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Mar 2022 • International Journal of Molecular Sciences 23 (7), 3811, 2022

Behavioral Neuroscience in the Era of Genomics: Tools and Lessons for Analyzing High-Dimensional Datasets

Assa Bentzur, Shahar Alon, Galit Shohat-Ophir

Behavioral neuroscience underwent a technology-driven revolution with the emergence of machine-vision and machine-learning technologies. These technological advances facilitated the generation of high-resolution, high-throughput capture and analysis of complex behaviors. Therefore, behavioral neuroscience is becoming a data-rich field. While behavioral researchers use advanced computational tools to analyze the resulting datasets, the search for robust and standardized analysis tools is still ongoing. At the same time, the field of genomics exploded with a plethora of technologies which enabled the generation of massive datasets. This growth of genomics data drove the emergence of powerful computational approaches to analyze these data. Here, we discuss the composition of a large behavioral dataset, and the differences and similarities between behavioral and genomics data. We then give examples of genomics-related tools that might be of use for behavioral analysis and discuss concepts that might emerge when considering the two fields together.

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Mar 2022 • ACS Energy Letters

Stabilizing High-Voltage Lithium-Ion Battery Cathodes Using Functional Coatings of 2D Tungsten Diselenide

Sandipan Maiti, Rajashree Konar, Hadar Sclar, Judith Grinblat, Michael Talianker, Maria Tkachev, Xiaohan Wu, Aleksandr Kondrakov, Gilbert Daniel Nessim, Doron Aurbach

Functional surface coatings were applied on high voltage spinel (LiNi0.5Mn1.5O4; LNMO) and Ni-rich (LiNi0.85Co0.1Mn0.05O2; NCM851005) NCM cathode materials using few-layered 2H tungsten diselenide (WSe2). Simple liquid-phase mixing with WSe2 in 2-propanol and low-temperature (130 °C) heat treatment in nitrogen flow dramatically improved electrochemical performance, including stable cycling, high-rate performance, and lower voltage hysteresis in Li coin cells at 30 and 55 °C. Significantly improved capacity retention at 30 °C [Q401/Q9 of 99% vs 38% for LNMO and Q322/Q23 of 64% vs 46% for NCM851005] indicated efficient functionality. TEM and XPS clarified the coating distribution and coordination with the cathode surface, while postcycling studies revealed its sustainability, enabling lower transition metal dissolution and minor morphological deformation/microcrack formation. A modified and …

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Mar 2022 • PLoS pathogens

Experimental evolution links post-transcriptional regulation to Leishmania fitness gain

Laura Piel, K Shanmugha Rajan, Giovanni Bussotti, Hugo Varet, Rachel Legendre, Caroline Proux, Thibaut Douché, Quentin Giai-Gianetto, Thibault Chaze, Thomas Cokelaer, Barbora Vojtkova, Nadav Gordon-Bar, Tirza Doniger, Smadar Cohen-Chalamish, Praveenkumar Rengaraj, Céline Besse, Anne Boland, Jovana Sadlova, Jean-François Deleuze, Mariette Matondo, Ron Unger, Petr Volf, Shulamit Michaeli, Pascale Pescher, Gerald F Späth

The protozoan parasite Leishmania donovani causes fatal human visceral leishmaniasis in absence of treatment. Genome instability has been recognized as a driver in Leishmania fitness gain in response to environmental change or chemotherapy. How genome instability generates beneficial phenotypes despite potential deleterious gene dosage effects is unknown. Here we address this important open question applying experimental evolution and integrative systems approaches on parasites adapting to in vitro culture. Phenotypic analyses of parasites from early and late stages of culture adaptation revealed an important fitness tradeoff, with selection for accelerated growth in promastigote culture (fitness gain) impairing infectivity (fitness costs). Comparative genomics, transcriptomics and proteomics analyses revealed a complex regulatory network associated with parasite fitness gain, with genome instability causing highly reproducible, gene dosage-independent and -dependent changes. Reduction of flagellar transcripts and increase in coding and non-coding RNAs implicated in ribosomal biogenesis and protein translation were not correlated to dosage changes of the corresponding genes, revealing a gene dosage-independent, post-transcriptional mechanism of regulation. In contrast, abundance of gene products implicated in post-transcriptional regulation itself correlated to corresponding gene dosage changes. Thus, RNA abundance during parasite adaptation is controled by direct and indirect gene dosage changes. We correlated differential expression of small nucleolar RNAs (snoRNAs) with changes in rRNA modification …

