Probing Non-Standard Neutrino Interactions with Neutrino Factories

We discuss the sensitivity reach of a neutrino factory measurement to non-standard neutrino interactions (NSI), which may exist as a low-energy manifestation of physics beyond the Standard Model. We use the muon appearance mode \nu_e --> \nu_\mu and consider two detectors, one at 3000 km and the other at 7000 km. Assuming the effects of NSI at the production and the detection are negligible, we discuss the sensitivities to NSI and the simultaneous determination of \theta_{13} and \delta by examining the effects in the neutrino propagation of various systems in which two NSI parameters \epsilon_{\alpha \beta} are switched on. The sensitivities to off-diagonal \epsilon's are found to be excellent up to small values of \theta_{13}. We demonstrate that the two-detector setting is powerful enough to resolve the \theta_{13}-NSI confusion problem. We believe that the results obtained in this paper open the door to the possibility of using neutrino factory as a discovery machine for NSI while keeping its primary function of performing precision measurements of the lepton mixing parameters.Comment: 47 pages, 22 figures. Color version of Figs. 18, 19 and 22 can be found in the article published in JHE

Perturbation Theory of Neutrino Oscillation with Nonstandard Neutrino Interactions

We discuss various physics aspects of neutrino oscillation with non-standard interactions (NSI). We formulate a perturbative framework by taking \Delta m^2_{21} / \Delta m^2_{31}, s_{13}, and the NSI elements \epsilon_{\alpha \beta} (\alpha, \beta = e, \mu, \tau) as small expansion parameters of the same order \epsilon. Within the \epsilon perturbation theory we obtain the S matrix elements and the neutrino oscillation probability formula to second order (third order in \nu_e related channels) in \epsilon. The formula allows us to estimate size of the contribution of any particular NSI element \epsilon_{\alpha beta} to the oscillation probability in arbitrary channels, and gives a global bird-eye view of the neutrino oscillation phenomena with NSI. Based on the second-order formula we discuss how all the conventional lepton mixing as well as NSI parameters can be determined. Our results shows that while \theta_{13}, \delta, and the NSI elements in \nu_e sector can in principle be determined, complete measurement of the NSI parameters in the \nu_\mu - \nu_\tau sector is not possible by the rate only analysis. The discussion for parameter determination and the analysis based on the matter perturbation theory indicate that the parameter degeneracy prevails with the NSI parameters. In addition, a new solar-atmospheric variable exchange degeneracy is found. Some general properties of neutrino oscillation with and without NSI are also illuminated.Comment: manuscript restructured, discussion of new type of parameter degeneracy added. 47 page

Recoilless Resonant Absorption of Monochromatic Neutrino Beam for Measuring Delta m^2_{31} and theta_{13}

We discuss, in the context of precision measurement of Delta m^2_{31} and theta_{13}, physics capabilities enabled by the recoilless resonant absorption of monochromatic antineutrino beam enhanced by the M\"ossbauer effect recently proposed by Raghavan. Under the assumption of small relative systematic error of a few tenth of percent level between measurement at different detector locations, we give analytical and numerical estimates of the sensitivities to Delta m^2_{31} and sin^2 2theta_{13}. The accuracies of determination of them are enormous; The fractional uncertainty in Delta m^2_{31} achievable by 10 point measurement is 0.6% (2.4%) for sin^2 2theta_{13} = 0.05, and the uncertainty of sin^2 2theta_{13} is 0.002 (0.008) both at 1 sigma CL with the optimistic (pessimistic) assumption of systematic error of 0.2% (1%). The former opens a new possibility of determining the neutrino mass hierarchy by comparing the measured value of Delta m^2_{31} with the one by accelerator experiments, while the latter will help resolving the theta_{23} octant degeneracy.Comment: 23 pages, 3 figures, version to appear in New Journal of Physic

Broad-Spectrum Matrix Metalloproteinase Inhibition Curbs Inflammation and Liver Injury but Aggravates Experimental Liver Fibrosis in Mice

