Deficient resident memory T-cell and Cd8 T-cell response to commensals in inflammatory bowel disease

Background Aims: The intestinal microbiota is closely associated with resident memory lymphocytes in mucosal tissue. We sought to understand how acquired cellular and humoral immunity to the microbiota differ in health versus inflammatory bowel disease (IBD). Methods Resident memory T-cells (Trm) in colonic biopsies and local antibody responses to intraepithelial microbes were analyzed. Systemic antigen-specific immune T- and B-cell memory to a panel of commensal microbes was assessed. Results Systemically, healthy blood showed CD4 and occasional CD8 memory T-cell responses to selected intestinal bacteria but few memory B-cell responses. In IBD, CD8 memory T-cell responses decreased although B-cell responses and circulating plasmablasts increased. Possibly secondary to loss of systemic CD8 T-cell responses in IBD, dramatically reduced numbers of mucosal CD8+ Trm and γδ T-cells were observed. IgA responses to intraepithelial bacteria were increased. Colonic Trm expressed CD39 and CD73 ectonucleotidases, characteristic of regulatory T-cells. Cytokines/factors required for Trm differentiation were identified, and in vitro-generated Trm expressed regulatory T-cell function via CD39. Cognate interaction between T-cells and dendritic cells induced T-bet expression in dendritic cells, a key mechanism in regulating cell-mediated mucosal responses. Conclusions A previously unrecognized imbalance exists between cellular and humoral immunity to the microbiota in IBD, with loss of mucosal T-cell-mediated barrier immunity and uncontrolled antibody responses. Regulatory function of Trm may explain their association with intestinal health. Promoting Trm and their interaction with dendritic cells rather than immunosuppression may reinforce tissue immunity, improve barrier function and prevent B-cell dysfunction in microbiota-associated disease and IBD etiology

An 8-mm diameter fibre robot positioner for massive spectroscopy surveys

This article has been accepted for publication in Monthly Notices of Royal Astronomical Society © 2015 The Authors. Published by Oxford University Press on behalf of the Royal Astronomical Society. All rights reservedMassive spectroscopic survey are becoming trendy in astrophysics and cosmology, as they can address new fundamental knowledge such as understanding the formation of the Milky Way and probing the nature of the mysterious dark energy. To enable massive spectroscopic surveys, new technology has been developed to place thousands of optical fibres at a given position on a focal plane. This technology needs to be: (1) accurate, with micrometer positional accuracy; (2) fast to minimize overhead; (3) robust to minimize failure; and (4) low cost. In this paper, we present the development, properties, and performance of a new single 8-mm in diameter fibre positioner robot, using two 4-mm DC-brushless gearmotors, that allows us to achieve accuracies up to 0.07 arcsec (5 μm). This device has been developed in the context of the Dark Energy Spectroscopic InstrumentWe acknowledge support from the Spanish MICINNs Consolider-Ingenio 2010 Program me under grant MultiDark CSD2009-00064, HEPHACOS S2009/ESP-1473, and MINECO Centro de Excelencia Severo Ochoa Programme under grant SEV-2012-0249. We also thank the support from a CSIC-AVS contract through MICINN grant AYA2010-21231-C02- 01, and CDTI grant IDC-20101033; and support from the Spanish MINECO research grants AYA2012-31101 and FPA2012-34694. JPK, PH and LM acknowledge support from the ERC advanced grant LIDA and from an SNF Interdisciplinary grant

An 8-mm diameter fibre robot positioner for massive spectroscopy surveys

Massive spectroscopic survey are becoming trendy in astrophysics and cosmology, as they can address new fundamental knowledge such as understanding the formation of the Milky Way and probing the nature of the mysterious dark energy. To enable massive spectroscopic surveys, new technology has been developed to place thousands of optical fibres at a given position on a focal plane. This technology needs to be: (1) accurate, with micrometer positional accuracy; (2) fast to minimize overhead; (3) robust to minimize failure; and (4) low cost. In this paper, we present the development, properties, and performance of a new single 8-mm in diameter fibre positioner robot, using two 4-mm DC-brushless gearmotors, that allows us to achieve accuracies up to 0.07arcsec (5 μm). This device has been developed in the context of the Dark Energy Spectroscopic Instrument.

