Infinite-contrast periodic composites with strongly nonlinear behavior: Effective-medium theory versus full-field simulations

This paper presents a combined numerical-theoretical study of the macroscopic behavior and local field distributions in a special class of two-dimensional periodic composites with viscoplastic phases. The emphasis is on strongly nonlinear materials containing pores or rigid inclusions. Full-field numerical simulations are carried out using a Fast-Fourier Transform algorithm [H. Moulinec, P. Suquet, C. R. Acad. Sci. Paris II 318, 1417 (1994)] Moulinec, P. Suquet, C. R. Acad. Sci. Paris II 318, 1417 (1994), while the theoretical results are obtained by means of the `second-order' nonlinear homogenization method [P. Ponte Castaneda, J. Mech. Phys. Solids 50, 737 (2002)]. The effect of nonlinearity and inclusion concentration is investigated in the context of power-law (with strain-rate sensitivity m) behavior for the matrix phase under in-plane shear loadings. Overall, the `second-order' estimates are found to be in good agreement with the numerical simulations, with the best agreement for the rigidly reinforced materials. For the porous systems, as the nonlinearity increases (m decreases), the strain field is found to localize along shear bands passing through the voids (the strain fluctuations becoming unbounded) and the effective stress exhibits a singular behavior in the dilute limit. More specifically, for small porosities and fixed nonlinearity m>0, the effective stress decreases linearly with increasing porosity. However, for ideally plastic behavior (m = 0), the dependence on porosity becomes non-analytic. On the other hand, for rigidly-reinforced composites, the strain field adopts a tile pattern with bounded strain fluctuations, and no singular behavior is observed (to leading order) in the dilute limit.Comment: 28 pages, 28 B&W figures, 2 tables of color maps, to be published in International Journal of Solids and Structures (in press

Toca-1 Mediates Cdc42-Dependent Actin Nucleation by Activating the N-WASP-WIP Complex

AbstractAn important signaling pathway to the actin cytoskeleton links the Rho family GTPase Cdc42 to the actin-nucleating Arp2/3 complex through N-WASP. Nevertheless, these previously identified components are not sufficient to mediate Cdc42-induced actin polymerization in a physiological context. In this paper, we describe the biochemical purification of Toca-1 (transducer of Cdc42-dependent actin assembly) as an essential component of the Cdc42 pathway. Toca-1 binds both N-WASP and Cdc42 and is a member of the evolutionarily conserved PCH protein family. Toca-1 promotes actin nucleation by activating the N-WASP-WIP/CR16 complex, the predominant form of N-WASP in cells. Thus, the cooperative actions of two distinct Cdc42 effectors, the N-WASP-WIP complex and Toca-1, are required for Cdc42-induced actin assembly. These findings represent a significantly revised view of Cdc42-signaling and shed light on the pathogenesis of Wiskott-Aldrich syndrome

Factors influencing the implementation, adoption, use, sustainability and scalability of eLearning for family medicine specialty training:A systematic review protocol

Background In 2013, there was a shortage of approximately 7.2 million health workers worldwide, which is larger among family physicians than among specialists. eLearning could provide a potential solution to some of these global workforce challenges. However, there is little evidence on factors facilitating or hindering implementation, adoption, use, scalability and sustainability of eLearning. This review aims to synthesise results from qualitative and mixed methods studies to provide insight on factors influencing implementation of eLearning for family medicine specialty education and training. Additionally, this review aims to identify the actions needed to increase effectiveness of eLearning and identify the strategies required to improve eLearning implementation, adoption, use, sustainability and scalability for family medicine speciality education and training. Methods A systematic search will be conducted across a range of databases for qualitative studies focusing on experiences, barriers, facilitators, and other factors related to the implementation, adoption, use, sustainability and scalability of eLearning for family medicine specialty education and training. Studies will be synthesised by using the framework analysis approach. Discussion This study will contribute to the evaluation of eLearning implementation, adoption, use, sustainability and scalability for family medicine specialty training and education and the development of eLearning guidelines for postgraduate medical education

The Adaptor Molecule Nck Localizes the WAVE Complex to Promote Actin Polymerization during CEACAM3-Mediated Phagocytosis of Bacteria

Background: CEACAM3 is a granulocyte receptor mediating the opsonin-independent recognition and phagocytosis of human-restricted CEACAM-binding bacteria. CEACAM3 function depends on an intracellular immunoreceptor tyrosine-based activation motif (ITAM)-like sequence that is tyrosine phosphorylated by Src family kinases upon receptor engagement. The phosphorylated ITAM-like sequence triggers GTP-loading of Rac by directly associating with the guanine nucleotide exchange factor (GEF) Vav. Rac stimulation in turn is critical for actin cytoskeleton rearrangements that generate lamellipodial protrusions and lead to bacterial uptake. Principal Findings: In our present study we provide biochemical and microscopic evidence that the adaptor proteins Nck1 and Nck2, but not CrkL, Grb2 or SLP-76, bind to tyrosine phosphorylated CEACAM3. The association is phosphorylation-dependent and requires the Nck SH2 domain. Overexpression of the isolated Nck1 SH2 domain, RNAi-mediated knock-down of Nck1, or genetic deletion of Nck1 and Nck2 interfere with CEACAM3-mediated bacterial internalization and with the formation of lamellipodial protrusions. Nck is constitutively associated with WAVE2 and directs the actin nucleation promoting WAVE complex to tyrosine phosphorylated CEACAM3. In turn, dominant-negative WAVE2 as well as shRNA-mediated knock-down of WAVE2 or the WAVE-complex component Nap1 reduce internalization of bacteria. Conclusions: Our results provide novel mechanistic insight into CEACAM3-initiated phagocytosis. We suggest that the CEACAM3 ITAM-like sequence is optimized to co-ordinate a minimal set of cellular factors needed to efficiently trigger actin-based lamellipodial protrusions and rapid pathogen engulfment

Rac1-Dependent Collective Cell Migration Is Required for Specification of the Anterior-Posterior Body Axis of the Mouse

Live imaging and analysis of conditional mutants show that the embryonic organizer that determines the anterior-posterior axis in the mouse embryo moves by Rac1-dependent collective cell migration