Hybrid propulsion technology program. Volume 1: Conceptional design package

A concept design study was performed to configure two sizes of hybrid boosters; one which duplicates the advanced shuttle rocket motor vacuum thrust time curve and a smaller, quarter thrust level booster. Two sizes of hybrid boosters were configured for either pump-fed or pressure-fed oxygen feed systems. Performance analyses show improved payload capability relative to a solid propellant booster. Size optimization and fuel safety considerations resulted in a 4.57 m (180 inch) diameter large booster with an inert hydrocarbon fuel. The preferred diameter for the quarter thrust level booster is 2.53 m (96 inches). As part of the design study critical technology issues were identified and a technology acquisition and demonstration plan was formulated

New consistency index based on inertial operating speed

The occurrence of road crashes depends on several factors, with design consistency (i.e., conformance of highway geometry to drivers' expectations) being one of the most important. A new consistency model for evaluating the performance of tangent-to-curve transitions on two-lane rural roads was developed. This model was based on the inertial consistency index (ICI) defined for each transition. The ICI was calculated at the beginning point of the curve as the difference between the average operating speed on the previous 1-km road segment (inertial operating speed) and the actual operating speed at this point. For the calibration of the ICI and its thresholds, 88 road segments, which included 1,686 tangent-to-curve transitions, were studied. The relationship between those results and the crash rate associated with each transition was analyzed. The results showed that the higher the ICI was, the higher the crash rate; thus, the probability of accidents increased. Similar results were obtained from the study of the relationship between the ICI and the weighted average crash rate of the corresponding group of transitions. A graphical and statistical analysis established that road consistency might be considered good when the ICI was lower than 10 km/h, poor when the ICI was higher than 20 km/h, and fair otherwise. A validation process that considered 20 road segments was performed. The ICI values obtained were highly correlated to the number of crashes that had occurred at the analyzed transitions. Thus, the ICI and its consistency thresholds resulted in a new approach for evaluation of consistency.The authors thank the Center for Studies and Experimentation of Public Works of the Spanish Ministry of Public Works, which partially subsidized the data collection, for obtaining the empirical operating speed profiles used in the validation process. The authors also thank the General Directorate of Public Works of the Infrastructure and Transportation Department of the Valencian government, the Valencian Province Council, and the General Directorate of Traffic of the Ministry of the Interior of the Government of Spain for their cooperation in data gathering.García García, A.; Llopis Castelló, D.; Camacho Torregrosa, FJ.; Pérez Zuriaga, AM. (2013). New consistency index based on inertial operating speed. Transportation Research Record. (2391):105-112. doi:10.3141/2391-10S1051122391Ng, J. C. ., & Sayed, T. (2004). Effect of geometric design consistency on road safety. Canadian Journal of Civil Engineering, 31(2), 218-227. doi:10.1139/l03-090Gibreel, G. M., Easa, S. M., Hassan, Y., & El-Dimeery, I. A. (1999). State of the Art of Highway Geometric Design Consistency. Journal of Transportation Engineering, 125(4), 305-313. doi:10.1061/(asce)0733-947x(1999)125:4(305)Hassan, Y. (2004). Highway Design Consistency: Refining the State of Knowledge and Practice. Transportation Research Record: Journal of the Transportation Research Board, 1881(1), 63-71. doi:10.3141/1881-08Polus, A., & Mattar-Habib, C. (2004). New Consistency Model for Rural Highways and Its Relationship to Safety. Journal of Transportation Engineering, 130(3), 286-293. doi:10.1061/(asce)0733-947x(2004)130:3(286)Cafiso, S., Di Graziano, A., Di Silvestro, G., La Cava, G., & Persaud, B. (2010). Development of comprehensive accident models for two-lane rural highways using exposure, geometry, consistency and context variables. Accident Analysis & Prevention, 42(4), 1072-1079. doi:10.1016/j.aap.2009.12.015Zuriaga, A. M. P., García, A. G., Torregrosa, F. J. C., & D’Attoma, P. (2010). Modeling Operating Speed and Deceleration on Two-Lane Rural Roads with Global Positioning System Data. Transportation Research Record: Journal of the Transportation Research Board, 2171(1), 11-20. doi:10.3141/2171-0

The Sloan Great Wall. Rich clusters

We present the results of the study of the substructure and galaxy content of ten rich clusters of galaxies in three different superclusters of the Sloan Great Wall. We determine the substructure in clusters using the 'Mclust' package from the 'R' statistical environment and analyse their galaxy content. We analyse the distribution of the peculiar velocities of galaxies in clusters and calculate the peculiar velocity of the first ranked galaxy. We show that clusters in our sample have more than one component; in some clusters different components also have different galaxy content. We find that in some clusters with substructure the peculiar velocities of the first ranked galaxies are large. All clusters in our sample host luminous red galaxies. They can be found both in the central areas of clusters as well as in the outskirts, some of them have large peculiar velocities. About 1/3 of red galaxies in clusters are spirals. The scatter of colours of red ellipticals is in most clusters larger than that of red spirals. The presence of substructure in rich clusters, signs of possible mergers and infall, as well as the large peculiar velocities of the first ranked galaxies suggest that the clusters in our sample are not yet virialized. We present merger trees of dark matter haloes in an N-body simulation to demonstrate the formation of present-day dark matter haloes via multiple mergers during their evolution. In simulated dark matter haloes we find a substructure similar to that in observed clusters.Comment: 19 pages, 44 figures, accepted for publication in Astronomy and Astrophysic

