Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Similarity searching using 2D structural fingerprints

This chapter reviews the use of molecular fingerprints for chemical similarity searching. The fingerprints encode the presence of 2D substructural fragments in a molecule, and the similarity between a pair of molecules is a function of the number of fragments that they have in common. Although this provides a very simple way of estimating the degree of structural similarity between two molecules, it has been found to provide an effective and an efficient tool for searching large chemical databases. The review describes the historical development of similarity searching since it was first described in the mid-1980s, reviews the many different coefficients, representations, and weightings that can be combined to form a similarity measure, describes quantitative measures of the effectiveness of similarity searching, and concludes by looking at current developments based on the use of data fusion and machine learning techniques

Searches for Gravitational Waves from Known Pulsars at Two Harmonics in the Second and Third LIGO-Virgo Observing Runs

We present a targeted search for continuous gravitational waves (GWs) from 236 pulsars using data from the third observing run of LIGO and Virgo (O3) combined with data from the second observing run (O2). Searches were for emission from the l = m = 2 mass quadrupole mode with a frequency at only twice the pulsar rotation frequency (single harmonic) and the l = 2, m = 1, 2 modes with a frequency of both once and twice the rotation frequency (dual harmonic). No evidence of GWs was found, so we present 95% credible upper limits on the strain amplitudes h (0) for the single-harmonic search along with limits on the pulsars' mass quadrupole moments Q (22) and ellipticities epsilon. Of the pulsars studied, 23 have strain amplitudes that are lower than the limits calculated from their electromagnetically measured spin-down rates. These pulsars include the millisecond pulsars J0437-4715 and J0711-6830, which have spin-down ratios of 0.87 and 0.57, respectively. For nine pulsars, their spin-down limits have been surpassed for the first time. For the Crab and Vela pulsars, our limits are factors of similar to 100 and similar to 20 more constraining than their spin-down limits, respectively. For the dual-harmonic searches, new limits are placed on the strain amplitudes C (21) and C (22). For 23 pulsars, we also present limits on the emission amplitude assuming dipole radiation as predicted by Brans-Dicke theory

Narrowband searches for continuous and long-duration transient gravitational waves from known pulsars in the LIGO-Virgo third observing run

Isolated neutron stars that are asymmetric with respect to their spin axis are possible sources of detectable continuous gravitational waves. This paper presents a fully coherent search for such signals from eighteen pulsars in data from LIGO and Virgo's third observing run (O3). For known pulsars, efficient and sensitive matched-filter searches can be carried out if one assumes the gravitational radiation is phase-locked to the electromagnetic emission. In the search presented here, we relax this assumption and allow both the frequency and the time derivative of the frequency of the gravitational waves to vary in a small range around those inferred from electromagnetic observations. We find no evidence for continuous gravitational waves, and set upper limits on the strain amplitude for each target. These limits are more constraining for seven of the targets than the spin-down limit defined by ascribing all rotational energy loss to gravitational radiation. In an additional search, we look in O3 data for long-duration (hours–months) transient gravitational waves in the aftermath of pulsar glitches for six targets with a total of nine glitches. We report two marginal outliers from this search, but find no clear evidence for such emission either. The resulting duration-dependent strain upper limits do not surpass indirect energy constraints for any of these targets

Searches for gravitational waves from known pulsars at two harmonics in the second and third LIGO-Virgo observing runs

We present a targeted search for continuous gravitational waves (GWs) from 236 pulsars using data from the third observing run of LIGO and Virgo (O3) combined with data from the second observing run (O2). Searches were for emission from the l = m = 2 mass quadrupole mode with a frequency at only twice the pulsar rotation frequency (single harmonic) and the l = 2, m = 1, 2 modes with a frequency of both once and twice the rotation frequency (dual harmonic). No evidence of GWs was found, so we present 95% credible upper limits on the strain amplitudes h0 for the single-harmonic search along with limits on the pulsars' mass quadrupole moments Q22 and ellipticities ε. Of the pulsars studied, 23 have strain amplitudes that are lower than the limits calculated from their electromagnetically measured spin-down rates. These pulsars include the millisecond pulsars J0437−4715 and J0711−6830, which have spin-down ratios of 0.87 and 0.57, respectively. For nine pulsars, their spin-down limits have been surpassed for the first time. For the Crab and Vela pulsars, our limits are factors of ∼100 and ∼20 more constraining than their spin-down limits, respectively. For the dual-harmonic searches, new limits are placed on the strain amplitudes C21 and C22. For 23 pulsars, we also present limits on the emission amplitude assuming dipole radiation as predicted by Brans-Dicke theory