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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 • 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 • 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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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 • 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 • 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 • Cell reports

A chaperone lid ensures efficient and privileged client transfer during tail-anchored protein targeting

Un Seng Chio, SangYoon Chung, Shimon Weiss, Shu-ou Shan

Molecular chaperones play key roles in maintaining cellular proteostasis. In addition to preventing client aggregation, chaperones often relay substrates within a network while preventing off-pathway chaperones from accessing the substrate. Here we show that a conserved lid motif lining the substrate-binding groove of the Get3 ATPase enables these important functions during the targeted delivery of tail-anchored membrane proteins (TAs) to the endoplasmic reticulum. The lid prevents promiscuous TA handoff to off-pathway chaperones, and more importantly, it cooperates with the Get4/5 scaffolding complex to enable rapid and privileged TA transfer from the upstream co-chaperone Sgt2 to Get3. These findings provide a molecular mechanism by which chaperones maintain the pathway specificity of client proteins in the crowded cytosolic environment.

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Jan 2019 • Communications biology

A high-throughput integrated microfluidics method enables tyrosine autophosphorylation discovery

Hadas Nevenzal, Meirav Noach-Hirsh, Or Skornik-Bustan, Lev Brio, Efrat Barbiro-Michaely, Yair Glick, Dorit Avrahami, Roxane Lahmi, Amit Tzur, Doron Gerber

Autophosphorylation of receptor and non-receptor tyrosine kinases is a common molecular switch with broad implications for pathogeneses and therapy of cancer and other human diseases. Technologies for large-scale discovery and analysis of autophosphorylation are limited by the inherent difficulty to distinguish between phosphorylation and autophosphorylation in vivo and by the complexity associated with functional assays of receptors kinases in vitro. Here, we report a method for the direct detection and analysis of tyrosine autophosphorylation using integrated microfluidics and freshly synthesized protein arrays. We demonstrate the efficacy of our platform in detecting autophosphorylation activity of soluble and transmembrane tyrosine kinases, and the dependency of in vitro autophosphorylation assays on membranes. Our method, Integrated Microfluidics for Autophosphorylation Discovery (IMAD), is high …

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Jan 2019 • Energies

Design optimization of a permanent-magnet saturated-core fault-current limiter

John Linden, Yasha Nikulshin, Alex Friedman, Yosef Yeshurun, Shuki Wolfus

Designs of saturated-cores fault current limiters (FCLs) usually implement conducting or superconducting DC coils serving to saturate the magnetic cores during nominal grid performance. The use of coils adds significantly to the operational cost of the system, consuming energy, and requiring maintenance. A derivative of the saturated-cores FCL is a design implementing permanent magnets as an alternative to the DC coils, eliminating practically all maintenance due to its entirely passive components. There are, however, various challenges such as the need to reach deep saturation with the currently available permanent magnets as well as the complications involved in the assembly process due to very powerful magnetic forces between the magnets and the cores. This paper presents several concepts, achieved by extensive magnetic simulations and verified experimentally, that help in maximizing the core saturation of the PMFCL (Permanent Magnet FCL), including optimization of the permanent magnet to core surface ratios and asymmetrical placement of the permanent magnets, both creating an increase in the cores’ magnetic flux at crucial points. In addition, we point to the importance of splitting the AC coils to leave the center core point exposed to best utilize their variable inductance parameters. This paper also describes the stages of design and assembly of a laboratory-scale single phase prototype model with the proposed PMFCL design recommendations, as well as an analysis of real-time results obtained while connecting this prototype to a 220 V grid during nominal and fault states. View Full-Text

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Jan 2019 • Journal of Controlled Release

Stimulating brain recovery after stroke using theranostic albumin nanocarriers loaded with nerve growth factor in combination therapy

Tivadar Feczkó, Albrecht Piiper, Saema Ansar, Frank W Blixt, Mukul Ashtikar, Susanne Schiffmann, Thomas Ulshöfer, Michael J Parnham, Yifat Harel, Liron Limor Israel, Jean-Paul Lellouche, Matthias G Wacker

