WorldWideScience

Sample records for bottom-up synthetic biology

  1. Social and ethical checkpoints for bottom-up synthetic biology, or protocells.

    Science.gov (United States)

    Bedau, Mark A; Parke, Emily C; Tangen, Uwe; Hantsche-Tangen, Brigitte

    2009-12-01

    An alternative to creating novel organisms through the traditional "top-down" approach to synthetic biology involves creating them from the "bottom up" by assembling them from non-living components; the products of this approach are called "protocells." In this paper we describe how bottom-up and top-down synthetic biology differ, review the current state of protocell research and development, and examine the unique ethical, social, and regulatory issues raised by bottom-up synthetic biology. Protocells have not yet been developed, but many expect this to happen within the next five to ten years. Accordingly, we identify six key checkpoints in protocell development at which particular attention should be given to specific ethical, social and regulatory issues concerning bottom-up synthetic biology, and make ten recommendations for responsible protocell science that are tied to the achievement of these checkpoints.

  2. Social and ethical checkpoints for bottom-up synthetic biology, or protocells

    OpenAIRE

    2009-01-01

    An alternative to creating novel organisms through the traditional “top-down” approach to synthetic biology involves creating them from the “bottom up” by assembling them from non-living components; the products of this approach are called “protocells.” In this paper we describe how bottom-up and top-down synthetic biology differ, review the current state of protocell research and development, and examine the unique ethical, social, and regulatory issues raised by bottom-up synthetic biology....

  3. A bottom-up characterization of transfer functions for synthetic biology designs: lessons from enzymology

    OpenAIRE

    Carbonell-Ballestero, M.; Duran-Nebreda, S.; Montanez, R.; Sole, R.; Macia, J.; Rodriguez-Caso, C.

    2014-01-01

    Within the field of synthetic biology, a rational design of genetic parts should include a causal understanding of their input-output responses-the so-called transfer function-and how to tune them. However, a commonly adopted strategy is to fit data to Hill-shaped curves without considering the underlying molecular mechanisms. Here we provide a novel mathematical formalization that allows prediction of the global behavior of a synthetic device by considering the actual information from the in...

  4. A bottom-up characterization of transfer functions for synthetic biology designs: lessons from enzymology.

    Science.gov (United States)

    Carbonell-Ballestero, Max; Duran-Nebreda, Salva; Montañez, Raúl; Solé, Ricard; Macía, Javier; Rodríguez-Caso, Carlos

    2014-12-16

    Within the field of synthetic biology, a rational design of genetic parts should include a causal understanding of their input-output responses-the so-called transfer function-and how to tune them. However, a commonly adopted strategy is to fit data to Hill-shaped curves without considering the underlying molecular mechanisms. Here we provide a novel mathematical formalization that allows prediction of the global behavior of a synthetic device by considering the actual information from the involved biological parts. This is achieved by adopting an enzymology-like framework, where transfer functions are described in terms of their input affinity constant and maximal response. As a proof of concept, we characterize a set of Lux homoserine-lactone-inducible genetic devices with different levels of Lux receptor and signal molecule. Our model fits the experimental results and predicts the impact of the receptor's ribosome-binding site strength, as a tunable parameter that affects gene expression. The evolutionary implications are outlined.

  5. Construction of membrane-bound artificial cells using microfluidics: a new frontier in bottom-up synthetic biology.

    Science.gov (United States)

    Elani, Yuval

    2016-06-15

    The quest to construct artificial cells from the bottom-up using simple building blocks has received much attention over recent decades and is one of the grand challenges in synthetic biology. Cell mimics that are encapsulated by lipid membranes are a particularly powerful class of artificial cells due to their biocompatibility and the ability to reconstitute biological machinery within them. One of the key obstacles in the field centres on the following: how can membrane-based artificial cells be generated in a controlled way and in high-throughput? In particular, how can they be constructed to have precisely defined parameters including size, biomolecular composition and spatial organization? Microfluidic generation strategies have proved instrumental in addressing these questions. This article will outline some of the major principles underpinning membrane-based artificial cells and their construction using microfluidics, and will detail some recent landmarks that have been achieved.