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Mar 2022 • Sciences

NIR fluorescence lifetime macroscopic imaging with a time-gated SPAD camera

X Michalet, A Ulku, J Smith, C Bruschini, S Weiss

The performance of SwissSPAD2 (SS2), a large scale, widefield time-gated CMOS SPAD imager developed for fluorescence lifetime imaging, has recently been described in the context of visible range and fluorescence lifetime imaging microscopy (FLIM) of dyes with lifetimes in the 2.5–4 ns range. Here, we explore its capabilities in the NIR regime relevant for small animal imaging, where its sensitivity is lower and typical NIR fluorescent dye lifetimes are much shorter (1 ns or less). We carry out this study in a simple macroscopic imaging setup based on a compact NIR picosecond pulsed laser, an engineered diffuser-based illumination optics, and NIR optimized imaging lens suitable for well-plate or small animal imaging. Because laser repetition rates can vary between models, but the synchronization signal frequency accepted by SS2 is fixed to 20 MHz, we first checked that a simple frequency-division scheme …

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Mar 2022 • High Contrast Metastructures XI, PC120110H, 2022

High-index topological insulator nanostructures for mid-infrared meta-optics

Sukanta Nandi, Danveer Singh, Pilkhaz Pilkhaz Nanikashvili, Shany Cohen, Doron Naveh, Tomer Lewi

Topological insulators (TIs) are a new class of condensed matter system that host topologically protected surface states, leading to dissipationless electron transport. This intrinsic characteristic makes them potential candidate for quantum computing owing to their ability to preserve quantum coherence. Recently, these systems and the concept of topology have been embraced by the photonics community as well. In this work, we study the mid-infrared optical properties of high index (n~5.2) TI bismuth selenide (Bi2Se3) nanobeams (NBs), grown by chemical vapor deposition. Using Finite-difference time-domain (FDTD) simulations and FTIR nanospectroscopy, we find that these NBs support size-tunable Mie-resonant modes across the infrared (~1-16 µm). Furthermore, polarized measurements reveal that the total optical response of these deep subwavelength NBs is composed of TE and TM resonant mode. Finally …

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Mar 2022 • Bulletin of the American Physical Society

Hidden magnetic memory and spontaneous superconducting vortices in alternating stacking compound 4Hb-TaS2

Eylon Persky, Anders Bjørlig, Irena Feldman, Avior Almoalem, Ehud Altman, Erez Berg, Itamar Kimchi, Jonathan Ruhman, Beena Kalisky

W61. 00009: Hidden magnetic memory and spontaneous superconducting vortices in alternating stacking compound 4Hb-TaS 2

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Mar 2022 • High Contrast Metastructures XI, PC120110U, 2022

Chalcogenides for static and active meta-optics

Tomer Lewi, Danveer Singh, Sukanta Nandi, Shany Cohen, Pilkhaz Nanikashvili, Michal Poplinger, Doron Naveh

We present a study of various compositions of the chalcogenide family used for static and active metasurfaces. We start with large area CVD grown amorphous spherical Selenium nanoparticles on various substrates and show that their Mie-resonant response spans the entire mid-infrared (MIR) range. By coupling Se Mie-resonators to ENZ substrates we demonstrate an order of magnitude increase in quality factor. Next, we investigate topological insulators Bi2Se3 and Bi2Te3 metasurfaces. We study the optical constants of single crystal Bi2Te3 in the NIR to the MIR range, followed by fabrication and characterization of metasurface disk arrays. We show that these high permittivity metasurfaces can yield very large absorption resonances using deep subwavelength structures. Finally, we demonstrate ultra-wide dynamic tuning of PbTe meta-atoms and metasurfaces, utilizing the anomalously large thermo-optic …

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Mar 2022 • Inorganics

Improved Electrochemical Behavior and Thermal Stability of Li and Mn-Rich Cathode Materials Modified by Lithium Sulfate Surface Treatment

Hadar Sclar, Sandipan Maiti, Rosy Sharma, Evan M Erickson, Judith Grinblat, Ravikumar Raman, Michael Talianker, Malachi Noked, Aleksandr Kondrakov, Boris Markovsky, Doron Aurbach

Mar 2022 • arXiv preprint arXiv:2203.00688

High-resolution absorption measurements with free-electron lasers using ghost spectroscopy

