Isoform-selective susceptibility of DISC1/phosphodiesterase-4 complexes to dissociation by elevated intracellular cAMP levels

Disrupted-in-schizophrenia 1 (DISC1) is a genetic susceptibility factor for schizophrenia and related severe psychiatric conditions. DISC1 is a multifunctional scaffold protein that is able to interact with several proteins, including the independently identified schizophrenia risk factor phosphodiesterase-4B (PDE4B). Here we report that the 100 kDa full-length DISC1 isoform (fl-DISC1) can bind members of each of the four gene, cAMP-specific PDE4 family. Elevation of intracellular cAMP levels, so as to activate protein kinase A, caused the release of PDE4D3 and PDE4C2 isoforms from fl-DISC1 while not affecting binding of PDE4B1 and PDE4A5 isoforms. Using a peptide array strategy, we show that PDE4D3 binds fl-DISC1 through two regions found in common with PDE4B isoforms, the interaction of which is supplemented because of the presence of additional PDE4B-specific binding sites. We propose that the additional binding sites found in PDE4B1 underpin its resistance to release during cAMP elevation. We identify, for the first time, a functional distinction between the 100 kDa long DISC1 isoform and the short 71 kDa isoform. Thus, changes in the expression pattern of DISC1 and PDE4 isoforms offers a means to reprogram their interaction and to determine whether the PDE4 sequestered by DISC1 is released after cAMP elevation. The PDE4B-specific binding sites encompass point mutations in mouse Disc1 that confer phenotypes related to schizophrenia and depression and that affect binding to PDE4B. Thus, genetic variation in DISC1 and PDE4 that influence either isoform expression or docking site functioning may directly affect psychopathology

Three-particle entanglement versus three-particle nonlocality

The notions of three-particle entanglement and three-particle nonlocality are discussed in the light of Svetlichny's inequality [Phys. Rev. D 35, 3066 (1987)]. It is shown that there exist sets of measurements which can be used to prove three-particle entanglement, but which are nevertheless useless at proving three-particle nonlocality. In particular, it is shown that the quantum predictions giving a maximal violation of Mermin's three-particle Bell inequality [Phys. Rev. Lett. 65, 1838 (1990)] can be reproduced by a hybrid hidden variables model in which nonlocal correlations are present only between two of the particles. It should be possible, however, to test the existence of both three-particle entanglement and three-particle nonlocality for any given quantum state via Svetlichny's inequality.Comment: REVTeX4, 4 pages, journal versio

Characterization of ovine strains of Mycobacterium paratuberculosis by restriction endonuclease analysis and DNA hybridization

Restriction endonuclease analysis and DNA hybridization revealed five ovine strains of Mycobacterium paratuberculosis from South Africa had identical DNA patterns to an ovine strain from Canada. Genetically this strain type has features in common with the two major groups of M. paratuberculosis.The articles have been scanned in colour with a HP Scanjet 5590; 600dpi. Adobe Acrobat XI Pro was used to OCR the text and also for the merging and conversion to the final presentation PDF-format.mn201

Hydrogen-Helium Mixtures at High Pressure

The properties of hydrogen-helium mixtures at high pressure are crucial to address important questions about the interior of Giant planets e.g. whether Jupiter has a rocky core and did it emerge via core accretion? Using path integral Monte Carlo simulations, we study the properties of these mixtures as a function of temperature, density and composition. The equation of state is calculated and compared to chemical models. We probe the accuracy of the ideal mixing approximation commonly used in such models. Finally, we discuss the structure of the liquid in terms of pair correlation functions.Comment: Proceedings article of the 5th Conference on Cryocrystals and Quantum Crystals in Wroclaw, Poland, submitted to J. Low. Temp. Phys. (2004

Strengthening mechanisms in an Al-Fe-Cr-Ti nano-quasicrystalline alloy and composites

We report a study of the structure-processing-property relationships in a high strength AlFeCrTi nano-quasicrystalline alloy and composites containing 10 and 20 vol% ductilising pure Al fibres. The superimposed contributions of several different strengthening mechanisms have been modelled analytically using data obtained from systematic characterisation of the monolithic alloy bar. An observed yield strength of 544 MPa has been substantiated from a combination of solid solution strengthening, work hardening, precipitation hardening and Hall-Petch grain size dependent effects. These materials have been shown by other authors in previous published work to be highly sensitive to the size distribution of particles in the powder from which they are made, and the subsequent thermomechanical processing conditions. The processing condition employed in this study provided micron-sized grains with a strong [111] preferential orientation along the extrusion direction and a bimodal size distribution of the icosahedral nano-quasicrystalline precipitates. Both were deemed to be a significant contributor to the high yield strength observed. The addition of pure Al fibres was found to decrease the yield strength linearly with increasing Al content, and to augment the ductility of the composites.Industrial collaborator ALPOCO Ltd. (and more specifically Steve McArthur) provided the powders. Dr. Karen Kruska and Dr. Alan Xu assisted with sample preparation of FIB lift-out specimens of the atomised powder for TEM analysis. EPSRC Project EP/E040608/1 provided financial support. M. Galano thanks the RAEng for their support by means of a Research Fellowship. F. Audebert and M. Galano thank PICT-Oxford2010/2831. F. Audebert also thanks UBACyT20020130100663 and FONARSEC FS Nano 2010/11 for financial support.Peer Reviewe

