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Jul 2019 • European journal of medicinal chemistry

An oligonucleotide probe incorporating the chromophore of green fluorescent protein is useful for the detection of HER-2 mRNA breast cancer marker

Abed Saady, Verena Böttner, Melissa Meng, Eli Varon, Yaron Shav-Tal, Christian Ducho, Bilha Fischer

Diagnosis and treatment of breast cancer can be greatly enhanced and personalized based on the quantitative detection of mRNA markers. Here, we targeted the development of a fluorescent oligonucleotide probe to detect specifically the HER-2 mRNA breast cancer marker. We have selected the chromophore of the Green Fluorescent Protein (GFP), 4-hydroxybenzylidene imidazolinone (HBI), as a fluorophore covalently bound to an oligonucleotide probe and potentially capable of intercalating within a probe-mRNA duplex. We first synthesized the two-ring scaffold of the HBI chromophore 5 and coupled it to 2′-deoxyuridine at C5-position via a 7-atom-spacer, to give 4. Indeed, in the highly viscous glycerol used to mimic the reduced conformational flexibility of the intercalated HBI, chromophore 4 displayed a quantum yield of 0.29 and brightness of 20600 M−1cm−1, while no fluorescent signal was observed in …

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Jul 2019 • Metallomics

The pivotal role of MBD4–ATP7B in the human Cu(i) excretion path as revealed by EPR experiments and all-atom simulations

Zena Qasem, Matic Pavlin, Ida Ritacco, Lada Gevorkyan-Airapetov, Alessandra Magistrato, Sharon Ruthstein

Copper's essentiality and toxicity require a meticulous mechanism for its acquisition, cellular distribution and excretion, which remains hitherto elusive. Herein, we jointly employed electron paramagnetic resonance spectroscopy and all-atom simulations to resolve the copper trafficking mechanism in humans considering the route travelled by Cu(i) from the metallochaperone Atox1 to the metal binding domains 3 and 4 of ATP7B. Our study shows that Cu(i) in the final part of its extraction pathway is most likely mediated by binding of Atox1 monomer to MBD4 of ATP7B. This interaction takes place through weak metal-stabilized protein–protein interactions.

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Jul 2019 • European Polymer Journal

Poly (styryl bisphosphonate) nanoparticles with a narrow size distribution: synthesis, characterization and antibacterial applications

Hanna P Steinmetz, Safra Rudnick-Glick, Michal Natan, Ehud Banin, Shlomo Margel

Bacterial resistance to antibiotics is a major challenge in health research. A recent approach to combat this resistance is by interfering with vital bacterial functional systems. Calcium ions play an important role in bacterial functions such as bacterial cell stability, regulation of virulence genes, and in the function of various intracellular proteins. Bisphosphonate compounds have a high affinity for calcium ions and the antibacterial activity of bisphosphonates in combination with antibiotics has been recently studied. However, the antibacterial behavior of the bisphosphonate group itself has hardly been investigated. New cross-linked poly(styryl bisphosphonate) nanoparticles (poly(StBP) NPs) with a narrow size distribution and high yield were engineered using a dispersion copolymerization of styryl bisphosphonate monomer with the cross-linking monomer triethylene glycol diacrylate and the primary amino monomer N …

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Jul 2019 • ACS Energy Letters 4 (8), 1907-1917, 2019

Diffusion-Induced Transient Stresses in Li-Battery Electrodes Imaged by Electrochemical Quartz Crystal Microbalance with Dissipation Monitoring and Environmental Scanning …

Netanel Shpigel, Mikhael D Levi, Xiaopeng Cheng, Tianci Cao, Rui Wu, Tyler S Mathis, Yuefei Zhang, Doron Aurbach, Yury Gogotsi

Quick charging of Li-ion batteries is often accompanied by rapid expansion of composite battery electrodes, resulting in the appearance of transient stresses inside the electrodes’ bulk. Although predicted theoretically, they have never been tracked by direct in situ measurements. Herein, using multiharmonic electrochemical quartz crystal microbalance with dissipation monitoring (EQCM-D), acoustic images of strong transient deformations in LiFePO4 electrodes were obtained in the form of giant resonance frequency and resonance width shifts. The formation of cracks was verified by scanning electron microscopy. The effects of charging rate, stiffness of the polymeric binder, and solution concentration have been identified. The attractive feature of EQCM-D is its high sensitivity for selective probing of average mechanical characteristics of the operated electrodes, especially of the particle–binder interactions, directly …

