66,719 research outputs found

    A Novel Approach to Small Form-Factor Spacecraft Structures for Usage in Precision Optical Payloads

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    Precision optical payloads will soon experience a boom in manufacturing scale with the onset of proliferated satellite constellation concepts. Presently, the cost of assembly for a single unit can reach upwards of $500,000. Reduction in recurring engineering and assembly complexity can reduce this figure by up to two orders of magnitude. This paper discusses one potential solution which relies on consistent structural components that are easily manufactured in bulk quantities to facilitate general uses while also enabling high-precision mounting in designated payload slots. This proposed approach combines standardized struts and panels able to be connected and stacked in a variety of ways to form a modular structure from 1U subsections. For the subsections in need of higher precision, slots are milled and reamed from the same standard panel. Within these slots, card-like brackets are mounted to within 10 micrometer precision with the use of low-tolerance gauge spheres. A technique called “screw-pulling” secures these brackets such that the gauge spheres act as nearly single-point-of-contact datums. This approach allows payloads to be tested externally with minimal alignment shifts when re-integrated into the structure and is demonstrated with a 2.2 μm pixel size CMOS sensor and a 23 mm focal length lens

    The imperfect hiding : some introductory concepts and preliminary issues on modularity

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    In this work we present a critical assessment of some problems and open questions on the debated notion of modularity. Modularity is greatly in fashion nowadays, being often proposed as the new approach to complex artefact production that enables to combine fast innovation pace, enhanced product variety and reduced need for co-ordination. In line with recent critical assessments of the managerial literature on modularity, we sustain that modularity is only one among several arrangements to cope with the complexity inherent in most high-technology artefact production, and by no means the best one. We first discuss relations between modularity and the broader (and much older within economics) notion of division of labour. Then we sustain that a modular approach to labour division aimed at eliminating technological interdependencies between components or phases of a complex production process may have, as a by-product, the creation of other types of interdependencies which may subsequently result in inefficiencies of various types. Hence, the choice of a modular design strategy implies the resolution of various tradeoffs. Depending on how such tradeoffs are solved, different organisational arrangements may be created to cope with ‘residual’ interdependencies. Hence, there is no need to postulate a perfect isomorphism, as some recent literature has proposed, between modularity at the product level and modularity at the organisational level

    Development of novel orthogonal genetic circuits, based on extracytoplasmic function (ECF) σ factors

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    The synthetic biology field aims to apply the engineering 'design-build-test-learn' cycle for the implementation of synthetic genetic circuits modifying the behavior of biological systems. In order to reach this goal, synthetic biology projects use a set of fully characterized biological parts that subsequently are assembled into complex synthetic circuits following a rational, model-driven design. However, even though the bottom-up design approach represents an optimal starting point to assay the behavior of the synthetic circuits under defined conditions, the rational design of such circuits is often restricted by the limited number of available DNA building blocks. These usually consist only of a handful of transcriptional regulators that additionally are often borrowed from natural biological systems. This, in turn, can lead to cross-reactions between the synthetic circuit and the host cell and eventually to loss of the original circuit function. Thus, one of the challenges in synthetic biology is to design synthetic circuits that perform the designated functions with minor cross-reactions (orthogonality). To overcome the restrictions of the widely used transcriptional regulators, this project aims to apply extracytoplasmic function (ECF) σ factors in the design novel orthogonal synthetic circuits. ECFs are the smallest and simplest alternative σ factors that recognize highly specific promoters. ECFs represent one of the most important mechanisms of signal transduction in bacteria, indeed, their activity is often controlled by anti-σ factors. Even though it was shown that the overexpression of heterologous anti-σ factors can generate an adverse effect on cell growth, they represent an attractive solution to control ECF activity. Finally, to date, we know thousands of ECF σ factors, widespread among different bacterial phyla, that are identifiable together with the cognate promoters and anti-σ factors, using bioinformatic approaches. All the above-mentioned features make ECF σ factors optimal candidates as core orthogonal regulators for the design of novel synthetic circuits. In this project, in order to establish ECF σ factors as standard building blocks in the synthetic biology field, we first established a high throughput experimental setup. This relies on microplate reader experiments performed using a highly sensitive luminescent reporter system. Luminescent reporters have a superior signal-to-noise ratio when compared to fluorescent reporters since they do not suffer from the high auto-fluorescence background of the bacterial cell. However, they also have a drawback represented by the constant light emission that can generate undesired cross-talk between neighboring wells on a microplate. To overcome this limitation, we developed a computational algorithm that corrects for luminescence bleed-through and estimates the “true” luminescence activity for each well of a microplate. We show that the correcting algorithm preserves low-level signals close to the background and that it is universally applicable to different experimental conditions. In order to simplify the assembly of large ECF-based synthetic circuits, we designed an ECF toolbox in E. coli. The toolbox allows for the combinatorial assembly of circuits into expression vectors, using a library of reusable genetic parts. Moreover, it also offers the possibility of integrating the newly generated synthetic circuits into four different phage attachment (att) sites present in the genome of E. coli. This allows for a flawless transition between plasmid-encoded and chromosomally integrated genetic circuits, expanding the possible genetic configurations of a given synthetic construct. Moreover, our results demonstrate that the four att sites are orthogonal in terms of the gene expression levels of the synthetic circuits. With the purpose of rationally design ECF-based synthetic circuits and taking advantage of the ECF toolbox, we characterized the dynamic behavior of a set of 15 ECF σ factors, their cognate promoters, and relative anti-σs. Overall, we found that ECFs are non-toxic and functional and that they display different binding affinities for the cognate target promoters. Moreover, our results show that it is possible to optimize the output dynamic range of the ECF-based switches by changing the copy number of the ECFs and target promoters, thus, tuning the input/output signal ratio. Next, by combining up to three ECF-switches, we generated a set of “genetic-timer circuits”, the first synthetic circuits harboring more than one ECF. ECF-based timer circuits sequentially activate a series of target genes with increasing time delays, moreover, the behavior of the circuits can be predicted by a set of mathematical models. In order to improve the dynamic response of the ECF-based constructs, we introduced anti-σ factors in our synthetic circuits. By doing so we first confirmed that anti-σ factors can exert an adverse effect on the growth of E. coli, thus we explored possible solutions. Our results demonstrate that anti-σ factors toxicity can be partially alleviated by generating truncated, soluble variants of the anti-σ factors and, eventually, completely abolished via chromosomal integration of the anti-σ factor-based circuits. Finally, after demonstrating that anti-σ factors can be used to generate a tunable time delay among ECF expression and target promoter activation, we designed ECF/AS-suicide circuits. Such circuits allow for the time-delayed cell-death of E. coli and will serve as a prototype for the further development of ECF/AS-based lysis circuits

