Non-ergodicity of the motion in three dimensional steep repelling dispersing potentials

It is demonstrated numerically that smooth three degrees of freedom Hamiltonian systems which are arbitrarily close to three dimensional strictly dispersing billiards (Sinai billiards) have islands of effective stability, and hence are non-ergodic. The mechanism for creating the islands are corners of the billiard domain.Comment: 6 pages, 8 figures, submitted to Chao

Dysfunctional transcripts are formed by alternative polyadenylation in OPMD

Molecular Technology and Informatics for Personalised Medicine and HealthFunctional Genomics of Muscle, Nerve and Brain Disorder

Measuring intra-individual physical activity variability using consumer-grade activity devices

Many existing sedentary behavior and physical activity studies focus on primary outcomes that assess change by comparing participants' activity from baseline to post-intervention. With the widespread availability of consumer-grade devices that track activity daily, researchers do not need to rely on those endpoint measurements alone. Using activity trackers, researchers can collect remote data about the process of behavior change and future maintenance of the change by measuring participants’ intra-individual physical activity variability. Measuring intra-individual physical activity variability can enable researchers to create tailored and dynamic interventions that account for different physical activity behavior change trajectories, and by that, improve participants' program adherence, enhance intervention design and management, and advance interventions measurements' reliability. We propose an application of intra-individual physical activity variability as a measurement and provide three use cases within interventions. Intra-individual physical activity variability can be used: prior to the intervention period, where relationships between participants' intra-individual physical activity variability and individual characteristics can be used to predict adherence and subsequently tailor interventions; during the intervention period, to assess progress and subsequently boost interventions; and after the intervention, to obtain a reliable representation of the change in primary outcome

Rumen cellulosomics : divergent fiber-degrading strategies revealed by comparative genome-wide analysis of six ruminococcal strains

Peer reviewedPublisher PD

Complexity of the Ruminococcus flavefaciens FD-1 cellulosome reflects an expansion of family-related protein-protein interactions

This work was supported in part by the European Union, Area NMP.2013.1.1–2: Self-assembly of naturally occurring nanosystems: CellulosomePlus Project number: 604530, and by the EU Seventh Framework Programme (FP7 2007–2013) under the WallTraC project (Grant Agreement no 263916), and BioStruct-X (grant agreement no 283570). This paper reflects the author’s views only. The European Community is not liable for any use that may be made of the information contained herein. CMGAF is also supported by Fundação para a Ciência e a Tecnologia (Lisbon, Portugal) through grants PTDC/BIA-PRO/103980/2008 and EXPL/BIA-MIC/1176/2012. EAB is also funded by a grant (No. 1349/13) from the Israel Science Foundation (ISF), Jerusalem, Israel and by a grant (No. 2013284) from the U.S.-Israel Binational Science Foundation (BSF). E.A.B. is the incumbent of The Maynard I. and Elaine Wishner Chair of Bio-organic Chemistry.Peer reviewedPublisher PD

Transferable interactions of Li+ and Mg2+ ions in polarizable models

Therapeutic implications of Li(+), in many cases, stem from its ability to inhibit certain Mg(2+)-dependent enzymes, where it interacts with or substitutes for Mg(2+). The underlying details of its action are, however, unknown. Molecular simulations can provide insights, but their reliability depends on how well they describe relative interactions of Li(+) and Mg(2+) with water and other biochemical groups. Here, we explore, benchmark, and recommend improvements to two simulation approaches: the one that employs an all-atom polarizable molecular mechanics (MM) model and the other that uses a hybrid quantum and MM implementation of the quasi-chemical theory (QCT). The strength of the former is that it describes thermal motions explicitly and that of the latter is that it derives local contributions from electron densities. Reference data are taken from the experiment, and also obtained systematically from CCSD(T) theory, followed by a benchmarked vdW-inclusive density functional theory. We find that the QCT model predicts relative hydration energies and structures in agreement with the experiment and without the need for additional parameterization. This implies that accurate descriptions of local interactions are essential. Consistent with this observation, recalibration of local interactions in the MM model, which reduces errors from 10.0 kcal/mol to 1.4 kcal/mol, also fixes aqueous phase properties. Finally, we show that ion–ligand transferability errors in the MM model can be reduced significantly from 10.3 kcal/mol to 1.2 kcal/mol by correcting the ligand’s polarization term and by introducing Lennard-Jones cross-terms. In general, this work sets up systematic approaches to evaluate and improve molecular models of ions binding to proteins

Quasiphasematched frequency doubling in a waveguide of a 1560 nm diode laser and locking to the rubidium D absorption lines

