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Feb 2019 • Scientific reports

Imaging of nanoparticle dynamics in live and apoptotic cells using temporally-modulated polarization

Omer Wagner, Moty Schultz, Eitan Edri, Rinat Meir, Eran Barnoy, Amihai Meiri, Hagay Shpaisman, Eli Sloutskin, Zeev Zalevsky

Gold nanoparticles are widely exploited in phototherapy. Owing to their biocompatibility and their strong visible-light surface plasmonic resonance, these particles also serve as contrast agents for cell image enhancement and super-resolved imaging. Yet, their optical signal is still insufficiently strong for many important real-life applications. Also, the differentiation between adjacent nanoparticles is usually limited by the optical resolution and the orientations of non-spherical particles are unknown. These limitations hamper the progress in cell research by direct optical microscopy and narrow the range of phototherapy applications. Here we demonstrate exploiting the optical anisotropy of non-spherical nanoparticles to achieve super-resolution in live cell imaging and to resolve the intracellular nanoparticle orientations. In particular, by modulating the light polarization and taking advantage of the polarization …

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Feb 2019 • Single Molecule Spectroscopy and Superresolution Imaging XII 10884, 1088406, 2019

3D super-resolution imaging using a generalized and scalable progressive refinement method on sparse recovery (PRIS)

Xiyu Yi, Rafael Piestun, Shimon Weiss

Within the family of super-resolution (SR) fluorescence microscopy, single-molecule localization microscopies (PALM[1], STORM[2] and their derivatives) afford among the highest spatial resolution (approximately 5 to 10 nm), but often with moderate temporal resolution. The high spatial resolution relies on the adequate accumulation of precise localizations, which requires a relatively low density of bright fluorophores. Several methods have demonstrated localization at higher densities in both two dimensions (2D)[3, 4] and three dimensions (3D)[5-7]. Additionally, with further advancements, such as functional super-resolution[8, 9] and point spread function (PSF) engineering with[8-11] or without[12] multi-channel observations, extra information (spectra, dipole orientation) can be encoded and recovered at the single molecule level. However, such advancements are not fully extended for high-density conditions in …

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Feb 2019 • Nano letters

Excitation and emission transition dipoles of type-II semiconductor nanorods

Subhabrata Ghosh, Anna M Chizhik, Gaoling Yang, Narain Karedla, Ingo Gregor, Dan Oron, Shimon Weiss, Jörg Enderlein, Alexey I Chizhik

The mechanisms of exciton generation and recombination in semiconductor nanocrystals are crucial to the understanding of their photophysics and for their application in nearly all fields. While many studies have been focused on type-I heterojunction nanocrystals, the photophysics of type-II nanorods, where the hole is located in the core and the electron is located in the shell of the nanorod, remain largely unexplored. In this work, by scanning single nanorods through the focal spot of radially and azimuthally polarized laser beams and by comparing the measured excitation patterns with a theoretical model, we determine the dimensionality of the excitation transition dipole of single type-II nanorods. Additionally, by recording defocused patterns of the emission of the same particles, we measure their emission transition dipoles. The combination of these techniques allows us to unambiguously deduce the …

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Feb 2019 • Developmental biology

Gonadal supporting cells acquire sex-specific chromatin landscapes during mammalian sex determination

S Alexandra Garcia-Moreno, Christopher R Futtner, Isabella M Salamone, Nitzan Gonen, Robin Lovell-Badge, Danielle M Maatouk

Cis-regulatory elements are critical for the precise spatiotemporal regulation of genes during development. However, identifying functional regulatory sites that drive cell differentiation in vivo has been complicated by the high numbers of cells required for whole-genome epigenetic assays. Here, we identified putative regulatory elements during sex determination by performing ATAC-seq and ChIP-seq for H3K27ac in purified XX and XY gonadal supporting cells before and after sex determination in mice. We show that XX and XY supporting cells initiate sex determination with similar chromatin landscapes and acquire sex-specific regulatory elements as they commit to the male or female fate. To validate our approach, we identified a functional gonad-specific enhancer downstream of Bmp2, an ovary-promoting gene. This work increases our understanding of the complex regulatory network underlying mammalian …

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Feb 2019 • Physical Review B

