University of Grenoble

About: University of Grenoble is a education organization based out in Saint-Martin-d'Hères, France. It is known for research contribution in the topics: Population & Context (language use). The organization has 25658 authors who have published 45143 publications receiving 909760 citations.

Chirality-Induced asymmetric magnetic nucleation in Pt/Co/AlOx ultrathin microstructures.

Abstract: The nucleation of reversed magnetic domains in Pt/Co/AlO(x) microstructures with perpendicular anisotropy was studied experimentally in the presence of an in-plane magnetic field. For large enough in-plane field, nucleation was observed preferentially at an edge of the sample normal to this field. The position at which nucleation takes place was observed to depend in a chiral way on the initial magnetization and applied field directions. A quantitative explanation of these results is proposed, based on the existence of a sizable Dzyaloshinskii-Moriya interaction in this sample. Another consequence of this interaction is that the energy of domain walls can become negative for in-plane fields smaller than the effective anisotropy field.

Sorafenib promotes graft-versus-leukemia activity in mice and humans through IL-15 production in FLT3-ITD-mutant leukemia cells.

Abstract: Individuals with acute myeloid leukemia (AML) harboring an internal tandem duplication (ITD) in the gene encoding Fms-related tyrosine kinase 3 (FLT3) who relapse after allogeneic hematopoietic cell transplantation (allo-HCT) have a 1-year survival rate below 20%. We observed that sorafenib, a multitargeted tyrosine kinase inhibitor, increased IL-15 production by FLT3-ITD+ leukemia cells. This synergized with the allogeneic CD8+ T cell response, leading to long-term survival in six mouse models of FLT3-ITD+ AML. Sorafenib-related IL-15 production caused an increase in CD8+CD107a+IFN-γ+ T cells with features of longevity (high levels of Bcl-2 and reduced PD-1 levels), which eradicated leukemia in secondary recipients. Mechanistically, sorafenib reduced expression of the transcription factor ATF4, thereby blocking negative regulation of interferon regulatory factor 7 (IRF7) activation, which enhanced IL-15 transcription. Both IRF7 knockdown and ATF4 overexpression in leukemia cells antagonized sorafenib-induced IL-15 production in vitro. Human FLT3-ITD+ AML cells obtained from sorafenib responders following sorafenib therapy showed increased levels of IL-15, phosphorylated IRF7, and a transcriptionally active IRF7 chromatin state. The mitochondrial spare respiratory capacity and glycolytic capacity of CD8+ T cells increased upon sorafenib treatment in sorafenib responders but not in nonresponders. Our findings indicate that the synergism of T cells and sorafenib is mediated via reduced ATF4 expression, causing activation of the IRF7-IL-15 axis in leukemia cells and thereby leading to metabolic reprogramming of leukemia-reactive T cells in humans. Therefore, sorafenib treatment has the potential to contribute to an immune-mediated cure of FLT3-ITD-mutant AML relapse, an otherwise fatal complication after allo-HCT.

Software configuration management: a roadmap

Abstract: This paper, in the first chapter summarizes the state of the art in SCM, showing the evolution along the last 25 years. Chapter 2 shows the current issues and current research work under way in the area. In chapter 3, the challenges SCM has to take up, as well as SCM future research are discussed.