Myxoma virus protein M029 is a dual function immunomodulator that inhibits PKR and also conscripts RHA/DHX9 to promote expanded host tropism and viral replication.

Myxoma virus (MYXV)-encoded protein M029 is a member of the poxvirus E3 family of dsRNA-binding proteins that antagonize the cellular interferon signaling pathways. In order to investigate additional functions of M029, we have constructed a series of targeted M029-minus (vMyx-M029KO and vMyx-M029ID) and V5-tagged M029 MYXV. We found that M029 plays a pivotal role in determining the cellular tropism of MYXV in all mammalian cells tested. The M029-minus viruses were able to replicate only in engineered cell lines that stably express a complementing protein, such as vaccinia E3, but underwent abortive or abated infection in all other tested mammalian cell lines. The M029-minus viruses were dramatically attenuated in susceptible host European rabbits and caused no observable signs of myxomatosis. Using V5-tagged M029 virus, we observed that M029 expressed as an early viral protein is localized in both the nuclear and cytosolic compartments in virus-infected cells, and is also incorporated into virions. Using proteomic approaches, we have identified Protein Kinase R (PKR) and RNA helicase A (RHA)/DHX9 as two cellular binding partners of M029 protein. In virus-infected cells, M029 interacts with PKR in a dsRNA-dependent manner, while binding with DHX9 was not dependent on dsRNA. Significantly, PKR knockdown in human cells rescued the replication defect of the M029-knockout viruses. Unexpectedly, this rescue of M029-minus virus replication by PKR depletion could then be reversed by RHA/DHX9 knockdown in human monocytic THP1 cells. This indicates that M029 not only inhibits generic PKR anti-viral pathways, but also binds and conscripts RHA/DHX9 as a pro-viral effector to promote virus replication in THP1 cells. Thus, M029 is a critical host range and virulence factor for MYXV that is required for replication in all mammalian cells by antagonizing PKR-mediated anti-viral functions, and also conscripts pro-viral RHA/DHX9 to promote viral replication specifically in myeloid cells

Monte Carlo Simulations of the Transition Radiation Detector of the AMS-02 Experiment

The Transition Radiation Detector of the AMS-02 experiment on the International Space Station is used for the separation of cosmic-ray positrons and electrons from protons and anti-protons, and for the identification of nuclei up to carbon (Z<=6). We present the Geant4 simulation that is used to describe the ionization and transition radiation processes and compare its results to flight data from AMS-02. After applying empirical corrections to the simulated data, the particle energy deposition and likelihood distributions in the TRD are described with high accuracy.Comment: 7 pages, 9 figures. Accepted for publication in Nuclear Inst. and Methods in Physics Research, A. CC-BY-NC-ND 4.0 licens

Evaluating a holistic energy benchmarking parameter of lift systems by using computer simulation

At present, there are benchmarking parameters to assess the energy performance of lifts, e.g. one in Germany adopted by VDI (4707-1/2), one internationally published by ISO (BS EN ISO 25745-2:2015), and the other in Hong Kong adopted by The Hong Kong Special Administrative Region (HKSAR) Government. These parameters are mainly checking the energy consumed by a lift drive without considering real time passenger demands and traffic conditions; the one in Hong Kong pinpointing a fully loaded up-journey under rated speed and the two in Europe pinpointing a round trip, bottom floor to top floor and return with an empty car, though including energy consumed by lighting, displays, ventilation etc. A holistic normalization method by Lam et al [1] was developed a number of years ago by one of the co-authors of this article, which can assess both drive efficiency and traffic control, termed J/kg-m, which is now adopted by the HKSAR Government as a good practice, but not specified in the mandatory code. In Europe, the energy unit of Wh has been used but here, Joule (J), i.e. Ws, is adopted to discriminate the difference between the two concepts. In this article, this parameter is evaluated under different lift traffic scenarios using computer simulation techniques, with an aim of arriving at a reasonable figure for benchmarking an energy efficient lift system with both an efficient drive as well as an efficient supervisory traffic control

