Borexino, a large volume detector for low energy neutrino spectroscopy, is currently running underground at the Laboratori Nazionali del Gran Sasso, Italy. The main goal of the experiment is the real-time measurement of sub MeV solar neutrinos, and particularly of the mono energetic (862 keV) Be7 electron capture neutrinos, via neutrino-electron scattering in an ultra-pure liquid scintillator. This paper is mostly devoted to the description of the detector structure, the photomultipliers, the electronics, and the trigger and calibration systems. The real performance of the detector, which always meets, and sometimes exceeds, design expectations, is also shown. Some important aspects of the Borexino project, i.e. the fluid handling plants, the purification techniques and the filling procedures, are not covered in this paper and are, or will be, published elsewhere (see Introduction and Bibliography)

Geo-neutrinos, electron anti-neutrinos produced in beta decays of naturally occurring radioactive isotopes in the Earth, are a unique direct probe of our planet's interior. We report the first observation at more than 3$\sigma$ C.L. of geo-neutrinos, performed with the Borexino detector at Laboratori Nazionali del Gran Sasso. Anti-neutrinos are detected through the neutron inverse beta decay reaction. With a 252.6 ton-yr fiducial exposure after all selection cuts, we detected 9.9^{+4.1}_{-3.4}(^{+14.6}_{-8.2}) geo-neutrino events, with errors corresponding to a 68.3%(99.73%) C.L. From the $\ln{\cal{L}}$ profile, the statistical significance of the Borexino geo-neutrino observation corresponds to a 99.997% C.L. Our measurement of the geo-neutrinos rate is 3.9^{+1.6}_{-1.3}(^{+5.8}_{-3.2}) events/(100ton-yr). This measurement rejects the hypothesis of an active geo-reactor in the Earth's core with a power above 3 TW at 95% C.L. The observed prompt positron spectrum above 2.6 MeV is compatible with that expected from european nuclear reactors (mean base line of approximately 1000 km). Our measurement of reactor anti-neutrinos excludes the non-oscillation hypothesis at 99.60% C.L

We report the direct measurement of the 7 Be solar neutrino signal rate performed with the Borexino detector at the Laboratori Nazionali del Gran Sasso. The interaction rate of the 0.862 MeV 7 Be neutrinos is 49±3stat±4syst counts/(day·100 ton). The hypothesis of no oscillation for 7 Be solar neutrinos is inconsistent with our measurement at the 4σ C.L.. Our result is the first direct measurement of the survival probability for solar νe in the transition region between matter-enhanced and vacuum-driven oscillations. The measurement improves the experimental determination of the flux of 7 Be, pp, and CNO solar νe, and the limit on the magnetic moment of neutrinos.PACS numbers: 13.35. Hb, 14.60.St, 26.65.+t, 95.55.Vj, 29.40.Mc Neutrino oscillations [1] are the established mechanism to explain the solar neutrino problem, which originated from observations in radiochemical experiments with a sub-MeV threshold [2,3] and from real time observation of high energy neutrinos [4,5]. Neutrino oscillations were also observed in atmospheric neutrinos [4] and have been confirmed with observation of reactorν e [6]. Borexino is the first experiment to report a real-time observation arXiv:0805.3843v2 [astro-ph]