  6. Abiotic synthesis of RNA in water: a common goal of prebiotic chemistry and bottom-up synthetic biology.

    Science.gov (United States)

    Cafferty, Brian J; Hud, Nicholas V

    2014-10-01

    For more than half a century chemists have searched for a plausible prebiotic synthesis of RNA. The initial advances of the 1960s and 1970s were followed by decades of measured progress and a growing pessimism about overcoming remaining challenges. Fortunately, the past few years have provided a number of important advances, including new abiotic routes for the synthesis of nucleobases, nucleosides, and nucleotides. Recent discoveries also provide additional support for the hypothesis that RNA is the product of evolution, being preceded by ancestral genetic polymers, or pre-RNAs, that are synthesized more easily than RNA. In some cases, parallel searches for plausible prebiotic routes to RNA and pre-RNAs have provided more than one experimentally verified synthesis of RNA substructures and possible predecessors. Just as the synthesis of a contemporary biological molecule cannot be understood without knowledge of cellular metabolism, it is likely that an integrated approach that takes into account both plausible prebiotic reactions and plausible prebiotic environments will ultimately provide the most satisfactory and unifying chemical scenarios for the origin of nucleic acids. In this context, recent advances towards the abiotic synthesis of RNA and candidates for pre-RNAs are beginning to suggest that some molecules (e.g., urea) were multi-faceted contributors to the origin of nucleic acids, and the origin of life.

  7. Mineralization of Synthetic Polymer Scaffolds: A Bottom-upApproach for the Development of Artificial Bone

    Energy Technology Data Exchange (ETDEWEB)

    Song, Jie; Viengkham, Malathong; Bertozzi, Carolyn R.

    2004-09-27

    The controlled integration of organic and inorganic components confers natural bone with superior mechanical properties. Bone biogenesis is thought to occur by templated mineralization of hard apatite crystals by an elastic protein scaffold, a process we sought to emulate with synthetic biomimetic hydrogel polymers. Crosslinked polymethacrylamide and polymethacrylate hydrogels were functionalized with mineral-binding ligands and used to template the formation of hydroxyapatite. Strong adhesion between the organic and inorganic materials was achieved for hydrogels functionalized with either carboxylate or hydroxy ligands. The mineral-nucleating potential of hydroxyl groups identified here broadens the design parameters for synthetic bone-like composites and suggests a potential role for hydroxylated collagen proteins in bone mineralization.

  8. Bottom-up engineering of biological systems through standard bricks: a modularity study on basic parts and devices.

    Directory of Open Access Journals (Sweden)

    Lorenzo Pasotti

    Full Text Available BACKGROUND: Modularity is a crucial issue in the engineering world, as it enables engineers to achieve predictable outcomes when different components are interconnected. Synthetic Biology aims to apply key concepts of engineering to design and construct new biological systems that exhibit a predictable behaviour. Even if physical and measurement standards have been recently proposed to facilitate the assembly and characterization of biological components, real modularity is still a major research issue. The success of the bottom-up approach strictly depends on the clear definition of the limits in which biological functions can be predictable. RESULTS: The modularity of transcription-based biological components has been investigated in several conditions. First, the activity of a set of promoters was quantified in Escherichia coli via different measurement systems (i.e., different plasmids, reporter genes, ribosome binding sites relative to an in vivo reference promoter. Second, promoter activity variation was measured when two independent gene expression cassettes were assembled in the same system. Third, the interchangeability of input modules (a set of constitutive promoters and two regulated promoters connected to a fixed output device (a logic inverter expressing GFP was evaluated. The three input modules provide tunable transcriptional signals that drive the output device. If modularity persists, identical transcriptional signals trigger identical GFP outputs. To verify this, all the input devices were individually characterized and then the input-output characteristic of the logic inverter was derived in the different configurations. CONCLUSIONS: Promoters activities (referred to a standard promoter can vary when they are measured via different reporter devices (up to 22%, when they are used within a two-expression-cassette system (up to 35% and when they drive another device in a functionally interconnected circuit (up to 44%. This paper

  9. Incorporating electron-transfer functionality into synthetic metalloproteins from the bottom-up.

    Science.gov (United States)

