Activated fibronectin-secretory phenotype of mesenchymal stromal cells in pre-fibrotic myeloproliferative neoplasms

We characterized bone marrow stromal cells (BMSC) from patients with pre-fibrotic myeloproliferative neoplasms (MPN). MPN-BMSC showed decreased capacity to stimulate the proliferation of colony-forming units of normal hematopoietic stem and progenitor cells and displayed increased matrix remodelling (in particular fibronectin deposition) compared to control BMSC. This finding was confirmed in pre-fibrotic MPN bone marrow biopsies in a tissue microarray (n = 34), which stained positive for fibronectin in the absence of reticulin as a standard myelofibrosis marker. Fibronectin expression correlated significantly with reduced haemoglobin levels in MPN-patients (p = 0.007; R2 = 0.42). Our data show significant cell-intrinsic alterations in MPN-MSC and suggest that Fibronectin expression might be applicable as a biomarker for the identification of early myelofibrotic transformation in reticulin-negative MPN

Receptor Tyrosine Kinase (RTK) Mediated Tyrosine Phosphor-Proteome from Drosophila S2 (ErbB1) Cells Reveals Novel Signaling Networks

Protein phosphorylation mediates many critical cellular responses and is essential for many biological functions during development. About one-third of cellular proteins are phosphorylated, representing the phosphor-proteome, and phosphorylation can alter a protein's function, activity, localization and stability. Tyrosine phosphorylation events mediated by aberrant activation of Receptor Tyrosine Kinase (RTK) pathways have been proven to be involved in the development of several diseases including cancer. To understand the systems biology of RTK activation, we have developed a phosphor-proteome focused on tyrosine phosphorylation events under insulin and EGF signaling pathways using the PhosphoScan® technique coupled with high-throughput mass spectrometry analysis. Comparative proteomic analyses of all these tyrosine phosphorylation events revealed that around 70% of these pY events are conserved in human orthologs and paralogs. A careful analysis of published in vivo tyrosine phosphorylation events from literature and patents revealed that around 38% of pY events from Drosophila proteins conserved on 185 human proteins are confirmed in vivo tyrosine phosphorylation events. Hence the data are validated partially based on available reports, and the credibility of the remaining 62% of novel conserved sites that are unpublished so far is very high but requires further follow-up studies. The novel pY events found in this study that are conserved on human proteins could potentially lead to the discovery of drug targets and biomarkers for the detection of various cancers and neurodegenerative diseases

A Generalized Linear Model for Estimating Spectrotemporal Receptive Fields from Responses to Natural Sounds

In the auditory system, the stimulus-response properties of single neurons are often described in terms of the spectrotemporal receptive field (STRF), a linear kernel relating the spectrogram of the sound stimulus to the instantaneous firing rate of the neuron. Several algorithms have been used to estimate STRFs from responses to natural stimuli; these algorithms differ in their functional models, cost functions, and regularization methods. Here, we characterize the stimulus-response function of auditory neurons using a generalized linear model (GLM). In this model, each cell's input is described by: 1) a stimulus filter (STRF); and 2) a post-spike filter, which captures dependencies on the neuron's spiking history. The output of the model is given by a series of spike trains rather than instantaneous firing rate, allowing the prediction of spike train responses to novel stimuli. We fit the model by maximum penalized likelihood to the spiking activity of zebra finch auditory midbrain neurons in response to conspecific vocalizations (songs) and modulation limited (ml) noise. We compare this model to normalized reverse correlation (NRC), the traditional method for STRF estimation, in terms of predictive power and the basic tuning properties of the estimated STRFs. We find that a GLM with a sparse prior predicts novel responses to both stimulus classes significantly better than NRC. Importantly, we find that STRFs from the two models derived from the same responses can differ substantially and that GLM STRFs are more consistent between stimulus classes than NRC STRFs. These results suggest that a GLM with a sparse prior provides a more accurate characterization of spectrotemporal tuning than does the NRC method when responses to complex sounds are studied in these neurons

π+\pi^+ photoproduction on the proton for photon energies from 0.725 to 2.875 GeV

Differential cross sections for the reaction $\gamma p \to n \pi^+$ have been measured with the CEBAF Large Acceptance Spectrometer (CLAS) and a tagged photon beam with energies from 0.725 to 2.875 GeV. Where available, the results obtained here compare well with previously published results for the reaction. Agreement with the SAID and MAID analyses is found below 1 GeV. The present set of cross sections has been incorporated into the SAID database, and exploratory fits have been made up to 2.7 GeV. Resonance couplings have been extracted and compared to previous determinations. With the addition of these cross sections to the world data set, significant changes have occurred in the high-energy behavior of the SAID cross-section predictions and amplitudes.Comment: 18 pages, 10 figure

