Super-Razor and Searches for Sleptons and Charginos at the LHC

Direct searches for electroweak pair production of new particles at the LHC are a difficult proposition, due to the large background and low signal cross sections. We demonstrate how these searches can be improved by a combination of new razor variables and shape analysis of signal and background kinematics. We assume that the pair-produced particles decay to charged leptons and missing energy, either directly or through a W boson. In both cases the final state is a pair of opposite sign leptons plus missing transverse energy. We estimate exclusion reach in terms of sleptons and charginos as realized in minimal supersymmetry. We compare this super-razor approach in detail to analyses based on other kinematic variables, showing how the super-razor uses more of the relevant kinematic information while achieving higher selection efficiency on signals, including cases with compressed spectra.Comment: 33 pages, 33 figure

Patient and researcher perspectives on facilitating patient and public involvement in rheumatology research

No abstract available

Distinct Types of Fibrocyte Can Differentiate from Mononuclear Cells in the Presence and Absence of Serum

Background: Ageing, immunity and stresstolerance are inherent characteristics of all organisms. In animals, these traits are regulated, at least in part, by forkhead transcription factors in response to upstream signals from the Insulin/Insulin–like growth factor signalling (IIS) pathway. In the nematode Caenorhabditis elegans, these phenotypes are molecularly linked such that activation of the forkhead transcription factor DAF-16 both extends lifespan and simultaneously increases immunity and stress resistance. It is known that lifespan varies significantly among the Caenorhabditis species but, although DAF-16 signalling is highly conserved, it is unclear whether this phenotypic linkage occurs in other species. Here we investigate this phenotypic covariance by comparing longevity, stress resistance and immunity in four Caenorhabditis species. Methodology/Principal Findings: We show using phenotypic analysis of DAF-16 influenced phenotypes that among four closely related Caenorhabditis nematodes, the gonochoristic species (Caenorhabditis remanei and Caenorhabditis brenneri) have diverged significantly with a longer lifespan, improved stress resistance and higher immunity than the hermaphroditic species (C. elegans and Caenorhabditis briggsae). Interestingly, we also observe significant differences in expression levels between the daf-16 homologues in these species using Real-Time PCR, which positively correlate with the observed phenotypes. Finally, we provide additional evidence in support of a role for DAF-16 in regulating phenotypic coupling by using a combination of wildtype isolates, constitutively active daf-16 mutants and bioinformatic analysis. Conclusions: The gonochoristic species display a significantly longer lifespan (p<0.0001) and more robust immune and stress response (p<0.0001, thermal stress; p<0.01, heavy metal stress; p<0.0001, pathogenic stress) than the hermaphroditic species. Our data suggests that divergence in DAF-16 mediated phenotypes may underlie many of the differences observed between these four species of Caenorhabditis nematodes. These findings are further supported by the correlative higher daf-16 expression levels among the gonochoristic species and significantly higher lifespan, immunity and stress tolerance in the constitutively active daf-16 hermaphroditic mutants

Moving beyond convergence in the pheromone system of the moth

No description supplie

Analysis of early changes in DNA methylation in synovial fibroblasts of RA patients before diagnosis

DNA methylation is an important epigenetic modification that is known to be altered in rheumatoid arthritis synovial fibroblasts (RASF). Here, we compared the status of promoter DNA methylation of SF from patients with very early RA with SF from patients with resolving arthritis, fully established RA and from non-arthritic patients. DNA was hybridized to Infinium Human methylation 450k and 850k arrays and differential methylated genes and pathways were identified. We could identify a significant number of CpG sites that differed between the SF of different disease stages, showing that epigenetic changes in SF occur early in RA development. Principal component analysis confirmed that the different groups of SF were separated according to their DNA methylation state. Furthermore, pathway analysis showed that important functional pathways were altered in both very early and late RASF. By focusing our analysis on CpG sites in CpG islands within promoters, we identified genes that have significant hypermethylated promoters in very early RASF. Our data show that changes in DNA methylation differ in RASF compared to other forms of arthritis and occur at a very early, clinically yet unspecific stage of disease. The identified differential methylated genes might become valuable prognostic biomarkers for RA development

Direct observations of the kinetics of migrating T-cells suggest active retention by endothelial cells with continual bidirectional migration.

The kinetics and regulatory mechanisms of T-cell migration through endothelium have not been fully defined. In experimental filter-based assays in vitro, transmigration of lymphocytes takes hours, compared to minutes in vivo. We cultured endothelial cell (EC) monolayers on filters, solid substrates or collagen gels, and treated them with tumour necrosis factor-α (TNF), interferon-γ (IFN), or both, prior to analysis of lymphocyte migration in the presence or absence of flow. Peripheral blood lymphocytes (PBL), CD4+ cells or CD8+ cells, took many hours to migrate through EC-filter constructs for all cytokine treatments. However, direct microscopic observations of EC-filters which had been mounted in a flow chamber showed that PBL crossed the endothelial monolayer in minutes and were highly motile in the subendothelial space. Migration through EC was also observed on clear plastic, with or without flow. After brief settling without flow, PBL and isolated CD3+ or CD4+ cells all crossed EC in minutes, but the numbers of migrated cells varied little with time. Close observation revealed that lymphocytes continuously migrated back and forth across endothelium. Under flow, migration kinetics and the proportions migrating back and forth were little altered. On collagen gels, PBL again crossed EC in minutes and migrated back and forth, but showed little penetration of the gel over hours.In contrast, neutrophils migrated efficiently through EC and into gels. These observations suggest a novel model for lymphoid migration, in which endothelial cells support migration but retain lymphocytes (as opposed to neutrophils), and additional signal(s) are required for onward migration

