Annexin A1 drives macrophage skewing to accelerate muscle regeneration through AMPK activation.

Understanding the circuits that promote an efficient resolution of inflammation is crucial to deciphering the molecular and cellular processes required to promote tissue repair. Macrophages play a central role in the regulation of inflammation, resolution, and repair/regeneration. Using a model of skeletal muscle injury and repair, herein we identified annexin A1 (AnxA1) as the extracellular trigger of macrophage skewing toward a pro-reparative phenotype. Brought into the injured tissue initially by migrated neutrophils, and then overexpressed in infiltrating macrophages, AnxA1 activated FPR2/ALX receptors and the downstream AMPK signaling cascade, leading to macrophage skewing, dampening of inflammation, and regeneration of muscle fibers. Mice lacking AnxA1 in all cells or only in myeloid cells displayed a defect in this reparative process. In vitro experiments recapitulated these properties, with AMPK-null macrophages lacking AnxA1-mediated polarization. Collectively, these data identified the AnxA1/FPR2/AMPK axis as an important pathway in skeletal muscle injury regeneration

Annexin A1 drives macrophage skewing towards a resolving phenotype to accelerate the regeneration of muscle injury through AMPK activation

Understanding the circuits that promote an efficient resolution of inflammation is crucial to deciphering the molecular and cellular processes required to promote tissue repair. Macrophages play a central role in the regulation of inflammation, resolution and repair/regeneration. Using a model of skeletal muscle injury and repair, herein we identify Annexin A1 (AnxA1) as the extracellular trigger of macrophage skewing towards a pro-reparative phenotype. Brought into the injured tissue initially by migrated neutrophils, and then over-expressed in infiltrating macrophages, AnxA1 activates FPR2/ALX receptors and the downstream AMPK signalling cascade leading to macrophage skewing, dampening of inflammation and regeneration of muscle fibres. Mice lacking AnxA1 in all cells or in myeloid cells only display a defect in this reparative process. In vitro experiments recapitulated these properties, with AMPK null macrophages lacking AnxA1-mediated polarization. Collectively, these data identify the AnxA1/FPR2/AMPK axis as a novel pathway in skeletal muscle injury regeneration.This work was supported by CNRS, French Society of Myology and Wellcome Trust Programme Grant 086867/Z/08/Z. GJ was supported by Fondation pour la Recherche Medicale (Equipe FRM DEQ20140329495

Drug-mediated inhibition of Fli-1 for the treatment of leukemia

The Ets transcription factor, Fli-1 is activated in murine erythroleukemia and overexpressed in various human malignancies including Ewing's sarcoma, induced by the oncogenic fusion protein EWS/Fli-1. Recent studies by our group and others have demonstrated that Fli-1 plays a key role in tumorigenesis, and disrupting its oncogenic function may serve as a potential treatment option for malignancies associated with its overexpression. Herein, we describe the discovery of 30 anti-Fli-1 compounds, characterized into six functional groups. Treatment of murine and human leukemic cell lines with select compounds inhibits Fli-1 protein or mRNA expression, resulting in proliferation arrest and apoptosis. This anti-cancer effect was mediated, at least in part through direct inhibition of Fli-1 function, as anti-Fli-1 drug treatment inhibited Fli-1 DNA binding to target genes, such as SHIP-1 and gata-1, governing hematopoietic differentiation and proliferation. Furthermore, treatment with select Fli-1 inhibitors revealed a positive relationship between the loss of DNA-binding activity and Fli-1 phosphorylation. Accordingly, anti-Fli-1 drug treatment significantly inhibited leukemogenesis in a murine erythroleukemia model overexpressing Fli-1. This study demonstrates the ability of this drug-screening strategy to isolate effective anti-Fli-1 inhibitors and highlights their potential use for the treatment of malignancies overexpressing this oncogene

Short-term wind power prediction based on extreme learning machine with error correction

