PubChem3D: Similar conformers

<p>Abstract</p> <p>Background</p> <p>PubChem is a free and open public resource for the biological activities of small molecules. With many tens of millions of both chemical structures and biological test results, PubChem is a sizeable system with an uneven degree of available information. Some chemical structures in PubChem include a great deal of biological annotation, while others have little to none. To help users, PubChem pre-computes "neighboring" relationships to relate similar chemical structures, which may have similar biological function. In this work, we introduce a "Similar Conformers" neighboring relationship to identify compounds with similar 3-D shape and similar 3-D orientation of functional groups typically used to define pharmacophore features.</p> <p>Results</p> <p>The first two diverse 3-D conformers of 26.1 million PubChem Compound records were compared to each other, using a shape Tanimoto (ST) of 0.8 or greater and a color Tanimoto (CT) of 0.5 or greater, yielding 8.16 billion conformer neighbor pairs and 6.62 billion compound neighbor pairs, with an average of 253 "Similar Conformers" compound neighbors per compound. Comparing the 3-D neighboring relationship to the corresponding 2-D neighboring relationship ("Similar Compounds") for molecules such as caffeine, aspirin, and morphine, one finds unique sets of related chemical structures, providing additional significant biological annotation. The PubChem 3-D neighboring relationship is also shown to be able to group a set of non-steroidal anti-inflammatory drugs (NSAIDs), despite limited PubChem 2-D similarity.</p> <p>In a study of 4,218 chemical structures of biomedical interest, consisting of many known drugs, using more diverse conformers per compound results in more 3-D compound neighbors per compound; however, the overlap of the compound neighbor lists per conformer also increasingly resemble each other, being 38% identical at three conformers and 68% at ten conformers. Perhaps surprising is that the average count of conformer neighbors per conformer increases rather slowly as a function of diverse conformers considered, with only a 70% increase for a ten times growth in conformers per compound (a 68-fold increase in the conformer pairs considered).</p> <p>Neighboring 3-D conformers on the scale performed, if implemented naively, is an intractable problem using a modest sized compute cluster. Methodology developed in this work relies on a series of filters to prevent performing 3-D superposition optimization, when it can be determined that two conformers cannot possibly be a neighbor. Most filters are based on Tanimoto equation volume constraints, avoiding incompatible conformers; however, others consider preliminary superposition between conformers using reference shapes.</p> <p>Conclusion</p> <p>The "Similar Conformers" 3-D neighboring relationship locates similar small molecules of biological interest that may go unnoticed when using traditional 2-D chemical structure graph-based methods, making it complementary to such methodologies. The computational cost of 3-D similarity methodology on a wide scale, such as PubChem contents, is a considerable issue to overcome. Using a series of efficient filters, an effective throughput rate of more than 150,000 conformers per second per processor core was achieved, more than two orders of magnitude faster than without filtering.</p

The clustering of intermediate redshift quasars as measured by the Baryon Oscillation Spectroscopic Survey

We measure the quasar two-point correlation function over the redshift range 2.2<z<2.8 using data from the Baryon Oscillation Spectroscopic Survey. We use a homogeneous subset of the data consisting of 27,129 quasars with spectroscopic redshifts---by far the largest such sample used for clustering measurements at these redshifts to date. The sample covers 3,600 square degrees, corresponding to a comoving volume of 9.7(Gpc/h)^3 assuming a fiducial LambdaCDM cosmology, and it has a median absolute i-band magnitude of -26, k-corrected to z=2. After accounting for redshift errors we find that the redshift space correlation function is fit well by a power-law of slope -2 and amplitude s_0=(9.7\pm 0.5)Mpc/h over the range 3<s<25Mpc/h. The projected correlation function, which integrates out the effects of peculiar velocities and redshift errors, is fit well by a power-law of slope -1 and r_0=(8.4\pm 0.6)Mpc/h over the range 4<R<16Mpc/h. There is no evidence for strong luminosity or redshift dependence to the clustering amplitude, in part because of the limited dynamic range in our sample. Our results are consistent with, but more precise than, previous measurements at similar redshifts. Our measurement of the quasar clustering amplitude implies a bias factor of b~3.5 for our quasar sample. We compare the data to models to constrain the manner in which quasars occupy dark matter halos at z~2.4 and infer that such quasars inhabit halos with a characteristic mass of ~10^{12}Msun/h with a duty cycle for the quasar activity of 1 per cent.Comment: 20 pages, 18 figures. Minor modifications to match version accepted by journa

