Crosstalk between G-protein and Ca2+ pathways switches intracellular cAMP levels

Cyclic adenosine monophosphate and cyclic guanosine monophosphate are universal intracellular messengers whose concentrations are regulated by molecular networks comprised of different isoforms of the synthases adenylate cyclase or guanylate cyclase and the phosphodiesterases which degrade these compounds. In this paper, we employ a systems biology approach to develop mathematical models of these networks that, for the first time, take into account the different biochemical properties of the isoforms involved. To investigate the mechanisms underlying the joint regulation of cAMP and cGMP, we apply our models to analyse the regulation of cilia beat frequency in Paramecium by Ca(2+). Based on our analysis of these models, we propose that the diversity of isoform combinations that occurs in living cells provides an explanation for the huge variety of intracellular processes that are dependent on these networks. The inclusion of both G-protein receptor and Ca(2+)-dependent regulation of AC in our models allows us to propose a new explanation for the switching properties of G-protein subunits involved in nucleotide regulation. Analysis of the models suggests that, depending on whether the G-protein subunit is bound to AC, Ca(2+) can either activate or inhibit AC in a concentration-dependent manner. The resulting analysis provides an explanation for previous experimental results that showed that alterations in Ca(2+) concentrations can either increase or decrease cilia beat frequency over particular Ca(2+) concentration ranges

F-theory and Neutrinos: Kaluza-Klein Dilution of Flavor Hierarchy

We study minimal implementations of Majorana and Dirac neutrino scenarios in F-theory GUT models. In both cases the mass scale of the neutrinos m_nu ~ (M_weak)^2/M_UV arises from integrating out Kaluza-Klein modes, where M_UV is close to the GUT scale. The participation of non-holomorphic Kaluza-Klein mode wave functions dilutes the mass hierarchy in comparison to the quark and charged lepton sectors, in agreement with experimentally measured mass splittings. The neutrinos are predicted to exhibit a "normal" mass hierarchy, with masses m_3,m_2,m_1 ~ .05*(1,(alpha_GUT)^(1/2),alpha_GUT) eV. When the interactions of the neutrino and charged lepton sectors geometrically unify, the neutrino mixing matrix exhibits a mild hierarchical structure such that the mixing angles theta_23 and theta_12 are large and comparable, while theta_13 is expected to be smaller and close to the Cabibbo angle: theta_13 ~ theta_C ~ (alpha_GUT)^(1/2) ~ 0.2. This suggests that theta_13 should be near the current experimental upper bound.Comment: v2: 83 pages, 10 figures, references adde

Results of the MAJORANA DEMONSTRATOR's Search for Double-Beta Decay of 76Ge to Excited States of 76Se

The MAJORANA DEMONSTRATOR is searching for double-beta decay of 76Ge to excited states (E.S.) in 76Se using a modular array of high purity Germanium detectors. 76Ge can decay into three E.S.s of 76Se. The E.S. decays have a clear event signature consisting of a ββ-decay with the prompt emission of one or two γ-rays, resulting in with high probability in a multi-site event. The granularity of the DEMONSTRATOR detector array enables powerful discrimination of this event signature from backgrounds. Using 21.3 kg-y of isotopic exposure, the DEMONSTRATOR has set world leading limits for each E.S. decay, with 90% CL lower half-life limits in the range of (0.56 2.1) ⋅ 1024 y. In particular, for the 2v transition to the first 0+ E.S. of 76Se, a lower half-life limit of 0.68 ⋅ 1024 at 90% CL was achieved

ADC Nonlinearity Correction for the Majorana Demonstrator

Imperfections in analog-to-digital conversion (ADC) cannot be ignored when signal digitization requirements demand both wide dynamic range and high resolution, as is the case for the Majorana Demonstrator 76Ge neutrinoless double-beta decay search. Enabling the experiment's high-resolution spectral analysis and efficient pulse shape discrimination required careful measurement and correction of ADC nonlinearities. A simple measurement protocol was developed that did not require sophisticated equipment or lengthy data-taking campaigns. A slope-dependent hysteresis was observed and characterized. A correction applied to digitized waveforms prior to signal processing reduced the differential and integral nonlinearities by an order of magnitude, eliminating these as dominant contributions to the systematic energy uncertainty at the double-beta decay Q value

