BINA

Kaposi’s sarcoma-associated herpesvirus (KSHV) is a transforming gammaherpesvirus. Like other herpesviruses, KSHV infection is for life long and there is no treatment that can cure patients from the virus. In addition, there is an urgent need to target viral genes to study their role during the infection cycle. The CRISPR-Cas9 technology offers a means to target viral genomes and thus may offer a novel strategy for viral cure as well as for better understanding of the infection process. We evaluated the suitability of this platform for the targeting of KSHV. We have used the recombinat KSHV BAC16 genome, which contains an expression cassette encoding hygromycin-resistance and a GFP marker gene. Three genes were targeted: gfp, which serves as a marker for infection; orf45 encoding a lytic viral protein; and orf73, encoding LANA which is crucial for latent infection. The fraction of cells expressing GFP, viral DNA levels and LANA expression were monitored and viral genomes were sequenced. We found that KSHV episomes can be targeted by CRISPR-Cas9. Interestingly, the quantity of KSHV DNA declined, even when target sites were not functionally important for latency. In addition, we show that antibiotic selection, used to maintain infection, interferes with the outcome of targeting. Our study provides insights into the use of this fundamental approach for the study and manipulation of KSHV. It provides guidelines for the targeting CRISPR-Cas9 to the viral genome and for outcomes interpretation.

These questions led to an increasing number of studies, resulting in evidence for the relevance of the above motivations. 4− 8 At the same time, the results raise new, or leave open, existing issues. Herein, we discuss some of these results that we view as central and issues arising from questions 1− 3 (question 4 is left for another occasion), with further questions presented in italics.

Lignocellulose biomass effectively produces chemicals and fuels, which are of importance for the establishment of a sustainable society. The conversion of cellulose, the main component of the biomass, into significant precursors that can be further converted to different chemicals or fuels under gentle conditions is a promising route. Organic acids such as acetic, glycolic and formic acid are significant examples. A novel method to produce important platform chemicals from micro-crystalline cellulose (MCC) was developed. MCC was degraded as a result of oxidation with potassium chlorate by microwave radiation in a one-pot procedure. Efficient reaction conditions such as short reaction time and full conversion of cellulose were identified. The reaction products were analyzed by 1H and 13C NMR, XPS, TGA and XRD.

Carbon dots (CDs) and their doped counterparts including nitrogen-doped CDs (N@CDs) have been synthesized by bottom-up or top-down approaches from different precursors. The attractiveness of such emerging 2D‑carbon-based nanosized materials is attributed to their excellent biocompatibility, preparation, aqueous dispersibility, and functionality. The antimicrobial, optical, and electrochemical properties of CDs have been advocated for two important biotechnological applications: bacterial eradication and sensing/biosensing. CDs as well as N@CDs act as antimicrobial agents as their surfaces encompass functional hydroxyl, carboxyl, and amino groups that generate free radicals. As a new class of photoluminescent nanomaterials, CDs can be employed in diversified analytics. CDs with surface carboxyl or amino groups form nanocomposites with nanomaterials or be conjugated with biorecognition …

The development of precious group metal-free (PGM-free) catalysts for the oxygen reduction reaction is considered as the main thrust for the cost reduction of fuel cell technologies and their mass production. Within the PGM-free category, molecular catalysts offer an advantage over other heat-treated PGM-free catalysts owing to their well-defined structure, which enables further design of more active, selective, and durable catalysts. Even though non-heat-treated molecular catalysts with exceptional performance have been reported in the past, they were rarely tested in a fuel cell. Herein, we report on a molecular catalyst under alkaline conditions: fluorinated iron phthalocyanine (FeFPc) supported on cheap and commercially available high-surface area carbon─BP2000 (FeFPc@BP2000). It exhibits the highest activity ever reported for molecular catalysts under alkaline conditions in half-cells and fuel cells.

A sports multi-bet is a bet on the results of a set of N games. One type of multi-bet offered by the Israeli government is WINNER 16, where participants guess the results of a set of 16 soccer games. The prizes in WINNER 16 are determined by the accumulated profit in previous rounds, and are split among all winning forms. When the reward increases beyond a certain threshold, a profitable strategy can be devised. Here, we present a machine-learning algorithm scheme to play WINNER 16. Our proposed algorithm is marginally profitable on average in a range of hyper-parameters, indicating inefficiencies in this game. To make a better prize-pricing mechanism we suggest a generalization of the single-bet approach. We studied the expected profit and risk of WINNER 16 after applying our suggestion. Our proposal can make the game more fair and more appealing without reducing the profitability. View Full-Text

We theoretically analyze the case of noisy Quantum walks (QWs) by introducing four qubit decoherence models into the coin degree of freedom of linear and cyclic QWs. These models include flipping channels (bit flip, phase flip and bit-phase flip), depolarizing channel, phase damping channel and generalized amplitude damping channel. Explicit expressions for the probability distribution of QWs on a line and on a cyclic path are derived under localized and delocalized initial states. We show that QWs which begin from a delocalized state generate mixture probability distributions, which could give rise to useful algorithmic applications related to data encoding schemes. Specifically, we show how the combination of delocalzed initial states and decoherence can be used for computing the binomial transform of a given set of numbers. However, the sensitivity of QWs to noisy environments may negatively affect various other applications based on QWs.

