P-Match: transcription factor binding site search by combining patterns and weight matrices

P-Match is a new tool for identifying transcription factor (TF) binding sites in DNA sequences. It combines pattern matching and weight matrix approaches thus providing higher accuracy of recognition than each of the methods alone. P-Match is closely interconnected with the TRANSFAC(®) database. In particular, P-Match uses the matrix library as well as sets of aligned known TF-binding sites collected in TRANSFAC(®) and therefore provides the possibility to search for a large variety of different TF binding sites. Using results of extensive tests of recognition accuracy, we selected three sets of optimized cut-off values that minimize either false negatives or false positives, or the sum of both errors. Comparison with the weight matrix approaches such as Match™ tool shows that P-Match generally provides superior recognition accuracy in the area of low false negative errors (high sensitivity). As familiar to the user of Match™, P-Match also allows to save user-specific profiles that include selected subsets of matrices with corresponding TF-binding sites or user-defined cut-off values. Furthermore, a number of tissue-specific profiles are provided that were compiled by the TRANSFAC(®) team. A public version of the P-Match tool is available at

PASADENA Hyperpolarization of Succinic Acid for MRI and NMR Spectroscopy

We use the PASADENA (parahydrogen and synthesis allow dramatically enhanced nuclear alignment) method to achieve ^(13)C polarization of ∼20% in seconds in 1-^(13)C-succinic-d_2 acid. The high-field ^(13)C multiplets are observed as a function of pH, and the line broadening of C1 is pronounced in the region of the pK values. The ^2J_(CH), ^3J_(CH), and ^3J_(HH) couplings needed for spin order transfer vary with pH and are best resolved at low pH leading to our use of pH ∼3 for both the molecular addition of parahydrogen to 1-^(13)C-fumaric acid-d_2 and the subsequent transfer of spin order from the nascent protons to C1 of the succinic acid product. The methods described here may generalize to hyperpolarization of other carboxylic acids. The C1 spin−lattice relaxation time at neutral pH and 4.7 T is measured as 27 s in H_2O and 56 s in D_2O. Together with known rates of succinate uptake in kidneys, this allows an estimate of the prospects for the molecular spectroscopy of metabolism

Relayed nuclear Overhauser enhancement sensitivity to membrane Cho phospholipids

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155956/1/mrm28258_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155956/2/mrm28258.pd

TRANSFAC(®) and its module TRANSCompel(®): transcriptional gene regulation in eukaryotes

The TRANSFAC(®) database on transcription factors, their binding sites, nucleotide distribution matrices and regulated genes as well as the complementing database TRANSCompel(®) on composite elements have been further enhanced on various levels. A new web interface with different search options and integrated versions of Match™ and Patch™ provides increased functionality for TRANSFAC(®). The list of databases which are linked to the common GENE table of TRANSFAC(®) and TRANSCompel(®) has been extended by: Ensembl, UniGene, EntrezGene, HumanPSD™ and TRANSPRO™. Standard gene names from HGNC, MGI and RGD, are included for human, mouse and rat genes, respectively. With the help of InterProScan, Pfam, SMART and PROSITE domains are assigned automatically to the protein sequences of the transcription factors. TRANSCompel(®) contains now, in addition to the COMPEL table, a separate table for detailed information on the experimental EVIDENCE on which the composite elements are based. Finally, for TRANSFAC(®), in respect of data growth, in particular the gain of Drosophila transcription factor binding sites (by courtesy of the Drosophila DNase I footprint database) and of Arabidopsis factors (by courtesy of DATF, Database of Arabidopsis Transcription Factors) has to be stressed. The here described public releases, TRANSFAC(®) 7.0 and TRANSCompel(®) 7.0, are accessible under

Phase Measurement for Driven Spin Oscillations in a Storage Ring

This paper reports the first simultaneous measurement of the horizontal and vertical components of the polarization vector in a storage ring under the influence of a radio frequency (rf) solenoid. The experiments were performed at the Cooler Synchrotron COSY in J\"ulich using a vector polarized, bunched $0.97\,\textrm{GeV/c}$ deuteron beam. Using the new spin feedback system, we set the initial phase difference between the solenoid field and the precession of the polarization vector to a predefined value. The feedback system was then switched off, allowing the phase difference to change over time, and the solenoid was switched on to rotate the polarization vector. We observed an oscillation of the vertical polarization component and the phase difference. The oscillations can be described using an analytical model. The results of this experiment also apply to other rf devices with horizontal magnetic fields, such as Wien filters. The precise manipulation of particle spins in storage rings is a prerequisite for measuring the electric dipole moment (EDM) of charged particles