Background Liver fibrosis is characterized by excessive synthesis of extracellular matrix proteins, which prevails over their enzymatic degradation, primarily by matrix metalloproteinases (MMPs). The effect of pharmacological MMP inhibition on fibrogenesis, however, is largely unexplored. Inflammation is considered a prerequisite and important co-contributor to fibrosis and is, in part, mediated by tumor necrosis factor (TNF)-α-converting enzyme (TACE). We hypothesized that treatment with a broad-spectrum MMP and TACE-inhibitor (Marimastat) would ameliorate injury and inflammation, leading to decreased fibrogenesis during repeated hepatotoxin-induced liver injury.Methodology/Principal Findings Liver fibrosis was induced in mice by repeated carbon tetrachloride (CCl4) administration, during which the mice received either Marimastat or vehicle twice daily. A single dose of CCl4was administered to investigate acute liver injury in mice pretreated with Marimastat, mice deficient in Mmp9, or mice deficient in both TNF-α receptors. Liver injury was quantified by alanine aminotransferase (ALT) levels and confirmed by histology. Hepatic collagen was determined as hydroxyproline, and expression of fibrogenesis and fibrolysis-related transcripts was determined by quantitative reverse-transcription polymerase chain reaction. Marimastat-treated animals demonstrated significantly attenuated liver injury and inflammation but a 25% increase in collagen deposition. Transcripts related to fibrogenesis were significantly less upregulated compared to vehicle-treated animals, while MMP expression and activity analysis revealed efficient pharmacologic MMP-inhibition and decreased fibrolysis following Marimastat treatment. Marimastat pre-treatment significantly attenuated liver injury following acute CCl4-administration, whereas Mmp9 deficient animals demonstrated no protection. Mice deficient in both TNF-α receptors exhibited an 80% reduction of serum ALT, confirming the hepatoprotective effects of Marimastat via the TNF-signaling pathway.Conclusions/Significance Inhibition of MMP and TACE activity with Marimastat during chronic CCl4administration counterbalanced any beneficial anti-inflammatory effect, resulting in a positive balance of collagen deposition. Since effective inhibition of MMPs accelerates fibrosis progression, MMP inhibitors should be used with caution in patients with chronic liver diseases

Gene expression profiles during hepatic stellate cell activation in culture and in vivo.

BACKGROUND and AIMS: Following hepatic injury, hepatic stellate cells (HSCs) transdifferentiate to become extracellular matrix-producing myofibroblasts and to promote hepatic fibrogenesis. In this study, we determine gene expression changes in 3 different models of HSC activation and investigate whether HSC culture activation reproduces gene expression changes of HSC in vivo activation. METHODS: HSCs were isolated by density centrifugation and magnetic antibody cell sorting from normal mice, CCl(4)-treated mice, and mice that underwent bile duct ligation (BDL). Gene expression was analyzed by microarray and confirmed by polymerase chain reaction and Western blot analysis. RESULTS: Two thousand seventy-three probe sets were differentially expressed in at least 1 of 3 models of HSC activation, including novel genes that encode proinflammatory and antiapoptotic mediators; transcription factors; cell surface receptors; and cytoskeleton components such as CXCL14, survivin, septin 4, osteopontin, PRX1, LMCD1, GPR91, leiomodin, and anillin. BDL- and CCl(4)-activated HSCs showed highly correlated gene expression patterns, whereas culture activation only partially reproduced the gene expression changes observed during BDL- and CCl(4)-induced activation. Coculture with Kupffer cells or lipopolysaccharide treatment during culture activation shifted the expression of most examined genes toward the pattern observed during in vivo activation, suggesting a role for these factors in the microenvironment that drives HSC activation. CONCLUSIONS: The almost identical HSC gene expression patterns after BDL or CCl(4) treatment indicate that HSCs exert similar functions in different types of liver injury. Because culture activation does not