hong Jin AU - Fan, Zhanxi AU - Gong, Cheng AU - Gong, Yongji AU - He, Qiyuan AU - Hong, Xun AU - Hu, Sheng AU - Hu, Weida AU - Huang, Wei AU - Huang, Yuan AU - Ji, Wei AU - Li, Dehui AU - Li, Lain Jong AU - Li, Qiang AU - Lin, Li AU - Ling, Chongyi AU - Liu, Minghua AU - Liu, Nan AU - Liu, Zhuang AU - Loh, Kian Ping AU - Ma, Jianmin AU - Miao, Feng AU - Peng, Hailin AU - Shao, Mingfei AU - Song, Li AU - Su, Shao AU - Sun, Shuo AU - Tan, Chaoliang AU - Tang, Zhiyong AU - Wang, Dingsheng AU - Wang, Huan AU - Wang, Jinlan AU - Wang, Xin AU - Wang, Xinran AU - Wee, Andrew T.S. AU - Wei, Zhongming AU - Wu, Yuen AU - Wu, Zhong Shuai AU - Xiong, Jie AU - Xiong, Qihua AU - Xu, Weigao AU - Yin, Peng AU - Zeng, Haibo AU - Zeng, Zhiyuan AU - Zhai, Tianyou AU - Zhang, Han AU - Zhang, Hui AU - Zhang, Qichun AU - Zhang, Tierui AU - Zhang, Xiang AU - Zhao, Li Dong AU - Zhao, Meiting AU - Zhao, Weijie AU - Zhao, Yunxuan AU - Zhou, Kai Ge AU - Zhou, Xing AU - Zhou, Yu AU - Zhu, Hongwei AU - Zhang, Hua AU - Liu, Zhongfan ID - 14800 IS - 12 JF - Acta Physico-Chimica Sinica SN - 1001-4861 TI - Recent progress on two-dimensional materials VL - 37 ER - TY - CONF AB - Neural-network classifiers achieve high accuracy when predicting the class of an input that they were trained to identify. Maintaining this accuracy in dynamic environments, where inputs frequently fall outside the fixed set of initially known classes, remains a challenge. The typical approach is to detect inputs from novel classes and retrain the classifier on an augmented dataset. However, not only the classifier but also the detection mechanism needs to adapt in order to distinguish between newly learned and yet unknown input classes. To address this challenge, we introduce an algorithmic framework for active monitoring of a neural network. A monitor wrapped in our framework operates in parallel with the neural network and interacts with a human user via a series of interpretable labeling queries for incremental adaptation. In addition, we propose an adaptive quantitative monitor to improve precision. An experimental evaluation on a diverse set of benchmarks with varying numbers of classes confirms the benefits of our active monitoring framework in dynamic scenarios. AU - Lukina, Anna AU - Schilling, Christian AU - Henzinger, Thomas A ID - 10206 KW - monitoring KW - neural networks KW - novelty detection SN - 0302-9743 T2 - 21st International Conference on Runtime Verification TI - Into the unknown: active monitoring of neural networks VL - 12974 ER - TY - JOUR AB - We consider the Fröhlich Hamiltonian with large coupling constant α. For initial data of Pekar product form with coherent phonon field and with the electron minimizing the corresponding energy, we provide a norm approximation of the evolution, valid up to times of order α2. The approximation is given in terms of a Pekar product state, evolved through the Landau-Pekar equations, corrected by a Bogoliubov dynamics taking quantum fluctuations into account. This allows us to show that the Landau-Pekar equations approximately describe the evolution of the electron- and one-phonon reduced density matrices under the Fröhlich dynamics up to times of order α2. AU - Leopold, Nikolai K AU - Mitrouskas, David Johannes AU - Rademacher, Simone Anna Elvira AU - Schlein, Benjamin AU - Seiringer, Robert ID - 14889 IS - 4 JF - Pure and Applied Analysis SN - 2578-5893 TI - Landau–Pekar equations and quantum fluctuations for the dynamics of a strongly coupled polaron VL - 3 ER - TY - JOUR AB - We consider a system of N interacting bosons in the mean-field scaling regime and construct corrections to the Bogoliubov dynamics that approximate the true N-body dynamics in norm to arbitrary precision. The N-independent corrections are given in terms of the solutions of the Bogoliubov and Hartree equations and satisfy a generalized form of Wick's theorem. We determine the n-point correlation functions of the excitations around the condensate, as well as the reduced densities of