M-BISON: Microarray-based integration of data sources using networks

BACKGROUND: The accurate detection of differentially expressed (DE) genes has become a central task in microarray analysis. Unfortunately, the noise level and experimental variability of microarrays can be limiting. While a number of existing methods partially overcome these limitations by incorporating biological knowledge in the form of gene groups, these methods sacrifice gene-level resolution. This loss of precision can be inappropriate, especially if the desired output is a ranked list of individual genes. To address this shortcoming, we developed M-BISON (Microarray-Based Integration of data SOurces using Networks), a formal probabilistic model that integrates background biological knowledge with microarray data to predict individual DE genes. RESULTS: M-BISON improves signal detection on a range of simulated data, particularly when using very noisy microarray data. We also applied the method to the task of predicting heat shock-related differentially expressed genes in S. cerevisiae, using an hsf1 mutant microarray dataset and conserved yeast DNA sequence motifs. Our results demonstrate that M-BISON improves the analysis quality and makes predictions that are easy to interpret in concert with incorporated knowledge. Specifically, M-BISON increases the AUC of DE gene prediction from .541 to .623 when compared to a method using only microarray data, and M-BISON outperforms a related method, GeneRank. Furthermore, by analyzing M-BISON predictions in the context of the background knowledge, we identified YHR124W as a potentially novel player in the yeast heat shock response. CONCLUSION: This work provides a solid foundation for the principled integration of imperfect biological knowledge with gene expression data and other high-throughput data sources

Transcutaneous measurement of volume blood flow

Blood flow velocity measurements, using Doppler velocimeter, are described. The ability to measure blood velocity using ultrasound is derived from the Doppler effect; the change in frequency which occurs when sound is reflected or transmitted from a moving target. When ultrasound of the appropriate frequency is transmitted through a moving blood stream, the blood cells act as point scatterers of ultrasonic energy. If this scattered ultrasonic energy is detected, it is found to be shifted in frequency according to the velocity of the blood cells, nu, the frequency of the incident sound, f sub o, the speed of sound in the medium, c, and the angle between the sound beam and the velocity vector, o. The relation describing this effect is known as the Doppler equation. Delta f = 2 f sub o x nu x cos alpha/c. The theoretical and experimental methods are evaluated

A Cryogenic Fluid System Simulation in Support of Integrated Systems Health Management

Simulations serve as important tools throughout the design and operation of engineering systems. In the context of sys-tems health management, simulations serve many uses. For one, the underlying physical models can be used by model-based health management tools to develop diagnostic and prognostic models. These simulations should incorporate both nominal and faulty behavior with the ability to inject various faults into the system. Such simulations can there-fore be used for operator training, for both nominal and faulty situations, as well as for developing and prototyping health management algorithms. In this paper, we describe a methodology for building such simulations. We discuss the design decisions and tools used to build a simulation of a cryogenic fluid test bed, and how it serves as a core technology for systems health management development and maturation

High-throughput screening in larval zebrafish identifies novel potent sedative-hypnotics

BACKGROUND: Many general anesthetics were discovered empirically, but primary screens to find new sedative-hypnotics in drug libraries have not used animals, limiting the types of drugs discovered. The authors hypothesized that a sedative-hypnotic screening approach using zebrafish larvae responses to sensory stimuli would perform comparably to standard assays, and efficiently identify new active compounds. METHODS: The authors developed a binary outcome photomotor response assay for zebrafish larvae using a computerized system that tracked individual motions of up to 96 animals simultaneously. The assay was validated against tadpole loss of righting reflexes, using sedative-hypnotics of widely varying potencies that affect various molecular targets. A total of 374 representative compounds from a larger library were screened in zebrafish larvae for hypnotic activity at 10 µM. Molecular mechanisms of hits were explored in anesthetic-sensitive ion channels using electrophysiology, or in zebrafish using a specific reversal agent. RESULTS: Zebrafish larvae assays required far less drug, time, and effort than tadpoles. In validation experiments, zebrafish and tadpole screening for hypnotic activity agreed 100% (n = 11; P = 0.002), and potencies were very similar (Pearson correlation, r > 0.999). Two reversible and potent sedative-hypnotics were discovered in the library subset. CMLD003237 (EC50, ~11 µM) weakly modulated γ-aminobutyric acid type A receptors and inhibited neuronal nicotinic receptors. CMLD006025 (EC50, ~13 µM) inhibited both N-methyl-D-aspartate and neuronal nicotinic receptors. CONCLUSIONS: Photomotor response assays in zebrafish larvae are a mechanism-independent platform for high-throughput screening to identify novel sedative-hypnotics. The variety of chemotypes producing hypnosis is likely much larger than currently known.This work was supported by grants from Shanghai Jiaotong University School of Medicine, Shanghai, China, and the Chinese Medical Association, Beijing, China (both to Dr. Yang). The Department of Anesthesia, Critical Care and Pain Medicine of Massachusetts General Hospital, Boston, Massachusetts, supported this work through a Research Scholars Award and an Innovation Grant (both to Dr. Forman). Contributions to this research from the Boston University Center for Molecular Discovery, Boston, Massachusetts (to Drs. Porco, Brown, Schaus, and Xu, and to Mr. Trilles), were supported by a grant from the National Institutes of Health, Bethesda, Maryland (grant No. R24 GM111625). (Shanghai Jiaotong University School of Medicine, Shanghai, China; Chinese Medical Association, Beijing, China; Department of Anesthesia, Critical Care and Pain Medicine of Massachusetts General Hospital, Boston, Massachusetts; R24 GM111625 - National Institutes of Health, Bethesda, Maryland)Accepted manuscript2019-09-0