For many years, delivering drug molecules across the blood brain barrier has been a major challenge. The neuropeptide nerve growth factor is involved in the regulation of growth and differentiation of cholinergic neurons and holds great potential in the treatment of stroke. However, as with many other compounds, the biomolecule is not able to enter the central nervous system. In the present study, nerve growth factor and ultra-small particles of iron oxide were co-encapsulated into a chemically crosslinked albumin nanocarrier matrix which was modified on the surface with apolipoprotein E. These biodegradable nanoparticles with a size of 212 ± 1 nm exhibited monodisperse size distribution and low toxicity. They delivered NGF through an artificial blood brain barrier and were able to induce neurite outgrowth in PC12 cells in vitro. In an animal model of stroke, the infarct size was significantly reduced compared …

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Jan 2019 • Nature

Loss of ADAR1 in tumours overcomes resistance to immune checkpoint blockade

Jeffrey J Ishizuka, Robert T Manguso, Collins K Cheruiyot, Kevin Bi, Arpit Panda, Arvin Iracheta-Vellve, Brian C Miller, Peter P Du, Kathleen B Yates, Juan Dubrot, Ilana Buchumenski, Dawn E Comstock, Flavian D Brown, Austin Ayer, Ian C Kohnle, Hans W Pope, Margaret D Zimmer, Debattama R Sen, Sarah K Lane-Reticker, Emily J Robitschek, Gabriel K Griffin, Natalie B Collins, Adrienne H Long, John G Doench, David Kozono, Erez Y Levanon, W Nicholas Haining

Most patients with cancer either do not respond to immune checkpoint blockade or develop resistance to it, often because of acquired mutations that impair antigen presentation. Here we show that loss of function of the RNA-editing enzyme ADAR1 in tumour cells profoundly sensitizes tumours to immunotherapy and overcomes resistance to checkpoint blockade. In the absence of ADAR1, A-to-I editing of interferon-inducible RNA species is reduced, leading to double-stranded RNA ligand sensing by PKR and MDA5; this results in growth inhibition and tumour inflammation, respectively. Loss of ADAR1 overcomes resistance to PD-1 checkpoint blockade caused by inactivation of antigen presentation by tumour cells. Thus, effective anti-tumour immunity is constrained by inhibitory checkpoints such as ADAR1 that limit the sensing of innate ligands. The induction of sufficient inflammation in tumours that are sensitized …

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Jan 2019 • BioRxiv

Grass silica mineralizer (GSM1) protein precipitates silica in sorghum silica cells

Santosh Kumar, Nurit Adiram-Filiba, Shula Blum, Javier Arturo Sanchez-Lopez, Oren Tzfadia, Ayelet Omid, Hanne Volpin, Yael Heifetz, Gil Goobes, Rivka Elbaum

• Silicon is absorbed by plant roots as silicic acid. In shoot tissues, silicic acid 27 mineralizes as silica by completely unknown mechanisms. Most prominently, leaf 28 epidermal cells called silica cells deposit silica in most of their volume. 29• Using bioinformatics tools, we identified a previously uncharacterized protein in 30 sorghum (Sorghum bicolor), which we named as Grass Silica Mineralizer (GSM1). 31 We characterized the expression profile and demonstrated its activity in vitro and in 32 vivo. 33• GSM1 is a basic protein with seven repeat units rich in proline, lysine and glutamic 34 acid. We found GSM1 expression in immature leaf and inflorescence tissues. In the 35 active silicification zone of sorghum leaf, GSM1 was localized to the cytoplasm or 36 near cell boundaries of silica cells. GSM1 was packed in vesicles and secreted to the 37 paramural space. A short peptide, repeating five times in the protein precipitated silica 38 in vitro at a biologically relevant silicic acid concentration. Raman and NMR 39 spectroscopies showed that the peptide attached the silica through lysine amine 40 groups, forming a mineral-peptide open structure. Transient overexpression of GSM1 41 in sorghum resulted in ectopic silica deposition in all leaf epidermal cell types. 42• Our results show that GSM1 precipitates silica in sorghum silica cells. 43

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Jan 2019 • Batteries & Supercaps

Cover Picture: The Electrochemical Sodiation of FeSb2: New Insights from Operando 57Fe Synchrotron Mössbauer and X‐Ray Absorption Spectroscopy (Batteries …

Marcus Fehse, Dimitrios Bessas, Ali Darwiche, Abdelfattah Mahmoud, Guy Rahamim, Camille La Fontaine, Raphael P Hermann, David Zitoun, Laure Monconduit, Lorenzo Stievano, Moulay T Sougrati

The Front Cover shows how synchrotron radiation is important to study battery materials for many different applications. In this work, operando synchrotron-based characterisation techniques, specifically X-ray absorption and Mössbauer spectroscopy, were applied to elucidate the FeSb 2 charge–discharge mechanism. More information can be found in the article by M. Fehse et al.(DOI: 10.1002/batt. 201800075).

