When Should One Substract Background Fluorescence in Two Color Microarrays?

Two color microarrays are a powerful tool for genomic analysis, but have noise components that make inferences regarding gene expression inefficient and potentially misleading. Background fluorescence,whether attributable to non-specific binding or other sources,is an important component of noise. The decision to subtract fluorescence surrounding spots of hybridization from spot fluorescence has been controversial, with no clear criteria for determining circumstances that may favor, or disfavor, background subtraction. While it is generally accepted that subtracting background reduces bias but increases variance in the estimates of the ratios of interest, no formal analysis of the bias-variance trade off of background subtraction has been undertaken. In this paper, we use simulation to systematically examine the bias-variance trade off under a variety of possible experimental conditions. Our simulation is based on data obtained from two self versus self microarray experiments and is free of distributional assumptions. Our results identify factors that are important for determining whether to background subtract, including the correlation of foreground to background intensity ratios. Using these results we develop recommendations for diagnostic visualizations that can help decisions about background subtraction

The influence of mitochondrial dynamics and function on retinal ganglion cell susceptibility in optic nerve disease

The important roles of mitochondrial function and dysfunction in the process of neurodegeneration are widely acknowledged. Retinal ganglion cells (RGCs) appear to be a highly vulnerable neuronal cell type in the central nervous system with respect to mitochondrial dysfunction but the actual reasons for this are still incompletely understood. These cells have a unique circumstance where unmyelinated axons must bend nearly 90° to exit the eye and then cross a translaminar pressure gradient before becoming myelinated in the optic nerve. This region, the optic nerve head, contains some of the highest density of mitochondria present in these cells. Glaucoma represents a perfect storm of events occurring at this location, with a combination of changes in the translaminar pressure gradient and reassignment of the metabolic support functions of supporting glia, which appears to apply increased metabolic stress to the RGC axons leading to a failure of axonal transport mechanisms. However, RGCs themselves are also extremely sensitive to genetic mutations, particularly in genes affecting mitochondrial dynamics and mitochondrial clearance. These mutations, which systemically affect the mitochondria in every cell, often lead to an optic neuropathy as the sole pathologic defect in affected patients. This review summarizes knowledge of mitochondrial structure and function, the known energy demands of neurons in general, and places these in the context of normal and pathological characteristics of mitochondria attributed to RGCs

Alfvén wave far field from steady-current tethers

We analyzed he Alfvén waves ignaturele ft behindi n the ionospherbe y orbiting insulatedt etherso peratinga s thrusterso r generatorws ith steadyc urrentsU. sing a recentd escription of tetherr adiationt o determineth e far field, we showt hat, at their leadinge dges,t heA lfv6n wingsh avea n Airy functionc rosswises tructureT. he field amplitudef alls off weakly as the inversec uber oot of the distancea longt he wavef ront.T he fronti tself, whichc arriesa negligible fractiono f the powerr adiateda sA lfven waves,b roadensp roportionallyto the cuber oot of that distanceW. e showt hatc ollisionadl ecayb ecomesim portanat t about1 03k m alongt he front.F or tethersl ongert han about2 km, the top andb ottoms tructures("wings")a re fully disjoint

Cross-platform Comparison of Two Pancreatic Cancer Phenotypes

Model-based approaches for combining gene expression data from multiple high throughput platforms can be sensitive to technological artifacts when the number of samples in each platform is small. This paper proposes simple tools for quantifying concordance in a small study of pancreatic cancer cells lines with an emphasis on visualizations that uncover intra- and inter-platform variation. Using this approach, we identify several transcripts from the integrative analysis whose over-or under-expression in pancreatic cancer cell lines was validated by qPCR

CAPG is required for Ebola virus infection by controlling virus egress from infected cells

