Sweet Sixteen Polka

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Structural basis of DNA gyrase inhibition by antibacterial QPT-1, anticancer drug etoposide and moxifloxacin

New antibacterials are needed to tackle antibiotic-resistant bacteria. Type IIA topoisomerases (topo2As), the targets of fluoroquinolones, regulate DNA topology by creating transient double-strand DNA breaks. Here we report the first co-crystal structures of the antibacterial QPT-1 and the anticancer drug etoposide with Staphylococcus aureus DNA gyrase, showing binding at the same sites in the cleaved DNA as the fluoroquinolone moxifloxacin. Unlike moxifloxacin, QPT-1 and etoposide interact with conserved GyrB TOPRIM residues rationalizing why QPT-1 can overcome fluoroquinolone resistance. Our data show etoposide’s antibacterial activity is due to DNA gyrase inhibition and suggests other anticancer agents act similarly. Analysis of multiple DNA gyrase co-crystal structures, including asymmetric cleavage complexes, led to a ‘pair of swing-doors’ hypothesis in which the movement of one DNA segment regulates cleavage and religation of the second DNA duplex. This mechanism can explain QPT-1’s bacterial specificity. Structure-based strategies for developing topo2A antibacterials are suggested

The water vapour continuum in near-infrared windows – current understanding and prospects for its inclusion in spectroscopic databases

Spectroscopic catalogues, such as GEISA and HITRAN, do not yet include information on the water vapour continuum that pervades visible, infrared and microwave spectral regions. This is partly because, in some spectral regions, there are rather few laboratory measurements in conditions close to those in the Earth’s atmosphere; hence understanding of the characteristics of the continuum absorption is still emerging. This is particularly so in the near-infrared and visible, where there has been renewed interest and activity in recent years. In this paper we present a critical review focusing on recent laboratory measurements in two near-infrared window regions (centred on 4700 and 6300 cm−1) and include reference to the window centred on 2600 cm−1 where more measurements have been reported. The rather few available measurements, have used Fourier transform spectroscopy (FTS), cavity ring down spectroscopy, optical-feedback – cavity enhanced laser spectroscopy and, in very narrow regions, calorimetric interferometry. These systems have different advantages and disadvantages. Fourier Transform Spectroscopy can measure the continuum across both these and neighbouring windows; by contrast, the cavity laser techniques are limited to fewer wavenumbers, but have a much higher inherent sensitivity. The available results present a diverse view of the characteristics of continuum absorption, with differences in continuum strength exceeding a factor of 10 in the cores of these windows. In individual windows, the temperature dependence of the water vapour self-continuum differs significantly in the few sets of measurements that allow an analysis. The available data also indicate that the temperature dependence differs significantly between different near-infrared windows. These pioneering measurements provide an impetus for further measurements. Improvements and/or extensions in existing techniques would aid progress to a full characterisation of the continuum – as an example, we report pilot measurements of the water vapour self-continuum using a supercontinuum laser source coupled to an FTS. Such improvements, as well as additional measurements and analyses in other laboratories, would enable the inclusion of the water vapour continuum in future spectroscopic databases, and therefore allow for a more reliable forward modelling of the radiative properties of the atmosphere. It would also allow a more confident assessment of different theoretical descriptions of the underlying cause or causes of continuum absorption

Response of composite cylinders subjected to near field underwater explosions

Experiments were conducted on woven E-glass/epoxy roll wrapped cylinders in three configurations; base composite, and base composite with a thin (100 % composite thickness) and thick (200 % composite thickness) polyurea coating. Each cylinder configuration was subjected to near-field UNDEX loading at charge standoff distances of 2.5 cm and 5.1 cm inside of a large diameter test tank. Results show that the application of a polyurea coating is effective for reducing damage in the cylinders

Near Field Underwater Explosion Response of Polyurea Coated Composite Plates

An experimental study with corresponding numerical simulations has been conducted to evaluate the response of E-Glass / Epoxy composite plates, including polyurea coating effects, subjected to near field underwater explosion (UNDEX) loading. Experiments are performed in a water filled blast tank in which the including transient plate response during the UNDEX loading is measured utilizing high speed photography coupled with Digital Image Correlation. The experimental results show that the transient response of the plate is improved through the use of a thicker plate or through the application of a polyurea coating, although there is a weight penalty associated with the additional material which should be considered. Corresponding computational models of the experiments have been conducted with the commercial finite element code LS-Dyna. The simulations are shown to have a high level of correlation to the experimental data

Experimental and computational investigation of the blast response of Carbon-Epoxy weathered composite materials

An experimental study with corresponding numerical simulations was conducted to investigate the blast response of weathered Carbon-Epoxy composite plates. The dynamic behavior of the composite plates with and without prior exposure to an aggressive marine environment was explored using a shock tube apparatus coupled with a high speed photography system. In order to simulate prolonged exposure in an aggressive marine environment, specimens were submerged in an elevated temperature, 3.5% salt solution for 0, 30 and 60 days. The saline solution temperature was maintained at 65 °C to accelerate the aging process. Finite Element Modeling (FEM) for the blast loading experiments was performed using the Ls-Dyna code. Models have been developed for both the simply supported and fixed boundary condition cases. Tensile and four point bend tests were performed to characterize the quasi-static mechanical behavior of the composite material before and after prolonged exposure to aggressive marine environments. After 30 and 60 days of submergence, the tensile modulus decreased by 11% and 13%, the ultimate tensile strength decreased by 12% and 13%, and the ultimate flexural strength decreased by 22% and 22%, respectively. Dynamic blast loading experiments were performed on simply supported and fully clamped specimens, to determine the effects of the boundary conditions on the Carbon-Epoxy specimen response. The Weathered (30 and 60 days) and Non-Weathered (0 day) specimens displayed dramatically different behavior after being subjected to a blast load. For the simply supported case, Non-Weathered specimens displayed an average maximum out of plane displacement of 20 mm and recovered elastically. Weathered specimens, both 30 and 60 days exhibited similar initial transient behavior but failed catastrophically due to through thickness cracking at the point of maximum deflection. For the fixed boundary condition, the Non-Weathered specimens displayed an average maximum out of plane displacement of 5.57 mm, whereas the 30 day and 60 day weathered specimens displayed a maximum out of plane displacement of 6.89 mm and 6.96 mm, respectively. The corresponding numerical simulations matched well with the experimental data. However, for the fixed boundary case, the beam vibration of the simulation was off phase with the experimental results due to imperfect boundary conditions in the experiments

Fast fourier transform analysis in cavity ring-down spectroscopy: application to an optical detector for atmospheric NO2

A fast Fourier transform (FFT) method for analysis of ring-down decays from a cavity ring-down (CRD) spectrometer has been tested and compared with alternative fitting methods. The ring-down times derived from the FFT method are obtained with a precision close to that of the Levenberg–Marquardt non-linear least-squares method, but the fitting algorithm is ~100 times faster, allowing real-time fitting of individual ring-down traces on a personal computer. Advantages of the FFT method are discussed, and the method is demonstrated for the measurement of NO2 partial pressures equivalent to mixing ratios of 150 pptv and above in laboratory air, using a CRD spectrometer based on an external cavity diode laser operating at wavelengths around 410 nm. The absorption by NO2 is distinguished from other cavity losses either by using synthetic (zero) air reference samples, or by diverting the sampled laboratory airflow through an NO2 chemical scrubber consisting of hydroxyapatite on a TiO2 substrate. Typical mixing ratios of NO2 in the laboratory air are ~25 ppbv