We report the measurement of ν-e elastic scattering from 8 B solar neutrinos with 3 MeV energy threshold by the Borexino detector in Gran Sasso (Italy). The rate of solar neutrino-induced electron scattering events above this energy in Borexino is 0.217 ± 0.038(stat) ± 0.008(syst) cpd/100 t, which corresponds to Φ ES 8 B = 2.4 ± 0.4± 0.1×10 6 cm −2 s −1 , in good agreement with measurements from SNO and SuperKamiokaNDE. Assuming the 8 B neutrino flux predicted by the high metallicity Standard Solar Model, the average 8 B νe survival probability above 3 MeV is measured to be 0.29±0.10. The survival probabilities for 7 Be and 8 B neutrinos as measured by Borexino differ by 1.9 σ. These results are consistent with the prediction of the MSW-LMA solution of a transition in the solar νe survival probability Pee between the low energy vacuum-driven and the high-energy matter-enhanced solar neutrino oscillation regimes.PACS numbers: 14.60. St, 26.65.+t, 95.55.Vj, 29.40.Mc INTRODUCTION Solar8 B-neutrino spectroscopy has been so far performed by the waterČerenkov detectors KamiokaNDE, SuperKamiokaNDE,. The first two experiments used elastic ν-e scattering for the detection of neutrinos, whereas SNO also exploited nuclear reaction channels on deuterium with heavy water as target. These experiments provided robust spectral measurements with ∼5 MeV threshold or higher for scattered electrons; a recent SNO analysis reached a 3.5 MeV threshold [5].We report the first observation of solar 8 B-neutrinos with a liquid scintillator detector, performed by the Borexino experiment [6,7] via elastic ν-e scattering. Borexino is the first experiment to succeed in suppressing all major backgrounds, above the 2.614 MeV γ from the decay of 208 Tl, to a rate below that of electron scatterings from solar neutrinos. This allows to reduce the energy threshold for scattered electrons by 8 B solar neutrinos to 3 MeV, the lowest ever reported for the electron scattering channel. To facilitate a comparison to the results of SuperKamiokaNDE [3] and SNO D 2 O phase [4], we also report the measured 8 B neutrino interaction rate with 5 MeV threshold.Since Borexino also detected low energy solar 7 Be neutri-2 nos [8,9], this is the first experiment where both branches of the solar pp-cycle have been measured simultaneously in the same target. The large mixing angle solution (LMA) of the MSW effect [10] predicts a transition in the ν e survival probability from the vacuum oscillation regime at low energies to the matter dominated regime at high energies. Results on solar 7 Be and 8 B neutrinos from Borexino, combined with prediction on the absolute neutrino fluxes from the Standard Solar Model [11][12][13], confirm that our data are in agreement with the MSW-LMA prediction within 1σ. EXPERIMENTAL APPARATUS AND ENERGY THRESHOLDThe Borexino detector is located at the underground Laboratori Nazionali del Gran Sasso (LNGS) in central Italy, at a depth of 3600 m.w.e.. Solar neutrinos are detected in Borexino exclusively via elastic ν-e scattering in a li...

There is an exponentially growing interest in targeting immune checkpoint molecules in breast cancer (BC), particularly in the triple-negative subtype where unmet treatment needs remain. This study was designed to analyze the expression, localization, and prognostic role of PD-1, PD-L1, PD-L2, CTLA-4, LAG3, and TIM3 in primary BC. Gene expression analysis using the METABRIC microarray dataset found that all six immune checkpoint molecules are highly expressed in basal-like and HER2-enriched compared to the other BC molecular subtypes. Flow cytometric analysis of fresh tissue homogenates from untreated primary tumors show that PD-1 is principally expressed on CD4+ or CD8+ T cells and CTLA-4 is expressed on CD4+ T cells. The global proportion of PD-L1+, PD-L2+, LAG3+, and TIM3+ tumor-infiltrating lymphocytes (TIL) was low and detectable in only a small number of tumors. Immunohistochemically staining fixed tissues from the same tumors was employed to score TIL and tertiary lymphoid structures (TLS). PD-L1+, PD-L2+, LAG3+, and TIM3+ cells were detected in some TLS in a pattern that resembles secondary lymphoid organs. This observation suggests that TLS are important sites of immune activation and regulation, particularly in tumors with extensive baseline immune infiltration. Significantly improved overall survival was correlated with PD-1 expression in the HER2-enriched and PD-L1 or CTLA-4 expression in basal-like BC. PD-1 and CTLA-4 proteins were most frequently detected on TIL, which supports the correlations observed between their gene expression and improved long-term outcome in basal-like and HER2-enriched BC. PD-L1 expression by tumor or immune cells is uncommon in BC. Overall, the data presented here distinguish PD-1 as a marker of T cell activity in both the T and B cell areas of BC associated TLS. We found that immune checkpoint molecule expression parallels the extent of TIL and TLS, although there is a noteworthy amount of heterogeneity between tumors even within the same molecular subtype. These data indicate that assessing the levels of immune checkpoint molecule expression in an individual patient has important implications for the success of therapeutically targeting them in BC.