A comprehensive re-analysis of the Golden Spike data: Towards a benchmark for differential expression methods

<p>Abstract</p> <p>Background</p> <p>The Golden Spike data set has been used to validate a number of methods for summarizing Affymetrix data sets, sometimes with seemingly contradictory results. Much less use has been made of this data set to evaluate differential expression methods. It has been suggested that this data set should not be used for method comparison due to a number of inherent flaws.</p> <p>Results</p> <p>We have used this data set in a comparison of methods which is far more extensive than any previous study. We outline six stages in the analysis pipeline where decisions need to be made, and show how the results of these decisions can lead to the apparently contradictory results previously found. We also show that, while flawed, this data set is still a useful tool for method comparison, particularly for identifying combinations of summarization and differential expression methods that are unlikely to perform well on real data sets. We describe a new benchmark, AffyDEComp, that can be used for such a comparison.</p> <p>Conclusion</p> <p>We conclude with recommendations for preferred Affymetrix analysis tools, and for the development of future spike-in data sets.</p

The Substrate-Bound Crystal Structure of a Baeyer–Villiger Monooxygenase Exhibits a Criegee-like Conformation

The Baeyer\u2013Villiger monooxygenases (BVMOs) are a family of bacterial flavoproteins that catalyze the synthetically useful Baeyer\u2013Villiger oxidation reaction. This involves the conversion of ketones into esters or cyclic ketones into lactones by introducing an oxygen atom adjacent to the carbonyl group. The BVMOs offer exquisite regio- and enantiospecificity while acting on a wide range of substrates. They use only NADPH and oxygen as cosubstrates, and produce only NADP+ and water as byproducts, making them environmentally attractive for industrial purposes. Here, we report the first crystal structure of a BVMO, cyclohexanone monooxygenase (CHMO) from Rhodococcus sp. HI-31 in complex with its substrate, cyclohexanone, as well as NADP+ and FAD, to 2.4 \uc5 resolution. This structure shows a drastic rotation of the NADP+ cofactor in comparison to previously reported NADP+-bound structures, as the nicotinamide moiety is no longer positioned above the flavin ring. Instead, the substrate, cyclohexanone, is found at this location, in an appropriate position for the formation of the Criegee intermediate. The rotation of NADP+ permits the substrate to gain access to the reactive flavin peroxyanion intermediate while preventing it from diffusing out of the active site. The structure thus reveals the conformation of the enzyme during the key catalytic step. CHMO is proposed to undergo a series of conformational changes to gradually move the substrate from the solvent, via binding in a solvent excluded pocket that dictates the enzyme\u2019s chemospecificity, to a location above the flavin\u2013peroxide adduct where catalysis occurs.Peer reviewed: YesNRC publication: Ye

Microanatomy of the trophosome region of Paracatenula cf. polyhymnia (Catenulida, Platyhelminthes) and its intracellular symbionts

Marine catenulid platyhelminths of the genus Paracatenula lack mouth, pharynx and gut. They live in a symbiosis with intracellular bacteria which are restricted to the body region posterior to the brain. The symbiont-housing cells (bacteriocytes) collectively form the trophosome tissue, which functionally replaces the digestive tract. It constitutes the largest part of the body and is the most important synapomorphy of this group. While some other features of the Paracatenula anatomy have already been analyzed, an in-depth analysis of the trophosome region was missing. Here, we identify and characterize the composition of the trophosome and its surrounding tissue by analyzing series of ultra-thin cross-sections of the species Paracatenula cf. polyhymnia. For the first time, a protonephridium is detected in a Paracatenula species, but it is morphologically reduced and most likely not functional. Cells containing needle-like inclusions in the reference species Paracatenula polyhymnia Sterrer and Rieger, 1974 were thought to be sperm, and the inclusions interpreted as the sperm nucleus. Our analysis of similar cells and their inclusions by EDX and Raman microspectroscopy documents an inorganic spicule consisting of a unique magnesium–phosphate compound. Furthermore, we identify the neoblast stem cells located underneath the epidermis. Except for the modifications due to the symbiotic lifestyle and the enigmatic spicule cells, the organization of Paracatenula cf. polyhymnia conforms to that of the Catenulida in all studied aspects. Therefore, this species represents an excellent model system for further studies of host adaptation to an obligate symbiotic lifestyle

Accounting for uncertainty when assessing association between copy number and disease: a latent class model

