Use of a cAMP BRET Sensor to Characterize a Novel Regulation of cAMP by the Sphingosine 1-Phosphate/G13 Pathway

Regulation of intracellular cyclic adenosine 3',5'-monophosphate (cAMP) is integral in mediating cell growth, cell differentiation, and immune responses in hematopoietic cells. To facilitate studies of cAMP regulation we developed a BRET (bioluminescence resonance energy transfer) sensor for cAMP, CAMYEL (cAMP sensor using YFP-Epac-RLuc), which can quantitatively and rapidly monitor intracellular concentrations of cAMP in vivo. This sensor was used to characterize three distinct pathways for modulation of cAMP synthesis stimulated by presumed Gs-dependent receptors for isoproterenol and prostaglandin E2. Whereas two ligands, uridine 5'-diphosphate and complement C5a, appear to use known mechanisms for augmentation of cAMP via Gq/calcium and Gi, the action of sphingosine 1-phosphate (S1P) is novel. In these cells, S1P, a biologically active lysophospholipid, greatly enhances increases in intracellular cAMP triggered by the ligands for Gs-coupled receptors while having only a minimal effect by itself. The enhancement of cAMP by S1P is resistant to pertussis toxin and independent of intracellular calcium. Studies with RNAi and chemical perturbations demonstrate that the effect of S1P is mediated by the S1P2 receptor and the heterotrimeric G13 protein. Thus in these macrophage cells, all four major classes of G proteins can regulate intracellular cAMP

Time-Shift in the OPERA set-up: proof against superluminal neutrinos without the need of knowing the CERN-LNGS distance and Reminiscences on the origin of the Gran Sasso Lab, of the 3rd neutrino and of the "Teramo Anomaly"

The LVD time stability allows to establish a time-shift in the OPERA experiment, thus providing the first proof against Superluminal neutrinos, using the horizontal muons of the "Teramo Anomaly". This proof is particularly interesting since does not need the knowledge of the distance between the place where the neutrinos are produced (CERN) and the place where they are detected (LNGS). Since the Superluminal neutrinos generated in the physics community a vivid interest in good and bad behaviour in physics research, the author thought it was appropriate to recall the origin of the Gran Sasso Lab, of the 3rd neutrino, of the horizontal muons due to the "Teramo Anomaly" and of the oscillation between leptonic flavours, when the CERN-Gran Sasso neutrino beam was included in the project for the most powerful underground Laboratory in the world.Comment: 35 pages, 25 Figures, Invited paper at the Gran Sasso mini-Workshop on LNGS results on the neutrino velocity topic, Gran Sasso, Italy, 28 March 201

Lepton flavor conserving Z -> l^+ l^-$ decays in the general two Higgs doublet model

We calculate the new physics effects to the branching ratios of the lepton flavor conserving decays Z -> l^+ l^- in the framework of the general two Higgs Doublet model. We predict the upper limits for the couplings |\bar{\xi}^{D}_{N,\mu\tau}| and |\bar{\xi}^{D}_{N,\tau\tau}| as 3\times 10^2 GeV and 1\times 10^2 GeV, respectively.Comment: 9 pages, 3 figure

Method for Flavor Tagging in Neutral B Meson Decays

A method is proposed for tagging the flavor of neutral $B$ mesons in the study of CP-violating decay asymmetries. The method makes use of a possible difference in interactions in $B \pi$ or $B^* \pi$ systems with isospins 1/2 and 3/2, and would be particularly clean if the $I = 1/2$ systems can be detected as ``$B^{**}$'' resonances.Comment: Submitted to Phys. Rev. D. 11 pages, LaTeX, Technion-PH-92-40 / PITHA 92/39 / EFI 92-5

Predicting the birth of a spoken word

Children learn words through an accumulation of interactions grounded in context. Although many factors in the learning environment have been shown to contribute to word learning in individual studies, no empirical synthesis connects across factors. We introduce a new ultradense corpus of audio and video recordings of a single child’s life that allows us to measure the child’s experience of each word in his vocabulary. This corpus provides the first direct comparison, to our knowledge, between different predictors of the child’s production of individual words. We develop a series of new measures of the distinctiveness of the spatial, temporal, and linguistic contexts in which a word appears, and show that these measures are stronger predictors of learning than frequency of use and that, unlike frequency, they play a consistent role across different syntactic categories. Our findings provide a concrete instantiation of classic ideas about the role of coherent activities in word learning and demonstrate the value of multimodal data in understanding children’s language acquisition

