Quantifying biogenic bias in screening libraries.

In lead discovery, libraries of 10(6) molecules are screened for biological activity. Given the over 10(60) drug-like molecules thought possible, such screens might never succeed. The fact that they do, even occasionally, implies a biased selection of library molecules. We have developed a method to quantify the bias in screening libraries toward biogenic molecules. With this approach, we consider what is missing from screening libraries and how they can be optimized

The Chemical Basis of Pharmacology

ABSTRACT: Molecular biology now dominates pharmacology so thoroughly that it is difficult to recall that only a generation ago the field was very different. To understand drug action today, we characterize the targets through which they act and new drug leads are discovered on the basis of target structure and function. Until the mid-1980s the information often flowed in reverse: investigators began with organic molecules and sought targets, relating receptors not by sequence or structure but by their ligands. Recently, investigators have returned to this chemical view of biology, bringing to it systematic and quantitative methods of relating targets by their ligands. This has allowed the discovery of new targets for established drugs, suggested the bases for their side effects, and predicted the molecular targets underlying phenotypic screens. The bases for these new methods, some of their successes and liabilities, and new opportunities for their use are described. So dominant has the molecular biology view of pharmacology become that it is difficult to remember that even 25 years ago it was little more than an aspiration. Today we understand the activity of drugs and reagents first through the specific, clonable receptor molecules with which they interact. To understan

Knee Injuries in NFL Lineman -- A Correlation with BMI

Knee Injuries in NFL Linemen - Correlation with BMI Dr. Michael Lem, MD; Dr. John Bianchi, DO; Austin Irwin, OMS II; Dr. Robert Farrell, MD; Cole Siegenfeld, OMS II Purpose: Knee injuries are among the most common injuries suffered in the NFL which in turn can decrease a player\u27s playing time in a given season and thus negatively impact future performance. Understanding characteristics like BMI can help modify and identify players at risk for knee injuries. Methods and Study Design: Data collected for this study was extracted from the official NFL database of injuries. Reported knee injuries for offensive and defensive lineman were collected and organized by week during the 2009-2022 seasons; final data was calculated for players with a BMI over 39.95. Pro-football-reference.com was cited for height, weight, career length and draft status. BMI was calculated based on height and weight. Comparisons were made between BMI and game status. Results: Among the players collected, offensive tackles were the most likely to appear on the injury report. Players with a BMI above 40 appeared most commonly as Probable (n=182), followed by Questionable (157), Out (134) then Doubtful (26). The average BMI for the players listed as probable was x=42.4 (SD=2.69); questionable x=41.2 (1.37); doubtful x=41.0 (.856); out x=40.9 (.991). There is a significant difference in the player’s BMI between “probable” game status and both “questionable” (p=.023) and “out” (p\u3c .001). Players with a BMI= +37 appeared as either out or doubtful 30.07% total. Players with a BMI under 37 appeared as either out or doubtful 30.81%. Conclusions: Based on our data, BMI may play a protective role on injury report placement for knee injuries. The abundance of “probable” game status also supports the notion that the injuries studied are lower-grade. More players appear on the injury list towards the end of the season, which may indicate there is a persisting effect to the injuries

Corrugated Silicon Platelet Feed Horn Array for CMB Polarimetry at 150 GHz

Next generation cosmic microwave background (CMB) polarization anisotropy measurements will feature focal plane arrays with more than 600 millimeter-wave detectors. We make use of high-resolution photolithography and wafer-scale etch tools to build planar arrays of corrugated platelet feeds in silicon with highly symmetric beams, low cross-polarization and low side lobes. A compact Au-plated corrugated Si feed designed for 150 GHz operation exhibited performance equivalent to that of electroformed feeds: ~-0.2 dB insertion loss, <-20 dB return loss from 120 GHz to 170 GHz, <-25 dB side lobes and <-23 dB cross-polarization. We are currently fabricating a 50 mm diameter array with 84 horns consisting of 33 Si platelets as a prototype for the SPTpol and ACTpol telescopes. Our fabrication facilities permit arrays up to 150 mm in diameter.Comment: 12 pages; SPIE proceedings for Millimeter, Submillimeter, and Far-Infrared Detectors and Instrumentation for Astronomy V (Conference 7741, June 2010, San Diego, CA, USA

The photometric properties of a vast stellar substructure in the outskirts of M33

We have surveyed $\sim40$sq.degrees surrounding M33 with CFHT MegaCam in the g and i filters, as part of the Pan-Andromeda Archaeological Survey. Our observations are deep enough to resolve the top 4mags of the red giant branch population in this galaxy. We have previously shown that the disk of M33 is surrounded by a large, irregular, low-surface brightness substructure. Here, we quantify the stellar populations and structure of this feature using the PAndAS data. We show that the stellar populations of this feature are consistent with an old population with $\sim-1.6$dex and an interquartile range in metallicity of $\sim0.5$dex. We construct a surface brightness map of M33 that traces this feature to $\mu_V\simeq33$mags\,arcsec$^{-2}$. At these low surface brightness levels, the structure extends to projected radii of $\sim40$kpc from the center of M33 in both the north-west and south-east quadrants of the galaxy. Overall, the structure has an "S-shaped" appearance that broadly aligns with the orientation of the HI disk warp. We calculate a lower limit to the integrated luminosity of the structure of $-12.7\pm0.5$mags, comparable to a bright dwarf galaxy such as Fornax or AndII and slightly less than $1\$ of the total luminosity of M33. Further, we show that there is tentative evidence for a distortion in the distribution of young stars near the edge of the HI disk that occurs at similar azimuth to the warp in HI. The data also hint at a low-level, extended stellar component at larger radius that may be a M33 halo component. We revisit studies of M33 and its stellar populations in light of these new results, and we discuss possible formation scenarios for the vast stellar structure. Our favored model is that of the tidal disruption of M33 in its orbit around M31.Comment: Accepted for publication in ApJ. 17 figures. ApJ preprint forma

PAndAS in the mist: The stellar and gaseous mass within the halos of M31 and M33

Large scale surveys of the prominent members of the Local Group have provided compelling evidence for the hierarchical formation of massive galaxies, revealing a wealth of substructure that is thought to be the debris from ancient and on-going accretion events. In this paper, we compare two extant surveys of the M31-M33 subgroup of galaxies; the Pan-Andromeda Archaeological Survey (PAndAS) of the stellar structure, and a combination of observations of the HI gaseous content, detected at 21cm. Our key finding is a marked lack of spatial correlation between these two components on all scales, with only a few potential overlaps between stars and gas.The paucity of spatial correlation significantly restricts the analysis of kinematic correlations, although there does appear to the HI kinematically associated with the Giant Stellar Stream where it passes the disk of M31. These results demonstrate that that different processes must significantly influence the dynamical evolution of the stellar and HI components of substructures, such as ram pressure driving gas away from a purely gravitational path. Detailed modelling of the offset between the stellar and gaseous substructure will provide a determination of the properties of the gaseous halo of M31 and M33.Comment: 11 pages, 6 figures. Accepted for publication in the Astrophysical Journal. Figure quality reduced. High quality version available at http://www.physics.usyd.edu.au/~gfl/Arxiv_Papers/PAndAS_Mist

Does "Liking" Lead to Loving? The Impact of Joining a Brand's Social Network on Marketing Outcomes

Does “liking” a brand on Facebook cause a person to view it more favorably? Or is “liking” simply a symptom of being fond of a brand? We disentangle these possibilities and find evidence for the latter: brand attitudes and purchasing are predicted by consumers’ preexisting fondness for brands and are the same regardless of when and whether consumers “like” brands. In addition, we explore possible second-order effects, examining whether “liking” brands might cause consumers’ friends to view that brand more favorably. When consumers see that a friend has “liked” a brand, they are less likely to buy the brand relative to a more meaningful social endorsement: learning that a friend likes a brand, in the offline sense. Taken together, five experiments and two meta-analyses (N > 14,000) suggest that turning “liking” into improved brand attitudes and increased purchasing by either consumers or their friends may require more than just the click of a button

PAndAS' cubs: discovery of two new dwarf galaxies in the surroundings of the Andromeda and Triangulum galaxies

