A statistical framework for testing functional categories in microarray data

Ready access to emerging databases of gene annotation and functional pathways has shifted assessments of differential expression in DNA microarray studies from single genes to groups of genes with shared biological function. This paper takes a critical look at existing methods for assessing the differential expression of a group of genes (functional category), and provides some suggestions for improved performance. We begin by presenting a general framework, in which the set of genes in a functional category is compared to the complementary set of genes on the array. The framework includes tests for overrepresentation of a category within a list of significant genes, and methods that consider continuous measures of differential expression. Existing tests are divided into two classes. Class 1 tests assume gene-specific measures of differential expression are independent, despite overwhelming evidence of positive correlation. Analytic and simulated results are presented that demonstrate Class 1 tests are strongly anti-conservative in practice. Class 2 tests account for gene correlation, typically through array permutation that by construction has proper Type I error control for the induced null. However, both Class 1 and Class 2 tests use a null hypothesis that all genes have the same degree of differential expression. We introduce a more sensible and general (Class 3) null under which the profile of differential expression is the same within the category and complement. Under this broader null, Class 2 tests are shown to be conservative. We propose standard bootstrap methods for testing against the Class 3 null and demonstrate they provide valid Type I error control and more power than array permutation in simulated datasets and real microarray experiments.Comment: Published in at http://dx.doi.org/10.1214/07-AOAS146 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Within, without, and amidst: A review of literacy educators’ perceptions of participatory media technologies

With strict no-cell phone policies in classrooms becoming commonplace, national and international electioneering campaigns eroding trust in social media platforms, and content posted years prior affecting students’ acceptance into the colleges of their choice, it is little wonder that educators often think twice about bringing participatory technologies into their instruction. This literature review seeks to address how literacy educators reckon with the risks and potentials of these participatory technologies in the midst of our current sociopolitical climate, through an examination of an array of factors and influences that shape and give rise to educators’ understandings of participatory technologies’ place in 21st-century education. The hope is that doing so will help delineate a clearer problem space for future investigation into the relationships between teacher perceptions, participatory technologies, and educational transformation

Student Scheduling

[First Paragraph] Developing the master schedule and subsequent student schedules is one of the most important administrative tasks of the principal. Ensuring that appropriate courses are offered and that teachers are teaching courses they want to teach can go a long way toward creating a positive climate and an atmosphere where learning occurs. There are three ways in which student schedules can be developed: Computer, arena, and manual. Each approach has its own strengths and weaknesses. Principals must decide which approach is best for the school based on philosophy and available resources

The Role of Dislodgement in the Territorial Ecology of the Owl Limpet, \u3cem\u3eLottia gigantea\u3c/em\u3e

Ascertaining the risks and benefits of different behaviors is a central goal of research on territoriality. Although most territorial behavior is ritualized, with concomitant reduced risks for both residents and intruders, this ritualization is generally found to be underpinned by rare, highly consequential, interactions. The agonistic behavior of the intertidal owl limpet, Lottia gigantea, involves defense of a feeding territory, and includes a relatively explosive thrusting response by territory holders against intruding conspecifics. We here ask whether this thrusting behavior is capable of entirely dislodging intruders from their rocky wave-swept substratum, thereby ridding the resident of future challenges by that intruder. Our field measurements of the strength of territorial thrusts, as well as thrust resistance, indicate that territorial limpets are strong enough to overcome the resistance of small to medium sized (\u3c40 mm) conspecifics encountered on their territories. Interestingly, at least 44% of the limpets dislodged from the rock substratum during a retreat or territorial response survived in a new location. Growth of these survivors was at least as rapid as that of undisturbed limpets in the old location. We conclude that shell thrusting during the territorial response of Lottia gigantea can reduce the cost of territorial defense by dislodging smaller conspecifics, thereby eliminating them from all future interactions. Conversely, the risk incurred by these smaller conspecifics while intruding onto territories of larger individuals is likely mitigated by the surprisingly high survival rate, and subsequent normal growth, of dislodged limpets