    Hong, Jing; Kharenko, Olesya A; Ogawa, Michael Y

    2006-12-11

    The alpha-helical coiled-coil motif serves as a robust scaffold for incorporating electron-transfer (ET) functionality into synthetic metalloproteins. These structures consist of a supercoiling of two or more aplha helices that are formed by the self-assembly of individual polypeptide chains whose sequences contain a repeating pattern of hydrophobic and hydrophilic residues. Early work from our group attached abiotic Ru-based redox sites to the most surface-exposed positions of two stranded coiled-coils and used electron-pulse radiolysis to study both intra- and intermolecular ET reactions in these systems. Later work used smaller metallopeptides to investigate the effects of conformational gating within electrostatic peptide-protein complexes. We have recently designed the C16C19-GGY peptide, which contains Cys residues located at both the "a" and "d" positions of its third heptad repeat in order to construct a nativelike metal-binding domain within its hydrophobic core. It was shown that the binding of both Cd(II) and Cu(I) ions induces the peptide to undergo a conformational change from a disordered random coil to a metal-bridged coiled-coil. However, whereas the Cd(II)-protein exists as a two-stranded coiled-coil, the Cu(I) derivative exists as a four-stranded coiled-coil. Upon the incorporation of other metal ions, metal-bridged peptide dimers, tetramers, and hexamers are formed. The Cu(I)-protein is of particular interest because it exhibits a long-lived (microsecond) room-temperature luminescence at 600 nm. The luminophore in this protein is thought to be a multinuclear CuI4Cys4(N/O)4 cage complex, which can be quenched by exogenous electron acceptors in solution, as shown by emission-lifetime and transient-absorption experiments. It is anticipated that further investigation into these systems will contribute to the expanding effort of bioinorganic chemists to prepare new kinds of functionally active synthetic metalloproteins.

  10. Synthetic biology, inspired by synthetic chemistry.

    Science.gov (United States)

    Malinova, V; Nallani, M; Meier, W P; Sinner, E K

    2012-07-16

    The topic synthetic biology appears still as an 'empty basket to be filled'. However, there is already plenty of claims and visions, as well as convincing research strategies about the theme of synthetic biology. First of all, synthetic biology seems to be about the engineering of biology - about bottom-up and top-down approaches, compromising complexity versus stability of artificial architectures, relevant in biology. Synthetic biology accounts for heterogeneous approaches towards minimal and even artificial life, the engineering of biochemical pathways on the organismic level, the modelling of molecular processes and finally, the combination of synthetic with nature-derived materials and architectural concepts, such as a cellular membrane. Still, synthetic biology is a discipline, which embraces interdisciplinary attempts in order to have a profound, scientific base to enable the re-design of nature and to compose architectures and processes with man-made matter. We like to give an overview about the developments in the field of synthetic biology, regarding polymer-based analogs of cellular membranes and what questions can be answered by applying synthetic polymer science towards the smallest unit in life, namely a cell.

  11. A Family of Highly Efficient CuI-Based Lighting Phosphors Prepared by a Systematic, Bottom-up Synthetic Approach.

    Science.gov (United States)

    Liu, Wei; Fang, Yang; Wei, George Z; Teat, Simon J; Xiong, Kecai; Hu, Zhichao; Lustig, William P; Li, Jing

    2015-07-29

    Copper(I) iodide (CuI)-based inorganic-organic hybrid materials in the general chemical formula of CuI(L) are well-known for their structural diversity and strong photoluminescence and are therefore considered promising candidates for a number of optical applications. In this work, we demonstrate a systematic, bottom-up precursor approach to developing a series of CuI(L) network structures built on CuI rhomboid dimers. These compounds combine strong luminescence due to the CuI inorganic modules and significantly enhanced thermal stability as a result of connecting individual building units into robust, extended networks. Examination of their optical properties reveals that these materials not only exhibit exceptionally high photoluminescence performance (with internal quantum yield up to 95%) but also that their emission energy and color are systematically tunable through modification of the organic component. Results from density functional theory calculations provide convincing correlations between these materials' crystal structures and chemical compositions and their optophysical properties. The advantages of cost-effective, solution-processable, easily scalable and fully controllable synthesis as well as high quantum efficiency with improved thermal stability, make this phosphor family a promising candidate for alternative, RE-free phosphors in general lighting and illumination. This solution-based precursor approach creates a new blueprint for the rational design and controlled synthesis of inorganic-organic hybrid materials.

