ChIPathlon: A competitive assessment for gene regulation tools.

When gene regulation of the cell cycle malfunctions, it frequently causes cancer. Adult, differentiated cells can be reprogrammed to induced pluripotent stem cell; which can then be reprogrammed to heart muscle, skin, etc, to repair damaged tissue (to limited extent in clinical practice). ChIPathlon: Evaluate the performance of all transcription factor mapping (peak calling) methods. To this end, we will develop a scalable and easy to use super computing pipeline to stage data, compare many different peak calling and differential binding site tools, and store all results into a single database

ChIPathlon: A competitive assessment for gene regulation tools.

When gene regulation of the cell cycle malfunctions, it frequently causes cancer. Adult, differentiated cells can be reprogrammed to induced pluripotent stem cell; which can then be reprogrammed to heart muscle, skin, etc, to repair damaged tissue (to limited extent in clinical practice). ChIPathlon: Evaluate the performance of all transcription factor mapping (peak calling) methods. To this end, we will develop a scalable and easy to use super computing pipeline to stage data, compare many different peak calling and differential binding site tools, and store all results into a single database

On the Relation between the Feynman Paradox and the Aharonov–Bohm Effects

The magnetic Aharonov–Bohm (A–B) effect occurs when a point charge interacts with a line of magnetic flux, while its reciprocal, the Aharonov–Casher (A–C) effect, occurs when a magnetic moment interacts with a line of charge. For the two interacting parts of these physical systems, the equations of motion are discussed in this paper. The generally accepted claim is that both parts of these systems do not accelerate, while Boyer has claimed that both parts of these systems do accelerate. Using the Euler–Lagrange equations we predict that in the case of unconstrained motion, only one part of each system accelerates, while momentum remains conserved. This prediction requires a time-dependent electromagnetic momentum. For our analysis of unconstrained motion, the A–B effects are then examples of the Feynman paradox. In the case of constrained motion, the Euler–Lagrange equations give no forces, in agreement with the generally accepted analysis. The quantum mechanical A–B and A–C phase shifts are independent of the treatment of constraint. Nevertheless, experimental testing of the above ideas and further understanding of the A–B effects that are central to both quantum mechanics and electromagnetism could be possible

A wide-angle electron grating bi-prism beam splitter

We demonstrate a wide-angle electron beam splitter capable of producing 1 cm beam separation at the detection plane. The beam splitter utilizes a nanofabricated periodic grating in combination with a bi-prism element. In contrast to devices utilizing only bi-prism elements, the use of the periodic grating causes amplitude, and not wavefront, splitting. Even at maximum separation, beam profiles remain undistorted, providing evidence that coherence is intact. This is a step towards the realization of a large area electron interferometer using such a grating bi-prism combination

Functional Evolution of PLP-dependent Enzymes based on Active-Site Structural Similarities

Families of distantly related proteins typically have very low sequence identity, which hinders evolutionary analysis and functional annotation. Slowly evolving features of proteins, such as an active site, are therefore valuable for annotating putative and distantly related proteins. To date, a complete evolutionary analysis of the functional relationship of an entire enzyme family based on active-site structural similarities has not yet been undertaken. Pyridoxal-5’-phosphate (PLP) dependent enzymes are primordial enzymes that diversified in the last universal ancestor. Using the Comparison of Protein Active Site Structures (CPASS) software and database, we show that the active site structures of PLP-dependent enzymes can be used to infer evolutionary relationships based on functional similarity. The enzymes successfully clustered together based on substrate specificity, function, and three-dimensional fold. This study demonstrates the value of using active site structures for functional evolutionary analysis and the effectiveness of CPASS

Image Harvest: an open-source platform for high-throughput plant image processing and analysis

High-throughput plant phenotyping is an effective approach to bridge the genotype-to-phenotype gap in crops. Phenomics experiments typically result in large-scale image datasets, which are not amenable for processing on desktop computers, thus creating a bottleneck in the image-analysis pipeline. Here, we present an open-source, flexible image-analysis framework, called Image Harvest (IH), for processing images originating from high-throughput plant phenotyping platforms. Image Harvest is developed to perform parallel processing on computing grids and provides an integrated feature for metadata extraction from large-scale file organization. Moreover, the integration of IH with the Open Science Grid provides academic researchers with the computational resources required for processing large image datasets at no cost. Image Harvest also offers functionalities to extract digital traits from images to interpret plant architecture-related characteristics. To demonstrate the applications of these digital traits, a rice (Oryza sativa) diversity panel was phenotyped and genome-wide association mapping was performed using digital traits that are used to describe different plant ideotypes. Three major quantitative trait loci were identified on rice chromosomes 4 and 6, which co-localize with quantitative trait loci known to regulate agronomically important traits in rice. Image Harvest is an open-source software for high-throughput image processing that requires a minimal learning curve for plant biologists to analyze phenomics datasets. Supplementary files (2) attached below

