Unbiased Boolean analysis of public gene expression data for cell cycle gene identification.

Cell proliferation is essential for the development and maintenance of all organisms and is dysregulated in cancer. Using synchronized cells progressing through the cell cycle, pioneering microarray studies defined cell cycle genes based on cyclic variation in their expression. However, the concordance of the small number of synchronized cell studies has been limited, leading to discrepancies in definition of the transcriptionally regulated set of cell cycle genes within and between species. Here we present an informatics approach based on Boolean logic to identify cell cycle genes. This approach used the vast array of publicly available gene expression data sets to query similarity to CCNB1, which encodes the cyclin subunit of the Cdk1-cyclin B complex that triggers the G2-to-M transition. In addition to highlighting conservation of cell cycle genes across large evolutionary distances, this approach identified contexts where well-studied genes known to act during the cell cycle are expressed and potentially acting in nondivision contexts. An accessible web platform enables a detailed exploration of the cell cycle gene lists generated using the Boolean logic approach. The methods employed are straightforward to extend to processes other than the cell cycle

Identification of histological features to predict MUC2 expression in colon cancer tissues

Colorectal cancer (CRC) is the third-most common form of cancer among Americans. Like normal colon tissue, CRC cells are sustained by a subpopulation of “stem cells” that possess the ability to self-renew and differentiate into more specialized cancer cell types. In normal colon tissue, the enterocytes, goblet cells and other epithelial cells in the mucosa region have distinct morphologies that distinguish them from the other cells in the lamina propria, muscularis mucosa, and submucosa. However, in a tumor, the morphology of the cancer cells varies dramatically. Cancer cells that express genes specific to goblet cells significantly differ in shape and size compared to their normal counterparts. Even though a large number of hematoxylin and eosin (H&E)-stained sections and the corresponding RNA sequencing (RNASeq) data from CRC are available from The Cancer Genome Atlas (TCGA), prediction of gene expression patterns from tissue histological features has not been attempted yet. In this manuscript, we identified histological features that are strongly associated with MUC2 expression patterns in a tumor. Specifically, we show that large nuclear area is associated with MUC2-high tumors (p < 0.001). This discovery provides insight into cancer biology and tumor histology and demonstrates that it may be possible to predict certain gene expressions from histological features

Computational Approach to Identifying Universal Macrophage Biomarkers.

Macrophages engulf and digest microbes, cellular debris, and various disease-associated cells throughout the body. Understanding the dynamics of macrophage gene expression is crucial for studying human diseases. As both bulk RNAseq and single cell RNAseq datasets become more numerous and complex, identifying a universal and reliable marker of macrophage cell becomes paramount. Traditional approaches have relied upon tissue specific expression patterns. To identify universal biomarkers of macrophage, we used a previously published computational approach called BECC (Boolean Equivalent Correlated Clusters) that was originally used to identify conserved cell cycle genes. We performed BECC analysis using the known macrophage marker CD14 as a seed gene. The main idea behind BECC is that it uses massive database of public gene expression dataset to establish robust co-expression patterns identified using a combination of correlation, linear regression and Boolean equivalences. Our analysis identified and validated FCER1G and TYROBP as novel universal biomarkers for macrophages in human and mouse tissues

Manufacturing and testing of an active compressor blade for aeroelastic studies

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Aeronautics and Astronautics, 2000.Also available online at the MIT Theses Online homepage .Includes bibliographical references (p. 145-146).This thesis deals with the manufacture of a 26-bladed 'active' rotor that will be used for developing an experimental database on turbomachinery aeroservoelastic phenomena, such as flutter and its control. The active rotor has blades made of two stress-bearing composite spars, aerodynamically shaped foam, piezoelectric actuators attached to the spar base and a root which allows the blade to be inserted into the rotor. The thesis analyzed the models developed for the active rotor blade design from previous studies and made suitable refinements in them. The following parameters were obtained - spar dimensions, their location and material, piezoelectric dimensions and material, foam material, and root structure and material. Next, technologies were developed for manufacturing the root and the twisted spar, packaging the piezoelectric actuators using copper-Kapton and bonding them to the spars, and wiring the spars and actuators. However, further investigation is necessary with regards to the issues of foam shaping, spar-foam attachment, and development of accurate leading and trailing edges of the blade. The final step involved testing the blade before and after spar-foam bonding. This required testing on the benchtop to obtain the blade performance limitations, and then testing it in vacuum while spinning inside a spin pit, which was constructed for this purpose. The latter gives the blade performance under rotation. The scope of the thesis is limited to the benchtop tests conducted on the active wired spars. Some of the blade and spin pit wiring issues need to be resolved before conducting the spin tests in vacuum. Also a rotor frame incorporating 26 active blades needs to developed to test under vacuum and in a wind tunnel. The results of the preliminary benchtop tests as well as the blade finite element model predict that the blade performance would be lower than the initial target. Several ways of improving its actuation capability considered were: (a) applying higher voltage with DC offset to the actuators, (b) using multi-wafer actuators, and (c) using active fiber composites. However, these issues need further work. The active rotor, when completed, will serve as a robust tool for aeroservoelastic testing over a significantly larger operating range than is currently possible.by Debashis Sahoo.S.M

