229 research outputs found
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Managing Climate Risk in Water Supply Systems
Using decadal prediction experiments from the WCRP/CMIP5 suite that were initialized every year from 1960-onward, we explore long-lead predictability of ENSO events. Both deterministic and probabilistic skill metrics are used to assess the ability of these decadal prediction systems to reproduce ENSO variability as represented by the NINO3.4 index (EN3.4). Several individual systems as well as the multi-model mean can predict ENSO events 3–4 years in advance, though not for every event during the hindcast period. This long-lead skill is beyond the previously documented predictability limits of initialized prediction systems. As part of the analysis, skill in reproducing the annual cycle of EN3.4, and the annual cycle of its interannual variability is examined. Most of the prediction systems reproduce the seasonal cycle of EN3.4, but are less able to capture the timing and magnitude of the variability. However, for the prediction systems used here, the fidelity of annual cycle characteristics does not appear to be related to the system’s ability to predict ENSO events. In addition, the performance of the multi-model ensemble mean is explored and compared to the multi-model mean based solely on the most skillful systems; the latter is found to yield better results for the deterministic metrics. Finally, an analysis of the near-surface temperature and precipitation teleconnections reveals that the ability of the systems to detect ENSO events far in advance could translate into predictive skill over land for several lead years, though with reduced amplitudes compared to observations
How control systems influence product innovation processes: examining the role of entrepreneurial orientation
This paper yields insights into the channels through which Management Accounting and Control Systems (MACS) exert an influence on product innovation by examining the extent to which different forms of control (i.e. value systems, diagnostic control systems, interactive control systems) are directly associated with the distinct phases of innovation processes. Using survey data collected from 118 medium and large Spanish companies, we find that: (1) value systems and interactive control systems have significant main effects on the creativity, coordination and knowledge integration, and filtering (sub-)phases of innovation processes; and (2) the significance and direction of these influences vary depending on the Entrepreneurial Orientation (EO) of firms. By highlighting the relevance of EO in shaping the influence of MACS on product innovation processes, this study calls for caution in generalising the expected effects of MACS on innovation
Search for non-relativistic Magnetic Monopoles with IceCube
The IceCube Neutrino Observatory is a large Cherenkov detector instrumenting
of Antarctic ice. The detector can be used to search for
signatures of particle physics beyond the Standard Model. Here, we describe the
search for non-relativistic, magnetic monopoles as remnants of the GUT (Grand
Unified Theory) era shortly after the Big Bang. These monopoles may catalyze
the decay of nucleons via the Rubakov-Callan effect with a cross section
suggested to be in the range of to
. In IceCube, the Cherenkov light from nucleon decays
along the monopole trajectory would produce a characteristic hit pattern. This
paper presents the results of an analysis of first data taken from May 2011
until May 2012 with a dedicated slow-particle trigger for DeepCore, a
subdetector of IceCube. A second analysis provides better sensitivity for the
brightest non-relativistic monopoles using data taken from May 2009 until May
2010. In both analyses no monopole signal was observed. For catalysis cross
sections of the flux of non-relativistic
GUT monopoles is constrained up to a level of at a 90% confidence level,
which is three orders of magnitude below the Parker bound. The limits assume a
dominant decay of the proton into a positron and a neutral pion. These results
improve the current best experimental limits by one to two orders of magnitude,
for a wide range of assumed speeds and catalysis cross sections.Comment: 20 pages, 20 figure
Searches for Extended and Point-like Neutrino Sources with Four Years of IceCube Data
We present results on searches for point-like sources of neutrinos using four
years of IceCube data, including the first year of data from the completed
86-string detector. The total livetime of the combined dataset is 1,373 days.
For an E spectrum the median sensitivity at 90\% C.L. is
TeVcms for energies between 1 TeV1 PeV in the northern
sky and TeVcms for energies between 100
TeV 100 PeV in the southern sky. The sensitivity has improved from both the
additional year of data and the introduction of improved reconstructions
compared to previous publications. In addition, we present the first results
from an all-sky search for extended sources of neutrinos. We update results of
searches for neutrino emission from stacked catalogs of sources, and test five
new catalogs; two of Galactic supernova remnants and three of active galactic
nuclei. In all cases, the data are compatible with the background-only
hypothesis, and upper limits on the flux of muon neutrinos are reported for the
sources considered.Comment: 36 pages, 15 figures. Submitted to the Astrophysical Journa
Observation of High-Energy Astrophysical Neutrinos in Three Years of IceCube Data
A search for high-energy neutrinos interacting within the IceCube detector
between 2010 and 2012 provided the first evidence for a high-energy neutrino
flux of extraterrestrial origin. Results from an analysis using the same
methods with a third year (2012-2013) of data from the complete IceCube
detector are consistent with the previously reported astrophysical flux in the
100 TeV - PeV range at the level of per flavor and reject a
purely atmospheric explanation for the combined 3-year data at .