  12. Synthetic biology in plastids.

    Science.gov (United States)

    Scharff, Lars B; Bock, Ralph

    2014-06-01

    Plastids (chloroplasts) harbor a small gene-dense genome that is amenable to genetic manipulation by transformation. During 1 billion years of evolution from the cyanobacterial endosymbiont to present-day chloroplasts, the plastid genome has undergone a dramatic size reduction, mainly as a result of gene losses and the large-scale transfer of genes to the nuclear genome. Thus the plastid genome can be regarded as a naturally evolved miniature genome, the gradual size reduction and compaction of which has provided a blueprint for the design of minimum genomes. Furthermore, because of the largely prokaryotic genome structure and gene expression machinery, the high transgene expression levels attainable in transgenic chloroplasts and the very low production costs in plant systems, the chloroplast lends itself to synthetic biology applications that are directed towards the efficient synthesis of green chemicals, biopharmaceuticals and other metabolites of commercial interest. This review describes recent progress with the engineering of plastid genomes with large constructs of foreign or synthetic DNA, and highlights the potential of the chloroplast as a model system in bottom-up and top-down synthetic biology approaches.

  13. Parallel- and serial-contact electrochemical metallization of monolayer nanopatterns: A versatile synthetic tool en route to bottom-up assembly of electric nanocircuits

    Directory of Open Access Journals (Sweden)

    Jonathan Berson

    2012-02-01

    Full Text Available Contact electrochemical transfer of silver from a metal-film stamp (parallel process or a metal-coated scanning probe (serial process is demonstrated to allow site-selective metallization of monolayer template patterns of any desired shape and size created by constructive nanolithography. The precise nanoscale control of metal delivery to predefined surface sites, achieved as a result of the selective affinity of the monolayer template for electrochemically generated metal ions, provides a versatile synthetic tool en route to the bottom-up assembly of electric nanocircuits. These findings offer direct experimental support to the view that, in electrochemical metal deposition, charge is carried across the electrode–solution interface by ion migration to the electrode rather than by electron transfer to hydrated ions in solution.

  14. Synthetic biology and personalized medicine.

    Science.gov (United States)

    Jain, K K

    2013-01-01

    Synthetic biology, application of synthetic chemistry to biology, is a broad term that covers the engineering of biological systems with structures and functions not found in nature to process information, manipulate chemicals, produce energy, maintain cell environment and enhance human health. Synthetic biology devices contribute not only to improve our understanding of disease mechanisms, but also provide novel diagnostic tools. Methods based on synthetic biology enable the design of novel strategies for the treatment of cancer, immune diseases metabolic disorders and infectious diseases as well as the production of cheap drugs. The potential of synthetic genome, using an expanded genetic code that is designed for specific drug synthesis as well as delivery and activation of the drug in vivo by a pathological signal, was already pointed out during a lecture delivered at Kuwait University in 2005. Of two approaches to synthetic biology, top-down and bottom-up, the latter is more relevant to the development of personalized medicines as it provides more flexibility in constructing a partially synthetic cell from basic building blocks for a desired task.

  15. The bottom-up approach to defining life : deciphering the functional organization of biological cells via multi-objective representation of biological complexity from molecules to cells

    Directory of Open Access Journals (Sweden)

    Sathish ePeriyasamy

    2013-12-01

    Full Text Available In silico representation of cellular systems needs to represent the adaptive dynamics of biological cells, recognizing a cell’s multi-objective topology formed by spatially and temporally cohesive intracellular structures. The design of these models needs to address the hierarchical and concurrent nature of cellular functions and incorporate the ability to self-organise in response to transitions between healthy and pathological phases, and adapt accordingly. The functions of biological systems are constantly evolving, due to the ever changing demands of their environment. Biological systems meet these demands by pursuing objectives, aided by their constituents, giving rise to biological functions. A biological cell is organised into an objective/task hierarchy. These objective hierarchy corresponds to the nested nature of temporally cohesive structures and representing them will facilitate in studying pleiotropy and polygeny by modeling causalities propagating across multiple interconnected intracellular processes. Although biological adaptations occur in physiological, developmental and reproductive timescales, the paper is focused on adaptations that occur within physiological timescales, where the biomolecular activities contributing to functional organisation, play a key role in cellular physiology. The paper proposes a multi-scale and multi-objective modelling approach from the bottom-up by representing temporally cohesive structures for multi-tasking of intracellular processes. Further the paper characterises the properties and constraints that are consequential to the organisational and adaptive dynamics in biological cells.