Neutrino masses from new generations

We reconsider the possibility that Majorana masses for the three known neutrinos are generated radiatively by the presence of a fourth generation and one right-handed neutrino with Yukawa couplings and a Majorana mass term. We find that the observed light neutrino mass hierarchy is not compatible with low energy universality bounds in this minimal scenario, but all present data can be accommodated with five generations and two right-handed neutrinos. Within this framework, we explore the parameter space regions which are currently allowed and could lead to observable effects in neutrinoless double beta decay, $\mu - e$ conversion in nuclei and $\mu \rightarrow e \gamma$ experiments. We also discuss the detection prospects at LHC.Comment: 28 pages, 4 figures. Version to be published. Some typos corrected. Improved figures 3 and

Neutrinoless double beta decay in seesaw models

We study the general phenomenology of neutrinoless double beta decay in seesaw models. In particular, we focus on the dependence of the neutrinoless double beta decay rate on the mass of the extra states introduced to account for the Majorana masses of light neutrinos. For this purpose, we compute the nuclear matrix elements as functions of the mass of the mediating fermions and estimate the associated uncertainties. We then discuss what can be inferred on the seesaw model parameters in the different mass regimes and clarify how the contribution of the light neutrinos should always be taken into account when deriving bounds on the extra parameters. Conversely, the extra states can also have a significant impact, cancelling the Standard Model neutrino contribution for masses lighter than the nuclear scale and leading to vanishing neutrinoless double beta decay amplitudes even if neutrinos are Majorana particles. We also discuss how seesaw models could reconcile large rates of neutrinoless double beta decay with more stringent cosmological bounds on neutrino masses.Comment: 34 pages, 5 eps figures and 1 axodraw figure. Final version published in JHEP. NME results available in Appendi

Expression of Interest for a Novel Search for CP Violation in the Neutrino Sector: DAEdALUS

Submitted to the DUSEL DirectorateSubmitted to the DUSEL DirectorateDAEdALUS, a Decay-At-rest Experiment for delta_CP studies At the Laboratory for Underground Science, provides a new approach to the search for CP violation in the neutrino sector. The design utilizes low-cost, high-power proton accelerators under development for commercial uses. These provide neutrino beams with energy up to 52 MeV from pion and muon decay-at-rest. The experiment searches for aninu_mu to antinu_e at short baselines corresponding to the atmospheric Delta m^2 region. The antinu_e will be detected, via inverse beta decay, in the 300 kton fiducial-volume Gd-doped water Cherenkov neutrino detector proposed for the Deep Underground Science and Engineering Laboratory (DUSEL). DAEdALUS opens new opportunities for DUSEL. It provides a high-statistics, low-background alternative for CP violation searches which matches the capability of the conventional long-baseline neutrino experiment, LBNE. Because of the complementary designs, when DAEdALUS antineutrino data are combined with LBNE neutrino data, the sensitivity of the CP-violation search improves beyond any present proposals, including the proposal for Project X. Also, the availability of an on-site neutrino beam opens opportunities for additional physics, both for the presently planned DUSEL detectors and for new experiments at a future 300 ft campus

ν\nu-Two Higgs Doublet Model and its Collider Phenomenology

Smallness of neutrino masses can be explained by introducing a tiny vacuum expectation value of an extra-Higgs doublet which couples to right-handed neutrinos ($N_R$). This situation is naturally realized in $\nu$-Two Higgs Doublet Model ($\nu$THDM), where a TeV-scale seesaw mechanism can work well. We investigate observable phenomenology of $\nu$THDM at LHC and ILC experiments. Charged Higgs boson ($H^\pm$) in $\nu$THDM is almost originated from the extra-Higgs doublet and its coupling strength to neutrinos are not small. Then this model induces rich phenomenology at the LHC, for example, when $m_{H^\pm}^{} < M_N$, observable charged tracks can be induced from long lived charged Higgs. On the other hand, when $m_{H^\pm}^{} > M_N$, right-handed neutrinos can be long-lived, and secondary vertices may be tagged at the LHC. The $\nu$THDM also predicts observable lepton number violating process at the ILC.Comment: 17 pages, 27 eps file

New CUORICINO Results On the Way to CUORE

CUORE is a 0.75 ton experiment to search for neutrinoless double beta decay of Te130 using 988 TeO2 bolometers. It aims at reaching a sensitivity on the effective neutrino mass of the order of few tens of meV. CUORICINO, a single CUORE tower running since 2003, plays an important role as a stand alone experiment and for developing the future CUORE setup. Present results already achieved and studies that are underway are here presented and discussed