Optimal replacement policy under a general failure and repair model: Minimal versus worse than old repair

We analyze the optimal replacement policy for a system subject to a general failure and repair model. Failures can be of one of two types: catastrophic or minor. The former leads to the replacement of the system, whereas minor failures are followed by repairs. The novelty of the proposed model is that, after repair, the system recovers the operational state but its condition is worse than that just prior to failure (worse than old). Undertrained operators or low quality spare parts explain this deficient maintenance. The corresponding failure process is based on the Generalized Pólya Process which presents both the minimal repair and the perfect repair as special cases. The system is replaced by a new one after the first catastrophic failure, and also undergoes two sorts of preventive maintenance based on age and after a predetermined number of minor failures whichever comes first. We derive the long-run average cost rate and study the optimal replacement policy. Some numerical examples illustrate the comparison between the as bad-as-old and the worse than old conditions

Ultra-high modulation depth exceeding 2,400% in the optically-controlled topological surface plasmons

Modulating light via coherent charge oscillations in solids is the subject of intense research topics in opto-plasmonics. Although a variety of methods are proposed to increase such modulation efficiency, one central challenge is to achieve a high modulation depth ( defined by a ratio of extinction with/without light) under small photon-flux injection, which becomes a fundamental trade-off issue both in metals and semiconductors. Here, by fabricating simple micro-ribbon arrays of topological insulator Bi2Se3, we report an unprecedentedly large modulation depth of 2,400% at 1.5 THz with very low optical fluence of 45 mu J cm(-2). This was possible, first because the extinction spectrum is nearly zero due to the Fano-like plasmon-phonon-destructive interference, thereby contributing an extremely small denominator to the extinction ratio. Second, the numerator of the extinction ratio is markedly increased due to the photoinduced formation of massive two-dimensional electron gas below the topological surface states, which is another contributor to the ultra-high modulation depth.112115Ysciescopu

Golgi Outpost Synthesis Impaired by Toxic Polyglutamine Proteins Contributes to Dendritic Pathology in Neurons

Dendrite aberration is a common feature of neurodegenerative diseases caused by protein toxicity, but the underlying mechanisms remain largely elusive. Here, we show that nuclear polyglutamine (polyQ) toxicity resulted in defective terminal dendrite elongation accompanied by a loss of Golgi outposts (GOPs) and a decreased supply of plasma membrane (PM) in Drosophila class IV dendritic arborization (da) (C4 da) neurons. mRNA sequencing revealed that genes downregulated by polyQ proteins included many secretory pathway-related genes, including COPII genes regulating GOP synthesis. Transcription factor enrichment analysis identified CREB3L1/CrebA, which regulates COPII gene expression. CrebA overexpression in C4 da neurons restores the dysregulation of COPII genes, GOP synthesis, and PM supply. Chromatin immunoprecipitation (ChIP)-PCR revealed that CrebA expression is regulated by CREB-binding protein (CBP), which is sequestered by polyQ proteins. Furthermore, co-overexpression of CrebA and Rac1 synergistically restores the polyQ-induced dendrite pathology. Collectively, our results suggest that GOPs impaired by polyQ proteins contribute to dendrite pathology through the CBP-CrebA-COPII pathway. ? 2017 The Author(s)113Ysciescopu

The Role of Interferon Regulatory Factor-1 and Interferon Regulatory Factor-2 in IFN-γ Growth Inhibition of Human Breast Carcinoma Cell Lines

Interferon (IFN) regulatory factor-1 (IRF-1) and IRF-2 play opposing roles in the regulation of many IFN-γ-inducible genes. To investigate the signal transduction pathway in response to IFN-γ in light of differences in growth effects, we selected four human breast carcinoma cell lines based on a spectrum of growth inhibition by IFN-γ. MDA468 growth was markedly inhibited by IFN-γ, and it showed substantial induction of IRF-1 mRNA but little IRF-2 induction. SKBR3 showed little growth inhibition and little induction of IRF-1 mRNA but significant induction of IRF-2 mRNA. HS578T and MDA436 growth inhibition and IRF-1/IRF-2 induction were intermediate. All four cell lines showed intact receptor at the cell surface and Stat1 translocation to the nucleus by immunostaining. By EMSA, there were marked differences in the induced ratio of IRF-1 and IRF-2 binding activity between the cell lines that correlated with growth inhibition. Finally, antisense oligonucleotides specific for IRF-1 attenuated IFN-γ growth inhibition in MDA436 and MDA468, confirming the direct role of IRF-1 in IFN-γ growth inhibition. Induction of IRF-1 causes growth inhibition in human breast cancer cell lines, and induction of IRF-2 can oppose this. The relative induction of IRF-1 to IRF-2 is a critical control point in IFN-γ response.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63111/1/10799900360708623.pd