    Synthetic Biology: A Bridge between Artificial and Natural Cells.

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    Artificial cells are simple cell-like entities that possess certain properties of natural cells. In general, artificial cells are constructed using three parts: (1) biological membranes that serve as protective barriers, while allowing communication between the cells and the environment; (2) transcription and translation machinery that synthesize proteins based on genetic sequences; and (3) genetic modules that control the dynamics of the whole cell. Artificial cells are minimal and well-defined systems that can be more easily engineered and controlled when compared to natural cells. Artificial cells can be used as biomimetic systems to study and understand natural dynamics of cells with minimal interference from cellular complexity. However, there remain significant gaps between artificial and natural cells. How much information can we encode into artificial cells? What is the minimal number of factors that are necessary to achieve robust functioning of artificial cells? Can artificial cells communicate with their environments efficiently? Can artificial cells replicate, divide or even evolve? Here, we review synthetic biological methods that could shrink the gaps between artificial and natural cells. The closure of these gaps will lead to advancement in synthetic biology, cellular biology and biomedical applications

    Synthetic biology—putting engineering into biology

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    Synthetic biology is interpreted as the engineering-driven building of increasingly complex biological entities for novel applications. Encouraged by progress in the design of artificial gene networks, de novo DNA synthesis and protein engineering, we review the case for this emerging discipline. Key aspects of an engineering approach are purpose-orientation, deep insight into the underlying scientific principles, a hierarchy of abstraction including suitable interfaces between and within the levels of the hierarchy, standardization and the separation of design and fabrication. Synthetic biology investigates possibilities to implement these requirements into the process of engineering biological systems. This is illustrated on the DNA level by the implementation of engineering-inspired artificial operations such as toggle switching, oscillating or production of spatial patterns. On the protein level, the functionally self-contained domain structure of a number of proteins suggests possibilities for essentially Lego-like recombination which can be exploited for reprogramming DNA binding domain specificities or signaling pathways. Alternatively, computational design emerges to rationally reprogram enzyme function. Finally, the increasing facility of de novo DNA synthesis—synthetic biology’s system fabrication process—supplies the possibility to implement novel designs for ever more complex systems. Some of these elements have merged to realize the first tangible synthetic biology applications in the area of manufacturing of pharmaceutical compounds.

    Network Virtual Machine (NetVM): A New Architecture for Efficient and Portable Packet Processing Applications

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    A challenge facing network device designers, besides increasing the speed of network gear, is improving its programmability in order to simplify the implementation of new applications (see for example, active networks, content networking, etc). This paper presents our work on designing and implementing a virtual network processor, called NetVM, which has an instruction set optimized for packet processing applications, i.e., for handling network traffic. Similarly to a Java Virtual Machine that virtualizes a CPU, a NetVM virtualizes a network processor. The NetVM is expected to provide a compatibility layer for networking tasks (e.g., packet filtering, packet counting, string matching) performed by various packet processing applications (firewalls, network monitors, intrusion detectors) so that they can be executed on any network device, ranging from expensive routers to small appliances (e.g. smart phones). Moreover, the NetVM will provide efficient mapping of the elementary functionalities used to realize the above mentioned networking tasks upon specific hardware functional units (e.g., ASICs, FPGAs, and network processing elements) included in special purpose hardware systems possibly deployed to implement network devices
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