Very long optical path-length from a compact multi-pass cell

The multiple-pass optical cell is an important tool for laser absorption spectroscopy and its many applications. For most practical applications, such as trace-gas detection, a compact and robust design is essential. Here we report an investigation into a multi-pass cell design based on a pair of cylindrical mirrors, with a particular focus on achieving very long optical paths. We demonstrate a path-length of 50.31 m in a cell with 40 mm diameter mirrors spaced 88.9 mm apart - a 3-fold increase over the previously reported longest path-length obtained with this type of cell configuration. We characterize the mechanical stability of the cell and describe the practical conditions necessary to achieve very long path-lengths

Transcriptomic profiling of programmed cell death 1 (PD-1) expressing T cells in early rheumatoid arthritis identifies a decreased CD4 + PD-1 + signature post-treatment.

Programmed cell death protein 1 (PD-1)-expressing T cells are expanded in individuals with established rheumatoid arthritis (RA). However, little is known about their functional role in the pathogenesis of early RA. To address this, we investigated the transcriptomic profiles of circulating CD4⁺ and CD8⁺ PD-1⁺ lymphocytes from patients with early RA (n = 5) using fluorescence activated cell sorting in conjunction with total RNA sequencing. Additionally, we assessed for alterations in CD4⁺PD-1⁺ gene signatures in previously published synovial tissue (ST) biopsy data (n = 19) (GSE89408, GSE97165) before and after six-months of triple disease modifying anti-rheumatic drug (tDMARD) treatment. Comparisons of gene signatures between CD4⁺PD-1⁺ vs. PD-1- cells identified significant upregulation of genes including CXCL13 and MAF, and in pathways including Th1 and Th2, cross talk between dendritic cells and NK cells, B cell development and antigen presentation. Gene signatures from early RA ST before and after six-month tDMARD treatment revealed downregulation of the CD4⁺PD-1⁺ signatures following treatment, identifying a mechanism through which tDMARDs exert their effect by influencing T cell populations. Furthermore, we identify factors associated with B cell help that are enhanced in the ST compared with PBMCs, highlighting their importance in driving synovial inflammation.Katie Lowe, Annabelle Small, Qingxuan Song, Ling, Yang Hao, William Murray, Brown, Susanna Proudman, Malcolm D. Smith, Sunil Nagpal, Mihir D. Wechaleka

Differential expansion of T peripheral helper cells in early rheumatoid arthritis and osteoarthritis synovium

Objectives: Programmed cell death protein 1 (PD-1)- expressing T cells are implicated in the pathogenesis of autoimmune inflammatory diseases such as rheumatoid arthritis. A subset of CXCR5− T cells, termed T peripheral helper (Tph) cells, which drive B cell differentiation, have been identified in ectopic lymphoid structures in established rheumatoid arthritis synovial tissue. Here, we aimed to characterise these in treatment-naïve, early rheumatoid arthritis to determine whether these cells accumulate prior to fully established disease. Methods: Fresh dissociated tissue and peripheral blood mononuclear cell (PBMC) suspensions were stained with Zombie UV, followed by anti-CD45RO, PD-1, CD3, ICOS, CD8, CD4, CD20, CXCR5, TIGIT and CD38 antibodies prior to analysis. For histology, rheumatoid arthritis synovial sections were prepared for Opal multispectral immunofluorescence with anti-CD45RO, CD20, PD-1 and CXCR5 antibodies. Images were acquired on the Perkin Elmer Vectra V.3.0 imaging system and analysed using InForm Advanced Image Analysis software. Results: Flow cytometry revealed T cell infiltration in the rheumatoid arthritis synovium with differential expression of PD-1, CD45RO, ICOS, TIGIT and CD38. We observed a higher frequency of PD1hiCXCR5− Tph in rheumatoid arthritis synovial tissue and PBMCs versus controls, and no significant difference in T follicular helper cell frequency. Microscopy identified a 10-fold increase of Tph cells in early rheumatoid arthritis synovial follicular and diffuse regions, and identified Tph adjacent to germinal centre B cells. Conclusions: These data demonstrate that PD-1hi Tph cells are present in early rheumatoid arthritis, but not osteoarthritis synovium, and therefore may provide a target for treatment of patients with early rheumatoid arthritis.William Murray-Brown, Yanxia Guo, Annabelle Small, Katie Lowe, Helen Weedon, Malcolm D Smith, Susan E Lester, Susanna M Proudman, Navin L Rao, Ling-Yang Hao, Sunil Nagpal, Mihir D Wechaleka

Identification of a Robust Methylation Classifier for Cutaneous Melanoma Diagnosis

Early diagnosis improves melanoma survival, yet the histopathological diagnosis of cutaneous primary melanoma can be challenging, even for expert dermatopathologists. Analysis of epigenetic alterations, such as DNA methylation, that occur in melanoma can aid in its early diagnosis. Using a genome-wide methylation screening, we assessed CpG methylation in a diverse set of 89 primary invasive melanomas, 73 nevi, and 41 melanocytic proliferations of uncertain malignant potential, classified based on interobserver review by dermatopathologists. Melanomas and nevi were split into training and validation sets. Predictive modeling in the training set using ElasticNet identified a 40-CpG classifier distinguishing 60 melanomas from 48 nevi. High diagnostic accuracy (area under the receiver operator characteristic curve = 0.996, sensitivity = 96.6%, and specificity = 100.0%)was independently confirmed in the validation set (29 melanomas, 25 nevi)and other published sample sets. The 40-CpG melanoma classifier included homeobox transcription factors and genes with roles in stem cell pluripotency or the nervous system. Application of the 40-CpG melanoma classifier to the diagnostically uncertain samples assigned melanoma or nevus status, potentially offering a diagnostic tool to assist dermatopathologists. In summary, the robust, accurate 40-CpG melanoma classifier offers a promising assay for improving primary melanoma diagnosis