Non-perturbative contributions to the plane-wave string mass matrix

D-instanton contributions to the mass matrix of arbitrary excited string states of type IIB string theory in the maximally supersymmetric plane-wave background are calculated to leading order in the string coupling using a supersymmetric light-cone boundary state formalism. The explicit non-perturbative dependence of the mass matrix on the complex string coupling, the plane-wave mass parameter and the mode numbers of the excited states is determined.Comment: 25 pages, 1 figure. v3: corrected minor typos, added referenc

Numerical Test of Disk Trial Wave function for Half-Filled Landau Level

The analyticity of the lowest Landau level wave functions and the relation between filling factor and the total angular momentum severely limits the possible forms of trial wave functions of a disk of electrons subject to a strong perpendicular magnetic field. For N, the number of electrons, up to 12 we have tested these disk trial wave functions for the half filled Landau level using Monte Carlo and exact diagonalization methods. The agreement between the results for the occupation numbers and ground state energies obtained from these two methods is excellent. We have also compared the profile of the occupation number near the edge with that obtained from a field-theoretical method. The results give qualitatively identical edge profiles. Experimental consequences are briefly discussed.Comment: To be published in Phys. Rev. B. 9 pages, 6 figure

Clinical and genomic assessment of PD-L1 SP142 expression in triple-negative breast cancer

Purpose: The SP142 PD-L1 assay is a companion diagnostic for atezolizumab in metastatic triple-negative breast cancer (TNBC). We strove to understand the biological, genomic, and clinical characteristics associated with SP142 PD-L1 positivity in TNBC patients. Methods: Using 149 TNBC formalin-fixed paraffin-embedded tumor samples, tissue microarray (TMA) and gene expression microarrays were performed in parallel. The VENTANA SP142 assay was used to identify PD-L1 expression from TMA slides. We next generated a gene signature reflective of SP142 status and evaluated signature distribution according to TNBCtype and PAM50 subtypes. A SP142 gene expression signature was identified and was biologically and clinically evaluated on the TNBCs of TCGA, other cohorts, and on other malignancies treated with immune checkpoint inhibitors (ICI). Results: Using SP142, 28.9% of samples were PD-L1 protein positive. The SP142 PD-L1-positive TNBC had higher CD8+ T cell percentage, stromal tumor-infiltrating lymphocyte levels, and higher rate of the immunomodulatory TNBCtype compared to PD-L1-negative samples. The recurrence-free survival was prolonged in PD-L1-positive TNBC. The SP142-guided gene expression signature consisted of 94 immune-related genes. The SP142 signature was associated with a higher pathologic complete response rate and better survival in multiple TNBC cohorts. In the TNBC of TCGA, this signature was correlated with lymphocyte-infiltrating signature scores, but not with tumor mutational burden or total neoantigen count. In other malignancies treated with ICIs, the SP142 genomic signature was associated with improved response and survival. Conclusions: We provide multi-faceted evidence that SP142 PDL1-positive TNBC have immuno-genomic features characterized as highly lymphocyte-infiltrated and a relatively favorable survival

Coherent π0 photoproduction on the deuteron up to 4 GeV

The differential cross section for 2H(γ,d)π0 has been measured at deuteron center-of-mass angles of 90° and 136°. This work reports the first data for this reaction above a photon energy of 1 GeV, and permits a test of the apparent constituent counting rule and reduced nuclear amplitude behavior as observed in elastic ed scattering. Measurements were performed up to a photon energy of 4.0 GeV, and are in good agreement with previous lower energy measurements. Overall, the data are inconsistent with both constituent-counting rule and reduced nuclear amplitude predictions