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Jul 2019 • Physical review letters

Nonadiabatic molecular association in thermal gases driven by radio-frequency pulses

Panagiotis Giannakeas, L Khaykovich, Jan-Michael Rost, Chris H Greene

The molecular association process in a thermal gas of Rb 85 is investigated where the effects of the envelope of the radio-frequency field are taken into account. For experimentally relevant parameters our analysis shows that with increasing pulse length the corresponding molecular conversion efficiency exhibits low-frequency interference fringes which are robust under thermal averaging over a wide range of temperatures. This dynamical interference phenomenon is attributed to Stückelberg phase accumulation between the low-energy continuum states and the dressed molecular state which exhibits a shift proportional to the envelope of the radio-frequency pulse intensity.

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Jul 2019 • Advanced Materials Interfaces

Nanostructure and Mechanism of Metal Deposition by a Laser‐Induced Photothermal Reaction

Ehud Greenberg, Nina Armon, Omree Kapon, Moshit Ben‐Ishai, Hagay Shpaisman

Laser‐induced photothermal reaction of metal ions is a promising one‐step method for production of conductive micropatterns for electronic devices and sensors. However, the mechanism that governs the process in which thermally activated materials are deposited on a substrate is not clear. Here, light is shed on the mechanism through systematic analysis of photothermal reaction products forming iron oxide and silver at different interfaces. Examination of the nanostructure of deposits on a substrate using high‐resolution transmission electron microscopy and selected area diffraction pattern analysis reveals a combination of both amorphous and crystalline moieties. It is found that focusing the laser inside the solution leads to exclusive formation of crystalline products, while focusing at the liquid/air interface leads to formation of amorphous products due to kinetic considerations. Ring‐shaped microstructures …

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Jul 2019 • Applied Physics Letters

Nonlocal quantum erasure of phase objects

Lu Gao, Yingwen Zhang, Eliahu Cohen, Avshalom C Elitzur, Ebrahim Karimi

Franson interference is a fourth order interference effect which, unlike the better known Hong-Ou-Mandel interference, does not require the entangled photon pairs to be present at the same space-time location for interference to occur—it is nonlocal. Here, we use a modified Franson interferometer to experimentally demonstrate the nonlocal erasure and correction of an image of a phase-object taken through coincidence imaging. This nonlocal quantum erasure technique can have several potential applications such as phase corrections in quantum imaging and microscopy and also user authentication of two foreign distant parties.

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Jul 2019 • Frontiers in immunology

Reduced function and diversity of T cell repertoire and distinct clinical course in patients with IL7RA mutation

Atar Lev, Amos J Simon, Ortal Barel, Eran Eyal, Efrat Glick-Saar, Omri Nayshool, Ohad Birk, Tali Stauber, Amit Hochberg, Arnon Broides, Shlomo Almashanu, Ayal Hendel, Yu Nee Lee, Raz Somech

The alpha subunit of IL-7 receptor (IL7R7) is critical for the differentiation of T cells, specifically for the development and maintenance of γT cells. Mutations in IL7RA are associated with Severe Combined Immunodeficiency (SCID). Infants with IL7 RA deficiency can be identified through newborn screening program. We aimed at defining the immunological and genetic parameters that are directly affected by the IL7RA mutation on the immune system of five unrelated patients which were identified by our newborn screening program for SCID. The patients were found to have a novel identical homozygote mutation in IL7RA (c.120 C>G; p.F40L). Both surface expression of IL7Rα and functionality of IL-7 signaling were impaired in patients compared to controls. Structural modeling demonstrated instability of the protein structure due to the mutation. Lastly the TRG immune repertoire of the patients showed reduced diversity, increased clonality and differential CDR3 characteristics. Interestingly, the patients displayed significant different clinical outcome with two displaying severe clinical picture of immunodeficiency and three had spontaneous recovery. Our data supports that the presented IL7RA mutation affects the IL-7 signaling and shaping of the TRG repertoire, reinforcing the role of IL7RA in the immune system, while non-genetic factors may exist that attribute to the ultimate clinical presentation and disease progression.

