發作性血色素尿症ニ就テ

The α4β2 nicotinic acetylcholine receptor (nAChR) is the most abundant subtype in the brain and exists in two functional stoichiometries: (α4)3(β2)2 and (α4)2(β2)3. A distinct feature of the (α4)3(β2)2 receptor is the biphasic activation response to the endogenous agonist acetylcholine, where it is activated with high potency and low efficacy when two α4-β2 binding sites are occupied and with low potency/high efficacy when a third α4-α4 binding site is occupied. Further, exogenous ligands can bind to the third α4-α4 binding site and potentiate the activation of the receptor by ACh that is bound at the two α4-β2 sites. We propose that perturbations of the recently described pre-activation step when a third binding site is occupied are a key driver of these distinct activation properties. To investigate this, we used a combination of simple linear kinetic models and voltage clamp electrophysiology to determine whether transitions into the pre-activated state were increased when three binding sites were occupied. We separated the binding at the two different sites with ligands selective for the α4-β2 site (Sazetidine-A and TC-2559) and the α4-α4 site (NS9283) and identified that when a third binding site was occupied, changes in the concentration-response curves were best explained by an increase in transitions into a pre-activated state. We propose that perturbations of transitions into a pre-activated state are essential to explain the activation properties of the (α4)3(β2)2 receptor by acetylcholine and other ligands. Considering the widespread clinical use of benzodiazepines, this discovery of a conserved mechanism that benzodiazepines and ACh potentiate receptor activation via a third binding site can be exploited to develop therapeutics with similar properties at other cys-loop receptors

Instrumentation, Field Network And Process Automation for the LHC Cryogenic Line Tests

This paper describes the cryogenic control system and associated instrumentation of the test facility for 3 pre-series units of the LHC Cryogenic Distribution Line. For each unit, the process automation is based on a Programmable Logic Con-troller implementing more than 30 closed control loops and handling alarms, in-terlocks and overall process management. More than 160 sensors and actuators are distributed over 150 m on a Profibus DP/PA network. Parameterization, cali-bration and diagnosis are remotely available through the bus. Considering the diversity, amount and geographical distribution of the instru-mentation involved, this is a representative approach to the cryogenic control system for CERN's next accelerator

Instrumentation, Field Network and Process Automation for the Cryogenic System of the LHC Test String

CERN is now setting up String 2, a full-size prototype of a regular cell of the LHC arc. It is composed of two quadrupole, six dipole magnets, and a separate cryogenic distribution line (QRL) for the supply and recovery of the cryogen. An electrical feed box (DFB), with up to 38 High Temperature Superconducting (HTS) leads, powers the magnets. About 700 sensors and actuators are distributed along four Profibus DP and two Profibus PA field buses. The process automation is handled by two controllers, running 126 Closed Control Loops (CCL). This paper describes the cryogenic control system, associated instrumentation, and their commissioning

Can Weakness in End-Range Plantar Flexion After Achilles Tendon Repair Be Prevented?

Background: Disproportionate end-range plantar flexion weakness, decreased passive stiffness, and inability to perform a heel rise on a decline after Achilles tendon repair are thought to reflect increased tendon compliance or tendon lengthening. Since this was first noted, we have performed stronger repairs and avoided stretching into dorsiflexion for the first 12 weeks after surgery. Hypothesis: Using stronger repairs and avoiding stretching into dorsiflexion would eliminate end-range plantar flexion weakness and normalize passive stiffness. Study Design: Case series; Level of evidence, 4. Methods: Achilles repairs with epitendinous augmentation were performed on 18 patients. Plantar flexion torque, dorsiflexion range of motion (ROM), passive joint stiffness, and standing single-legged heel rise on a decline were assessed at 43 ± 24 months after surgery (range, 9 months to 8 years). Maximum isometric plantar flexion torque was measured at 20° and 10° of dorsiflexion, neutral position, and 10° and 20° of plantar flexion. Passive dorsiflexion ROM was measured with a goniometer. Passive joint stiffness was computed from the increase in passive torque from 10° to 20° of dorsiflexion. Tendon thickness was measured by use of digital calipers. Plantar flexion electromyographic (EMG) data were recorded during strength and functional tests. Analysis of variance and chi-square tests were used to assess weakness and function. Results: Marked weakness was evident on the involved side at 20° of plantar flexion (deficit, 26% ± 18%; Conclusion: The use of stronger repair techniques and attempts to limit tendon elongation by avoiding dorsiflexion stretching did not eliminate weakness in end-range plantar flexion. EMG data confirmed that end-range weakness was not due to neural inhibition. Physiological changes that alter the force transmission capability of the healing tendon may be responsible for this continued impairment. This weakness has implications for high-demand jumping and sprinting after Achilles tendon repair