An external-cavity 1560-nm diode laser was frequency doubled in a 3-cm-long periodically poled LiNbO 3 waveguide doubler with 120% W 21 conversion efficiency. The 780-nm light was used to detect the D 2 transitions of Rb, and the laser frequency was locked to Doppler-broadened lines of Rb. Furthermore, the ϳ1 mW of second-harmonic power was sufficient for detecting the sub-Doppler lines of Rb, and the laser was locked to a 87 Rb crossover line. © 1996 Optical Society of America Lasers operating at f ixed and known frequencies near the 1550-nm transmission window of optical fibers are required for densely packed multiwavelength communication systems. 1 Such lasers may also be required for coherent optical communication systems to ease the acquisition and locking of a local oscillator laser to a transmitter laser and for achieving coldstart communication. 2 In addition, absolutely stabilized sources may be applicable to fiber-optic sensors and as frequency standards for high-resolution spectroscopy. Optical frequency standards can be realized by locking to atomic or molecular transitions. Molecular absorptions in the 1550-nm wavelength range, e.g., ammonia, 3 acetylene, 4,5 and hydrogen iodide, 6 are usually weak overtone or combination bands. Lasers at 1550 nm were locked to Doppler-broadened transitions of these molecules. 5 Atomic transitions that can be used as frequency references, e.g., transitions between excited states in noble gases (Ar, Kr, etc.) 2 and transitions between upper levels in Rb, 7 do not originate from the ground state. Hence additional excitation, electrical (with a discharge lamp 2 ) or optical (with another laser 7 ), is required for populating one of these upper levels. An alternative approach that may overcome the difficulties associated with frequency references near 1550 nm is second-harmonic generation (SHG) and locking to absorption lines near 780 nm. A thoroughly characterized reference at 780.25 nm is the atomicRb D 2 line. 8 This reference was already used to stabilize 1560-nm laser diodes with the internally generated second harmonic of diode lasers, 9 but the SHG power was only 2 pW. Recently bulk external SHG in KNbO 3 crystal with a second-harmonic power of 2.2 nW was employed for the same goal. 10 Locking to a Doppler-broadened line was possible, but the power level was not sufficient to saturate the absorption for locking to sub-Doppler lines. Frequency doubling in KNbO 3 was also used to lock to K at 770 nm, 11 with a second-harmonic power of 20 nW. Because the power levels of diode lasers near 1550 nm are quite low (typically a few milliwatts), higher-eff iciency frequency conversion is required for detection and locking to sub-Doppler lines as well as to improve the signal-to-noise ratio for locking to Dopplerbroadened lines. A technique that may achieve this goal is quasi-phase-matched 12 (QPM) frequency conversion in a waveguide. In QPM doubling, a periodic modulation of the material nonlinear coefficient compensates for the phase velocity mismatch between the fundamental and the second-harmonic waves. This technique permits the use of large nonlinear coefficients, e.g., d 33 , in LiNbO 3 that are not accessible by birefringent phase matching. In LiNbO 3 the improvement in conversion eff iciency compared with birefringent phase matching is ͑2d 33 ͞pd 31 ͒ 2 ϳ 20, where 2͞p is the QPM reduction factor and d 31 is the effective nonlinear coeff icient for birefringent phase matching. Further improvement in conversion efficiency is obtained by waveguide confinement. Furthermore, room-temperature operation, as well as relaxed temperature and wavelength tolerances, is possible. The use of QPM waveguides for optical frequency standards at the 1300-nm fiber-optic transmission window has already been demonstrated 13 : the second harmonic of a 1319-nm Nd:YAG laser was locked to I 2 transitions near 660 nm. We applied the technique of waveguide QPM frequency conversion for efficient single-pass doubling of a 1560-nm external-cavity diode laser. The second-harmonic power was sufficiently high that we could detect sub-Doppler lines, and the laser was locked to Doppler-broadened lines as well as to subDoppler lines of Rb near 780 nm. The experimental setup for locking to Doppler-broadened lines of Rb is shown i

Spatial determinants of specificity in insulin action

Insulin is a potent stimulator of intermediary metabolism, however the basis for the remarkable specificity of insulin's stimulation of these pathways remains largely unknown. This review focuses on the role compartmentalization plays in insulin action, both in signal initiation and in signal reception. Two examples are discussed: (1) a novel signalling pathway leading to the phosphorylation of the caveolar coat protein caveolin, and (2) a recently identified scaffolding protein, PTG, involved directly in the regulation of enzymes controlling glycogen metabolism.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45334/1/11010_2004_Article_156837.pd

Whole Genome Amplification of DNA for Genotyping Pharmacogenetics Candidate Genes

Whole genome amplification (WGA) technologies can be used to amplify genomic DNA when only small amounts of DNA are available. The Multiple Displacement Amplification Phi polymerase based amplification has been shown to accurately amplify DNA for a variety of genotyping assays; however, it has not been tested for genotyping many of the clinically relevant genes important for pharmacogenetic studies, such as the cytochrome P450 genes, that are typically difficult to genotype due to multiple pseudogenes, copy number variations, and high similarity to other related genes. We evaluated whole genome amplified samples for Taqman™ genotyping of SNPs in a variety of pharmacogenetic genes. In 24 DNA samples from the Coriell human diversity panel, the call rates, and concordance between amplified (∼200-fold amplification) and unamplified samples was 100% for two SNPs in CYP2D6 and one in ESR1. In samples from a breast cancer clinical trial (Trial 1), we compared the genotyping results in samples before and after WGA for three SNPs in CYP2D6, one SNP in CYP2C19, one SNP in CYP19A1, two SNPs in ESR1, and two SNPs in ESR2. The concordance rates were all >97%. Finally, we compared the allele frequencies of 143 SNPs determined in Trial 1 (whole genome amplified DNA) to the allele frequencies determined in unamplified DNA samples from a separate trial (Trial 2) that enrolled a similar population. The call rates and allele frequencies between the two trials were 98 and 99.7%, respectively. We conclude that the whole genome amplified DNA is suitable for Taqman™ genotyping for a wide variety of pharmacogenetically relevant SNPs