Jun 2023 • Molecular Therapy-Methods & Clinical Development
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 …
Show moreJun 2023 • ACS Applied Materials & Interfaces
Poushali Das, Masoomeh Sherazee, Parham Khoshbakht Marvi, Syed Rahin Ahmed, Aharon Gedanken, Seshasai Srinivasan, Amin Reza Rajabzadeh
Hospital-acquired (nosocomial) infections account for the majority of adverse health effects during care delivery, placing an immense financial strain on healthcare systems around the world. For the first time, the present article provides evidence of a straightforward pollution-free technique to fabricate a heteroatom-doped carbon dot immobilized fluorescent biopolymer composite for the development of functional textiles with antioxidant and antimicrobial properties. A simple, facile, and eco-friendly approach was devised to prepare heteroatom-doped carbon dots from waste green tea and a biopolymer. The carbon dots showed an excitation-dependent emission behavior, and the XPS data unveiled that they are co-doped with nitrogen and sulfur. A facile physical compounding strategy was adopted to fabricate a carbon dot reinforced biopolymeric composite followed by immobilization onto the textile. The composite …
Show moreJun 2023 • arXiv preprint arXiv:2306.15985
Dominik Szombathy, Miklós Antal Werner, Cătălin Paşcu Moca, Örs Legeza, Assaf Hamo, Shahal Ilani, Gergely Zaránd
The collective tunneling of a a Wigner necklace - a crystalline state of a small number of strongly interacting electrons confined to a suspended nanotube and subject to a double well potential - is theoretically analyzed and compared with experiments in [Shapir , Science , 870 (2019)]. Density Matrix Renormalization Group computations, exact diagonalization, and instanton theory provide a consistent description of this very strongly interacting system, and show good agreement with experiments. Experimentally extracted and theoretically computed tunneling amplitudes exhibit a scaling collapse. Collective quantum fluctuations renormalize the tunneling, and substantially enhance it as the number of electrons increases.
Show moreJun 2023 • Developmental Cell
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 …
Show moreJun 2023 • 2023 IEEE International Conference on Acoustics, Speech, and Signal …, 2023
Ofek Ophir, Orit Shefi, Ofir Lindenbaum
The brain is likely the most complex organ, given the variety of functions it controls, the number of cells it comprises, and their corresponding connectivity and diversity. Identifying and studying neurons, the major building blocks of the brain, is a crucial milestone and is essential for understanding brain functionality in health and disease. Recent developments in machine learning have provided advanced abilities for classifying neurons, mainly according to their morphology. This paper aims to provide an explainable deep-learning framework to classify neurons based on their electrophysiological activity. Our analysis is performed on data provided by the Allen Cell Types database. The data contains a survey of biological features derived from single-cell recordings from mice. Neurons are classified into subtypes based on Cre mouse lines using an inherently interpretable locally sparse deep neural network model …
Show moreJun 2023 • ACS Omega
Alon Tzroya, Shoshana Erblich, Hamootal Duadi, Dror Fixler
Clean water is essential for maintaining human health. To ensure clean water, it is important to use sensitive detection methods that can identify contaminants in real time. Most techniques do not rely on optical properties and require calibrating the system for each level of contamination. Therefore, we suggest a new technique to measure water contamination using the full scattering profile, which is the angular intensity distribution. From this, we extracted the iso-pathlength (IPL) point which minimizes the effects of scattering. The IPL point is an angle where the intensity values remain constant for different scattering coefficients while the absorption coefficient is set. The absorption coefficient does not affect the IPL point but only attenuates its intensity. In this paper, we show the appearance of the IPL in single scattering regimes for small concentrations of Intralipid. We extracted a unique point for each sample diameter …
Show moreJun 2023 • Molecular Cell, 2023
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 …
Show moreJun 2023 • Molecules
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 …
Show moreJun 2023 • Journal of Power Sources
Shubham Garg, Sarah Taragin, Arka Saha, Olga Brontvein, Kevin Leung, Malachi Noked
