A New High-intensity, Low-momentum Muon Beam for the Generation of Low-energy Muons at PSI

At the Paul Scherrer Institute (PSI, Villigen, Switzerland) a new high-intensity muon beam line with momentum p < 40MeV/c is currently being commissioned. The beam line is especially designed to serve the needs of the low-energy, polarized positive muon source (LE-μ+) and LE-μ SR spectrometer at PSI. The beam line replaces the existing μ E4 muon decay channel. A large acceptance is accomplished by installing two solenoidal magnetic lenses close to the muon production target E that is hit by the 590-MeV PSI proton beam. The muons are then transported by standard large aperture quadrupoles and bending magnets to the experiment. Several slit systems and an electrostatic separator allow the control of beam shape, momentum spread, and to reduce the background due to beam positrons or electrons. Particle intensities of up to 3.5 × 108 μ+/s and 107 μ−/s are expected at 28MeV/c beam momentum and 1.8mA proton beam current. This will translate into a LE-μ+ rate of 7,000/s being available at the LE-μ SR spectrometer, thus achieving μ+ fluxes, that are comparable to standard μ SR facilitie

Fast neurotransmitter release regulated by the endocytic scaffold intersectin.

Sustained fast neurotransmission requires the rapid replenishment of release-ready synaptic vesicles (SVs) at presynaptic active zones. Although the machineries for exocytic fusion and for subsequent endocytic membrane retrieval have been well characterized, little is known about the mechanisms underlying the rapid recruitment of SVs to release sites. Here we show that the Down syndrome-associated endocytic scaffold protein intersectin 1 is a crucial factor for the recruitment of release-ready SVs. Genetic deletion of intersectin 1 expression or acute interference with intersectin function inhibited the replenishment of release-ready vesicles, resulting in short-term depression, without significantly affecting the rate of endocytic membrane retrieval. Acute perturbation experiments suggest that intersectin-mediated vesicle replenishment involves the association of intersectin with the fissioning enzyme dynamin and with the actin regulatory GTPase CDC42. Our data indicate a role for the endocytic scaffold intersectin in fast neurotransmitter release, which may be of prime importance for information processing in the brain

Training Auto-encoder-based Optimizers for Terahertz Image Reconstruction

Terahertz (THz) sensing is a promising imaging technology for a wide variety of different applications. Extracting the interpretable and physically meaningful parameters for such applications, however, requires solving an inverse problem in which a model function determined by these parameters needs to be fitted to the measured data. Since the underlying optimization problem is nonconvex and very costly to solve, we propose learning the prediction of suitable parameters from the measured data directly. More precisely, we develop a model-based autoencoder in which the encoder network predicts suitable parameters and the decoder is fixed to a physically meaningful model function, such that we can train the encoding network in an unsupervised way. We illustrate numerically that the resulting network is more than 140 times faster than classical optimization techniques while making predictions with only slightly higher objective values. Using such predictions as starting points of local optimization techniques allows us to converge to better local minima about twice as fast as optimization without the network-based initialization.Comment: This is a pre-print of a conference paper published in German Conference on Pattern Recognition (GCPR) 201

The Spectrometer/Telescope for Imaging X-rays (STIX)

Aims. The Spectrometer Telescope for Imaging X-rays (STIX) on Solar Orbiter is a hard X-ray imaging spectrometer, which covers the energy range from 4 to 150 keV. STIX observes hard X-ray bremsstrahlung emissions from solar flares and therefore provides diagnostics of the hottest (⪆10 MK) flare plasma while quantifying the location, spectrum, and energy content of flare-accelerated nonthermal electrons. Methods. To accomplish this, STIX applies an indirect bigrid Fourier imaging technique using a set of tungsten grids (at pitches from 0.038 to 1 mm) in front of 32 coarsely pixelated CdTe detectors to provide information on angular scales from 7 to 180 arcsec with 1 keV energy resolution (at 6 keV). The imaging concept of STIX has intrinsically low telemetry and it is therefore well-suited to the limited resources available to the Solar Orbiter payload. To further reduce the downlinked data volume, STIX data are binned on board into 32 selectable energy bins and dynamically-adjusted time bins with a typical duration of 1 s during flares. Results. Through hard X-ray diagnostics, STIX provides critical information for understanding the acceleration of electrons at the Sun and their transport into interplanetary space and for determining the magnetic connection of Solar Orbiter back to the Sun. In this way, STIX serves to link Solar Orbiter’s remote and in-situ measurements