Variability selected high-redshift quasars on SDSS Stripe 82

The SDSS-III BOSS Quasar survey will attempt to observe z>2.15 quasars at a density of at least 15 per square degree to yield the first measurement of the Baryon Acoustic Oscillations in the Ly-alpha forest. To help reaching this goal, we have developed a method to identify quasars based on their variability in the u g r i z optical bands. The method has been applied to the selection of quasar targets in the SDSS region known as Stripe 82 (the Southern equatorial stripe), where numerous photometric observations are available over a 10-year baseline. This area was observed by BOSS during September and October 2010. Only 8% of the objects selected via variability are not quasars, while 90% of the previously identified high-redshift quasar population is recovered. The method allows for a significant increase in the z>2.15 quasar density over previous strategies based on optical (ugriz) colors, achieving a density of 24.0 deg^{-2} on average down to g~22 over the 220 deg^2 area of Stripe 82. We applied this method to simulated data from the Palomar Transient Factory and from Pan-STARRS, and showed that even with data that have sparser time sampling than what is available in Stripe 82, including variability in future quasar selection strategies would lead to increased target selection efficiency in the z>2.15 redshift range. We also found that Broad Absorption Line quasars are preferentially present in a variability than in a color selection.Comment: 14 pages, 21 figures, accepted for publication in A&

Impaired decisional impulsivity in pathological videogamers

Abstract Background Pathological gaming is an emerging and poorly understood problem. Impulsivity is commonly impaired in disorders of behavioural and substance addiction, hence we sought to systematically investigate the different subtypes of decisional and motor impulsivity in a well-defined pathological gaming cohort. Methods Fifty-two pathological gaming subjects and age-, gender- and IQ-matched healthy volunteers were tested on decisional impulsivity (Information Sampling Task testing reflection impulsivity and delay discounting questionnaire testing impulsive choice), and motor impulsivity (Stop Signal Task testing motor response inhibition, and the premature responding task). We used stringent diagnostic criteria highlighting functional impairment. Results In the Information Sampling Task, pathological gaming participants sampled less evidence prior to making a decision and scored fewer points compared with healthy volunteers. Gaming severity was also negatively correlated with evidence gathered and positively correlated with sampling error and points acquired. In the delay discounting task, pathological gamers made more impulsive choices, preferring smaller immediate over larger delayed rewards. Pathological gamers made more premature responses related to comorbid nicotine use. Greater number of hours played also correlated with a Motivational Index. Greater frequency of role playing games was associated with impaired motor response inhibition and strategy games with faster Go reaction time. Conclusions We show that pathological gaming is associated with impaired decisional impulsivity with negative consequences in task performance. Decisional impulsivity may be a potential target in therapeutic management

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Rates and risks for prolonged grief disorder in a sample of orphaned and widowed genocide survivors

<p>Abstract</p> <p>Background</p> <p>The concept of Prolonged Grief Disorder (PGD) has been defined in recent years by Prigerson and co-workers, who have developed and empirically tested consensus and diagnostic criteria for PGD. Using these most recent criteria defining PGD, the aim of this study was to determine rates of and risks for PGD in survivors of the 1994 Rwandan genocide who had lost a parent and/or the husband before, during or after the 1994 events.</p> <p>Methods</p> <p>The PG-13 was administered to 206 orphans or half orphans and to 194 widows. A regression analysis was carried out to examine risk factors of PGD.</p> <p>Results</p> <p>8.0% (<it>n </it>= 32) of the sample met criteria for PGD with an average of 12 years post-loss. All but one person had faced multiple losses and the majority indicated that their grief-related loss was due to violent death (70%). Grief was predicted mainly by time since the loss, by the violent nature of the loss, the severity of symptoms of posttraumatic stress disorder (PTSD) and the importance given to religious/spiritual beliefs. By contrast, gender, age at the time of bereavement, bereavement status (widow versus orphan), the number of different types of losses reported and participation in the funeral ceremony did not impact the severity of prolonged grief reactions.</p> <p>Conclusions</p> <p>A significant portion of the interviewed sample continues to experience grief over interpersonal losses and unresolved grief may endure over time if not addressed by clinical intervention. Severity of grief reactions may be associated with a set of distinct risk factors. Subjects who lose someone through violent death seem to be at special risk as they have to deal with the loss experience as such and the traumatic aspects of the loss. Symptoms of PTSD may hinder the completion of the mourning process. Religious beliefs may facilitate the mourning process and help to find meaning in the loss. These aspects need to be considered in the treatment of PGD.</p

A Search for Dark Higgs Bosons

Recent astrophysical and terrestrial experiments have motivated the proposal of a dark sector with GeV-scale gauge boson force carriers and new Higgs bosons. We present a search for a dark Higgs boson using 516 fb-1 of data collected with the BABAR detector. We do not observe a significant signal and we set 90% confidence level upper limits on the product of the Standard Model-dark sector mixing angle and the dark sector coupling constant.Comment: 7 pages, 5 postscript figures, published version with improved plots for b/w printin

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO