Luminosity measurement method for the LHC: The detector requirements studies

Absolute normalisation of the LHC measurements with a precision of O(1%) is desirable but beyond the reach of the present LHC detectors. This series of papers proposes and evaluates a measurement method capable to achieve such a precision target. In our earlier paper we have selected the phase-space region where the lepton pair production cross section in pp collisions at the LHC can be controlled with < 1 % precision and is large enough to reach a comparable statistical accuracy of the absolute luminosity measurement on the day-by-day basis. In the present one the performance requirements for a dedicated detector, indispensable to efficiently select events in the proposed phase-space region, are discussed.Comment: 26 pages, 13 figure

Luminosity Measurement Method for LHC: The theoretical precision and the experimental challenges

This is the first of the series of papers which present a precision method of the day-by-day monitoring of the absolute LHC luminosity. The method is based on the measurement of the rate of coplanar lepton pairs produced in peripheral collisions of the beams' particles. In the present paper we evaluate the modeling precision of the lepton pair production processes in proton-proton collisions, optimize the measurement region to achieve better than 1% accuracy of the predicted rates, and discuss the experimental challenges to filter out the luminosity monitoring lepton pairs at LHC

The design and development of a community based multisensory room

This case study describes the design and development of a multisensory environment for use by a local community, in response to local needs. Multisensory environments allow users to control the sensory inputs they experience from the environment. This autonomy may be especially impactful for those living with autism or dementia. The evidence base supporting the design, development and implementation of multisensory environments has been limited to date. This case study explores the evolution of the interdisciplinary team from a request for collaboration to the creation of a functioning multisensory room. It describes the experiences of the group of researchers finding shared understandings and evolving to a transdisciplinary approach

Source Monitoring and Evaluation of Sediment Inputs for Peoria Lake

NOTE: ISWS Library copies were labeled as ISWS CR 514, but this designation is not included in the report itself. and there was no ISWS Contract Report CR-514 listed on the ISWS website or ISWS pubs database.Ope

Documented spatial data set containing the subdivision of the basins into groundwater systems and subsystems, the selected locations per subsystem and a description of these sites, available data and projected additional measurements and equipment

The establishment of tools for trends analysis in groundwater is essential for the prediction and evaluation of measures taken within context of the Water Framework Directive and the draft Groundwater Directive. This report describes the spatial data sets which will be used for the purpose of detection, aggregation and extrapolation of temporal trends in groundwater quality. Trend analysis methods will be applied and tested at various scales and in various hydrogeological situations. The report contains a description of the studied sub-basins in TREND 2, including information on hydrogeology, land use and pressures, available data and projected additional measurements. Major differences between the sub-basins and the data sets are described to examine consequences for the work on trend detection. One of the challenges for TREND 2 is to define criteria for the application of various statistical and deterministic trend approaches for a range of hydrogeological conditions, spatial scales and types of groundwater monitoring. An overview of these conditions, scales and monitoring types is provided in the present report.FP6 Integrated Project AquaTerra Integrated Modelling of the river-sediment-soil-groundwater system; advanced tools for the management of catchment areas and river basins in the context of global change (Project no. 505428 - GOCE

Methods for high-dimensonal analysis of cells dissociated from cyropreserved synovial tissue

