Automated design of gene circuits with optimal mushroom-bifurcation behavior

Recent advances in synthetic biology are enabling exciting technologies, including the next generation of biosensors, the rational design of cell memory, modulated synthetic cell differentiation, and generic multifunctional biocircuits. These novel applications require the design of gene circuits leading to sophisticated behaviors and functionalities. At the same time, designs need to be kept minimal to avoid compromising cell viability. Bifurcation theory addresses such challenges by associating circuit dynamical properties with molecular details of its design. Nevertheless, incorporating bifurcation analysis into automated design processes has not been accomplished yet. This work presents an optimization-based method for the automated design of synthetic gene circuits with specified bifurcation diagrams that employ minimal network topologies. Using this approach, we designed circuits exhibiting the mushroom bifurcation, distilled the most robust topologies, and explored its multifunctional behavior. We then outline potential applications in biosensors, memory devices, and synthetic cell differentiation

Automatic synthesis of analog layout : a survey

A review of recent research in the automatic synthesis of physical geometry for analog integrated circuits is presented. On introduction, an explanation of the difficulties involved in analog layout as opposed to digital layout is covered. Review of the literature then follows. Emphasis is placed on the exposition of general methods for addressing problems specific to analog layout, with the details of specific systems only being given when they surve to illustrate these methods well. The conclusion discusses problems remaining and offers a prediction as to how technology will evolve to solve them. It is argued that although progress has been and will continue to be made in the automation of analog IC layout, due to fundamental differences in the nature of analog IC design as opposed to digital design, it should not be expected that the level of automation of the former will reach that of the latter any time soon

Developing new perfusion capabilities for ambr(R) micro and mini bioreactors

In recent years a strong trend towards intensified and continuous biopharmaceutical processing has gathered momentum, enabled by key cell culture technologies such as ATF and TFF. However, small-scale application has been limited to traditional benchtop bioreactor formats that are manually intensive, relatively low throughput and costly to operate. Automated high throughput single-use bioreactor systems have transformed fed-batch cell culture bioprocess development over the last decade and new capabilities to support perfusion culture in these micro and mini bioreactor formats could facilitate and accelerate an industry wide transition to intensified and continuous perfusion cell culture processes. Working in close collaboration with biopharm industry development partners, the design of the ‘ambr 250 high throughput’ bioreactor system has been modified to include hardware, software and single use components required to operate up to 24 parallel bioreactors with ATF or TFF cell retention modes. Iterative prototype testing with development partners has resulted in a novel ambr 250 system design capable of operating for extended culture durations and supporting high cell densities. In addition, a new Generation 2 ambr 15 cell culture system has been developed and demonstrated with technical capabilities facilitating perfusion mimic applications. Case studies will be presented on the utility of new ambr 15 system features for perfusion mimic (20-40M cell/ml) via cell settling and centrifugation methods, together with a range of industry case studies and novel performance data for the new ‘ambr 250 perfusion’ system (24 parallel perfusion cultures; \u3e30d; \u3e100M cell/ml; 0.25 vs. 5L; fully automated VCD control). As previously established with ambr systems for fed-batch processes, the new Generation 2 ambr 15 and ambr 250 perfusion systems together have the potential to provide the biopharm industry with a step change in perfusion process development capacity, enabling high throughput bioreactor screening and DoE optimization approaches for accelerated perfusion process development

Scalable macromodelling methodology for the efficient design of microwave filters

The complexity of the design of microwave filters increases steadily over the years. General design techniques available in literature yield relatively good initial designs, but electromagnetic (EM) optimisation is often needed to meet the specifications. Although interesting optimisation strategies exist, they depend on computationally expensive EM simulations. This makes the optimisation process time consuming. Moreover, brute force optimisation does not provide physical insights into the design and it is only applicable to one set of specifications. If the specifications change, the design and optimisation process must be redone. The authors propose a scalable macromodel-based design approach to overcome this. Scalable macromodels can be generated in an automated way. So far the inclusion of scalable macromodels in the design cycle of microwave filters has not been studied. In this study, it is shown that scalable macromodels can be included in the design cycle of microwave filters and re-used in multiple design scenarios at low computational cost. Guidelines to properly generate and use scalable macromodels in a filter design context are given. The approach is illustrated on a state-of-the-art microstrip dual-band bandpass filter with closely spaced pass bands and a complex geometrical structure. The results confirm that scalable macromodels are proper design tools and a valuable alternative to a computationally expensive EM simulator-based design flow

On the suitability and development of layout templates for analog layout reuse and layout-aware synthesis

