Wasted opportunities: Problematic alcohol and drug use among gay men and bisexual men

This report describes the findings from a qualitative and quantitative study of alcohol and drug use among gay and bisexual men and other men that have sex with men (MSM) in England. The qualitative element describes the experiences and understandings of men who identified themselves as being concerned about their alcohol or drug use. The quantitative element shows the broader picture of use and concern about use among MSM. So we go from a broad picture of the extent of alcohol and drug use and concern about it, to a narrower and more detailed focus on men experiencing concern and problems related to alcohol and drug use. The aims of the study are to qualitatively explore the contexts and attendant needs of men who are concerned about their substance use, to locate that use within the broader MSM population and to suggest ways in which the drug-related needs of MSM might be better met. So we have specifically recruited men who were concerned about their substance use and investigated the way these men used drugs and alcohol, what drugs and alcohol mean to them and the harms caused by drugs and alcohol. Many men, perhaps the majority, use alcohol and other drugs without any mishap or unhappiness. However, the range of experiences described highlight the pervasive and often detrimental role that alcohol and other drugs play in the social and personal lives of many men. Although there is some research which examines the effects of substance use treatments on sexual risk behaviour (that is, do drugs services reduce unsafe sex), there is little or no research which investigates the accessibility, acceptability or effectiveness of current substance use services for gay men and other MSM. So in the qualitative interviews we also sought information about the role services played in meeting drug-related needs, for example information, motivational and practical support

Veganism and \u27The Analytic Question\u27

The (practical) dilemma I explore in this paper concerns two advocacy-oriented aims which, though not mutually exclusive per se, are nonetheless quite difficult for vegans to jointly satisfy in practice. The first concerns the need for individual vegans to rebuff (by example) certain familiar stereotypes about vegans as ‘militant,’ ‘angry,’ ‘self-righteous,’ etc.; the second concerns the need to tactfully resist familiar prompts to, as it were, conversationally parse the logic of one’s own convictions ad nauseam. To better explain, and partially respond to, this dilemma, I exploit an instructive analogy with the (so-called) ‘analytic question’ in epistemology (roughly, what are the severally necessary and jointly sufficient conditions for knowledge?). I conclude by suggesting that, just as not having a fully worked-out theoretical answer to this question is not (good) grounds for epistemic skepticism, neither is not having a fully developed ‘theory of veganism’ a (good) reason for not becoming vegan

DarwinDock and GAG-Dock: Methods and Applications for Small Molecule Docking

Computational modeling is an effective tool in studying complex biological systems. Docking of small molecule ligands in particular is useful both in understanding the functioning of proteins as well as in the development of pharmaceuticals. Together with experiment, modeling can often provide a thorough picture of a given system. Computation can often provide details that are difficult or impossible to determine experimentally, while experiments provide guidance on what calculations are useful or interesting. Our goal is to extend computational modeling, specifically ligand docking, to systems not previously possible, such as the challenging glycosaminoglycan (GAG) systems. In order to do this it was first necessary to develop an automatic way of performing docking without extensive user input and experimental knowledge to narrow the list of candidate poses. DarwinDock represents our efforts in this respect. It is a method for small-molecule docking that separates pose generation and scoring into separate stages, which allows for complete binding site sampling followed by efficient, hierarchical sampling. Our convergence criteria for complete sampling allows for diverse systems to be studied without prior knowledge of how large a set of poses needs to be to span a given binding site, making the procedure more automatic. We also replace bulky, nonpolar residues with alanine, which we refer to as "alanization". This allows the ligand to interact more closely with polar sidechains, which help to orient the ligand. Additionally, alanization reduces the impact of incorrect sidechain placement on ligand placement, a concern that sometimes requires user intervention. With DarwinDock working for standard small molecules, it was then necessary to modify the procedure to work on challenging GAG ligands, which are large and have strong negative charges. A modification to DarwinDock – GAG-Dock – allows the method to be applied to GAGs and protein surface interactions. GAGs are large, linear polysaccharides with strong negative charge. They typically interact with the surfaces of proteins, rather than the cavities favored by most small-molecule drugs. GAG-Dock systematically samples the protein surface for unknown binding sites and modifies the pose generation to allow for large, surface-interacting ligands. GAG-Dock allowed us to study several systems important for neuronal development and answer interesting questions posed by experiment. Finally, we needed a way to validate our predictions for GAG binding sites. We used a systematic approach to identify sets of beneficial mutations to the GAG binding sites by building up from individual in silico mutations. Standard mutation experiments typically employ large mutations, such as arginine to alanine, which decrease or destroy binding. However, such information is not always definitive, as large mutations can have wide-ranging effects beyond direct protein-ligand interactions. Mutations that increase binding, however, are less ambiguous because they must form new interactions with the ligand in order to affect binding energies or affinity. Therefore, we have identified and proposed sets of mutations for our GAG predictions for PTPs, NgR1, NgR3, and EphB3. We encourage our experimentalist colleagues to try these mutations and validate our predictions.</p

