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Jun 2023 • Science

Facile mechanochemical cycloreversion of polymer cross-linkers enhances tear resistance

Shu Wang, Yixin Hu, Tatiana B Kouznetsova, Liel Sapir, Danyang Chen, Abraham Herzog-Arbeitman, Jeremiah A Johnson, Michael Rubinstein, Stephen L Craig

The mechanical properties of covalent polymer networks often arise from the permanent end-linking or cross-linking of polymer strands, and molecular linkers that break more easily would likely produce materials that require less energy to tear. We report that cyclobutane-based mechanophore cross-linkers that break through force-triggered cycloreversion lead to networks that are up to nine times as tough as conventional analogs. The response is attributed to a combination of long, strong primary polymer strands and cross-linker scission forces that are approximately fivefold smaller than control cross-linkers at the same timescales. The enhanced toughness comes without the hysteresis associated with noncovalent cross-linking, and it is observed in two different acrylate elastomers, in fatigue as well as constant displacement rate tension, and in a gel as well as elastomers.

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Jun 2023 • Molecular cell 83 (15), 2624-2640, 2023

Spatial and temporal organization of the genome: Current state and future aims of the 4D nucleome project

Job Dekker, Frank Alber, Sarah Aufmkolk, Brian J Beliveau, Benoit G Bruneau, Andrew S Belmont, Lacramioara Bintu, Alistair Boettiger, Riccardo Calandrelli, Christine M Disteche, David M Gilbert, Thomas Gregor, Anders S Hansen, Bo Huang, Danwei Huangfu, Reza Kalhor, Christina S Leslie, Wenbo Li, Yun Li, Jian Ma, William S Noble, Peter J Park, Jennifer E Phillips-Cremins, Katherine S Pollard, Susanne M Rafelski, Bing Ren, Yijun Ruan, Yaron Shav-Tal, Yin Shen, Jay Shendure, Xiaokun Shu, Caterina Strambio-De-Castillia, Anastassiia Vertii, Huaiying Zhang, Sheng Zhong

The four-dimensional nucleome (4DN) consortium studies the architecture of the genome and the nucleus in space and time. We summarize progress by the consortium and highlight the development of technologies for (1) mapping genome folding and identifying roles of nuclear components and bodies, proteins, and RNA, (2) characterizing nuclear organization with time or single-cell resolution, and (3) imaging of nuclear organization. With these tools, the consortium has provided over 2,000 public datasets. Integrative computational models based on these data are starting to reveal connections between genome structure and function. We then present a forward-looking perspective and outline current aims to (1) delineate dynamics of nuclear architecture at different timescales, from minutes to weeks as cells differentiate, in populations and in single cells, (2) characterize cis-determinants and trans-modulators of …

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Jun 2023 • Quantum 2.0, QTh3A. 2, 2023

Nanometric-scale phase contrast imaging with undetected x-ray photons

Haim Aknin, Sharon Shwartz

We show that a system using down conversion of x-ray photons into optical photons together with the concept of quantum imaging with undetected photons can provide nanoscale resolution even for radiation sensitive samples.

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Jun 2023 • Optics Continuum

Remote sensing of human skin temperature by AI speckle pattern analysis

Ofir Ben David, Yevgeny Beiderman, Sergey Agdarov, Yafim Beiderman, Zeev Zalevsky

Analysis of dynamic differential speckle patterns, scattered from human tissues illuminated by a laser beam, has been found by many researchers to be applicable for noncontact sensing of various biomedical parameters. The COVID-19 global pandemic brought the need for massive rapid-remote detection of a fever in closed public spaces. The existing non-contact temperature measurement methods have a significant tradeoff between the measurement distance and accuracy. This paper aims to prove the feasibility of an accurate temperature measurement system based on speckle patterns analysis, enabling the sensing of human temperature from an extended distance greater than allowed by the existing methods. In this study, we used speckle patterns analysis combined with artificial intelligence (AI) methods for human temperature extraction, starting with fever/no fever binary classification and continuing with …