In their seminal paper, Caves and Schumaker presented a new formalism for quantum optics, intended to serve as a building block for describing two-photon processes, in terms of new, generalized qudratures. The important, revolutionary concept in their formalism was that it was fundamentally two-mode, i.e. the related observables could not be attributed to any single one of the comprising modes, but rather to a generalized complex quadrature that could only be attributed to both of them. Here, we propose a subtle, but fundamentally meaningful modification to their important work. Unlike the above proposal, we deliberately choose a frequency-agnostic definition of the two-mode quadrature, that we motivate on physical grounds. This simple modification has far-reaching implications to the formalism – the real and imaginary parts of the quadratures now coincide with the famous EPR variables, and our two-mode …

We experimentally demonstrate ghost imaging in the frequency domain based on frequency speckle patterns as references. Our method is suitable for measuring the spectrum of ultrafast signals with high repetition rates. We study the reconstruction resolution as a function of the signal periodicity and found the maximal signal periodicity which can be reconstructed. We also study the reconstruction resolution as a function of the speckle size and show that the speckle size determines the quality of the ghost image. Finally, we perform numerical and analytical calculations which agree with our experimental measured results. Our method is simple, broadband, and utilizes a low cost bucket detector for ultrafast spectral measurements.

Correction to: Specific Susceptibility to COVID-19 in Adults with Down Syndrome NCBI NCBI Logo Skip to main content Skip to navigation Resources How To About NCBI Accesskeys Sign in to NCBI PMC US National Library of Medicine National Institutes of Health Search database Search term Search Advanced Journal list Help Try out PMC Labs and tell us what you think. Learn More. Journal List Nature Public Health Emergency Collection PMC8602985 Logo of phenaturepg Neuromolecular Med. 2021 Nov 19 : 1–2. doi: 10.1007/s12017-021-08695-7 [Epub ahead of print] PMCID: PMC8602985 PMID: 34797469 Correction to: Specific Susceptibility to COVID-19 in Adults with Down Syndrome Tomer Illouz, 1, 2 Arya Biragyn, 3 Milana Frenkel-Morgenstern, 4 Orly Weissberg, 4 Alessandro Gorohovski, 4 Eugene Merzon, 5 Ilan Green, 5 Florencia Iulita, 6, 7, 8, 9 Lisi Flores-Aguilar, 10 Mara Dierssen, 11, 12, 13 Ilario …

Cancer is a leading cause of death with rates expected to grow with life expectancy. Among leading treatments, cisplatin, widely used to combat cancer, suffers from low stability and selectivity. Here, we covalently conjugated an analog of cisplatin to biocompatible polydopamine nanoparticles (PDA-NPs) to increase both properties. Dynamic light scattering and electron microscopy studies suggest that the platinum-conjugated PDA particles (Pt–PDA-NPs) are monodispersed and spherical with a diameter of about 200 nm with platinum atoms mostly in the shell. Particles were also characterized with inductively coupled plasma mass atomic emission spectroscopy, energy-dispersive X-ray spectroscopy, and X-ray photoelectron spectroscopy to determine the localization and amount of Pt atoms. The chelated metal did not leach from the conjugated particles under normal physiological conditions, while it was released …

Extracting the theoretically high capacity of LiCoO2 (LCO) is desirable for enhancing the energy density of currently used lithium‐ion batteries (LIBs) for portable devices. The bottleneck for exhibiting the high capacity is associated with the limited cut‐off positive voltages beyond which degradation of electrode/electrolyte takes place. In this work, we apply hybrid organic‐inorganic alucone thin film grown directly on LCO by a molecular layer deposition (MLD) method, using sequential exposure to Al‐based and organic‐based precursors. The alucone thin films enabled the high voltage operation of the LCO cathode (>4.5 V), acting as a protection layer. Electrochemical studies proved that alucone coated LCO show enhanced electrochemical performances with improved cycling stability and enhanced specific capacity, relative to uncoated LCO. Amongst the studied films, 10 nm ethylene glycol/Al coated LCO have …

One of the greatest challenges toward rechargeable magnesium batteries is the development of noncorrosive electrolyte solutions with high anodic stability that can support reversible Mg deposition/dissolution. In the last few years, magnesium electrolyte solutions based on Cl-free fluorinated alkoxyborates were investigated for Mg batteries due to their high anodic stability and ionic conductivity and the possibility of reversible deposition/dissolution in ethereal solvents. Here, the electrochemical performance of Mg[B(hexafluoroisopropanol)4]2/dimethoxyethane (Mg[B(HFIP)4]2/DME) solutions was examined. These electrolyte solutions require a special “conditioning” pretreatment that removes undesirable active moieties. Such a process was developed and explored, and basic scientific issues related to the mechanism by which it affects Mg deposition/dissolution were addressed. The chemical changes that occur …

