At present, part of the forward RPC muon system of the CMS detector at the CERN LHC remains uninstrumented in the high-η region. An international collaboration is investigating the possibility of ...covering the 1.6 <; |η| <; 2.4 region of the muon endcaps with large-area triple-GEM detectors. Given their good spatial resolution, high rate capability, and radiation hardness, these micro-pattern gas detectors are an appealing option for simultaneously enhancing muon tracking and triggering capabilities in a future upgrade of the CMS detector. A general overview of this feasibility study will be presented. The design and construction of small (10×10 cm 2 ) and full-size trapezoidal (1 × 0.5 m 2 ) triple-GEM prototypes will be described. During detector assembly, different techniques for stretching the GEM foils were tested. Results from measurements with x-rays and from test beam campaigns at the CERN SPS will be shown for the small and large prototypes. Preliminary simulation studies on the expected muon reconstruction and trigger performances of this proposed upgraded muon system will be reported.
Acute axonal injury in multiple sclerosis Bitsch, A.; Schuchardt, J.; Bunkowski, S. ...
Brain (London, England : 1878),
06/2000, Volume:
123, Issue:
6
Journal Article
Peer reviewed
Damage to axons is taken as a key factor of disability in multiple sclerosis, but its pathogenesis is largely unknown. Axonal injury is believed to occur as a consequence of demyelination and was ...recently shown to be a feature even of the early disease stages. The present study was aimed at characterizing the association of axonal injury and histopathological hallmarks of multiple sclerosis such as demyelination, cellular infiltration and expression of inflammatory mediators. Therefore, axon reduction and signs of acute axonal damage were quantified in early lesion development of chronic multiple sclerosis and correlated with demyelinating activity and inflammation. Patients with secondary progressive multiple sclerosis revealed the most pronounced axonal injury, whereas primary progressive multiple sclerosis patients surprisingly showed relatively little acute axonal injury. Acute axonal damage, as defined by the accumulation of amyloid precursor protein (APP), was found to occur not only in active demyelinating but also in remyelinating and inactive demyelinated lesions with a large inter-individual variability. Only few remyelinating lesions were adjacent to areas of active demyelination. In this minority of lesions, axonal damage may have originated from the neighbourhood. APP expression in damaged axons correlated with the number of macrophages and CD8-positive T lymphocytes within the lesions, but not with the expression of tumour necrosis factor-alpha (TNF-α) or inducible nitric oxide synthase (iNOS). Axonal injury is therefore, at least in part, independent of demyelinating activity, and its pathogenesis may be different from demyelination. This has major implications for therapeutic strategies, which aim at preventing both demyelination and axonal loss.
IMS
is an Integrated Medical Software system for the analysis of Ion Mobility Spectrometry (IMS) data. It assists medical staff with the following IMS data processing steps: acquisition, ...visualization, classification, and annotation. IMS
provides data analysis and interpretation features on the one hand, and also helps to improve the classification by increasing the number of the pre-classified datasets on the other hand. It is designed to facilitate early detection of lung cancer, one of the most common cancer types with one million deaths each year around the world.
After reviewing the IMS technology, we first describe the software architecture of IMS
and then the integrated classification module, including necessary pre-processing steps and different classification methods. The Lung Hospital Hemer (Germany) provided IMS data of 35 patients suffering from lung cancer and 72 samples of healthy persons. IMS
correctly classifies 99% of the samples, evaluated using 10-fold cross-validation.
Gas Electron Multipliers (GEM) are an interesting technology under consideration for the future upgrade of the forward region of the CMS muon system, specifically in the 1.6 <; |η| <; 2:4 endcap ...region. With a sufficiently fine segmentation GEMs can provide precision tracking as well as fast trigger information. The main objective is to contribute to the improvement of the CMS muon trigger. The construction of large-area GEM detectors is challenging both from the technological and production aspects. In view of the CMS upgrade we have designed and built the largest full-size Triple-GEM muon detector, which is able to meet the stringent requirements given the hostile environment at the high-luminosity LHC. Measurements were performed during several test beam campaigns at the CERN SPS in 2010 and 2011. The main issues under study are efficiency, spatial resolution and timing performance with different inter-electrode gap configurations and gas mixtures. In this paper results of the performance of the prototypes at the beam tests will be discussed.