the N-body system, to arbitrary accuracy, given only the knowledge of the two-point functions of a quasi-free state and the solution of the Hartree equation. In this way, the complex problem of computing all n-point correlation functions for an interacting N-body system is essentially reduced to the problem of solving the Hartree equation and the PDEs for the Bogoliubov two-point functions. AU - Bossmann, Lea AU - Petrat, Sören P AU - Pickl, Peter AU - Soffer, Avy ID - 14890 IS - 4 JF - Pure and Applied Analysis SN - 2578-5893 TI - Beyond Bogoliubov dynamics VL - 3 ER - TY - JOUR AB - We consider random n×n matrices X with independent and centered entries and a general variance profile. We show that the spectral radius of X converges with very high probability to the square root of the spectral radius of the variance matrix of X when n tends to infinity. We also establish the optimal rate of convergence, that is a new result even for general i.i.d. matrices beyond the explicitly solvable Gaussian cases. The main ingredient is the proof of the local inhomogeneous circular law [arXiv:1612.07776] at the spectral edge. AU - Alt, Johannes AU - Erdös, László AU - Krüger, Torben H ID - 15013 IS - 2 JF - Probability and Mathematical Physics SN - 2690-0998 TI - Spectral radius of random matrices with independent entries VL - 2 ER - TY - JOUR AB - Clathrin-mediated endocytosis is the major route of entry of cargos into cells and thus underpins many physiological processes. During endocytosis, an area of flat membrane is remodeled by proteins to create a spherical vesicle against intracellular forces. The protein machinery which mediates this membrane bending in plants is unknown. However, it is known that plant endocytosis is actin independent, thus indicating that plants utilize a unique mechanism to mediate membrane bending against high-turgor pressure compared to other model systems. Here, we investigate the TPLATE complex, a plant-specific endocytosis protein complex. It has been thought to function as a classical adaptor functioning underneath the clathrin coat. However, by using biochemical and advanced live microscopy approaches, we found that TPLATE is peripherally associated with clathrin-coated vesicles and localizes at the rim of endocytosis events. As this localization is more fitting to the protein machinery involved in membrane bending during endocytosis, we examined cells in which the TPLATE complex was disrupted and found that the clathrin structures present as flat patches. This suggests a requirement of the TPLATE complex for membrane bending during plant clathrin–mediated endocytosis. Next, we used in vitro biophysical assays to confirm that the TPLATE complex possesses protein domains with intrinsic membrane remodeling activity. These results redefine the role of the TPLATE complex and implicate it as a key component of the evolutionarily distinct plant endocytosis mechanism, which mediates endocytic membrane bending against the high-turgor pressure in plant cells. AU - Johnson, Alexander J AU - Dahhan, Dana A AU - Gnyliukh, Nataliia AU - Kaufmann, Walter AU - Zheden, Vanessa AU - Costanzo, Tommaso AU - Mahou, Pierre AU - Hrtyan, Mónika AU - Wang, Jie AU - Aguilera Servin, Juan L AU - van Damme, Daniël AU - Beaurepaire, Emmanuel AU - Loose, Martin AU - Bednarek, Sebastian Y AU - Friml, Jiří ID - 9887 IS - 51 JF - Proceedings of the National Academy of Sciences TI - The TPLATE complex mediates membrane bending during plant clathrin-mediated endocytosis VL - 118 ER - TY - GEN AB - Raw data generated from the publication - The TPLATE complex mediates membrane bending during plant clathrin-mediated endocytosis by Johnson et al., 2021 In PNAS AU - Johnson, Alexander J ID - 14988 TI - Raw data from Johnson et al, PNAS, 2021 ER - TY - GEN AB - Superconductor-semiconductor hybrids are platforms for realizing effective p-wave superconductivity. Spin-orbit coupling, combined with the proximity effect, causes the two-dimensional semiconductor to inherit p±ip