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Jan 2021 • Molecules

Metal–Metal Bond in the Light of Pauling’s Rules

Elena Levi, Doron Aurbach, Carlo Gatti

About 70 years ago, in the framework of his theory of chemical bonding, Pauling proposed an empirical correlation between the bond valences (or effective bond orders (BOs)) and the bond lengths. Till now, this simple correlation, basic in the bond valence model (BVM), is widely used in crystal chemistry, but it was considered irrelevant for metal–metal bonds. An extensive analysis of the quantum chemistry data computed in the last years confirms very well the validity of Pauling’s correlation for both localized and delocalized interactions. This paper briefly summarizes advances in the application of the BVM for compounds with TM–TM bonds (TM= transition metal) and provides further convincing examples. In particular, the BVM model allows for very simple but precise calculations of the effective BOs of the TM–TM interactions. Based on the comparison between formal and effective BOs, we can easily describe steric and electrostatic effects. A possible influence of these effects on materials stability is discussed. View Full-Text

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Jan 2021 • AIP Advances

DNA origami based superconducting nanowires

Lior Shani, Philip Tinnefeld, Yafit Fleger, Amos Sharoni, Boris Ya Shapiro, Avner Shaulov, Oleg Gang, Yosef Yeshurun

Utilizing self-assembled DNA structures in the development of nanoelectronic circuits requires transforming the DNA strands into highly conducting wires. Toward this end, we investigate the use of DNA self-assembled nanowires as templates for the deposition of a superconducting material. Nanowires formed by the deposition of superconducting NbN exhibit thermally activated and quantum phase slips as well as exceptionally large negative magnetoresistance. The latter effect can be utilized to suppress a significant part of the low temperature resistance caused by the quantum phase slips.

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Jan 2021 • bioRxiv

Genome instability drives epistatic adaptation in the human pathogen Leishmania

Giovanni Bussotti, Laura Piel, Pascale Pescher, Malgorzata Anna Domagalska, K Shanmugha Rajan, Tirza Doniger, Disha Gajanan Hiregange, Peter J Myler, Ron Unger, Shulamit J Michaeli, Gerald Frank Spaeth

How genome instability is harnessed for fitness gain despite its potential deleterious effects is largely elusive. An ideal system to address this important open question is provided by the protozoan pathogen Leishmania that exploits frequent variations in chromosome and gene copy number to regulate expression levels. Using ecological genomics and experimental evolution approaches we provide first evidence that Leishmania adaptation relies on epistatic interactions between functionally associated gene copy number variations that can inform on pathways driving fitness gain in a given environment. We further uncover post-transcriptional regulation as a key mechanism that compensates for deleterious gene dosage effects and provides phenotypic robustness to genetically heterogenous parasite populations. Finally, we correlate dynamic variations in snoRNA gene dosage to changes in rRNA 2′-O-methylation and pseudouridylation, proposing translational control as an additional layer of parasite adaptation. Leishmania genome instability is thus harnessed for fitness gain by genome-dependent variations in gene expression, and genome-independent, compensatory mechanisms. This allows for polyclonal adaptation and maintenance of genetic heterogeneity despite strong selection. Epistatic adaptation described here needs to be considered in Leishmania epidemiology and biomarker discovery, and may be relevant to other fast evolving, eukaryotic cells that exploit genome instability for adaptation, such as fungal pathogens or cancer.

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Jan 2021 • bioRxiv

Protein degradation analysis by affinity microfluidics

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

Protein degradation mediated by the ubiquitin-proteasome pathway regulates signaling events in all eukaryotic cells, with implications in pathological conditions such as cancer and neurodegenerative diseases. Detection of protein degradation is an elementary need in basic and translational research. In vitro degradation assays, in particular, have been instrumental in the understanding of how cell proliferation and other fundamental cellular processes are regulated. These assays are direct, quantitative 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 device for discovery and analysis of ubiquitin mediated proteolysis. The platform accommodates microchambers on which protein degradation is assayed quickly and simultaneously in physiologically relevant environments, using minute amount of reagents. Essentially, pDOC provides a multiplexed, sensitive and colorimetric alternative to the conventional degradation assays, with relevance to biomedical and translational research.