Black holes and Hawking radiation in spacetime and its analogues

These notes introduce the fundamentals of black hole geometry, the thermality of the vacuum, and the Hawking effect, in spacetime and its analogues. Stimulated emission of Hawking radiation, the trans-Planckian question, short wavelength dispersion, and white hole radiation in the setting of analogue models are also discussed. No prior knowledge of differential geometry, general relativity, or quantum field theory in curved spacetime is assumed.Comment: 31 pages, 9 figures; to appear in the proceedings of the IX SIGRAV School on 'Analogue Gravity', Como (Italy), May 2011, eds. D. Faccio et. al. (Springer

The effect of hyperbaric oxygen and blood platelet injection therapy on the healing of hamstring injuries in rugby players

There are a number of ultra-structural and immuno-histochemical studies involving hyperbaric oxygen treatment in skeletal muscle, as well as soft tissue healing. Hyperbaric oxygen therapy, in conjunction with blood platelet injection therapy, serves as a valuable addition to previously known and trusted rehabilitation techniques and protocols for the healing of musculoskeletal or soft tissue injuries. The primary aim of this case report is to describe the effect on the recovery time of hamstring injuries when combining hyperbaric oxygen therapy (HBOT) and platelet rich plasma (PRP) injection therapy with exercise rehabilitation. A retrospective, post-intervention data analysis was used in this case series report. Data, obtained through collaboration with a professional rugby union and an accredited Hyperbaric Medicine (HBOT) Centre, were analysed using the Statistical Programme for the Social Sciences (SPSS) software. The significance value was set at 5%. A significant decrease in the injury time of the hamstring injuries in rugby players was noted, with a 38% reduction in injury time in players with a grade-one injury, and 45.7% reduction in players with a grade-two injury. In terms of recurrent injuries, 62% of players with grade-one injuries remained uninjured after treatment, and the percentage of re-injured players with grade-two injuries was 0% after HBOT, PRP and physical therapy treatment. The notion that the healing time of hamstring injuries will decrease when HBOT and PRP are administered in conjunction with traditional rehabilitation therapy is indicated by the data of this report.http://www.ajol.info/journal_index.php?jid=153&ab=ajpherd2017-11-30am201

Nuclear effects in the Drell-Yan process at very high energies

We study Drell-Yan (DY) dilepton production in proton(deuterium)-nucleus and in nucleus-nucleus collisions within the light-cone color dipole formalism. This approach is especially suitable for predicting nuclear effects in the DY cross section for heavy ion collisions, as it provides the impact parameter dependence of nuclear shadowing and transverse momentum broadening, quantities that are not available from the standard parton model. For p(D)+A collisions we calculate nuclear shadowing and investigate nuclear modification of the DY transverse momentum distribution at RHIC and LHC for kinematics corresponding to coherence length much longer than the nuclear size. Calculations are performed separately for transversely and longitudinally polarized DY photons, and predictions are presented for the dilepton angular distribution. Furthermore, we calculate nuclear broadening of the mean transverse momentum squared of DY dileptons as function of the nuclear mass number and energy. We also predict nuclear effects for the cross section of the DY process in heavy ion collisions. We found a substantial nuclear shadowing for valence quarks, stronger than for the sea.Comment: 46 pages, 18 figures, title changed and some discussion added, accepted for publication in PR

Low-noise AlGaAsSb avalanche photodiodes for 1550 nm light detection

Avalanche photodiodes (APD) can improve the signal to noise ratio in applications such as LIDAR, range finding and optical time domain reflectometry. However, APDs operating at eye-safe wavelengths around 1550 nm currently limit the sensitivity because the APDs’ impact ionization coefficients in the avalanche layers are too similar, leading to poor excess noise performance. The material AlGaAsSb has highly dissimilar impact ionization coefficients (with electrons dominating the avalanche gain) so is an excellent avalanche material for 1550 nm wavelength APDs. We previously reported a 1550 nm wavelength AlGaAsSb SAM APD with extremely low excess noise factors, 1.93 at a gain of 10 and 2.94 at a gain of 20. Using a more optimized design, we have now realized an AlGaAsSb SAM APD with a lower dark current (7 nA at a gain of 10 from a 230 μm diameter APD), a higher responsivity (0.97 A/W) and a lower excess noise (1.9 at a gain of 40), compared to our previous SAM APD. Noise-equivalent-power (NEP) measurements of our APD with a simple transimpedance amplifier circuit produced an NEP 12 times lower than a state-of-the-art APD under identical test conditions, confirming the advantage of low-noise AlGaAsSb SAM APDs