Myosin motor Myo1c and its receptor NEMO/IKK-γ promote TNF-α–induced serine307 phosphorylation of IRS-1

Tumor necrosis factor-α (TNF-α) signaling through the IκB kinase (IKK) complex attenuates insulin action via the phosphorylation of insulin receptor substrate 1 (IRS-1) at Ser307. However, the precise molecular mechanism by which the IKK complex phosphorylates IRS-1 is unknown. In this study, we report nuclear factor κB essential modulator (NEMO)/IKK-γ subunit accumulation in membrane ruffles followed by an interaction with IRS-1. This intracellular trafficking of NEMO requires insulin, an intact actin cytoskeletal network, and the motor protein Myo1c. Increased Myo1c expression enhanced the NEMO–IRS-1 interaction, which is essential for TNF-α– induced phosphorylation of Ser307–IRS-1. In contrast, dominant inhibitory Myo1c cargo domain expression diminished this interaction and inhibited IRS-1 phosphorylation. NEMO expression also enhanced TNF-α–induced Ser307–IRS-1 phosphorylation and inhibited glucose uptake. In contrast, a deletion mutant of NEMO lacking the IKK-β–binding domain or silencing NEMO blocked the TNF-α signal. Thus, motor protein Myo1c and its receptor protein NEMO act cooperatively to form the IKK–IRS-1 complex and function in TNF-α–induced insulin resistance

Optimizing the timing of 3.6 mg Pegfilgrastim Administration for Dose-Dense Chemotherapy in Japanese Patients with Breast Cancer

Perioperative dose-dense chemotherapy (DDCT) with pegfilgrastim (Peg) prophylaxis is a standard treatment for high-risk breast cancer. We explored the optimal timing of administration of 3.6 mg Peg, the dose approved in Japan. In the phase II feasibility study of DDCT (adriamycin+cyclophosphamide or epirubicin+cyclophosphamide followed by paclitaxel) for breast cancer, we investigated the feasibility, safety, neutrophil transition, and optimal timing of Peg treatment by administering Peg at days 2, 3, and 4 post-chemotherapy (P2, P3, and P4 groups, respectively). Among the 52 women enrolled, 13 were aged > 60 years. The anthracycline sequence was administered to P2 (n=33), P3 (n=5), and P4 (n=14) patients, and the taxane sequence to P2 (n=38) and P3 (n=6) patients. Both sequences showed no interaction between Peg administration timing and treatment discontinuation, treatment delay, or dose reduction. However, the relative dose intensity (RDI) was significantly different among the groups. The neutrophil count transition differed significantly among the groups receiving the anthracycline sequence. However, the neutrophil count remained in the appropriate range for both sequences in the P2 group. The timing of Peg administration did not substantially affect the feasibility or safety of DDCT. Postoperative day 2 might be the optimal timing for DDCT

Gamma ray vortices from nonlinear inverse Compton scattering of circularly polarized light

Inverse Thomson scattering is a well-known radiation process that produces high-energy photons both in nature and in the laboratory. Nonlinear inverse Thomson scattering occurring inside an intense light field is a process which generates higher harmonic photons. In this paper, we theoretically showthat the higher harmonic gamma-ray produced by nonlinear inverse Thomson scattering of circularly polarized light is a gamma-ray vortex, which means that it possesses a helical wave front and carries orbital angular momentum. Our work explains a recent experimental result regarding nonlinear inverse Thomson scattering that clearly shows an annular intensity distribution as a remarkable feature of a vortex beam. Our work implies that gamma-ray vortices should be produced in various situations in astrophysics in which high-energy electrons and intense circularly polarized light fields coexist. Nonlinear inverse Thomson scattering is a promising radiation process for realizing a gamma-ray vortex source based on currently available laser and accelerator technologies, which would be an indispensable tool for exploring gamma-ray vortex science

(E)-3-[4-(Pent-4-en-1-yloxy)phenyl]acrylicc Acid

(E)-3-[4-(Pent-4-en-1-yloxy)phenyl]acetic acid is one of the useful components of liquid crystal materials which can be produced through Williamson ether synthesis by synthesizing 4-hydroxy-cinnamic acid and 5-bromo-1-pentene. Although Williamson ether synthesis is generally slow under conventional external heating conditions, microwave irradiation was effective for significant acceleration of the etherification. Furthermore, we demonstrated the rapid and continuous synthesis of (E)-3-[4-(pent-4-en-1-yloxy)phenyl]acetic acid, using a microwave-assisted flow reactor developed by us, in which the blockage by salt precipitation was suppressed by the continuous addition of an aqueous methanol solution after the reaction cavity