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Jan 2021 • Journal of Food Science and Technology

Making salty cucumbers and honeyed apples by applying the sonochemical method

Belal Abu Salha, Nina Perkas, Aharon Gedanken

Sonochemistry was applied in the last few years for coating surfaces of various substrates for imparting desired properties to the surface. In the current paper the coating of cucumbers with NaCl nanoparticles and apples with honey nanoparticles was accomplished by applying the sonochemical method. In both coating the nanoparticles were deposited from aqueous solutions. The products were characterized by Inductively coupled plasma, Dynamic light scattering, Scanning electron microscopy, and Nuclear magnetic resonance.

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Jan 2021 • bioRxiv

Germline polymorphisms and alternative splicing of human immunoglobulin light chain genes

Ivana Mikocziova, Ayelet Peres, Moriah Gidoni, Victor Greiff, Gur Yaari, Ludvig M Sollid

Immunoglobulin loci are rich in germline polymorphisms and identification of novel polymorphic variants can be facilitated by germline inference of B cell receptor repertoires. Germline gene inference is complicated by somatic hypermutations, errors arising from PCR amplification, and DNA sequencing as well as from the varying length of reference alleles. Inference of light chain genes is even more challenging than inference of heavy chain genes due to large gene duplication events on the kappa locus as well as absence of D genes in the rearranged light chain transcripts. Here, we analyzed the light chain cDNA sequences from naïve BCR repertoires of a Norwegian cohort of 100 individuals. We optimized light chain allele inference by tweaking parameters within TIgGER functions, extending the germline reference sequences, and establishing mismatch frequency patterns at polymorphic positions to filter out false positive candidates. As a result, we identified 48 previously unreported variants of light chain variable genes. Altogether, we selected 14 candidates for novel light chain polymorphisms for validation and successfully validated 11 by Sanger sequencing. Additional clustering of light chain 5′UTR, L-PART1 and L-PART2 revealed partial intron retention in alternative splice variants in 11 kappa and 9 lambda V alleles. The alternatively spliced transcripts were only observed in genes with low expression levels, suggesting a possible role in expression regulation. Our results provide novel insight into germline variation in human light chain immunoglobulin loci.

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Jan 2021 • International journal of molecular sciences

Loss of fer jeopardizes metabolic plasticity and mitochondrial homeostasis in lung and breast carcinoma cells

Linoy Mehazri, Sally Shpungin, Shai Bel, Uri Nir

Metabolic plasticity is a hallmark of the ability of metastatic cancer cells to survive under stressful conditions. The intracellular Fer kinase is a selective constituent of the reprogramed mitochondria and metabolic system of cancer cells. In the current work, we deciphered the modulatory roles of Fer in the reprogrammed metabolic systems of metastatic, lung (H358), non-small cell lung cancer (NSCLC), and breast (MDA-MB-231), triple-negative breast cancer (TNBC), carcinoma cells. We show that H358 cells devoid of Fer (H358ΔFer), strictly depend on glucose for their proliferation and growth, and fail to compensate for glucose withdrawal by oxidizing and metabolizing glutamine. Furthermore, glucose deficiency caused increased reactive oxygen species (ROS) production and induction of a DNA damage response (DDR), accompanied by the onset of apoptosis and attenuated cell-cycle progression. Analysis of mitochondrial function revealed impaired respiratory and electron transport chain (ETC) complex 1 (comp. I) activity in the Fer-deficient H358ΔFer cells. This was manifested by decreased levels of NAD+ and ATP and relatively low abundance of tricarboxylic acid (TCA) cycle metabolites. Impaired electron transport chain comp. I activity and dependence on glucose were also confirmed in Fer-deficient, MDA-MB-231ΔFer cells. Although both H358ΔFer and MDA-MB-231ΔFer cells showed a decreased aspartate level, this seemed to be compensated by the predominance of pyrimidines synthesis over the urea cycle progression. Notably, absence of Fer significantly impeded the growth of H358ΔFer and MDA-MB-231ΔFer xenografts in mice …

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Jan 2021 • Applied Sciences

Knowledge of Quantum Hidden Variables Enables Backwards-In-Time Signaling

Avishy Carmi, Eliahu Cohen, Lorenzo Maccone, Hrvoje Nikolić

Bell’s theorem implies that any completion of quantum mechanics which uses hidden variables (that is, preexisting values of all observables) must be nonlocal in the Einstein sense. This customarily indicates that knowledge of the hidden variables would permit superluminal communication. Such superluminal signaling, akin to the existence of a preferred reference frame, is to be expected. However, here we provide a protocol that allows an observer with knowledge of the hidden variables to communicate with her own causal past, without superluminal signaling. That is, such knowledge would contradict causality, irrespectively of the validity of relativity theory. Among the ways we propose for bypassing the paradox there is the possibility of hidden variables that change their values even when the state does not, and that means that signaling backwards in time is prohibited in Bohmian mechanics. View Full-Text

