Gene set bagging for estimating replicability of gene set analyses

Background: Significance analysis plays a major role in identifying and ranking genes, transcription factor binding sites, DNA methylation regions, and other high-throughput features for association with disease. We propose a new approach, called gene set bagging, for measuring the stability of ranking procedures using predefined gene sets. Gene set bagging involves resampling the original high-throughput data, performing gene-set analysis on the resampled data, and confirming that biological categories replicate. This procedure can be thought of as bootstrapping gene-set analysis and can be used to determine which are the most reproducible gene sets. Results: Here we apply this approach to two common genomics applications: gene expression and DNA methylation. Even with state-of-the-art statistical ranking procedures, significant categories in a gene set enrichment analysis may be unstable when subjected to resampling. Conclusions: We demonstrate that gene lists are not necessarily stable, and therefore additional steps like gene set bagging can improve biological inference of gene set analysis.Comment: 3 Figure

Synthesis of chemotherapeutic agents derived from 2:3-benz-γ-carboline and 2:3:4':3'-quinoquinoline

1. From diethylethoxymethylene malonate and the appropriate aniline, 4-chloroquinoline, 6-methoxy-4-chloroquinoline and L.:6-dichloroquinoline have been prepared. 2. These chloro compounds have been used in the synthesis of 2:3-benz-γ-carboline, 15-methoxy-2:3-benz-γ-carboline and 15- chloro -2:3- benz -ycarboline. The unambiguous synthesis of the former base has cleared up certain discrepancies which existed in the literature. 3. The 2:3-benz-γ-carbolines have been treated with diethylaminoethyl chloride to obtain basic side chain derivatives. In this way, the following have been prepared: 1-diethylaminoethyl- 2:3-benz-γ- carboline . 4-diethylaminoethyl-2:3-benz-γ-isocarboline. 5-methoxy-4-diethylaminoethyl-2:3-benz-γ-isocarboline. 15-chloro-l-diethylaminoethyl-2:3-benz-γ-carboline. 15-chloro-4-diethylaminoethyl-2:3-benz-γ-isocarboline. In addition, 4-methyl-2:3-benz-γ-isocarboline and 15-chloro-4-methyl-2:3-benz-γ-isocarboline were also prepared. 4. The constitution of 1-diethylaminoethyl-2:3:4'-3'0benz-γ-carboline (and by analogy, of the corresponding 15-methoxy- and 15-chloro-compounds) has been established from a study of its methiodides. 5. The synthesis of 2:3:4':3'-quinoquinolo-4-one, 6'-methoxy-2:3:4':3'-quinoquinolo-4-one, 6'-chloro-2:3:4':3'-quinoquinolo-4-one, and of 4-chloro-2:3:4':3'-quinoquinoline, 6'-methoxy-4-chloro-2:3:4':3'-quinoquinoline and 4:6'-dichloro-2:3:4':3'-quinoquinoline from the corresponding 4-anilinoquinoline-3-carboxylic acids, has been described. These compounds are isomeric with the 5-chloropyridoacridines, which they resemble markedly in properties. 6. From the above chloroquinoquinolines, bases have been obtained by condensing them with amines such as ammonia, diethylaminoethylamine and 2-amino-5-diethylaminopentane. The constitution of the products obtained is still uncertain

Preparation for Teaching

As is common practice in all Colleges of Education, our students have to spend thirteen weeks in schools during their three year course, engaged either in observation or on actual teaching practice. We have our students with us in the department for the first two terms before they spend their first month in schools. They have a further nine week practice in term eight - this being the time when we expect them to show, in their teaching, that they have not only a sound philosophy of their own, but are able to interpret this and work with pupils producing thought provoking, design based problems in a variety of materials

Hurting the healers: Stalking and stalking-related behavior perpetrated against counselors.

The increased risk of stalking faced by mental health professionals (MHPs) raises many important questions for practitioners. For instance, what factors place MHPs at greater risk of being stalked, and what perceptions do MHPs have about stalking? The present study investigates these and other understudied questions pertaining to stalking and stalking-related behavior perpetrated toward MHPs in the context of their work, by surveying a sample of 346 registered clinical counselors in British Columbia, Canada. Results indicated that many respondents had experienced individual stalking-related behaviors, and 7% (n = 23) had been stalked by a client. Work-related stalking and stalking-related behavior was perpetrated by clients, coworkers, and the acquaintances of clients. Respondents treating clients for forensic, substance abuse, and sexuality issues as well as for sexual abuse were at greater risk of being victimized. However, respondents treating clients out of their residence were not at greater risk. Less than half (47%) of respondents were aware of their heightened risk of being stalked, and many (50%) endorsed the view that poor clinical skill can increase stalking victimization. The majority of respondents reported that they would call police or terminate therapy in the event that they were being stalked by a client and three-quarters wanted to receive training on stalking. Findings suggest the need and desire for training that raises the awareness and abilities of MHPs to manage stalking behavior, but that also challenges unfounded and potentially harmful beliefs that some MHPs hold about their victimized colleagues

Variations in the spatial distribution of 11 Micron radiation from omicron Ceti

The spatial distribution of 11 micron radiation from omicron Ceti was observed at various phases of its light cycle using a stellar interferometer. Changes were seen which can be attributed to variation in the strength of thermal emission from circumstellar dust relative to the stellar continuum at 11 microns. These changes are shown to be correlated with the changes in luminosity of micron Ceti in such a way that dust grain emission at 11 microns was increased more than the continuum during the period of maximum luminosity. The degree of the change in dust grain emission implies that the maximum dust temperature is in the range of 500 K to 700 K during minimum stellar luminosity

The brightness distribution of IRC +10216 at 11 microns

The brightness distribution of IRC +10216 at a wavelength of 11 microns was measured in detail using a spatial interferometer. This brightness distribution appears to have azimuthal symmetry; an upper limit of 1.1 may be set to the ellipticity at 11 microns if the object has a major axis oriented either along or perpendicular to the major axis of the optical image. The radial distribution shows both compact and extended emission. The extended component, which is due to thermal emission from circumstellar dust, contributes 91% of the total flux and has a 1/e diameter of 0.90 minutes. The tapered shape of this component is consistent with a l/r squared dust density dependence. The compact component is unresolved (less than 0.2 minutes in diameter) and represents emission from the central star seen through the circumstellar envelope