Polymorphic Aβ42 fibrils adopt similar secondary structure but differ in cross-strand side chain stacking interactions within the same β-sheet.

Formation of polymorphic amyloid fibrils is a common feature in neurodegenerative diseases involving protein aggregation. In Alzheimer's disease, different fibril structures may be associated with different clinical sub-types. Structural basis of fibril polymorphism is thus important for understanding the role of amyloid fibrils in the pathogenesis and progression of these diseases. Here we studied two types of Aβ42 fibrils prepared under quiescent and agitated conditions. Quiescent Aβ42 fibrils adopt a long and twisted morphology, while agitated fibrils are short and straight, forming large bundles via lateral association. EPR studies of these two types of Aβ42 fibrils show that the secondary structure is similar in both fibril polymorphs. At the same time, agitated Aβ42 fibrils show stronger interactions between spin labels across the full range of the Aβ42 sequence, suggesting a more tightly packed structure. Our data suggest that cross-strand side chain packing interactions within the same β-sheet may play a critical role in the formation of polymorphic fibrils

Charged particle detection performances of CMOS pixel sensors produced in a 0.18 um process with a high resistivity epitaxial layer

The apparatus of the ALICE experiment at CERN will be upgraded in 2017/18 during the second long shutdown of the LHC (LS2). A major motivation for this upgrade is to extend the physics reach for charmed and beauty particles down to low transverse momenta. This requires a substantial improvement of the spatial resolution and the data rate capability of the ALICE Inner Tracking System (ITS). To achieve this goal, the new ITS will be equipped with 50 um thin CMOS Pixel Sensors (CPS) covering either the 3 innermost layers or all the 7 layers of the detector. The CPS being developed for the ITS upgrade at IPHC (Strasbourg) is derived from the MIMOSA 28 sensor realised for the STAR-PXL at RHIC in a 0.35 um CMOS process. In order to satisfy the ITS upgrade requirements in terms of readout speed and radiation tolerance, a CMOS process with a reduced feature size and a high resistivity epitaxial layer should be exploited. In this respect, the charged particle detection performance and radiation hardness of the TowerJazz 0.18 um CMOS process were studied with the help of the first prototype chip MIMOSA 32. The beam tests performed with negative pions of 120 GeV/c at the CERN-SPS allowed to measure a signal-to-noise ratio (SNR) for the non-irradiated chip in the range between 22 and 32 depending on the pixel design. The chip irradiated with the combined dose of 1 MRad and 10^13 n_eq/cm^2 was observed to yield a SNR ranging between 11 and 23 for coolant temperatures varying from 15 C to 30 C. These SNR values were measured to result in particle detection efficiencies above 99.5% and 98% before and after irradiation respectively. These satisfactory results allow to validate the TowerJazz 0.18 um CMOS process for the ALICE ITS upgrade.Comment: (v2) Added hyper-links; (v3) A typo correcte

Cerebellar encoding of multiple candidate error cues in the service of motor learning

or learning to occur through trial and error, the nervous system must effectively detect and encode performance errors. To examine this process, we designed a set of oculomotor learning tasks with more than one visual object providing potential error cues, as would occur in a natural visual scene. A task-relevant visual target and a task-irrelevant visual background both influenced vestibulo-ocular reflex learning in rhesus monkeys. Thus, motor learning does not identify a single error cue based on behavioral relevance, but can be simultaneously influenced by more than one cue. Moreover, the relative weighting ofthe differentcues could vary. Ifthe speed ofthe visual target's motion on the retina was low (≪1°/s), background motion dominated learning, but if target speed was high, the effects of the background were suppressed. The target and background motion had similar, nonlinear effects on the putative neural instructive signals carried by cerebellar climbing fibers, but with a stronger influence ofthe backgroundon the climbing fibers than on learning. In contrast, putative neuralinstructive signals carriedby the simple spikes of Purkinje cells were influenced solely by the motion of the visual target. Because they are influenced by different cues during training, joint control of learning by the climbing fibers and Purkinje cells may expand the learning capacity of the cerebellar circuit

Development of CMOS Pixel Sensors fully adapted to the ILD Vertex Detector Requirements

CMOS Pixel Sensors are making steady progress towards the specifications of the ILD vertex detector. Recent developments are summarised, which show that these devices are close to comply with all major requirements, in particular the read-out speed needed to cope with the beam related background. This achievement is grounded on the double- sided ladder concept, which allows combining signals generated by a single particle in two different sensors, one devoted to spatial resolution and the other to time stamp, both assembled on the same mechanical support. The status of the development is overviewed as well as the plans to finalise it using an advanced CMOS process.Comment: 2011 International Workshop on Future Linear Colliders (LCWS11), Granada, Spain, 26-30 September 201

Development of Single- and Double-sided Ladders for the ILD Vertex Detectors

We discuss two projects exploring the integration of thin CMOS pixel sensors in order to prototype ladders matching the geometry needed for the ILD vertex detector. The PLUME project has designed and fabricated full-size and fully functional double- sided layers which currently reach 0.6 % X0 and aim for 0.3 % X0 in mid-2012. Another approach, SERNWIETE, consists in wrapping the sensors in a polyimide-based micro-cable to obtain a supportless single-sided ladder with a material budget around 0.15 % X0. First promising samples have been produced and the full-size prototype is expected in spring 2012.Comment: International Workshop on Future Linear Colliders, LCWS 2011, Granada, Spain, 2011, 26-30 Septembe