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Structural basis for antibiotic action of the B1 antivitamin 2′-methoxy-thiamine
No full textThe natural antivitamin 2′-methoxy-thiamine (MTh) is implicated in the suppression of microbial growth. However, its mode of action and enzyme-selective inhibition mechanism have remained elusive. Intriguingly, MTh inhibits some thiamine diphosphate (ThDP) enzymes, while being coenzymatically active in others. Here we report the strong inhibition of Escherichia coli transketolase activity by MTh and unravel its mode of action and the structural basis thereof. The unique 2′-methoxy group of MTh diphosphate (MThDP) clashes with a canonical glutamate required for cofactor activation in ThDP-dependent enzymes. This glutamate is forced into a stable, anticatalytic low-barrier hydrogen bond with a neighboring glutamate, disrupting cofactor activation. Molecular dynamics simulations of transketolases and other ThDP enzymes identify active-site flexibility and the topology of the cofactor-binding locale as key determinants for enzyme-selective inhibition. Human enzymes either retain enzymatic activity with MThDP or preferentially bind authentic ThDP over MThDP, while core bacterial metabolic enzymes are inhibited, demonstrating therapeutic potential
Variable period undulator with tunable polarization
No full textThe proposed magnetic structure allows to control all the parameters of the sinusoidal magnetic field of permanent magnet undulator: amplitude , period length , and phase . The magnetic structure consists of diametrically magnetized cylindrical magnets at fixed positions. The field is adjusted by motorized rotation of each magnet. Tuning of radiated wavelength by changing the period length instead of field amplitude is more effective and results in a wider wavelength range and higher photon flux, especially for free electron lasers. Individual adjustment of the magnets allows for creating arbitrary shaped magnetic field and also for embedding other elements like phase shifters, dipoles, or multipole lenses into the undulator magnetic structure
Cu and Zr surface sites in photocatalytic activity of nanoparticles: The effect of Zr distribution
No full textThe present work is focused on the role of modification in theperformance of CuO modified . Zirconia loading leads to formationof more resistant photocatalytic layers compared to samples modifiedwith only copper containing species. Surface modification of mixedphase with CuO/ZrO improves the degradation of Reactive blue 19 dye under simulated solar irradiation. An in-depth investigation of thecatalysts showed that in case of CuO/ZrO modification, the covering ofthe surface with zirconium containing species preventsmorphological and harmful energetic changes induced by copper speciesformed on the rutile phase at a higher copper loading
Toward Optimization of Centrifugal Barrel Polishing P rocedure for Treatment of Niobium Cavities
No full textCentrifugal barrel polishing (CBP) is a simple and environmentally friendly method that can be applied for mechanical abrasion of the cavity interior in order to remove the mechanically damaged surface after its production. The CBP recipes described in the literature, however, require CBP to be performed in many stages, require long processing times and nevertheless are unable to provide good cavity RF performance without additional chemical processing. Here, we report new results on characterization of cavity surfaces treated with a typical CBP recipe, including the contamination with abrasive particles, plastic deformation and hydrogen contamination, and critically evaluate it. Methods to reduce the depth of significant plastic deformation as well as the modified commercially viable CBP procedure followed by final electropolishing are proposed and tested on samples
High-flux XAFS-beamline P64 at PETRA III
No full textBeamline P64 at PETRA III is dedicated to x-ray absorption spectroscopy experiments which require high flux, like quick extended x-ray absorption fine structure spectroscopy on the sub-second time scale, high-resolution resonant emission spectroscopy, and x-ray absorption fine-structure spectroscopy of highly diluted systems. The beamline is installed at the high-energy storage ring PETRA III. The source is a 2 m-long undulator. The beamline covers an energy-range from 4 keV to 44 keV, which was required by the user community. Mirrors can be used to reduce the intensity of higher harmonics, and to focus the beam. A conventional photo-diode and a 100-pixel high-purity Ge-detector are used in fluorescence extended x-ray absorption fine-structure spectroscopy for diluted samples
Surface Phases and Surface Freezing in an Ionic Liquid
No full textRoom temperature ionic liquids (RTILs), a novel class of liquid salts, are intensively studied for their basic science and numerous emerging applications. When undercooled, RTILs comprising long alkyl chains often exhibit liquid crystal (LC) bulk phases. However, only one molecular-resolution experimental structure study was published for their LC surface phases. We measured the temperature evolution of another LC surface phase, using surface specific Å-resolution X-ray methods. This phase’s existence range, 90 °C, much exceeds the corresponding bulk phase’s 3 °C. Its thickness, L, confirms the theory-predicted logarithmic temperature dependence, with an amplitude equaling the bulk correlation length. Surprisingly, at L’s divergence temperature, a ∼20 Å thick, hexagonally packed, crystalline monolayer forms at, and fully covers, the sample’s surface. It is identified as a surface-frozen Langmuir–Gibbs film and fundamentally differs from the only reported RTIL surface crystal, a Coulomb-dominated, four-layer, island phase, covering only 5%–15% of the surface
Constraints on the emission region of 3C 279 during strong flares in 2014 and 2015 through VHE γ -ray observations with H.E.S.S.