Computer Simulation Aided Study of a Real-time Energy Benchmarking Parameter for Lift Systems under different Traffic Control Schemes

At present, there are benchmarking procedures to assess the energy performance of lifts, e.g. VDI (4707-1/2) adopted in Germany as a pioneer, then replaced by ISO (BS EN ISO 25745-1:2012 and 25745-2:2015) in Europe, and the other in Hong Kong adopted by The Hong Kong Special Administrative Region (HKSAR) Government. The Hong Kong procedure focuses on the design performance of lift drives. The ISO standard further estimates the annual energy. To facilitate real time monitoring of energy performance of lift systems, a holistic normalization method (So et al 2005, Lam et al 2006) was developed more than ten years ago, which can simultaneously assess both drive efficiency and traffic control performance on a real-time basis, termed which is the name of the parameter measured in unit, J/kgm, and is now adopted by the HKSAR Government as a good practice in the Technical Guidelines of the Energy Code, but not yet enforced in the mandatory code. Values, not just the procedures, for benchmarking are demanded. In this article, such a parameter is evaluated under different drives and lift traffic control scenarios by using computer simulations, with the aim of arriving at a reasonable figure for benchmarking an energy efficient lift system with both an efficient drive as well as an efficient supervisory traffic control. This parameter could also be used to compare the performance of different types of intelligent car dispatchers. The simulation suggested a value of 50 J/kgm as acceptable while 40 J/kgm as good

TLR ligand-induced podosome disassembly in dendritic cells is ADAM17 dependent

Toll-like receptor (TLR) signaling induces a rapid reorganization of the actin cytoskeleton in cultured mouse dendritic cells (DC), leading to enhanced antigen endocytosis and a concomitant loss of filamentous actin–rich podosomes. We show that as podosomes are lost, TLR signaling induces prominent focal contacts and a transient reduction in DC migratory capacity in vitro. We further show that podosomes in mouse DC are foci of pronounced gelatinase activity, dependent on the enzyme membrane type I matrix metalloprotease (MT1-MMP), and that DC transiently lose the ability to degrade the extracellular matrix after TLR signaling. Surprisingly, MMP inhibitors block TLR signaling–induced podosome disassembly, although stimulated endocytosis is unaffected, which demonstrates that the two phenomena are not obligatorily coupled. Podosome disassembly caused by TLR signaling occurs normally in DC lacking MT1-MMP, and instead requires the tumor necrosis factor α–converting enzyme ADAM17 (a disintegrin and metalloprotease 17), which demonstrates a novel role for this “sheddase” in regulating an actin-based structure

Double layer charging driven carbon dioxide adsorption limits the rate of electrochemical carbon dioxide reduction on Gold.

Electrochemical CO[Formula: see text] reduction is a potential route to the sustainable production of valuable fuels and chemicals. Here, we perform CO[Formula: see text] reduction experiments on Gold at neutral to acidic pH values to elucidate the long-standing controversy surrounding the rate-limiting step. We find the CO production rate to be invariant with pH on a Standard Hydrogen Electrode scale and conclude that it is limited by the CO[Formula: see text] adsorption step. We present a new multi-scale modeling scheme that integrates ab initio reaction kinetics with mass transport simulations, explicitly considering the charged electric double layer. The model reproduces the experimental CO polarization curve and reveals the rate-limiting step to be *COOH to *CO at low&nbsp;overpotentials, CO[Formula: see text] adsorption at intermediate&nbsp;ones, and CO[Formula: see text] mass transport at high overpotentials. Finally, we show the Tafel slope to arise from the electrostatic interaction&nbsp;between the dipole of&nbsp;*CO[Formula: see text] and the interfacial field. This work highlights the importance of surface charging for electrochemical kinetics and mass transport

Directional optical switching and transistor functionality using optical parametric oscillation in a spinor polariton fluid

