Somatic mutations in receptor tyrosine kinase FGFR3 cause excessive cell proliferation, leading to cancer or skin overgrowth. Remarkably, the same mutations inhibit chondrocyte proliferation and ...differentiation in developing bones, resulting in skeletal dysplasias, such as hypochondroplasia, achondroplasia, SADDAN and thanatophoric dysplasia. A similar phenotype is observed in Noonan syndrome, Leopard syndrome, hereditary gingival fibromatosis, neurofibromatosis type 1, Costello syndrome, Legius syndrome and cardiofaciocutaneous syndrome. Collectively termed RASopathies, the latter syndromes are caused by germline mutations in components of the RAS/ERK MAP kinase signaling pathway. This article considers the evidence suggesting that FGFR3 activation in chondrocytes mimics the activation of major oncogenes signaling via the ERK pathway. Subsequent inhibition of chondrocyte proliferation in FGFR3-related skeletal dysplasias and RASopathies is proposed to result from activation of defense mechanisms that originally evolved to safeguard mammalian organisms against cancer.
The process of breathing is interpreted as forced periodic motion of a viscoelastic deformable porous medium with gas exchange between the interior and exterior, driven by forces acting on its ...boundary. Energy and mass are supplied to the system by muscle activity, and also possibly by external ventilation in case of assisted breathing for patients with lungs insufficiency. Hysteresis in the pressure–volume characteristic and possible degeneracy of the pressure-dependent terms are also taken into account. The main result consists in proving the existence of a periodic solution under arbitrary periodic forcing in suitable function spaces.
Piezomicropositioning actuators, which are widely used in micropositioning applications, exhibit strong rate-dependent hysteresis nonlinearities that affect the accuracy of these micropositioning ...systems when used in open-loop control systems, and may also even lead to system instability of closed-loop control systems. Feedback control techniques could compensate for the rate-dependent hysteresis in piezomicropositioning actuators. However, accurate sensors over a wide range of excitation frequencies and the feedback control techniques inserted in the closed-loop control systems may limit the use of the piezomicropositioning and nanopositioning systems in different micropositioning and nanopositioning applications. We show that open-loop control techniques, also called feedforward techniques, can compensate for rate-dependent hysteresis nonlinearities over different excitation frequencies. An inverse rate-dependent Prandtl-Ishlinskii model is utilized for feedforward compensation of the rate-dependent hysteresis nonlinearities in a piezomicropositioning stage. The exact inversion of the rate-dependent model holds under the condition that the distances between the thresholds do not decrease in time. The inverse of the rate-dependent model is applied as a feedforward compensator to compensate for the rate-dependent hysteresis nonlinearities of a piezomicropositioning actuator at a range of different excitation frequencies between 0.05-100 Hz. The results show that the inverse compensator suppresses the rate-dependent hysteresis nonlinearities, and the maximum positioning error in the output displacement at different excitation frequencies.
To the Editor:
Savarirayan et al. (July 4 issue)
1
report increased skeletal growth in patients with achondroplasia (a common type of dwarfism caused by activating mutations in the tyrosine kinase ...fibroblast growth factor receptor 3 gene
FGFR3
) who received vosoritide, a stable analogue of C-type natriuretic peptide. Their study is a breakthrough in treatment for achondroplasia, and it offers an intriguing possibility of broader clinical applications. FGFR3 is a negative regulator of growth, as evidenced by skeletal overgrowth in mice with deleted
fgfr3
and tall stature in humans with loss-of-function mutations in
FGFR3
.
2
In contrast, C-type natriuretic peptide increases growth . . .
Inverse compensation of rate-dependent Prandtl–Ishlinskii operators with finitely many thresholds can be carried out explicitly under some structural conditions. However, if the number of thresholds ...is very high, the formulas become complicated. A simple and elegant framework for the investigation of such problems encompasses a recently proposed extension of the class of rate-dependent Prandtl–Ishlinskii operators to the case of a whole continuum of play operators with time-dependent thresholds. Indeed, such a theory allows for reducing the number of necessary thresholds in the compensation procedure and estimating the errors of the memory-discrete compensation in terms of the distance between the thresholds and weights of the individual plays. Following these results, our goal in this work is the validation of these theoretical models via numerical simulations and experimental results. In particular, we show that high accuracy of the hysteresis compensation algorithm can be achieved even with a relatively small number of thresholds.
•Inverse compensation of rate-dependent Prandtl–Ishlinskii operators with less operators.•The theory allows for reducing the number of necessary thresholds.•Validation of these theoretical models via numerical simulations and experimental results.•High accuracy of the hysteresis compensation algorithm with a relatively small number of thresholds.
•Mechanical behaviour of a polymeric foam at large strain and in a wide range of strain rates represented by a visco-hyperelastic model.•Straightforward parameter identification procedure consisting ...in combining viscoelastic tests at small strain from DMA with cyclic tests at large strain from UTM.•Formulation making use of the continuous relaxation time spectrum and nonlinear setting of large strains.•Identification procedure able to take into account variability of experimental DMA tests.
The prediction of compressive properties of foams at large strains and in a wide range of strain rates is still an open issue. In this work we propose a visco-hyperelastic formulation, suitable for large finite strain applications, for the prediction of the compressive response of foams that takes into account the viscoelasticity of the polymer, nonlinear damping, nonlinear behaviour of the cellular structure and effect of gas permeability through the pores at high strain rates. A mathematical expression of the continuous relaxation spectrum is proposed to model the viscoelastic behaviour of the polymer. The relaxation spectrum is then discretized with the desired accuracy required for the subsequent numerical simulations. The model parameters are identified by coupling dynamic measurements at small strain with static ones at large strain. The results are validated by comparing numerical predictions with experimental data from compressive tests up to 50% strain performed at strain rates spanning over 6 degrees of magnitude.
A problem of motion of a piezoelectric actuator in contact with an elasto-plastic obstacle is reformulated as a PDE in one spatial dimension with hysteresis in the bulk and on the contact boundary. ...The model is shown to dissipate energy in agreement with the principles of thermodynamics. The main result includes existence, uniqueness, and continuous data dependence of solutions.
A controllability problem for a diffusion equation with a complex hysteresis operator is proposed here and consists in finding a control which guarantees that the solution reaches a desired value at ...a given time. We propose a constructive method based on a two-parameter penalty argument. One small parameter penalizes the distance of the solution at final time from the expected value, the second one is used to approximate the underlying rate independent variational inequalities in the hysteresis term by smooth viscous constitutive relations. We prove that a solution to the controllability problem can be obtained by passing to the limit in a doubly degenerate control system, and the convergence is strong in space and uniform in time.
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