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Jan 2021 • Journal of The Electrochemical Society

Improved High-Energy Na-NCM Cathode Prepared by Ion Exchange Route via Application of Various ALD Treatments

Meital Turgeman, Miryam Fayena-Greenstein, Shaul Bublil, Netanel Shpigel, Merav Nadav Tsubery, Munseok Chae, Yuval Elias, Doron Aurbach

The application of layered oxide compounds as cathode materials for sodium-ion batteries is considered a promising direction for the development of high-energy Na-ion batteries. However, despite many efforts, practical implementation of such electrodes is still challenging, mainly due to structural and surface instabilities associated with the high operating voltage of these cathodes. One of the most effective ways to mitigate these undesirable phenomena is the use of atomic layer deposition (ALD) to form a Nano-sized protective layer on the electrode surface. Application of ALD treatment results in increased electrode stability by preventing irreversible interactions between the electrolyte and cathode material. In search of optimal coating formulations, the effect of various ALD coatings viz. sodium-aluminate, lithium-aluminate, and alumina on the electrochemical performance of Na-NCM cathode synthesized by ion …

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Jan 2021 • bioRxiv

Post-transcriptional regulation of Leishmania fitness gain

Laura Piel, K Shanmugha Rajan, Giovanni Bussotti, Hugo Varet, Rachel Legendre, Caroline Proux, Thibaut Douché, Quentin Giai Gianetto, Thibaut Chaze, 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 Frank Spaeth

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 (fitness gain) impairing infectivity (fitness costs). Comparative genomics, transcriptomics and proteomics analyses revealed a complex regulatory network driving parasite fitness, with genome instability causing highly reproducible, gene dosage-dependent changes in protein linked to post-transcriptional regulation. These in turn were associated with a gene dosage-independent reduction in flagellar transcripts and a coordinated increase in abundance of coding and non-coding RNAs known to regulate ribosomal biogenesis and protein translation. We correlated differential expression of small nucleolar RNAs (snoRNAs) with changes in rRNA modification, providing first evidence that Leishmania fitness gain may be controlled by post-transcriptional and epitranscriptomic regulation. Our findings propose a novel model for Leishmania fitness gain, where differential regulation of mRNA stability and the generation of fitness-adapted ribosomes may potentially filter deleterious …

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Jan 2021 • Membranes

Exploring the effect of iron metal-organic framework particles in polylactic acid membranes for the azeotropic separation of organic/organic mixtures by pervaporation

Asma Msahel, Francesco Galiano, Martina Pilloni, Francesca Russo, Amor Hafiane, Roberto Castro-Muñoz, Vijay Bhooshan Kumar, Aharon Gedanken, Guido Ennas, Ze’ev Porat, Alessandra Scano, Sofiane Ben Hamouda, Alberto Figoli

A microporous carboxylate metal-organic framework MIL-100 Fe was prepared as submicron particles by microwave-assisted hydrothermal synthesis (Fe-MOF-MW). This product was explored, for the first time, for the preparation of polylactic acid (PLA) mixed matrix membranes. The produced MOF was characterised by powder X-ray diffraction (PXRD), environmental scanning electron microscopy (ESEM) as well as by thermogravimetric analysis (TGA) and nitrogen adsorption/desorption. The effect of different Fe-MOF-MW concentrations (0.1 and 0.5 wt%) on the membrane properties and performance were evaluated. These membranes were used in the pervaporation process for the separation of methanol/methyl tert-butyl-ether mixtures at the azeotropic point. The influence of the feed temperature and vacuum pressure on the membrane performance was evaluated and the results were compared with PLA pristine membranes. Moreover, the produced membranes have been characterised in terms of morphology, MOF dispersion in the polymeric membrane matrix, wettability, thickness, mechanical resistance and swelling propensity. The presence of Fe-MOF-MW was found to have a beneficial effect in improving the selectivity of mixed matrix membranes towards methanol at both concentrations. The highest selectivity was obtained for the PLA membranes embedded with 0.5 wt% of Fe-MOF-MW and tested at the temperature of 25 C and vacuum pressure of 0.09 mbar. View Full-Text

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Jan 2021 • Nano Energy

MXene conductive binder for improving performance of sodium-ion anodes in water-in-salt electrolyte