Homoepitaxial Growth of Single Crystal Diamond Membranes for Quantum Information Processing

Fabrication of devices designed to fully harness the unique properties of quantum mechanics through their coupling to quantum bits (qubits) is a prominent goal in the field of quantum information processing (QIP). Among various qubit candidates, nitrogen vacancy (NV) centers in diamond have recently emerged as an outstanding platform for room temperature QIP. However, formidable challenges still remain in processing diamond and in the fabrication of thin diamond membranes, which are necessary for planar photonic device engineering. Here we demonstrate epitaxial growth of single crystal diamond membranes using a conventional microwave chemical vapor deposition (CVD) technique. The grown membranes, only a few hundred nanometers thick, show bright luminescence, excellent Raman signature and good NV center electronic spin coherence times. Microdisk cavities fabricated from these membranes exhibit quality factors of up to 3000, overlapping with NV center emission. Our methodology offers a scalable approach for diamond device fabrication for photonics, spintronics, optomechanics and sensing applications.Engineering and Applied Science

Stromal Fibroblasts in Tertiary Lymphoid Structures: A Novel Target in Chronic Inflammation

Tertiary lymphoid structures (TLS) are organized aggregates of lymphocytes, myeloid, and stromal cells that provide ectopic hubs for acquired immune responses. TLS share phenotypical and functional features with secondary lymphoid organs (SLO); however, they require persistent inflammatory signals to arise and are often observed at target sites of autoimmune disease, chronic infection, cancer, and organ transplantation. Over the past 10 years, important progress has been made in our understanding of the role of stromal fibroblasts in SLO development, organization, and function. A complex and stereotyped series of events regulate fibroblast differentiation from embryonic life in SLOs to lymphoid organ architecture observed in adults. In contrast, TLS-associated fibroblasts differentiate from postnatal, locally activated mesenchyme, predominantly in settings of inflammation and persistent antigen presentation. Therefore, there are critical differences in the cellular and molecular requirements that regulate SLO versus TLS development that ultimately impact on stromal and hematopoietic cell function. These differences may contribute to the pathogenic nature of TLS in the context of chronic inflammation and malignant transformation and offer a window of opportunity for therapeutic interventions in TLS associated pathologies

Sub-Antarctic and High Antarctic Notothenioid Fishes: Ecology and Adaptational Biology Revealed by the ICEFISH 2004 Cruise of RVIB Nathaniel B. Palmer

The goal of the ICEFISH 2004 cruise, which was conducted on board RVIB Nathaniel B. Palmer and traversed the transitional zones linking the South Atlantic to the Southern Ocean, was to compare the evolution, ecology, adaptational biology, community structure, and population dynamics of Antarctic notothenioid fishes relative to the cool/temperate notothenioids of the sub-Antarctic. To place this work in a comprehensive ecological context, cruise participants surveyed the benthos and geology of the biogeographic provinces and island shelves on either side of the Antarctic Polar Front (or Antarctic Convergence). Genome-enabled comparison of the responses of cold-living and temperate notothenioids to heat stress confirmed the sensitivity of the former to a warming Southern Ocean. Successful implementation of the international and interdisciplinary ICEFISH research cruise provides a model for future exploration of the sub-Antarctic sectors of the Indian and Pacific Oceans

Combined collider constraints on neutralinos and charginos

Searches for supersymmetric electroweakinos have entered a crucial phase, as the integrated luminosity of the Large Hadron Collider is now high enough to compensate for their weak production cross-sections. Working in a framework where the neutralinos and charginos are the only light sparticles in the Minimal Supersymmetric Standard Model, we use gambit to perform a detailed likelihood analysis of the electroweakino sector. We focus on the impacts of recent ATLAS and CMS searches with 36 fb$^{-1}$ of 13 TeV proton-proton collision data. We also include constraints from LEP and invisible decays of the $Z$ and Higgs bosons. Under the background-only hypothesis, we show that current LHC searches do not robustly exclude any range of neutralino or chargino masses. However, a pattern of excesses in several LHC analyses points towards a possible signal, with neutralino masses of $(m_{\tilde{\chi}_1^0}, m_{\tilde{\chi}_2^0}, m_{\tilde{\chi}_3^0}, m_{\tilde{\chi}_4^0})$ = (8-155, 103-260, 130-473, 219-502) GeV and chargino masses of $(m_{\tilde{\chi}_1^{\pm}}, m_{\tilde{\chi}_2^{\pm}})$ = (104-259, 224-507) GeV at the 95% confidence level. The lightest neutralino is mostly bino, with a possible modest Higgsino or wino component. We find that this excess has a combined local significance of $3.3\sigma$, subject to a number of cautions. If one includes LHC searches for charginos and neutralinos conducted with 8 TeV proton-proton collision data, the local significance is lowered to 2.9$\sigma$. We briefly consider the implications for dark matter, finding that the correct relic density can be obtained through the Higgs-funnel and $Z$-funnel mechanisms, even assuming that all other sparticles are decoupled. All samples, gambit input files and best-fit models from this study are available on Zenodo.Comment: 38 pages, 16 figures, v3 is the version accepted by EPJ