Kerr-lens mode-locking (KLM) is the work-horse mechanism for generation of ultrashort pulses, where a non-linear lens forms an effective ultrafast saturable absorber within the laser cavity. According to standard theory, the pulse in the cavity is a soliton, with a temporal profile and power determined by the non-linearity to exactly counteract diffraction and dispersion, resulting in pulses, whose power and shape are fixed across a wide range of pump powers. We show numerically and demonstrate experimentally that the non-local effect of the Kerr lens in a linear cavity allows the laser to deviate from the soliton model by breaking the spatial symmetry in the cavity between the forward and backward halves of the round-trip, and hence to extract more power in a single pulse, while maintaining stable cavity propagation. We confirm this prediction experimentally in a mode-locked Ti:Sapphire laser with a quantitative agreement to the simulation results. Our numerical tool opens new avenues to optimization and enhancement of the mode-locking performance based on direct examination of the Kerr medium and the spatio-temporal dynamics within it, which is difficult (or even impossible) to observe experimentally.

We explore experimentally synchronization and persistent beating dynamics in coupled non-degenerate parametric oscillators. We demonstrate that synchronization is completely prevented due to mode competition, which is unique to non-degenerate oscillators.

Recently proposed direct-detection laser range finders transmit low power, periodic, unipolar (ON-OFF) coded signal, instead of the commonly used strong narrow single pulse. The combination of non-coherent pulse compression (NCPC) and appropriate binary sequences produces a sidelobe-free periodic delay response. The continuous wave (CW) nature of the signal results in overlaps between returns from multiple targets. When envelope detected, the overlaps can create intermodulation that may hurt the sidelobe-free range response. The paper studies the effect of different sequence types and different envelope detector response profiles and suggests measures to mitigate the influence of multiple targets by calibration of envelope detector.

The virial theorem, and the equipartition theorem in the case of quadratic degrees of freedom, are handy constraints on the statistics of equilibrium systems. Their violation is instrumental in determining how far from equilibrium a driven system might be. We extend the virial theorem to nonequilibrium conditions for Langevin dynamics with nonlinear friction and multiplicative noise. In particular, we generalize the equipartition theorem for confined laser-cooled atoms in the semi-classical regime. The resulting relation between the lowest moments of the atom position and velocity allows to measure in experiments how dissipative the cooling mechanism is. Moreover, its violation can reveal the departure from a strictly harmonic confinement or from the semi-classical regime.

This review summarizes the recent advances in the enantioselective separation of small molecules using biomolecules/macromolecules built up by natural inherent chiral moieties. Although different kinds of chiral selectors are known to date, the microspheres based on biomolecules have received paramount importance in view of their green synthesis, selective and sensitive separation of enantiomers from the racemic mixture. Direct separation of enantiomers devoid of using high-performance liquid chromatography adds to the elegance of this approach. We have covered the preparation of various biomolecules spheres by different methods. The enantiomeric separation of amino acids, drugs and other racemates and the underlying plausible mechanism is discussed.

Copper is a trace element vital to many cellular functions. Yet its abnormal levels are toxic to cells, provoking a variety of severe diseases. The high affinity Copper Transporter 1 (CTR1), being the main in-cell copper (Cu (I)) entry route, tightly regulates its cellular uptake via a still elusive mechanism. Here, all-atoms simulations unlock the molecular terms of Cu (I) transport in eukaryotes disclosing that the two Methionine triads, forming the selectivity filter, play an unprecedented dual role both enabling selective Cu (I) transport and regulating its uptake-rate thanks to an intimate coupling between the conformational plasticity of their bulky side chains and the number of bound Cu (I) ions. Namely, the Met residues act as a gate reducing the Cu (I) import-rate when two ions simultaneously bind to CTR1. This may represent an elegant autoregulatory mechanism through which CTR1 protects the cells from excessively high, and hence toxic, in-cell Cu (I) levels. Overall, these outcomes resolve fundamental questions in CTR1 biology and open new windows of opportunity to tackle diseases associated with an imbalanced copper uptake.

Inherited retinal diseases (IRDs) are a clinically complex and heterogenous group of visual impairment phenotypes caused by pathogenic variants in at least 277 nuclear and mitochondrial genes, affecting different retinal regions, and depleting the vision of affected individuals. Genes that cause IRDs when mutated are unique by possessing differing genotype-phenotype correlations, varying inheritance patterns, hypomorphic alleles, and modifier genes thus complicating genetic interpretation. Next-generation sequencing has greatly advanced the identification of novel IRD-related genes and pathogenic variants in the last decade. For this review, we performed an in-depth literature search which allowed for compilation of the Global Retinal Inherited Disease (GRID) dataset containing 4798 discrete variants and 17,299 alleles published in 31 papers, showing a wide range of frequencies and complexities among …