Infinite-randomness fixed point of the quantum superconductor-metal transitions in amorphous thin films

Nicholas A Lewellyn, Ilana M Percher, JJ Nelson, Javier Garcia-Barriocanal, Irina Volotsenko, Aviad Frydman, Thomas Vojta, Allen M Goldman

The magnetic-field-tuned quantum superconductor-insulator transitions of disordered amorphous indium oxide films are a paradigm in the study of quantum phase transitions and exhibit power-law scaling behavior. For superconducting indium oxide films with low disorder, such as the ones reported on here, the high-field state appears to be a quantum-corrected metal. Resistance data across the superconductor-metal transition in these films are shown here to obey an activated scaling form appropriate to a quantum phase transition controlled by an infinite-randomness fixed point in the universality class of the random transverse-field Ising model. Collapse of the field-dependent resistance vs temperature data is obtained using an activated scaling form appropriate to this universality class, using values determined through a modified form of power-law scaling analysis. This exotic behavior of films exhibiting a …

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Feb 2019 • Optics express

X-ray computational ghost imaging with single-pixel detector

Y Klein, A Schori, IP Dolbnya, K Sawhney, S Shwartz

We demonstrate computational ghost imaging at X-ray wavelengths with only one single-pixel detector. We show that, by using a known designed mask as a diffuser that induces intensity fluctuations in the probe beam, it is possible to compute the propagation of the electromagnetic field in the absence of the investigated object. We correlate these calculations with the measured data when the object is present in order to reconstruct the images of 50 μm and 80 μm slits. Our results open the possibilities for X-ray high-resolution imaging with partially coherent X-ray sources and can lead to a powerful tool for X-ray three-dimensional imaging.

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Feb 2019 • Nucleic acids research

The effect of macromolecular crowding on single-round transcription by Escherichia coli RNA polymerase

SangYoon Chung, Eitan Lerner, Yan Jin, Soohong Kim, Yazan Alhadid, Logan Wilson Grimaud, Irina X Zhang, Charles M Knobler, William M Gelbart, Shimon Weiss

Previous works have reported significant effects of macromolecular crowding on the structure and behavior of biomolecules. The crowded intracellular environment, in contrast to in vitro buffer solutions, likely imparts similar effects on biomolecules. The enzyme serving as the gatekeeper for the genome, RNA polymerase (RNAP), is among the most regulated enzymes. Although it was previously demonstrated that macromolecular crowding affects association of RNAP to DNA, not much is known about how crowding acts on late initiation and promoter clearance steps, which are considered to be the rate-determining steps for many promoters. Here, we demonstrate that macromolecular crowding enhances the rate of late initiation and promoter clearance using in vitro quenching-based single-molecule kinetics assays. Moreover, the enhancement’s dependence on crowder size notably deviates from predictions …

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Jan 2019 • Physical review letters

From non-normalizable boltzmann-gibbs statistics to infinite-ergodic theory

Erez Aghion, David A Kessler, Eli Barkai

We study a particle immersed in a heat bath, in the presence of an external force which decays at least as rapidly as 1/x, eg, a particle interacting with a surface through a Lennard-Jones or a logarithmic potential. As time increases, our system approaches a non-normalizable Boltzmann state. We study observables, such as the energy, which are integrable with respect to this asymptotic thermal state, calculating both time and ensemble averages. We derive a useful canonical-like ensemble which is defined out of equilibrium, using a maximum entropy principle, where the constraints are normalization, finite averaged energy, and a mean-squared displacement which increases linearly with time. Our work merges infinite-ergodic theory with Boltzmann-Gibbs statistics, thus extending the scope of the latter while shedding new light on the concept of ergodicity.

