We present an analysis of atmospheric neutrino data from a 33.0 kton yr (535-day) exposure of the Super-Kamiokande detector. The data exhibit a zenith angle dependent deficit of muon neutrinos which is inconsistent with expectations based on calculations of the atmospheric neutrino flux. Experimental biases and uncertainties in the prediction of neutrino fluxes and cross sections are unable to explain our observation. The data are consistent, however, with two-flavor n m $ n t oscillations with sin 2 2u . Atmospheric neutrinos are produced as decay products in hadronic showers resulting from collisions of cosmic rays with nuclei in the upper atmosphere. Production of electron and muon neutrinos is dominated by the processes p 1 ! m 1 1 n m followed by m 1 ! e 1 1 n m 1 n e (and their charge conjugates) giving an expected ratio 1562 0031-9007͞98͞81(8)͞1562(6)$15.00

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White adipocytes are unique in that they contain large unilocular lipid droplets that occupy most of the cytoplasm. To identify genes involved in the maintenance of mature adipocytes, we expressed dominant-negative PPARγ in 3T3-L1 cells and performed a microarray screen. The fat-specific protein of 27 kDa (FSP27) was strongly downregulated in this context. FSP27 expression correlated with induction of differentiation in cultured preadipocytes, and the protein localized to lipid droplets in murine white adipocytes in vivo. Ablation of FSP27 in mice resulted in the formation of multilocular lipid droplets in these cells. Furthermore, FSP27-deficient mice were protected from diet-induced obesity and insulin resistance and displayed an increased metabolic rate due to increased mitochondrial biogenesis in white adipose tissue (WAT). Depletion of FSP27 by siRNA in murine cultured white adipocytes resulted in the formation of numerous small lipid droplets, increased lipolysis, and decreased triacylglycerol storage, while expression of FSP27 in COS cells promoted the formation of large lipid droplets. Our results suggest that FSP27 contributes to efficient energy storage in WAT by promoting the formation of unilocular lipid droplets, thereby restricting lipolysis. In addition, we found that the nature of lipid accumulation in WAT appears to be associated with maintenance of energy balance and insulin sensitivity.

A total of 614 upward through-going muons of minimum energy 1.6 GeV are observed by Super-Kamiokande during 537 detector live days. The measured muon flux is (1.74 ± 0.07(stat.) ± 0.02(sys.)) × 10 −13 cm −2 s −1 sr −1 compared to an expected flux of (1.97 ± 0.44(theo.)) × 10 −13 cm −2 s −1 sr −1 . The absolute measured flux is in agreement with the prediction within the errors. However, the zenith angle dependence of the observed upward through-going muon flux does not agree with no-oscillation predictions. The observed distortion in shape is consistent with the νµ ↔ ντ oscillation hypothesis with sin 2 2θ > 0.4 and 1 × 10 −3 < ∆m 2 < 1 × 10 −1 eV 2 at 90 % confidence level.

cAMP can be either mitogenic or anti-mitogenic, depending on the cell type. We demonstrated previously that cAMP inhibited the proliferation of normal renal epithelial cells and stimulated the proliferation of cells derived from the cysts of polycystic kidney disease (PKD) patients. The protein products of the genes causing PKD, polycystin-1 and polycystin-2, are thought to regulate intracellular calcium levels, suggesting that abnormal polycystin function may affect calcium signaling and thus cause a switch to the cAMP growth-stimulated phenotype. To test this hypothesis, we disrupted intracellular calcium mobilization by treating immortalized mouse M-1 collecting duct cells and primary cultures of human kidney epithelial cells with calcium channel blockers and by lowering extracellular calcium with EGTA. Calcium restriction for 3-5 h converted both cell types from a normal cAMP growth-inhibited phenotype to an abnormal cAMP growth-stimulated phenotype, characteristic of PKD. In M-1 cells, we showed that calcium restriction was associated with an elevation in B-Raf protein levels and cAMP-stimulated, Ras-dependent activation of B-Raf and ERK. Moreover, the activity of Akt, a negative regulator of B-Raf, was decreased by calcium restriction. Inhibition of Akt or phosphatidylinositol 3-kinase also allowed cAMP-dependent activation of B-Raf and ERK in normal calcium. These results suggest that calcium restriction causes an inhibition of the phosphatidylinositol 3-kinase/Akt pathway, which relieves the inhibition of B-Raf to allow the cAMP growth-stimulated phenotypic switch. Finally, M-1 cells stably overexpressing an inducible polycystin-1 C-terminal cytosolic tail construct were shown to exhibit a cAMP growth-stimulated phenotype involving B-Raf and ERK activation, which was reversed by the calcium ionophore A23187. We conclude that disruption of calcium mobilization in cells that are normally growthinhibited by cAMP can derepress the B-Raf/ERK pathway, thus converting these cells to a phenotype that is growth-stimulated by cAMP.