  16. Bottom-Up Earley Deduction

    CERN Document Server

    Erbach, G

    1995-01-01

    We propose a bottom-up variant of Earley deduction. Bottom-up deduction is preferable to top-down deduction because it allows incremental processing (even for head-driven grammars), it is data-driven, no subsumption check is needed, and preference values attached to lexical items can be used to guide best-first search. We discuss the scanning step for bottom-up Earley deduction and indexing schemes that help avoid useless deduction steps.

  17. Plant synthetic biology.

    Science.gov (United States)

    Liu, Wusheng; Stewart, C Neal

    2015-05-01

    Plant synthetic biology is an emerging field that combines engineering principles with plant biology toward the design and production of new devices. This emerging field should play an important role in future agriculture for traditional crop improvement, but also in enabling novel bioproduction in plants. In this review we discuss the design cycles of synthetic biology as well as key engineering principles, genetic parts, and computational tools that can be utilized in plant synthetic biology. Some pioneering examples are offered as a demonstration of how synthetic biology can be used to modify plants for specific purposes. These include synthetic sensors, synthetic metabolic pathways, and synthetic genomes. We also speculate about the future of synthetic biology of plants.

  18. Designing synthetic biology.

    Science.gov (United States)

    Agapakis, Christina M

    2014-03-21

    Synthetic biology is frequently defined as the application of engineering design principles to biology. Such principles are intended to streamline the practice of biological engineering, to shorten the time required to design, build, and test synthetic gene networks. This streamlining of iterative design cycles can facilitate the future construction of biological systems for a range of applications in the production of fuels, foods, materials, and medicines. The promise of these potential applications as well as the emphasis on design has prompted critical reflection on synthetic biology from design theorists and practicing designers from many fields, who can bring valuable perspectives to the discipline. While interdisciplinary connections between biologists and engineers have built synthetic biology via the science and the technology of biology, interdisciplinary collaboration with artists, designers, and social theorists can provide insight on the connections between technology and society. Such collaborations can open up new avenues and new principles for research and design, as well as shed new light on the challenging context-dependence-both biological and social-that face living technologies at many scales. This review is inspired by the session titled "Design and Synthetic Biology: Connecting People and Technology" at Synthetic Biology 6.0 and covers a range of literature on design practice in synthetic biology and beyond. Critical engagement with how design is used to shape the discipline opens up new possibilities for how we might design the future of synthetic biology.

  19. Is synthetic biology mechanical biology?

    Science.gov (United States)

    Holm, Sune

    2015-12-01

    A widespread and influential characterization of synthetic biology emphasizes that synthetic biology is the application of engineering principles to living systems. Furthermore, there is a strong tendency to express the engineering approach to organisms in terms of what seems to be an ontological claim: organisms are machines. In the paper I investigate the ontological and heuristic significance of the machine analogy in synthetic biology. I argue that the use of the machine analogy and the aim of producing rationally designed organisms does not necessarily imply a commitment to mechanical biology. The ideal of applying engineering principles to biology is best understood as expressing recognition of the machine-unlikeness of natural organisms and the limits of human cognition. The paper suggests an interpretation of the identification of organisms with machines in synthetic biology according to which it expresses a strategy for representing, understanding, and constructing living systems that are more machine-like than natural organisms.