intraband pairing, and application of magnetic field can then result in transitions to the normal state, partial Bogoliubov Fermi surfaces, or topological phases with Majorana modes. Experimentally probing the hybrid superconductor-semiconductor interface is challenging due to the shunting effect of the conventional superconductor. Consequently, the nature of induced pairing remains an open question. Here, we use the circuit quantum electrodynamics architecture to probe induced superconductivity in a two dimensional Al-InAs hybrid system. We observe a strong suppression of superfluid density and enhanced dissipation driven by magnetic field, which cannot be accounted for by the depairing theory of an s-wave superconductor. These observations are explained by a picture of independent intraband p±ip superconductors giving way to partial Bogoliubov Fermi surfaces, and allow for the first characterization of key properties of the hybrid superconducting system. AU - Phan, Duc T AU - Senior, Jorden L AU - Ghazaryan, Areg AU - Hatefipour, M. AU - Strickland, W. M. AU - Shabani, J. AU - Serbyn, Maksym AU - Higginbotham, Andrew P ID - 10029 T2 - arXiv TI - Breakdown of induced p±ip pairing in a superconductor-semiconductor hybrid ER - TY - DATA AB - This .zip File contains the transport data for figures presented in the main text and supplementary material of "Enhancement of Proximity Induced Superconductivity in Planar Germanium" by K. Aggarwal, et. al. The measurements were done using Labber Software and the data is stored in the hdf5 file format. The files can be opened using either the Labber Log Browser (https://labber.org/overview/) or Labber Python API (http://labber.org/online-doc/api/LogFile.html). AU - Katsaros, Georgios ID - 9291 TI - Raw transport data for: Enhancement of proximity induced superconductivity in planar germanium ER - TY - DATA AU - Higginbotham, Andrew P ID - 9636 TI - Data for "Breakdown of induced p ± ip pairing in a superconductor-semiconductor hybrid" ER - TY - JOUR AB - A semiconducting nanowire fully wrapped by a superconducting shell has been proposed as a platform for obtaining Majorana modes at small magnetic fields. In this study, we demonstrate that the appearance of subgap states in such structures is actually governed by the junction region in tunneling spectroscopy measurements and not the full-shell nanowire itself. Short tunneling regions never show subgap states, whereas longer junctions always do. This can be understood in terms of quantum dots forming in the junction and hosting Andreev levels in the Yu-Shiba-Rusinov regime. The intricate magnetic field dependence of the Andreev levels, through both the Zeeman and Little-Parks effects, may result in robust zero-bias peaks—features that could be easily misinterpreted as originating from Majorana zero modes but are unrelated to topological superconductivity. AU - Valentini, Marco AU - Peñaranda, Fernando AU - Hofmann, Andrea C AU - Brauns, Matthias AU - Hauschild, Robert AU - Krogstrup, Peter AU - San-Jose, Pablo AU - Prada, Elsa AU - Aguado, Ramón AU - Katsaros, Georgios ID - 8910 IS - 6550 JF - Science SN - 00368075 TI - Nontopological zero-bias peaks in full-shell nanowires induced by flux-tunable Andreev states VL - 373 ER - TY - DATA AB - This .zip File contains the data for figures presented in the main text and supplementary material of "A singlet triplet hole spin qubit in planar Ge" by D. Jirovec, et. al. The measurements were done using Labber Software and the data is stored in the hdf5 file format. The files can be opened using either the Labber Log Browser (https://labber.org/overview/) or Labber Python API (http://labber.org/online-doc/api/LogFile.html). A single file is acquired with QCodes and features the corresponding data type. XRD data are in .dat format and a code to open the data is provided. The code for simulations is as well provided in Python. AU - Jirovec, Daniel ID - 9323 TI - Research data for "A singlet-triplet hole spin qubit planar Ge" ER -