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Jun 2023 • arXiv preprint arXiv:2306.16110

Deep-subwavelength Phase Retarders at Mid-Infrared Frequencies with van der Waals Flakes

Michael T Enders, Mitradeep Sarkar, Aleksandra Deeva, Maxime Giteau, Hanan Herzig Sheinfux, Mehrdad Shokooh-Saremi, Frank HL Koppens, Georgia T Papadakis

Phase retardation is a cornerstone of modern optics, yet, at mid-infrared (mid-IR) frequencies, it remains a major challenge due to the scarcity of simultaneously transparent and birefringent crystals. Most materials resonantly absorb due to lattice vibrations occurring at mid-IR frequencies, and natural birefringence is weak, calling for hundreds of microns to millimeters-thick phase retarders for sufficient polarization rotation. We demonstrate mid-IR phase retardation with flakes of -molybdenum trioxide (-MoO) that are more than ten times thinner than the operational wavelength, achieving 90 degrees polarization rotation within one micrometer of material. We report conversion ratios above 50% in reflection and transmission mode, and wavelength tunability by several micrometers. Our results showcase that exfoliated flakes of low-dimensional crystals can serve as a platform for mid-IR miniaturized integrated polarization control.

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Jun 2023 • Molecular Therapy-Methods & Clinical Development

OCT4 induces long-lived dedifferentiated kidney progenitors poised to redifferentiate in 3D kidney spheroids

Dorit Omer, Osnat Cohen Zontag, Yehudit Gnatek, Orit Harari-Steinberg, Oren Pleniceanu, Michael Namestnikov, Ayelet-Hashahar Cohen, Malka Nissim-Rafinia, Gal Tam, Tomer Kalisky, Eran Meshorer, Benjamin Dekel

Upscaling of kidney epithelial cells is crucial for renal regenerative medicine. Nonetheless, the adult kidney lacks a distinct stem cell hierarchy, limiting the ability to long-term propagate clonal populations of primary cells that retain renal identity. Toward this goal, we tested the paradigm of shifting the balance between differentiation and stemness in the kidney by introducing a single pluripotency factor, OCT4. Here we show that ectopic expression of OCT4 in human adult kidney epithelial cells (hKEpC) induces the cells to dedifferentiate, stably proliferate, and clonally emerge over many generations. Control hKEpC dedifferentiate, assume fibroblastic morphology, and completely lose clonogenic capacity. Analysis of gene expression and histone methylation patterns revealed that OCT4 represses the HNF1B gene module, which is critical for kidney epithelial differentiation, and concomitantly activates stemness …

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Jun 2023

Free electron laser stochastic spectroscopy revealing silicon bond softening dynamics

Jakub Szlachetko, Dario De Angelis, Emiliano Principi, Filippo Bencivenga, Daniele Fausti, Laura Foglia, Yishay Klein, Michele Manfredda, Riccardo Mincigrucci, Angela Montanaro, Emanuele Pedersoli, Jacopo Stefano Pelli Cresi, Giovanni Perosa, Kevin C Prince, Elia Razzoli, Sharon Shwartz, Alberto Simoncig, Simone Spampinati, Cristian Svetina, Alok Tripathi, Ivan A Vartanyants, Marco Zangrando, Flavio Capotondi

