BeadDataPackR: A Tool to Facilitate the Sharing of Raw Data from Illumina BeadArray Studies

Microarray technologies have been an increasingly important tool in cancer research in the last decade, and a number of initiatives have sought to stress the importance of the provision and sharing of raw microarray data. Illumina BeadArrays provide a particular problem in this regard, as their random construction simultaneously adds value to analysis of the raw data and obstructs the sharing of those data

Evolution of Ada technology in the flight dynamics area: Implementation/testing phase analysis

An analysis is presented of the software engineering issues related to the use of Ada for the implementation and system testing phases of four Ada projects developed in the flight dynamics area. These projects reflect an evolving understanding of more effective use of Ada features. In addition, the testing methodology used on these projects has changed substantially from that used on previous FORTRAN projects

beachmat: A Bioconductor C++ API for accessing high-throughput biological data from a variety of R matrix types.

Biological experiments involving genomics or other high-throughput assays typically yield a data matrix that can be explored and analyzed using the R programming language with packages from the Bioconductor project. Improvements in the throughput of these assays have resulted in an explosion of data even from routine experiments, which poses a challenge to the existing computational infrastructure for statistical data analysis. For example, single-cell RNA sequencing (scRNA-seq) experiments frequently generate large matrices containing expression values for each gene in each cell, requiring sparse or file-backed representations for memory-efficient manipulation in R. These alternative representations are not easily compatible with high-performance C++ code used for computationally intensive tasks in existing R/Bioconductor packages. Here, we describe a C++ interface named beachmat, which enables agnostic data access from various matrix representations. This allows package developers to write efficient C++ code that is interoperable with dense, sparse and file-backed matrices, amongst others. We evaluated the performance of beachmat for accessing data from each matrix representation using both simulated and real scRNA-seq data, and defined a clear memory/speed trade-off to motivate the choice of an appropriate representation. We also demonstrate how beachmat can be incorporated into the code of other packages to drive analyses of a very large scRNA-seq data set

Retrograde transport pathways utilised by viruses and protein toxins

A model has been presented for retrograde transport of certain toxins and viruses from the cell surface to the ER that suggests an obligatory interaction with a glycolipid receptor at the cell surface. Here we review studies on the ER trafficking cholera toxin, Shiga and Shiga-like toxins, Pseudomonas exotoxin A and ricin, and compare the retrograde routes followed by these protein toxins to those of the ER trafficking SV40 and polyoma viruses. We conclude that there is in fact no obligatory requirement for a glycolipid receptor, nor even with a protein receptor in a lipid-rich environment. Emerging data suggests instead that there is no common pathway utilised for retrograde transport by all of these pathogens, the choice of route being determined by the particular receptor utilised

Syntaxin 16 and syntaxin 5 are required for efficient retrograde transport of several exogenous and endogenous cargo proteins

Retrograde transport allows proteins and lipids to leave the endocytic pathway to reach other intracellular compartments, such as trans-Golgi network (TGN)/Golgi membranes, the endoplasmic reticulum and, in some instances, the cytosol. Here, we have used RNA interference against the SNARE proteins syntaxin 5 and syntaxin 16, combined with recently developed quantitative trafficking assays, morphological approaches and cell intoxication analysis to show that these SNARE proteins are not only required for efficient retrograde transport of Shiga toxin, but also for that of an endogenous cargo protein - the mannose 6-phosphate receptor - and for the productive trafficking into cells of cholera toxin and ricin. We have found that the function of syntaxin 16 was specifically required for, and restricted to, the retrograde pathway. Strikingly, syntaxin 5 RNA interference protected cells particularly strongly against Shiga toxin. Since our trafficking analysis showed that apart from inhibiting retrograde endosome-to-TGN transport, the silencing of syntaxin 5 had no additional effect on Shiga toxin endocytosis or trafficking from TGN/Golgi membranes to the endoplasmic reticulum, we hypothesize that syntaxin 5 also has trafficking-independent functions. In summary, our data demonstrate that several cellular and exogenous cargo proteins use elements of the same SNARE machinery for efficient retrograde transport between early/recycling endosomes and TGN/Golgi membranes

Choosing Important Health Outcomes for Comparative Effectiveness Research: An Updated Review and Identification of Gaps

<div><p>Background</p><p>The COMET (Core Outcome Measures in Effectiveness Trials) Initiative promotes the development and application of core outcome sets (COS), including relevant studies in an online database. In order to keep the database current, an annual search of the literature is undertaken. This study aimed to update a previous systematic review, in order to identify any further studies where a COS has been developed. Furthermore, no prioritization for COS development has previously been undertaken, therefore this study also aimed to identify COS relevant to the world’s most prevalent health conditions.</p><p>Methods</p><p>The methods used in this updated review followed the same approach used in the original review and the previous update. A survey was also sent to the corresponding authors of COS identified for inclusion in this review, to ascertain what lessons they had learnt from developing their COS. Additionally, the COMET database was searched to identify COS that might be relevant to the conditions with the highest global prevalence.</p><p>Results</p><p>Twenty-five reports relating to 22 new studies were eligible for inclusion in the review. Further improvements were identified in relation to the description of the scope of the COS, use of the Delphi technique, and the inclusion of patient participants within the development process. Additionally, 33 published and ongoing COS were identified for 13 of the world’s most prevalent conditions.</p><p>Conclusion</p><p>The development of a reporting guideline and minimum standards should contribute towards future improvements in development and reporting of COS. This study has also described a first approach to identifying gaps in existing COS, and to priority setting in this area. Important gaps have been identified, on the basis of global burden of disease, and the development and application of COS in these areas should be considered a priority.</p></div

Measurement of the Dielectric Strength of Titanium Dioxide Ceramics

Titanium dioxide ceramics (TiO2) are candidate materials for high energy density pulsed power devices. Experiments to quantify the dielectric strength of TiO2 have been performed on a limited number of unoptimized samples. A high voltage test set was constructed to test the titanium dioxide. All samples had a relative dielectric constant of 100, all samples were of 3 mm nominal thickness, and all tests were performed in water dielectric to reduce the effect of the triple point field enhancement at the electrode edge. Both single layer and laminated samples were tested and the breakdown field strengths were recorded. Voltage risetimes varied slightly around 400 ns depending upon the size of the test sample area. Areas varied from \u3c 0.2 cm^2 to \u3e 100 cm^2. Both single layer and laminated material showed a strong area effect where the dielectric strength dropped off as area to the -0.17 and -0.1 power respectively. Effective areas of the electrodes were calculated using a field solver program. Breakdown field strengths varied from 469 kV/cm to 124 kV/cm in the single layer specimens, and from 556 kV/cm to 261 kV/cm in the laminates over an increasing area range. Energy density calculations for the material show that at areas of approximately 100 cm^2 the laminates can store nearly 3 times more energy than single layers