The data are consistent with expectations for equal fluxes of all three
neutrino flavors and with isotropic arrival directions, suggesting either
numerous or spatially extended sources. The three-year dataset, with a livetime
of 988 days, contains a total of 37 neutrino candidate events with deposited
energies ranging from 30 to 2000 TeV. The 2000 TeV event is the highest-energy
neutrino interaction ever observed.Comment: 8 pages, 5 figures. Accepted by PRL. The event catalog, event
displays, and other data tables are included after the final page of the
article. Changed from the initial submission to reflect referee comments,
expanding the section on atmospheric backgrounds, and fixes offsets of up to
0.9 seconds in reported event times. Address correspondence to: J. Feintzeig,
C. Kopper, N. Whitehor
The IceCube Neutrino Observatory Part VI: Ice Properties, Reconstruction and Future Developments
Papers on ice properties, reconstruction and future developments submitted to
the 33nd International Cosmic Ray Conference (Rio de Janeiro 2013) by the
IceCube Collaboration.Comment: 28 pages, 38 figures; Papers submitted to the 33nd International
Cosmic Ray Conference, Rio de Janeiro 2013; version 2 corrects errors in the
author lis
HDL Interfere with the Binding of T Cell Microparticles to Human Monocytes to Inhibit Pro-Inflammatory Cytokine Production
BACKGROUND: Direct cellular contact with stimulated T cells is a potent mechanism that induces cytokine production in human monocytes in the absence of an infectious agent. This mechanism is likely to be relevant to T cell-mediated inflammatory diseases such as rheumatoid arthritis and multiple sclerosis. Microparticles (MP) generated by stimulated T cells (MPT) display similar monocyte activating ability to whole T cells, isolated T cell membranes, or solubilized T cell membranes. We previously demonstrated that high-density lipoproteins (HDL) inhibited T cell contact- and MPT-induced production of IL-1beta but not of its natural inhibitor, the secreted form of IL-1 receptor antagonist (sIL-1Ra).
METHODOLOGY/PRINCIPAL FINDINGS: Labeled MPT were used to assess their interaction with monocytes and T lymphocytes by flow cytometry. Similarly, interactions of labeled HDL with monocytes and MPT were assessed by flow cytometry. In parallel, the MPT-induction of IL-1beta and sIL-1Ra production in human monocytes and the effect of HDL were assessed in cell cultures. The results show that MPT, but not MP generated by activated endothelial cells, bond monocytes to trigger cytokine production. MPT did not bind T cells. The inhibition of IL-1beta production by HDL correlated with the inhibition of MPT binding to monocytes. HDL interacted with MPT rather than with monocytes suggesting that they bound the activating factor(s) of T cell surface. Furthermore, prototypical pro-inflammatory cytokines and chemokines such as TNF, IL-6, IL-8, CCL3 and CCL4 displayed a pattern of production induced by MPT and inhibition by HDL similar to IL-1beta, whereas the production of CCL2, like that of sIL-1Ra, was not inhibited by HDL.
CONCLUSIONS/SIGNIFICANCE: HDL inhibit both MPT binding to monocytes and the MPT-induced production of some but not all cytokines, shedding new light on the mechanism by which HDL display their anti-inflammatory functions
Zidovudine plus lamivudine in Human T-Lymphotropic Virus type-I-associated myelopathy: a randomised trial
BACKGROUND: No therapies have been proven to persistently improve the outcome of HTLV-I-associated myelopathy. Clinical benefit has been reported with zidovudine and with lamivudine in observational studies. We therefore conducted a randomised, double blind, placebo controlled study of six months combination therapy with these nucleoside analogues in sixteen patients. RESULTS: Primary outcomes were change in HTLV-I proviral load in PBMCs and clinical measures. Secondary endpoints were changes in T-cell subsets and markers of activation and proliferation. Six patients discontinued zidovudine. No significant changes in pain, bladder function, disability score, gait, proviral load or markers of T-cell activation or proliferation were seen between the two arms. Active therapy was associated with an unexplained decrease in CD8 and non-T lymphocyte counts. CONCLUSION: Failure to detect clinical improvement may have been due irreversible nerve damage in these patients with a long clinical history and future studies should target patients presenting earlier. The lack of virological effect but may reflect a lack of activity of these nucleoside analogues against HTLV-I RT in vivo, inadequate intracellular concentrations of the active moiety or the contribution of new cell infection to maintaining proviral load at this stage of infection may be relatively small masking the effects of RT inhibition
Assessment of immune functions and MRI disease activity in relapsing-remitting multiple sclerosis patients switching from natalizumab to fingolimod (ToFingo-Successor)
B cells and monocytes from patients with active multiple sclerosis exhibit increased surface expression of both HERV-H Env and HERV-W Env, accompanied by increased seroreactivity
<p>Abstract</p> <p>Background</p> <p>The etiology of the neurogenerative disease multiple sclerosis (MS) is unknown. The leading hypotheses suggest that MS is the result of exposure of genetically susceptible individuals to certain environmental factor(s). Herpesviruses and human endogenous retroviruses (HERVs) represent potentially important factors in MS development. Herpesviruses can activate HERVs, and HERVs are activated in MS patients.</p> <p>Results</p> <p>Using flow cytometry, we have analyzed HERV-H Env and HERV-W Env epitope expression on the surface of PBMCs from MS patients with active and stable disease, and from control individuals. We have also analyzed serum antibody levels to the expressed HERV-H and HERV-W Env epitopes. We found a significantly higher expression of HERV-H and HERV-W Env epitopes on B cells and monocytes from patients with active MS compared with patients with stable MS or control individuals. Furthermore, patients with active disease had relatively higher numbers of B cells in the PBMC population, and higher antibody reactivities towards HERV-H Env and HERV-W Env epitopes. The higher antibody reactivities in sera from patients with active MS correlate with the higher levels of HERV-H Env and HERV-W Env expression on B cells and monocytes. We did not find such correlations for stable MS patients or for controls.</p> <p>Conclusion</p> <p>These findings indicate that both HERV-H Env and HERV-W Env are expressed in higher quantities on the surface of B cells and monocytes in patients with active MS, and that the expression of these proteins may be associated with exacerbation of the disease.</p
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