Yishai Klein, Edward Strizhevsky, Flavio Capotondi, Dario De Angelis, Luca Giannessi, Matteo Pancaldi, Emanuele Pedersoli, Giuseppe Penco, Kevin C Prince, Or Sefi, Young Yong Kim, Ivan A Vartanyants, Sharon Shwartz

We demonstrate a simple and robust high-resolution ghost spectroscopy approach for x-ray and extreme ultraviolet absorption spectroscopy at free-electron laser sources. Our approach requires an on-line spectrometer before the sample and a downstream bucket detector. We use this method to measure the absorption spectrum of silicon, silicon carbide and silicon nitride membranes in the vicinity of the silicon L2,3-edge. We show that ghost spectroscopy allows the high-resolution reconstruction of the sample spectral response using a coarse energy scan with self-amplified spontaneous emission radiation. For the conditions of our experiment the energy resolution of the ghost-spectroscopy reconstruction is higher than the energy resolution reached by scanning the energy range by narrow spectral bandwidth radiation produced by the seeded free-electron laser. When we set the photon energy resolution of the ghost spectroscopy to be equal to the resolution of the measurement with the seeded radiation, the measurement time with the ghost spectroscopy method is shorter than scanning the photon energy with seeded radiation. The exact conditions for which ghost spectroscopy can provide higher resolution at shorter times than measurement with narrow band scans depend on the details of the measurements and on the properties of the samples and should be addressed in future studies.

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Mar 2022 • High Contrast Metastructures XI, PC120110S, 2022

CVD grown selenium spherical resonators for mid-infrared meta-optics

Danveer Singh, Tomer Lewi, Doron Naveh, Michal Poplinger

Efficient light manipulation at subwavelength scales in the mid-infrared (MIR) region is essential for various applications and can be harnessed from intrinsic low-loss dielectric resonators. Here, we demonstrate the fabrication of truncated spherical selenium (Se) resonators with tunable high-quality (Q) factor Mie resonances. Large area amorphous Se subwavelength resonators of varying sizes were grown on different substrates, using a novel CVD process. We demonstrate size-tunable Mie resonances spanning the 2-16 µm range, for single isolated resonators and large area ensembles, respectively. We show strong tunable absorption resonances (90%) in ensembles of resonators in a significantly broad MIR range. Moreover, by coupling resonators to epsilon-near-zero (ENZ) substrates, we engineer high-Q resonances as high as Q=40. We also show the resonance pinning effect near the substrate ENZ value …

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Mar 2022 • Proc. of SPIE Vol

A magnetic modulation biosensing-based molecular assay for rapid and highly sensitive clinical diagnosis of COVID-19

Michael Margulis, Oran Erster, Shira Roth, Michal Mandelboim, Amos Danielli

The COVID-19 pandemic demands fast, sensitive, and specific diagnostic tools for virus surveillance and containment. Current methods for diagnosing the COVID-19 are based on direct detection of either viral antigens or viral ribonucleic acids (RNA) in swab samples. Antigen-targeting tests are simple, have fast turnaround times, and allow rapid testing. Unfortunately, compared with viral RNA-targeting tests, their sensitivity is low, especially during the initial stages of the disease, which limits their adoption and implementation. Direct detection of SARS-CoV-2 RNA using reversetranscription quantitative polymerase chain reaction (RT-qPCR) is sensitive and specific, making it a golden standard in SARS-CoV-2 detection. However, it had not seen a significant update since its introduction three decades ago. It has a long turnaround time, requires a high number of amplification cycles, and a complicated and …

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Mar 2022 • Bulletin of the American Physical Society

Electronic Tuning of 2D Materials with Zwitterionic and Functional Polymers

James Nicolas Pagaduan, Nicholas Hight-Huf, Yehiel Nagar, Avdhoot Datar, Doron Naveh, Michael Barnes, Ashwin Ramasubramaniam, Reika Katsumata, Todd Emrick

Functional polymers are increasingly recognized for their ability to engineer the electronic properties of 2D materials for device performance enhancement. Although dipole-rich polymer zwitterions have shown significant work function modulation of 2D materials, the contribution of zwitterion structure is not well understood. To this end, a series of zwitterionic sulfobetaine-based random copolymers with varying substituents has been prepared and applied as negative-tone resists on graphene, enabling evaluation of surface potential contrast. The influence of steric footprint on calculated dipole moment and resulting work function measured by ultraviolet photoelectron spectroscopy will be presented. To assess the nature of graphene surface doping by polymer zwitterions, a sample geometry that permits direct access to either the polymer or graphene side is employed using a zwitterionic phosphorylcholine-based …