Control of acoustics and store separation in a cavity in supersonic flow

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Aeronautics and Astronautics, 2005.Includes bibliographical references (p. 137-140).The supersonic flight community is currently faced with two cavity-under-cross-flow related problems, one being the high noise levels inside the cavity and the other being the return of a store into the cavity after being released from inside. This thesis provides a systematic framework to understand the dominant physics in both problems and to provide solutions for ameliorating the problems. For the first problem, an innovative cavity acoustics model is developed that rigorously explains the role of leading edge microjets in cavity noise suppression and predicts the magnitude of noise reduction for a given control input (that is the steady pressure at which the microjets are fired). The model is validated through comparison of its noise reduction predictions with experiments done using the Florida State University cavity and wind tunnel for different microjet pressures and under Mach 2.0 and Reynolds number 3 million flow, with the microjets being of diameter 400 microns. Based on the cavity acoustics model, optimization of the control input is performed for microjet-based noise suppression of a general cavity under external cross-flow. The resulting control strategy for the FSU cavity is that of an open loop steady microjet firing with the pressure being uniform along the leading edge. This corresponds to a noise reduction of 9 dB OASPL and 20 dB SPL at the dominant tone. The cavity also exhibits saturation in noise reduction for microjet pressures higher than 30 psig. The second problem that the thesis is concerned with, is that of unsuccessful store drops from an external bay of an aircraft in flight. A group of researchers under the DARPA-funded HIFEX Program is currently developing an effective control mechanism to ensure safe release(cont.) of a slender axi-symmetric store from a rectangular cavity under supersonic external cross-flow. The actuator being tested under this program is based on a tandem array of microjet flow injectors distributed in the spanwise direction near the leading edge of the cavity, and the control input is the steady pressure levels at which the microjets are fired. In order to optimize the control input to ensure safe store departure, a low order model that reliably predicts the trend in the store drop trajectory in the presence of microjets becomes necessary. In this thesis, a suitable low-order model is developed with separate components to predict the pitch and plunge motion of the store when it is inside the cavity, when it is passing through the shear layer at the mouth of the cavity and when it is completely outside the cavity. The model is based on slender axi-symmetric body aerodynamics, thin shear layer at the cavity mouth, high Reynolds number external cross-flow, plane shock waves associated with the microjet actuators, no-flow condition inside the cavity and inconsideration of the cavity acoustic field. The model is validated by comparing with the results of store drop experiments performed under the HIFEX Program at Mach 2.0 and 2.46 using a generic sub-scale weapons bay for different control inputs. The store drop was observed experimentally and predicted by the model to fail when microjets were switched off and successful with microjets on. However, with an increase in microjet pressure, the store drop became unsuccessful ...by Debashis Sahoo.Ph.D

Relativistic Coupled-Cluster Theory of Atomic Parity Nonconservation: Application to 137^{137}Ba+^+

We report the result of our {\it ab initio} calculation of the $6s ^2S_{1/2} \to 5d ^2D_{3/2}$ parity nonconserving electric dipole transition amplitude in $^{137}\text{Ba}^+$ based on relativistic coupled-cluster theory. Considering single, double and partial triple excitations, we have achieved an accuracy of less than one percent. If the accuracy of our calculation can be matched by the proposed parity nonconservation experiment in Ba$^+$ for the above transition,then the combination of the two results would provide an independent non accelerator test of the Standard Model of particle physics.Comment: 4 pages, 1 figure, Submitted to PR

Extracting binary signals from microarray time-course data

This article presents a new method for analyzing microarray time courses by identifying genes that undergo abrupt transitions in expression level, and the time at which the transitions occur. The algorithm matches the sequence of expression levels for each gene against temporal patterns having one or two transitions between two expression levels. The algorithm reports a P-value for the matching pattern of each gene, and a global false discovery rate can also be computed. After matching, genes can be sorted by the direction and time of transitions. Genes can be partitioned into sets based on the direction and time of change for further analysis, such as comparison with Gene Ontology annotations or binding site motifs. The method is evaluated on simulated and actual time-course data. On microarray data for budding yeast, it is shown that the groups of genes that change in similar ways and at similar times have significant and relevant Gene Ontology annotations