The Mu2e experiment at Fermilab will search for charged lepton flavor violation via the coherent conversion process mu- N --> e- N with a sensitivity approximately four orders of magnitude better ...than the current world's best limits for this process. The experiment's sensitivity offers discovery potential over a wide array of new physics models and probes mass scales well beyond the reach of the LHC. We describe herein the preliminary design of the proposed Mu2e experiment. This document was created in partial fulfillment of the requirements necessary to obtain DOE CD-2 approval.
The Mu2e experiment at Fermilab will search for the neutrinoless μ−→e− conversion in the field of an aluminum nucleus. The Mu2e data-taking plan assumes two running periods, Run I and Run II, ...separated by an approximately two-year-long shutdown. This paper presents an estimate of the expected Mu2e Run I search sensitivity and includes a detailed discussion of the background sources, uncertainties of their prediction, analysis procedures, and the optimization of the experimental sensitivity. The expected Run I 5σ discovery sensitivity is Rμe=1.2×10−15, with a total expected background of 0.11±0.03 events. In the absence of a signal, the expected upper limit is Rμe<6.2×10−16 at 90% CL. This represents a three order of magnitude improvement over the current experimental limit of Rμe<7×10−13 at 90% CL set by the SINDRUM II experiment.
This article presents a measurement of \(\nu_e\) interactions without pions in the final state using the MicroBooNE experiment and an investigation into the excess of low-energy electromagnetic ...events observed by the MiniBooNE collaboration. The measurement is performed in exclusive channels with (1\(e\)N\(p\)0\(\pi\)) and without (1\(e\)0\(p\)0\(\pi\)) visible final-state protons using 6.86\(\times 10^{20}\) protons on target of data collected from the Booster Neutrino Beam at Fermilab. Events are reconstructed with the Pandora pattern recognition toolkit and selected using additional topological information from the MicroBooNE liquid argon time projection chamber. Using a goodness-of-fit test the data are found to be consistent with the predicted number of events with nominal flux and interaction models with a \(p\)-value of 0.098 in the two channels combined. A model based on the low-energy excess observed in MiniBooNE is introduced to quantify the strength of a possible \(\nu_e\) excess. The analysis suggests that if an excess is present, it is not consistent with a simple scaling of the \(\nu_e\) contribution to the flux. Combined, the 1\(e\)N\(p\)0\(\pi\) and 1\(e\)0\(p\)0\(\pi\) channels do not give a conclusive indication about the tested model, but separately they both disfavor the low-energy excess model at \(>\)90% CL. The observation in the most sensitive 1\(e\)N\(p\)0\(\pi\) channel is below the prediction and consistent with no excess. In the less sensitive 1\(e\)0\(p\)0\(\pi\) channel the observation at low energy is above the prediction, while overall there is agreement over the full energy spectrum.
Microparticles (MPs) are membrane vesicles harboring cell surface proteins and containing cytoplasmic components of the original cell. High levels of circulating MPs have been detected in ...pathological states associated with vascular dysfunction. We took advantage of the self-assembly method of tissue engineering to produce in vitro three vascular constructs from human vascular smooth muscle cells and fibroblasts to investigate the role of the adventitia in the modulation of vascular tone by MPs, comparing the contractile response of each of these constructs to histamine. The first two were composed of an adventitia (tissue-engineered vascular adventitia (TEVA)) or a media (tissue-engineered vascular media (TEVM)) solely, and the third one contained a media and an adventitia (tissue-engineered vascular media and adventitia (TEVMA)). In the three constructs, the results show that histamine induces contraction insensitive to blockade of inducible nitric oxide (NO) synthase (iNOS) and cyclooxygenase-2 (COX-2) and not affected by MP treatment. MPs decreased NO production and nuclear factor (NF)-kappaB expression but did not affect superoxide anion (O(2)(-)) release in TEVA. MPs enhanced NF-kappaB expression but did not affect iNOS and COX-2 expression or NO or O(2)(-) release in TEVM. In TEVMA, MPs did not enhance NF-kappaB expression, but COX-2 expression was higher, and O(2)(-) release was lower. Thus, MPs affected NO, O(2)(-), NF-kappaB, and COX-2 in a subtle fashion to maintain the contractile response to histamine. The use of tissue-engineered vascular constructs results in a better understanding of the effect of MPs on human adventitia and media.
Abstract Experimental evidence suggests that reactive free radicals are generated during brain ischemia. We investigated the effect of a novel brain penetrant, low molecular weight, non-peptidyl ...carbon, oxygen- and nitrogen-centered radical scavenger, IAC, on infarct volume and sensory-motor performance in a rat transient middle cerebral artery occlusion model (tMCAO). Rats received 90 min tMCAO and treated with i.p. or i.v. injections of vehicle or IAC following tMCAO. Sensory-motor performance was evaluated by neuroscore tests (NS). Cerebral infarct volume was evaluated at 72 h after tMCAO. Rats treated with IAC i.p. (1 or 6 h after the onset of tMCAO) or i.v. (1 h after the onset of tMCAO) showed significant improvement in NS during the 3 or 21 day follow-up period when compared to vehicle treated rats. Cerebral infarct volumes were significantly decreased compared to vehicle in rats receiving IAC i.p. 1 h or 6 h after occlusion, ∼ 30.5% decrease compared to vehicle, or i.v. 1 h after the onset of tMCAO, 48.6% decrease compared to vehicle. These results demonstrate that IAC has neuroprotective properties with a wide therapeutic window following tMCAO in rats. IAC could therefore be a candidate for the treatment of stroke.
The metabolic syndrome (MetS) is a cluster of interrelated risk factors for cardiovascular disease and atherosclerosis including hyperglycemia, dyslipidemia, hypertension and obesity. We have ...previously shown that circulating levels of microparticles (MPs), small vesicles released from plasma membrane, from MetS patients induce endothelial dysfunction.
Here, we analyze whether MPs from MetS patients may participate to the alteration of smooth muscle cells (SMC) function described during the atherosclerosis development.
Circulating MPs of non-MetS subjects and MetS patients have been isolated from plasma and characterized by proteomic analysis. Then, the involvement of Rap1 in the effects of MPs on human aortic SMC (HASMC) proliferation and migration was analyzed.
Differential proteomic analysis of MPs from both types of individuals identifies Rap1, a small GTPase, as two-fold overexpressed in MPs from MetS compared with non-MetS subjects. In addition, Rap1 is in active state, that is, GTP-associated, in both type of MPs. When HASMC are incubated with MPs for 24h, both types of MPs significantly promote proliferation and migration. Even more, MetS MPs are able to increase the expression of the pro-inflammatory molecules MCP-1 and IL-6. Neutralization of Rap-1 by specific antibody or pharmacological inhibition of Rap-1 with GGTI-298 either partially or completely prevents the effects of MPs from MetS patients but not those from non-MetS MPs. These effects includes HASMC proliferation, migration, inflammation and increase of p38 and ERK5 phosphorylation.
These data suggest that overexpression of Rap1 in MetS MPs might participate in the enhanced SMC proliferation, migration and activation of MAPK/ERK pathway leading to atherosclerosis.
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