<p>Abstract</p> <p>Background</p> <p>Copy number variations (CNVs) may play an important role in disease risk by altering dosage of genes and other regulatory elements, which may have functional and, ultimately, phenotypic consequences. Therefore, determining whether a CNV is associated or not with a given disease might be relevant in understanding the genesis and progression of human diseases. Current stage technology give CNV probe signal from which copy number status is inferred. Incorporating uncertainty of CNV calling in the statistical analysis is therefore a highly important aspect. In this paper, we present a framework for assessing association between CNVs and disease in case-control studies where uncertainty is taken into account. We also indicate how to use the model to analyze continuous traits and adjust for confounding covariates.</p> <p>Results</p> <p>Through simulation studies, we show that our method outperforms other simple methods based on inferring the underlying CNV and assessing association using regular tests that do not propagate call uncertainty. We apply the method to a real data set in a controlled MLPA experiment showing good results. The methodology is also extended to illustrate how to analyze aCGH data.</p> <p>Conclusion</p> <p>We demonstrate that our method is robust and achieves maximal theoretical power since it accommodates uncertainty when copy number status are inferred. We have made <monospace>R</monospace> functions freely available.</p

MMASS: an optimized array-based method for assessing CpG island methylation

We describe an optimized microarray method for identifying genome-wide CpG island methylation called microarray-based methylation assessment of single samples (MMASS) which directly compares methylated to unmethylated sequences within a single sample. To improve previous methods we used bioinformatic analysis to predict an optimized combination of methylation-sensitive enzymes that had the highest utility for CpG-island probes and different methods to produce unmethylated representations of test DNA for more sensitive detection of differential methylation by hybridization. Subtraction or methylation-dependent digestion with McrBC was used with optimized (MMASS-v2) or previously described (MMASS-v1, MMASS-sub) methylation-sensitive enzyme combinations and compared with a published McrBC method. Comparison was performed using DNA from the cell line HCT116. We show that the distribution of methylation microarray data is inherently skewed and requires exogenous spiked controls for normalization and that analysis of digestion of methylated and unmethylated control sequences together with linear fit models of replicate data showed superior statistical power for the MMASS-v2 method. Comparison with previous methylation data for HCT116 and validation of CpG islands from PXMP4, SFRP2, DCC, RARB and TSEN2 confirmed the accuracy of MMASS-v2 results. The MMASS-v2 method offers improved sensitivity and statistical power for high-throughput microarray identification of differential methylation

Identification of SERPINA1 as single marker for papillary thyroid carcinoma through microarray meta analysis and quantification of its discriminatory power in independent validation

<p>Abstract</p> <p>Background</p> <p>Several DNA microarray based expression signatures for the different clinically relevant thyroid tumor entities have been described over the past few years. However, reproducibility of these signatures is generally low, mainly due to study biases, small sample sizes and the highly multivariate nature of microarrays. While there are new technologies available for a more accurate high throughput expression analysis, we show that there is still a lot of information to be gained from data deposited in public microarray databases. In this study we were aiming (1) to identify potential markers for papillary thyroid carcinomas through meta analysis of public microarray data and (2) to confirm these markers in an independent dataset using an independent technology.</p> <p>Methods</p> <p>We adopted a meta analysis approach for four publicly available microarray datasets on papillary thyroid carcinoma (PTC) nodules versus nodular goitre (NG) from N2-frozen tissue. The methodology included merging of datasets, bias removal using distance weighted discrimination (DWD), feature selection/inference statistics, classification/crossvalidation and gene set enrichment analysis (GSEA). External Validation was performed on an independent dataset using an independent technology, quantitative RT-PCR (RT-qPCR) in our laboratory.</p> <p>Results</p> <p>From meta analysis we identified one gene (SERPINA1) which identifies papillary thyroid carcinoma against benign nodules with 99% accuracy (n = 99, sensitivity = 0.98, specificity = 1, PPV = 1, NPV = 0.98). In the independent validation data, which included not only PTC and NG, but all major histological thyroid entities plus a few variants, SERPINA1 was again markedly up regulated (36-fold, p = 1:3*10^-10) in PTC and identification of papillary carcinoma was possible with 93% accuracy (n = 82, sensitivity = 1, specificity = 0.90, PPV = 0.76, NPV = 1). We also show that the extracellular matrix pathway is strongly activated in the meta analysis data, suggesting an important role of tumor-stroma interaction in the carcinogenesis of papillary thyroid carcinoma.</p> <p>Conclusions</p> <p>We show that valuable new information can be gained from meta analysis of existing microarray data deposited in public repositories. While single microarray studies rarely exhibit a sample number which allows robust feature selection, this can be achieved by combining published data using DWD. This approach is not only efficient, but also very cost-effective. Independent validation shows the validity of the results from this meta analysis and confirms SERPINA1 as a potent mRNA marker for PTC in a total (meta analysis plus validation) of 181 samples.</p

BeadArray Expression Analysis Using Bioconductor

Illumina whole-genome expression BeadArrays are a popular choice in gene profiling studies. Aside from the vendor-provided software tools for analyzing BeadArray expression data (GenomeStudio/BeadStudio), there exists a comprehensive set of open-source analysis tools in the Bioconductor project, many of which have been tailored to exploit the unique properties of this platform. In this article, we explore a number of these software packages and demonstrate how to perform a complete analysis of BeadArray data in various formats. The key steps of importing data, performing quality assessments, preprocessing, and annotation in the common setting of assessing differential expression in designed experiments will be covered