Pharmaceuticals that contain polycyclic hydrocarbon scaffolds

Numerous variations on structural motifs exist within pharmaceutical compounds that have entered the clinic. These variations have amounted over many decades based on years of drug development associated with screening natural products and de novo synthetic systems. Caged (or bridged) bicyclic structural elements offer a variety of diverse features, encompassing three-dimensional shape, and assorted pharmacokinetic properties. This review highlights approximately 20 all carbon cage containing pharmaceuticals, ranging in structure from bicyclo[2.2.1] through to adamantane, including some in the top-selling pharmaceutical bracket. Although, a wide variety of human diseases, illnesses and conditions are treated with drugs containing the bicyclic motif, a common feature is that many of these lipophilic systems display CNS and/or neurological activity. In addition, to an extensive overview of the history and biology associated with each drug, a survey of synthetic methods used to construct these entities is presented. An analysis section compares natural products to synthetics in drug discovery, and entertains the classical caged hydrocarbon systems potentially missing from the clinic. Lastly, this unprecedented review is highly pertinent at a time when big pharma is desperately trying to escape flatland drugs

Two Time Scales for The Price Of One (Almost)

Although differences exist between seasonal- and decadal-scale climate variability, predictability, and prediction, investment in observations, prediction systems, and decision systems for either time scale can benefit both

The energy based devices for vaginal "rejuvenation," urinary incontinence, vaginal cosmetic procedures, and other vulvo-vaginal disorders: An international multidisciplinary expert panel opinion

Aims: Energy-based devices using radiofrequency and laser technologies have gained popularity as therapies for vaginal atrophy, urinary incontinence, and vaginal prolapse. They have been promoted by cosmetic and aesthetic industries for vaginal "laxity" and vaginal "rejuvenation," both of which are undefined conditions and terms. This article aims to review the current available literature and its quality on this emerging technology. Methods: An international panel of gynaecologists, urogynaecologists, and urologists undertook a review of the available published literature, identifying articles, guidance, and society statements on the use vaginal energy-based devices. Results: There is currently no formal guidance for the use of vaginal energy based therapies. No randomized controlled trials have been published. No comparative studies to existing treatment has been carried out. Studies suggest that vaginal laser can be used in the treatment of vaginal prolapse or "vaginal laxity" and stress urinary incontinence with no quality evidence supporting the use of the therapy for vaginal atrophy or lichen sclerosis. Conclusions: This international group propose that whilst there remains a paucity of good quality data describing the safety, benefits, and appropriate use of vaginal radiofrequency or laser treatments in gynaecology and urogynaecology, a consensus best practice document by an established scientific community needs to be developed.info:eu-repo/semantics/publishedVersio

El Niño Dynamics

Bringer of storms and droughts, the El Niño∕Southern Oscillation results from the complex, sometimes chaotic interplay of ocean and atmosphere

El Niño Dynamics

Bringer of storms and droughts, the El Niño∕Southern Oscillation results from the complex, sometimes chaotic interplay of ocean and atmosphere

X-Ray, UV, and Optical Observations of Supernova 2006bp with Swift: Detection of Early X-Ray Emission

We present results on the X-ray and optical/UV emission from the type IIP SN 2006bp and the interaction of the SN shock with its environment, obtained with the X-Ray Telescope (XRT) and UV/Optical Telescope (UVOT) on-board the Swift observatory. SN 2006bp is detected in X-rays at a 4.5 sigma level of significance in the merged XRT data from days 1 to 12 after the explosion. If the X-ray luminosity of (1.8+/-0.4)E39 ergs/s is caused by interaction of the SN shock with circumstellar material (CSM), deposited by a stellar wind from the progenitor's companion star, a mass-loss rate of ~E-05 M_sun/yr is inferred. The mass-loss rate is consistent with the non-detection in the radio with the VLA on days 2, 9, and 11 after the explosion and characteristic of a red supergiant progenitor with a mass around 12-15 M_sun prior to the explosion. In combination with a follow-up XMM-Newton observation obtained on day 21 after the explosion, an X-ray rate of decline with index 1.2+/-0.6 is inferred. Since no other SN has been detected in X-rays prior to the optical peak and since type IIP SNe have an extended 'plateau' phase in the optical, we discuss the scenario that the X-rays might be due to inverse Compton scattering of photospheric optical photons off relativistic electrons produced in circumstellar shocks. However, due to the high required value of the Lorentz factor (~10-100) we conclude that Inverse Compton scattering is an unlikely explanation for the observed X-ray emission. The fast evolution of the optical/ultraviolet spectral energy distribution and the spectral changes observed with Swift reveal the onset of metal line-blanketing and cooling of the expanding photosphere during the first few weeks after the outburst.Comment: 8 pages, 5 figures, accepted for publication in Ap

