2,666 research outputs found

    Magnetic Moments of the Baryon Decuplet in a Relativistic Quark Model

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    The magnetic moments of the baryon decuplet are calculated in a relativistic constituent quark model using the light-front formalism. Of particular interest are the magnetic moments of the Ω−\Omega^- and Δ++\Delta^{++} for which new recent experimental measurements are available. Our calculation for the magnetic moment ratio ÎŒ(Δ++)/ÎŒ(p)\mu(\Delta^{++})/\mu(p) is in excellent agreement with the experimental ratio, while our ratio ÎŒ(Ω−)/ÎŒ(Λ0)\mu(\Omega^-)/\mu(\Lambda^0) is slightly higher than the experimental ratio.Comment: 10 pages ReVTeX, SLAC-PUB-621

    Sigma1 Targeting to Suppress Aberrant Androgen Receptor Signaling in Prostate Cancer.

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    Suppression of androgen receptor (AR) activity in prostate cancer by androgen depletion or direct AR antagonist treatment, although initially effective, leads to incurable castration-resistant prostate cancer (CRPC) via compensatory mechanisms including resurgence of AR and AR splice variant (ARV) signaling. Emerging evidence suggests that Sigma1 (also known as sigma-1 receptor) is a unique chaperone or scaffolding protein that contributes to cellular protein homeostasis. We reported previously that some Sigma1-selective small molecules can be used to pharmacologically modulate protein homeostasis pathways. We hypothesized that these Sigma1-mediated responses could be exploited to suppress AR protein levels and activity. Here we demonstrate that treatment with a small-molecule Sigma1 inhibitor prevented 5α- dihydrotestosterone-mediated nuclear translocation of AR and induced proteasomal degradation of AR and ARV, suppressing the transcriptional activity and protein levels of both full-length and splice-variant AR. Consistent with these data, RNAi knockdown of Sigma1 resulted in decreased AR levels and transcriptional activity. Furthermore, Sigma1 physically associated with ARV7 and A

    HTLV-1 and -2 envelope SU subdomains and critical determinants in receptor binding

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    BACKGROUND: Human T-cell leukemia virus (HTLV) -1 and -2 are deltaretroviruses that infect a wide range of cells. Glut1, the major vertebrate glucose transporter, has been shown to be the HTLV Env receptor. While it is well established that the extracellular surface component (SU) of the HTLV envelope glycoprotein (Env) harbors all of the determinants of interaction with the receptor, identification of SU subdomains that are necessary and sufficient for interaction with the receptor, as well as critical amino acids therein, remain to be precisely defined. Although highly divergent in the rest of their genomes, HTLV and murine leukemia virus (MLV) Env appear to be related and based on homologous motifs between the HTLV and MLV SU, we derived chimeric HTLV/MLV Env and soluble HTLV-1 and -2 truncated amino terminal SU subdomains. RESULTS: Using these SU constructs, we found that the 183 and 178 amino terminal residues of the HTLV-1 and -2 Env, respectively, were sufficient to efficiently bind target cells of different species. Binding resulted from bona fide interaction with the HTLV receptor as isolated SU subdomains specifically interfered with HTLV Env-mediated binding, cell fusion, and cell-free as well as cell-to-cell infection. Therefore, the HTLV receptor-binding domain (RBD) lies in the amino terminus of the SU, immediately upstream of a central immunodominant proline rich region (Env residues 180 to 205), that we show to be dispensible for receptor-binding and interference. Moreover, we identified a highly conserved tyrosine residue at position 114 of HTLV-1 Env, Tyr(114), as critical for receptor-binding and subsequent interference to cell-to-cell fusion and infection. Finally, we observed that residues in the vicinity of Tyr(114 )have lesser impact on receptor binding and had various efficiency in interference to post-binding events. CONCLUSIONS: The first 160 residues of the HTLV-1 and -2 mature cleaved SU fold as autonomous domains that contain all the determinants required for binding the HTLV receptor

    Intrahost variations in the envelope receptor-binding domain (RBD) of HTLV-1 and STLV-1 primary isolates

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    Four primate (PTLV), human (HTLV) and simian (STLV) T-cell leukemia virus types, have been characterized thus far, with evidence of a simian zoonotic origin for HTLV-1, HTLV-2 and HTLV-3 in Africa. The PTLV envelope glycoprotein surface component (SUgp46) comprises a receptor-binding domain (RBD) that alternates hypervariable and highly conserved sequences. To further delineate highly conserved motifs in PTLV RBDs, we investigated the intrahost variability of HTLV-1 and STLV-1 by generating and sequencing libraries of DNA fragments amplified within the RBD of the SUgp46 env gene. Using new and highly cross-reactive env primer pairs, we observed the presence of Env quasispecies in HTLV-1 infected individuals and STLV-1 naturally infected macaques, irrespective of the clinical status. These intrahost variants helped us to define highly conserved residues and motifs in the RBD. The new highly sensitive env PCR described here appears suitable for the screening of all known variants of the different PTLV types and should, therefore, be useful for the analysis of seroindeterminate samples

    Hyb-Seq for flowering plant systematics

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    High-throughput DNA sequencing (HTS) presents great opportunities for plant systematics, yet genomic complexity needs to be reduced for HTS to be effectively applied. We highlight Hyb-Seq as a promising approach, especially in light of the recent development of probes enriching 353 low-copy nuclear genes from any flowering plant taxon