Fyodor Malchik, Netanel Shpigel, Mikhael D Levi, Tirupathi Rao Penki, Bar Gavriel, Gil Bergman, Meital Turgeman, Doron Aurbach, Yury Gogotsi

While many studies have been devoted to the development of new active materials for Na-ion aqueous batteries, much less attention has been given to the binders and other passive components, which largely determine the battery performance. This study demonstrates a beneficial use of MXene as a highly efficient binder for Na-ion anodes operating in aqueous electrolyte solutions. The high conductivity of 2D titanium carbide (Ti3C2Tx; T = terminal groups, mostly –OH, 0 < x < 2) denoted as MXene and the strong attractive interactions between its sheets and active material particles enable their effective encapsulation providing electronically conductive paths, fast ion transfer, and capacitive contribution to the stored charge. Using highly concentrated NaClO4 as an electrolyte solution providing a stable potential operation window, successful integration of NaTi2(PO3)4 (NTP) particles with MXene as a binding …

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Jan 2021 • Sensors

Rapid and sensitive inhibitor screening using magnetically modulated biosensors

Shira Roth, Amos Danielli

Inhibitor screening is an important tool for drug development, especially during the COVID-19 pandemic. The most used in vitro inhibitor screening tool is an enzyme-linked immunosorbent assay (ELISA). However, ELISA-based inhibitor screening is time consuming and has a limited dynamic range. Using fluorescently and magnetically modulated biosensors (MMB), we developed a rapid and sensitive inhibitor screening tool. This study demonstrates its performance by screening small molecules and neutralizing antibodies as potential inhibitors of the interaction between the spike protein 1 (S1) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the angiotensin-converting enzyme 2 (ACE2) receptor. The MMB-based assay is highly sensitive, has minimal non-specific binding, and is much faster than the commonly used ELISA (2 h vs. 7–24 h). We anticipate that our method will lead to a remarkable advance in screening for new drug candidates.

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Jan 2021 • bioRxiv

Optical probing of local membrane potential with fluorescent polystyrene beads

Zehavit Shapira, Nurit Degani-Katzav, Shimon Yudovich, Asaf Grupi, Shimon Weiss

Studying the electrical activity in single cells and in local circuits of excitable cells, like neurons, requires an easy to use and high throughput methodology that enables the measurement of membrane potential. Studying the electrical properties in particular sub-compartments of neurons, or in a specific type of neurons produces additional complexity. An optical voltage-imaging technique that allows high spatial and temporal resolution could be an ideal solution. However, most of the valid voltage imaging techniques are nonspecific; The ones that are more site-directed require much pre-work and specific adaptations in addition to other disadvantages. Here, a new technique for membrane voltage imaging, based on FRET between fluorescent polystyrene (FPS) beads and Dipicrylamine (DPA) is explored. Not only fluorescent intensity is demonstrated to be correlated with membrane potential, but more importantly, single particle voltage detection is demonstrated. Among other advantages, FPS beads can be synthesized with functional surface groups, and be further targeted to specific proteins via conjugation of recognition molecules. Therefore, FPS beads, in the presence of DPA, constitute single-particle detectors for membrane voltage, with a potential to be localized to specific membrane compartments. This new and accessible platform for targeted optical voltage imaging may further elucidate the mechanisms of neuronal electrical activity.

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Jan 2021 • Physical Review Letters

Faceting and flattening of emulsion droplets: A mechanical model

Ireth García-Aguilar, Piermarco Fonda, Eli Sloutskin, Luca Giomi

When cooled down, emulsion droplets stabilized by a frozen interface of alkane molecules and surfactants have been observed to undergo a spectacular sequence of morphological transformations: from spheres to faceted liquid icosahedra, down to flattened liquid platelets. While generally ascribed to the interplay between the elasticity of the frozen interface and surface tension, the physical mechanisms underpinning these transitions have remained elusive, despite different theoretical pictures having been proposed in recent years. In this Letter, we introduce a comprehensive mechanical model of morphing emulsion droplets, which quantitatively accounts for various experimental observations, including the size scaling behavior of the faceting transition. Our analysis highlights the role of gravity and the spontaneous curvature of the frozen interface in determining the specific transition pathway.

