Very-large-scale motions in rough-bed open-channel flow

Acknowledgements The study has been supported by two EPSRC/UK grants, ‘High-resolution numerical and experimental studies of turbulence-induced sediment erosion and near-bed transport’ (EP/G056404/1) and ‘Bed friction in rough-bed free-surface flows: a theoretical framework, roughness regimes, and quantification’ (EP/K041169/1). Discussions with I. Marusic and comments of three anonymous reviewers are greatly appreciated.Peer reviewedPublisher PD

The role and therapeutic targeting of α-, β- and γ-secretase in Alzheimer's disease

Alzheimer's disease (AD) is the most common form of dementia in the elderly and its prevalence is set to increase rapidly in coming decades. However, there are as yet no available drugs that can halt or even stabilize disease progression. One of the main pathological features of AD is the presence in the brain of senile plaques mainly composed of aggregated β amyloid (Aβ), a derivative of the longer amyloid precursor protein (APP). The amyloid hypothesis proposes that the accumulation of Aβ within neural tissue is the initial event that triggers the disease. Here we review research efforts that have attempted to inhibit the generation of the Aβ peptide through modulation of the activity of the proteolytic secretases that act on APP and discuss whether this is a viable therapeutic strategy for treating AD.<p></p> Alzheimer's disease (AD) is the most common form of dementia in the elderly but as yet there are no drugs that can halt the progression of this disease. In a theory called the ‘amyloid hypothesis’, researchers have proposed that the accumulation of a small protein fragment called beta amyloid or Aβ within brain tissue is the event which triggers Alzheimer's disease. Aβ is a derivative of the longer amyloid precursor protein (APP). Here we review research efforts that have attempted to inhibit the generation of Aβ through modulation of proteins called secretases which cut APP into Aβ. Author edits made on: 20 May 2015

Room temperature spin relaxation in GaAs/AlGaAs multiple quantum wells

We have explored the dependence of electron spin relaxation in undoped GaAs/AlGaAs quantum wells on well width (confinement energy) at 300 K. For wide wells, the relaxation rate tends to the intrinsic bulk value due to the D'yakonov-Perel (DP) mechanism with momentum scattering by phonons. In narrower wells, there is a strong dependence of relaxation rate on well width, as expected for the DP mechanism, but also considerable variation between samples from different sources, which we attribute to differences in sample interface morphology. (C) 1998 American Institute of Physics. [S0003-6951(98)02541-8].</p

Selective inhibition of phosphodiesterases 4, 5 and 9 induces HSP20 phosphorylation and attenuates amyloid beta 1-42 mediated cytotoxicity

Phosphodiesterase (PDE) inhibitors are currently under evaluation as agents that may facilitate the improvement of cognitive impairment associated with Alzheimer's disease. Our aim was to determine whether inhibitors of PDEs 4,5 and 9 could alleviate the cytotoxic effects of amyloid beta 1–42 (Aβ1-42) via a mechanism involving the small heatshock protein HSP20. We show that inhibition of PDEs 4,5 and 9 but not 3 induces the phosphorylation of HSP20 which, in turn, increases the co-localisation between the chaperone and Aβ1-42 to significantly decrease the toxic effect of the peptide. We conclude that inhibition of PDE9 is most effective to combat Aβ1-42 cytotoxicity in our cell model

High magnetic field studies of the Vortex Lattice structure in YBa2Cu3O7

We report on small angle neutron scattering measurements of the vortex lattice in twin-free YBa2Cu3O7, extending the previously investigated maximum field of 11~T up to 16.7~T with the field applied parallel to the c axis. This is the first microscopic study of vortex matter in this region of the superconducting phase. We find the high field VL displays a rhombic structure, with a field-dependent coordination that passes through a square configuration, and which does not lock-in to a field-independent structure. The VL pinning reduces with increasing temperature, but is seen to affect the VL correlation length even above the irreversibility temperature of the lattice structure. At high field and temperature we observe a melting transition, which appears to be first order, with no detectable signal from a vortex liquid above the transition

Building a 3.5 m prototype interferometer for the Q & A vacuum birefringence experiment and high precision ellipsometry

We have built and tested a 3.5 m high-finesse Fabry-Perot prototype inteferometer with a precision ellipsometer for the QED test and axion search (Q & A) experiment. We use X-pendulum-double-pendulum suspension designs and automatic control schemes developed by the gravitational-wave detection community. Verdet constant and Cotton-Mouton constant of the air are measured as a test. Double modulation with polarization modulation 100 Hz and magnetic-field modulation 0.05 Hz gives 10^{-7} rad phase noise for a 44-minute integration.Comment: This draft has been presented in the 5th Edoardo Amaldi Conference on Gravitational Wave

Ras/Raf-1/MAPK pathway mediates response to tamoxifen but not chemotherapy in breast cancer patients

&lt;b&gt;Purpose&lt;/b&gt;: The expression and activation of the Ras/Raf-1/mitogen-activated protein kinase (MAPK) pathway plays an important role in the development and progression of cancer, and may influence response to treatments such as tamoxifen and chemotherapy. In this study we investigated whether the expression and activation of the key components of this pathway influenced clinical outcome, to test the hypothesis that activation of the MAPK pathway drives resistance to tamoxifen and chemotherapy in women with breast cancer. &lt;b&gt;Experimental Design&lt;/b&gt;: Breast tumors from patients at the Glasgow Royal Infirmary and others treated within the BR9601 trial were analyzed for expression of the three Ras isoforms, total Raf-1, active and inactive forms of Raf-1 [pRaf(ser338) and pRaf(ser259), respectively], MAPK, and phospho-MAPK using an immunohistochemical approach. Analyses were done with respect to disease free-survival and overall survival. &lt;b&gt;Results&lt;/b&gt;: Expression and activation of the Ras pathway was associated with loss of benefit from treatment with tamoxifen but not chemotherapy. Overexpression of pRaf(ser338) was associated with shortened disease-free and overall survival time in univariate analyses. Multivariate analysis suggested pRaf(ser338) was independent of known prognostic markers in predicting outcome following tamoxifen treatment (&lt;i&gt;P&lt;/i&gt;=0.03). &lt;b&gt;Conclusion&lt;/b&gt;: This study suggests that activation of the Ras pathway predicts for poor outcome on tamoxifen but not chemotherapy, and identifies pRaf(ser338) as a potential marker of resistance to estrogen receptor–targeted therapy. In addition, it suggests that expression of pRaf(ser338) could identify patients for whom tamoxifen alone is insufficient adjuvant systemic therapy, but for whom the addition of chemotherapy may be of benefit

Measurement of Orbital Decay in the Double Neutron Star Binary PSR B2127+11C

We report the direct measurement of orbital period decay in the double neutron star pulsar system PSR B2127+11C in the globular cluster M15 at the rate of $(-3.95 \pm 0.13) \times 10^{-12}$, consistent with the prediction of general relativity at the $\sim 3$ level. We find the pulsar mass to be $m_p = (1.358 \pm 0.010) M_\odot$ and the companion mass $m_c = (1.354 \pm 0.010) M_\odot$. We also report long-term pulse timing results for the pulsars PSR B2127+11A and PSR B2127+11B, including confirmation of the cluster proper motion.Comment: 12 pages, 4 figures, accepted for publication in ApJ