Ornamental plants, 1982: a summary of research

Growth of Taxus cuspidata 'Thayeri' produced in containers / Elton M. Smith and Sharon A. Treaster -- A comparison of plant growth in poly bags produced on capillary irrigation / Elton M. Smith and Sharon A. Treaster -- Sodium chloride phytotoxicity to sugar maple / Elton M. Smith and Sharon A. Treaster -- Effects of fertilizer in the propagation medium and extended photo period on rooting of Acer rubrum 'Red Sunset' / Steven M. Still and Bryce H. Lane -- Comparisons of growth for chrysanthemums and poinsettias produced in prototypes of a new container and four potting media / Richard P. Ventanovetz and John C. Peterson -- Effects of pH upon nutrient availability in a commercial soilless root medium utilized for floral crop production / John C. Peterson -- An evaluation of pre-emergence herbicides on tulip and narcissus / Elton M. Smith and Sharon A. Treaster -- An evaluation of hot sauce for prevention of mice and deer damage in a commercial nursery / Elton M. Smith and Thomas M. Stockdale -- Test results of fungicides for control of diseases of ornamentals / C. C. Powell -- Virus-indexed rose plants: first-year performance results / C. C. Powel

Consequences of sexual harassment in sport for female athletes

Sexual harassment research was first undertaken in the workplace and educational settings. Research on sexual harassment in sport is scarce but has grown steadily since the mid-1980s. Even so, very little is known about the causes and/or characteristics and/or consequences of sexual harassment in sport settings. This article reports on the findings from interviews with 25 elite female athletes in Norway who indicated in a prior survey (N =572) that they had experienced sexual harassment from someone in sport. The consequences of the incidents of sexual harassment that were reported were mostly negative, but some also reported that their experiences of sexual harassment had had no consequences for them. “Thinking about the incidents”, a “destroyed relationship to the coach”, and “more negative view of men in general” were the most often negative consequences mentioned. In addition, a surprising number had chosen to move to a different sport or to drop out of elite sport altogether because of the harassment

Circumstellar Emission from Type Ib and Ic Supernovae

The presumed Wolf-Rayet star progenitors of Type Ib/c supernovae have fast, low density winds and the shock waves generated by the supernova interaction with the wind are not expected to be radiative at typical times of observation. The injected energy spectrum of radio emitting electrons typically has an observed index p=3, which is suggestive of acceleration in cosmic ray dominated shocks. The early, absorbed part of the radio light curves can be attributed to synchrotron self-absorption, which leads to constraints on the magnetic field in the emitting region and on the circumstellar density. The range of circumstellar densities inferred from the radio emission is somewhat broader than that for Galactic Wolf-Rayet stars, if similar efficiencies of synchrotron emission are assumed in the extragalactic supernovae. For the observed and expected ranges of circumstellar densities to roughly overlap, a high efficiency of magnetic field production in the shocked region is required (epsilon_B ~ 0.1). For the expected densities around a Wolf-Rayet star, a nonthermal mechanism is generally required to explain the observed X-ray luminosities of Type Ib/c supernovae. Although the inverse Compton mechanism can explain the observed X-ray emission from SN 2002ap if the wind parameters are taken from the radio model, the mechanism is not promising for other supernovae unless the postshock magnetic energy density is much smaller than the electron energy density. In some cases another mechanism is definitely needed and we suggest that it is X-ray synchrotron emission in a case where the shock wave is cosmic ray dominated so that the electron energy spectrum flattens at high energy. More comprehensive X-ray observations of a Type Ib/c supernova are needed to determine whether this suggestion is correct.Comment: 31 pages, 2 figures, ApJ, accepted, corrected typ