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Jul 2019 • arXiv preprint arXiv:1907.03971

Type and degree of covalence: Empirical derivation and implications

Yevgeny Rakita, Thomas Kirchartz, Gary Hodes, David Cahen

The way atoms attach to each other defines the function(s), e.g., mechanical, optical, electronic, of a given material. The nature of the chemical bond is, therefore, one of the most fundamental issues in materials. Both ionic interactions, i.e., resulting from electrical charges associated with the atoms, and covalent ones, i.e., the sharing of electrons between nuclei of different atoms, are usually viewed as forces that attract between atoms to form a rigid structure. Although less common for solid materials, it was shown theoretically to be possible for covalent interactions at the chemically-active electronic shell (or valence-band maximum) of semiconductors to reverse their more common nature and become repulsive, i.e., act against bonding. Some semiconductors with such predicted anti-bonding valence-band maximum levels (such as halide perovskites) show experimentally some amazing (opto-) electronic properties. Predictions that anti-bonding character can allow tolerance for existing defects, at least in part, can explain the superior properties of such semiconductors. Although there are known experimental ways to estimate the degree of the covalent nature (e.g., electronegativity), this was not possible hitherto for the type, i.e., distinguishing whether a material exhibits bonding or anti-bonding covalent interactions. We have developed a simple way to reveal the complete nature (both type and degree) of chemical bonds, using experimental data. After confirming our development with classical models and theoretical predictions, with a set of ~40 different functional semi-conductors, we show how knowledge of the complete nature of covalent …

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Jul 2019 • Nanomedicine

Gold nanoparticles for multimodal high-resolution imaging of transplanted cells for retinal replacement therapy

Yoav Chemla, Oshra Betzer, Amos Markus, Nairouz Farah, Menachem Motiei, Rachela Popovtzer, Yossi Mandel

Aim: Longitudinal tracking of transplanted cells in clinical and experimental setups is crucial for evaluating the efficiency of retinal cell replacement therapies. Materials & methods: Gold nanoparticle-labeled photoreceptor precursors were transplanted in the vitreous and subretinal space of rats and were longitudinally tracked for over a month using optical coherence tomography, computed tomography and fluorescence fundus imaging. Results: This multimodal imaging approach enabled high-resolution long-term tracking and estimation of cell survival in the retina and vitreous, while displaying no toxic effects on the cells or the retina. Conclusion: These observations highlight the applicability of using gold nanoparticle for retinal cell tracking in existing experimental settings and its translational potential for providing more efficient retinal cell therapy in humans.

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Jul 2019 • ACS omega

Rapid and sensitive detection of repetitive nucleic acid sequences using magnetically modulated biosensors

Michael Margulis, Amos Danielli

Repetitive DNA sequences are abundant in the genome of most biological species. These sequences are naturally “preamplified”, which makes them a preferential target for a variety of biological assays. Current methods to detect specific DNA sequences are based on the quantitative polymerase chain reaction (PCR), which relies on target amplification by Taq polymerase and uses a fluorescent resonance energy transfer (FRET)-based probe. Here, to rapidly detect a repetitive DNA sequence, we combine a highly sensitive magnetic modulation biosensing (MMB) system and a modified double-quenched FRET-based probe. The high numbers of copies of the female-specific XhoI sequence of the domestic chicken (Gallus gallus), combined with the low background fluorescence levels of the modified double-quenched probe and the high sensitivity of the MMB system, allow us to determine the chick sex in ovo …

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Jul 2019 • ACS Catalysis

Dual Alkaline Ion Route to Chemical De-insertion in Oxygen Evolution Olivine Electrocatalysts

