Optimal topology design of continuum structures with stress concentration alleviation via level set method

Although the phenomenon of stress concentration is of paramount importance to engineers when they are designing load‐carrying structures, stiffness is often used as the solely concerned objective or constraint functional in the studies of optimal topology design of continuum structures. Sometimes this will lead to optimal designs with severe stress concentrations that may be highly responsible for the fracture, creep, and fatigue of structures. The aim of the present work is to develop some effective numerical techniques for designing stiff structures with less stress concentrations. This is achieved by introducing some specific stress measures, which are sensitive to the existence of high local stresses, in the problem formulation and resolving the corresponding optimization problem numerically in a level set framework. Our study indicates that with use of the proposed numerical schemes, some intrinsic difficulties in stress‐related topology optimization of continuum structures can be overcome in a natural way. Copyright © 2012 John Wiley & Sons, Ltd.     

Modelling HIV-1 2-LTR dynamics following raltegravir intensification

A model of reservoir activation and viral replication is introduced accounting for the production of 2-LTR HIV-1 DNA circles following antiviral intensification with the HIV integrase inhibitor raltegravir, considering contributions of de novo infection events and exogenous sources of infected cells, including quiescent infected cell activation. The model shows that a monotonic increase in measured 2-LTR concentration post intensification is consistent with limited de novo infection primarily maintained by sources of infected cells unaffected by raltegravir, such as quiescent cell activation, while a transient increase in measured 2-LTR concentration is consistent with significant levels of efficient (R₀ > 1) de novo infection. The model is validated against patient data from the INTEGRAL study and is shown to have a statistically significant fit relative to the null hypothesis of random measurement variation about a mean. We obtain estimates and confidence intervals for the model parameters, including 2-LTR half-life. Seven of the 13 patients with detectable 2-LTR concentrations from the INTEGRAL study have measured 2-LTR dynamics consistent with significant levels of efficient replication of the virus prior to treatment intensification.     

A methodology for user directed search in evolutionary design

A designer should be able to express their intentions with a design tool. This work describes a methodology that enables the architect to directly interact with the encoding of designs they find aesthetically pleasing. Broadening interaction beyond simple evaluation increases the amount of feedback and bias a user can apply to the search. Increased feedback will have the effect of directing the algorithm to more fruitful areas of the search space. We conduct trials on two interfaces for making localised changes to a design in order to evaluate if the user is capable of directing search. In addition, an examination of the locality of changes made by the users provides an insight into how they explore the search space. The results show that a suitably designed interface is capable of directing search and that the participants used different magnitudes of change during directed search.     

A linear-encoding model explains the variability of the target morphology in regeneration

A fundamental assumption of today''s molecular genetics paradigm is that complex morphology emerges from the combined activity of low-level processes involving proteins and nucleic acids. An inherent characteristic of such nonlinear encodings is the difficulty of creating the genetic and epigenetic information that will produce a given self-assembling complex morphology. This ‘inverse problem’ is vital not only for understanding the evolution, development and regeneration of bodyplans, but also for synthetic biology efforts that seek to engineer biological shapes. Importantly, the regenerative mechanisms in deer antlers, planarian worms and fiddler crabs can solve an inverse problem: their target morphology can be altered specifically and stably by injuries in particular locations. Here, we discuss the class of models that use pre-specified morphological goal states and propose the existence of a linear encoding of the target morphology, making the inverse problem easy for these organisms to solve. Indeed, many model organisms such as Drosophila, hydra and Xenopus also develop according to nonlinear encodings producing linear encodings of their final morphologies. We propose the development of testable models of regeneration regulation that combine emergence with a top-down specification of shape by linear encodings of target morphology, driving transformative applications in biomedicine and synthetic bioengineering.