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Jan 2019 • Infrared Physics & Technology

The opportunity of using InGaAsN/AlGaAs quantum wells for extended short-wavelength infrared photodetection

Asaf Albo, Dan Fekete, Gad Bahir

We propose and demonstrate a novel concept to address high-performance, extended short wavelength (e-SWIR) photodetectors. Our approach is based on shifting the well-developed GaAs quantum-well infrared photodetector (QWIP) technology to e-SWIR wavelengths. In order to increase the available conduction band offsets (CBOs), we suggest incorporating nitrogen (N) atoms into the quantum well material. The incorporation of N atoms into III-Vs results in dilute-nitride highly mismatched alloys with lower bandgaps and higher CBOs. In our work, we demonstrate CBO values reaching up to ∼1 eV in InGaAsN/AlGaAs QWIPs. This large CBO makes these structures suitable for e-SWIR detection. The large CBO reduces the dark current dramatically and allows efficient detection at room temperature.In our study, we devised two similar InGaAsN/AlGaAs QWIP devices with twofold, 1% and 2% N composition …

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Jan 2019 • Cell death & disease

sPIF promotes myoblast differentiation and utrophin expression while inhibiting fibrosis in Duchenne muscular dystrophy via the H19/miR-675/let-7 and miR-21 pathways

Daria Morgoulis, Peter Berenstein, Simona Cazacu, Gila Kazimirsky, Amir Dori, Eytan R Barnea, Chaya Brodie

Duchenne muscular dystrophy (DMD) is a progressive, lethal, X-linked disease of skeletal and cardiac muscles caused by mutations in the dystrophin gene. Loss of dystrophin leads to muscle fiber damage and impairment of satellite cell asymmetric division, which are essential for muscle regeneration. These processes ultimately result in muscle wasting and the replacement of the degenerating muscles by fibrogenic cells, a process that leads to the generation of fibrotic tissues. Preimplantation factor (PIF) is an evolutionary conserved 15-amino acid peptide secreted by viable mammalian embryos. Synthetic PIF (sPIF) reproduces the protective/regenerative effects of the endogenous peptide in immune disorders and transplantation models. In this study, we demonstrated that sPIF treatment promoted mouse and human myoblast differentiation and inhibited the expression of collagen 1A1, collagen 1A2, and TGF-β …

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Jan 2019 • arXiv preprint arXiv:1901.06202

Dynamics of coupled parametric oscillators beyond coupled Ising spins

Leon Bello, Marcello Calvanese Strinati, Emanuele G Dalla Torre, Avi Pe'er

Coupled parametric oscillators have been recently employed as simulators of artificial Ising networks, with the potential to efficiently solve computationally hard minimization problems. We report on a detailed study of two coupled degenerate parametric oscillators, exploring the entire phase diagram, in terms of pump power, phase and coupling strength, both analytically and experimentally in a radio-frequency (RF) experiment. In addition to a regime where the oscillators act as coupled spin-1/2 degrees of freedom, we predict and observe a wide range of parameters in the vicinity of the oscillation threshold where the spin-1/2 description does not apply. In this regime, the oscillators never synchronize, but rather show persistent, full-scale, coherent beats, whose frequency reflects the coupling strength. Our comprehensive study can be used as the the building block of a coherent Ising machines that combine …

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Jan 2019 • The Impact and Prospects of Green Chemistry for Textile Technology, 161-198, 2019

The sonochemical functionalization of textiles

I Perelshtein, N Perkas, A Gedanken

This chapter reviews the research that has been done for functionalization of textile with inorganic nanoparticles (CuO, ZnO, MgO, and novel Zn-CuO) by the sonochemical method. The Introduction outlines the role of nanotechnology in the development of antibacterial textile. The metal nano-oxides have a large surface area and can be finely spread on the fabrics. This property makes them a good alternative to triclosan, quaternary ammonium salts, and other toxic compounds that now dominate the antimicrobial market. In the second section, the mechanism that makes sonochemistry a prospective instrument for highly stable, effective, and environmentally friendly antibacterial coating of textile is discussed. In addition, the antibacterial efficiency of the sonochemically coated textiles was validated after 65 washing cycles. The third part of the review reports on the progress in colorization of textiles by sonochemistry …

