Open Source ImmGen: network perspective on metabolic diversity among mononuclear phagocytes

We dissect metabolic variability of mononuclear phagocyte (MNP) subpopulations across different tissues through integrative analysis of three large scale datasets. Specifically, we introduce ImmGen MNP Open Source dataset that profiled 337 samples and extended previous ImmGen effort which included 202 samples of mononuclear phagocytes and their progenitors. Next, we analysed Tabula Muris Senis dataset to extract data for 51,364 myeloid cells from 18 tissues. Taken together, a compendium of data assembled in this work covers phagocytic populations found across 38 different tissues. To analyse common metabolic features, we developed novel network-based computational approach for unbiased identification of key metabolic subnetworks based on cellular transcriptional profiles in large-scale datasets. Using ImmGen MNP Open Source dataset as baseline, we define 9 metabolic subnetworks that encapsulate the metabolic differences within mononuclear phagocytes, and demonstrate that these features are robustly found across all three datasets, including lipid metabolism, cholesterol biosynthesis, glycolysis, and a set of fatty acid related metabolic pathways, as well as nucleotide and folate metabolism. We systematically define major features specific to macrophage and dendritic cell subpopulations. Among other things, we find that cholesterol synthesis appears particularly active within the migratory dendritic cells. We demonstrate that interference with this pathway through statins administration diminishes migratory capacity of the dendritic cells in vivo. This result demonstrates the power of our approach and highlights importance of metabolic diversity among mononuclear phagocytes

A Probabilistic Approach to the Problem of Automatic Selection of Data Representations

The design and implementation of efficient aggregate data structures has been an important issue in functional programming. It is not clear how to select a good representation for an aggregate when access patterns to the aggregate are highly variant, or even unpredictable. Previous approaches rely on compile--time analyses or programmer annotations. These methods can be unreliable because they try to predict program behaviors before they are executed. We propose a probabilistic approach, which is based on Markov processes, for automatic selection of data representations. The selection is modeled as a random process moving in a graph with weighted edges. The proposed approach employs coin tossing at run--time to aid choosing suitable data representations. The transition probability function used by the coin tossing is constructed in a simple and common way from a measured cost function. We show that, under this setting, random selection of data representations can be quite effective. Th..

The Space Shuttle Liftoff Pressure Wave

The pressure wave produced during the launch of the Space Shuttle and its dynamic effects on ground support structures are studied in this paper. The discrete form of the Fourier transform and the fast Fourier transform algorithm are employed to characterize the pressure wave and to generate design and evaluation data. Analysis is performed on pressure recordings collected from eight pressure transducers mounted on the roof and walls of a building approximately 90 m West of Launch Pad 39A at the Kennedy Space Center. A total of 23 pressure pulses were sampled every 0.25 ms for a 10 s duration from six different launches. The analysis produces a pressure-time plot and power spectrum, representing the frequency content of the pressure wave which identifies its ability to excite a structure. Also produced are response spectra for each pressure wave for various amounts of damping. These spectra may be used to predict the dynamic response of a structure located near a launch site

Microfluidic perfusion system for maintaining viable heart tissue with real-time electrochemical monitoring of reactive oxygen species

A microfluidic device has been developed to maintain viable heart tissue samples in a biomimetic microenvironment. This device allows rat or human heart tissue to be studied under pseudo in vivo conditions. Effluent levels of lactate dehydrogenase and hydrogen peroxide were used as markers of damaged tissue in combination with in situ electrochemical measurement of the release of reactive oxygen species (ROS). The parameters for perfusion were optimized to maintain biopsies of rat right ventricular or human right atrial tissue viable for up to 5 and 3.5 hours, respectively. Electrochemical assessment of the oxidation current of total ROS, employing cyclic voltammetry, gave results in real-time that were in good agreement to biochemical assessment using conventional, off-chip, commercial assays. This proof-of-principle, integrated microfluidic device, may be exploited in providing a platform technology for future cardiac research, offering an alternative approach for investigating heart pathophysiology and facilitating the development of new therapeutic strategies

Molecular identification of a mystery rail from Panama results in the first country record of King Rail Rallus elegans

Volume: 136Start Page: 291End Page: 29