A B S T R A C T The objective of this paper is to determine the very long fatigue life of ferrous alloys up to 1×10 10 cycles at an ultrasonic frequency of 20 kHz. A good agreement is found with the results from conventional tests at a frequency of 25 Hz by Renault between 10 5 and 10 7 cycles for a spheroidal graphite cast iron. The experimental results show that fatigue failure can occur over 10 7 cycles, and the fatigue endurance stress S max continues to decrease with increasing number of cycles to failure between 10 6 and 10 9 cycles. The evolution of the temperature of the specimen caused by the absorption of ultrasonic energy is studied. The temperature increases rapidly with increasing stress amplitudes. There is a maximum temperature between 10 6 and 10 7 cycles which may be related to the crack nucleation phase. Observations of fracture surfaces were also made by scanning electron microscopy (SEM). Subsurface cracking has been established as the initiation mechanism in ultra-high-cycle fatigue (>10 7 cycles). A surfacesubsurface transition in crack initiation location is described for the four low-alloy high-strength steels and a SG cast iron.

The major therapeutic goal for immune thrombocytopenia (ITP) is to restore normal platelet counts using drugs to promote platelet production or by interfering with mechanisms responsible for platelet destruction. 80% of patients possess anti-integrin αIIbβ3 (GPIIbIIIa) IgG autoantibodies causing platelet opsonization and phagocytosis. The spleen is considered the primary site of autoantibody production by autoreactive B cells and platelet destruction. The immediate failure in ~50% of patients to recover a normal platelet count after anti-CD20 Rituximab-mediated B cell depletion and splenectomy suggest that autoreactive, rituximab-resistant, IgG-secreting B cells (IgG-SC) reside in other anatomical compartments. We analyzed >3,300 single IgG-SC from spleen, bone marrow and/or blood of 27 patients with ITP revealing high inter-individual variability in affinity for GPIIbIIIa with variations over 3 logs. IgG-SC dissemination and range of affinities were however similar per patient. Longitudinal analysis of autoreactive IgG-SC upon treatment with anti-CD38 mAb daratumumab demonstrated variable outcomes, from complete remission to failure with persistence of high-affinity anti-GPIIbIIIa IgG-SC in the bone marrow. This study demonstrates the existence and dissemination of high-affinity autoreactive plasma cells in multiple anatomical compartments of patients with ITP that may cause the failure of current therapies.

Abstract-Model driven engineering advocates the separation of concerns during the design time of a system, which leads to the creation of several different models, using several different syntaxes. However, to reason on the overall system, we need to compose these models. Unfortunately, composition of models is done in an ad hoc way, preventing comparison, capitalisation and reuse of the composition operators. In order to improve comprehension and allow comparison of merging and weaving operators, we use category theory to propose a unified framework to formally define merging and weaving of models. We successfully use this framework to compare them, both through the way they are transformed in the formalism, and through several properties, such as completeness or nonredundancy. Finally, we validate this framework by checking that it correctly identifies three tools as performing merging or weaving of models.

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