Leptoquark production in ultrahigh-energy neutrino interactions revisited

The prospects for producing leptoquarks (LQs) in ultrahigh-energy (UHE) neutrino nucleon collisions are re-examined in the light of recent interpretations of HERA data in terms of leptoquark production. We update predictions for cross-sections for the production of first- and second-generation leptoquarks in UHE nu-N and nubar-N collisions including (i) recent experimental limits on masses and couplings from the LEP and TEVATRON colliders as well as rare processes, (ii) modern parton distributions, and (iii) radiative corrections to single leptoquark production. If the HERA events are due to an SU(2) doublet leptoquark which couples mainly to (e+,q) states, we argue that there are likely other LQ states which couple to neutrinos which are close in mass, due to constraints from precision electroweak measurements.Comment: 12 pages, LaTeX, 3 separate postscript figures. Added 1 reference plus discussion, updated another referenc

A Comprehensive Study of Leptoquark Bounds

We make a comprehensive study of indirect bounds on scalar leptoquarks that couple chirally and diagonally to the first generation by examining available data from low energy experiments as well as from high energy e+ e- and p pbar accelerators. The strongest bounds turn out to arise from low energy data: For leptoquarks that couple to right--handed quarks, the most stringent bound comes from atomic parity violation. For leptoquarks that couple to left--handed quarks, there are two mass regions: At low masses the bounds arise from atomic parity violation or from universality in leptonic pi decays. At masses above a few hundred GeV's, the dominant bounds come from the FCNC processes that are unavoidable in these leptoquarks: The FCNC bound of the up sector, that arises from D-Dbar mixing, combines with the FCNC bounds from the down sector, that arise from rare K decays and K-Kbar mixing, to a bound on the flavour CONSERVING coupling to the first generation. The bounds restrict leptoquarks that couple with electromagnetic strength to lie above 600 GeV or 630 GeV for leptoquarks that couple to RH quarks, and above 1040 GeV, 440 GeV, and 750 GeV for the SU(2)_W scalar, doublet and triplet leptoquarks that couple to LH quarks. These bounds are considerably stronger than the first results from the direct searches at HERA. Our bounds also already exclude large regions in the parameter space that could be examined by various methods proposed for indirect leptoquark searches.Comment: 23 Pages (LaTeX), including 3 uufiled postscript figures. WIS--93/90/Sept--PH. To appear in PRD. Changes: updated numbers ---> stronger bound

Transverse Tau Polarization in Decays of the Top and Bottom Quarks in the Weinberg Model of CP Non-conservation

We show that the transverse polarization asymmetry of the $\tau$-lepton in the decay $t\rightarrow b \tau \nu$ is extremely sensitive to CP violating phases arising from the charged Higgs exchange in the Weinberg model of CP non-conservation. Qualitatively, the polarization asymmetries are enhanced over rate or energy asymmetries by a factor of $\approx {m_t\over m_\tau}\approx O(100)$. Thus for optimal values of the parameters the method requires $\approx 10^4$ top pairs to be observable rather than $10^7$ needed for rate or energy asymmetries. We also examine $\tau$ polarization in b decays via $b \rightarrow c \nu \tau$ and find that it can also be very effective in constraining the CP violation parameters of the extended Higgs sector.Comment: 11,1 figure, SLAC-PUB-608

Probing impulsive strain propagation with x-ray pulses

Pump-probe time-resolved x-ray diffraction of allowed and nearly forbidden reflections in InSb is used to follow the propagation of a coherent acoustic pulse generated by ultrafast laser-excitation. The surface and bulk components of the strain could be simultaneously measured due to the large x-ray penetration depth. Comparison of the experimental data with dynamical diffraction simulations suggests that the conventional model for impulsively generated strain underestimates the partitioning of energy into coherent modes.Comment: 4 pages, 2 figures, LaTeX, eps. Accepted for publication in Phys. Rev. Lett. http://prl.aps.or