Non-Standard Errors

In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty: Non-standard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for better reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants

Cell-based screening: extracting meaning from complex data.

Unbiased discovery approaches have the potential to uncover neurobiological insights into CNS disease and lead to the development of therapies. Here, we review lessons learned from imaging-based screening approaches and recent advances in these areas, including powerful new computational tools to synthesize complex data into more useful knowledge that can reliably guide future research and development

Significant gene content variation characterizes the genomes of inbred mouse strains

The contribution to genetic diversity of genomic segmental copy number variations (CNVs) is less well understood than that of single-nucleotide polymorphisms (SNPs). While less frequent than SNPs, CNVs have greater potential to affect phenotype. In this study, we have performed the most comprehensive survey to date of CNVs in mice, analyzing the genomes of 42 Mouse Phenome Consortium priority strains. This microarray comparative genomic hybridization (CGH)-based analysis has identified 2094 putative CNVs, with an average of 10 Mb of DNA in 51 CNVs when individual mouse strains were compared to the reference strain C57BL/6J. This amount of variation results in gene content that can differ by hundreds of genes between strains. These genes include members of large families such as the major histocompatibility and pheromone receptor genes, but there are also many singleton genes including genes with expected phenotypic consequences from their deletion or amplification. Using a whole-genome association analysis, we demonstrate that complex multigenic phenotypes, such as food intake, can be associated with specific copy number changes

Detection of functional nicotinic receptors blocked by alpha-bungarotoxin on PC12 cells and dependence of their expression on post-translational events

A major class of nicotinic receptors in the nervous system is one that binds �-bungarotoxin and contains the �7 gene product. PC12 cells, frequently used to study nicotinic receptors, express the �7 gene and have binding sites for the toxin, but previous attempts to elicit currents from the putative receptors have failed. Using whole-cell patch-clamp recording techniques and rapid application of agonist, we find a rapidly desensitizing acetylcholine-induced current in the cells that can be blocked by �-bungarotoxin. The current amplitude varies dramatically among three populations of PC12 cells but correlates well with the number of toxin-binding receptors. In contrast, the current shows no correlation with �7 transcript; cells with high levels of �7 mRNA can be negative for toxin binding and yet have other functional nicotinic receptors. Northern blot analysis and reverse transcription-PCR reveal no defects in �

Thermoelectric Cooled Expansion Cloud Chamber

The University of Missouri-Rolla cloud stimulation chamber is an expansion cloud chamber in which the interior walls are cooled by thermoelectric modules in synchronization with the cooling of the gas by expansion. To achieve the temperature uniformity required for the effective simulation of atomospheric processes the interior surface has been divided into 28 individually controlled areas. The chamber operating range extends from plus 40 degree to minus 40 degree C with cooling rates of up to 6 degree C/min in the upper two-thirds of the range

Evidence that encoded shRNA did not influence HCT-116 clonal cell growth <i>in vivo</i>.

<p>(A) Distribution of the 4,109 unique barcodes retrieved most abundantly from the three xenograft tumors (marked with red vertical lines) across the entire shRNA population distribution in the shRNA library. (B) Detection of a large fraction of the most abundant barcodes from the three xenograft tumors (marked in red) in the shRNA population most toxic to HCT-116 upon Doxycycline induction <i>in vitro</i> for 15 days (measured by a negative Log2 ratio of mean read counts for individual shRNA at Day 15 following Doxycycline to mean read counts at Day 0).</p

Evidence that encoded shRNA are not induced in the absence of Doxycycline <i>in vitro.</i>

<p>(A) A lentiviral library containing 27,500 unique barcodes was used to transduce HCT-116 cells at a MOI of 0.3. After 72 hours, of puromycin selection, cells were continuously passaged for 15 days in the absence of Doxycycline. Day 0 and Day 15 cell aliquots were obtained and total DNA from both time points were subjected to the barcode high-throughput sequencing retrieval procedure. (B) Correlation plot for Day 15 measurement against Day 0. shRNA barcode reads for all samples from all time points were first normalized to 2×10⁷ reads. Values for triplicate samples were averaged. At Day 15, strong repression of shRNA expression in the absence of Doxycycline is evident in the correlations with the Day 0 reference. Plot of log10 mean normalized reads for Day 0 against Day 15 (Pearson correlation: R = 0.99).</p