Objective:
Axons in the cerebral white matter are affected in inflammatory, hypoglycemic, ischemic, traumatic and degenerative central nervous system diseases. Here we describe the contribution of ...white matter pathology to central nervous system injury in bacterial meningitis.
Methods:
1. Various brain regions from the autopsies of five patients who died 2 to 86 days after the onset of clinical symptoms of meningitis were embedded in paraffin. 2. New Zealand White rabbits (weight 1.8–2.5kg) were infected intracisternally with 106 colony-forming units Streptococcus pneumoniae type 3 and treated with ceftriaxone 16h after infection (n=15). Six rabbits died 18–23.5h after infection. 24h after infection, the other nine animals were killed. 3. On sections stained by amyloid precursor protein (APP) immunohistochemistry, the severity of subcortical white matter lesions was classified by a semiquantitative score: 0 (no axonal damage), 1 (mild axonal injury in one location), 2 (strong axonal injury in one location or mild axonal injury in more than one location), 3 (strong axonal injury in more than one location).
Results:
In both human cases, where MRI scans were available, subcortical hyperintense lesions were visible on T2-weighted images. These lesions most likely corresponded to ischemic white matter infarcts which were detected histologically in these cases. Focal vasculitis leading to the obstruction of the lumen of small arteries within the brain parenchyma was visualized. In the subarachnoid space, veins obstructed by infiltrating granulocytes or fibrin were visible, whereas the walls of large arteries in the subarachnoid space were not or only scarcely infiltrated.
Axonal lesions in the white matter showed an intense staining for APP in the center and at the border of white matter infarcts. Diffuse axonal injury affecting single fascicles was not associated with morphological features of ischemia on HE staining. Axonal injury of different degrees was detected in all humans and in 11 of 15 animals: two rabbits scored 1, four rabbits scored 2, and five rabbits scored 3.
Conclusion:
Subcortical ischemia leading to axonal injury is a frequent and neglected event in bacterial meningitis.
Neuronal apoptosis in the dentate gyrus has been observed in animal models of bacterial meningitis and in humans dying in the course of the disease. To evaluate the mechanisms of neuronal cell death, ...hippocampal sections of 20 patients dying from bacterial meningitis were investigated by immunohistochemistry using antibodies against the proform of caspase-3 and the active enzyme, bcl-2, bax and p53. In the dentate granule cell layer, the median density of neurons with an apoptotic morphology was 7.6/mm2 (0-15.6/mm2). The median density of immunoreactive neurons was 2.3/mm2 (procaspase-3), 0.9/mm2 (activated caspase-3), 1.8/mm2 (bcl-2), 1.1/mm2 (bax) and 0.4/mm2 (p53). 80% of neurons immunoreactive for active caspase-3 had an apoptotic morphology, whereas only 10% of all procaspase-3 stained neurons showed signs of apoptosis. Apoptotic cell death is present in humans dying in the course of bacterial meningitis in the dentate gyrus of the Formatio hippocampi. Neuronal expression of caspase-3, bcl-2 and bax suggests an involvement of these proteins in neuronal death.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Apoptosis of dentate granule cells is a typical feature of several animal models of disease. In 20 autopsy cases of subarachnoid hemorrhage (SAH) and global cerebral hypoxia caused by protracted ...shock or respiratory failure, we evaluated by light microscopy and in situ tailing whether this pattern of neuronal damage also occurs in humans. In subarachnoid hemorrhage, 4.0/mm2 (0–13.0/mm2) a poptotic neurons were observed in the dentate gyrus, in cerebral hypoxia 3.6/mm2 (0–19.9/mm2) (p>0.05), and in 10 aged‐matched control cases dying rapidly from non‐neurological diseases 0/mm2 (0–0/mm2) (median range) (p<0.001 versus SAH and hypoxia). Neuronal apoptosis in the dentate gyrus was most frequent, when death occurred later than 24 hours and less than 11 days after disease onset. Neuronal damage in the hippocampus was always necrotic. It was more severe in hypoxia than in SAH (median neuronal damage score 3 range: 0–3 versus 0 0–3, p<0.001).