Yelena Gershinsky, Melina Zysler, Victor Shokhen, Yakov Stone, David Zitoun

The oxygen evolution reaction (OER) is an essential reaction for the sustainable synthesis of fuels from renewable feedstocks. In recent years, cathode materials for Li-ion batteries have been successfully utilized as OER electrocatalysts, and among them are the lithiated transition-metal phosphates possessing an olivine crystallographic phase. The LiMPO4 (M = Ni, Fe, Co) olivine materials display a potentially suitable overpotential for OER, which can be further enhanced by delithiation. Herein, we report the synthesis of olivine phases with both Li and Na as alkaline ions. The combination of alkaline ions stabilizes the olivine structure with low alkaline ion content, which is instrumental to reach low OER overpotential. The dual alkaline ion approach has been demonstrated for a single transition metal (Co) as well as different combinations of Co–Fe–Ni to form olivine solid solutions of the chemical formula Li(Na)Co …

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Jul 2019 • Electrochimica Acta

Electropolymerization of PGM-free molecular catalyst for formation of 3D structures with high density of catalytic sites

Ariel Friedman, Irena Saltsman, Zeev Gross, Lior Elbaz

Precious group metal-free catalysts are considered essential for promotion of sustainable polymer electrolyte membrane fuel cells technology. The major advantage of molecular catalysts relative to still better performing materials based on pyrolysis of metallomacrocycles is that the catalytic center in the former is much more well-defined, which allows rational design and tuning of catalysts along with precise measurements of catalytic and degradation processes. We now report our approach that is aimed to gain the benefits of both molecular and material-based catalyst: electropolymerization of a molecular catalyst- 5,15-bis(p-aminophenyl),10-pentafluorophenylcorrolato cobalt (III), CoBAC. The polymeric material polyCoBAC is obtained in a three-dimensional cauliflower-like structure with ranging sizes of particles with beyond the state-of-the-art catalytic site density: 1.44*1020 sites/cm [3]. A comparison between …

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Jul 2019 • Biomedical Materials

Silver and gold doped hydroxyapatite nanocomposites for enhanced bone regeneration

Vijay Bhooshan Kumar, Deepak Kumar Khajuria, David Karasik, Aharon Gedanken

We report the osteogenic potential of silver (Ag), gold (Au), or silver–gold doped hydroxyapatite nanoparticles (Ag-Au-HA) in zebrafish (ZF) jawbone regeneration (JBR) model. The hydroxyapatite (HA, Ca 10 (PO 4) 6 (OH) 2), Ag-HA, Au-HA, and Ag-Au-HA nanomaterials were synthesized by the co-precipitation procedure. The surface structures of Ag-HA, Au-HA, HA, and Ag-Au-HA were analysed by scanning electron microscopy, transmission-electron microscopy (TEM), x-ray diffraction, Fourier transform infrared (FTIR), UV–vis, energy dispersive x-ray spectroscopy (EDS), elemental mapping, and laser fluorescent spectroscopy. The TEM and EDS analysis confirmed that the Ag and Au are associated with the surface of HA nanoparticle. The chemical structure of HA, Ag-HA, Au-HA, and Ag-Au-HA nanoparticles was validated by FTIR and EDS analysis. We observed that Ag and Au are associated with HA …

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Jul 2019 • Physical Review E

Single-big-jump principle in physical modeling

Alessandro Vezzani, Eli Barkai, Raffaella Burioni

The big-jump principle is a well-established mathematical result for sums of independent and identically distributed random variables extracted from a fat-tailed distribution. It states that the tail of the distribution of the sum is the same as the distribution of the largest summand. In practice, it means that when in a stochastic process the relevant quantity is a sum of variables, the mechanism leading to rare events is peculiar: Instead of being caused by a set of many small deviations all in the same direction, one jump, the biggest of the lot, provides the main contribution to the rare large fluctuation. We reformulate and elevate the big-jump principle beyond its current status to allow it to deal with correlations, finite cutoffs, continuous paths, memory, and quenched disorder. Doing so we are able to predict rare events using the extended big-jump principle in Lévy walks, in a model of laser cooling, in a scattering process on …

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Jul 2019 • Physical review letters

Effect of liquid state organization on nanostructure and strength of model multicomponent solids

Kulveer Singh, Yitzhak Rabin

When a multicomponent liquid composed of particles with random interactions is slowly cooled below the freezing temperature, the fluid reorganizes in order to increase (decrease) the number of strong (weak) attractive interactions and solidifies into a structure composed of domains of strongly and of weakly interacting particles. Using Langevin dynamics simulations of a model system we find that the tensile strength, mode of fracture, and thermal stability of such solids differ from those of one-component solids and that these properties can be controlled by the method of preparation.

