The Chemical Space of Flavours

The flavour of foods is determined by the interaction of taste molecules with receptors in the mouth, and fragrances or aroma with receptors in the upper part of the nose. Here, we discuss the properties of taste and fragrance molecules, from the public databases Superscent, Flavornet, SuperSweet and BitterDB, taken collectively as flavours, in the perspective of the chemical space. We survey simple descriptor profiles in comparison with the public collections ChEMBL (bioactive small molecules), ZINC (commercial drug-like molecules) and GDB-13 (all possible organic molecules up to 13 atoms of C, N, O, S, Cl). A global analysis of the chemical space of flavours is also presented based on molecular quantum numbers (MQN) and SMILES fingerprints (SMIfp). While taste molecules span a very broad property range, fragrances occupy a narrow area of the chemical space consisting of generally very small and relatively nonpolar molecules distinct of standard drug molecules. Proximity searching in the chemical space is exemplified as a simple method to facilitate the search for new fragrances.

CHEOPS: a space telescope for ultra-high precision photometry of exoplanet transits

The CHaracterising ExOPlanet Satellite (CHEOPS) is a joint ESA-Switzerland space mission (expected to launch in 2017) dedicated to search for exoplanet transits by means of ultra-high precision photometry. CHEOPS will provide accurate radii for planets down to Earth size. Targets will mainly come from radial velocity surveys. The CHEOPS instrument is an optical space telescope of 30 cm clear aperture with a single focal plane CCD detector. The tube assembly is passively cooled and thermally controlled to support high precision, low noise photometry. The telescope feeds a re-imaging optic, which supports the straylight suppression concept to achieve the required Signal to Noise. © (2014) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.

Search for neutral Higgs bosons of the minimal supersymmetric standard model in pp collisions at sqrts = 8 TeV with the ATLAS detector

A search for the neutral Higgs bosons predicted by the Minimal Supersymmetric Standard Model (MSSM) is reported. The analysis is performed on data from proton-proton collisions at a centre-of-mass energy of 8 TeV collected with the ATLAS detector at the Large Hadron Collider. The samples used for this search were collected in 2012 and correspond to integrated luminosities in the range 19.5-20.3 fb−1. The MSSM Higgs bosons are searched for in the τ τ final state. No significant excess over the expected background is observed, and exclusion limits are derived for the production cross section times branching fraction of a scalar particle as a function of its mass. The results are also interpreted in the MSSM parameter space for various benchmark scenarios.

Search for pair-produced third-generation squarks decaying via charm quarks or in compressed supersymmetric scenarios in pp collisions at √s=8 TeV with the ATLAS detector

Results of a search for supersymmetry via direct production of third-generation squarks are reported, using 20.3  fb −1 of proton-proton collision data at √s =8  TeV recorded by the ATLAS experiment at the LHC in 2012. Two different analysis strategies based on monojetlike and c -tagged event selections are carried out to optimize the sensitivity for direct top squark-pair production in the decay channel to a charm quark and the lightest neutralino (t 1 →c+χ ˜ 0 1 ) across the top squark–neutralino mass parameter space. No excess above the Standard Model background expectation is observed. The results are interpreted in the context of direct pair production of top squarks and presented in terms of exclusion limits in the m ˜t 1, m ˜ X0 1 ) parameter space. A top squark of mass up to about 240 GeV is excluded at 95% confidence level for arbitrary neutralino masses, within the kinematic boundaries. Top squark masses up to 270 GeV are excluded for a neutralino mass of 200 GeV. In a scenario where the top squark and the lightest neutralino are nearly degenerate in mass, top squark masses up to 260 GeV are excluded. The results from the monojetlike analysis are also interpreted in terms of compressed scenarios for top squark-pair production in the decay channel t ˜ 1 →b+ff ′ +χ ˜ 0 1 and sbottom pair production with b ˜ 1 →b+χ ˜ 0 1 , leading to a similar exclusion for nearly mass-degenerate third-generation squarks and the lightest neutralino. The results in this paper significantly extend previous results at colliders.

