Axonal degeneration as a therapeutic target in the CNS

Degeneration of the axon is an important step in the pathomechanism of traumatic, inflammatory and degenerative neurological diseases. Increasing evidence suggests that axonal degeneration occurs early in the course of these diseases and therefore represents a promising target for future therapeutic strategies. We review the evidence for axonal destruction from pathological findings and animal models with particular emphasis on neurodegenerative and neurotraumatic disorders. We discuss the basic morphological and temporal modalities of axonal degeneration (acute, chronic and focal axonal degeneration and Wallerian degeneration). Based on the mechanistic concepts, we then delineate in detail the major molecular mechanisms that underlie the degenerative cascade, such as calcium influx, axonal transport, protein aggregation and autophagy. We finally concentrate on putative therapeutic targets based on the mechanistic prerequisites

Hunting for CDF Multi-Muon "Ghost" Events at Collider and Fixed-Target Experiments

In 2008 the CDF collaboration discovered a large excess of events containing two or more muons, at least one of which seemed to have been produced outside the beam pipe. We investigate whether similar "ghost" events could (and should) have been seen in already completed experiments. The CDF di-muon data can be reproduced by a simple model where a relatively light X particle undergoes four-body decay. This model predicts a large number of ghost events in Fermilab fixed-target experiments E772, E789 and E866, applying the cuts optimized for analyses of Drell-Yan events. A correct description of events with more than two muons requires a more complicated model, where two X particles are produced from a very broad resonance Y. This model can be tested in fixed-target experiments only if the cut on the angles, or rapidities, of the muons can be relaxed. Either way, the UA1 experiment at the CERN ppbar collider should have observed O(100) ghost events.Comment: 15 pages, 9 figure

Interrelation of inflammation and APP in sIBM: IL-1 beta induces accumulation of beta-amyloid in skeletal muscle.

Distinct interrelationships between inflammation and beta-amyloid-associated degeneration, the two major hallmarks of the skeletal muscle pathology in sporadic inclusion body myositis (sIBM), have remained elusive. Expression of markers relevant for these pathomechanisms were analysed in biopsies of sIBM, polymyositis (PM), dermatomyositis (DM), dystrophic and non-myopathic muscle as controls, and cultured human myotubes. By quantitative PCR, a higher upregulation was noted for the mRNA-expression of CXCL-9, CCL-3, CCL-4, IFN-gamma, TNF-alpha and IL-1 beta in sIBM muscle compared to PM, DM and controls. All inflammatory myopathies displayed overexpression of degeneration-associated markers, yet only in sIBM, expression of the mRNA of amyloid precursor protein (APP) significantly and consistently correlated with inflammation in the muscle and mRNA-levels of chemokines and IFN-gamma. Only in sIBM, immunohistochemical analysis revealed that inflammatory mediators including IL-1 beta co-localized to beta-amyloid depositions within myofibres. In human myotubes, exposure to IL-1 beta caused upregulation of APP with subsequent intracellular aggregation of beta-amyloid. Our data suggest that, in sIBM muscle, production of high amounts of pro-inflammatory mediators specifically induces beta-amyloid-associated degeneration. The observations may help to design targeted treatment strategies for chronic inflammatory disorders of the skeletal muscle

The H1 Forward Proton Spectrometer at HERA

The forward proton spectrometer is part of the H1 detector at the HERA collider. Protons with energies above 500 GeV and polar angles below 1 mrad can be detected by this spectrometer. The main detector components are scintillating fiber detectors read out by position-sensitive photo-multipliers. These detectors are housed in so-called Roman Pots which allow them to be moved close to the circulating proton beam. Four Roman Pot stations are located at distances between 60 m and 90 m from the interaction point.Comment: 20 pages, 10 figures, submitted to Nucl.Instr.and Method

Comparison of SpatialAnalyzer and Different Adjustment Programs

Net adjustment is one of the basic tools for various surveying tasks. Among transformation of coordinates or the analysis and comparison of geometries, the adjustment of geodetic networks is an important part of the surveyor\u27s work. The market offers a number of software solutions, both commercial and freeware. All the programs have the ability to process terrestrial observations (distance, zenith angle, horizontal direction) in common. Apart from that, the programs differ in various aspects, which are important for the customer\u27s choice. For instance, the net dimensions are not the same with each piece of software. Some programs do not offer a proper 3D adjustment. They handle horizontal position and height separately and therefore ignore the mathematical dependencies between the two components. Seeing the range of software solutions, the question arises, whether the programs give equivalent results. Earlier evaluations of net adjustment programs, including New River Kinematics\u27 SpatialAnalyzer (SA), revealed on the one hand almost identical adjustment results for the classic programs. On the other hand, the evaluations showed that SA, using a different mathematical model (bundle adjustment) yields clearly distinguishable deviations. Hence, in this paper the authors focused on SA with the classic programs as reference. The first part of the comparison deals with the results of evaluating a terrestrial network. Due to the fact that the programs do not account for the earth\u27s curvature in a standardized way, the network is of small size to overcome the need of pre-processing. The second part of the paper compares the results of the evaluation of basic geometries (plane, circle, cylinder, sphere) using SA and other software packages with the least squares solution obtained in a rigorous Gauss Helmert model

Prototype design of a timing and fast control system in the CBM experiment

The Compressed Baryonic Matter (CBM) experiment is designed to handle interaction rates of up to 10 MHz and up to 1 TB/s of raw data generated. With triggerless streaming data acquisition in the experiment and beam intensity fluctuations, it is expected that occasional data bursts will surpass bandwidth capabilities of the Data Acquisition System (DAQ) system. In order to preserve integrity of event data, the bandwidth of DAQ must be throttled in an organised way with minimum information loss. The Timing and Fast Control (TFC) system provides a latency-optimised datapath for throttling commands and distributes a system clock together with a global timestamp. This paper describes a prototype design of the system with focus on synchronisation and its evaluation

Prototype design of a timing and fast control system in the CBM experiment

The Compressed Baryonic Matter (CBM) experiment is designed to handle interaction rates of up to 10 MHz and up to 1 TB/s of raw data generated. With triggerless streaming data acquisition in the experiment and beam intensity fluctuations, it is expected that occasional data bursts will surpass bandwidth capabilities of the Data Acquisition System (DAQ) system. In order to preserve integrity of event data, the bandwidth of DAQ must be throttled in an organised way with minimum information loss. The Timing and Fast Control (TFC) system provides a latency-optimised datapath for throttling commands and distributes a system clock together with a global timestamp. This paper describes a prototype design of the system with focus on synchronisation and its evaluation

A 3D track finder for the Belle II CDC L1 trigger

Machine learning methods are integrated into the pipelined first level (L1) track trigger of the upgraded flavor physics experiment Belle II at KEK in Tsukuba, Japan. The novel triggering techniques cope with the severe background from events outside the small collision region provided by the new SuperKEKB asymmetric-energy electron-positron collider. Using the precise drift-time information of the central drift chamber which provides axial and stereo wire layers, a neural network L1 trigger estimates the 3D track parameters of tracks, based on input from the axial wire planes provided by a 2D track finder. An extension of this 2D Hough track finder to a 3D finder is proposed, where the single hit representations in the Hough plane are trained using Monte Carlo. This 3D finder improves the track finding efficiency by including the stereo sense wires as input. The estimated polar track angle allows a specialization of the subsequent neural networks to sectors in the polar angle