Time-resolved x-ray emission/absorption spectroscopy (Tr-XES/XAS) is an informative experimental tool sensitive to electronic dynamics in materials, widely exploited in diverse research fields. Typically, Tr-XES/XAS requires x-ray pulses with both a narrow bandwidth and subpicosecond pulse duration, a combination that in principle finds its optimum with Fourier transform-limited pulses. In this work, we explore an alternative experimental approach, capable of simultaneously retrieving information about unoccupied (XAS) and occupied (XES) states from the stochastic fluctuations of broadband extreme ultraviolet pulses of a free electron laser. We used this method, in combination with singular-value decomposition and Tikhonov regularization procedures, to determine the XAS/XES response from a crystalline silicon sample at the L2, 3 edge, with an energy resolution of a few tens of meV. Finally, we combined this spectroscopic method with a pump-probe approach to measure structural and electronic dynamics of a silicon membrane. Tr-XAS/XES data obtained after photoexcitation with an optical laser pulse at 390 nm allowed us to observe perturbations of the band structure, which are compatible with the formation of the predicted precursor state of a nonthermal solid-liquid phase transition associated with a bond softening phenomenon.

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Jun 2023 • Materials Today Chemistry

Thin coating of silica/polystyrene core-shell nano/microparticles with hierarchical morphology onto polymeric films for fabrication of superhydrophobic surfaces

S Hayne, S Margel

A novel coating process applied directly onto polymeric films offers a long-term alternative to short-term surface treatment of low surface energy polymers. In this paper, we report (i) an improved synthesis of a coating of raspberry-like particles directly onto polymeric surfaces and (ii) a novel method to obtain films with out-of-the ordinary superhydrophobic and self-cleaning properties. Inspired by the ‘lotus effect’ observed in nature, superhydrophobic surfaces were fabricated by combining dual-scale hierarchical coatings with low surface energy fluoroalkanes. Raspberry-like core-shell microparticles (MPs) composed of polystyrene (PS) core coated with silica (SiO2) shell (SiO2/PS) were synthesized by in situ dispersion polymerization of styrene directly on the surface of corona-treated polypropylene films. The PS MPs covered surface was then coated with SiO2 nano/microparticles (N/MPs) forming a hierarchical …

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Jun 2023 • Investigative Ophthalmology & Visual Science

RNA editing of mutations causing inherited retinal diseases using the cellular deaminase acting on RNA (ADAR) enzyme

Dror Sharon, Nina Schneider, Johanna Valensi, Ricky Steinberg, Amit Eylon, Eyal Banin, Erez Levanon, Shay Ben-Aroya

Purpose: Single nucleotide editing can be performed at the RNA level using the human deaminase acting on RNA (ADAR) enzyme and can serve as a tool for gene therapy of inherited diseases, including inherited retinal diseases (IRDs). ADAR-based RNA editing requires the delivery of an efficient guideRNA (gRNA) that is designed to recruit the endogenously expressed ADAR enzyme to a mutated RNA. Our aim is to design and test gRNAs that induce targeted ADAR editing for relatively common IRD-causing mutations including nonsense, missense, and splice-site mutations.Methods: A yeast model was used to identify candidate gRNAs for nonsense mutations by measuring yeast survival and percent editing using next generation sequencing (NGS). A fluorescence-expressing plasmid reporter system was used in HeLa cells overexpressing either ADAR1/2. The cells were transfected by a plasmid that includes …

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Jun 2023 • arXiv preprint arXiv:2306.13621

Ergodic properties of Brownian motion under stochastic resetting

Eli Barkai, Rosa Flaquer-Galmes, Vicenç Méndez

We study ergodic properties of one-dimensional Brownian motion with resetting. Using generic classes of statistics of times between resets, we find respectively for thin/fat tailed distributions, the normalized/non-normalised invariant density of this process. The former case corresponds to known results in the resetting literature and the latter to infinite ergodic theory. Two types of ergodic transitions are found in this system. The first is when the mean waiting time between resets diverges, when standard ergodic theory switches to infinite ergodic theory. The second is when the mean of the square root of time between resets diverges and the properties of the invariant density are drastically modified. We then find a fractional integral equation describing the density of particles. This finite time tool is particularly useful close to the ergodic transition where convergence to asymptotic limits is logarithmically slow. Our study implies rich ergodic behaviors for this non-equilibrium process which should hold far beyond the case of Brownian motion analyzed here.

