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Oct 2022 • Communications Biology

Affinity microfluidics enables high-throughput protein degradation analysis in cell-free extracts

Lev Brio, Danit Wasserman, Efrat Michaely-Barbiro, Gal Barazany-Gal, Doron Gerber, Amit Tzur

Protein degradation mediated by the ubiquitin-proteasome pathway regulates signaling events in many physiological and pathological conditions. In vitro degradation assays have been instrumental in the understanding of how cell proliferation and other fundamental cellular processes are regulated. These assays are direct, time-specific and highly informative but also laborious, typically relying on low-throughput polyacrylamide gel-electrophoresis followed by autoradiography or immunoblotting. We present protein degradation on chip (pDOC), a MITOMI-based integrated microfluidic technology for discovery and analysis of proteins degradation in cell-free extracts. The platform accommodates hundreds of microchambers on which protein degradation is assayed quickly, simultaneously and using minute amounts of reagents in one or many physiochemical environments. Essentially, pDOC provides a sensitive …

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Oct 2022 • Journal of The Electrochemical Society

Pulsed Charging Protocols with Non-Zero Relaxation Time for Lithium-Ion Batteries

Lautaro N Acosta, Guillermo Garaventta, Mikhael Levi, Doron Aurbach, Victoria Flexer

Lithium-ion batteries are commonly charged following the constant current-constant voltage (CC-CV) protocol. Current flow during charging implies an equivalent ionic flow through the battery materials. Intercalation and de-intercalation of Li+ are accompanied by concentration gradients that are reflected by the rise in the cells' potentials that is required to maintain the constant current during the CC regime. In this work, two new pulsed charging protocols were tested. Firstly, a square current pulse is applied to the cell until the cut-off voltage is reached, followed by a pulsed square voltage protocol (PV). The second methodology keeps the same current pulse, however, after the limiting voltage was reached, the pulsing regime consisted in alternating between a maximum voltage value and a minimum, non-zero, constant current value. Different voltage pulse widths and frequencies were tested, in order to study the …

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Oct 2022 • Advanced Science

Highly Stable 4.6 V LiCoO2 Cathodes for Rechargeable Li Batteries by Rubidium‐Based Surface Modifications

Tianju Fan, Yujie Wang, Villa Krishna Harika, Amey Nimkar, Kai Wang, Xiaolang Liu, Meng Wang, Leimin Xu, Yuval Elias, Munseok S Chae, Yonggang Min, Yuhao Lu, Netanel Shpigel, Doron Aurbach

Among extensively studied Li‐ion cathode materials, LiCoO2 (LCO) remains dominant for portable electronic applications. Although its theoretical capacity (274 mAh g−1) cannot be achieved in Li cells, high capacity (≤240 mAh g−1) can be obtained by raising the charging voltage up to 4.6 V. Unfortunately, charging Li‐LCO cells to high potentials induces surface and structural instabilities that result in rapid degradation of cells containing LCO cathodes. Yet, significant stabilization is achieved by surface coatings that promote formation of robust passivation films and prevent parasitic interactions between the electrolyte solutions and the cathodes particles. In the search for effective coatings, the authors propose RbAlF4 modified LCO particles. The coated LCO cathodes demonstrate enhanced capacity (>220 mAh g−1) and impressive retention of >80/77% after 500/300 cycles at 30/45 °C. A plausible mechanism …

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Oct 2022 • 2022 IEEE International Topical Meeting on Microwave Photonics (MWP), 1-4, 2022

Electro-Opto-Mechanical Microwave-Frequency Oscillator in a Surface Acoustic Wave Silicon-Photonic Circuit

Maayan Priel, Saawan Kumar Bag, Matan Slook, Leroy Dokhanian, Inbar Shafir, Etai Grunwald, Moshe Katzman, Mirit Hen, Avi Zadok

An electro-opto-mechanical microwave frequency oscillator is demonstrated through a silicon photonic circuit. An electrical signal modulates an optical pump wave input. Modulation is converted to a surface acoustic wave on the silicon circuit through absorption in a metallic grating and thermoelastic expansion. The acoustic wave is delayed and converted back to optics through photoelastic modulation of a continuous optical input probe wave in a racetrack resonator waveguide. The output probe is detected, and the obtained voltage is amplified and fed back to modulate the input optical pump wave. With sufficient feedback gain, the electro-opto-mechanical loop is driven to oscillations at 2.21 GHz frequency. The oscillator can be useful for integrated microwave photonics signal processing.