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Jan 2019 • The Electrochemical Society Interface

Current Trends in Electrolytes

Bryan D McCloskey, Kang Xu

oxides, and LISICON-type conductors, have been reported to have ion conductivities that rival, and in some cases surpass, liquid electrolytes. However, their poor processability severely impedes their commercial viability. It is envisioned that by combining polymer and inorganic solid state ion conductors in a composite structure, the best properties of both systems—polymer processability plus inorganic conductivity—can be achieved. Gupta and Sakamoto provide a detailed study on understanding transport mechanisms through a polymer-inorganic thin film composite interface, with the goal of guiding rational design for future organic-inorganic electrolyte configurations.In the fourth article, Doron Aurbach and colleagues provide a perspective on electrolytes for the so-called “beyond LIB” chemistries: Mg-ion, Li-S, and Li-air batteries. These chemistries, while all related given their high theoretical energy densities …

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Jan 2019 • bioRxiv

Molecular model of the nuclear pore complex reveals a thermoreversible FG-network with distinct territories occupied by different FG motifs

Kai Huang, Mario Tagliazucchi, Sung Hyun Park, Yitzhak Rabin, Igal Szleifer

Despite the intensive study of the nuclear pore complex (NPC), its functional core, the central transporter, remains poorly understood. Here, we investigate this unfolded and dynamic part of the NPC using a molecular theory that addresses both entropic and enthalpic effects of the intrinsically disordered phenylalanine-glycine-rich nucleoporins (FG-Nups). Our model shows that the cooperative effect of FG-pairing, specific spacer cohesion, and charge interaction leads to a remarkably elaborate gating structure inside the NPC. In particular, we find sequence-programmed “phase separation” between charge-rich and charge-poor regions, and a polarized electrostatic potential throughout the NPC. The model predicts a thermoreversible FG-network with inhomogeneous FG-pairing fraction in space, which features distinct territories of different types of FG motifs. Our theoretical anatomy of the central transporter reveals a clear sequence-structure-function relationship of the FG-Nups, and explains in a self-consistent way how nucleocytoplasmic transport can be efficient yet specific.

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Jan 2019 • Journal of biophotonics

Hyperlipidemic mice as a model for a real‐time in vivo detection of atherosclerosis by gold nanorods‐based diffusion reflection technique

Ruchira Chakraborty, Rinat Ankri, Dorit Leshem‐Lev, Edith Hochhauser, Ran Kornowski, Menachem Motiei, Eli I Lev, Dror Fixler

Atherosclerosis (AS), the leading cause of morbidity and mortality in cardiovascular disease, needs an early detection for treatment and prevention of fatal events. Here, for the first time, we applied gold nanorods (GNRs)‐assisted diffusion reflection (DR), a noninvasive technique for in vivo detection of AS in a high‐fat‐diet‐induced c57bl mouse model, which resembles the manifestation of AS in humans. DR simply detects the change in light reflection profile of tissue due to the accumulation of GNRs in the AS plaques and enables clear detection of AS lesions in carotid and femoral arteries of these hyperlipidemic mice. After 24 hours post‐GNRs injection, DR showed the highest efficiency of AS detection. Moreover, the sensitivity of the DR method is much higher than computed tomography (CT) and is comparable to ex vivo high‐resolution CT. Our results strongly suggest that the DR method can detect early …

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Jan 2019 • Cell Press

Anode-electrolyte interfaces in secondary magnesium batteries

Ran Attias, Michael Salama, Baruch Hirsch, Yosef Goffer, Doron Aurbach

Secondary magnesium batteries are still in the research stage, after the first prototype of a magnesium-based battery was demonstrated almost two decades ago. Since this breakthrough, despite tremendous efforts by numerous research groups, we are not aware of any system that exhibits better performance in terms of Coulombic efficiency over prolonged cycling. The scientific community is now focusing on the basic phenomena that hinder development of practical magnesium-based rechargeable batteries. Today, we have a better understanding of the structure of electrolyte solutions relevant to rechargeable Mg batteries and its effect on the electrochemical performance. New electrolyte solutions that are not based on organometallic moieties currently surpass the performance of the first generations of complex solutions. There is even an attempt to test alternative anode materials for magnesium-based energy …

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Jan 2019 • APL Photonics

Distributed opto-mechanical analysis of liquids outside standard fibers coated with polyimide