An Experimental Characterization of Tip Leakage Flows and Corresponding Effects on Multistage Compressor Performance

The effect of rotor tip clearances in turbomachinery applications has been a primary research interest for nearly 80 years. Over that time, studies have shown increased tip clearance in axial flow compressors typically has a detrimental effect on overall pressure rise capability, isentropic efficiency, and stall margin. With modern engine designs trending toward decreased core sizes to increase propulsive efficiency (by increasing bypass ratio) or additional compression stages to increase thermal efficiency by increasing the overall pressure ratio, blade heights in the rear stages of the high pressure compressor are expected to decrease. These rear stages typically feature smaller blade aspect ratios, for which endwall flows are more important, and the rotor tip clearance height represents a larger fraction of blade span. As a result, data sets collected with large relative rotor tip clearance heights are necessary to facilitate these future small core design goals

Multi-color carrier-envelope-phase stabilization for high-repetition-rate multi-pulse coherent synthesis

Using a zero-offset carrier-envelope locking technique, we have synthesized an octave-spanning composite frequency comb exhibiting 132-attosecond timing jitter between the constituent pulses over a one-second observation window. In the frequency domain, this composite comb has a modal structure and coherence which are indistinguishable from those of a comb that might be produced by a hypothetical single mode locked oscillator of equivalent bandwidth. The associated phase stability enables the participating multi-color pulse sequences to be coherently combined, representing an example of multi-pulse synthesis using a femtosecond oscillator

An Improved Red Spectrum of the Methane or T-dwarf SDSS 1624+0029: Role of the Alkali Metals

A Keck~II low resolution spectrum shortward of ome-micron is presented for SDSS 1624+0029, the first field methane or T dwarf discovered in the Sloan Digital Sky Survey. Significant flux is detected down to the spectrum's short wavelength limit of 6200\AA. The spectrum exhibits a broad absorption feature centered at 7700\AA, which we interpret as the K~I 7665/7699 resonance doublet. The observed flux declines shortward of 7000\AA, due most likely to the red wing of the Na~I doublet. Both Cs~I doublet lines are detected more strongly than in an earlier red spectrum. Neither Li~I absorption nor H$\alpha$ emission are detected. An exploratory model fit to the spectrum suggests that the shape of the red spectrum can be primarily accounted for by the broad wings of the K~I and Na~I doublets. This behavior is consistent with the argument proffered by Burrows, Marley and Sharp that strong alkali absorption is principally responsible for depressing T dwarf spectra shortward of 1$\mu$m. In particular, there seems no compelling reason at this time to introduce dust or an additional opacity source in the atmosphere of the SDSS object. The width of the K~I and strengths of the Cs~I lines also indicate that the Sloan object is warmer than Gl~229B.Comment: accepted March 3, 2000 for Ap.J. Letters, LaTeX, 2 figure

HST Spectral Mapping of L/T Transition Brown Dwarfs Reveals Cloud Thickness Variations

