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http://www.archive.org/details/widebandperforma00counU.S. Navy (U.S.N.) author

Pseudophosphorylation of tau at S422 enhances SDS-stable dimer formation and impairs both anterograde and retrograde fast axonal transport

AbstractIn Alzheimer's disease (AD), tau undergoes numerous modifications, including increased phosphorylation at serine-422 (pS422). In the human brain, pS422 tau protein is found in prodromal AD, correlates well with cognitive decline and neuropil thread pathology, and appears associated with increased oligomer formation and exposure of the N-terminal phosphatase-activating domain (PAD). However, whether S422 phosphorylation contributes to toxic mechanisms associated with disease-related forms of tau remains unknown. Here, we report that S422-pseudophosphorylated tau (S422E) lengthens the nucleation phase of aggregation without altering the extent of aggregation or the types of aggregates formed. When compared to unmodified tau aggregates, the S422E modification significantly increased the amount of SDS-stable tau dimers, despite similar levels of immunoreactivity with an oligomer-selective antibody (TOC1) and another antibody that reports PAD exposure (TNT1). Vesicle motility assays in isolated squid axoplasm further revealed that S422E tau monomers inhibited anterograde, kinesin-1 dependent fast axonal transport (FAT). Unexpectedly, and unlike unmodified tau aggregates, which selectively inhibit anterograde FAT, aggregates composed of S422E tau were found to inhibit both anterograde and retrograde FAT. Highlighting the relevance of these findings to human disease, pS422 tau was found to colocalize with tau oligomers and with a fraction of tau showing increased PAD exposure in the human AD brain. This study identifies novel effects of pS422 on tau biochemical properties, including prolonged nucleation and enhanced dimer formation, which correlate with a distinct inhibitory effect on FAT. Taken together, these findings identify a novel mechanistic basis by which pS422 confers upon tau a toxic effect that may directly contribute to axonal dysfunction in AD and other tauopathies

Patient-reported outcome data generated in a clinical intervention in community mental health care - psychometric properties

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

The acute muscular response to two distinct blood flow restriction protocols

The purpose of this study was to determine acute physiological and perceptual responses to two commonly implemented blood flow restriction protocols. Using a within-subject design, 15 participants (age ∼25) performed four sets of unilateral elbow flexion with each arm. One arm exercised using a 3-cm elastic cuff inflated to 160 mmHg, whereas the other arm exercised using a 5-cm nylon cuff inflated to 40% of the individual’s arterial occlusion pressure. While both protocols elicited increases in acute muscle thickness [pre: 4.5 (0.2) cm, post: 5.0 (0.2) cm; p < 0.001] and electromyography amplitude [first 3 reps: 55 (5) %MVC; last 3 reps: 87 (10) %MVC], there were no differences between conditions. Both protocols produced decreases in post-exercise strength (pre: 70 Nm, post: 51 Nm; p < 0.001) with no difference between conditions. The nylon protocol resulted in more repetitions during sets 2 [13 (2) vs. 9 (4); p = 0.001] and 3 [10 (2) vs. 7 (4); p = 0.05], while producing lower levels of discomfort following each set (average 3 vs. 4; p < 0.05). In conclusion, both protocols produced similar acute responses thought to be important for promoting muscle growth. However, the use of arbitrary pressures may place some individuals under complete arterial occlusion which may increase the potential risk of an adverse event

A magnetically-driven piston pump for ultra-clean applications

A magnetically driven piston pump for xenon gas recirculation is presented. The pump is designed to satisfy extreme purity and containment requirements, as is appropriate for the recirculation of isotopically enriched xenon through the purification system and large liquid xenon TPC of EXO-200. The pump, using sprung polymer gaskets, is capable of pumping more than 16 standard liters per minute (SLPM) of xenon gas with 750 torr differential pressure.Comment: 6 pages, 5 figure

Observation of two new Ξb−\Xi_b^- baryon resonances

Two structures are observed close to the kinematic threshold in the $\Xi_b^0 \pi^-$ mass spectrum in a sample of proton-proton collision data, corresponding to an integrated luminosity of 3.0 fb$^{-1}$ recorded by the LHCb experiment. In the quark model, two baryonic resonances with quark content $bds$ are expected in this mass region: the spin-parity $J^P = \frac{1}{2}^+$ and $J^P=\frac{3}{2}^+$ states, denoted $\Xi_b^{\prime -}$ and $\Xi_b^{*-}$. Interpreting the structures as these resonances, we measure the mass differences and the width of the heavier state to be $m(\Xi_b^{\prime -}) - m(\Xi_b^0) - m(\pi^{-}) = 3.653 \pm 0.018 \pm 0.006$ MeV$/c^2$, $m(\Xi_b^{*-}) - m(\Xi_b^0) - m(\pi^{-}) = 23.96 \pm 0.12 \pm 0.06$ MeV$/c^2$, $\Gamma(\Xi_b^{*-}) = 1.65 \pm 0.31 \pm 0.10$ MeV, where the first and second uncertainties are statistical and systematic, respectively. The width of the lighter state is consistent with zero, and we place an upper limit of $\Gamma(\Xi_b^{\prime -}) < 0.08$ MeV at 95% confidence level. Relative production rates of these states are also reported.Comment: 17 pages, 2 figure