Search for squarks and gluinos with the ATLAS detector in final states with jets and missing transverse momentum using √s=8 TeV proton--proton collision data

A search for squarks and gluinos in final states containing high-pT jets, missing transverse momentum and no electrons or muons is presented. The data were recorded in 2012 by the ATLAS experiment in √s = 8TeV proton-proton collisions at the Large Hadron Collider, with a total integrated luminosity of 20.3 fb−1. Results are interpreted in a variety of simplified and specific supersymmetry-breaking models assuming that R-parity is conserved and that the lightest neutralino is the lightest supersymmetric particle. An exclusion limit at the 95% confidence level on the mass of the gluino is set at 1330GeV for a simplified model incorporating only a gluino and the lightest neutralino. For a simplified model involving the strong production of first- and second-generation squarks, squark masses below 850GeV (440GeV) are excluded for a massless lightest neutralino, assuming mass degenerate (single light-flavour) squarks. In mSUGRA/CMSSM models with tan β = 30, A0 = −2m0 and μ > 0, squarks and gluinos of equal mass are excluded for masses below 1700GeV. Additional limits are set for non-universal Higgs mass models with gaugino mediation and for simplified models involving the pair production of gluinos, each decaying to a top squark and a top quark, with the top squark decaying to a charm quark and a neutralino. These limits extend the region of supersymmetric parameter space excluded by previous searches with the ATLAS detector.

Intra-articular corticosteroid for knee osteoarthritis.

BACKGROUND Knee osteoarthritis is a leading cause of chronic pain, disability, and decreased quality of life. Despite the long-standing use of intra-articular corticosteroids, there is an ongoing debate about their benefits and safety. This is an update of a Cochrane review first published in 2005. OBJECTIVES To determine the benefits and harms of intra-articular corticosteroids compared with sham or no intervention in people with knee osteoarthritis in terms of pain, physical function, quality of life, and safety. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE (from inception to 3 February 2015), checked trial registers, conference proceedings, reference lists, and contacted authors. SELECTION CRITERIA We included randomised or quasi-randomised controlled trials that compared intra-articular corticosteroids with sham injection or no treatment in people with knee osteoarthritis. We applied no language restrictions. DATA COLLECTION AND ANALYSIS We calculated standardised mean differences (SMDs) and 95% confidence intervals (CI) for pain, function, quality of life, joint space narrowing, and risk ratios (RRs) for safety outcomes. We combined trials using an inverse-variance random-effects meta-analysis. MAIN RESULTS We identified 27 trials (13 new studies) with 1767 participants in this update. We graded the quality of the evidence as 'low' for all outcomes because treatment effect estimates were inconsistent with great variation across trials, pooled estimates were imprecise and did not rule out relevant or irrelevant clinical effects, and because most trials had a high or unclear risk of bias. Intra-articular corticosteroids appeared to be more beneficial in pain reduction than control interventions (SMD -0.40, 95% CI -0.58 to -0.22), which corresponds to a difference in pain scores of 1.0 cm on a 10-cm visual analogue scale between corticosteroids and sham injection and translates into a number needed to treat for an additional beneficial outcome (NNTB) of 8 (95% CI 6 to 13). An I(2) statistic of 68% indicated considerable between-trial heterogeneity. A visual inspection of the funnel plot suggested some asymmetry (asymmetry coefficient -1.21, 95%CI -3.58 to 1.17). When stratifying results according to length of follow-up, benefits were moderate at 1 to 2 weeks after end of treatment (SMD -0.48, 95% CI -0.70 to -0.27), small to moderate at 4 to 6 weeks (SMD -0.41, 95% CI -0.61 to -0.21), small at 13 weeks (SMD -0.22, 95% CI -0.44 to 0.00), and no evidence of an effect at 26 weeks (SMD -0.07, 95% CI -0.25 to 0.11). An I(2) statistic of ≥ 63% indicated a moderate to large degree of between-trial heterogeneity up to 13 weeks after end of treatment (P for heterogeneity≤0.001), and an I(2) of 0% indicated low heterogeneity at 26 weeks (P=0.43). There was evidence of lower treatment effects in trials that randomised on average at least 50 participants per group (P=0.05) or at least 100 participants per group (P=0.013), in trials that used concomittant viscosupplementation (P=0.08), and in trials that used concomitant joint lavage (P≤0.001).Corticosteroids appeared to be more effective in function improvement than control interventions (SMD -0.33, 95% CI -0.56 to -0.09), which corresponds to a difference in functions scores of -0.7 units on standardised Western Ontario and McMaster Universities Arthritis Index (WOMAC) disability scale ranging from 0 to 10 and translates into a NNTB of 10 (95% CI 7 to 33). An I(2) statistic of 69% indicated a moderate to large degree of between-trial heterogeneity. A visual inspection of the funnel plot suggested asymmetry (asymmetry coefficient -4.07, 95% CI -8.08 to -0.05). When stratifying results according to length of follow-up, benefits were small to moderate at 1 to 2 weeks after end of treatment (SMD -0.43, 95% CI -0.72 to -0.14), small to moderate at 4 to 6 weeks (SMD -0.36, 95% CI -0.63 to -0.09), and no evidence of an effect at 13 weeks (SMD -0.13, 95% CI -0.37 to 0.10) or at 26 weeks (SMD 0.06, 95% CI -0.16 to 0.28). An I(2) statistic of ≥ 62% indicated a moderate to large degree of between-trial heterogeneity up to 13 weeks after end of treatment (P for heterogeneity≤0.004), and an I(2) of 0% indicated low heterogeneity at 26 weeks (P=0.52). We found evidence of lower treatment effects in trials that randomised on average at least 50 participants per group (P=0.023), in unpublished trials (P=0.023), in trials that used non-intervention controls (P=0.031), and in trials that used concomitant viscosupplementation (P=0.06).Participants on corticosteroids were 11% less likely to experience adverse events, but confidence intervals included the null effect (RR 0.89, 95% CI 0.64 to 1.23, I(2)=0%). Participants on corticosteroids were 67% less likely to withdraw because of adverse events, but confidence intervals were wide and included the null effect (RR 0.33, 95% CI 0.05 to 2.07, I(2)=0%). Participants on corticosteroids were 27% less likely to experience any serious adverse event, but confidence intervals were wide and included the null effect (RR 0.63, 95% CI 0.15 to 2.67, I(2)=0%).We found no evidence of an effect of corticosteroids on quality of life compared to control (SMD -0.01, 95% CI -0.30 to 0.28, I(2)=0%). There was also no evidence of an effect of corticosteroids on joint space narrowing compared to control interventions (SMD -0.02, 95% CI -0.49 to 0.46). AUTHORS' CONCLUSIONS Whether there are clinically important benefits of intra-articular corticosteroids after one to six weeks remains unclear in view of the overall quality of the evidence, considerable heterogeneity between trials, and evidence of small-study effects. A single trial included in this review described adequate measures to minimise biases and did not find any benefit of intra-articular corticosteroids.In this update of the systematic review and meta-analysis, we found most of the identified trials that compared intra-articular corticosteroids with sham or non-intervention control small and hampered by low methodological quality. An analysis of multiple time points suggested that effects decrease over time, and our analysis provided no evidence that an effect remains six months after a corticosteroid injection.

