Genetic Dissection of the Function of Hindbrain Axonal Commissures

The Robo3 receptor controls midline crossing by axons. Deleting Robo3 in specific commissural neurons with a conditional knockout reveals their contribution to sensory and motor integration, and models human neurological conditions

Novel Cell-Based Assay for Alpha-3 Nicotinic Receptor Antibodies Detects Antibodies Exclusively in Autoimmune Autonomic Ganglionopathy

BACKGROUND AND OBJECTIVES: Autoantibodies against α3-subunit-containing nicotinic acetylcholine receptors (α3-nAChRs), usually measured by radioimmunoprecipitation assay (RIPA), are detected in patients with autoimmune autonomic ganglionopathy (AAG). However, low α3-nAChR antibody levels are frequently detected in other neurologic diseases with questionable significance. Our objective was to develop a method for the selective detection of the potentially pathogenic α3-nAChR antibodies, seemingly present only in patients with AAG. METHODS: The study involved sera from 55 patients from Greece, suspected for autonomic failure, and 13 patients from Italy diagnosed with autonomic failure, positive for α3-nAChR antibodies by RIPA. In addition, sera from 52 patients with Ca2+ channel or Hu antibodies and from 2,628 controls with various neuroimmune diseases were included. A sensitive live cell-based assay (CBA) with α3-nAChR-transfected cells was developed to detect antibodies against the cell-exposed α3-nAChR domain. RESULTS: Twenty-five patients were found α3-nAChR antibody positive by RIPA. Fifteen of 25 patients were also CBA positive. Of interest, all 15 CBA-positive patients had AAG, whereas all 10 CBA-negative patients had other neurologic diseases. RIPA antibody levels of the CBA-negative sera were low, although our CBA could detect dilutions of AAG sera corresponding to equally low RIPA antibody levels. No serum bound to control-transfected cells, and none of the 2,628 controls was α3-CBA positive. DISCUSSION: This study showed that in contrast to the established RIPA for α3-nAChR antibodies, which at low levels is of moderate disease specificity, our CBA seems AAG specific, while at least equally sensitive with the RIPA. This study provides Class II evidence that α3-nAChR CBA is a specific assay for AAG. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that an α3-nAChR cell-based assay is a more specific assay for AAG than the standard RIPA. Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology

Novel Cell-Based Assay for Alpha-3 Nicotinic Receptor Antibodies Detects Antibodies Exclusively in Autoimmune Autonomic Ganglionopathy

BACKGROUND AND OBJECTIVES: Autoantibodies against α3-subunit-containing nicotinic acetylcholine receptors (α3-nAChRs), usually measured by radioimmunoprecipitation assay (RIPA), are detected in patients with autoimmune autonomic ganglionopathy (AAG). However, low α3-nAChR antibody levels are frequently detected in other neurologic diseases with questionable significance. Our objective was to develop a method for the selective detection of the potentially pathogenic α3-nAChR antibodies, seemingly present only in patients with AAG. METHODS: The study involved sera from 55 patients from Greece, suspected for autonomic failure, and 13 patients from Italy diagnosed with autonomic failure, positive for α3-nAChR antibodies by RIPA. In addition, sera from 52 patients with Ca2+ channel or Hu antibodies and from 2,628 controls with various neuroimmune diseases were included. A sensitive live cell-based assay (CBA) with α3-nAChR-transfected cells was developed to detect antibodies against the cell-exposed α3-nAChR domain. RESULTS: Twenty-five patients were found α3-nAChR antibody positive by RIPA. Fifteen of 25 patients were also CBA positive. Of interest, all 15 CBA-positive patients had AAG, whereas all 10 CBA-negative patients had other neurologic diseases. RIPA antibody levels of the CBA-negative sera were low, although our CBA could detect dilutions of AAG sera corresponding to equally low RIPA antibody levels. No serum bound to control-transfected cells, and none of the 2,628 controls was α3-CBA positive. DISCUSSION: This study showed that in contrast to the established RIPA for α3-nAChR antibodies, which at low levels is of moderate disease specificity, our CBA seems AAG specific, while at least equally sensitive with the RIPA. This study provides Class II evidence that α3-nAChR CBA is a specific assay for AAG. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that an α3-nAChR cell-based assay is a more specific assay for AAG than the standard RIPA. Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology

EARLINET: A European Aerosol Research Lidar Network to establish an aerosol climatology

The European Aerosol Research Lidar Network (EARLINET) has been established in 2000 to derive a comprehensive and statistically relevant quantitative data base of the aerosol vertical distribution over Europe. For this purpose, regular lidar measurements have been performed at 22 locations in 13 European countries. Most of the measurements have been taken on a fixed schedule at preselected times and days to avoid a fair weather bias in the statistics. Additional measurements have been performed to investigate special topics like Saharan dust outbreaks, temporal cycles, the modification of aerosol on its way through Europe or long range transport of aerosol to Europe. All instruments have been quality controlled in extensive intercomparison experiments. The algorithms used to derive aerosol backscatter and extinction have been tested separately using synthetic lidar data. The EARLINET quality assurance is presented in detail in MPI report 337. This report gives the main results of the EARLINET project which have been achieved up to spring 2003. Most relevant topics are - data base on aerosol vertical profiles and backtrajectories - temporal cycles of the aerosol distribution - observation of special events, e.g. Saharan dust and forest fires - impact of the aerosol vertical distribution on satellite retrievals - aerosol modification during transport over Europe - influence of orography on aerosol vertical transport - stratospheric aerosol - differences between rural and urban aerosol - effect of aerosol on UV-B radiation - statistical analysis of the aerosol vertical profiles - lidar ratio statistical analysis - long range transport of aerosol to Europe - algorithms to derive aerosol microphysics from lidar dat

Development of the CMS detector for the CERN LHC Run 3

Since the initial data taking of the CERN LHC, the CMS experiment has undergone substantial upgrades and improvements. This paper discusses the CMS detector as it is configured for the third data-taking period of the CERN LHC, Run 3, which started in 2022. The entire silicon pixel tracking detector was replaced. A new powering system for the superconducting solenoid was installed. The electronics of the hadron calorimeter was upgraded. All the muon electronic systems were upgraded, and new muon detector stations were added, including a gas electron multiplier detector. The precision proton spectrometer was upgraded. The dedicated luminosity detectors and the beam loss monitor were refurbished. Substantial improvements to the trigger, data acquisition, software, and computing systems were also implemented, including a new hybrid CPU/GPU farm for the high-level trigger

Development of the CMS detector for the CERN LHC Run 3

A preprint version of this article is available at arXiv:2309.05466v1 [physics.ins-det], https://arxiv.org/abs/2309.05466v1 . Comments: Submitted to the Journal of Instrumentation. All figures and tables can be found at https://cms-results.web.cern.ch/cms-results/public-results/publications/PRF-21-001 (CMS Public Pages). Report number: CMS-PRF-21-001, CERN-EP-2023-136.Since the initial data taking of the CERN LHC, the CMS experiment has undergone substantial upgrades and improvements. This paper discusses the CMS detector as it is configured for the third data-taking period of the CERN LHC, Run 3, which started in 2022. The entire silicon pixel tracking detector was replaced. A new powering system for the superconducting solenoid was installed. The electronics of the hadron calorimeter was upgraded. All the muon electronic systems were upgraded, and new muon detector stations were added, including a gas electron multiplier detector. The precision proton spectrometer was upgraded. The dedicated luminosity detectors and the beam loss monitor were refurbished. Substantial improvements to the trigger, data acquisition, software, and computing systems were also implemented, including a new hybrid CPU/GPU farm for the high-level trigger.SCOAP3