Differential branching fraction and angular analysis of Λb0→Λμ+μ−\Lambda^{0}_{b} \rightarrow \Lambda \mu^+\mu^- decays

The differential branching fraction of the rare decay $\Lambda^{0}_{b} \rightarrow \Lambda \mu^+\mu^-$ is measured as a function of $q^{2}$, the square of the dimuon invariant mass. The analysis is performed using proton-proton collision data, corresponding to an integrated luminosity of 3.0 \mbox{ fb}^{-1}, collected by the LHCb experiment. Evidence of signal is observed in the $q^2$ region below the square of the $J/\psi$ mass. Integrating over 15 < q^{2} < 20 \mbox{ GeV}^2/c^4 the branching fraction is measured as d\mathcal{B}(\Lambda^{0}_{b} \rightarrow \Lambda \mu^+\mu^-)/dq^2 = (1.18 ^{+ 0.09} _{-0.08} \pm 0.03 \pm 0.27) \times 10^{-7} ( \mbox{GeV}^{2}/c^{4})^{-1}, where the uncertainties are statistical, systematic and due to the normalisation mode, $\Lambda^{0}_{b} \rightarrow J/\psi \Lambda$, respectively. In the $q^2$ intervals where the signal is observed, angular distributions are studied and the forward-backward asymmetries in the dimuon ($A^{l}_{\rm FB}$) and hadron ($A^{h}_{\rm FB}$) systems are measured for the first time. In the range 15 < q^2 < 20 \mbox{ GeV}^2/c^4 they are found to be A^{l}_{\rm FB} = -0.05 \pm 0.09 \mbox{ (stat)} \pm 0.03 \mbox{ (syst)} and A^{h}_{\rm FB} = -0.29 \pm 0.07 \mbox{ (stat)} \pm 0.03 \mbox{ (syst)}.Comment: 27 pages, 10 figures, Erratum adde

Observation of associated production of a ZZ boson with a DD meson in the~forward region

A search for associated production of a $Z$ boson with an open charm meson is presented using a data sample, corresponding to an integrated luminosity of $1.0\,\mathrm{fb}^{-`}$ of proton--proton collisions at a centre-of-mass energy of 7\,TeV, collected by the LHCb experiment. %% Seven candidate events for associated production of a $Z$ boson with a $D^0$ meson and four candidate events for a $Z$ boson with a $D^+$ meson are observed with a combined significance of 5.1standard deviations. The production cross-sections in the forward region are measured to be $$\sigma_{Z\rightarrow\mu^+\mu^-\!,D^0} = 2.50\pm1.12\pm0.22pb$$ $$\sigma_{Z\rightarrow\mu^+\mu^-\!,D^+} = 0.44\pm0.23\pm0.03pb,$$ where the first uncertainty is statistical and the second systematic.Comment: 18 pages, 2 figure

First observation and amplitude analysis of the B−→D+K−π−B^{-}\to D^{+}K^{-}\pi^{-} decay

The $B^{-}\to D^{+}K^{-}\pi^{-}$ decay is observed in a data sample corresponding to $3.0~\rm{fb}^{-1}$ of $pp$ collision data recorded by the LHCb experiment during 2011 and 2012. Its branching fraction is measured to be ${\cal B}(B^{-}\to D^{+}K^{-}\pi^{-}) = (7.31 \pm 0.19 \pm 0.22 \pm 0.39) \times 10^{-5}$ where the uncertainties are statistical, systematic and from the branching fraction of the normalisation channel $B^{-}\to D^{+}\pi^{-}\pi^{-}$, respectively. An amplitude analysis of the resonant structure of the $B^{-}\to D^{+}K^{-}\pi^{-}$ decay is used to measure the contributions from quasi-two-body $B^{-}\to D_{0}^{*}(2400)^{0}K^{-}$, $B^{-}\to D_{2}^{*}(2460)^{0}K^{-}$, and $B^{-}\to D_{J}^{*}(2760)^{0}K^{-}$ decays, as well as from nonresonant sources. The $D_{J}^{*}(2760)^{0}$ resonance is determined to have spin~1.Comment: 39 pages, 10 figures, submitted to Phys. Rev. D. Updated following erratum 10.1103/PhysRevD.93.11990