Mechanisms, models and biomarkers in amyotrophic lateral sclerosis

The last 30 years have seen a major advance in the understanding of the clinical and pathological heterogeneity of amyotrophic lateral sclerosis (ALS), and its overlap with frontotemporal dementia. Multiple, seemingly disparate biochemical pathways converge on a common clinical syndrome characterized by progressive loss of upper and lower motor neurons. Pathogenic themes in ALS include excitotoxicity, oxidative stress, mitochondrial dysfunction, neuroinflammation, altered energy metabolism, and most recently RNA mis-processing. The transgenic rodent, overexpressing mutant superoxide dismutase-1, is now only one of several models of ALS pathogenesis. The nematode, fruit fly and zebrafish all offer fresh insight, and the development of induced pluripotent stem cell-derived motor neurons holds promise for the screening of candidate therapeutics. The lack of useful biomarkers in ALS contributes to diagnostic delay, and the inability to stratify patients by prognosis may be an important factor in the failure of therapeutic trials. Biomarkers sensitive to disease activity might lessen reliance on clinical measures and survival as trial endpoints and reduce study length. Emerging proteomic markers of neuronal loss and glial activity in cerebrospinal fluid, a cortical signature derived from advanced structural and functional MRI, and the development of more sensitive measurements of lower motor neuron physiology are leading a new phase of biomarker-driven therapeutic discovery

Measurement of the muon flux from 400 GeV/c protons interacting in a thick molybdenum/tungsten target

The SHiP experiment is proposed to search for very weakly interacting particles beyond the Standard Model which are produced in a 400 GeV/c proton beam dump at the CERN SPS. About 1011 muons per spill will be produced in the dump. To design the experiment such that the muon-induced background is minimized, a precise knowledge of the muon spectrum is required. To validate the muon flux generated by our Pythia and GEANT4 based Monte Carlo simulation (FairShip), we have measured the muon flux emanating from a SHiP-like target at the SPS. This target, consisting of 13 interaction lengths of slabs of molybdenum and tungsten, followed by a 2.4 m iron hadron absorber was placed in the H4 400 GeV/c proton beam line. To identify muons and to measure the momentum spectrum, a spectrometer instrumented with drift tubes and a muon tagger were used. During a 3-week period a dataset for analysis corresponding to (3.27±0.07) × 1011 protons on target was recorded. This amounts to approximatively 1% of a SHiP spill

Track reconstruction and matching between emulsion and silicon pixel detectors for the SHiP-charm experiment

In July 2018 an optimization run for the proposed charm cross section measurement for SHiP was performed at the CERN SPS. A heavy, moving target instrumented with nuclear emulsion films followed by a silicon pixel tracker was installed in front of the Goliath magnet at the H4 proton beam-line. Behind the magnet, scintillating-fibre, drift-tube and RPC detectors were placed. The purpose of this run was to validate the measurement's feasibility, to develop the required analysis tools and fine-tune the detector layout. In this paper, we present the track reconstruction in the pixel tracker and the track matching with the moving emulsion detector. The pixel detector performed as expected and it is shown that, after proper alignment, a vertex matching rate of 87% is achieved

The BaBar detector: Upgrades, operation and performance

Contains fulltext : 121729.pdf (preprint version ) (Open Access

The Design, Construction, Operation and Performance of the Belle II Silicon Vertex Detector

The Silicon Vertex Detector of Belle II is a state-of-the-art tracking an vertexing system based on double-sided silicon strip sensors, designed and fabricated by a large international collaboration in the period 2012--2018. Since 2019 it has been in operation providing high quality data with a small number of defective channels (99%), a good signal-to-noise ratio (well in excess of 10 for all sensor configurations and tracks). Toghether with the good control over the alignment, these are all essential factors to achieve good tracking reconstruction and physics performance. In this extended paper we try to document all the aspects of the SVD challenges and achievements, in the spirit of providing information to the broader community and help the development of high quality detector systems, which are fundamental tools to carry out physics research

The Design, Construction, Operation and Performance of the Belle II Silicon Vertex Detector

The Silicon Vertex Detector of Belle II is a state-of-the-art tracking an vertexing system based on double-sided silicon strip sensors, designed and fabricated by a large international collaboration in the period 2012--2018. Since 2019 it has been in operation providing high quality data with a small number of defective channels (99%), a good signal-to-noise ratio (well in excess of 10 for all sensor configurations and tracks). Toghether with the good control over the alignment, these are all essential factors to achieve good tracking reconstruction and physics performance. In this extended paper we try to document all the aspects of the SVD challenges and achievements, in the spirit of providing information to the broader community and help the development of high quality detector systems, which are fundamental tools to carry out physics research