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Jun 2023 • Physical Review B

Free electron laser stochastic spectroscopy revealing silicon bond softening dynamics

Dario De Angelis, Emiliano Principi, Filippo Bencivenga, Daniele Fausti, Laura Foglia, Yishay Klein, Michele Manfredda, Riccardo Mincigrucci, Angela Montanaro, Emanuele Pedersoli, Jacopo Stefano Pelli Cresi, Giovanni Perosa, Kevin C Prince, Elia Razzoli, Sharon Shwartz, Alberto Simoncig, Simone Spampinati, Cristian Svetina, Jakub Szlachetko, Alok Tripathi, Ivan A Vartanyants, Marco Zangrando, Flavio Capotondi

Time-resolved x-ray emission/absorption spectroscopy (Tr-XES/XAS) is an informative experimental tool sensitive to electronic dynamics in materials, widely exploited in diverse research fields. Typically, Tr-XES/XAS requires x-ray pulses with both a narrow bandwidth and subpicosecond pulse duration, a combination that in principle finds its optimum with Fourier transform-limited pulses. In this work, we explore an alternative experimental approach, capable of simultaneously retrieving information about unoccupied (XAS) and occupied (XES) states from the stochastic fluctuations of broadband extreme ultraviolet pulses of a free electron laser. We used this method, in combination with singular-value decomposition and Tikhonov regularization procedures, to determine the XAS/XES response from a crystalline silicon sample at the L 2, 3 edge, with an energy resolution of a few tens of meV. Finally, we combined this …

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Jun 2023 • Preprints, 2023

Isothermal Titration Calorimetry: The Heat of Dilution, Racemization, and What Lies In Between

Matan Oliel, Yitzhak Mastai

Chiral interactions play a crucial role in both chemistry and biology. Understanding the behavior of chiral molecules and their interactions with other molecules is essential, and chiral interactions in solutions are particularly important for studying chiral compounds. Chirality influences the physical and chemical properties of molecules, including solubility, reactivity, and biological activity. In this work, we used Isothermal Titration Calorimetry (ITC), a powerful technique for studying molecular interactions, including chiral interactions in solutions. We conducted a series of ITC measurements to investigate the heat of dilution and the heat of racemization of several amino acids (Asn, His, Ser, Ala, Met, and Phe). We also performed ITC measurements under different solute concentrations and temperatures to examine the effects of these parameters on chiral interactions, as well as the heat of dilution and racemization. The results of our measurements indicated that the heat of dilution, specifically the interactions between the solvent (water) and solute (chiral molecules), had a significant impact compared to the chiral interactions in the solution, which were found to be negligible. This suggests that the interactions between chiral molecules and the solvent play a more dominant role in determining the overall behavior and properties of the system. By studying chiral interactions in solutions, we can gain valuable insights into the behavior of chiral compounds, which can have implications in various fields, including drug design, chemical synthesis, and biological processes.

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Jun 2023 • Molecular Cell, 2023

Spatial and temporal organization of the genome: Current state and future aims of the 4D nucleome project

Job Dekker, Frank Alber, Sarah Aufmkolk, Brian J Beliveau, Benoit G Bruneau, Andrew S Belmont, Lacramioara Bintu, Alistair Boettiger, Riccardo Calandrelli, Christine M Disteche, David M Gilbert, Thomas Gregor, Anders S Hansen, Bo Huang, Danwei Huangfu, Reza Kalhor, Christina S Leslie, Wenbo Li, Yun Li, Jian Ma, William S Noble, Peter J Park, Jennifer E Phillips-Cremins, Katherine S Pollard, Susanne M Rafelski, Bing Ren, Yijun Ruan, Yaron Shav-Tal, Yin Shen, Jay Shendure, Xiaokun Shu, Caterina Strambio-De-Castillia, Anastassiia Vertii, Huaiying Zhang, Sheng Zhong