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Feb 2022 • ACS nano

Wafer-Scalable Single-Layer Amorphous Molybdenum Trioxide

Md Hasibul Alam, Sayema Chowdhury, Anupam Roy, Xiaohan Wu, Ruijing Ge, Michael A Rodder, Jun Chen, Yang Lu, Chen Stern, Lothar Houben, Robert Chrostowski, Scott R Burlison, Sung Jin Yang, Martha I Serna, Ananth Dodabalapur, Filippo Mangolini, Doron Naveh, Jack C Lee, Sanjay K Banerjee, Jamie H Warner, Deji Akinwande

Feb 2022 • Nature communications

Multi-parameter photon-by-photon hidden Markov modeling

Paul David Harris, Alessandra Narducci, Christian Gebhardt, Thorben Cordes, Shimon Weiss, Eitan Lerner

Single molecule Förster resonance energy transfer (smFRET) is a unique biophysical approach for studying conformational dynamics in biomacromolecules. Photon-by-photon hidden Markov modeling (H2MM) is an analysis tool that can quantify FRET dynamics of single biomolecules, even if they occur on the sub-millisecond timescale. However, dye photophysical transitions intertwined with FRET dynamics may cause artifacts. Here, we introduce multi-parameter H2MM (mpH2MM), which assists in identifying FRET dynamics based on simultaneous observation of multiple experimentally-derived parameters. We show the importance of using mpH2MM to decouple FRET dynamics caused by conformational changes from photophysical transitions in confocal-based smFRET measurements of a DNA hairpin, the maltose binding protein, MalE, and the type-III secretion system effector, YopO, from Yersinia species …

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Feb 2022 • Biophysical Journal

Characterization of a large gated SPAD array for widefield NIR fluorescence lifetime imaging in vitro and in vivo

Jason T Smith, Alena Rudkouskaya, Shan Gao, Arin Ulku, Claudio Bruschini, Edoardo Charbon, Shimon Weiss, Margarida MR Barroso, Xavier Intes, Xavier Michalet

Optical imaging (OI) has become the most used alternative imaging tool for pre-clinical studies. Among all molecular imaging modalities, fluorescence optical imaging is central thanks to its high sensitivity, the numerous molecular probes available (either endogenous or exogenous) and its ability to simultaneously image multiple biomarkers or biological processes at various spatio-temporal scales. Especially, fluorescence lifetime imaging (FLI) has become an increasingly popular method, as it provides unique insights into the cellular micro-environment by non-invasively examining numerous intracellular parameters such as metabolic status, reactive oxygen species and intracellular pH. Moreover, FLI’s exploitation of native fluorescent signatures has been extensively investigated for enhanced diagnostic of numerous pathologies. However, to perform such measurements in intact, live specimen, it is required to …

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Feb 2022 • Biophysical Journal

A novel single molecule fluorescence quenching technique for measuring distances below 3 nm

Benjamin Ambrose, Victoria E Hill, Robert A Shaw, Tristan Johnston-Wood, Matthew Willmott, Callum Johnston, Rebecca Mächtel, Thorben Cordes, Eitan Lerner, JG Hill, Shimon Weiss, Timothy D Craggs

Single-molecule FRET (smFRET) is a powerful biophysical tool for measuring intramolecular distances in biomolecules, however FRET is only effective over a 3-10nm scale. In this work we advance a quenching based method which uses Cy3B and Atto647N, a common dye pair used for smFRET. The quenching effect arising from this dye pair is sensitive to distance changes below 3nm, which is significantly lower than its R0 of 6.2 nm. It has previously been used to measure binary on/off transitions, such as local DNA melting in polymerase complexes. However, by using a series of DNAs labelled at various positions we have shown that we can quantitatively distinguish between slight changes in labelling separation. This quenching method is sufficiently sensitive to distinguish between DNAs labelled with dyes 1bp 3′ of each other from those labelled 5′ of each other. Additionally, this effect has been validated …

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Feb 2022 • arXiv preprint arXiv:2202.03640

Special purpose quantum graphs for guaranteed and fast search times

Quancheng Liu, David A Kessler, Eli Barkai

We design monitored quantum walks with the aim of optimizing state transfer and target search. We show how to construct walks with the property that all the eigenvalues of the non-Hermitian survival operator, describing the mixed effect of unitary dynamics and the back-action of measurement, coalesce to zero, corresponding to an exceptional point whose degree is the size of the Hilbert space. Generally, this search is guaranteed to succeed in a bounded time for any initial condition. It also performs better than the classical random walk search or quantum search on typical graphs. For example, a crawler can be designed such that, starting on a node of the graph, the walker is detected on any of the nodes with probability one at predetermined times. It also allows perfect quantum state transfer from one node of the system to any other, with or without monitoring. Interestingly, this crawler is described as a massless Dirac quasi-particle.