Radio Location of Partial Discharge Sources: A Support Vector Regression Approach

Partial discharge (PD) can provide a useful forewarning of asset failure in electricity substations. A significant proportion of assets are susceptible to PD due to incipient weakness in their dielectrics. This paper examines a low cost approach for uninterrupted monitoring of PD using a network of inexpensive radio sensors to sample the spatial patterns of PD received signal strength. Machine learning techniques are proposed for localisation of PD sources. Specifically, two models based on Support Vector Machines (SVMs) are developed: Support Vector Regression (SVR) and Least-Squares Support Vector Regression (LSSVR). These models construct an explicit regression surface in a high dimensional feature space for function estimation. Their performance is compared to that of artificial neural network (ANN) models. The results show that both SVR and LSSVR methods are superior to ANNs in accuracy. LSSVR approach is particularly recommended as practical alternative for PD source localisation due to it low complexity

Crystallization Characteristics of CaO-Al2O3-Based Mold Flux and Their Effects on In-Mold Performance during High-Aluminum TRIP Steels Continuous Casting

Crystallization behaviors of the newly developed lime-alumina-based mold fluxes for high-aluminum transformation induced plasticity (TRIP) steels casting were experimentally studied, and compared with those of lime-silica-based mold fluxes. The effects of mold flux crystallization characteristics on heat transfer and lubrication performance in casting high-Al TRIP steels were also evaluated. The results show that the crystallization temperatures of lime-alumina-based mold fluxes are much lower than those of lime-silica-based mold fluxes. Increasing B2O3 addition suppresses the crystallization of lime-alumina-based mold fluxes, while Na2O exhibits an opposite effect. In continuous cooling of lime-alumina-based mold fluxes with high B2O3 contents and a CaO/Al2O3 ratio of 3.3, faceted cuspidine precipitates first, followed by needle-like CaO center dot B2O3 or 9CaO center dot 3B(2)O(3)center dot CaF2. In lime-alumina-based mold flux with low B2O3 content (5.4 mass pct) and a CaO/Al2O3 ratio of 1.2, the formation of fine CaF2 takes place first, followed by blocky interconnected CaO center dot 2Al(2)O(3) as the dominant crystalline phase, and rod-like 2CaO center dot B2O3 precipitates at lower temperature during continuous cooling of the mold flux. In B2O3-free mold flux, blocky interconnected 3CaO center dot Al2O3 precipitates after CaF2 and 3CaO center dot 2SiO(2) formation, and takes up almost the whole crystalline fraction. The casting trials show that the mold heat transfer rate significantly decreases near the meniscus during the continuous casting using lime-alumina-mold fluxes with higher crystallinity, which brings a great reduction of surface depressions on cast slabs. However, excessive crystallinity of mold flux causes poor lubrication between mold and solidifying steel shell, which induces various defects such as drag marks on cast slab. Among the studied mold fluxes, lime-alumina-based mold fluxes with higher B2O3 contents and a CaO/Al2O3 ratio of 3.3 show comparatively improved performance.ope

Process Simulation and Control Optimization of a Blast Furnace Using Classical Thermodynamics Combined to a Direct Search Algorithm

Several numerical approaches have been proposed in the literature to simulate the behavior of modern blast furnaces: finite volume methods, data-mining models, heat and mass balance models, and classical thermodynamic simulations. Despite this, there is actually no efficient method for evaluating quickly optimal operating parameters of a blast furnace as a function of the iron ore composition, which takes into account all potential chemical reactions that could occur in the system. In the current study, we propose a global simulation strategy of a blast furnace, the 5-unit process simulation. It is based on classical thermodynamic calculations coupled to a direct search algorithm to optimize process parameters. These parameters include the minimum required metallurgical coke consumption as well as the optimal blast chemical composition and the total charge that simultaneously satisfy the overall heat and mass balances of the system. Moreover, a Gibbs free energy function for metallurgical coke is parameterized in the current study and used to fine-tune the simulation of the blast furnace. Optimal operating conditions and predicted output stream properties calculated by the proposed thermodynamic simulation strategy are compared with reference data found in the literature and have proven the validity and high precision of this simulation

Meta-analysis of exome array data identifies six novel genetic loci for lung function

Background: Over 90 regions of the genome have been associated with lung function to date, many of which have also been implicated in chronic obstructive pulmonary disease. Methods: We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and the ratio of FEV1 to FVC (FEV1/FVC). These analyses by the SpiroMeta and CHARGE consortia included 60,749 individuals of European ancestry from 23 studies, and 7,721 individuals of African Ancestry from 5 studies in the discovery stage, with follow-up in up to 111,556 independent individuals. Results: We identified significant (P<2·8x10-7) associations with six SNPs: a nonsynonymous variant in RPAP1, which is predicted to be damaging, three intronic SNPs (SEC24C, CASC17 and UQCC1) and two intergenic SNPs near to LY86 and FGF10. Expression quantitative trait loci analyses found evidence for regulation of gene expression at three signals and implicated several genes, including TYRO3 and PLAU. Conclusions: Further interrogation of these loci could provide greater understanding of the determinants of lung function and pulmonary disease