Measurement of distributed strain and temperature based on higher order and higher mode Bragg conditions

A Bragg grating sensor for measuring distributed strain and temperature at the same time comprises an optical fiber having a single mode operating wavelength region and below a cutoff wavelength of the fiber having a multimode operating wavelength region. A saturated, higher order Bragg grating having first and second order Bragg conditions is fabricated in the optical fiber. The first order of Bragg resonance wavelength of the Bragg grating is within the single mode operating wavelength region of the optical fiber and the second order of Bragg resonance wavelength is below the cutoff wavelength of the fiber within the multimode operating wavelength region. The reflectivities of the saturated Bragg grating at the first and second order Bragg conditions are less than two orders of magnitude of one another. In use, the first and second order Bragg conditions are simultaneously created in the sensor at the respective wavelengths and a signal from the sensor is demodulated with respect to each of the wavelengths corresponding to the first and second order Bragg conditions. Two Bragg conditions have different responsivities to strain and temperature, thus allowing two equations for axial strain and temperature to be found in terms of the measure shifts in the primary and second order Bragg wavelengths. This system of equations can be solved for strain and temperature

Self-Assembly of VPS41 Promotes Sorting Required for Biogenesis of the Regulated Secretory Pathway

The regulated release of polypeptides has a central role in physiology, behavior, and development, but the mechanisms responsible for production of the large dense core vesicles (LDCVs) capable of regulated release have remained poorly understood. Recent work has implicated cytosolic adaptor protein AP-3 in the recruitment of LDCV membrane proteins that confer regulated release. However, AP-3 in mammals has been considered to function in the endolysosomal pathway and in the biosynthetic pathway only in yeast. We now find that the mammalian homolog of yeast VPS41, a member of the homotypic fusion and vacuole protein sorting (HOPS) complex that delivers biosynthetic cargo to the endocytic pathway in yeast, promotes LDCV formation through a common mechanism with AP-3, indicating a conserved role for these proteins in the biosynthetic pathway. VPS41 also self-assembles into a lattice, suggesting that it acts as a coat protein for AP-3 in formation of the regulated secretory pathway

Radiotherapy Followed by Aurora Kinase Inhibition Targets Tumor-Propagating Cells in Human Glioblastoma

Glioblastoma (GBM) is the most common malignant primary brain tumor. Radiotherapy fails to eliminate subpopulations of stem-like tumor-propagating cells (TPC), resulting in tumor regrowth. To identify kinases that promote TPC self-renewal rather than increasing proliferation in human GBM cultures, we screened a library of 54 nonselective tool compounds and determined their kinase inhibitor profiles in vitro. Most compounds inhibited aurora kinase (AURK) activity and blocked TPC self-renewal, while inducing GBM cell polynucleation and apoptosis. To prevent regrowth by TPCs, we used a priming dose of radiation followed by incubation with the pan-AURK inhibitor VX680 to block self-renewal and induce apoptosis in GBM cultures. In mice xenografted with human GBM cells, radiotherapy followed by VX680 treatment resulted in reduced tumor growth and increased survival relative to either monotherapy alone or VX680 treatment before radiation. Our results indicate that AURK inhibition, subsequent to radiation, may enhance the efficacy of radiotherapy by targeting radioresistant TPCs in human GBMs