© 2018 The Author(s). Background: Detailed molecular analyses of cells from rheumatoid arthritis (RA) synovium hold promise in identifying cellular phenotypes that drive tissue pathology and joint damage. The Accelerating Medicines Partnership RA/SLE Network aims to deconstruct autoimmune pathology by examining cells within target tissues through multiple high-dimensional assays. Robust standardized protocols need to be developed before cellular phenotypes at a single cell level can be effectively compared across patient samples. Methods: Multiple clinical sites collected cryopreserved synovial tissue fragments from arthroplasty and synovial biopsy in a 10% DMSO solution. Mechanical and enzymatic dissociation parameters were optimized for viable cell extraction and surface protein preservation for cell sorting and mass cytometry, as well as for reproducibility in RNA sequencing (RNA-seq). Cryopreserved synovial samples were collectively analyzed at a central processing site by a custom-designed and validated 35-marker mass cytometry panel. In parallel, each sample was flow sorted into fibroblast, T-cell, B-cell, and macrophage suspensions for bulk population RNA-seq and plate-based single-cell CEL-Seq2 RNA-seq. Results: Upon dissociation, cryopreserved synovial tissue fragments yielded a high frequency of viable cells, comparable to samples undergoing immediate processing. Optimization of synovial tissue dissociation across six clinical collection sites with ~ 30 arthroplasty and ~ 20 biopsy samples yielded a consensus digestion protocol using 100 μg/ml of Liberase™ TL enzyme preparation. This protocol yielded immune and stromal cell lineages with preserved surface markers and minimized variability across replicate RNA-seq transcriptomes. Mass cytometry analysis of cells from cryopreserved synovium distinguished diverse fibroblast phenotypes, distinct populations of memory B cells and antibody-secreting cells, and multiple CD4+ and CD8+ T-cell activation states. Bulk RNA-seq of sorted cell populations demonstrated robust separation of synovial lymphocytes, fibroblasts, and macrophages. Single-cell RNA-seq produced transcriptomes of over 1000 genes/cell, including transcripts encoding characteristic lineage markers identified. Conclusions: We have established a robust protocol to acquire viable cells from cryopreserved synovial tissue with intact transcriptomes and cell surface phenotypes. A centralized pipeline to generate multiple high-dimensional analyses of synovial tissue samples collected across a collaborative network was developed. Integrated analysis of such datasets from large patient cohorts may help define molecular heterogeneity within RA pathology and identify new therapeutic targets and biomarkers

The immune cell landscape in kidneys of patients with lupus nephritis.

Lupus nephritis is a potentially fatal autoimmune disease for which the current treatment is ineffective and often toxic. To develop mechanistic hypotheses of disease, we analyzed kidney samples from patients with lupus nephritis and from healthy control subjects using single-cell RNA sequencing. Our analysis revealed 21 subsets of leukocytes active in disease, including multiple populations of myeloid cells, T cells, natural killer cells and B cells that demonstrated both pro-inflammatory responses and inflammation-resolving responses. We found evidence of local activation of B cells correlated with an age-associated B-cell signature and evidence of progressive stages of monocyte differentiation within the kidney. A clear interferon response was observed in most cells. Two chemokine receptors, CXCR4 and CX3CR1, were broadly expressed, implying a potentially central role in cell trafficking. Gene expression of immune cells in urine and kidney was highly correlated, which would suggest that urine might serve as a surrogate for kidney biopsies

A practical tool for assessing ecosystem services enhancement and degradation associated with invasive alien species

Current approaches for assessing the effects of invasive alien species (IAS) are biased toward the negative effects of these species, resulting in an incomplete picture of their real effects. This can result in an inefficient IAS management. We address this issue by describing the INvasive Species Effects Assessment Tool (INSEAT) that enables expert elicitation for rapidly assessing the ecological consequences of IAS using the ecosystem services (ES) framework. INSEAT scores the ecosystem service “gains and losses” using a scale that accounted for the magnitude and the reversibility of its effects. We tested INSEAT on 18 IAS in Great Britain. Here, we highlighted four case studies: Harmonia axyridis (Harlequin ladybird), Astacus leptodactylus (Turkish crayfish), Pacifastacus leniusculus (Signal crayfish) and Impatiens glandulifera (Himalayan balsam). The results demonstrated that a collation of different experts’ opinions using INSEAT could yield valuable information on the invasive aliens’ ecological and social effects. The users can identify certain IAS as ES providers and the trade-offs between the ES provision and loss associated with them. This practical tool can be useful for evidence-based policy and management decisions that consider the potential role of invasive species in delivering human well-being.</p

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD