BINA

We consider the extreme value statistics of N independent and identically distributed random variables, which is a classic problem in probability theory. When N→∞, fluctuations around the maximum of the variables are described by the Fisher-Tippett-Gnedenko theorem, which states that the distribution of maxima converges to one out of three limiting forms. Among these lies the Gumbel distribution, for which the convergence rate with N is of a logarithmic nature. Here, we present a theory that allows one to use the Gumbel limit to accurately approximate the exact extreme value distribution. We do so by representing the normalization sequences as power series, and by a transformation of the underlying distribution. We consider functional corrections to the Gumbel limit as well, showing they are obtainable via Taylor expansion. Our method improves the description of large deviations from the mean extreme value. It …

Adenosine-to-inosine editing is catalyzed by ADAR1 at thousands of sites transcriptome-wide. Despite intense interest in ADAR1 from physiological, bioengineering, and therapeutic perspectives, the rules of ADAR1 substrate selection are poorly understood. Here, we used large-scale systematic probing of ∼2,000 synthetic constructs to explore the structure and sequence context determining editability. We uncover two structural layers determining the formation and propagation of A-to-I editing, independent of sequence. First, editing is robustly induced at fixed intervals of 35 bp upstream and 30 bp downstream of structural disruptions. Second, editing is symmetrically introduced on opposite sites on a double-stranded structure. Our findings suggest a recursive model for RNA editing, whereby the structural alteration induced by the editing at one site iteratively gives rise to the formation of an additional editing site …

In the search for replacement of the platinum‐based catalysts for fuel cells, MN4 molecular catalysts based on abundant transition metals play a crucial role in modeling and investigation of the influence of the environment near the active site in platinum‐group metal‐free (PGM‐free) oxygen reduction reaction (ORR) catalysts. To understand how the ORR activity of molecular catalysts can be controlled by the active site structure through modification by the pH and substituent functional groups, the change of the ORR onset potential and the electron number in a broad pH range was examined for three different metallocorroles. Experiments revealed a switch between two different ORR mechanisms and a change from 2e− to 4e− pathway in the pH range of 3.5‐6. This phenomenon was shown by density functional theory (DFT) calculations to be related to the protonation of the nitrogen atoms and carboxylic acid …

Trimetallic double hydroxide NiFeCoÀ OH is prepared by coprecipitation, from which three different catalysts are fabricated by different heat treatments, all at 350 C maximum temperature. Among the prepared catalysts, the one prepared at a heating and cooling rate of 2 C minÀ 1 in N2 atmosphere (designated NiFeCoÀ N2-2 C) displays the best catalytic properties after stability testing, exhibiting a high current density (9.06 mA cmÀ 2 at 320 mV), low Tafel slope (72.9 mVdecÀ 1), good stability (over 20 h), high turnover frequency (0.304 sÀ 1), and high mass activity (46.52 AgÀ 1 at 320 mV). Stability tests reveal that the hydroxide phase is less suitable for long-term use than catalysts with an oxide phase. Two causes are identified for the loss of stability in the hydroxide phase: a) Modeling of the distribution function of relaxation times (DFRT) reveals the increase in resistance contributed by various relaxation processes; b) density functional theory (DFT) surface energy calculations reveal that the higher surface energy of the hydroxide-phase catalyst impairs the stability. These findings represent a new strategy to optimize catalysts for water splitting.

We formalize the concept of the modular energy operator within the Page and Wooters timeless framework. As a result, this operator is elevated to the same status as the more studied modular operators of position and momentum. In analogy with dynamical nonlocality in space associated with the modular momentum, we introduce and analyze the nonlocality in time associated with the modular energy operator. Some applications of our formalization are provided through illustrative examples.

Articular cartilage (AC) is a specialized connective tissue able to provide a low‐friction gliding surface supporting shock‐absorption, reducing stresses, and guaranteeing wear‐resistance thanks to its structure and mechanical and lubrication properties. Being an avascular tissue, AC has a limited ability to heal defects. Nowadays, conventional strategies show several limitations, which results in ineffective restoration of chondral defects. Several tissue engineering approaches have been proposed to restore the AC's native properties without reproducing its mechanical and lubrication properties yet. This work reports the fabrication of a bilayered structure made of gellan gum (GG) and poly (ethylene glycol) diacrylate (PEGDA), able to mimic the mechanical and lubrication features of both AC superficial and deep zones. Through appropriate combinations of GG and PEGDA, cartilage Young's modulus is effectively …

The generation and amplification of photons by parametric down-conversion in quadratic nonlinear media is used as a source of entangled photons, squeezed light, and short optical pulses at difficult to access wavelengths. Optical nonlinearities are inherently weak, and therefore the pump energy required to produce sufficient gain for efficient down-conversion has been limited to energies in excess of nanojoules. Here we use dispersion-engineered nonlinear nanowaveguides driven by femtosecond pulses to demonstrate efficient down-conversion at the picojoule level; we observe parametric gains in excess of 70 decibels with pump pulse energies as little as 4 picojoules. When driven with pulse energies in excess of 10 picojoules these waveguides amplify vacuum fluctuations to 10\% of the pump power, and the generated bandwidth broadens to span an octave. These results represent a new class of parametric devices that combine sub-wavelength spatial confinement with femtosecond pulses to achieve efficient operation with remarkably low energy.

This paper is an initial proof of concept for an optical speckled-based method for the evaluation of facial nerve paralysis. Differences between the affected and the healthy sides of the face were measured in patients with Bell's palsy—a peripheral facial nerve paralysis. The patients’ faces were illuminated with two symmetrical spots on their nasolabial folds and the reflected speckle patterns were analyzed. Muscle activity was evaluated by muscle tone contraction-release motion inducing associated skin tilting movements. The skin movements were imaged with a defocused lens, which enables extraction of the speckle pattern's time changing trajectory. We found an asymmetry ratio expression that may be the key for the estimation of the degeneration level in Bell's palsy.

Genetic diagnostic tools including whole-exome sequencing (WES) have advanced our understanding in human diseases and become common practice in diagnosing patients with suspected primary immune deficiencies. Establishing a genetic diagnosis is of paramount importance for tailoring adequate therapeutic regimens, including identifying the need for hematopoietic stem cell transplantation (HSCT) and genetic-based therapies. Here, we genetically studied two adult patients who were clinically diagnosed during infancy with severe combined immune deficiency (SCID). Two unrelated patients, both of consanguineous kindred, underwent WES in adulthood, 2 decades after their initial clinical manifestations. Upon clinical presentation, immunological workup was performed, which led to a diagnosis of SCID. The patients presented during infancy with failure to thrive, generalized erythematous rash, and …

The Cu (II)‐diacetyl‐bis (N4‐methylthiosemicarbazone) complex (ATSM− Cu (II)) has been suggested as a promising positron emission tomography (PET) agent for hypoxia imaging. Several in‐vivo studies have shown its potential to detect hypoxic tumors. However, its uptake mechanism and its specificity to various cancer cell lines have been less studied. Herein, we tested ATSM− Cu (II) toxicity, uptake, and reduction, using four different cell types:(1) mouse breast cancer cells (DA‐3),(2) human embryonic kidney cells (HEK‐293),(3) breast cancer cells (MCF‐7), and (4) cervical cancer cells (Hela) under normoxic and hypoxic conditions. We showed that ATSM− Cu (II) is toxic to breast cancer cells under normoxic and hypoxic conditions; however, it is not toxic to normal HEK‐293 non‐cancer cells. We showed that the Cu (I) content in breast cancer cell after treatment with ATSM− Cu (II) under hypoxic conditions is …

Advances in the development of Pt-group metal-free (PGM-free) catalysts for oxygen reduction reaction in fuel cells produced active catalysts that allow to reduce the performance gap to the incumbent Ptbased materials. However, the utilization of the state-of-the-art PGM-free catalysts in commercial applications is currently impeded by their relatively low durability. Methods designed to study catalyst degradation in operating fuel cells are critical for the understanding and ultimately solving the durability issues. This work is the first report on the use of Fourier-transformed alternating current voltammetry (FTacV) as an electrochemical method for accurately quantifying the electrochemical site density of PGM-free ORR catalysts, and following their degradation during the operation of polymer electrolyte fuel cells. Using this method we were capable of detecting changes in performance of electrochemically active species (electrocatalytic centers in this case), allowing us, for the first time, to calculate the electrochemical active site density (EASD) which is necessary for the elucidation of the degradation mechanisms of PGM-free ORR catalysts in situ fuel cells.