Preparation of Fe3O4Spherical Nanoporous Particles Facilitated by Polyethylene Glycol 4000

Much interest has been attracted to the magnetic materials with porous structure because of their unique properties and potential applications. In this report, Fe3O4nanoporous particles assembled from small Fe3O4nanoparticles have been prepared by thermal decomposition of iron acetylacetonate in the presence of polyethylene glycol 4000. The size of the spherical nanoporous particles is 100–200 nm. Surface area measurement shows that these Fe3O4nanoporous particles have a high surface area of 87.5 m2/g. Magnetization measurement and Mössbauer spectrum indicate that these particles are nearly superparamagnetic at room temperature. It is found that the morphology of the products is greatly influenced by polyethylene glycol concentration and the polymerization degree of polyethylene glycol. Polyethylene glycol molecules are believed to facilitate the formation of the spherical assembly

Signal Transmission in the Auditory System

Contains table of contents for Section 3 and reports on nine research projects.National Institutes of Health (Grant 5 P01 NS13126)National Institutes of Health (Grant 5 P01 NS23734)National Institutes of Health (Grant 5 R01 NS18682)National Institutes of Health (Grant 5 RO1 NS25995)National Institutes of Health (Grant 5 R01 NS20269)National Institutes of Health (Grant 5 R01 NS20322)National Institutes of Health (Grant 5 T32 NS07047)Johnson and Johnson Foundatio

Signal Transmission in the Auditory System

Contains table of contents for Section 3, an introduction, and reports on seven research projects.National Institutes of Health Grant 5 R01 DC00194National Institutes of Health Grant P01 DC00119National Institutes of Health Grant F32 DC00073National Institutes of Health Grant 5 R01 DC00473National Institutes of Health Grant 2 R01 DC00238National Institutes of Health Grant 2 R01 DC00235National Institutes of Health Grant 5 P01 DC00361National Institutes of Health Grant T32 DC00006Whitaker Health Sciences Fun

The rationale and design of the perindopril genetic association study (PERGENE): A pharmacogenetic analysis of angiotensin-converting enzyme inhibitor therapy in patients with stable coronary artery disease

Background: Angiotensin-converting enzyme (ACE) inhibitors reduce clinical symptoms and improve outcome in patients with hypertension, heart failure, and stable coronary artery disease (CAD) and are among the most frequently used drugs in these patient groups. For hypertension, treatment is guided by the level of blood pressure. In the secondary prevention setting, there are no means of guiding therapy. Prior attempts to target ACE-inhibitors to those patients that are most likely to benefit have not been successful, mainly due to the consistency in the treatment effect in clinical subgroups. Still, for prolonged prophylactic treatment with ACE-inhibitors it would be best to target treatment to only those patients most likely to benefit, which would considerably lower the number needed to treat and increase cost-effectiveness. A new approach for such "tailored-therapy" may be to integrate information on the genetic variation between patients. Until now, pharmacogenetic research of the efficacy of ACE-inhibitor therapy in CAD patients is still in a preliminary stage. Methods: The PERindopril GENEtic association study (PERGENE) is a substudy of the EUROPA trial, a randomized double-blind placebo-controlled multicentre clinical trial which demonstrated a beneficial effect of the ACE-inhibitor perindopril in reducing cardiovascular morbidity and mortality in 12.218 patients with stable coronary artery disease (mean follow-up 4.2 years). Blood tubes were received from patients at the beginning of the EUROPA trial and buffy coats were stored at -40°C at the central core laboratory. Candidate genes were selected in the renin-angiotensin-system and bradykinin pathways. Polymorphisms were selected based on haplotype tagging principles using the HapMap genome project, Seattle and other up-to-date genetic database platforms to comprehensively cover all common genetic variation within the genes. Selection also took into consideration the functionality of SNP's, location within the gene (promoter) and existing relevant literature. The main outcome measure of PERGENE is the effect of genetic factors on the treatment benefit with ACE-inhibitors. The size of this pharmacogenetic substudy allows detection with a statistical power of 98% to detect a difference in hazard ratios (treatment effect) of 20% between genotypes with minor allele frequency of 0.20 (two-sided alpha 0.05). Conclusion: The PERGENE study is a large cardiovascular pharmacogenetic study aimed to assess the feasibility of pharmacogenetic profiling of the treatment effect of ACE-inhibitor use with the perspective to individualize treatment in patients with stable coronary artery disease