Phosphorylation independent eIF4E translational reprogramming of selective mRNAs determines tamoxifen resistance in breast cancer

Eukaryotic translation initiation factor 4E (eIF4E) selectively promotes translation of mRNAs with atypically long and structured 5′-UTRs and has been implicated in drug resistance. Through genome-wide transcriptome and translatome analysis we revealed eIF4E overexpression could promote cellular activities mediated by ERα and FOXM1 signalling pathways. Whilst eIF4E overexpression could enhance the translation of both ERα and FOXM1, it also led to enhanced transcription of FOXM1. Polysome fractionation experiments confirmed eIF4E could modulate the translation of ERα and FOXM1 mRNA. The enhancement of FOXM1 transcription was contingent upon the presence of ERα, and it was the high levels of FOXM1 that conferred Tamoxifen resistance. Furthermore, tamoxifen resistance was conferred by phosphorylation independent eIF4E overexpression. Immunohistochemistry on 134 estrogen receptor (ER+) primary breast cancer samples confirmed that high eIF4E expression was significantly associated with increased ERα and FOXM1, and significantly associated with tamoxifen resistance. Our study uncovers a novel mechanism whereby phosphorylation independent eIF4E translational reprogramming in governing the protein synthesis of ERα and FOXM1 contributes to anti-estrogen insensitivity in ER+ breast cancer. In eIF4E overexpressing breast cancer, the increased ERα protein expression in turn enhances FOXM1 transcription, which together with its increased translation regulated by eIF4E, contributes to tamoxifen resistance. Coupled with eIF4E translational regulation, our study highlights an important mechanism conferring tamoxifen resistance via both ERα dependent and independent pathways

A travel guide to the canonical bundle formula

We survey known results on the canonical bundle formula and its applications in algebraic geometry.Comment: 17 pages, to appear in the Proceedings of the conference Birational Geometry and Moduli Space

Parallelization of BiCGMisR method with cache-cache elements preconditioning

We consider Krylov subspace methods for solving a linear system of equations on parallel computer with distributed memory. For speed-up of parallel computation, it is necessary to shorten the communication time among processors. However, in paral- lelized Krylov subspace methods, global synchronization points for inner products cause increment of communication time. Thus, we created the strategy for reduction of synchro- nization points of parallel Krylov subspace methods. We transform the computation of parameter βk to reduce the number of synchronization points of various Krylov subspace methods per one iteration. In this paper, we apply this strategy to three-term recurrence and propose parallel BiCGMisR method as the effective solver suited to parallel computer with distributed memory. Furthermore, through several numerical experiments, we make clear that parallel BiCGMisR method outperforms other methods from the viewpoints of both elapsed time and speed-up on parallel computer with distributed memory

Non-equilibrium Studies in Switching Arc Plasmas in Japan

This paper briefly introduce research work examples of non-equilibrium studies in switching arcs. In understanding arc behavior, one often assumes local thermodynamic equilibrium (LTE) condition in the arc plasma. However, actual arc plasmas are not completely and not always in LTE state because of strong temperature change temporally and spatially, and high electric field application etc. Recently, we have a collaboration work in numerical simulations and experimental approaches for decaying arcs without LTE assumption. First, our numerical model is presented for decaying arcs without chemical equilibrium assumption. Secondly, two experimental methods are introduced for measuring electron density in decaying arcs without LTE assumption: Laser Thomson Scattering method and the Schack-Hartmann method. Finally, comparison results is shown between the LTE simulation, the chemically non-equilibrium simulation, and the above experimental measurements

Inverse Anticipating Synchronization

We report a new type of chaos synchronization:inverse anticipating synchronization, where a time delay chaotic system can drive another system in such a way that the driven system anticipates the driver by synchronizing with its inverse future state. We extend the concept of inverse anticipating chaos synchronization to cascaded systems. We propose means for the experimental observation of inverse anticipating chaos synchronization in external cavity lasers.Comment: LaTex 6 pages, resubmitted to PR

Extension of holomorphic functions and cohomology classes from non reduced analytic subvarieties

The goal of this survey is to describe some recent results concerning the L 2 extension of holomorphic sections or cohomology classes with values in vector bundles satisfying weak semi-positivity properties. The results presented here are generalized versions of the Ohsawa-Takegoshi extension theorem, and borrow many techniques from the long series of papers by T. Ohsawa. The recent achievement that we want to point out is that the surjectivity property holds true for restriction morphisms to non necessarily reduced subvarieties, provided these are defined as zero varieties of multiplier ideal sheaves. The new idea involved to approach the existence problem is to make use of L 2 approximation in the Bochner-Kodaira technique. The extension results hold under curvature conditions that look pretty optimal. However, a major unsolved problem is to obtain natural (and hopefully best possible) L 2 estimates for the extension in the case of non reduced subvarieties -- the case when Y has singularities or several irreducible components is also a substantial issue.Comment: arXiv admin note: text overlap with arXiv:1703.00292, arXiv:1510.0523

Coexistence of Ferroelectric Triclinic Phases and Origin of Large Piezoelectric Responses in Highly Strained BiFeO3 films

The structural evolution of the strain-driven morphotropic phase boundary (MPB) in BiFeO3 films has been investigated using synchrotron x-ray diffractometry in conjunction with scanning probe microscopy. Our results demonstrate the existence of mixed-phase regions that are mainly made up of two heavily tilted ferroelectric triclinic phases. Analysis of first-principles computations suggests that these two triclinic phases originate from a phase separation of a single monoclinic state accompanied by elastic matching between the phase-separated states. These first-principle calculations further reveal that the intrinsic piezoelectric response of these two low-symmetry triclinic phases is not significantly large, which thus implies that the ease of phase transition between these two energetically close triclinic phases is likely responsible for the large piezoelectric response found in the BiFeO3 films near its MPB. These findings not only enrich the understandings of the lattice and domain structure of epitaxial BiFeO3 films but may also shed some light on the origin of enhanced piezoelectric response near MPB.Comment: 19 pages, 3 figures and 1 tabl

Parameter Mismatches and Perfect Anticipating Synchronization in bi-directionally coupled external cavity laser diodes

We study perfect chaos synchronization between two bi-directionally coupled external cavity semiconductor lasers and demonstrate for the first time that mismatches in laser photon decay rates can explain the experimentally observed anticipating time in synchronization.Comment: Latex 4 page