    Complementary Patents and Market Structure

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    Many high technology goods are based on standards that require several essential patents owned by different IP holders. This gives rise to a complements and a double mark-up problem. We compare the welfare effects of two different business strategies dealing with these problems. Vertical integration of an IP holder and a downstream producer solves the double mark-up problem between these firms. Nevertheless, it may raise royalty rates and reduce output as compared to non-integration. Horizontal integration of IP holders solves the complements problem but not the double mark-up problem. Vertical integration discourages entry and reduces innovation incentives, while horizontal integration always benefits from entry and innovatio

    High-fidelity transmission of entanglement over a high-loss freespace channel

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    Quantum entanglement enables tasks not possible in classical physics. Many quantum communication protocols require the distribution of entangled states between distant parties. Here we experimentally demonstrate the successful transmission of an entangled photon pair over a 144 km free-space link. The received entangled states have excellent, noise-limited fidelity, even though they are exposed to extreme attenuation dominated by turbulent atmospheric effects. The total channel loss of 64 dB corresponds to the estimated attenuation regime for a two-photon satellite quantum communication scenario. We confirm that the received two-photon states are still highly entangled by violating the CHSH inequality by more than 5 standard deviations. From a fundamental point of view, our results show that the photons are virtually not subject to decoherence during their 0.5 ms long flight through air, which is encouraging for future world-wide quantum communication scenarios.Comment: 5 pages, 3 figures, replaced paper with published version, added journal referenc

    Toxoplasma gondii Rhoptry Kinase ROP16 Activates STAT3 and STAT6 Resulting in Cytokine Inhibition and Arginase-1-Dependent Growth Control

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    The ROP16 kinase of Toxoplasma gondii is injected into the host cell cytosol where it activates signal transducer and activator of transcription (STAT)-3 and STAT6. Here, we generated a ROP16 deletion mutant on a Type I parasite strain background, as well as a control complementation mutant with restored ROP16 expression. We investigated the biological role of the ROP16 molecule during T. gondii infection. Infection of mouse bone marrow-derived macrophages with rop16-deleted (ΔROP16) parasites resulted in increased amounts of IL-12p40 production relative to the ROP16-positive RH parental strain. High level IL-12p40 production in ΔROP16 infection was dependent on the host cell adaptor molecule MyD88, but surprisingly was independent of any previously recognized T. gondii triggered pathway linking to MyD88 (TLR2, TLR4, TLR9, TLR11, IL-1ß and IL-18). In addition, ROP16 was found to mediate the suppressive effects of Toxoplasma on LPS-induced cytokine synthesis in macrophages and on IFN-γ-induced nitric oxide production by astrocytes and microglial cells. Furthermore, ROP16 triggered synthesis of host cell arginase-1 in a STAT6-dependent manner. In fibroblasts and macrophages, failure to induce arginase-1 by ΔROP16 tachyzoites resulted in resistance to starvation conditions of limiting arginine, an essential amino acid for replication and virulence of this parasite. ΔROP16 tachyzoites that failed to induce host cell arginase-1 displayed increased replication and dissemination during in vivo infection. We conclude that encounter between Toxoplasma ROP16 and the host cell STAT signaling cascade has pleiotropic downstream effects that act in multiple and complex ways to direct the course of infection

    MAPPING THE NUCLEAR OUTFLOW OF THE MILKY WAY: STUDYING THE KINEMATICS AND SPATIAL EXTENT OF THE NORTHERN FERMI BUBBLE

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    We report new observations from a systematic, spectroscopic, ultraviolet absorption-line survey that maps the spatial and kinematic properties of the high-velocity gas in the Galactic Center region. We examine the hypothesis that this gas traces the biconical nuclear outflow. We use ultraviolet spectra of 47 background QSOs and halo stars projected inside and outside the northern Fermi Bubble from the Hubble Space Telescope to study the incidence of high velocity absorption around it. We use five lines of sight inside the northern Fermi Bubble to constrain the velocity and column densities of outflowing gas traced by O I, Al II, C II, C IV, Si II, Si III, Si IV and other species. All five lines of sight inside the northern Fermi Bubble exhibit blueshifted high velocity absorption components, whereas only 9 out of the 42 lines of sight outside the northern Fermi Bubble exhibit blueshifted high velocity absorption components. The observed outflow velocity profile decreases with Galactic latitude and radial distance (R) from the Galactic Center. The observed blueshifted velocities change from vGSRv_{GSR}=-265 km/s at R~2.3 kpc to vGSRv_{GSR}=-91 km/s at R~6.5 kpc. We derive the metallicity of the entrained gas along the 1H1613-097 sightline, which passes through the center of the northern Fermi Bubble, finding [O/H] ≳−0.54±0.15\gtrsim -0.54 \pm 0.15. A simple kinematic model tuned to match the observed absorption component velocities along the five lines of sight inside the Bubble, constrains the outflow velocities to ~1000−-1300 km/s, and the age of the outflow to be ~ 6−-9 Myr. We estimate a minimum mass outflow rate for the nuclear outflow to be ≳\gtrsim 0.2 M⊙  yr−1\rm{ M_{\odot}\; yr^{-1}}. Combining the age and mass outflow rates, we determine a minimum mass of total UV absorbing cool gas entrained in the Fermi Bubbles to be ≳2×106M⊙\gtrsim \rm{ 2 \times 10^{6} M_{\odot}}.Comment: 24 pages, 9 9 figures, Accepted for Publication in Ap
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