Hilel Hagai Diamandi, Yosef London, Gil Bashan, Avi Zadok

The analysis of surrounding media has been a long-standing challenge of optical fiber sensors. Measurements are difficult due to the confinement of light to the inner core of standard fibers. Over the last two years, new sensor concepts have enabled the analysis of liquids outside the cladding boundary, where light does not reach. Sensing is based on opto-mechanical, forward stimulated Brillouin scattering (F-SBS) interactions between guided light and sound waves. In most previous studies, however, the protective polymer coating of the fiber had to be removed first. In this work, we report the opto-mechanical analysis of liquids outside commercially available, standard single-mode fibers with polyimide coating. The polyimide layer provides mechanical protection but can also transmit acoustic waves from the fiber cladding toward outside media. The comprehensive analysis of opto-mechanical coupling in coated …

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Jan 2019 • Journal of Physics D: Applied Physics

Layer by layer deposition of alternate carbon nanotubes and Ni films for efficient multilayer thin film temperature gauges

Shrutidhara Sarma, Ilias Fekas, Kyriakos Filintoglou, J Arvanitidis, Dimitris Christofilos, Euripides Hatzikraniotis, Ortal Lidor, Yitzhak Mastai, Aynur Unal, P Patsalas

This study reports a novel approach for growing multilayer thin films consisting of alternate layers of carbon nanotubes (CNT) and nickel on Si (1 0 0) substrates and justifies their use in thin film temperature sensors. A low pressure chemical vapor deposition system was employed for synthesizing CNT films, while Ni films were deposited by electrodeposition. Porous-Si was used as substrate to increase adhesion between the layers of the multilayer structure. The structure of the multilayer films and the quality of the CNT grown were analyzed using several characterization methods, including scanning electron microscopy, x-ray photoelectron spectroscopy, x-ray auger electron spectroscopy and Raman spectroscopy. The electrical characteristics were investigated using a van der Pauw setup and the effect of the increasing number of CNT layers in the multilayer structure was studied. The sensitivity of the multilayer …

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Jan 2019 • Small

Improving the sensitivity of fluorescence‐based immunoassays by photobleaching the autofluorescence of magnetic beads

Shira Roth, Orr Hadass, Meir Cohen, Jasenka Verbarg, Jennifer Wilsey, Amos Danielli

In fluorescence‐based assays, usually a target molecule is captured using a probe conjugated to a capture surface, and then detected using a second fluorescently labeled probe. One of the most common capture surfaces is a magnetic bead. However, magnetic beads exhibit strong autofluorescence, which often overlaps with the emission of the reporter fluorescent dyes and limits the analytical performance of the assay. Here, several widely used magnetic beads are photobleached and their autofluorescence is reduced to 1% of the initial value. Their autofluorescence properties, including their photobleaching decay rates and autofluorescence spectra pre‐ and post‐photobleaching, and the stability of the photobleaching over a period of two months are analyzed. The photobleached beads are stable over time and their surface functionality is retained. In a high‐sensitivity LX‐200 system using photobleached …

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Jan 2019 • Small

Photobleaching: improving the sensitivity of fluorescence‐based immunoassays by photobleaching the autofluorescence of magnetic beads (Small 3/2019)

Shira Roth, Orr Hadass, Meir Cohen, Jasenka Verbarg, Jennifer Wilsey, Amos Danielli

In fluorescence-based assays, the autofluorescence of capture surfaces produces strong background noise. In article number 1803751, Amos Danielli and co-workers use photobleaching as a method to reduce the autofluorescence of magnetic beads, a commonly used capture surface. The technique yields a 3-fold improvement in the limit of detection and signal-to-noise ratio of a fluorescence-based immunoassay.

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Jan 2019 • Current topics in developmental biology 134, 223-252, 2019

The regulation of Sox9 expression in the gonad

Nitzan Gonen, Robin Lovell-Badge

The bipotential nature of cell types in the early developing gonad and the process of sex determination leading to either testis or ovary differentiation makes this an interesting system in which to study transcriptional regulation of gene expression and cell fate decisions. SOX9 is a transcription factor with multiple roles during development, including being a key player in mediating testis differentiation and therefore subsequent male development. Loss of Sox9 expression in both humans and mice results in XY female development, whereas its inappropriate activation in XX embryonic gonads can give male development. Multiple cases of Disorders of Sex Development in human patients or sex reversal in mice and other vertebrates can be explained by mutations affecting upstream regulators of Sox9 expression, such as the product of the Y chromosome gene Sry that triggers testis differentiation. Other cases are due …

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Jan 2019 • JoVE (Journal of Visualized Experiments)