Differential cross sections and spin density matrix elements for the reaction gamma p -> p omega

High-statistics differential cross sections and spin density matrix elements for the reaction gamma p -> p omega have been measured using the CLAS at Jefferson Lab for center-of-mass (CM) energies from threshold up to 2.84 GeV. Results are reported in 112 10-MeV wide CM energy bins, each subdivided into cos(theta_CM) bins of width 0.1. These are the most precise and extensive omega photoproduction measurements to date. A number of prominent structures are clearly present in the data. Many of these have not previously been observed due to limited statistics in earlier measurements

Search for the Θ+\Theta^+ pentaquark in the reaction γd→pK−K+n\gamma d \to p K^- K^+ n

A search for the \thp in the reaction $\gamma d \to pK^-K^+n$ was completed using the CLAS detector at Jefferson Lab. A study of the same reaction, published earlier, reported the observation of a narrow \thp resonance. The present experiment, with more than 30 times the integrated luminosity of our earlier measurement, does not show any evidence for a narrow pentaquark resonance. The angle-integrated upper limit on \thp production in the mass range of 1.52 to 1.56 GeV/c$^2$ for the $\gamma d \to pK^-\Theta^+$ reaction is 0.3 nb (95% CL). This upper limit depends on assumptions made for the mass and angular distribution of \thp production. Using \lamstar production as an empirical measure of rescattering in the deuteron, the cross section upper limit for the elementary $\gamma n \to K^-\Theta^+$ reaction is estimated to be a factor of 10 higher, {\it i.e.}, $\sim 3$ nb (95% CL).Comment: 5 figures, submitted to PRL, revised for referee comment

Photodisintegration of 4^4He into p+t

The two-body photodisintegration of $^4$He into a proton and a triton has been studied using the CEBAF Large-Acceptance Spectrometer (CLAS) at Jefferson Laboratory. Real photons produced with the Hall-B bremsstrahlung-tagging system in the energy range from 0.35 to 1.55 GeV were incident on a liquid $^4$He target. This is the first measurement of the photodisintegration of $^4$He above 0.4 GeV. The differential cross sections for the $\gamma$$^4$He$\to pt$ reaction have been measured as a function of photon-beam energy and proton-scattering angle, and are compared with the latest model calculations by J.-M. Laget. At 0.6-1.2 GeV, our data are in good agreement only with the calculations that include three-body mechanisms, thus confirming their importance. These results reinforce the conclusion of our previous study of the three-body breakup of $^3$He that demonstrated the great importance of three-body mechanisms in the energy region 0.5-0.8 GeV .Comment: 13 pages submitted in one tgz file containing 2 tex file and 22 postscrip figure

Exclusive ρ0\rho^0 electroproduction on the proton at CLAS

The $e p\to e^\prime p \rho^0$ reaction has been measured, using the 5.754 GeV electron beam of Jefferson Lab and the CLAS detector. This represents the largest ever set of data for this reaction in the valence region. Integrated and differential cross sections are presented. The $W$, $Q^2$ and $t$ dependences of the cross section are compared to theoretical calculations based on $t$-channel meson-exchange Regge theory on the one hand and on quark handbag diagrams related to Generalized Parton Distributions (GPDs) on the other hand. The Regge approach can describe at the $\approx$ 30% level most of the features of the present data while the two GPD calculations that are presented in this article which succesfully reproduce the high energy data strongly underestimate the present data. The question is then raised whether this discrepancy originates from an incomplete or inexact way of modelling the GPDs or the associated hard scattering amplitude or whether the GPD formalism is simply inapplicable in this region due to higher-twists contributions, incalculable at present.Comment: 29 pages, 29 figure

First Measurement of Beam-Recoil Observables Cx and Cz in Hyperon Photoproduction

Spin transfer from circularly polarized real photons to recoiling hyperons has been measured for the reactions $\vec\gamma + p \to K^+ + \vec\Lambda$ and $\vec\gamma + p \to K^+ + \vec\Sigma^0$. The data were obtained using the CLAS detector at Jefferson Lab for center-of-mass energies $W$ between 1.6 and 2.53 GeV, and for $-0.85<\cos\theta_{K^+}^{c.m.}< +0.95$. For the $\Lambda$, the polarization transfer coefficient along the photon momentum axis, $C_z$, was found to be near unity for a wide range of energy and kaon production angles. The associated transverse polarization coefficient, $C_x$, is smaller than $C_z$ by a roughly constant difference of unity. Most significantly, the {\it total} $\Lambda$ polarization vector, including the induced polarization $P$, has magnitude consistent with unity at all measured energies and production angles when the beam is fully polarized. For the $\Sigma^0$ this simple phenomenology does not hold. All existing hadrodynamic models are in poor agreement with these results.Comment: 28 pages, 18 figures, Submitted to Physical Review