Private Summation in the Multi-Message Shuffle Model

The shuffle model of differential privacy (Erlingsson et al. SODA 2019; Cheu et al. EUROCRYPT 2019) and its close relative encode-shuffle-analyze (Bittau et al. SOSP 2017) provide a fertile middle ground between the well-known local and central models. Similarly to the local model, the shuffle model assumes an untrusted data collector who receives privatized messages from users, but in this case a secure shuffler is used to transmit messages from users to the collector in a way that hides which messages came from which user. An interesting feature of the shuffle model is that increasing the amount of messages sent by each user can lead to protocols with accuracies comparable to the ones achievable in the central model. In particular, for the problem of privately computing the sum of $n$ bounded real values held by $n$ different users, Cheu et al. showed that $O(\sqrt{n})$ messages per user suffice to achieve $O(1)$ error (the optimal rate in the central model), while Balle et al. (CRYPTO 2019) recently showed that a single message per user leads to $\Theta(n^{1/3})$ MSE (mean squared error), a rate strictly in-between what is achievable in the local and central models. This paper introduces two new protocols for summation in the shuffle model with improved accuracy and communication trade-offs. Our first contribution is a recursive construction based on the protocol from Balle et al. mentioned above, providing $\mathrm{poly}(\log \log n)$ error with $O(\log \log n)$ messages per user. The second contribution is a protocol with $O(1)$ error and $O(1)$ messages per user based on a novel analysis of the reduction from secure summation to shuffling introduced by Ishai et al. (FOCS 2006) (the original reduction required $O(\log n)$ messages per user).Comment: Published at CCS'2

Discontinuous Transition from a Real Bound State to Virtual Bound State in a Mixed-Valence State of SmS

Golden SmS is a paramagnetic, mixed-valence system with a pseudogap. With increasing pressure across a critical pressure Pc, the system undergoes a discontinuous transition into a metallic, anti-ferromagnetically ordered state. By using a combination of thermodynamic, transport, and magnetic measurements, we show that the pseudogap results from the formation of a local bound state with spin singlet. We further argue that the transition Pc is regarded as a transition from an insulating electron-hole gas to a Kondo metal, i.e., from a spatially bound state to a Kondo virtually bound state between 4f and conduction electrons.Comment: 5 pages, 5 figure

Vectorial dissipative solitons in vertical-cavity surface-emitting Lasers with delays

We show that the nonlinear polarization dynamics of a vertical-cavity surface-emitting laser placed into an external cavity leads to the formation of temporal vectorial dissipative solitons. These solitons arise as cycles in the polarization orientation, leaving the total intensity constant. When the cavity round-trip is much longer than their duration, several independent solitons as well as bound states (molecules) may be hosted in the cavity. All these solutions coexist together and with the background solution, i.e. the solution with zero soliton. The theoretical proof of localization is given by the analysis of the Floquet exponents. Finally, we reduce the dynamics to a single delayed equation for the polarization orientation allowing interpreting the vectorial solitons as polarization kinks.Comment: quasi final resubmission version, 12 pages, 9 figure

Dependence of transient dynamics in a class-C laser upon variation of inversion with time

The transient statistics of a gain-switched coherently pumped class-C laser displays a linear correlation between the first passage time and subsequent peak intensity. Measurements are reported showing a positive or negative sign of this linear correlation, controlled through the switching time and the laser detuning. Further measurements of the small-signal laser gain combined with calculations involving a three-level laser model indicate that this sign fundamentally depends upon the way the laser inversion varies during the gain switching, despite the added dynamics of the laser polarization in the class-C laser. [S1050-2947(97)07112-6]