Future of Master’s Level Education in Information Systems Panel Presentation

Panels concerning Information System (IS) education issues and curriculum recommendations are part of a rich tradition and they have been well attended at past AIS conferences. This panel hopes to continue build on this foundation by focusing on master’s level programs and curricula in IS. Specifically, this panel will: 1) give the members of the audience an opportunity to review state-of-the-art practices in and innovative ideas related to master’s level education in IS, 2) start to engage the IS community in the process of revising the graduate level model curriculum and 3) present a number of alternative approaches to master’s level graduate programs in IS and to stimulate a discussion that will encourage the audience to consider different options for their programs

Spinal motor neurite outgrowth over glial scar inhibitors is enhanced by coculture with bone marrow stromal cells

Background context Transplantation of bone marrow cells into spinal cord lesions promotes functional recovery in animal models, and recent clinical trials suggest possible recovery also in humans. The mechanisms responsible for these improvements are still unclear. Purpose To characterize spinal cord motor neurite interactions with human bone marrow stromal cells (MSCs) in an in vitro model of spinal cord injury (SCI). Study design/setting Previously, we have reported that human MSCs promote the growth of extending sensory neurites from dorsal root ganglia (DRG), in the presence of some of the molecules present in the glial scar, which are attributed with inhibiting axonal regeneration after SCI. We have adapted and optimized this system replacing the DRG with a spinal cord culture to produce a central nervous system (CNS) model, which is more relevant to the SCI situation. Methods We have developed and characterized a novel spinal cord culture system. Human MSCs were cocultured with spinal motor neurites in substrate choice assays containing glial scar-associated inhibitors of nerve growth. In separate experiments, MSC-conditioned media were analyzed and added to spinal motor neurites in substrate choice assays. Results As has been reported previously with DRG, substrate-bound neurocan and Nogo-A repelled spinal neuronal adhesion and neurite outgrowth, but these inhibitory effects were abrogated in MSC/spinal cord cocultures. However, unlike DRG, spinal neuronal bodies and neurites showed no inhibition to substrates of myelin-associated glycoprotein. In addition, the MSC secretome contained numerous neurotrophic factors that stimulated spinal neurite outgrowth, but these were not sufficient stimuli to promote spinal neurite extension over inhibitory concentrations of neurocan or Nogo-A. Conclusions These findings provide novel insight into how MSC transplantation may promote regeneration and functional recovery in animal models of SCI and in the clinic, especially in the chronic situation in which glial scars (and associated neural inhibitors) are well established. In addition, we have confirmed that this CNS model predominantly comprises motor neurons via immunocytochemical characterization. We hope that this model may be used in future research to test various other potential interventions for spinal injury or disease states

The California Planet Survey. I. Four New Giant Exoplanets

We present precise Doppler measurements of four stars obtained during the past decade at Keck Observatory by the California Planet Survey (CPS). These stars, namely, HD 34445, HD 126614, HD 13931, and Gl 179, all show evidence for a single planet in Keplerian motion. We also present Doppler measurements from the Hobby-Eberly Telescope (HET) for two of the stars, HD 34445 and Gl 179, that confirm the Keck detections and significantly refine the orbital parameters. These planets add to the statistical properties of giant planets orbiting near or beyond the ice line, and merit follow-up by astrometry, imaging, and space-borne spectroscopy. Their orbital parameters span wide ranges of planetary minimum mass (M sin i = 0.38-1.9 M(Jup)), orbital period (P = 2.87-11.5 yr), semimajor axis (a = 2.1-5.2 AU), and eccentricity (e = 0.02-0.41). HD 34445 b (P = 2.87 yr, M sin i = 0.79 MJup, e = 0.27) is a massive planet orbiting an old, G-type star. We announce a planet, HD 126614 Ab, and an M dwarf, HD 126614 B, orbiting the metal-rich star HD 126614 (which we now refer to as HD 126614 A). The planet, HD 126614 Ab, has minimum mass M sin i = 0.38 MJup and orbits the stellar primary with period P = 3.41 yr and orbital separation a = 2.3 AU. The faint M dwarf companion, HD 126614 B, is separated from the stellar primary by 489 mas (33 AU) and was discovered with direct observations using adaptive optics and the PHARO camera at Palomar Observatory. The stellar primary in this new system, HD 126614 A, has the highest measured metallicity ([ Fe/ H] = + 0.56) of any known planet-bearing star. HD 13931 b (P = 11.5 yr, M sin i = 1.88 MJup, e = 0.02) is a Jupiter analog orbiting a near solar twin. Gl 179 b (P = 6.3 yr, M sin i = 0.82 M(Jup), e = 0.21) is a massive planet orbiting a faint M dwarf. The high metallicity of Gl 179 is consistent with the planet-metallicity correlation among M dwarfs, as documented recently by Johnson & Apps.NSF AST-0702821NASA NNX06AH52GMcDonald Observator