We present the discovery of two new dwarf galaxies, Andromeda XXI and Andromeda XXII, located in the surroundings of the Andromeda and Triangulum galaxies (M31 and M33). These discoveries stem from the first year data of the Pan-Andromeda Archaeological Survey (PAndAS), a photometric survey of the M31/M33 group conducted with the Megaprime/MegaCam wide-field camera mounted on the Canada-France-Hawaii Telescope. Both satellites appear as spatial overdensities of stars which, when plotted in a color-magnitude diagram, follow metal-poor, [Fe/H]=-1.8, red giant branches at the distance of M31/M33. Andromeda XXI is a moderately bright dwarf galaxy (M_V=-9.9+/-0.6), albeit with low surface brightness, emphasizing again that many relatively luminous M31 satellites still remain to be discovered. It is also a large satellite, with a half-light radius close to 1 kpc, making it the fourth largest Local Group dwarf spheroidal galaxy after the recently discovered Andromeda XIX, Andromeda II and Sagittarius around the Milky Way, and supports the trend that M31 satellites are larger than their Milky Way counterparts. Andromeda XXII is much fainter (M_V=-6.5+/-0.8) and lies a lot closer in projection to M33 than it does to M31 (42 vs. 224 kpc), suggesting that it could be the first Triangulum satellite to be discovered. Although this is a very exciting possibility in the context of a past interaction of M33 with M31 and the fate of its satellite system, a confirmation will have to await a good distance estimate to confirm its physical proximity to M33. Along with the dwarf galaxies found in previous surveys of the M31 surroundings, these two new satellites bring the number of dwarf spheroidal galaxies in this region to 20.Comment: 10 pages, 6 figures, accepted for publication in ApJ; v2: minor typographical correction

Horn Coupled Multichroic Polarimeters for the Atacama Cosmology Telescope Polarization Experiment

Multichroic polarization sensitive detectors enable increased sensitivity and spectral coverage for observations of the Cosmic Microwave Background (CMB). An array optimized for dual frequency detectors can provide 1.7 times gain in sensitivity compared to a single frequency array. We present the design and measurements of horn coupled multichroic polarimeters encompassing the 90 and 150 GHz frequency bands and discuss our plans to field an array of these detectors as part of the ACTPol project

The clinical and cost effectivementss of cognitive behavioural therapy plus treatment as usual for the treatment of depression in advanced cancer (CanTalk):study protocol for a radomised controlled trial

BACKGROUND: The prevalence of depressive disorder in adults with advanced cancer is around 20 %. Although cognitive behavioural therapy (CBT) is recommended for depression and may be beneficial in depressed people with cancer, its use for depression in those with advanced disease for whom cure is not likely has not been explored. METHODS: People aged 18 years and above with advanced cancer attending General Practitioner (GP), oncology or hospice outpatients from centres across England will be screened to establish a DSM-IV diagnosis of depression. Self-referral is also accepted. Eligible consenters will be randomised to a single blind, multicentre, randomised controlled trial of the addition to treatment as usual (TAU) of up to 12 one-hour weekly sessions of manualised CBT versus TAU alone. Sessions are delivered in primary care through Increasing Access to Psychological Care (IAPT) service, and the manual includes a focus on issues for people approaching the end of life. The main outcome is the Beck Depression Inventory-II (BDI-II). Subsidiary measures include the Patient Health Questionnaire, quality of life measure EQ-5D, Satisfaction with care, Eastern Cooperative Oncology Group-Performance Status and a modified Client Service Receipt Inventory. At 90 % power, we require 240 participants to enter the trial. Data will be analysed using multi-level (hierarchical) models for data collected at baseline, 6, 12, 18 and 24 weeks. Cost effectiveness analysis will incorporate costs related to the intervention to compare overall healthcare costs and QALYs between the treatment arms. We will conduct qualitative interviews after final follow-up on patient and therapist perspectives of the therapy. DISCUSSION: This trial will provide data on the clinical and cost effectiveness of CBT for people with advanced cancer and depression. We shall gain an understanding of the feasibility of delivering care to this group through IAPT. Our findings will provide evidence for policy-makers, commissioners and clinicians in cancer and palliative care, and in the community. TRIAL REGISTRATION: Controlled Trials ISRCTN07622709 , registered 15 July 2011