Synthetic Biology promises low-cost, exponentially scalable products and global health solutions in the form of self-replicating organisms, or “living devices.” As these promises are realized, proof-of-concept systems will gradually migrate from tightly regulated laboratory or industrial environments into private spaces as, for instance, probiotic health products, food, and even do-it-yourself bioengineered systems. What additional steps, if any, should be taken before releasing engineered self-replicating organisms into a broader user space? In this review, we explain how studies of genetically modified organisms lay groundwork for the future landscape of biosafety. Early in the design process, biological engineers are anticipating potential hazards and developing innovative tools to mitigate risk. Here, we survey lessons learned, ongoing efforts to engineer intrinsic biocontainment, and how different stakeholders in synthetic biology can act to accomplish best practices for biosafety.
Recent advances in nanophotonic light trapping open up the new gateway to enhance the absorption of solar energy beyond the so called Yablonovitch Limit. It addresses the urgent needs in developing low cost thin-film solar photovoltaic technologies. However, current design strategy mainly relies on the parametric approach that is subject to the predefined topological design concepts based on physical intuition. Incapable of dealing with the topological variation severely constrains the design of optimal light trapping structure. Inspired by natural evolution process, here we report a design framework driven by topology optimization based on genetic algorithms to achieve a highly efficient light trapping structure. It has been demonstrated that the optimal light trapping structures obtained in this study exhibit more than 3-fold increase over the Yablonovitch Limit with the broadband absorption efficiency of 48.1%, beyond the reach of intuitive designs.
User-centred design (UCD) is a type of user interface design in which the needs and desires of users are taken into account at each stage of the design process for a service or product; often for software applications and websites. Its goal is to facilitate the design of software that is both useful and easy to use. To achieve this, you must characterise users' requirements, design suitable interactions to meet their needs, and test your designs using prototypes and real life scenarios.For bioinformatics, there is little practical information available regarding how to carry out UCD in practice. To address this we describe a complete, multi-stage UCD process used for creating a new bioinformatics resource for integrating enzyme information, called the Enzyme Portal (http://www.ebi.ac.uk/enzymeportal). This freely-available service mines and displays data about proteins with enzymatic activity from public repositories via a single search, and includes biochemical reactions, biological pathways, small molecule chemistry, disease information, 3D protein structures and relevant scientific literature.We employed several UCD techniques, including: persona development, interviews, ‘canvas sort’ card sorting, user workflows, usability testing and others. Our hope is that this case study will motivate the reader to apply similar UCD approaches to their own software design for bioinformatics. Indeed, we found the benefits included more effective decision-making for design ideas and technologies; enhanced team-working and communication; cost effectiveness; and ultimately a service that more closely meets the needs of our target audience.
Small-diameter (<4 mm) vascular constructs are urgently needed for patients requiring replacement of their peripheral vessels. However, successful development of constructs remains a significant challenge. In this study, we successfully developed small-diameter vascular constructs with high patency using our integrally designed computer-controlled bioreactor system. This computer-controlled bioreactor system can confer physiological mechanical stimuli and fluid flow similar to physiological stimuli to the cultured grafts. The medium circulating system optimizes the culture conditions by maintaining fixed concentration of O(2) and CO(2) in the medium flow and constant delivery of nutrients and waste metabolites, as well as eliminates the complicated replacement of culture medium in traditional vascular tissue engineering. Biochemical and mechanical assay of newly developed grafts confirm the feasibility of the bioreactor system for small-diameter vascular engineering. Furthermore, the computer-controlled bioreactor is superior for cultured cell proliferation compared with the traditional non-computer-controlled bioreactor. Specifically, our novel bioreactor system may be a potential alternative for tissue engineering of large-scale small-diameter vascular vessels for clinical use.
MOTIVATION: Biochemical reaction networks in the form of coupled ordinary differential equations (ODEs) provide a powerful modeling tool for understanding the dynamics of biochemical processes. During the early phase of modeling, scientists have to deal with a large pool of competing nonlinear models. At this point, discrimination experiments can be designed and conducted to obtain optimal data for selecting the most plausible model. Since biological ODE models have widely distributed parameters due to, e.g., biologic variability or experimental variations, model responses become distributed. Therefore, a robust optimal experimental design (OED) for model discrimination can be used to discriminate models based on their response probability distribution functions (PDFs). RESULTS: In this work we present an optimal control based methodology for designing optimal stimulus experiments aimed at robust model discrimination. For estimating the time-varying model response PDF, which results from the nonlinear propagation of the parameter PDF under the ODE dynamics, we suggest using the Sigma-Point approach. Using the model overlap (expected likelihood) as a robust discrimination criterion to measure dissimilarities between expected model response PDFs, we benchmark the proposed nonlinear design approach against linearization with respect to prediction accuracy and design quality for two nonlinear biological reaction networks. As we show, the Sigma-Point outperforms the linearization approach in the case of widely distributed parameter sets and/or existing multiple steady states. Since the Sigma-Point approach scales linearly with the number of model parameter, it can be applied to large systems for robust experimental planing. AVAILABILITY: An implementation of the method in MATLAB/AMPL is available at http://www.uni-magdeburg.de/ivt/svt/person/rf/roed.html. CONTACT: email@example.com SUPPLEMENTARY INFORMATION: Supplementary details and discussions are available at Bioinformatics online.