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Oct 2022 • Proceedings of the National Academy of Sciences

Sequestration of gut pathobionts in intraluminal casts, a mechanism to avoid dysregulated T cell activation by pathobionts

Martina Sassone-Corsi, Shalhevet Azriel, Ariel Simon, Deepshika Ramanan, Adriana Ortiz-Lopez, Felicia Chen, Nissan Yissachar, Diane Mathis, Christophe Benoist

T cells that express the transcription factor RORγ, regulatory (Treg), or conventional (Th17) are strongly influenced by intestinal symbionts. In a genetic approach to identify mechanisms underlying this influence, we performed a screen for microbial genes implicated, in germfree mice monocolonized with Escherichia coli Nissle. The loss of capsule-synthesis genes impaired clonal expansion and differentiation of intestinal RORγ+ T cells. Mechanistic exploration revealed that the capsule-less mutants remained able to induce species-specific immunoglobulin A (IgA) and were highly IgA-coated. They could still trigger myeloid cells, and more effectively damaged epithelial cells in vitro. Unlike wild-type microbes, capsule-less mutants were mostly engulfed in intraluminal casts, large agglomerates composed of myeloid cells extravasated into the gut lumen. We speculate that sequestration in luminal casts of potentially …

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Oct 2022 • Biomedical Photonics for Diabetes Research

11 Noninvasive Photonic Sensing

Nisan Ozana, Zeev Zalevsky

241 11.3 243 11.4 Magneto-Optic Effect-Based Measurements..................................................................... 245 11.5 Speckle-Based Sensing of Chemicals by an Acoustic Excitation in Aqueous Solutions... 249 Remote Sensing of Tissue Perfusion in the Lower Limbs.................................................. 250 11.6 11.7 Summary............................................................................................................................ 251 252 Acknowledgments References

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Oct 2022 • Scientific Reports

Non-contact optical in-vivo sensing of cilia motion by analyzing speckle patterns

Doron Duadi, Nadav Shabairou, Adi Primov-Fever, Zeev Zalevsky

Cilia motion is an indicator of pathological-ciliary function, however current diagnosis relies on biopsies. In this paper, we propose an innovative approach for sensing cilia motility. We present an endoscopic configuration for measuring the motion frequency of cilia in the nasal cavity. The technique is based on temporal tracking of the reflected spatial distribution of defocused speckle patterns while illuminating the cilia with a laser. The setup splits the optical signal into two channels; One imaging channel is for the visualization of the physician and another is, defocusing channel, to capture the speckles. We present in-vivo measurements from healthy subjects undergoing endoscopic examination. We found an average motion frequency of around 7.3 Hz and 9.8 Hz in the antero-posterior nasal mucus (an area rich in cilia), which matches the normal cilia range of 7–16 Hz. Quantitative and precise measurements of …

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Oct 2022 • Protein Science

Copper coordination states affect the flexibility of copper Metallochaperone Atox1: Insights from molecular dynamics simulations

Renana Schwartz, Sharon Ruthstein, Dan Thomas Major

Copper is an essential element in nature but in excess it is toxic to the living cell. The human metallochaperone Atox1 participates in copper homeostasis and is responsible for copper transmission. In a previous multiscale simulation study, we noticed a change in the coordination state of the Cu(I) ion, from 4 bound cysteine residues to 3, in agreement with earlier studies. Here we perform and analyse classical molecular dynamic simulations of various coordination states: 2, 3, and 4. The main observation is an increase in protein flexibility as a result of a decrease in coordination state. Additionally, we identified several populated conformations that correlate well with double electron‐electron resonance distance distributions or an X‐ray structure of Cu(I)‐bound Atox1. We suggest that the increased flexibility might benefit the process of ion transmission between interacting proteins. Further experiments can …