Over the past decade, spontaneously emerging patterns in the density of polaritons in semiconductor microcavities were found to be a promising candidate for all-optical switching. But recent approaches were mostly restricted to scalar fields, did not benefit from the polariton's unique spin-dependent properties, and utilized switching based on hexagon far-field patterns with 60{\deg} beam switching (i.e. in the far field the beam propagation direction is switched by 60{\deg}). Since hexagon far-field patterns are challenging, we present here an approach for a linearly polarized spinor field, that allows for a transistor-like (e.g., crucial for cascadability) orthogonal beam switching, i.e. in the far field the beam is switched by 90{\deg}. We show that switching specifications such as amplification and speed can be adjusted using only optical means

Constructing a simulation surrogate with partially observed output

Gaussian process surrogates are a popular alternative to directly using computationally expensive simulation models. When the simulation output consists of many responses, dimension-reduction techniques are often employed to construct these surrogates. However, surrogate methods with dimension reduction generally rely on complete output training data. This article proposes a new Gaussian process surrogate method that permits the use of partially observed output while remaining computationally efficient. The new method involves the imputation of missing values and the adjustment of the covariance matrix used for Gaussian process inference. The resulting surrogate represents the available responses, disregards the missing responses, and provides meaningful uncertainty quantification. The proposed approach is shown to offer sharper inference than alternatives in a simulation study and a case study where an energy density functional model that frequently returns incomplete output is calibrated.Comment: submitted to Technometric

Strain-gradient-induced magnetic anisotropy in straight-stripe mixed-phase bismuth ferrites: An insight into flexomagnetic phenomenon

Implementation of antiferromagnetic compounds as active elements in spintronics has been hindered by their insensitive nature against external perturbations which causes difficulties in switching among different antiferromagnetic spin configurations. Electrically-controllable strain gradient can become a key parameter to tune the antiferromagnetic states of multiferroic materials. We have discovered a correlation between an electrically-written straight-stripe mixed-phase boundary and an in-plane antiferromagnetic spin axis in highly-elongated La-5%-doped BiFeO$_{3}$ thin films by performing polarization-dependent photoemission electron microscopy in conjunction with cluster model calculations. Model Hamiltonian calculation for the single-ion anisotropy including the spin-orbit interaction has been performed to figure out the physical origin of the link between the strain gradient present in the mixed phase area and its antiferromagnetic spin axis. Our findings enable estimation of the strain-gradient-induced magnetic anisotropy energy per Fe ion at around 5$\times$10$^{-12}$ eV m, and provide a new pathway towards an electric-field-induced 90$^{\circ}$ rotation of antiferromagnetic spin axis at room temperature by flexomagnetism.Comment: 32 pages, 5 figure

Subquadratic Encodings for Point Configurations

For many algorithms dealing with sets of points in the plane, the only relevant information carried by the input is the combinatorial configuration of the points: the orientation of each triple of points in the set (clockwise, counterclockwise, or collinear). This information is called the order type of the point set. In the dual, realizable order types and abstract order types are combinatorial analogues of line arrangements and pseudoline arrangements. Too often in the literature we analyze algorithms in the real-RAM model for simplicity, putting aside the fact that computers as we know them cannot handle arbitrary real numbers without some sort of encoding. Encoding an order type by the integer coordinates of a realizing point set is known to yield doubly exponential coordinates in some cases. Other known encodings can achieve quadratic space or fast orientation queries, but not both. In this contribution, we give a compact encoding for abstract order types that allows efficient query of the orientation of any triple: the encoding uses O(n^2) bits and an orientation query takes O(log n) time in the word-RAM model with word size w >= log n. This encoding is space-optimal for abstract order types. We show how to shorten the encoding to O(n^2 {(log log n)}^2 / log n) bits for realizable order types, giving the first subquadratic encoding for those order types with fast orientation queries. We further refine our encoding to attain O(log n/log log n) query time at the expense of a negligibly larger space requirement. In the realizable case, we show that all those encodings can be computed efficiently. Finally, we generalize our results to the encoding of point configurations in higher dimension