Accelerating the synthesis of increasingly complex analog integrated circuits is key to bridge the widening gap between what we can integrate and what we can design while meeting ever-tightening time-to-market constraints. It is a well-known fact in the semiconductor industry that such goal can only be attained by means of adequate CAD methodologies, techniques, and accompanying tools. This is particularly important in analog physical synthesis (a.k.a. layout generation), where large sensitivities of the circuit performances to the many subtle details of layout implementation (device matching, loading and coupling effects, reliability, and area features are of utmost importance to analog designers), render complete automation a truly challenging task. To approach the problem, two directions have been traditionally considered, knowledge-based and optimization-based, both with their own pros and cons. Besides, recently reported solutions oriented to speed up the overall design flow by means of reuse-based practices or by cutting off time-consuming, error-prone spins between electrical and layout synthesis (a technique known as layout-aware synthesis), rely on a outstandingly rapid yet efficient layout generation method. This paper analyses the suitability of procedural layout generation based on templates (a knowledge-based approach) by examining the requirements that both layout reuse and layout-aware solutions impose, and how layout templates face them. The ability to capture the know-how of experienced layout designers and the turnaround times for layout instancing are considered main comparative aspects in relation to other layout generation approaches. A discussion on the benefit-cost trade-off of using layout templates is also included. In addition to this analysis, the paper delves deeper into systematic techniques to develop fully reusable layout templates for analog circuits, either for a change of the circuit sizing (i.e., layout retargeting) or a change of the fabrication process (i.e., layout migration). Several examples implemented with the Cadence's Virtuoso tool suite are provided as demonstration of the paper's contributions.Ministerio de Educación y Ciencia TEC2004-0175

Synthetic biology and microdevices : a powerful combination

Recent developments demonstrate that the combination of microbiology with micro-and nanoelectronics is a successful approach to develop new miniaturized sensing devices and other technologies. In the last decade, there has been a shift from the optimization of the abiotic components, for example, the chip, to the improvement of the processing capabilities of cells through genetic engineering. The synthetic biology approach will not only give rise to systems with new functionalities, but will also improve the robustness and speed of their response towards applied signals. To this end, the development of new genetic circuits has to be guided by computational design methods that enable to tune and optimize the circuit response. As the successful design of genetic circuits is highly dependent on the quality and reliability of its composing elements, intense characterization of standard biological parts will be crucial for an efficient rational design process in the development of new genetic circuits. Microengineered devices can thereby offer a new analytical approach for the study of complex biological parts and systems. By summarizing the recent techniques in creating new synthetic circuits and in integrating biology with microdevices, this review aims at emphasizing the power of combining synthetic biology with microfluidics and microelectronics

Final report: Workshop on: Integrating electric mobility systems with the grid infrastructure

EXECUTIVE SUMMARY: This document is a report on the workshop entitled “Integrating Electric Mobility Systems with the Grid Infrastructure” which was held at Boston University on November 6-7 with the sponsorship of the Sloan Foundation. Its objective was to bring together researchers and technical leaders from academia, industry, and government in order to set a short and longterm research agenda regarding the future of mobility and the ability of electric utilities to meet the needs of a highway transportation system powered primarily by electricity. The report is a summary of their insights based on workshop presentations and discussions. The list of participants and detailed Workshop program are provided in Appendices 1 and 2. Public and private decisions made in the coming decade will direct profound changes in the way people and goods are moved and the ability of clean energy sources – primarily delivered in the form of electricity – to power these new systems. Decisions need to be made quickly because of rapid advances in technology, and the growing recognition that meeting climate goals requires rapid and dramatic action. The blunt fact is, however, that the pace of innovation, and the range of business models that can be built around these innovations, has grown at a rate that has outstripped our ability to clearly understand the choices that must be made or estimate the consequences of these choices. The group of people assembled for this Workshop are uniquely qualified to understand the options that are opening both in the future of mobility and the ability of electric utilities to meet the needs of a highway transportation system powered primarily by electricity. They were asked both to explain what is known about the choices we face and to define the research issues most urgently needed to help public and private decision-makers choose wisely. This report is a summary of their insights based on workshop presentations and discussions. New communication and data analysis tools have profoundly changed the definition of what is technologically possible. Cell phones have put powerful computers, communication devices, and position locators into the pockets and purses of most Americans making it possible for Uber, Lyft and other Transportation Network Companies to deliver on-demand mobility services. But these technologies, as well as technologies for pricing access to congested roads, also open many other possibilities for shared mobility services – both public and private – that could cut costs and travel time by reducing congestion. Options would be greatly expanded if fully autonomous vehicles become available. These new business models would also affect options for charging electric vehicles. It is unclear, however, how to optimize charging (minimizing congestion on the electric grid) without increasing congestion on the roads or creating significant problems for the power system that supports such charging capacity. With so much in flux, many uncertainties cloud our vision of the future. The way new mobility services will reshape the number, length of trips, and the choice of electric vehicle charging systems and constraints on charging, and many other important behavioral issues are critical to this future but remain largely unknown. The challenge at hand is to define plausible future structures of electric grids and mobility systems, and anticipate the direct and indirect impacts of the changes involved. These insights can provide tools essential for effective private ... [TRUNCATED]Workshop funded by the Alfred P. Sloan Foundatio