Apoptosis appears to be the predominant mechanism of death in dentate granule cells irrespective of the underlying disease, whereas neuronal death in the hippocampus generally is of necrotic morphology.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The RPC muon trigger electronics of the CMS detector performs a number of tasks: synchronization of detector signals, optical data transmission from the detector to the trigger electronics, pattern ...recognition, muon momentum measurement, selection of track candidates. For the diagnostic purposes, as well as for the calibration and real-time monitoring of the RPC detectors and electronic hardware, a set of flexible diagnostic modules was designed and implemented into the FPGAs on which the trigger electronics is based. These include: multi-channel counters, timing histograms, test pulses, and data spying ("snapshots" of the data stream). Tests results presented in this paper, including test with LHC-like muon beam, illustrate the performance and usefulness of these diagnostic modules.
We report a patient who suffered from acute inflammatory CNS demyelination and underwent two consecutive diagnostic stereotactic brain biopsies during the early disease course. The first lesion was ...drawn 33 days after the onset of disseminated neurological symptoms. Macrophages and T lymphocytes diffusely infiltrated small vessel walls and the white matter. mRNA for tumor necrosis factor alpha (TNFalpha) and inducible nitric oxide synthase (iNOS) was abundantly expressed. Myelin sheaths were entirely preserved. The second biopsy 76 days later showed confluent demyelinating lesions with a diffuse infiltration of macrophages that were positive for myelin debris, activation markers and TNFalpha and iNOS mRNA. IgG and C9neo deposits were found along myelin sheaths. The patient had received intravenous immunoglobulins (IVIG) prior to biopsy. Findings from this single patient affirm that demyelination follows the migration of inflammatory cells from the circulation into the white matter with subsequent inflammation and demyelination. Inflammation alone may be sufficient to cause significant clinical deficits without demyelination. Inflammatory mediators such as TNFalpha and NO are involved at very early stages in the pathogenetic process. IVIG treatment may lead to the deposition of immunoglobulins and to the activation of the complement cascade, but the clinical relevance of this particular finding remains uncertain.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
In the fall of 1870, nearly 800 residents in the Butler County area formed a vigilance committee to address widespread livestock theft. By mid-December, they had executed eight men of questionable ...guilt. The sheriff issued warrants for the arrest of 89 of the vigilantes, yet local law enforcement proved unsuccessful in containing their armed resistance. The confrontation ended when the adjutant general and an attorney representing the vigilantes negotiated a resolution. The vigilantes claimed that incompetence and corruption within the legal system made it necessary for them to employ extralegal means to remove this threat to their lives and property. The evidence, however, does not fully support their argument. Despite their size, and the number of victims, the Butler County vigilantes have received little scholarly attention. This study provides an in-depth examination of the episode. Historical interpretations of western vigilantism do not fully address the complexities of the event. This project augments the historical examinations with theoretical approaches borrowed from the disciplines of philosophy, psychology, sociology, and anthropology to generate a more comprehensive interpretive model. This model is comprised of four components. (1) Context and Conduciveness: an overview of the regional history, legal traditions, and the history of their law enforcement system. (2) Mobilization: an examination of the manner in which community leaders shaped the discourse surrounding the events and the selection of a scapegoat or deviant group on whom they attached responsibility. (3) Action and Reaction: an examination of the written accounts of the lynchings, as well as the physical evidence. (4) Evaluation: an assessment of the residents' perceptions and the evolution of a community myth defining the events. This approach offers a more comprehensive assessment of the intersection of contributory factors that led to vigilantism. It also provides a method for examining what these events meant to local residents, the manner in which the community survived this phase of its history, and how the residents reconstructed their community identity.
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