Optical Light Curve Observations to Determine Attitude States of Space Debris

The currently proposed space debris remediation measures include the active removal of large objects and “just in time” collision avoidance by deviating the objects using, e.g., ground-based lasers. Both techniques require precise knowledge of the attitude state and state changes of the target objects. In the former case, to devise methods to grapple the target by a tug spacecraft, in the latter, to precisely propagate the orbits of potential collision partners as disturbing forces like air drag and solar radiation pressure depend on the attitude of the objects. Non-resolving optical observations of the magnitude variations, so-called light curves, are a promising technique to determine rotation or tumbling rates and the orientations of the actual rotation axis of objects, as well as their temporal changes. The 1-meter telescope ZIMLAT of the Astronomical Institute of the University of Bern has been used to collect light curves of MEO and GEO objects for a considerable period of time. Recently, light curves of Low Earth Orbit (LEO) targets were acquired as well. We present different observation methods, including active tracking using a CCD subframe readout technique, and the use of a high-speed scientific CMOS camera. Technical challenges when tracking objects with poor orbit redictions, as well as different data reduction methods are addressed. Results from a survey of abandoned rocket upper stages in LEO, examples of abandoned payloads and observations of high area-to-mass ratio debris will be resented. Eventually, first results of the analysis of these light curves are provided.