Designing Porous Silicon Films as Carriers of Nerve Growth Factor

Michal Rosenberg, Neta Zilony, Orit Shefi, Ester Segal

Despite the great potential of NGF for treating neurodegenerative diseases, its therapeutic administration represents a significant challenge as the protein does not cross the blood-brain barrier, owing to its chemical properties, and thus requires long-term delivery to the brain to have a biological effect. This work describes fabrication of nanostructured PSi films as degradable carriers of NGF for sustained delivery of this sensitive protein. The PSi carriers are specifically tailored to obtain high loading efficacy and continuous release of NGF for a period of four weeks, while preserving its biological activity. The behavior of the NGF-PSi carriers as a NGF delivery system is investigated in vitro by examining their capability to induce neuronal differentiation and outgrowth of PC12 cells and dissociated DRG neurons. Cell viability in the presence of neat and NGF-loaded PSi carriers is evaluated. The bioactivity of NGF released from the PSi carriers is compared to the conventional treatment of repetitive free NGF administrations. PC12 cell differentiation is analyzed and characterized by the measurement of three different morphological parameters of differentiated cells; (i) the number of neurites extracting from the soma (ii) the total neurites' length and (iii) the number of branching points. PC12 cells treated with the NGF-PSi carriers demonstrate a profound differentiation throughout the release period. Furthermore, DRG neuronal cells cultured with the NGF-PSi carriers show an extensive neurite initiation, similar to neurons treated with repetitive free NGF administrations. The studied tunable carriers demonstrate the long-term implants for NGF release with a …

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Jan 2019 • European Congress of Radiology-ECR 2019

Radiation dose reduced 3-D x-ray imager for radiology

Z Zalevsky, D Abraham, Y Danan

Aims and objectivesObjectives: To develop novel imaging-like concept for computerized tomography (CT) yielding 3-D images with significantly reduced x-ray dose irradiated at patients without damaging the image quality. The technological advantages of the proposed approach can be summarized in Figure 1. Figure 1. The advantages of the proposed technology. The need: The radiation dose efficiency of existing CT systems is relatively low. There is an exposure of not only the patients but also for the medical staff. Several health organizations and regulatory authorities already set a goal...

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Jan 2019 • PloS one

Spatial visual function in anomalous trichromats: Is less more?

Ravid Doron, Anna Sterkin, Moshe Fried, Oren Yehezkel, Maria Lev, Michael Belkin, Mordechai Rosner, Arieh S Solomon, Yossi Mandel, Uri Polat

Color deficiency is a common inherited disorder affecting 8% of Caucasian males with anomalous trichromacy (AT); it is the most common type of inherited color vision deficiency. Anomalous trichromacy is caused by alteration of one of the three cone-opsins’ spectral sensitivity; it is usually considered to impose marked limitations for daily life as well as for choice of occupation. Nevertheless, we show here that anomalous trichromat subjects have superior basic visual functions such as visual acuity (VA), contrast sensitivity (CS), and stereo acuity, compared with participants with normal color vision. Both contrast sensitivity and stereo acuity performance were correlated with the severity of color deficiency. We further show that subjects with anomalous trichromacy exhibit a better ability to detect objects camouflaged in natural gray scale figures. The advantages of color-deficient subjects in spatial vision performance could explain the relatively high prevalence of color-vision polymorphism in humans.

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Jan 2019 • OSA Continuum

Self calibration iso-pathlength point in cylindrical tissue geometry: solution of steady-state photon diffusion based on the extrapolated zero-boundary

Hamootal Duadi, Daqing Piao, Dror Fixler

Near-infrared optical techniques permit tissue diagnosis by surface measurement. However, the geometrical shape of this interface profiles the intensity of the surface measurement, which is found to have an iso-pathlength (IPL) point allowing for absorption identification independent of tissue scattering. The IPL point was projected in Monte Carlo (MC) simulation, validated experimentally in cylindrical tissues, but remains under-appreciated through analytical approaches. In this work, we present an analytical solution of an IPL point for steady-state diffusion based on the extrapolated zero-boundary condition. The same IPL points were found when comparing this solution to 3-D MC simulations for a tissue radius range of 5-8mm.

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