GENERATION OF FLAT-LASER COMPTON SCATTERING GAMMA-RAY BEAM IN UVSOR

Flat-Laser Compton Scattering Gamma-ray beam (F-LCS), which has a flat distribution in the energy spectrum and the spatial distribution with a small beam size, has been developed to study an isotope selective CT Imaging application in the beamline BL1U in UVSOR. We pro-pose generation of an F-LCS beam by using a circular motioned electron beam, which can be generated by a helical undulator installed in a storage ring, and collision with an intense laser beam. A simulation study on the LCS beamline BL1U in UVSOR shows a weak magnetic field (K=0.2) can generate an F-LCS beam. A demonstra-tion experiment has been carried out in UVSOR with the APPLE-II undulator. The spectra of the LCS beams were measured by using a 120% Ge detector. As a result, the energy bandwidth of the LCS peak was observed. The energy bandwidth measured in the energy spectra and the distribution map agreed with the EGS5 simulation

Generation of flat-laser Compton scattering γ-ray beam

To develop an isotope selective computed tomography imaging technique, a flat-laser Compton scattering γ-ray beam (F-LCS) by using a helical undulator installed in a storage ring has been proposed. An LCS beam with a broad energy spectrum and spatial distribution, keeping a small beam size, is preferable for multi-isotope imaging and qualitative evaluation. egs5 simulations assuming the BL1U beamline in UVSOR have been carried out and the result shows that the energy bandwidth of the LCS beam is widened from 2.7% to 22% (FWHM) with a beam size of 2 mm in diameter by varying the undulator K value from 0 to 0.4. A proof of principle (POP) experiment has been carried out in the BL1U, where the APPLE-II undulator has been installed. The K value dependency of the energy spectrum of the generated LCS beam was measured. As a result, a broader energy bandwidth of the LCS beam was observed as the undulator K value increased. The measured energy spectra agreed with the egs5 results

Selective Isotope CT Imaging Based on Nuclear Resonance Fluorescence Transmission Method

The isotope selectivity of computed tomography (CT) imaging based on nuclear resonance fluorescence (NRF) transmission method using a quasi-monochromatic laser Compton scattering (LCS) gamma-ray beam in the MeV region was demonstrated at the Ultra Violet Synchrotron Orbital Radiation–III (UVSOR-III) Synchrotron Radiation Facility (Institute of Molecular Science, National Institute of Natural Science) for two enriched lead isotope rods ( 206 Pb and 208 Pb) implanted in an aluminum cylinder. Since these two rods show the same gamma-ray attenuation in atomic processes, it is impossible to differentiate between them using a standard Gamma-CT technique based on atomic attenuation of gamma rays. The LCS gamma-ray beam had a maximum energy of 5.528 MeV and an intensity of approximately 5.5 photons/s/eV at the resonance energy ( Jπ=1− at 5.512 MeV in 208 Pb). A lead collimator with a hole diameter of 1 mm was used to define the size of the LCS gamma-ray beam at the CT target. The CT image of the 208 Pb rod was selectively obtained with a 2-mm pixel size resolution, which was determined by the horizontal step size of the CT stage

GENERATION OF FLAT-LASER COMPTON SCATTERING GAMMA-RAY BEAM IN UVSOR

Laser Compton Scattering Gamma-ray beam (F-LCS), which has a flat distribution in the energy spectrum and the spatial distribution with a small beam size, has been developed to study an isotope selective CT Imaging ap-plication in the beamline BL1U in UVSOR. We propose generation of an F-LCS beam by using a circular mo-tioned electron beam, which can be generated by a helical undulator installed in a storage ring, and collision with an intense laser beam. A simulation study on the LCS beam-line BL1U in UVSOR shows a weak magnetic field (K=0.2) can generate an F-LCS beam. A demonstration experiment has been carried out in UVSOR with the AP-PLE-II undulator. The spectra of the LCS beams were measured by using a 120% Ge detector. As a result, the energy bandwidth of the LCS peak was observed. The energy bandwidth measured in the energy spectra and the distribution map agreed with the EGS5 simulation.The 13th International Particle Accelerator Conferenc