A platform for the discovery of new macrolide antibiotics.

The chemical modification of structurally complex fermentation products, a process known as semisynthesis, has been an important tool in the discovery and manufacture of antibiotics for the treatment of various infectious diseases. However, many of the therapeutics obtained in this way are no longer effective, because bacterial resistance to these compounds has developed. Here we present a practical, fully synthetic route to macrolide antibiotics by the convergent assembly of simple chemical building blocks, enabling the synthesis of diverse structures not accessible by traditional semisynthetic approaches. More than 300 new macrolide antibiotic candidates, as well as the clinical candidate solithromycin, have been synthesized using our convergent approach. Evaluation of these compounds against a panel of pathogenic bacteria revealed that the majority of these structures had antibiotic activity, some efficacious against strains resistant to macrolides in current use. The chemistry we describe here provides a platform for the discovery of new macrolide antibiotics and may also serve as the basis for their manufacture

Morgellons disease, illuminating an undefined illness: a case series

<p>Abstract</p> <p>Introduction</p> <p>This review of 25 consecutive patients with Morgellons disease (MD) was undertaken for two primary and extremely fundamental reasons. For semantic accuracy, there is only one "proven" MD patient: the child first given that label. The remainder of inclusive individuals adopted the label based on related descriptions from 1544 through 1884, an internet description quoted from Sir Thomas Browne (1674), or was given the label by practitioners using similar sources. Until now, there has been no formal characterization of MD from detailed examination of all body systems. Our second purpose was to differentiate MD from Delusions of Parasitosis (DP), another "informal" label that fit most of our MD patients. How we defined and how we treated these patients depended literally on factual data that would determine outcome. How they were labeled in one sense was irrelevant, except for the confusing conflict rampant in the medical community, possibly significantly skewing treatment outcomes.</p> <p>Case presentation</p> <p>Clinical information was collected from 25 of 30 consecutive self-defined patients with Morgellons disease consisting of laboratory data, medical history and physical examination findings. Abnormalities were quantified and grouped by system, then compared and summarized, but the numbers were too small for more complex mathematical analysis. The quantification of physical and laboratory abnormalities allowed at least the creation of a practical clinical boundary, separating probable Morgellon<it>s</it> from non-Morgellons patients. All the 25 patients studied meet the most commonly used DP definitions.</p> <p>Conclusions</p> <p>These data suggest Morgellons disease can be characterized as a physical human illness with an often-related delusional component in adults. All medical histories support that behavioral aberrancies onset only after physical symptoms. The identified abnormalities include both immune deficiency and chronic inflammatory markers that correlate strongly with immune cytokine excess. The review of 251 current NLM DP references leads us to the possibility that Morgellons disease and DP are grossly truncated labels of the same illness but with the reversal of the cause-effect order. Further, the patients' data suggest that both illnesses have an infectious origin.</p

Empirical pathway analysis, without permutation

Resampling-based expression pathway analysis techniques have been shown to preserve type I error rates, in contrast to simple gene-list approaches that implicitly assume the independence of genes in ranked lists. However, resampling is intensive in computation time and memory requirements. We describe accurate analytic approximations to permutations of score statistics, including novel approaches for Pearson's correlation, and summed score statistics, that have good performance for even relatively small sample sizes. Our approach preserves the essence of permutation pathway analysis, but with greatly reduced computation. Extensions for inclusion of covariates and censored data are described, and we test the performance of our procedures using simulations based on real datasets. These approaches have been implemented in the new R package safeExpress