Experimental evidence of a natural parity state in 26^{26}Mg and its impact to the production of neutrons for the s process

We have studied natural parity states in $^{26}$Mg via the $^{22}$Ne($^{6}$Li,d)$^{26}$Mg reaction. Our method significantly improves the energy resolution of previous experiments and, as a result, we report the observation of a natural parity state in $^{26}$Mg. Possible spin-parity assignments are suggested on the basis of published $\gamma$-ray decay experiments. The stellar rate of the $^{22}$Ne($\alpha$,$\gamma$)$^{26}$Mg reaction is reduced and may give rise to an increase in the production of s-process neutrons via the $^{22}$Ne($\alpha$,n)$^{25}$Mg reaction.Comment: Published in PR

Automatic Detection of Expanding HI Shells Using Artificial Neural Networks

The identification of expanding HI shells is difficult because of their variable morphological characteristics. The detection of HI bubbles on a global scale therefore never has been attempted. In this paper, an automatic detector for expanding HI shells is presented. The detection is based on the more stable dynamical characteristics of expanding shells and is performed in two stages. The first one is the recognition of the dynamical signature of an expanding bubble in the velocity spectra, based on the classification of an artificial neural network. The pixels associated with these recognized spectra are identified on each velocity channel. The second stage consists in looking for concentrations of those pixels that were firstly pointed out, and to decide if they are potential detections by morphological and 21-cm emission variation considerations. Two test bubbles are correctly detected and a potentially new case of shell that is visually very convincing is discovered. About 0.6% of the surveyed pixels are identified as part of a bubble. These may be false detections, but still constitute regions of space with high probability of finding an expanding shell. The subsequent search field is thus significantly reduced. We intend to conduct in the near future a large scale HI shells detection over the Perseus Arm using our detector.Comment: 39 pages, 11 figures, accepted by PAS

Kinematics of galaxies in Compact Groups. Studying the B-band Tully-Fisher relation

We obtained new Fabry-Perot data cubes and derived velocity fields, monochromatic and velocity dispersion maps for 28 galaxies in the Hickson compact groups 37, 40, 47, 49, 54, 56, 68, 79 and 93. We find that one third of the non-barred compact group galaxies have position angle misalignments between the stellar and gaseous components. This and the asymmetric rotation curves are clear signatures of kinematic perturbations, probably due to interactions among compact group galaxies. A comparison between the B-band Tully-Fisher relation for compact group galaxies and that for the GHASP field-galaxy sample shows that, despite the high fraction of compact group galaxies with asymmetric rotation curves, these lie on the Tully-Fisher relation defined by galaxies in less dense environments, although with more scatter. This is in agreement with previous results, but now confirmed for a larger sample of 41 galaxies. We confirm the tendency for compact group galaxies at the low-mass end of the Tully-Fisher relation (HCG 49b, 89d, 96c, 96d and 100c) to have either a magnitude that is too bright for its mass (suggesting brightening by star formation) and/or a low maximum rotational velocity for its luminosity (suggesting tidal stripping). These galaxies are outside the Tully Fisher relation, at the 1 sigma level, even when the minimum acceptable values of inclinations are used to compute their maximum velocities. The inclusion of such galaxies with v<100 km/s in the determination of the zero point and slope of the compact group B-band Tully-Fisher relation would strongly change the fit, making it different from the relation for field galaxies, a fact that has to be kept in mind when studying scaling relations of interacting galaxies, specially at high redshifts.Comment: 17 figures. Accepted for publication in Astronomy and Astrophysics. Hickson compact groups Fabry-Perot data are available at http://fabryperot.oamp.fr/PerotFabry