Coordinate‐transformation‐inspired optical devices have been mostly examined in the continuous‐wave regime: the performance of an invisibility cloak, which has been demonstrated for monochromatic excitation, is likely to deteriorate for short pulses. Here, pulse dynamics of flexural waves propagating in transformed plates is investigated. A practical realization of a waveshifter and a rotator for flexural waves based on the coordinate transformation method is proposed. Time‐resolved measurements reveal how the waveshifter deviates a short pulse from its initial trajectory, with no reflection at the bend and no spatial and temporal distortion of the pulse. Extending the strategy to cylindrical coordinates, a wave rotator is designed. It is demonstrated experimentally how a pulsed plane wave is twisted inside the rotator, while its wavefront is recovered behind the rotator and the pulse shape is preserved, with no extra …

During the past several decades, a variety of imaging modalities in fluorescence microscopy have emerged as powerful tools for probing the spatial and temporal dimensions in fixed and living cells and tissues to uncover structural and dynamic information. Recently, our journal accepted a paper in this topic, and we received comments. We found it as opportunity to discuss this important topic for additional angles. We believe that this discussion will be interesting and helpful to the whole community.

A method for fast non-scanning remote photoacoustic imaging is presented and experimentally demonstrated. The approach is based on speckle contrast measurement, proceeding the previously developed method for speckle contrast based photoacoustic detection. This previously developed method is now presented without the need for raster scanning of the sample, an advantage rarely found in optical photoacoustic detection, and offers 50 times faster as well as a simpler remote photoacoustic scheme in respect to interferometric available solutions.

Aerogels offer a great platform for heterogeneous electrocatalysis owing to their high surface area and porosity. Atomically dispersed transition metal ions can be imbedded in these platforms at ultra‐high site density to make them catalytically active for various reactions. Herein, the synthesis of a new class of conjugated microporous organic aerogels that are used as covalent 3D frameworks for the electrocatalysis of oxygen reduction reaction (ORR) is reported. Modified aerogels functionalized with bipyridine ligands enable copper ion complexation in a single‐step synthesis. The aerogels’ structures are fully characterized using a wide array of spectroscopic and microscopic methods, and heat‐treated in order to make them electronically conductive. After heat treatment at 600 °C, the aerogels maintained their macrostructure and became active ORR catalysts in alkaline environment, showing high mass activity …

Owing to their inherent features like smaller size and higher surface area exposed to reactants, iron oxide nanoparticles have gained enormous interest and are extensively used as magnetically recyclable catalysts for various organic reactions. Herein, we report highly hydrophilic, non-aggregated, and strongly positively charged (ζ potential:+ 45.7 mV) ultra-small cerium cations/complexes-stabilized maghemite nanoparticles in water as an efficient and reusable nanoscaled catalyst for the nucleophilic addition reaction of various amines with α, β-unsaturated carbonyl compounds to give corresponding β-amino derivatives under ultrasonic irradiation. The developed protocol provides several merits such as high product yields, mild reaction conditions, reusable catalyst and easy workup.

We demonstrate strong coupling between a single J-aggregate and an inverse bowtie plasmonic structure, when the J-aggregate is located at a specific axial distance from the metallic surface. Three hybrid modes are clearly observed, witnessing a strong interaction, with a Rabi splitting of up to 290 meV, the precise value of which significantly depends on the orientation of the J-aggregate with respect to the symmetry axis of the plasmonic structure. We repeated our experiments with a set of triangular hole arrays, showing consistent formation of three or more hybrid modes, in good agreement with numerical simulations.

Kaposi’s sarcoma-associated herpesvirus (KSHV) is a cancer-related herpesvirus. Like other herpesviruses, the KSHV icosahedral capsid includes a portal vertex, composed of 12 protein subunits encoded by open reading frame (ORF) 43, which enables packaging and release of the viral genome into the nucleus through the nuclear pore complex (NPC). Capsid vertex-specific component (CVSC) tegument proteins, which directly mediate docking at the NPCs, are organized on the capsid vertices and are enriched on the portal vertex. Whether and how the portal vertex is selected for docking at the NPC is unknown. Here, we investigated the docking of incoming ORF43-null KSHV capsids at the NPCs, and describe a significantly lower fraction of capsids attached to the nuclear envelope compared to wild-type (WT) capsids. Like WT capsids, nuclear envelope-associated ORF43-null capsids co-localized with different nucleoporins (Nups) and did not detach upon salt treatment. Inhibition of nuclear export did not alter WT capsid docking. As ORF43-null capsids exhibit lower extent of association with the NPCs, we conclude that although not essential, the portal has a role in mediating the interaction of the CVSC proteins with Nups, and suggest a model whereby WT capsids can dock at the nuclear envelope through a non-portal penton vertex, resulting in an infection ‘dead end’. View Full-Text