PDB-Explorer: a web-based interactive map of the protein data bank in shape space

Background The RCSB Protein Data Bank (PDB) provides public access to experimentally determined 3D-structures of biological macromolecules (proteins, peptides and nucleic acids). While various tools are available to explore the PDB, options to access the global structural diversity of the entire PDB and to perceive relationships between PDB structures remain very limited. Methods A 136-dimensional atom pair 3D-fingerprint for proteins (3DP) counting categorized atom pairs at increasing through-space distances was designed to represent the molecular shape of PDB-entries. Nearest neighbor searches examples were reported exemplifying the ability of 3DP-similarity to identify closely related biomolecules from small peptides to enzyme and large multiprotein complexes such as virus particles. The principle component analysis was used to obtain the visualization of PDB in 3DP-space. Results The 3DP property space groups proteins and protein assemblies according to their 3D-shape similarity, yet shows exquisite ability to distinguish between closely related structures. An interactive website called PDB-Explorer is presented featuring a color-coded interactive map of PDB in 3DP-space. Each pixel of the map contains one or more PDB-entries which are directly visualized as ribbon diagrams when the pixel is selected. The PDB-Explorer website allows performing 3DP-nearest neighbor searches of any PDB-entry or of any structure uploaded as protein-type PDB file. All functionalities on the website are implemented in JavaScript in a platform-independent manner and draw data from a server that is updated daily with the latest PDB additions, ensuring complete and up-to-date coverage. The essentially instantaneous 3DP-similarity search with the PDB-Explorer provides results comparable to those of much slower 3D-alignment algorithms, and automatically clusters proteins from the same superfamilies in tight groups. Conclusion A chemical space classification of PDB based on molecular shape was obtained using a new atom-pair 3D-fingerprint for proteins and implemented in a web-based database exploration tool comprising an interactive color-coded map of the PDB chemical space and a nearest neighbor search tool. The PDB-Explorer website is freely available at www.​cheminfo.​org/​pdbexplorer and represents an unprecedented opportunity to interactively visualize and explore the structural diversity of the PDB.

Denoising Your Monte Carlo Renders: Recent Advances in Image Space-Adaptive Sampling and Reconstruction

With the ongoing shift in the computer graphics industry toward Monte Carlo rendering, there is a need for effective, practical noise-reduction techniques that are applicable to a wide range of rendering effects and easily integrated into existing production pipelines. This course surveys recent advances in image-space adaptive sampling and reconstruction algorithms for noise reduction, which have proven very effective at reducing the computational cost of Monte Carlo techniques in practice. These approaches leverage advanced image-filtering techniques with statistical methods for error estimation. They are attractive because they can be integrated easily into conventional Monte Carlo rendering frameworks, they are applicable to most rendering effects, and their computational overhead is modest.

Search for satellites near comet 67P/Churyumov-Gerasimenko using Rosetta/OSIRIS images

Context. The European Space Agency Rosetta mission reached and started escorting its main target, the Jupiter-family comet 67P/Churyumov-Gerasimenko, at the beginning of August 2014. Within the context of solar system small bodies, satellite searches from approaching spacecraft were extensively used in the past to study the nature of the visited bodies and their collisional environment. Aims. During the approaching phase to the comet in July 2014, the OSIRIS instrument onboard Rosetta performed a campaign aimed at detecting objects in the vicinity of the comet nucleus and at measuring these objects' possible bound orbits. In addition to the scientific purpose, the search also focused on spacecraft security to avoid hazardous material in the comet's environment. Methods. Images in the red spectral domain were acquired with the OSIRIS Narrow Angle Camera, when the spacecraft was at a distance between 5785 km and 5463 km to the comet, following an observational strategy tailored to maximize the scientific outcome. From the acquired images, sources were extracted and displayed to search for plausible displacements of all sources from image to image. After stars were identified, the remaining sources were thoroughly analyzed. To place constraints on the expected displacements of a potential satellite, we performed Monte Carlo simulations on the apparent motion of potential satellites within the Hill sphere. Results. We found no unambiguous detections of objects larger than similar to 6 m within similar to 20 km and larger than similar to 1 m between similar to 20 km and similar to 110 km from the nucleus, using images with an exposure time of 0.14 s and 1.36 s, respectively. Our conclusions are consistent with independent works on dust grains in the comet coma and on boulders counting on the nucleus surface. Moreover, our analysis shows that the comet outburst detected at the end of April 2014 was not strong enough to eject large objects and to place them into a stable orbit around the nucleus. Our findings underline that it is highly unlikely that large objects survive for a long time around cometary nuclei.