Extracellular-matrix tethering regulates stem-cell fate.

To investigate how substrate properties influence stem-cell fate, we cultured single human epidermal stem cells on polydimethylsiloxane (PDMS) and polyacrylamide (PAAm) hydrogel surfaces, 0.1 kPa-2.3 MPa in stiffness, with a covalently attached collagen coating. Cell spreading and differentiation were unaffected by polydimethylsiloxane stiffness. However, cells on polyacrylamide of low elastic modulus (0.5 kPa) could not form stable focal adhesions and differentiated as a result of decreased activation of the extracellular-signal-related kinase (ERK)/mitogen-activated protein kinase (MAPK) signalling pathway. The differentiation of human mesenchymal stem cells was also unaffected by PDMS stiffness but regulated by the elastic modulus of PAAm. Dextran penetration measurements indicated that polyacrylamide substrates of low elastic modulus were more porous than stiff substrates, suggesting that the collagen anchoring points would be further apart. We then changed collagen crosslink concentration and used hydrogel-nanoparticle substrates to vary anchoring distance at constant substrate stiffness. Lower collagen anchoring density resulted in increased differentiation. We conclude that stem cells exert a mechanical force on collagen fibres and gauge the feedback to make cell-fate decisions.

The role of androgens in fetal growth: observational study in two genetic models of disordered androgen signalling.

OBJECTIVE: To examine the role of androgens on birth weight in genetic models of altered androgen signalling. SETTING: Cambridge Disorders of Sex Development (DSD) database and the Swedish national screening programme for congenital adrenal hyperplasia (CAH). PATIENTS: (1) 29 girls with XY karyotype and mutation positive complete androgen insensitivity syndrome (CAIS); (2) 43 girls and 30 boys with genotype confirmed CAH. MAIN OUTCOME MEASURES: Birth weight, birth weight-for-gestational-age (birth weight standard deviation score (SDS)) calculated by comparison with national references. RESULTS: Mean birth weight SDS in CAIS XY infants was higher than the reference for girls (mean, 95% CI: 0.4, 0.1 to 0.7; p=0.02) and was similar to the national reference for boys (0.1, -0.2 to 0.4). Birth weight SDS in CAH girls was similar to the national reference for girls (0.0, -0.2 to 0.2) and did not vary by severity of gene mutation. Birth weight SDS in CAH boys was also similar to the national reference for boys (0.2, -0.2 to 0.6). CONCLUSION: CAIS XY infants have a birth weight distribution similar to normal male infants and birth weight is not increased in infants with CAH. Alterations in androgen signalling have little impact on birth weight. Sex dimorphism in birth size is unrelated to prenatal androgen exposure.

Notch and strain rate sensitivity of non-crimp fabric composites

The notch and strain rate sensitivity of non-crimp glass fibre/vinyl-ester laminates subjected to uniaxial tensile loads has been investigated experimentally. Two sets of notch configurations were tested; one where circular holes were drilled and another where fragment simulating projectiles were fired through the plate creating a notch. Experiments were conducted for strain rates ranging from 10-4 s-1 to 102 s-1 using servo hydraulic machines. A significant increase in strength with increasing strain rate was observed for both notched and un-notched specimens. High speed photography revealed changes in failure mode, for certain laminate configurations, as the strain rate increased. The tested laminate configurations showed fairly small notch sensitivity for the whole range of strain rates. © 2008 Elsevier Ltd. All rights reserved.

Notch and strain rate sensitivity of non crimp fabric composites

The notch and strain rate sensitivity of non-crimp glass fibre/vinyl-ester laminates subjected to uniaxial tensile loads has been investigated experimentally. Two set of notch configurations were tested; one where circular holes were drilled and another where fragment simulating projectiles were fired through the plate creating a notch. Experiments were conducted for strain rates ranging from 10-4/s to 102/s using servo hydraulic machines. A significant increase in strength with increasing strain rate was observed for both notched and unnotched specimens. High speed photography revealed changes in failure mode, for certain laminate configurations, as the strain rate increased. The tested laminate configurations showed fairly small notch sensitivity for the whole range of strain rates.

A fracture criterion for the notch strength of high strength steels in the presence of hydrogen

High strength steels can suffer from a loss of ductility when exposed to hydrogen, and this may lead to sudden failure. The hydrogen is either accommodated in the lattice or is trapped at defects, such as dislocations, grain boundaries and carbides. The challenge is to identify the effect of hydrogen located at different sites upon the drop in tensile strength of a high strength steel. For this purpose, literature data on the failure stress of notched and un-notched steel bars are re-analysed; the bars were tested over a wide range of strain rates and hydrogen concentrations. The local stress state at failure has been determined by the finite element (FE) method, and the concentration of both lattice and trapped hydrogen is predicted using Oriani's theory along with the stress-driven diffusion equation. The experimental data are rationalised in terms of a postulated failure locus of peak maximum principal stress versus lattice hydrogen concentration. This failure locus is treated as a unique material property for the given steel and heat treatment condition. We conclude that the presence of lattice hydrogen increases the susceptibility to hydrogen embrittlement whereas trapped hydrogen has only a negligible effect. It is also found that the observed failure strength of hydrogen charged un-notched bars is less than the peak local stress within the notched geometries. Weakest link statistics are used to account for this stressed volume effect. © 2013 Elsevier Ltd.

Single event molecular signalling for estimation and control

Cell biology is characterised by low molecule numbers and coupled stochastic chemical reactions with intrinsic noise permeating and dominating the interactions between molecules. Recent work [9] has shown that in such environments there are hard limits on the accuracy with which molecular populations can be controlled and estimated. These limits are predicated on a continuous diffusion approximation of the target molecule (although the remainder of the system is non-linear and discrete). The principal result of [9] assumes that the birth rate of the signalling species is linearly dependent on the target molecule population size. In this paper, we investigate the situation when the entire system is kept discrete, and arbitrary non-linear coupling is allowed between the target molecule and downstream signalling molecules. In this case it is possible, by relying solely on the event triggered nature of control and signalling reactions, to define non-linear reaction rate modulation schemes that achieve improved performance in certain parameter regimes. These schemes would not appear to be biologically relevant, raising the question of what are an appropriate set of assumptions for obtaining biologically meaningful results. © 2013 EUCA.