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Jan 2019 • Polyhedron

Preparation and characterization of bis (guanidinium) and bis (aminotetrazolium) dodecahydroborate salts: Green high energy nitrogen and boron rich compounds

Pessia Sharon, Michal Afri, Sergey Mitlin, Levi Gottlieb, Bruria Schmerling, Dan Grinstein, Shmuel Welner, Aryeh A Frimer

This paper describes the syntheses, crystallization, characterization and energetic properties (calorimetry) of closo-dodecahydroborate salts with guanidinium and aminotetrazolium based cations. The salts were readily produced in good yields by metathesis (ion exchange) reactions depending on the water solubility of the dodecahydroborate salts. Water insoluble salts can be synthesized from the potassium or sodium salts by a simple metathesis reaction with the corresponding halide of the desired organic cation. Water soluble salts can be prepared via two consecutive metathesis reactions: the halide is first converted to the corresponding sulfate, which is reacted in turn with barium dodecahydroborate, yielding the water soluble organic closo(B12H12)2− salt and the insoluble BaSO4. The product salt is conveniently isolated by water evaporation. The aminotetrazolium salt 12d gives nice crystals when …

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Jan 2019 • Quantum Electronics

Coherent elastographic tomography via speckle time multiplexing

A Schwarz, N Ozana, R Califa, A Shemer, H Genish, Z Zalevsky

A method is suggested for separating photons coming from different depths of tissue while externally stimulating tissue via infra-sonic vibration. The process of tomographic information extraction using the speckle time multiplexing approach is presented. Use is also made of a modulated laser combining a speckle-pattern tracking method for sensing surface tilting changes with an interferometer for sensing surface z-axis changes at the same scan time.

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Jan 2019 • Quantum Electronics

Confocal Raman imaging of skin sections containing hair follicles using classical least squares regression and multivariate curve resolution–alternating least squares

Johannes Schleusener, V Carrer, A Patzelt, S Guo, T Bocklitz, L Coderch, Jürgen Lademann, Maksim Evgen'evich Darvin

Confocal Raman microscopy (CRM) is applied ex vivo for imaging of the spatial distribution of different skin components in skin sections containing hair follicles. For multivariate data analysis, different methods are used in order to spectrally decompose the reference spectra of the skin components (dermis, viable epidermis, stratum corneum and hair). Classical least squares regression (CLS) and multivariate curve resolution–alternating least squares (MCR-ALS) are chosen as suitable methods. In comparison to other optical methods, the advantage of CRM is molecular specificity and dispensability of labelling dyes, which is eg necessary in fluorescence microscopy. Therefore, a useful future application of CRM in combination with multivariate data analysis lies in the analysis of penetration routes of topically applied substances, such as cosmetic formulations or drugs into the skin, which is particularly interesting in …

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Jan 2019 • Graefe's Archive for Clinical and Experimental Ophthalmology

Antibacterial and physical properties of a novel sonochemical-assisted Zn-CuO contact lens nanocoating

Yoav Nahum, Reut Israeli, Gabriel Mircus, Ilana Perelshtein, Miriam Ehrenberg, Shay Gutfreund, Aharon Gedanken, Irit Bahar

PurposeThis work examined the antibacterial and physical effects of a novel Zn-CuO nanocoating applied on a silicone hydrogel contact lens.MethodsZn-CuO coating of PureVision balafilcon-A soft contact lenses (Bausch&Lomb, Rochester, NY) was performed by sonochemical deposition using a high-intensity ultrasonic horn. Non-coated PureVision lenses served as a control in all experiments. Adhesion assays for P. aerueginosa and S. epidermidis to the coated lenses were performed to identify the minimal coating concentration which still possessed antibacterial activity. Lens water content, oxygen transfer light transfer, leaching, and electron microscopy studies were performed using this concentration.ResultsCoated lenses showed 3–5 log reductions in adhesion of both species. The lowest tested coating …

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