Despite having the ability to deliver 650 W h kg−1 in addition to the impressive rate capability, superior thermal stability, and facilitated electronic and ionic lithium conduction, LiNi0.5Mn1.5O4 (LNMO) is far from commercial applications. LNMO suffers from irreversible electrolytic degradation on its surface under high voltage operations leading to capacity fading and poor battery life. Therefore, this work aims to improve the stability and electrochemical behavior of LNMO by creating a Zn-enriched cathode layer interface via eccentric and facile diethyl zinc-assisted atomic surface reduction (Zn-ASR). In-depth surface characterization tools and computational calculations demonstrates a conformal 7-8 nm thin Zn-O and C-O enriched layer encapsulating the cathode particles resulting from Zn-ASR. The intensive comparative electrochemical and spectroscopic analysis, indicates superior electrochemical performance of …
Show moreJun 2023 • Annals of the Rheumatic Diseases 82, 1217, 2023
G Halpert, O Moskovitch, A Anaki, T Caller, O Gendelman, A Watad, R Shai, R Popovtzer, H Amital
Background Progress has been achieved with the introduction of biologics for the management of inflammatory/autoimmune diseases such as rheumatoid arthritis (RA), however such medications induce immune suppression, which is nonselective to the pathogenesis of the disease, resulting in higher rates of infections. Therefore, there are unmet medical needs in the treatment of such diseases, which should be addressed by novel approaches. Accumulating evidence suggests that extracellular vesicles (EVs) play a role in the establishment, maintenance and modulation of autoimmune processes.Objectives In the current study, we hypothesized that isolation of circulating autologous tissue-specific homing EVs from RA patients - may improve the delivery of current FDA-approved anti-inflammatory drugs, which will be encapsulated into these EVs. The drug-loaded EVs will be injected back to the diseased subjects …
Show moreJun 2023 • Journal of Investigative Dermatology
Miriam Karmon, Eli Kopel, Aviv Barzilai, Polina Geva, Eli Eisenberg, Erez Y Levanon, Shoshana Greenberger
Atopic dermatitis (AD) is associated with dysregulated type 1 IFN‒mediated responses, in parallel with the dominant type 2 inflammation. However, the pathophysiology of this dysregulation is largely unknown. Adenosine-to-inosine RNA editing plays a critical role in immune regulation by preventing double-stranded RNA recognition by MDA5 and IFN activation. We studied global adenosine-to-inosine editing in AD to elucidate the role played by altered editing in the pathophysiology of this disease. Analysis of three RNA-sequencing datasets of AD skin samples revealed reduced levels of adenosine-to-inosine RNA editing in AD. This reduction was seen globally throughout Alu repeats as well as in coding genes and in specific pre-mRNA loci expected to create long double-stranded RNA, the main substrate of MDA5 leading to type I IFN activation. Consistently, IFN signature genes were upregulated. In contrast …
Show moreJun 2023 • arXiv preprint arXiv:2306.16209
René IP Sedmik, Alexander Urech, Zeev Zalevsky, Itai Carmeli
Casimir forces, related to London-van der Waals forces, arise if the spectrum of electromagnetic fluctuations is restricted by boundaries. There is great interest both from fundamental science and technical applications to control these forces on the nano scale. Scientifically, the Casimir effect being the only known quantum vacuum effect manifesting between macroscopic objects, allows to investigate the poorly known physics of the vacuum. In this work, we experimentally investigate the influence of self-assembled molecular bio and organic thin films on the Casimir force between a plate and a sphere. We find that molecular thin films, despite being a mere few nanometers thick, reduce the Casimir force by up to 14%. To identify the molecular characteristics leading to this reduction, five different bio-molecular films with varying chemical and physical properties were investigated. Spectroscopic data reveal a broad absorption band whose presence can be attributed to the mixing of electronic states of the underlying gold layer and those of the molecular film due to charge rearrangement in the process of self-assembly. Using Lifshitz theory we calculate that the observed change in the Casimir force is consistent with the appearance of the new absorption band due to the formation of molecular layers. The desired Casimir force reduction can be tuned by stacking several monolayers, using a simple self-assembly technique in a solution. The molecules - each a few nanometers long - can penetrate small cavities and holes, and cover any surface with high efficiency. This process seems compatible with current methods in the production of micro …
Show moreJun 2023 • arXiv preprint arXiv:2306.16702
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.