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Oct 2022

Characterization of nanometric thin films with far-field light

Adi Salomon, Omer Shavit, Carine Julien, Ilya Olevsko, Mohamed Hamode, Yossi Abulafia, Hervé Suaudeau, Vincent Armand, Martin Oheim

The fabrication and characterisation of ultra-thin, transparent lms is paramount for protective layers on semiconductors, solar cells, as well as for nano-composite materials and optical coatings. Similarly, the probe volume of nano-sensors, as well the calibration of axial distances in super-resolution microscopies, all require the metrology of axial uorophore distances. However, the reliable production and precise characterisation of such nanometric thin layers are di cult and labor-intense and they require specialized equipment and trained personnel. In our present work, we describe a simple, non-invasive, all-optical technique for simultaneously measuring the refractive index, thickness, and homogeneity of such thin lms. We assemble transparent layers from My-133-MC, a biomimetic transparent polymer with a refractive index of 1.33, amenable for applications in the life sciences. All parameters characterising the lms are obtained in a single measurement from the analysis of supercritical angle uorescence radiation patterns acquired on a minimally modi ed inverted microscope. Results compare favorably to those obtained through a combination of atomic force and electron microscopy, surface-plasmon resonance spectroscopy and ellipsometry. To illustrate the utility of our technique, we present two applications, one in metrology and one in bio-imaging;(i), the calibration of axial uorophore distance in a total internal re ection uorescence geometry; and,(ii), live-cell super-resolution imaging of organelle dynamics in cortical astrocytes, an important type of brain cell. Our approach is cheap, versatile and it has obvious applications in pro lometry …

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Oct 2022 • ACS Applied Materials & Interfaces

NiN-Passivated NiO Hole-Transport Layer Improves Halide Perovskite-Based Solar Cell

Anat Itzhak, Xu He, Adi Kama, Sujit Kumar, Michal Ejgenberg, Antoine Kahn, David Cahen

The interfaces between inorganic selective contacts and halide perovskites (HaPs) are possibly the greatest challenge for making stable and reproducible solar cells with these materials. NiOx, an attractive hole-transport layer as it fits the electronic structure of HaPs, is highly stable and can be produced at a low cost. Furthermore, NiOx can be fabricated via scalable and controlled physical deposition methods such as RF sputtering to facilitate the quest for scalable, solvent-free, vacuum-deposited HaP-based solar cells (PSCs). However, the interface between NiOx and HaPs is still not well-controlled, which leads at times to a lack of stability and Voc losses. Here, we use RF sputtering to fabricate NiOx and then cover it with a NiyN layer without breaking vacuum. The NiyN layer protects NiOx doubly during PSC production. Firstly, the NiyN layer protects NiOx from Ni3+ species being reduced to Ni2+ by Ar plasma …

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Oct 2022 • Biosensors

A Contact-Free Optical Device for the Detection of Pulmonary Congestion—A Pilot Study

Ilan Merdler, Aviram Hochstadt, Eihab Ghantous, Lior Lupu, Ariel Borohovitz, David Zahler, Philippe Taieb, Ben Sadeh, Zeev Zalevsky, Javier Garcia-Monreal, Michael Shergei, Maxim Shatsky, Yoav Beck, Sagi Polani, Yaron Arbel

Background: The cost of heart failure hospitalizations in the US alone is over USD 10 billion per year. Over 4 million Americans are hospitalized every year due to heart failure (HF), with a median length of stay of 4 days and an in-hospital mortality rate that exceeds 5%. Hospitalizations of patients with HF can be prevented by early detection of lung congestion. Our study assessed a new contact-free optical medical device used for the early detection of lung congestion. Methods: The Gili system is an FDA-cleared device used for measuring chest motion vibration data. Lung congestion in the study was assessed clinically and verified via two cardiologists. An algorithm was developed using machine learning techniques, and cross-validation of the findings was performed to estimate the accuracy of the algorithm. Results: A total of 227 patients were recruited (101 cases vs. 126 controls). The sensitivity and specificity for the device in our study were 0.91 (95% CI: 0.86–0.93) and 0.91 (95% CI: 0.87–0.94), respectively. In all instances, the observed estimates of PPVs and NPVs were at least 0.82 and 0.90, respectively. The accuracy of the algorithm was not affected by different covariates (including respiratory or valvular conditions). Conclusions: This study demonstrates the efficacy of a contact-free optical device for detecting lung congestion. Further validation of the study results across a larger and precise scale is warranted.