The replication of Ebola virus (EBOV) is dependent upon actin functionality, especially at cell entry through macropinocytosis and at release of virus from cells. Previously, major actin-regulatory factors involved in actin nucleation, such as Rac1 and Arp2/3, were shown important in both steps. However, downstream of nucleation, many other cell factors are needed to control actin dynamics. How these regulate EBOV infection remains largely unclear. Here, we identified the actin-regulating protein, CAPG, as important for EBOV replication. Notably, knockdown of CAPG specifically inhibited viral infectivity and yield of infectious particles. Cell-based mechanistic analysis revealed a requirement of CAPG for virus production from infected cells. Proximity ligation and split-green fluorescent protein reconstitution assays revealed strong association of CAPG with VP40 that was mediated through the S1 domain of CAPG. Overall, CAPG is a novel host factor regulating EBOV infection through connecting actin filament stabilization to viral egress from cells

Extratropical storm inundation testbed : intermodel comparisons in Scituate, Massachusetts

Author Posting. © American Geophysical Union, 2013. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research: Oceans 118 (2013): 5054–5073, doi:10.1002/jgrc.20397.The Integrated Ocean Observing System Super-regional Coastal Modeling Testbed had one objective to evaluate the capabilities of three unstructured-grid fully current-wave coupled ocean models (ADCIRC/SWAN, FVCOM/SWAVE, SELFE/WWM) to simulate extratropical storm-induced inundation in the US northeast coastal region. Scituate Harbor (MA) was chosen as the extratropical storm testbed site, and model simulations were made for the 24–27 May 2005 and 17–20 April 2007 (“Patriot's Day Storm”) nor'easters. For the same unstructured mesh, meteorological forcing, and initial/boundary conditions, intermodel comparisons were made for tidal elevation, surface waves, sea surface elevation, coastal inundation, currents, and volume transport. All three models showed similar accuracy in tidal simulation and consistency in dynamic responses to storm winds in experiments conducted without and with wave-current interaction. The three models also showed that wave-current interaction could (1) change the current direction from the along-shelf direction to the onshore direction over the northern shelf, enlarging the onshore water transport and (2) intensify an anticyclonic eddy in the harbor entrance and a cyclonic eddy in the harbor interior, which could increase the water transport toward the northern peninsula and the southern end and thus enhance flooding in those areas. The testbed intermodel comparisons suggest that major differences in the performance of the three models were caused primarily by (1) the inclusion of wave-current interaction, due to the different discrete algorithms used to solve the three wave models and compute water-current interaction, (2) the criterions used for the wet-dry point treatment of the flooding/drying process simulation, and (3) bottom friction parameterizations.This project was supported by NOAA via the U.S.IOOS Office (award: NA10NOS0120063 and NA11NOS0120141) and was managed by the Southeastern Universities Research Association. The Scituate FVCOM setup was supported by the NOAA-funded IOOS NERACOOS program for NECOFS and the MIT Sea Grant College Program through grant 2012-R/RC-127.2014-04-0

On passion and moral behavior in achievement settings: The mediating role of pride

The Dualistic Model of Passion (Vallerand et al., 2003) distinguishes two types of passion: harmonious passion (HP) and obsessive passion (OP) that predict adaptive and less adaptive outcomes, respectively. In the present research, we were interested in understanding the role of passion in the adoption of moral behavior in achievement settings. It was predicted that the two facets of pride (authentic and hubristic; Tracy & Robins, 2007) would mediate the passion-moral behavior relationship. Specifically, because people who are passionate about a given activity are highly involved in it, it was postulated that they should typically do well and thus experience high levels of pride when engaged in the activity. However, it was also hypothesized that while both types of passion should be conducive to authentic pride, only OP should lead to hubristic pride. Finally, in line with past research on pride (Carver, Sinclair, & Johnson, 2010; Tracy et al., 2009), only hubristic pride was expected to negatively predict moral behavior, while authentic pride was expected to positively predict moral behavior. Results of two studies conducted with paintball players (N=163, Study 1) and athletes (N=296, Study 2) supported the proposed model. Future research directions are discussed in light of the Dualistic Model of Passion