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 $1\,\mathrm{km}^3$ 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 $10^{-27}\,\mathrm{cm^2}$ to $10^{-21}\,\mathrm{cm^2}$. 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 $10^{-22}\,(10^{-24})\,\mathrm{cm^2}$ the flux of non-relativistic GUT monopoles is constrained up to a level of $\Phi_{90} \le 10^{-18}\,(10^{-17})\,\mathrm{cm^{-2}s^{-1}sr^{-1}}$ 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$^{-2}$ spectrum the median sensitivity at 90\% C.L. is $\sim 10^{-12}$ TeV$^{-1}$cm$^{-2}$s$^{-1}$ for energies between 1 TeV$-$1 PeV in the northern sky and $\sim 10^{-11}$ TeV$^{-1}$cm$^{-2}$s$^{-1}$ 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 $10^{-8}\, \mathrm{GeV}\, \mathrm{cm}^{-2}\, \mathrm{s}^{-1}\, \mathrm{sr}^{-1}$ per flavor and reject a purely atmospheric explanation for the combined 3-year data at $5.7 \sigma$. 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

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

Circulating microparticles: square the circle

Background: The present review summarizes current knowledge about microparticles (MPs) and provides a systematic overview of last 20 years of research on circulating MPs, with particular focus on their clinical relevance. Results: MPs are a heterogeneous population of cell-derived vesicles, with sizes ranging between 50 and 1000 nm. MPs are capable of transferring peptides, proteins, lipid components, microRNA, mRNA, and DNA from one cell to another without direct cell-to-cell contact. Growing evidence suggests that MPs present in peripheral blood and body fluids contribute to the development and progression of cancer, and are of pathophysiological relevance for autoimmune, inflammatory, infectious, cardiovascular, hematological, and other diseases. MPs have large diagnostic potential as biomarkers; however, due to current technological limitations in purification of MPs and an absence of standardized methods of MP detection, challenges remain in validating the potential of MPs as a non-invasive and early diagnostic platform. Conclusions: Improvements in the effective deciphering of MP molecular signatures will be critical not only for diagnostics, but also for the evaluation of treatment regimens and predicting disease outcomes