Show moreJun 2023 • Optics Continuum
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 …
Show moreJun 2023 • Preprints, 2023
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.
Show moreJun 2023 • Electrochimica Acta
Sankalpita Chakrabarty, Yuri Glagovsky, Ananya Maddegalla, Natalia Fridman, Dmitry Bravo-Zhivotovski, Doron Aurbach, Ayan Mukherjee, Malachi Noked
The electrochemical response of ethereal solutions containing magnesium organohaloaluminate complexes has drawn great interest in recent decades owing to their relevance to rechargeable magnesium batteries, as demonstrated with solutions containing complexes formed by reacting R2Mg and AlCl2R moieties in ethers like tetrahydrofuran (THF). However, most of previous reports focused on battery related performances, and less on the structure of the active species. Herein, we focus on (1) identifying electroactive species and (2) correlating the electrochemical properties of their solutions to the preparation modes: either through reactions of their precursors in THF, or by dissolving isolated crystallized products in the ether solvent. Specifically, we explore the products of the reaction of the Grignard reagent t-BuMgCl with AlCl3 (1:1) in THF, and how their presence in solutions affect their electrochemical …
Show moreJun 2023 • Molecular cell 83 (15), 2624-2640, 2023
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 …
Show moreJun 2023 • arXiv preprint arXiv:2306.16319
Avraham Samama, Eli Barkai
Since the times of Holtsmark (1911), statistics of fields in random environments have been widely studied, for example in astrophysics, active matter, and line-shape broadening. The power-law decay of the two-body interaction, of the form , and assuming spatial uniformity of the medium particles exerting the forces, imply that the fields are fat-tailed distributed, and in general are described by stable L\'evy distributions. With this widely used framework, the variance of the field diverges, which is non-physical, due to finite size cutoffs. We find a complementary statistical law to the L\'evy-Holtsmark distribution describing the large fields in the problem, which is related to the finite size of the tracer particle. We discover bi-scaling, with a sharp statistical transition of the force moments taking place when the order of the moment is , where is the dimension. The high-order moments, including the variance, are described by the framework presented in this paper, which is expected to hold for many systems. The new scaling solution found here is non-normalized similar to infinite invariant densities found in dynamical systems.
Show moreJun 2023 • Journal of Power Sources
Shubham Garg, Sarah Taragin, Arka Saha, Olga Brontvein, Kevin Leung, Malachi Noked
Despite having the ability to deliver 650 W h kg−1 in addition to the impressive rate capability, superior thermal stability, and facilitated electronic and ionic lithium conduction, LiNi0.5Mn1.5O4 (LNMO) is far from commercial applications. LNMO suffers from irreversible electrolytic degradation on its surface under high voltage operations leading to capacity fading and poor battery life. Therefore, this work aims to improve the stability and electrochemical behavior of LNMO by creating a Zn-enriched cathode layer interface via eccentric and facile diethyl zinc-assisted atomic surface reduction (Zn-ASR). In-depth surface characterization tools and computational calculations demonstrates a conformal 7-8 nm thin Zn-O and C-O enriched layer encapsulating the cathode particles resulting from Zn-ASR. The intensive comparative electrochemical and spectroscopic analysis, indicates superior electrochemical performance of …
Show moreJun 2023 • arXiv preprint arXiv:2306.13621
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.
Show moreJun 2023 • arXiv preprint arXiv:2306.13621
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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