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Oct 2022 • ACS Energy Letters

Solvent-Assisted Hopping Mechanism Enables Ultrafast Charging of Lithium-Ion Batteries

Xiaoteng Huang, Ruhong Li, Chuangchao Sun, Haikuo Zhang, Shuoqing Zhang, Ling Lv, Yiqiang Huang, Liwu Fan, Lixin Chen, Malachi Noked, Xiulin Fan

Fast charging is regarded as one of the most coveted technologies for commercial Li-ion batteries (LIBs), but the lack of suitable electrolytes with sufficient ionic conductivity and effective passivation properties hinders its development. Herein, we designed a mixed-solvent electrolyte (1 M LiPF6 in fluoroethylene carbonate/acetonitrile, FEC/AN, 7/3 by vol.) to overcome these two limitations by achieving an FEC-dominated solvation structure and an AN-rich environment. The specific AN-assisted Li+ hopping transport behavior shortens the Li+ diffusion time, doubling the ionic conductivity to 12 mS cm–1, thus endowing the graphite anode with >300 mAh g–1 at 20C and reversible (de)intercalation over a wide temperature range (from −20 to +60 °C). Furthermore, the designed electrolyte triples the capacity of the 1 Ah graphite||LiNi0.8Mn0.1Co0.1O2 (NMC811) pouch cells at 8C in comparison with the commercial …

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Oct 2022 • Advanced Quantum Technologies 5 (2), 2100121, 2022

Geometric phases and the Sagnac effect: Foundational aspects and sensing applications

Ismael L Paiva, Rain Lenny, Eliahu Cohen

Geometric phase is a key player in many areas of quantum science and technology. In this review article, we outline several foundational aspects of quantum geometric phases and their relations to classical geometric phases. We then discuss how the Aharonov-Bohm and Sagnac effects fit into this context. Moreover, we present a concise overview of technological applications of the latter, with special emphasis on gravitational sensing, like in gyroscopes and gravitational wave detectors.

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Oct 2022 • Journal of The Electrochemical Society

Improving Li Anode Reversibility in Li–S Batteries by ZnO Coated Separators Using Atomic Layer Deposition

Shalev Blanga, Reut Yemini, Eti Teblum, Merav Nadav Tsubery, Sarah Taragin, Malachi Noked

Lithium-sulfur batteries (LSBs) are considered a very attractive alternative to lithium-ion batteries due to their high theoretical capacity and the low cost of the active materials. However, the realization of LSBs remains hostage to many challenges associated with the cathode and anode response to the electrochemical conditions inside the battery cell. While working with LSBs, elemental sulfur undergoes multielectron reduction reactions until it is reduced to Li2S. The intermediate long chain lithium-polysulfide (LiPS) species are soluble, and hence diffuse through the electrolyte solution from the cathode side to the anode. This “shuttle” phenomenon is considered to be one of the main issues of LSB. Most effort in investigating LSBs has focused on the cathode side while few have considered the importance of the lithium anode reversibility and the separator role in preventing the “shuttle” phenomenon. In the current …

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Oct 2022 • Applied Sciences

Kerr-Lens Mode-Locking: Numerical Simulation of the Spatio-Temporal Dynamics on All Time Scales

