Residents and migrants use their environment very differently – the former remain in a given habitat throughout the year, whereas the latter are repeatedly confronted with unfamiliar environments. The difference in ecology may influence decision‐making processes whether, when and to which extent to explore an unfamiliar environment. We have investigated spatial neophobia and spatial neophilia – two important novelty reactions that may underlie decision‐making – in two closely related warbler species, the resident Sardinian warbler and the migratory garden warbler. Individuals of both species could access an unfamiliar room from a familiar cage. We assessed the conflict between the motivation to enter the novel room (spatial neophilia) and the motivation to avoid it (spatial neophobia) as the frequency and duration of perching on the dowel in the cage, which led to the unfamiliar room before entering it. Furthermore, we measured the latency to enter the novel room and compared the number of individuals of each species entering the room. The combination of the parameters measured allowed assessing the degree of both neophobia and neophilia. Finally, the time spent on each branch in the novel room was taken as a measure for spatial exploration. The migrants perched less often and spent less time on the dowel leading to the room, and entered the novel room quicker than the residents. Additionally, more migrants than residents entered the room. The migrants’ decision to enter the novel room can best be explained with a combination of low spatial neophobia coupled with high spatial neophilia, whereas the residents’ decision‐making is best explained with high spatial neophobia coupled with high spatial neophilia. The differences in neophobia support the migrant‐neophobia hypothesis. When in the room, the migrants spent less time on each branch than the residents, possibly indicating that the former collect less spatial information than the latter.
This paper analyses the progressive mixed mode delamination failure in unidirectional and multidirectional composite laminates using fracture experiments, finite element (FE) simulations and an analytical solution. The numerical model of the laminate is described as an assembly of damageable layers and bilinear interface elements subjected to mixed mode bending. The analytical approach is used to estimate the total mixed mode and decomposed fracture energies for laminates with different stacking sequences, which is also validated through experiments. It is concluded that the interlaminar fracture toughness of multidirectional laminates is considerably higher than that of the unidirectional ones. The effect of initial interfacial stiffness and element size is studied and it is also shown that their value must not exceed a definite limit for the numerical simulations to converge. The model can also be further extended to simulate the mixed mode fracture in hybrid fiber metal laminates.
ImportanceAutoimmune disorders can affect various organs and if refractory, can be life threatening. Recently, CD19-targeting–chimeric antigen receptor (CAR) T cells were efficacious as an immune suppressive agent in 6 patients with refractory systemic lupus erythematosus and in 1 patient with antisynthetase syndrome.ObjectiveTo test the safety and efficacy of CD19-targeting CAR T cells in a patient with severe antisynthetase syndrome, a complex autoimmune disorder with evidence for B- and T-cell involvement.Design, Setting, and ParticipantsThis case report describes a patient with antisynthetase syndrome with progressive myositis and interstitial lung disease refractory to available therapies (including rituximab and azathioprine), who was treated with CD19-targeting CAR T cells in June 2022 at University Hospital Tübingen in Tübingen, Germany, with the last follow-up in February 2023. Mycophenolate mofetil was added to the treatment to cotarget CD8+ T cells, hypothesized to contribute to disease activity.ExposurePrior to treatment with CD19-targeting CAR T cells, the patient received conditioning therapy with fludarabine (25 mg/m2 [5 days before until 3 days before]) and cyclophosphamide (1000 mg/m2 [3 days before]) followed by infusion of CAR T cells (1.23×106/kg [manufactured by transduction of autologous T cells with a CD19 lentiviral vector and amplification in the CliniMACS Prodigy system]) and mycophenolate mofetil (2 g/d) 35 days after CD19-targeting CAR T-cell infusion.Main Outcomes and MeasuresThe patient’s response to therapy was followed by magnetic resonance imaging of the thigh muscle, Physician Global Assessment, functional muscle and pulmonary tests, and peripheral blood quantification of anti-Jo-1 antibody levels, lymphocyte subsets, immunoglobulins, and serological muscle enzymes.ResultsRapid clinical improvement was observed after CD19-targeting CAR T-cell infusion. Eight months after treatment, the patient’s scores on the Physician Global Assessment and muscle and pulmonary function tests improved, and there were no detectable signs of myositis on magnetic resonance imaging. Serological muscle enzymes (alanine aminotransferase, aspartate aminotransferase, creatinine kinase, and lactate dehydrogenase), CD8+ T-cell subsets, and inflammatory cytokine secretion in the peripheral blood mononuclear cells (interferon gamma, interleukin 1 [IL-1], IL-6, and IL-13) were all normalized. Further, there was a reduction in anti-Jo-1 antibody levels and a partial recovery of IgA (to 67% of normal value), IgG (to 87%), and IgM (to 58%).Conclusions and RelevanceCD19-targeting CAR T cells directed against B cells and plasmablasts deeply reset B-cell immunity. Together with mycophenolate mofetil, CD19-targeting CAR T cells may break pathologic B-cell, as well as T-cell responses, inducing remission in refractory antisynthetase syndrome.
At room temperature the macroscopic tensile behavior of TiAl alloys is extremely microstructure sensitive. In general the microstructures of TiAl alloys are heterogeneous at micro and meso scale. The materials micromechanisms that occur at different length scale have to be linked for a proper understanding of the macroscopic response. In order to explore those micromechanisms, methodologies combining advanced experimental and computational analysis have been proposed. Linking microstructure and properties using a two-scale numerical model we are able to explain the stress-strain and hardening behavior of this alloy.
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