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Jan 2021 • Nanomaterials

Solvent-Free Mechanochemical Synthesis of ZnO Nanoparticles by High-Energy Ball Milling of ε-Zn(OH)2 Crystals

Gil Otis, Michal Ejgenberg, Yitzhak Mastai

A detailed investigation is presented for the solvent-free mechanochemical synthesis of zinc oxide nanoparticles from ε-Zn (OH) 2 crystals by high-energy ball milling. Only a few works have ever explored the dry synthetic route from ε-Zn (OH) 2 to ZnO. The milling process of ε-Zn (OH) 2 was done in ambient conditions with a 1: 100 powder/ball mass ratio, and it produced uniform ZnO nanoparticles with sizes of 10–30 nm, based on the milling duration. The process was carefully monitored and the effect of the milling duration on the powder composition, nanoparticle size and strain, optical properties, aggregate size, and material activity was examined using XRD, TEM, DLS, UV-Vis, and FTIR. The mechanism for the transformation of ε-Zn (OH) 2 to ZnO was studied by TGA and XPS analysis. The study gave proof for a reaction mechanism starting with a phase transition of crystalline ε-Zn (OH) 2 to amorphous Zn (OH) 2, followed by decomposition to ZnO and water. To the best of our knowledge, this mechanochemical approach for synthesizing ZnO from ε-Zn (OH) 2 is completely novel. ε-Zn (OH) 2 crystals are very easy to obtain, and the milling process is done in ambient conditions; therefore, this work provides a simple, cheap, and solvent-free way to produce ZnO nanoparticles in dry conditions. We believe that this study could help to shed some light on the solvent-free transition from ε-Zn (OH) 2 to ZnO and that it could offer a new synthetic route for synthesizing ZnO nanoparticles. View Full-Text

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Jan 2021 • Sensors

Remote photoacoustic sensing using single speckle analysis by an ultra-fast four quadrant photo-detector

Benjamin Lengenfelder, Martin Hohmann, Moritz Späth, Daniel Scherbaum, Manuel Weiß, Stefan J Rupitsch, Michael Schmidt, Zeev Zalevsky, Florian Klämpfl

The need for tissue contact makes photoacoustic imaging not applicable for special medical applications like wound imaging, endoscopy, or laser surgery. An easy, stable, and contact-free sensing technique might thus help to broaden the applications of the medical imaging modality. In this work, it is demonstrated for the first time that remote photoacoustic sensing by speckle analysis can be performed in the MHz sampling range by tracking a single speckle using a four quadrant photo-detector. A single speckle, which is created by self-interference of surface back-reflection, is temporally analyzed using this photo-detector. Phantoms and skin samples are measured in transmission and reflection mode. The potential for miniaturization for endoscopic application is demonstrated by fiber bundle measurements. In addition, sensing parameters are discussed. Photoacoustic sensing in the MHz sampling range by single speckle analysis with the four quadrant detector is successfully demonstrated. Furthermore, the endoscopic applicability is proven, and the sensing parameters are convenient for photoacoustic sensing. It can be concluded that a single speckle contains all the relevant information for remote photoacoustic signal detection. Single speckle sensing is therefore an easy, robust, contact-free photoacoustic detection technique and holds the potential for economical, ultra-fast photoacoustic sensing. The new detection technique might thus help to broaden the field of photoacoustic imaging applications in the future. View Full-Text

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Jan 2021 • Science

Expansion sequencing: Spatially precise in situ transcriptomics in intact biological systems

Shahar Alon, Daniel R Goodwin, Anubhav Sinha, Asmamaw T Wassie, Fei Chen, Evan R Daugharthy, Yosuke Bando, Atsushi Kajita, Andrew G Xue, Karl Marrett, Robert Prior, Yi Cui, Andrew C Payne, Chun-Chen Yao, Ho-Jun Suk, Ru Wang, Chih-Chieh Jay Yu, Paul Tillberg, Paul Reginato, Nikita Pak, Songlei Liu, Sukanya Punthambaker, Eswar PR Iyer, Richie E Kohman, Jeremy A Miller, Ed S Lein, Ana Lako, Nicole Cullen, Scott Rodig, Karla Helvie, Daniel L Abravanel, Nikhil Wagle, Bruce E Johnson, Johanna Klughammer, Michal Slyper, Julia Waldman, Judit Jané-Valbuena, Orit Rozenblatt-Rosen, Aviv Regev, IMAXT Consortium19, George M Church, Adam H Marblestone, Edward S Boyden