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Jun 2019 • Biomedical optics express

Algorithm for in vivo detection of tissue type from multiple scattering light phase images

I Yariv, H Duadi, R Chakraborty, D Fixler

In vivo physiological assessments are typically done by either imaging techniques or by sensing changes in the attenuation coefficient. Using visible or near-infrared (NIR), imaging is mainly possible for thin tissues. On the other hand, clinical information can also be detected by examining changes in tissue optical properties. The most challenging aspect in sensing techniques is the spectral dependent scattering, which varies with the physiological state and tissue type. We have previously published our novel noninvasive nanophotonics technique for detecting tissue scattering based on reflectance measurements: the iterative multi-plane optical property extraction (IMOPE). The IMOPE reconstructs the reemitted light phase using an iterative algorithm and extracts the scattering properties based on a theoretical model. This paper presents the in vivo application of distinguishing between different mouse tissue areas …

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Jun 2019 • Current opinion in cell biology 58, 69-75, 2019

The dynamic lifecycle of mRNA in the nucleus

Rakefet Ben-Yishay, Yaron Shav-Tal

The mRNA molecule roams through the nucleus on its way out to the cytoplasm. mRNA encounters and is bound by many protein factors, from the moment it begins to emerge from RNA polymerase II and during its travel in the nucleoplasm, where it will come upon chromatin and nuclear bodies. Some of the protein factors that engage with the mRNA can process it, until finally reaching a mature state fit for export through the nuclear pore complex (NPC). Examining the lifecycle of mRNAs in living cells using mRNA tagging techniques opens a window into our understanding of the rules that drive the dynamics of gene expression from transcription to mRNA export.

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Jun 2019 • Materials Science and Engineering: C

In vivo and in vitro study of a novel nanohydroxyapatite sonocoated scaffolds for enhanced bone regeneration

Julia Rogowska-Tylman, Janis Locs, Ilze Salma, Bartosz Woźniak, Mara Pilmane, Vita Zalite, Jacek Wojnarowicz, Aleksandra Kędzierska-Sar, Tadeusz Chudoba, Karol Szlązak, Adrian Chlanda, Wojciech Święszkowski, Aharon Gedanken, Witold Łojkowski

There still remains a need for new methods of healing large bone defects, i.e., gaps in bone tissue that are too big to naturally heal. Bone regrowth scaffolds can fill the bone gap and enhance the bone regeneration by providing cells with a support to for new tissue formation. Coating of the scaffolds surface with nanocrystalline hydroxyapatite may enhance the osteoinductivity or osteoconductivity of such scaffolds. Here we present the sonocoating method to coat scaffolds with bioactive hydroxyapatite nanoparticles. We show a method, where the material to be coated is immersed in a colloidal suspension of nanoparticles with mean sizes of 10 nm and 43 nm in water, and high-power ultrasound waves are applied to the suspension for 15 min at 30 °C. High power ultrasounds lead to growth of cavitation bubbles in liquid, which implode at a critical size. The implosion energy propels the nanoparticles towards the …

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Jun 2019 • Optical Society of America

Sharper and dipper laser beam shaping for super-resolved imaging in silicon

Maor Tiferet, Zeev Zalevsky, Moshe Sinvani

Enhanced laser beam shaping for super-resolved imaging in silicon is demonstrated by applying pico-seconds pulsed pump at 775nm having increased penetration-depth into the silicon (than pump at 532nm) and yielding sharper PSF due to reduced diffusion effect of the generated free-charge-carriers.

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Jun 2019 • Optics letters

Non-contact photoacoustic imaging using laser speckle contrast analysis

Matan Benyamin, Hadar Genish, Ran Califa, Ariel Schwartz, Zeev Zalevsky, Nisan Ozana

A novel method for non-contact and continuous detection of photoacoustic signals is presented and experimentally demonstrated. The approach is based on analysis of the contrast of time-varying speckle patterns, and suggests a more robust alternative in respect to interferometric and refractometric available solutions.

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