Antioxidant therapeutic advances in COPD

Chronic obstructive pulmonary disease (COPD) is associated with a high incidence of morbidity and mortality. Cigarette smoke-induced oxidative stress is intimately associated with the progression and exacerbation of COPD and therefore targeting oxidative stress with antioxidants or boosting the endogenous levels of antioxidants is likely to have beneficial outcome in the treatment of COPD. Among the various antioxidants tried so far, thiol antioxidants and mucolytic agents, such as glutathione, N-acetyl-L-cysteine, N-acystelyn, erdosteine, fudosteine and carbocysteine; Nrf2 activators; and dietary polyphenols (curcumin, resveratrol, and green tea catechins/quercetin) have been reported to increase intracellular thiol status along with induction of GSH biosynthesis. Such an elevation in the thiol status in turn leads to detoxification of free radicals and oxidants as well as inhibition of ongoing inflammatory responses. In addition, specific spin traps, such as α-phenyl-N-tert-butyl nitrone, a catalytic antioxidant (ECSOD mimetic), porphyrins (AEOL 10150 and AEOL 10113), and a SOD mimetic M40419 have also been reported to inhibit cigarette smoke-induced inflammatory responses in vivo in the lung. Since a variety of oxidants, free radicals and aldehydes are implicated in the pathogenesis of COPD, it is possible that therapeutic administration of multiple antioxidants and mucolytics will be effective in management of COPD. However, a successful outcome will critically depend upon the choice of antioxidant therapy for a particular clinical phenotype of COPD, whose pathophysiology should be first properly understood. This article will review the various approaches adopted to enhance lung antioxidant levels, antioxidant therapeutic advances and recent past clinical trials of antioxidant compounds in COPD

Search for Tensor, Vector, and Scalar Polarizations in the Stochastic Gravitational-Wave Background

The detection of gravitational waves with Advanced LIGO and Advanced Virgo has enabled novel tests of general relativity, including direct study of the polarization of gravitational waves. While general relativity allows for only two tensor gravitational-wave polarizations, general metric theories can additionally predict two vector and two scalar polarizations. The polarization of gravitational waves is encoded in the spectral shape of the stochastic gravitational-wave background, formed by the superposition of cosmological and individually unresolved astrophysical sources. Using data recorded by Advanced LIGO during its first observing run, we search for a stochastic background of generically polarized gravitational waves. We find no evidence for a background of any polarization, and place the first direct bounds on the contributions of vector and scalar polarizations to the stochastic background. Under log-uniform priors for the energy in each polarization, we limit the energy densities of tensor, vector, and scalar modes at 95% credibility to Ω0T<5.58×10-8, Ω0V<6.35×10-8, and Ω0S<1.08×10-7 at a reference frequency f0=25 Hz. © 2018 American Physical Society

Sequence-related off-target effect of Dz13 against human tumor cells and safety in adult and fetal mice following systemic administration

The oligonucleotide Dz13, a DNA enzyme that cleaves c-Jun mRNA, is capable of inhibiting various model tumors in mice. However, to date, a thorough examination of its target specificity in tumor cells has not been performed. In addition, an evaluation of its safety in a mammalian whole organism system has not been carried out. Dz13 mutated oligonucleotides were designed and tested in a proliferation assay. Dz13 was also tested for its safety in vivo when administered intravenously in a bolus dose, or systemically in an in utero assay. While Dz13 down-regulated target gene (c-Jun) expression in human tumor cells, c-Jun siRNA failed to cause cell growth inhibition. Furthermore, alteration of contiguous G motifs in Dz13 flanking arms inhibits cell death activity, but removal of the same from the catalytic core can increase cell death activity. A 20mer (truncated) derivative Dz13 exhibited similar activity. Dz13 was not toxic to blood and solid tissues in adult or fetal mice, though slight hepatotoxicity was noted with histology. It was also void of adverse effects to the physiological processes of angiogenesis and apoptosis. Collectively, the data support the safety of Dz13 and its activity attributed to off-target effects

Evaluation of the use of non-pathogenic porcine circovirus type 1 as a vaccine delivery virus vector to express antigenic epitopes of porcine reproductive and respiratory syndrome virus

The polarization transfer from longitudinally polarized electrons to protons in the elastic scattering $p(\overrightarrow{e},e'\overrightarrow{p} )$ has been measured around $Q^2$ = 0.4 (GeV/$c$)$^2$ with the three-spectrometer facility at the Mainz microtron MAMI. From this polarization transfer the ratio $G_{{\rm E}p}/(G_{{\rm M}p}/\mu_p)$ has been determined. The ratio is found to be slightly less than unity in agreement with recent results from other laboratories and from the Rosenbluth separation of cross-sections measured with unpolarized electrons

The horizontal drift chambers for the focal plane proton-polarimeter of the 3-spectrometer setup at MAMI

Large-area horizontal drift chambers have been built for use in a proton polarimeter. A gas mixture of 20% argon and 80% ethane is used. The left–right assignment is achieved by measuring the difference of the signals induced on neighboring potential wires. A spatial resolution of 300 μm is achieved

The focal plane proton-polarimeter for the 3-spectrometer setup at MAMI

For (e- gt ,e prime p- gt ) experiments the 3-spectrometer setup of the A1 collaboration at MAMI has been supplemented by a focal plane proton-polarimeter. To this end, a carbon analyzer of variable thickness and two double-planes of horizontal drift chambers have been added to the standard detector system of Spectrometer A. Due to the spin precession in the spectrometer magnets, all three polarization components at the target can be measured simultaneously. The performance of the polarimeter has been studied using elastic p(e- gt ,e prime p- gt ) scattering