Phosphorylation of PDE4A5 by MAPKAPK2 attenuates fibrin degradation via p75 signalling

Phosphodiesterases (PDEs) shape local cAMP gradients to underpin the specificity of receptor function. Key to this process is the highly defined nature of the intra-cellular location of PDEs in the cell. PDE4A5 is a PDE isoform that specifically degrades cAMP and is known to associate with the p75 neurotrophin receptor (p75NTR) where it modulates cAMP signalling cascades that regulate extracellular matrix remodelling in the lungs. Here we map and validate novel protein–protein interaction sites that are important for formation of the PDE4A5–p75NTR complex and show, for the first time, that phosphorylation of PDE4A5 by MAPKAPK2 enhances PDE4A5 interaction with p75NTR and that this, in turn, serves to attenuate fibrin degradation

Molecular Study of Interactions between Hematopoietic Stem Cells and Stromal Cells

Multipotent hematopoietic stem cells (HSCs) are progenitors of all types of hematopoietic cells, and the efficient isolation and propagation of HSCs will significantly enhance our ability to manage many human disorders with bone marrow transplantation, stem cell transplantation and gene therapy. We employed "Signal Sequence Trap (SST)" method with yeast invertase to clone proteins on the surface of or secreted by stromal cells that enhance or inhibit the propagation of HSC’s in culture. AFT024, a mouse fetal liver stromal cell line that maintains stem cell activity in long-term culture, was subjected to SST analysis. We identified more than 60 signal sequences or transmembrane domain containing genes expressed by AFT024 cells. We compared their expression levels between AFT024 cells and BFC012 cells, a mouse fetal liver stromal cell line that was developed in the same way as for AFT024 cells but could not support HSC in long-term culture. Pleiotrophin, T16, Sca-1, deltalike and cytokine receptor like-1(CLF-1) are expressed significantly higher in AFT024 cells than in BFC012 cells. We recently employed Affymatrix genechip technology to study the interaction of HSCs and their microenvironment. In genechip experiments, Sca-1, deltalike, pleiotrophin and CLF-1 are among the most differentially expressed genes between AFT024 and BFC012 cells, while T16 was not represented on the chip. In addition, osteopontin, pigment epithelium-derived factor, proliferins, activin subunit, CXC chemokines GRO1 and LIX are more abundant in AFT024 cells than in BFC012 cells. Genechip technology was also applied to bone marrow stromal cell lines, including MS5, S17 and OP9 cells. Two murine multipotent hematopoietic cell lines, FDCP.mix and EML cells, were also analyzed. Data from these experiments are presented.Singapore-MIT Alliance (SMA

Quantum coherence in a degenerate two-level atomic ensemble: for a transition Fe=0↔Fg=1F_e=0\leftrightarrow F_g=1

For a transition $F_e=0\leftrightarrow F_g=1$ driven by a linearly polarized light and probed by a circularly light, quantum coherence effects are investigated. Due to the coherence between the drive Rabi frequency and Zeeman splitting, electromagnetically induced transparency, electromagnetically induced absorption, and the transition from positive to negative dispersion are obtained, as well as the populations coherently oscillating in a wide spectral region. At the zero pump-probe detuning, the subluminal and superluminal light propagation is predicted. Finally, coherent population trapping states are not highly sensitive to the refraction and absorption in such ensemble.Comment: 9 pages, 6 figure

Sequential design of computer experiments for the estimation of a probability of failure

This paper deals with the problem of estimating the volume of the excursion set of a function $f:\mathbb{R}^d \to \mathbb{R}$ above a given threshold, under a probability measure on $\mathbb{R}^d$ that is assumed to be known. In the industrial world, this corresponds to the problem of estimating a probability of failure of a system. When only an expensive-to-simulate model of the system is available, the budget for simulations is usually severely limited and therefore classical Monte Carlo methods ought to be avoided. One of the main contributions of this article is to derive SUR (stepwise uncertainty reduction) strategies from a Bayesian-theoretic formulation of the problem of estimating a probability of failure. These sequential strategies use a Gaussian process model of $f$ and aim at performing evaluations of $f$ as efficiently as possible to infer the value of the probability of failure. We compare these strategies to other strategies also based on a Gaussian process model for estimating a probability of failure.Comment: This is an author-generated postprint version. The published version is available at http://www.springerlink.co

Measurement of the branching fraction for Υ(1S)→τ+τ−\Upsilon (1S) \to \tau^+ \tau^-

We have studied the leptonic decay of the $\Upsilon (1S)$ resonance into tau pairs using the CLEO II detector. A clean sample of tau pair events is identified via events containing two charged particles where exactly one of the particles is an identified electron. We find $B(\Upsilon(1S) \to \tau^+ \tau^-) = (2.61~\pm~0.12~{+0.09\atop{-0.13}})$. The result is consistent with expectations from lepton universality.Comment: 9 pages, RevTeX, two Postscript figures available upon request, CLNS 94/1297, CLEO 94-20 (submitted to Physics Letters B