INTRODUCTION Cells and tissues are made up of diverse molecular building blocks, organized with nanoscale precision over extended length scales. Newly developed techniques that enable highly multiplexed, nanoscale, and subcellular analysis of such systems are required. Although much progress has been made on methods for multiplexed RNA imaging, these methods have been limited in their spatial precision, especially in the context of three-dimensional systems such as tissues. Because of this limitation, interrogation of tissues has been performed with either high spatial resolution or high molecular multiplexing capacity, but not both.RATIONALE We reasoned that physically expanding specimens by adapting expansion microscopy could help support spatially precise in situ sequencing. The physical expansion of specimens provides two benefits: First, it enables ordinary microscopes to achieve …

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Jan 2021 • Entropy

Non-normalizable quasi-equilibrium solution of the Fokker–Planck equation for nonconfining fields

Celia Anteneodo, Lucianno Defaveri, Eli Barkai, David A Kessler

We investigate the overdamped Langevin motion for particles in a potential well that is asymptotically flat. When the potential well is deep as compared to the temperature, physical observables, like the mean square displacement, are essentially time-independent over a long time interval, the stagnation epoch. However, the standard Boltzmann-Gibbs (BG) distribution is non-normalizable, given that the usual partition function is divergent. For this regime, we have previously shown that a regularization of BG statistics allows for the prediction of the values of dynamical and thermodynamical observables in the non-normalizable quasi-equilibrium state. In this work, based on the eigenfunction expansion of the time-dependent solution of the associated Fokker–Planck equation with free boundary conditions, we obtain an approximate time-independent solution of the BG form, being valid for times that are long, but still short as compared to the exponentially large escape time. The escaped particles follow a general free-particle statistics, where the solution is an error function, which is shifted due to the initial struggle to overcome the potential well. With the eigenfunction solution of the Fokker–Planck equation in hand, we show the validity of the regularized BG statistics and how it perfectly describes the time-independent regime though the quasi-stationary state is non-normalizable.

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Jan 2021 • Materials Today

Periodical concentration of surface plasmon polaritons by wave interference in metallic film with nanocavity array

Xiaotian Xue, Yihang Fan, Elad Segal, Weipeng Wang, Fei Yang, Yanfeng Wang, Fengtong Zhao, Wangyang Fu, Yunhan Ling, Adi Salomon, Zhengjun Zhang

Metallic thin films with nanocavity arrays provide ideal platforms for plasmonics, non-linear optics, surface chemistry and corresponding applications. A general understanding of electromagnetic (EM) field distributions is needed for further creation, manipulation and designation of near-field enhancements. Herein, we study the distribution of plasmonic hot spots over Ag thin films with triangular nanocavities in hexagonal arrays with a variable of lattice parameters. We propose that the concentration and interference of surface plasmon polaritons (SPP) dominates the distribution of plasmonic hot spots. The localized surface plasmonic resonance (LSPR) at nanocavities excites SPPs to propagate on the thin film, whose concentration and interference lead to an extremely strong near-field enhancement at the surface of the thin film, the location of which can also be termed as plasmonic hot spot. For this model, the …

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Jan 2021 • International Journal of Molecular Sciences 22 (4), 2050, 2021

Advances in Understanding of the Copper Homeostasis in Pseudomonas aeruginosa

Lukas Hofmann, Melanie Hirsch, Sharon Ruthstein

Thirty-five thousand people die as a result of more than 2.8 million antibiotic-resistant infections in the United States of America per year. Pseudomonas aeruginosa (P. aeruginosa) is classified a serious threat, the second-highest threat category of the US Department of Health and Human Services. Among others, the World Health Organization (WHO) encourages the discovery and development of novel antibiotic classes with new targets and mechanisms of action without cross-resistance to existing classes. To find potential new target sites in pathogenic bacteria, such as P. aeruginosa, it is inevitable to fully understand the molecular mechanism of homeostasis, metabolism, regulation, growth, and resistances thereof. P. aeruginosa maintains a sophisticated copper defense cascade comprising three stages, resembling those of public safety organizations. These stages include copper scavenging, first responder, and second responder. Similar mechanisms are found in numerous pathogens. Here we compare the copper-dependent transcription regulators cueR and copRS of Escherichia coli (E. coli) and P. aeruginosa. Further, phylogenetic analysis and structural modelling of mexPQ-opmE reveal that this efflux pump is unlikely to be involved in the copper export of P. aeruginosa. Altogether, we present current understandings of the copper homeostasis in P. aeruginosa and potential new target sites for antimicrobial agents or a combinatorial drug regimen in the fight against multidrug resistant pathogens. View Full-Text

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