scholarly journals USING DIRECTED INFORMATION TO BUILD BIOLOGICALLY RELEVANT INFLUENCE NETWORKS

Author(s):  
Arvind Rao ◽  
Alfred O. Hero ◽  
David J. States ◽  
James Douglas Engel
2008 ◽  
Vol 06 (03) ◽  
pp. 493-519 ◽  
Author(s):  
ARVIND RAO ◽  
ALFRED O. HERO ◽  
DAVID J. STATES ◽  
JAMES DOUGLAS ENGEL

The systematic inference of biologically relevant influence networks remains a challenging problem in computational biology. Even though the availability of high-throughput data has enabled the use of probabilistic models to infer the plausible structure of such networks, their true interpretation of the biology of the process is questionable. In this work, we propose a network inference methodology, based on the directed information (DTI) criterion, that incorporates the biology of transcription within the framework so as to enable experimentally verifiable inference. We use publicly available embryonic kidney and T-cell microarray datasets to demonstrate our results. We present two variants of network inference via DTI — supervised and unsupervised — and the inferred networks relevant to mammalian nephrogenesis and T-cell activation. Conformity of the obtained interactions with the literature as well as comparison with the coefficient of determination (CoD) method are demonstrated. Apart from network inference, the proposed framework enables the exploration of specific interactions, not just those revealed by data. To illustrate the latter point, a DTI-based framework to resolve interactions between transcription factor modules and target coregulated genes is proposed. Additionally, we show that DTI can be used in conjunction with mutual information to infer higher-order influence networks involving cooperative gene interactions.


Author(s):  
S. Lehner ◽  
H.E. Bauer ◽  
R. Wurster ◽  
H. Seiler

In order to compare different microanalytical techniques commercially available cation exchange membrane SC-1 (Stantech Inc, Palo Alto), was loaded with biologically relevant elements as Na, Mg, K, and Ca, respectively, each to its highest possible concentration, given by the number concentration of exchangeable binding sites (4 % wt. for Ca). Washing in distilled water, dehydration through a graded series of ethanol, infiltration and embedding in Spurr’s low viscosity epoxy resin was followed by thin sectioning. The thin sections (thickness of about 50 nm) were prepared on carbon foils and mounted on electron microscopical finder grids.The samples were analyzed with electron microprobe JXA 50A with transmitted electron device, EDX system TN 5400, and on line operating image processing system SEM-IPS, energy filtering electron microscope CEM 902 with EELS/ESI and Auger spectrometer 545 Perkin Elmer.With EDX, a beam current of some 10-10 A and a beam diameter of about 10 nm, a minimum-detectable mass of 10-20 g Ca seems within reach.


Author(s):  
Etienne de Harven ◽  
Hilary Christensen ◽  
Richard Leung ◽  
Cameron Ackerley

The T-derived subset of human peripheral blood normal lymphocytes has been selected as a model system to study the usefulness of 5 nm gold markers for quantification of single epitopes expressed on cell surfaces. The chosen epitopes are parts of the CD3 and CD5 molecules and can be specifically identified by hybridoma produced monoclonal antibodies (MoAbs; LEU-4 and LEU-1; Becton-Dick- inson, Mountain view, CA) . An indirect immunolabeling procedure, with goat anti-murine IgG adsorbed on the surface of 5 nm colloidal gold particles (GAM-G5, Janssen Pharmaceutica, Beerse, Belgium) has been used. Backscattered Electron Imaging (BEI) in a field emission scanning electronmicroscope (SEM) and transmission electron microscopy of thin sections of lymphocytes labeled before plastic embedding, were both used to identify and quantitate gold labeled cell surface sites, Estimating that the thickness of “silver” sections is approximately 60 nm and counting the number of gold particles on the entire cell perimeter, we calculated that, for LEU-4, the number of markers per um2 of cell surface is in the 140-160 range (Fig.l). Cell contour length measurements indicated that the surface of one lymphocyte is approximately 130-160 um2 that of a smooth sphere of identical diameter, reflecting the role of microvilli in expanding the surface area. The total number of gold labeled sites on the surface of one lymphocyte averages, therefore between 20,000 and 24,000 per cell.


1994 ◽  
Vol 33 (01) ◽  
pp. 157-160 ◽  
Author(s):  
S. Kruse-Andersen ◽  
J. Kolberg ◽  
E. Jakobsen

Abstract:Continuous recording of intraluminal pressures for extended periods of time is currently regarded as a valuable method for detection of esophageal motor abnormalities. A subsequent automatic analysis of the resulting motility data relies on strict mathematical criteria for recognition of pressure events. Due to great variation in events, this method often fails to detect biologically relevant pressure variations. We have tried to develop a new concept for recognition of pressure events based on a neural network. Pressures were recorded for over 23 hours in 29 normal volunteers by means of a portable data recording system. A number of pressure events and non-events were selected from 9 recordings and used for training the network. The performance of the trained network was then verified on recordings from the remaining 20 volunteers. The accuracy and sensitivity of the two systems were comparable. However, the neural network recognized pressure peaks clearly generated by muscular activity that had escaped detection by the conventional program. In conclusion, we believe that neu-rocomputing has potential advantages for automatic analysis of gastrointestinal motility data.


2019 ◽  
Author(s):  
Victor Bloemendal ◽  
Floris P. J. T. Rutjes ◽  
Thomas J. Boltje ◽  
Daan Sondag ◽  
Hidde Elferink ◽  
...  

<p>In this manuscript we describe a modular pathway to synthesize biologically relevant (–)-<i>trans</i>-Δ<sup>8</sup>-THC derivatives, which can be used to modulate the pharmacologically important CB<sub>1</sub> and CB<sub>2</sub> receptors. This pathway involves a one-pot Friedel-Crafts alkylation/cyclization protocol, followed by Suzuki-Miyaura cross-coupling reactions and gives rise to a series of new Δ<sup>8</sup>-THC derivatives. In addition, we demonstrate using extensive NMR evidence that similar halide-substituted Friedel-Crafts alkylation/cyclization products in previous articles were wrongly assigned as the para-isomers, which also has consequence for the assignment of the subsequent cross-coupled products and interpretation of their biological activity. </p> <p>Considering the importance of the availability of THC derivatives in medicinal chemistry research and the fact that previously synthesized compounds were wrongly assigned, we feel this research is describing a straightforward pathway into new cannabinoids.</p>


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