The four-dimensional nucleome (4DN) consortium studies the architecture of the genome and the nucleus in space and time. We summarize progress by the consortium and highlight the development of technologies for (1) mapping genome folding and identifying roles of nuclear components and bodies, proteins, and RNA, (2) characterizing nuclear organization with time or single-cell resolution, and (3) imaging of nuclear organization. With these tools, the consortium has provided over 2,000 public datasets. Integrative computational models based on these data are starting to reveal connections between genome structure and function. We then present a forward-looking perspective and outline current aims to (1) delineate dynamics of nuclear architecture at different timescales, from minutes to weeks as cells differentiate, in populations and in single cells, (2) characterize cis-determinants and trans-modulators of …

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Jun 2023 • Developmental Cell

Genetic perturbation of AMP biosynthesis extends lifespan and restores metabolic health in a naturally short-lived vertebrate

Gwendoline Astre, Tehila Atlan, Uri Goshtchevsky, Adi Oron-Gottesman, Margarita Smirnov, Kobi Shapira, Ariel Velan, Joris Deelen, Tomer Levy, Erez Y Levanon, Itamar Harel

During aging, the loss of metabolic homeostasis drives a myriad of pathologies. A central regulator of cellular energy, the AMP-activated protein kinase (AMPK), orchestrates organismal metabolism. However, direct genetic manipulations of the AMPK complex in mice have, so far, produced detrimental phenotypes. Here, as an alternative approach, we alter energy homeostasis by manipulating the upstream nucleotide pool. Using the turquoise killifish, we mutate APRT, a key enzyme in AMP biosynthesis, and extend the lifespan of heterozygous males. Next, we apply an integrated omics approach to show that metabolic functions are rejuvenated in old mutants, which also display a fasting-like metabolic profile and resistance to high-fat diet. At the cellular level, heterozygous cells exhibit enhanced nutrient sensitivity, reduced ATP levels, and AMPK activation. Finally, lifelong intermittent fasting abolishes the longevity …

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Jun 2023 • NATURE

Magnetic memory and spontaneous vortices in a van der Waals superconductor (vol 607, pg 692, 2022)

Eylon Persky, Anders V Bjorlig, Irena Feldman, Avior Almoalem, Ehud Altman, Erez Berg, Itamar Kimchi, Jonathan Ruhman, Amit Kanigel, Beena Kalisky


Jun 2023 • Molecules

Stable High-Capacity Elemental Sulfur Cathodes with Simple Process for Lithium Sulfur Batteries

Shunsuke Sawada, Hideki Yoshida, Shalom Luski, Elena Markevich, Gregory Salitra, Yuval Elias, Doron Aurbach

Lithium sulfur batteries are suitable for drones due to their high gravimetric energy density (2600 Wh/kg of sulfur). However, on the cathode side, high specific capacity with high sulfur loading (high areal capacity) is challenging due to the poor conductivity of sulfur. Shuttling of Li-sulfide species between the sulfur cathode and lithium anode also limits specific capacity. Sulfur-carbon composite active materials with encapsulated sulfur address both issues but require expensive processing and have low sulfur content with limited areal capacity. Proper encapsulation of sulfur in carbonaceous structures along with active additives in solution may largely mitigate shuttling, resulting in cells with improved energy density at relatively low cost. Here, composite current collectors, selected binders, and carbonaceous matrices impregnated with an active mass were used to award stable sulfur cathodes with high areal specific capacity. All three components are necessary to reach a high sulfur loading of 3.8 mg/cm2 with a specific/areal capacity of 805 mAh/g/2.2 mAh/cm2. Good adhesion between the carbon-coated Al foil current collectors and the composite sulfur impregnated carbon matrices is mandatory for stable electrodes. Swelling of the binders influenced cycling retention as electroconductivity dominated the cycling performance of the Li-S cells comprising cathodes with high sulfur loading. Composite electrodes based on carbonaceous matrices in which sulfur is impregnated at high specific loading and non-swelling binders that maintain the integrated structure of the composite electrodes are important for strong performance. This basic design can …