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Feb 2022 • Physical Review E

Generalized virial equation for nonlinear multiplicative Langevin dynamics: Application to laser-cooled atoms

Gianmaria Falasco, Eli Barkai, Marco Baiesi

The virial theorem, and the equipartition theorem in the case of quadratic degrees of freedom, are handy constraints on the statistics of equilibrium systems. Their violation is instrumental in determining how far from equilibrium a driven system might be. We extend the virial theorem to nonequilibrium conditions for Langevin dynamics with nonlinear friction and multiplicative noise. In particular, we generalize it for confined laser-cooled atoms in the semiclassical regime. The resulting relation between the lowest moments of the atom position and velocity allows to measure in experiments how dissipative the cooling mechanism is. Moreover, its violation can reveal the departure from a strictly harmonic confinement or from the semiclassical regime.

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Feb 2022 • Cancer Research

Abstract PD6-03: Spatio-molecular dissection of the breast cancer metastatic microenvironment

Daniel L Abravanel, Johanna Klughammer, Timothy Blosser, Yury Goltsev, Sizun Jiang, Yunjao Bai, Evan Murray, Shahar Alon, Yi Cui, Daniel R Goodwin, Anubhav Sinha, Ofir Cohen, Michal Slyper, Orr Ashenberg, Danielle Dionne, Judit Jané-Valbuena, Caroline BM Porter, Asa Segerstolpe, Julia Waldman, Sébastien Vigneau, Karla Helvie, Allison Frangieh, Laura DelloStritto, Miraj Patel, Jingyi We, Kathleen Pfaff, Nicole Cullen, Ana Lako, Madison Turner, Isaac Wakiro, Sara Napolitano, Abhay Kanodia, Rebecca Ortiz, Colin MacKichan, Stephanie Inga, Judy Chen, Aaron R Thorner, Asaf Rotem, Scott Rodig, Fei Chen, Edward S Boyden, Garry P Nolan, Xiaowei Zhuang, Orit Rozenblatt-Rosen, Bruce E Johnson, Aviv Regev, Nikhil Wagle

Metastatic breast cancer (MBC) remains incurable due to inevitable development of therapeutic resistance. Although tumor cell intrinsic mechanisms of resistance in MBC are beginning to be elucidated by bulk sequencing studies, the roles of the tumor microenvironment and intratumor heterogeneity in therapeutic resistance remain underexplored due to both technological barriers and limited availability of samples. To comprehensively capture these characteristics we have adapted a research biopsy protocol to collect tissue for an array of single-cell and spatio-molecular assays whose performance we have optimized for MBC, including single-cell and single-nucleus RNA sequencing, Slide-Seq, Multiplexed Error-Robust FISH (MERFISH), Expansion Sequencing (ExSEQ), Co-detection by Indexing (CODEX) and Multiplexed Ion Beam Imaging (MIBI). To date, we have successfully performed single-cell or single …

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Feb 2022 • Proc. of SPIE Vol 11979, 1197901-1, 2022

Frontiers in Biological Detection: From Nanosensors to Systems XIV

Benjamin L Miller, Sharon M Weiss

The papers in this volume were part of the technical conference cited on the cover and title page. Papers were selected and subject to review by the editors and conference program committee. Some conference presentations may not be available for publication. Additional papers and presentation recordings may be available online in the SPIE Digital Library at SPIEDigitalLibrary. org.

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Feb 2022 • Physical Review Applied

Visualizing Current in Superconducting Networks

X Wang, M Laav, I Volotsenko, A Frydman, B Kalisky

We present an experimental study of local magnetic imaging in order to visualize the current flow in superconducting networks. We track the evolution of the spatial distribution of the current flow as the network is driven from fully superconducting to fully normal phases. Our results highlight the factors that contribute to the disordered flow in superconducting networks during their collapse, and demonstrate that the current is never uniformly distributed in the network. These results can assist the design and development of circuits based on superconductors and Josephson junctions.

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