Most directly imaged giant exoplanets are fainter than brown dwarfs with similar spectra. To explain their relative underluminosity unusually cloudy atmospheres have been proposed. However, with multiple parameters varying between any two objects, it remained difficult to observationally test this idea. We present a new method, sensitive time-resolved Hubble Space Telescope near-infrared spectroscopy, to study two rotating L/T transition brown dwarfs (2M2139 and SIMP0136). The observations provide spatially and spectrally resolved mapping of the cloud decks of the brown dwarfs. The data allow the study of cloud structure variations while other parameters are unchanged. We find that both brown dwarfs display variations of identical nature: J- and H-band brightness variations with minimal color and spectral changes. Our light curve models show that even the simplest surface brightness distributions require at least three elliptical spots. We show that for each source the spectral changes can be reproduced with a linear combination of only two different spectra, i.e. the entire surface is covered by two distinct types of regions. Modeling the color changes and spectral variations together reveal patchy cloud covers consisting of a spatially heterogenous mix of low-brightness, low-temperature thick clouds and brighter, thin and warm clouds. We show that the same thick cloud patches seen in our varying brown dwarf targets, if extended to the entire photosphere, predict near-infrared colors/magnitudes matching the range occupied by the directly imaged exoplanets that are cooler and less luminous than brown dwarfs with similar spectral types. This supports the models in which thick clouds are responsible for the near infrared properties of these underluminous exoplanets.Comment: Astrophysical Journal, in pres

Vertical Atmospheric Structure in a Variable Brown Dwarf: Pressure-dependent Phase Shifts in Simultaneous Hubble Space Telescope-Spitzer Light Curves

Heterogeneous clouds or temperature perturbations in rotating brown dwarfs produce variability in the observed flux. We report time-resolved simultaneous observations of the variable T6.5 brown dwarf 2MASSJ22282889-431026 over the wavelength ranges 1.1-1.7 microns and broadband 4.5 microns. Spectroscopic observations were taken with Wide Field Camera 3 on board the Hubble Space Telescope and photometry with the Spitzer Space Telescope. The object shows sinusoidal infrared variability with a period of 1.4 hr at most wavelengths with peak-to-peak amplitudes between 1.45% and 5.3% of the mean flux. While the light curve shapes are similar at all wavelengths, their phases differ from wavelength to wavelength with a maximum difference of more than half of a rotational period. We compare the spectra with atmospheric models of different cloud prescriptions, from which we determine the pressure levels probed at different wavelengths. We find that the phase lag increases with decreasing pressure level, or higher altitude. We discuss a number of plausible scenarios that could cause this trend of light curve phase with probed pressure level. These observations are the first to probe heterogeneity in an ultracool atmosphere in both horizontal and vertical directions, and thus are an ideal test case for realistic three dimensional simulations of the atmospheric structure with clouds in brown dwarfs and extrasolar planets.Comment: Accepted to ApJL, 6 pages, 3 figures. Minor language updates from v1 to match published versio

Discovery of An Unusually Blue L Dwarf Within 10 pc of the Sun

We report the discovery of an unusually blue L5 dwarf within 10 pc of the Sun from a search of Sloan Digital Sky Survey (SDSS) spectra. A spectrophotometric distance estimate of 8.0+/-1.6 pc places SDSS J141624.08+134826.7 among the six closest known L dwarfs. SDSS 1416+13 was overlooked in infrared color-based searches because of its unusually blue J-K_S color, which also identifies it as the nearest member of the blue L dwarf subclass. We present additional infrared and optical spectroscopy from the IRTF/SpeX and Magellan/MagE spectrographs and determine UVW motions that indicate thin disk kinematics. The inclusion of SDSS 1416+13 in the 20 pc sample of L dwarfs increases the number of L5 dwarfs by 20% suggesting that the L dwarf luminosity function may be far from complete.Comment: 15 pages, 3 figures, accepted for publication in AJ; updated version includes corrected radial velocit