Idan Parshani, Leon Bello, Mallachi-Elia Meller, Avi Pe’er

We present a complete numerical analysis and simulation of the full spatio-temporal dynamics of Kerr-lens mode-locking in a laser. This dynamic, which is the workhorse mechanism for generating ultrashort pulses, relies on the intricate coupling between the spatial nonlinear propagation and the temporal nonlinear compression. Our numerical tool emulates the dynamical evolution of the optical field in the cavity on all time-scales: the fast time scale of the pulse envelope within a single round trip, and the slow time-scale between round-trips. We employ a nonlinear ABCD formalism that fully handles all relevant effects in the laser, namely—self focusing and diffraction, dispersion and self-phase modulation, and space-dependent loss and gain saturation. We confirm the validity of our model by reproducing the pulse-formation in all aspects: The evolution of the pulse energy, duration, and gain during the entire cavity buildup, demonstrating the nonlinear mode competition in full, as well as the dependence of the final pulse in steady state on the interplay between gain bandwidth, dispersion, and self-phase modulation. The direct observation of the nonlinear evolution of the pulse in space-time is a key enabler to analyze and optimize the Kerr-lens mode-locking operation, as well as to explore new nonlinear phenomena.

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Oct 2022 • Communications Materials

Nanomechanical signatures of degradation-free influence of water on halide perovskite mechanics

Isaac Buchine, Irit Rosenhek-Goldian, Naga Prathibha Jasti, Davide R Ceratti, Sujit Kumar, David Cahen, Sidney R Cohen

Humidity is often reported to compromise the stability of lead halide perovskites or of devices based on them. Here we measure the humidity dependence of the elastic modulus and hardness for two series of lead halide perovskite single crystals, varying either by cation or by anion type. The results reveal a dependence on bond length between, hydrogen bonding with, and polarizability/polarization of these ions. The results show an intriguing inverse relation between modulus and hardness, in contrast to their positive correlation for most other materials. This anomaly persists and is strengthened by the effect of humidity. This, and our overall findings are ascribed to the materials’ unique atomic-scale structure and properties, viz nano-polar domains and strong dynamic disorder, yet high-quality average order. Our conclusions are based on comparing results obtained from several different nano-indentation …

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Oct 2022 • Journal of Personalized Medicine

Trace Elements in Tears: Comparison of Rural and Urban Populations Using Particle Induced X-ray Emission

Olga Girshevitz, Noa Cohen-Sinai, Alon Zahavi, Yoav Vardizer, Dror Fixler, Nitza Goldenberg-Cohen

We aimed to evaluate the types and concentrations of trace elements in tears of individuals living in urban and rural environments using particle induced X-ray emission (PIXE) and the possible association with exposure to air pollution and suggest a novel method for tear-based biomonitoring studies. This cross-sectional pilot study comprised 42 healthy subjects, 28 living in a rural area and 14 in an industrial city. Tears were collected with Schirmer paper and characterized by PIXE. Trace element concentrations from both eyes were averaged together with environmental pollution data. Main outcome measures were between-group differences in types and concentrations of trace elements in tears and comparison to environmental data. The rural group included 12/28 men, mean age 45.2 ± 14.8 years. The urban group consisted of 11/14 men of mean age 27 ± 5.9 years. Six rural and all urban were active smokers. Air pollution data showed more toxic elements in the rural environment. On PIXE analysis, chlorine, sodium, and potassium were found in similar concentrations in all samples. Normalizing to chlorine yielded higher values of aluminum, iron, copper, and titanium in the rural group; aluminum was found only in the rural group. The higher levels of certain trace elements in the rural group may, in part, be a consequence of exposure to specific environmental conditions. No direct association was found with air pollution data. PIXE is useful to analyze trace elements in tears, which might serve as a marker for individual exposure to environmental pollutants in biomonitoring studies.

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Oct 2022 • arXiv preprint arXiv:2210.07732

The identification of mean quantum potential with Fisher information leads to a strong uncertainty relation

Yakov Bloch, Eliahu Cohen

The Cramer-Rao bound, satisfied by classical Fisher information, a key quantity in information theory, has been shown in different contexts to give rise to the Heisenberg uncertainty principle of quantum mechanics. In this paper, we show that the identification of the mean quantum potential, an important notion in Bohmian mechanics, with the Fisher information, leads, through the Cramer-Rao bound, to an uncertainty principle which is stronger, in general, than both Heisenberg and Robertson-Schrodinger uncertainty relations, allowing to experimentally test the validity of such an identification.