Study of the B^0 Semileptonic Decay Spectrum at the Upsilon(4S) Resonance

We have made a first measurement of the lepton momentum spectrum in a sample of events enriched in neutral B's through a partial reconstruction of B0 --> D*- l+ nu. This spectrum, measured with 2.38 fb**-1 of data collected at the Upsilon(4S) resonance by the CLEO II detector, is compared directly to the inclusive lepton spectrum from all Upsilon(4S) events in the same data set. These two spectra are consistent with having the same shape above 1.5 GeV/c. From the two spectra and two other CLEO measurements, we obtain the B0 and B+ semileptonic branching fractions, b0 and b+, their ratio, and the production ratio f+-/f00 of B+ and B0 pairs at the Upsilon(4S). We report b+/b0=0.950 (+0.117-0.080) +- 0.091, b0 = (10.78 +- 0.60 +- 0.69)%, and b+ = (10.25 +- 0.57 +- 0.65)%. b+/b0 is equivalent to the ratio of charged to neutral B lifetimes, tau+/tau0.Comment: 14 page, postscript file also available at http://w4.lns.cornell.edu/public/CLN

Measurement of the Decay Asymmetry Parameters in Λc+→Λπ+\Lambda_c^+ \to \Lambda\pi^+ and Λc+→Σ+π0\Lambda_c^+ \to \Sigma^+\pi^0

We have measured the weak decay asymmetry parameters (\aLC ) for two \LC\ decay modes. Our measurements are \aLC = -0.94^{+0.21+0.12}_{-0.06-0.06} for the decay mode $\Lambda_c^+ \to \Lambda\pi^+$ and \aLC = -0.45\pm 0.31 \pm 0.06 for the decay mode $\Lambda_c \to \Sigma^+\pi^0$. By combining these measurements with the previously measured decay rates, we have extracted the parity-violating and parity-conserving amplitudes. These amplitudes are used to test models of nonleptonic charmed baryon decay.Comment: 11 pages including the figures. Uses REVTEX and psfig macros. Figures as uuencoded postscript. Also available as http://w4.lns.cornell.edu/public/CLNS/1995/CLNS95-1319.p

Observation of the Ξc+\Xi_c^+ Charmed Baryon Decays to Σ+K−π+\Sigma^+ K^-\pi^+, Σ+Kˉ∗0\Sigma^+ \bar{K}^{*0}, and ΛK−π+π+\Lambda K^-\pi^+\pi^+

We have observed two new decay modes of the charmed baryon $\Xi_c^+$ into $\Sigma^+ K^-\pi^+$ and $\Sigma^+ \bar{K}^{*0}$ using data collected with the CLEO II detector. We also present the first measurement of the branching fraction for the previously observed decay mode $\Xi_c^+\to\Lambda K^-\pi^+\pi^+$. The branching fractions for these three modes relative to $\Xi_c^+\to\Xi^-\pi^+\pi^+$ are measured to be $1.18 \pm 0.26 \pm 0.17$, $0.92 \pm 0.27 \pm 0.14$, and $0.58 \pm 0.16 \pm 0.07$, respectively.Comment: 12 page uuencoded postscript file, postscript file also available through http://w4.lns.cornell.edu/public/CLN

Wnt signalling and cancer stem cells

[Abstract] Intracellular signalling mediated by secreted Wnt proteins is essential for the establishment of cell fates and proper tissue patterning during embryo development and for the regulation of tissue homeostasis and stem cell function in adult tissues. Aberrant activation of Wnt signalling pathways has been directly linked to the genesis of different tumours. Here, the components and molecular mechanisms implicated in the transduction of Wnt signal, along with important results supporting a central role for this signalling pathway in stem cell function regulation and carcinogenesis will be briefly reviewed.Ministerio de Ciencia e Innovación; SAF2008-0060

Studies of the Cabbibo-Suppressed Decays D+→π0ℓ+νD^+ \to \pi^0 \ell^+ \nu and D+→ηe+νeD^+ \to \eta e^+ \nu_e

Using 4.8 fb$^{-1}$ of data taken with the CLEO II detector, the branching fraction for the Cabibbo-suppressed decay $D^+\to\pi^0\ell^+\nu$ measured relative to the Cabibbo favored decay $D^+\to\bar{K^0}\ell^+\nu$ is found to be $0.046\pm 0.014\pm 0.017$. Using $V_{cs}$ and $V_{cd}$ from unitarity constraints, we determine $| f_+^{\pi}(0)/f_+^K(0)|^2=0.9\pm 0.3\pm 0.3$ We also present a 90% confidence level upper limit for the branching ratio of the decay $D^+ \to \eta e^+\nu_e$ relative to that for $D^+ \to \pi^0 e^+\nu_e$ of 1.5.Comment: 10 page postscript file, postscript file also available through http://w4.lns.cornell.edu/public/CLN