No full textThe flat spectrum radio quasar 3C 279 is known to exhibit pronounced variability in the high-energy (100 MeV 100 GeV) γ-ray domain. While the observation in 2014 provides an upper limit, the observation in 2015 results in a signal with 8.7σ significance above an energy threshold of 66 GeV. No VHE variability was detected during the 2015 observations. The VHE photon spectrum is soft and described by a power-law index of 4.2 ± 0.3. The H.E.S.S. data along with a detailed and contemporaneous multiwavelength data set provide constraints on the physical parameters of the emission region. The minimum distance of the emission region from the central black hole was estimated using two plausible geometries of the broad-line region and three potential intrinsic spectra. The emission region is confidently placed at r ≳ 1.7 × 10 cm from the black hole, that is beyond the assumed distance of the broad-line region. Time-dependent leptonic and lepto-hadronic one-zone models were used to describe the evolution of the 2015 flare. Neither model can fully reproduce the observations, despite testing various parameter sets. Furthermore, the H.E.S.S. data were used to derive constraints on Lorentz invariance violation given the large redshift of 3C 279
In Situ Structural Characterization of Functionally Graded Ni–Ti Shape Memory Alloy During Tensile Loading
No full textA functionally graded NiTi shape memory alloywire was investigated by in situ synchrotron radiationbasedX-ray diffraction (SR-XRD) during cyclic tensiledeformation. The transformation temperatures were determinedby DSC and the thermomechanical behaviour wasanalysed by three-point bending test. The present studyfocussed on the localized heat treatment (Joule heat effect,reaching 300 C, 350 and 400 C pulses for 10 min) ofNiTi wires, using an equipment that allows a large varietyof graded conditions. Structural, mechanical and thermomechanicalcharacterization is presented to get a perspectiveof the different types of graded functionality. Acombination of two strategies has been used for the in situanalysis by SR-XRD of the tensile tests: (i) continuouslyfollowing the structural evolution at one single point (at thecenter of the heat-treated segment) all long the load/unloadcycle and (ii) scanning the full heat-treated segmentatpreviously defined discrete steps of the stress–strain curve.The combined information from both types of testsprovided detailed information about the phase transformationstaking place in different regions of the functionallygraded segment, at different steps of the tensile load/unloadcycle, giving a better understanding of the overallmechanical, namely the evidence of the sequence B2 B190 for the direct and reverse transformations
simsurvey : estimating transient discovery rates for the Zwicky transient facility
No full textWhen planning a survey for astronomical transients, many factors such as cadence, filter choice, sky coverage, and depth of observations need to be balanced in order to optimize the scientific gain of the survey. Here we present a software package called simsurvey for simulating the supernova lightcurves that are expected based on a survey strategy, which can then be used to determine the potential for discoveries of each strategy in question. The code is set up in a modular fashion that allows easy modification of small details of the survey and enables the user to adapt it to any survey design and transient template that they wish to use in planning their survey. As an example of its utility, we use simsurvey to simulate the lightcurve of several types of supernovae that the recently started Zwicky Transient Facility (ZTF) is expected to find and compare the results to the discoveries made during its early operations. We conclude that ZTF will find thousands of bright supernovae per year, of which about 10 could potentially be found with two days of explosion. Over the course of three years the survey will obtain lightcurves of about 1800 type Ia supernovae with z < 0.1 that can be used as distance indicators in cosmology if they are spectroscopically classified using additional telescopes. In a comparison to detections from the ZTF public survey, we found good agreement with the numbers of detections expected from the simulation
NewBG: A surrogate corticosteroid-binding globulin with an unprecedentedly high ligand release efficacy
No full textThe introduction of ligand-binding sites into proteins and the engineering of molecular allosteric coupling pathways are topical issues in protein design. Here, we show that these issues can be addressed concurrently, using the serpin human α1-antichymotrypsin (ACT) as a model. We have introduced up to 15 amino acid substitutions into ACT, converting it into a surrogate corticosteroid-binding globulin (CBG), thereby creating a new binding globulin (NewBG). Human CBG and ACT share 46% sequence identity, and CBG served as the blue-print for our design, which was guided by side-chain-packing calculations, ITC measurements and crystal structure determinations. Upon transfer of ligand-interacting residues from CBG to ACT and mutation of specific second shell residues, a NewBG variant was obtained, which binds cortisol with 1.5 µM affinity. This novel serpin (NewBG-III) binds cortisol with a 33-fold lower affinity than CBG, but shares a similar ligand-binding profile and binding mode when probed with different steroid ligands and site-directed mutagenesis. An additional substitution, i.e. A349R, created NewBG-III-allo, which introduced an allosteric coupling between ligand binding and the serpin-like S-to-R transition in ACT. In NewBG-III-allo, the proteinase-triggered S-to-R transition leads to a greater than 200-fold reduction in ligand affinity, and crystal structures suggest that this is mediated by the L55V and A349R substitutions. This reduction significantly exceeds the 10-fold reduction in binding affinity observed in human CBG