An experiment to search for light sterile neutrinos is conducted at a reactor with a thermal power of 2.8 GW located at the Hanbit nuclear power complex. The search is done with a detector consisting of a ton of Gd-loaded liquid scintillator in a tendon gallery approximately 24 m from the reactor core. The measured antineutrino event rate is 1976 per day with a signal to background ratio of about 22. The shape of the antineutrino energy spectrum obtained from the eight-month data-taking period is compared with a hypothesis of oscillations due to activesterile antineutrino mixing. No strong evidence of 3+1 neutrino oscillation is found. An excess around the 5 MeV prompt energy range is observed as seen in existing longer-baseline experiments. The mixing parameter sin 2 2θ14 is limited up to less than 0.1 for ∆m The mixing among three neutrinos has been well established by experiments performed in the past two decades since the discovery of neutrino oscillations [1][2][3]. Consistent measurements of the two mass differences and the three mixing angles of the standard, three-neutrino mixing model have been reported by oscillation experiments using atmospheric, solar, reactor, and accelerator neutrinos [4]. Nevertheless, the mass hierarchy, the mass of the lightest neutrino, the Dirac or Majorana nature of the neutrino, and the CP phase are yet to be determined [5].Even though the number of active light neutrinos is limited to three by Z boson decay-width measurements [6], it is still possible to have additional neutrinos if they are sterile. Sterile neutrinos can be identified by the occurrence of activesterile neutrino oscillations. A hint for this is the LSND experiment's report of an observation ofν µ →ν e mixing with a frequency corresponding to a mass-squared difference larger than 0.01 eV 2 [7]. Results from the MiniBooNE's test of the LSND signal are, however, inconclusive [8].In addition to the LSND result, there are two other anomalies that could possibly be signs of active-sterile neutrino oscillations. An apparent ν e disappearance over a baseline of a few meters in the GALLEX and SAGE gallium experiments exposed to radioactive sources was reported [9]; the ratio of the numbers of measured and predicted events is 0.88 ± 0.05. A number of short-baseline reactor antineutrino experiments established limits on the presence of neutrino oscillations with eV mass differences by shape analyses of the measured neutrino energy spectra. Among those experiments, the Bugey experimental limits on sterile neutrinos are the most stringent [10]. Mueller et al. [11] found about a 6% deficit in reactor antineutrino event rates compared with the theoretical expectations for the short-baseline reactor experiments, which is the so-called "reactor antineutrino anomaly" (RAA). It can be interpreted as an active-sterile neutrino oscillation with three active neutrinos plus one or more sterile neutrinos, i.e., a 3 + n ν scenario [12,13], compatible with the LSND result. Recent reactor experiments that measured the θ 13 mixing an...
Mesenchymal stem cells (MSCs) are of particular interest for the treatment of immune-related diseases owing to their immunosuppressive properties. In this study, we aimed to identify the effect of interferon (IFN)-γ priming on immunomodulation by MSCs and elucidate the possible mechanism underlying their properties for the clinical treatment of allogeneic conflicts. Infusion of MSCs primed with IFN-γ significantly reduced the symptoms of graft-versus-host disease (GVHD) in NOD-SCID mice, thereby increasing survival rate when compared with naïve MSC-infused mice. However, infusion of IFN-γ-primed MSCs in which indoleamine 2,3-dioxygenase (IDO) was downregulated did not elicit this effect. The IDO gene was expressed in MSCs via the IFN-γ-Janus kinase (JAK)-signal transducer and activator of transcription 1 (STAT1) pathway, and the infusion of IDO-over-expressing MSCs increased survival rate in an in vivo GVHD model, similar to infusion of IFN-γ-primed MSCs. These data indicate that IFN-γ production by activated T-cells is correlated with the induction of IDO expression in MSCs via the IFN-γ-JAK-STAT1 pathway, which in turn results in the suppression of T-cell proliferation. Our findings also suggest that cell therapy based on MSCs primed with IFN-γ can be used for the clinical treatment of allogeneic conflicts, including GVHD.
Culture of mesenchymal stem cells (MSCs) under ambient conditions does not replicate the low oxygen environment of normal physiological or pathological states and can result in cellular impairment during culture. To overcome these limitations, we explored the effect of hypoxia (1 % O 2 ) on the biological characteristics of MSCs over the course of different culture periods. The following biological characteristics were examined in human bone marrow-derived MSCs cultured under hypoxia for 8 weeks: proliferation rate, morphology, cell size, senescence, immunophenotypic characteristics, and the expression levels of stemness-associated factors and cytokine and chemokine genes. MSCs cultured under hypoxia for approximately 2 weeks showed increased proliferation and viability. During long-term culture, hypoxia delayed phenotypic changes in MSCs, such as increased cell volume, altered morphology, and the expression of senescence-associated-β-gal, without altering their characteristic immunophenotypic characteristics. Furthermore, hypoxia increased the expression of stemness and chemokine-related genes, including OCT4 and CXCR7, and did not decrease the expression of KLF4, C-MYC, CCL2, CXCL9, CXCL10, and CXCR4 compared with levels in cells cultured under normoxia. In conclusion, low oxygen tension improved the biological characteristics of MSCs during ex vivo expansion. These data suggest that hypoxic culture could be a useful method for increasing the efficacy of MSC cell therapies.
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