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Jun 2023 • arXiv preprint arXiv:2306.16702

Monte Carlo Simulations for Ghost Imaging Based on Scattered Photons

RH Shukrun, S Shwartz

X-ray based imaging modalities are widely used in research, industry, and in the medical field. Consequently, there is a strong motivation to improve their performances with respect to resolution, dose, and contrast. Ghost imaging (GI) is an imaging technique in which the images are reconstructed from measurements with a single-pixel detector using correlation between the detected intensities and the intensity structures of the input beam. The method that has been recently extended to X-rays provides intriguing possibilities to overcome several fundamental challenges of X-ray imaging. However, understanding the potential of the method and designing X-ray GI systems pose challenges since in addition to geometric optic effects, radiation-matter interactions must be considered. Such considerations are fundamentally more complex than those at longer wavelengths as relativistic effects such as Compton scattering become significant. In this work we present a new method for designing and implementing GI systems using the particle transport code FLUKA, that rely on Monte Carlo (MC) sampling. This new approach enables comprehensive consideration of the radiation-matter interactions, facilitating successful planning of complex GI systems. As an example of an advanced imaging system, we simulate a high-resolution scattered photons GI technique.

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Jun 2023 • arXiv preprint arXiv:2306.16258

Synchrotron-based x ray fluorescence ghost imaging

Mathieu Manni, Adi Ben-Yehuda, Yishay Klein, Bratislav Lukic, Andrew Kingston, Alexander Rack, Sharon Shwartz, Nicola Viganò

X-ray Fluorescence Ghost Imaging (XRF-GI) was recently demonstrated for x-ray lab sources. It has the potential to reduce acquisition time and deposited dose by choosing their trade-off with spatial resolution, while alleviating the focusing constraints of the probing beam. Here, we demonstrate the realization of synchrotron-based XRF-GI: We present both an adapted experimental setup and its corresponding required computational technique to process the data. This not only extends the above-mentioned advantages to synchrotron XRF imaging, it also presents new possibilities for developing strategies to improve precision in nano-scale imaging measurements.

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Jun 2023 • Optics Continuum

Remote sensing of human skin temperature by AI speckle pattern analysis

Ofir Ben David, Yevgeny Beiderman, Sergey Agdarov, Yafim Beiderman, Zeev Zalevsky


May 2023 • Journal of Applied Physics

Parallel array of planar Hall effect sensors for high resolution magnetometry

Hariharan Nhalil, Moty Schultz, Shai Amrusi, Asaf Grosz, Lior Klein

We introduce a planar Hall effect magnetometer in the form of a parallel array of permalloy-based elliptical sensors. The number of ellipses in the array and other fabrication parameters are optimized with the support of numerical simulations. We obtain equivalent magnetic noise (EMN) of 16 pT/ffiffiffiffiffiffi Hz p at 100 Hz, 25 pT/ffiffiffiffiffiffi Hz p at 10 Hz, 98 pT/ffiffiffiffiffiffi Hz p at 1 Hz, and 470 pT/ffiffiffiffiffiffi Hz p at 0.1 Hz. The exceptional EMN without the use of magnetic flux concentrators highlights the advantages of the design. The presented magnetometer, characterized by its simplicity, affordability, and ability to operate at room temperature, is anticipated to be useful for applications requiring pT resolution.

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May 2023 • Nature Physics

Interdependent superconducting networks

Ivan Bonamassa, Bnaya Gross, Maayan Laav, Irina Volotsenko, Aviad Frydman, Shlomo Havlin

Interdependent networks display many interesting properties, but have not been studied in laboratory experiments because of the lack of a platform that manifests appropriate couplings. Now, a network of disordered superconductors accomplishes this.

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