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Oct 2022 • Biology

The Gut-Ex-Vivo System (GEVS) Is a Dynamic and Versatile Tool for the Study of DNBS-Induced IBD in BALB/C and C57BL/6 Mice, Highlighting the Protective Role of Probiotics

Romina Monzani, Mara Gagliardi, Nausicaa Clemente, Valentina Saverio, Elżbieta Pańczyszyn, Claudio Santoro, Nissan Yissachar, Annalisa Visciglia, Marco Pane, Angela Amoruso, Marco Corazzari

Simple Summary IBD is considered a modern and western diet-related disease characterized by uncontrolled immune activation, resulting in chronic bowel inflammation and tissue damage. Although the precise causes of the onset of the disease are still elusive, it seems that both the environment, genetic predisposition and the dysregulation of the intestinal microbiota are actively involved. The development of a model to study the etiopathology of this disease characterized by an increasing incidence in the population is urgently needed. We have recently developed an organ-on-chip system (Gut-Ex-Vivo System, GEVS) to model IBD induced by DNBS in the colon of mice of the BALB/c strain. Here, we provide data demonstrating that the process can also be efficiently induced in mice of another strain, C57BL/6, which is usually less sensitive to this treatment, using our GEVS. Furthermore, we have shown that the system also replicates other characteristics of human pathology, such as the induction of the two most represented cell death pathways responsible for the tissue damage characteristic of IBD. Finally, we demonstrate that our system can be used efficiently to test new therapeutic interventions, such as those based on the use of probiotics. Indeed, we demonstrated the positive impact of both Lactobacilli and Bifidobacteria. Abstract Background: IBD is a spectrum of pathologies characterized by dysregulated immune activation leading to uncontrolled response against the intestine, thus resulting in chronic gut inflammation and tissue damage. Due to its complexity, the molecular mechanisms responsible for …

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Oct 2022 • Advanced Engineering Materials

Printed Cu–Ag Phases Using Laser‐Induced Forward Transfer

Niv Gorodesky, Sharona Sedghani-Cohen, Ofer Fogel, Marc Altman, Gili Cohen-Taguri, Zvi Kotler, Zeev Zalevsky

Laser‐induced forward transfer (LIFT) is an additive manufacturing technique where short laser pulses are focused through a transparent substrate onto a thin, uniform, metal layer jetting micrometer‐scale droplets yielding high‐resolution 3D metal structures. Herein, LIFT printing from multilayered metal donors, and from compositional metal mixtures, is explored and presented. A comprehensive study of this sort has been lacking so far. LIFT printing from Cu–Ag structured donors is thoroughly studied. X‐ray diffraction (XRD) analysis reveals the formation of a metastable Cu–Ag phase reflecting the high cooling rate of the metal droplets. Tuning properties of the printed metal structures is made possible by controlling the pulse width and the donor layers’ properties. Longer pulses (10 ns) jetting from cosputtered donors yield better homogeneity than shorter pulses (1 ns) from donors made of distinct sputtered …

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Oct 2022 • Communications materials

Nanomechanical signatures of degradation-free influence of water on halide perovskite mechanics

Isaac Buchine, Irit Rosenhek-Goldian, Naga Prathibha Jasti, Davide R Ceratti, Sujit Kumar, David Cahen, Sidney R Cohen

Humidity is often reported to compromise the stability of lead halide perovskites or of devices based on them. Here we measure the humidity dependence of the elastic modulus and hardness for two series of lead halide perovskite single crystals, varying either by cation or by anion type. The results reveal a dependence on bond length between, hydrogen bonding with, and polarizability/polarization of these ions. The results show an intriguing inverse relation between modulus and hardness, in contrast to their positive correlation for most other materials. This anomaly persists and is strengthened by the effect of humidity. This, and our overall findings are ascribed to the materials’ unique atomic-scale structure and properties, viz nano-polar domains and strong dynamic disorder, yet high-quality average order. Our conclusions are based on comparing results obtained from several different nano-indentation …

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