Kettering University

About: Kettering University is a education organization based out in Flint, Michigan, United States. It is known for research contribution in the topics: RNA & Antigen. The organization has 6842 authors who have published 7689 publications receiving 337503 citations. The organization is also known as: GMI Engineering & Management Institute & General Motors Institute.

A hybrid blob-slice model for accurate and efficient detection of fluorescence labeled nuclei in 3D

Abstract: Background: To exploit the flood of data from advances in high throughput imaging of optically sectioned nuclei, image analysis methods need to correctly detect thousands of nuclei, ideally in real time. Variability in nuclear appearance and undersampled volumetric data make this a challenge. Results: We present a novel 3D nuclear identification method, which subdivides the problem, first segmenting nuclear slices within each 2D image plane, then using a shape model to assemble these slices into 3D nuclei. This hybrid 2D/3D approach allows accurate accounting for nuclear shape but exploits the clear 2D nuclear boundaries that are present in sectional slices to avoid the computational burden of fitting a complex shape model to volume data. When tested over C. elegans, Drosophila, zebrafish and mouse data, our method yielded 0 to 3.7% error, up to six times more accurate as well as being 30 times faster than published performances. We demonstrate our method’s potential by reconstructing the morphogenesis of the C. elegans pharynx. This is an important and much studied developmental process that could not previously be followed at this single cell level of detail. Conclusions: Because our approach is specialized for the characteristics of optically sectioned nuclear images, it can achieve superior accuracy in significantly less time than other approaches. Both of these characteristics are necessary for practical analysis of overwhelmingly large data sets where processing must be scalable to hundreds of thousands of cells and where the time cost of manual error correction makes it impossible to use data with high error rates. Our approach is fast, accurate, available as open source software and its learned shape model is easy to retrain. As our pharynx development example shows, these characteristics make single cell analysis relatively easy and will enable novel experimental methods utilizing complex data sets.

Targeting cap-dependent translation blocks converging survival signals by AKT and PIM kinases in lymphoma

Abstract: New anticancer drugs that target oncogenic signaling molecules have greatly improved the treatment of certain cancers. However, resistance to targeted therapeutics is a major clinical problem and the redundancy of oncogenic signaling pathways provides back-up mechanisms that allow cancer cells to escape. For example, the AKT and PIM kinases produce parallel oncogenic signals and share many molecular targets, including activators of cap-dependent translation. Here, we show that PIM kinase expression can affect the clinical outcome of lymphoma chemotherapy. We observe the same in animal lymphoma models. Whereas chemoresistance caused by AKT is readily reversed with rapamycin, PIM-mediated resistance is refractory to mTORC1 inhibition. However, both PIM- and AKT-expressing lymphomas depend on cap-dependent translation, and genetic or pharmacological blockade of the translation initiation complex is highly effective against these tumors. The therapeutic effect of blocking cap-dependent translation is mediated, at least in part, by decreased production of short-lived oncoproteins including c-MYC, Cyclin D1, MCL1, and the PIM1/2 kinases themselves. Hence, targeting the convergence of oncogenic survival signals on translation initiation is an effective alternative to combinations of kinase inhibitors.

The Clinical Significance of Alterations in Transaminase Activities of Serum and Other Body Fluids

Abstract: Publisher Summary This chapter presents the mechanisms of alterations in serum transaminase activity, and discusses the clinical significance of alterations in transminase activity of serum and other body fluids. Extensive biochemical studies of enzymatic transamination have foreshadowed the clinical implications of transaminase activity in body fluids. Although a number of transaminase activities have been demonstrated in human serum (M2), the two serum transaminases currently of clinical import are serum glutamic-oxaloacetic transaminase (SGO-T) and serum glutamic-pyruvic transaminase (SGP-T). Both serum enzymes have been measured chromatographically , spectrophotometrically, and colorimetrically. Significant alterations of these serum enzymes have been observed during the course of cardiac, hepatic, and muscular diseases, and reflected enzyme changes at the intracellular level of the respective tissues. Although a multiplicity of diseases is associated with serum transaminase elevations, diagnostic aid is afforded when these serum enzyme alterations are correlated with the clinical facts. The chapter demonstrates that the assessment of the clinical significance of alterations in transaminase activity in body fluids other than serum requires further study.

Detached-Eddy Simulation over a Reference Ahmed Car Model

Abstract: This paper presents a Spalart-Allmaras based Detached-Eddy Simulation (DES) of the Ahmed reference car model with 25° and 35° slant angles using unstructured grids and the solverCobalt. Comparisons are made to experimental laser doppler velocity measurements as well as total and surface pressure integrated drag. The Reynolds number based on body length was 2.78 ×106, making the boundary layers approaching the slant fully turbulent. The flow over the base slant in the experiments is attached at 25° and separated at 35°. This causes a large drop in the drag with the increased slant angle as the vortices on the side of the slant are weakened due to the separation. These cases stress turbulence models due to the need to accurately predict the boundary layer separation over the slant as well as predict the pressures in the massively separated base region accurately. The DES results are compared to the experiments as well as the Spalart-Allmaras RANS model. DES is seen to predict separation at 25◦ slant angle, in contrast to the experiments. Drag is relatively close to the experiments, but the distribution of drag is more on the rear than on the slant due to the separation. At the 35 ° slant angle, DES is in good agreement to the experimental drag, with the correct distribution, while RANS over-predicts the drag.

Overexpression of RRE-derived sequences inhibits HIV-1 replication in CEM cells.

Abstract: Overexpression of sequences corresponding to the major Rev-binding site in the Rev response element of human immunodeficiency virus type 1 (HIV-1) (RRE decoys) was used to render cells resistant to HIV-1 replication. This was accomplished by the use of a chimeric tRNA-RRE transcription unit in a double-copy murine retroviral vector to express high levels of HIV-1 RRE-containing transcripts in CEM SS cells. Replication of HIV-1 was inhibited more than 90% in cells expressing chimeric tRNA-RRE transcripts, as determined by in situ immunofluorescence analysis and a p24 antigen ELISA test. Analysis of RNA from HIV-1-infected cells suggests that expression of RRE-containing sequences in CEM SS cells inhibits HIV-1 replication by interfering with Rev function, presumably by competing for Rev binding to its physiological target. The use of a subfragment of RRE as decoy RNA reduces the likelihood that essential cellular factors will be sequestered in cells expressing the decoy RNA. Thus, use of RRE-based decoy RNA to inhibit HIV-1 replication may represent a safer alternative to the use of TAR decoy RNA.