Introduction: Large-scale integration of wind generation brings great challenges to the secure operation of the power systems due to the intermittence nature of wind. The fluctuation of the wind generation has a great impact on the unit commitment. Thus accurate wind power forecasting plays a key role in dealing with the challenges of power system operation under uncertainties in an economical and technical way. Methods: In this paper, a combined approach based on Extreme Learning Machine (ELM) and an error correction model is proposed to predict wind power in the short-term time scale. Firstly an ELM is utilized to forecast the short-term wind power. Then the ultra-short-term wind power forecasting is acquired based on processing the short-term forecasting error by persistence method. Results: For short-term forecasting, the Extreme Learning Machine (ELM) doesn’t perform well. The overall NRMSE (Normalized Root Mean Square Error) of forecasting results for 66 days is 21.09 %. For the ultra-short term forecasting after error correction, most of forecasting errors lie in the interval of [−10 MW, 10 MW]. The error distribution is concentrated and almost unbiased. The overall NRMSE is 5.76 %. Conclusion: The ultra-short-term wind power forecasting accuracy is further improved by using error correction in terms of normalized root mean squared error (NRMSE)

Photochemistry Of Monochloro Complexes Of Copper(ii) In Methanol Probed By Ultrafast Transient Absorption Spectroscopy

Ultrafast transient absorption spectra in the deep to near UV range (212-384 nm) were measured for the [Cu-II(MeOH)(5)Cl](+) complexes in methanol following 255-nm excitation of the complex into the ligand-to-metal charge-transfer excited state. The electronically excited complex undergoes sub-200 fs radiationless decay, predominantly via back electron transfer, to the hot electronic ground state followed by fast vibrational relaxation on a 0.4-4 Ps time scale. A minor photochemical channel is Cu-Cl bond dissociation, leading to the reduction of copper(H) to copper(I) and the formation of MeOH center dot Cl charge-transfer complexes. The depletion of ground-state [Cu-II(MeOH)(5)Cl](+) perturbs the equilibrium between several forms of copper(II) complexes present in solution. Complete re-equilibration between [Cu-II(MeOH)(5)Cl](+) and [Cu-II(MeOH)(4)Cl-2] is established on a 10-500 ps time scale, slower than methanol diffusion, suggesting that the involved ligand exchange mechanism is dissociative

On the Complexity of Counting the Hilbert Basis of a Linear Diophantine System

Rapport interne.We investigate the computational complexity of counting the Hilbert basis of a homogeneous system of linear Diophantine equations. We establish lower and upper bound on the complexity of this problem by showing that counting the Hilbert basis is #P-hard and belongs to the class #NP. Moreover, we investigate the complexity of variants obtained by restricting the number of occurrences of the variables in the system

15 T, 4.2 K field-swept \u3csup\u3e27\u3c/sup\u3eAl NMR spectroscopy

A field-swept NMR spectrometer has been constructed based on a 16 T (4.2 K operation) superconducting magnet, the largest magnetic field yet used for field-swept NMR. We find that the experiment is relatively easy to perform for 27Al NMR and the spectra for α-Al2O3 are of high quality. There are two important advantages that we discuss herein: (1) resonances with exceedingly wide line widths can be studied and (2) operation at 4.2 K largely eliminates proton hopping and the resulting motional averaging of the electric field gradient at the aluminum sites. © 1994

Simulation tools for speech processing

This thesis describes a system that may establish the groundwork for the advancement of the digital speech processing field in the Philippines. This can be achieved by the development of a software that can be employed in conducting study-and concept-verification in the said field. The software is a windows-based application that can simulate several speech processing systems. It is capable of evaluating and analyzing speech signals to better visualize and understand the concepts involved in certain speech processing systems that a researcher or a user may intend to study. The software application run on Windows 95 or 98 environment and was developed using the compiler Borland C++ Builder version 4. The application receives input either from a wave file or an audio (au) file. Then, the user has the option on what kind of speech processes he would like to employ