Multicenter evaluation of the vitek MS matrix-assisted laser desorption ionization-time of flight mass spectrometry system for identification of gram-positive aerobic bacteria

Matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF) is gaining momentum as a tool for bacterial identification in the clinical microbiology laboratory. Compared with conventional methods, this technology can more readily and conveniently identify a wide range of organisms. Here, we report the findings from a multicenter study to evaluate the Vitek MS v2.0 system (bioMérieux, Inc.) for the identification of aerobic Gram-positive bacteria. A total of 1,146 unique isolates, representing 13 genera and 42 species, were analyzed, and results were compared to those obtained by nucleic acid sequence-based identification as the reference method. For 1,063 of 1,146 isolates (92.8%), the Vitek MS provided a single identification that was accurate to the species level. For an additional 31 isolates (2.7%), multiple possible identifications were provided, all correct at the genus level. Mixed-genus or single-choice incorrect identifications were provided for 18 isolates (1.6%). Although no identification was obtained for 33 isolates (2.9%), there was no specific bacterial species for which the Vitek MS consistently failed to provide identification. In a subset of 463 isolates representing commonly encountered important pathogens, 95% were accurately identified to the species level and there were no misidentifications. Also, in all but one instance, the Vitek MS correctly differentiated Streptococcus pneumoniae from other viridans group streptococci. The findings demonstrate that the Vitek MS system is highly accurate for the identification of Gram-positive aerobic bacteria in the clinical laboratory setting

A simplified mesoscale 3D model for characterizing fibrinolysis under flow conditions

One of the routine clinical treatments to eliminate ischemic stroke thrombi is injecting a biochemical product into the patient’s bloodstream, which breaks down the thrombi’s fibrin fibers: intravenous or intravascular thrombolysis. However, this procedure is not without risk for the patient; the worst circumstances can cause a brain hemorrhage or embolism that can be fatal. Improvement in patient management drastically reduced these risks, and patients who benefited from thrombolysis soon after the onset of the stroke have a significantly better 3-month prognosis, but treatment success is highly variable. The causes of this variability remain unclear, and it is likely that some fundamental aspects still require thorough investigations. For that reason, we conducted in vitro flow-driven fibrinolysis experiments to study pure fibrin thrombi breakdown in controlled conditions and observed that the lysis front evolved non-linearly in time. To understand these results, we developed an analytical 1D lysis model in which the thrombus is considered a porous medium. The lytic cascade is reduced to a second-order reaction involving fibrin and a surrogate pro-fibrinolytic agent. The model was able to reproduce the observed lysis evolution under the assumptions of constant fluid velocity and lysis occurring only at the front. For adding complexity, such as clot heterogeneity or complex flow conditions, we propose a 3-dimensional mesoscopic numerical model of blood flow and fibrinolysis, which validates the analytical model’s results. Such a numerical model could help us better understand the spatial evolution of the thrombi breakdown, extract the most relevant physiological parameters to lysis efficiency, and possibly explain the failure of the clinical treatment. These findings suggest that even though real-world fibrinolysis is a complex biological process, a simplified model can recover the main features of lysis evolution.</p

Technical trading and cryptocurrencies

This paper carries out a comprehensive examination of technical trading rules in cryptocurrency markets, using data from two Bitcoin markets and three other popular cryptocurrencies. We employ almost 15,000 technical trading rules from the main five classes of technical trading rules and find significant predictability and profitability for each class of technical trading rule in each cryptocurrency. We find that the breakeven transaction costs are substantially higher than those typically found in cryptocurrency markets. To safeguard against data-snooping, we implement a number of multiple hypothesis procedures which confirms our findings that technical trading rules do offer significant predictive power and profitability to investors. We also show that the technical trading rules offer substantially higher risk-adjusted returns than the simple buy-and-hold strategy, showing protection against lengthy and severe drawdowns associated with cryptocurrency markets. However there is no predictability for Bitcoin in the out-of-sample period, although predictability remains in other cryptocurrency markets

Astro2020 APC White Paper: The MegaMapper: a z &gt; 2 spectroscopic instrument for the study of Inflation and Dark Energy

MegaMapper is a proposed ground-based experiment to measure Inflation parameters and Dark Energy from galaxy redshifts at