Spin tune mapping as a novel tool to probe the spin dynamics in storage rings

Precision experiments, such as the search for electric dipole moments of charged particles using storage rings, demand for an understanding of the spin dynamics with unprecedented accuracy. The ultimate aim is to measure the electric dipole moments with a sensitivity up to 15 orders in magnitude better than the magnetic dipole moment of the stored particles. This formidable task requires an understanding of the background to the signal of the electric dipole from rotations of the spins in the spurious magnetic fields of a storage ring. One of the observables, especially sensitive to the imperfection magnetic fields in the ring is the angular orientation of stable spin axis. Up to now, the stable spin axis has never been determined experimentally, and in addition, the JEDI collaboration for the first time succeeded to quantify the background signals that stem from false rotations of the magnetic dipole moments in the horizontal and longitudinal imperfection magnetic fields of the storage ring. To this end, we developed a new method based on the spin tune response of a machine to artificially applied longitudinal magnetic fields. This novel technique, called \textit{spin tune mapping}, emerges as a very powerful tool to probe the spin dynamics in storage rings. The technique was experimentally tested in 2014 at the cooler synchrotron COSY, and for the first time, the angular orientation of the stable spin axis at two different locations in the ring has been determined to an unprecedented accuracy of better than $2.8\mu$rad.Comment: 32 pages, 15 figures, 7 table

Phase locking the spin precession in a storage ring

This letter reports the successful use of feedback from a spin polarization measurement to the revolution frequency of a 0.97 GeV/$c$ bunched and polarized deuteron beam in the Cooler Synchrotron (COSY) storage ring in order to control both the precession rate ($\approx 121$ kHz) and the phase of the horizontal polarization component. Real time synchronization with a radio frequency (rf) solenoid made possible the rotation of the polarization out of the horizontal plane, yielding a demonstration of the feedback method to manipulate the polarization. In particular, the rotation rate shows a sinusoidal function of the horizontal polarization phase (relative to the rf solenoid), which was controlled to within a one standard deviation range of $\sigma = 0.21$ rad. The minimum possible adjustment was 3.7 mHz out of a revolution frequency of 753 kHz, which changes the precession rate by 26 mrad/s. Such a capability meets a requirement for the use of storage rings to look for an intrinsic electric dipole moment of charged particles

Modeling Ligand Exchange Kinetics in Iridium Complexes Catalyzing SABRE Nuclear Spin Hyperpolarization

Large signal enhancements can be obtained for NMR analytes using the process of nuclear spin hyperpolarization. Organometallic complexes that bind parahydrogen can themselves become hyperpolarized. Moreover, if parahydrogen and a to-be-hyperpolarized analyte undergo chemical exchange with the organometallic complex it is possible to catalytically sensitize the detection of the analyte via hyperpolarization transfer through spin-spin coupling in this organometallic complex. This process is called Signal Amplification By Reversible Exchange (SABRE). Signal intensity gains of several orders of magnitude can thus be created for various compounds in seconds. The chemical exchange processes play a defining role in controlling the efficiency of SABRE because the lifetime of the complex must match the spin-spin couplings. Here, we show how analyte dissociation rates in the key model substrates pyridine (the simplest six-membered heterocycle), 4-aminopyridine (a drug), and nicotinamide (an essential vitamin biomolecule) can be examined. This is achieved for the most widely employed SABRE motif that is based on IrIMes-derived catalysts by 1H 1D and 2D exchange NMR spectroscopy techniques. Several kinetic models are evaluated for their accuracy and simplicity. By incorporating variable temperature analysis, the data yields key enthalpies and entropies of activation that are critical for understanding the underlying SABRE catalyst properties and subsequently optimizing behavior through rational chemical design. While several studies of chemical exchange in SABRE have been reported, this work also aims to establish a toolkit on how to quantify chemical exchange in SABRE and ensure that data can be compared reliably.(Figure presented.