On the relation between the Feynman paradox and Aharonov-Bohm effects

The magnetic Aharonov-Bohm (A-B) effect occurs when a point charge interacts with a line of magnetic flux, while its dual, the Aharonov-Casher (A-C) effect, occurs when a magnetic moment interacts with a line of charge. For the two interacting parts of these physical systems, the equations of motion are discussed in this paper. The generally accepted claim is that both parts of these systems do not accelerate, while Boyer has claimed that both parts of these systems do accelerate. Using the Euler-Lagrange equations we predict that in the case of unconstrained motion only one part of each system accelerates, while momentum remains conserved. This prediction requires a time dependent electromagnetic momentum. For our analysis of unconstrained motion the A-B effects are then examples of the Feynman paradox. In the case of constrained motion, the Euler-Lagrange equations give no forces in agreement with the generally accepted analysis. The quantum mechanical A-B and A-C phase shifts are independent of the treatment of constraint. Nevertheless, experimental testing of the above ideas and further understanding of A-B effects which is central to both quantum mechanics and electromagnetism may be possible.Comment: 21 pages, 5 figures, recently submitted to New Journal of Physic

ISPTM: an Iterative Search Algorithm for Systematic Identification of Post-translational Modifications from Complex Proteome Mixtures

Identifying protein post-translational modifications (PTMs) from tandem mass spectrometry data of complex proteome mixtures is a highly challenging task. Here we present a new strategy, named iterative search for identifying PTMs (ISPTM), for tackling this challenge. The ISPTM approach consists of a basic search with no variable modification, followed by iterative searches of many PTMs using a small number of them (usually two) in each search. The performance of the ISPTM approach was evaluated on mixtures of 70 synthetic peptides with known modifications, on an 18-protein standard mixture with unknown modifications and on real, complex biological samples of mouse nuclear matrix proteins with unknown modifications. ISPTM revealed that many chemical PTMs were introduced by urea and iodoacetamide during sample preparation and many biological PTMs, including dimethylation of arginine and lysine, were significantly activated by Adriamycin treatment in NM associated proteins. ISPTM increased the MS/MS spectral identification rate substantially, displayed significantly better sensitivity for systematic PTM identification than the conventional all-in-one search approach and offered PTM identification results that were complementary to InsPecT and MODa, both of which are established PTM identification algorithms. In summary, ISPTM is a new and powerful tool for unbiased identification of many different PTMs with high confidence from complex proteome mixtures

Searching the protein structure database for ligand-binding site similarities using CPASS v.2

<p>Abstract</p> <p>Background</p> <p>A recent analysis of protein sequences deposited in the NCBI RefSeq database indicates that ~8.5 million protein sequences are encoded in prokaryotic and eukaryotic genomes, where ~30% are explicitly annotated as "hypothetical" or "uncharacterized" protein. Our Comparison of Protein Active-Site Structures (CPASS v.2) database and software compares the sequence and structural characteristics of experimentally determined ligand binding sites to infer a functional relationship in the absence of global sequence or structure similarity. CPASS is an important component of our Functional Annotation Screening Technology by NMR (FAST-NMR) protocol and has been successfully applied to aid the annotation of a number of proteins of unknown function.</p> <p>Findings</p> <p>We report a major upgrade to our CPASS software and database that significantly improves its broad utility. CPASS v.2 is designed with a layered architecture to increase flexibility and portability that also enables job distribution over the Open Science Grid (OSG) to increase speed. Similarly, the CPASS interface was enhanced to provide more user flexibility in submitting a CPASS query. CPASS v.2 now allows for both automatic and manual definition of ligand-binding sites and permits pair-wise, one versus all, one versus list, or list versus list comparisons. Solvent accessible surface area, ligand root-mean square difference, and Cβ distances have been incorporated into the CPASS similarity function to improve the quality of the results. The CPASS database has also been updated.</p> <p>Conclusions</p> <p>CPASS v.2 is more than an order of magnitude faster than the original implementation, and allows for multiple simultaneous job submissions. Similarly, the CPASS database of ligand-defined binding sites has increased in size by ~ 38%, dramatically increasing the likelihood of a positive search result. The modification to the CPASS similarity function is effective in reducing CPASS similarity scores for false positives by ~30%, while leaving true positives unaffected. Importantly, receiver operating characteristics (ROC) curves demonstrate the high correlation between CPASS similarity scores and an accurate functional assignment. As indicated by distribution curves, scores ≥ 30% infer a functional similarity. Software URL: <url>http://cpass.unl.edu</url>.</p

Feynman’s Relativistic Electrodynamics Paradox and the Aharonov-Bohm Effect

An analysis is done of a relativistic paradox posed in the Feynman Lectures of Physics involving two interacting charges. The physical system presented is compared with similar systems that also lead to relativistic paradoxes. The momentum conservation problem for these systems is presented. The relation between the presented analysis and the ongoing debates on momentum conservation in the Aharonov-Bohm problem is discussed