Investigation of the Stereoselective Synthesis of the Indane Dimer PH46A, a New Potential Anti-inflammatory Agent

PH46A, belonging to a class of 1,2-Indane dimers, has been developed by our research group as a potential therapeutic agent for the treatment of inflammatory and autoimmune diseases. The initial synthetic route to PH46A gave a low overall yield, due in large part to the generation of undesired diastereoisomer 5 and the unwanted enantiomer (R,R)-8 during the synthesis. The aim of this work was to carry out a comprehensive investigation into the stereoselective synthesis of PH46A. Significant progress was made on the ketone reduction step, where the use of triisobutylaluminum [TiBA, Al(iBu)3] afforded high selectivity for the target diastereoisomer (rac)-6, compared to the unfavorable ratio obtained using a previous process. This enabled a multikilo scale synthesis of PH46A in a GMP environment. Further, a brief proof-of-principle investigation was carried out using an achiral phase transfer catalyst (PTC) for alkylation at the methine carbon of the parent indanone

Carbon Monoxide in type II supernovae

Infrared spectra of two type II supernovae 6 months after explosion are presented. The spectra exhibit a strong similarity to the observations of SN 1987A and other type II SNe at comparable epochs. The continuum can be fitted with a cool black body and the hydrogen lines have emissivities that are approximately those of a Case B recombination spectrum. The data extend far enough into the thermal region to detect emission by the first overtone of carbon monoxide. The molecular emission is modeled and compared with that in the spectra of SN 1987A. It is found that the flux in the CO first overtone is comparable to that found in SN 1987A. We argue that Carbon Monoxide forms in the ejecta of all type II SNe during the first year after explosion.Comment: 6 pages, 6 figures, accepted for publications in A&

Photochemically Mediated Ring Expansion of Indoles and Pyrroles with Chlorodiazirines: Synthetic Methodology and Thermal Hazard Assessment

We demonstrate that arylchlorodiazirines serve as photo-activated halocarbene precursors for the selective one-carbon ring expansion of N-substituted pyrroles and indoles to the corresponding pyridinium and quinolinium salts. Preliminary investigations indicate that the same strategy also enables the conversion of N-substituted pyrazoles to pyrimidinium salts. The N-substituent of the substrate plays an essential role in: (1) increasing substrate scope by preventing product degradation, (2) enhancing yields by suppressing co-product inhibition, and (3) activating the azinium products towards subsequent synthetic manipulations. This latter point is illustrated by subjecting the quinolinium salts to four complementary partial reductions, which provide concise access to ring-expanded products with different degrees of increased C(sp3) character. Thermal analysis of the diazirines by differential scanning calorimetry (DSC) provides detailed insight into their energetic properties, and highlights the safety benefits of photolyzing—rather than thermolyzing—these reagents

Global Models of Runaway Accretion in White Dwarf Debris Disks

A growing sample of white dwarfs (WDs) with metal-enriched atmospheres are accompanied by excess infrared emission, indicating that they are encircled by a compact dusty disk of solid debris. Such `WD debris disks' are thought to originate from the tidal disruption of asteroids or other minor bodies, but the precise mechanism(s) responsible for transporting matter to the WD surface remains unclear, especially in those systems with the highest inferred metal accretion rates dM_Z/dt ~ 1e8-1e10 g/s. Here we present global time-dependent calculations of the coupled evolution of the gaseous and solid components of WD debris disks. Solids transported inwards (initially due to PR drag) sublimate at tens of WD radii, producing a source of gas that accretes onto the WD surface and viscously spreads outwards in radius, where it overlaps with the solid disk. If the aerodynamic coupling between the solids and gaseous disks is sufficiently strong (and/or the gas viscosity sufficiently weak), then gas builds up near the sublimation radius faster than it can viscously spread away. Since the rate of drag-induced solid accretion increases with gas density, this results in a runaway accretion process, during which the WD accretion rate reaches values orders of magnitude higher than can be achieved by PR drag alone. We explore the evolution of WD debris disks across a wide range of physical conditions and calculate the predicted distribution of observed accretion rates dM_Z/dt, finding reasonable agreement with the current sample. Although the conditions necessary for runaway accretion are at best marginally satisfied given the minimal level of aerodynamic drag between circular gaseous and solid disks, the presence of other stronger forms of solid-gas coupling---such as would result if the gaseous disk is only mildly eccentric---substantially increase the likelihood of runaway accretion.Comment: 23 pages, 20 figures, submitted to MNRA

Agatha: : disentangling periodic signals from correlated noise in a periodogram framework