Captive breeding and rearing are central elements in conservation, management, and recovery planning for many endangered species including Rio Grande Silvery Minnow, a North American freshwater cyprinid. Traditionally, the sole purpose of hatcheries was to produce as many fish as feasible for stocking and harvest. Production quotas are also an important consideration in hatchery programs for endangered species, but they must also maintain and maximize genetic diversity of fish produced through implementation of best breeding practices. Here, we assessed genetic outcomes and measures of productivity (number of eggs and larval viability) for three replicates of three mating designs that are used for this small, pelagic-spawning fish. These were 1) monogamous mating, 2) hormone-induced communal spawning, and 3) environmentally cued communal spawning. A total of 180 broodstock and 450 progeny were genotyped. Genetic diversity and egg productivity did not differ significantly among spawning designs (H e : F = 0.52, P = 0.67; H o : F = 0.12, P = 0.89; number of eggs: F = 3.59, P = 0.09), and there was evidence for variance in reproductive success among individuals in all three designs. Allelic richness declined from the broodstock to progeny generation in all breeding designs. There was no significant difference in the genetic effective size (regardless of the method used) among designs. Significantly more viable eggs were produced in environmentally cued communal spawn compared to the alternative strategies (F = 5.72, P = 0.04), but this strategy is the most difficult to implement.
The accuracy of prostheses affects clinical success and is, in turn, affected by the accuracy of the scanner and CAD programs. Thus, their accuracy is important. The first aim of this study was to evaluate the accuracy of an intraoral scanner with active triangulation (Cerec Omnicam), an intraoral scanner with a confocal laser (3Shape Trios), and an extraoral scanner with active triangulation (D810). The second aim of this study was to compare the accuracy of the digital crowns designed with two different scanner/CAD combinations. The accuracy of the intraoral scanners and extraoral scanner was clinically acceptable. Marginal and internal fit of the digital crowns fabricated using the intraoral scanner and CAD programs were inferior to those fabricated using the extraoral scanner and CAD programs.
This study presents design, digital implementation and performance validation of a lead-lag controller for a 2-degree-of-freedom (DOF) translational optical image stabilizer (OIS) installed with a digital image sensor in mobile camera phones. Nowadays, OIS is an important feature of modern commercial mobile camera phones, which aims to mechanically reduce the image blur caused by hand shaking while shooting photos. The OIS developed in this study is able to move the imaging lens by actuating its voice coil motors (VCMs) at the required speed to the position that significantly compensates for imaging blurs by hand shaking. The compensation proposed is made possible by first establishing the exact, nonlinear equations of motion (EOMs) for the OIS, which is followed by designing a simple lead-lag controller based on established nonlinear EOMs for simple digital computation via a field-programmable gate array (FPGA) board in order to achieve fast response. Finally, experimental validation is conducted to show the favorable performance of the designed OIS; i.e., it is able to stabilize the lens holder to the desired position within 0.02 s, which is much less than previously reported times of around 0.1 s. Also, the resulting residual vibration is less than 2.2-2.5 μm, which is commensurate to the very small pixel size found in most of commercial image sensors; thus, significantly minimizing image blur caused by hand shaking.
Tools to systematically reprogram cellular behavior are crucial to address pressing challenges in manufacturing, the environment, or healthcare. Recombinases can very efficiently encode Boolean and history-dependent logic in many species, yet current designs are performed on a case-by-case basis, limiting their scalability and requiring time-consuming optimization. Here we present an automated workflow for designing recombinase logic devices executing Boolean functions. Our theoretical framework uses a reduced library of computational modules distributed into different cellular subpopulations which are then composed in various manners to implement all desired logic functions at the multicellular level. Our design platform called CALIN (Composable Asynchronous Logic using Integrase Networks) is broadly accessible via a web server taking truth tables as inputs and providing corresponding DNA designs and sequences as outputs (available at: http:/synbio.cbs.cnrs.fr/calin).
The purpose of the current work was to study the pattern and dynamics of biofilm formation in clinical isolates of Staphylococcus aureus and S. epidermidis in the presence of 10 antibiotics with different action mechanisms.