This article has been accepted for publication in Monthly Notices of the Royal Astronomical Society. ©: 2017 The Authors. Published by Oxford University Press on behalf of the Royal Astronomical Society. All rights reserved.Periodograms are used as a key significance assessment and visualisation tool to display the significant periodicities in unevenly sampled time series. We introduce a framework of periodograms, called "Agatha", to disentangle periodic signals from correlated noise and to solve the 2-dimensional model selection problem: signal dimension and noise model dimension. These periodograms are calculated by applying likelihood maximization and marginalization and combined in a self-consistent way. We compare Agatha with other periodograms for the detection of Keplerian signals in synthetic radial velocity data produced for the Radial Velocity Challenge as well as in radial velocity datasets of several Sun-like stars. In our tests we find Agatha is able to recover signals to the adopted detection limit of the radial velocity challenge. Applied to real radial velocity, we use Agatha to confirm previous analysis of CoRoT-7 and to find two new planet candidates with minimum masses of 15.1 $M_\oplus$ and 7.08 $M_\oplus$ orbiting HD177565 and HD41248, with periods of 44.5 d and 13.4 d, respectively. We find that Agatha outperforms other periodograms in terms of removing correlated noise and assessing the significances of signals with more robust metrics. Moreover, it can be used to select the optimal noise model and to test the consistency of signals in time. Agatha is intended to be flexible enough to be applied to time series analyses in other astronomical and scientific disciplines. Agatha is available at http://www.agatha.herts.ac.uk.Peer reviewe

Scientific Objectives of Einstein Telescope

The advanced interferometer network will herald a new era in observational astronomy. There is a very strong science case to go beyond the advanced detector network and build detectors that operate in a frequency range from 1 Hz-10 kHz, with sensitivity a factor ten better in amplitude. Such detectors will be able to probe a range of topics in nuclear physics, astronomy, cosmology and fundamental physics, providing insights into many unsolved problems in these areas.Comment: 18 pages, 4 figures, Plenary talk given at Amaldi Meeting, July 201

Modelling human visual navigation using multi-view scene reconstruction

It is often assumed that humans generate a 3D reconstruction of the environment, either in egocentric or world-based coordinates, but the steps involved are unknown. Here, we propose two reconstruction-based models, evaluated using data from two tasks in immersive virtual reality. We model the observer’s prediction of landmark location based on standard photogrammetric methods and then combine location predictions to compute likelihood maps of navigation behaviour. In one model, each scene point is treated independently in the reconstruction; in the other, the pertinent variable is the spatial relationship between pairs of points. Participants viewed a simple environment from one location, were transported (virtually) to another part of the scene and were asked to navigate back. Error distributions varied substantially with changes in scene layout; we compared these directly with the likelihood maps to quantify the success of the models. We also measured error distributions when participants manipulated the location of a landmark to match the preceding interval, providing a direct test of the landmark-location stage of the navigation models. Models such as this, which start with scenes and end with a probabilistic prediction of behaviour, are likely to be increasingly useful for understanding 3D vision

Making subaltern shikaris: histories of the hunted in colonial central India

Academic histories of hunting or shikar in India have almost entirely focused on the sports hunting of British colonists and Indian royalty. This article attempts to balance this elite bias by focusing on the meaning of shikar in the construction of the Gond ‘tribal’ identity in late nineteenth and early twentieth-century colonial central India. Coining the term ‘subaltern shikaris’ to refer to the class of poor, rural hunters, typically ignored in this historiography, the article explores how the British managed to use hunting as a means of state penetration into central India’s forest interior, where they came to regard their Gond forest-dwelling subjects as essentially and eternally primitive hunting tribes. Subaltern shikaris were employed by elite sportsmen and were also paid to hunt in the colonial regime’s vermin eradication programme, which targeted tigers, wolves, bears and other species identified by the state as ‘dangerous beasts’. When offered economic incentives, forest dwellers usually willingly participated in new modes of hunting, even as impact on wildlife rapidly accelerated and became unsustainable. Yet as non-indigenous approaches to nature became normative, there was sometimes also resistance from Gond communities. As overkill accelerated, this led to exclusion of local peoples from natural resources, to their increasing incorporation into dominant political and economic systems, and to the eventual collapse of hunting as a livelihood. All of this raises the question: To what extent were subaltern subjects, like wildlife, ‘the hunted’ in colonial India

Global warming and recurrent mass bleaching of corals

During 2015–2016, record temperatures triggered a pan-tropical episode of coral bleaching, the third global-scale event since mass bleaching was first documented in the 1980s. Here we examine how and why the severity of recurrent major bleaching events has varied at multiple scales, using aerial and underwater surveys of Australian reefs combined with satellite-derived sea surface temperatures. The distinctive geographic footprints of recurrent bleaching on the Great Barrier Reef in 1998, 2002 and 2016 were determined by the spatial pattern of sea temperatures in each year. Water quality and fishing pressure had minimal effect on the unprecedented bleaching in 2016, suggesting that local protection of reefs affords little or no resistance to extreme heat. Similarly, past exposure to bleaching in 1998 and 2002 did not lessen the severity of bleaching in 2016. Consequently, immediate global action to curb future warming is essential to secure a future for coral reefs