  20. Culture from the Bottom Up

    Science.gov (United States)

    Atkinson, Dwight; Sohn, Jija

    2013-01-01

    The culture concept has been severely criticized for its top-down nature in TESOL, leading arguably to its falling out of favor in the field. But what of the fact that people do "live culturally" (Ingold, 1994)? This article describes a case study of culture from the bottom up--culture as understood and enacted by its individual users.…

  1. Building from the Bottom Up

    Science.gov (United States)

    2003-05-01

    through billions of years of prebiotic and molecular selection and evolution, there are bio-organic by Shuguang Zhang Building from the bottom up... Health , Du Pont-MIT Alliance, and the Whitaker Foundation. I also gratefully acknowledge Intel Corporation Academic Program for the generous donation

  2. "Bottom-up" transparent electrodes.

    Science.gov (United States)

    Morag, Ahiud; Jelinek, Raz

    2016-11-15

    Transparent electrodes (TEs) have attracted significant scientific, technological, and commercial interest in recent years due to the broad and growing use of such devices in electro-optics, consumer products (touch-screens for example), solar cells, and others. Currently, almost all commercial TEs are fabricated through "top-down" approaches (primarily lithography-based techniques), with indium tin oxide (ITO) as the most common material employed. Several problems are encountered, however, in this field, including the cost and complexity of TE production using top-down technologies, the limited structural flexibility, high-cost of indium, and brittle nature and low transparency in the far-IR spectral region of ITO. Alternative routes based upon bottom-up processes, have recently emerged as viable alternatives for production of TEs. Bottom up technologies are based upon self-assembly of building blocks - atoms, molecules, or nanoparticles - generating thin patterned films that exhibit both electrical conductivity and optical transparency. In this Feature Article we discuss the recent progress in this active and exciting field, including bottom-up TE systems produced from carbon materials (carbon nanotubes, graphene, graphene-oxide), silver, gold, and other metals. The current hurdles encountered for broader use of bottom-up strategies along with their significant potential are analyzed.

  3. Professionalization as a governance strategy for synthetic biology.

    Science.gov (United States)

    Weir, Lorna; Selgelid, Michael J

    2009-12-01

    This article considers professionalization as a governance strategy for synthetic biology, reporting on social science interviews done with scientists, science journal editors, members of science advisory boards and authors of nongovernmental policy reports on synthetic biology. After summarizing their observations about the potential advantages and disadvantages of the professionalization of synthetic biology, we analyze professionalization as a strategy that overcomes dichotomies found in the current debates about synthetic biology governance, specifically "top down" versus "bottom up" governance and scientific fact versus public values. Professionalization combines community and state, fact and value. Like all governance options, professionalization has limitations, particularly regarding war and peace. It is best conceptualized as potentially part of a wider range of governance mechanisms working in concert: a "web of prevention".

  4. Opportunities in plant synthetic biology.

    Science.gov (United States)

    Cook, Charis; Martin, Lisa; Bastow, Ruth

    2014-05-01

    Synthetic biology is an emerging field uniting scientists from all disciplines with the aim of designing or re-designing biological processes. Initially, synthetic biology breakthroughs came from microbiology, chemistry, physics, computer science, materials science, mathematics, and engineering disciplines. A transition to multicellular systems is the next logical step for synthetic biologists and plants will provide an ideal platform for this new phase of research. This meeting report highlights some of the exciting plant synthetic biology projects, and tools and resources, presented and discussed at the 2013 GARNet workshop on plant synthetic biology.

  5. [From synthetic biology to synthetic humankind].

    Science.gov (United States)

    Nouvel, Pascal

    2015-01-01

    In this paper, we propose an historical survey of the expression "synthetic biology" in order to identify its main philosophical components. The result of the analysis is then used to investigate the meaning of the notion of "synthetic man". It is shown that both notions share a common philosophical background that can be summed up by the short but meaningful assertion: "biology is technology". The analysis allows us to distinguish two notions that are often confused in transhumanist literature: the notion of synthetic man and the notion of renewed man. The consequences of this crucial distinction are discussed.

  6. Synthetic Biology: opportunities for Chilean bioindustry and education.

    Science.gov (United States)

    Federici, Fernán; Rudge, Timothy J; Pollak, Bernardo; Haseloff, Jim; Gutiérrez, Rodrigo A

    2013-01-01

    In an age of pressing challenges for sustainable production of energy and food, the new field of Synthetic Biology has emerged as a promising approach to engineer biological systems. Synthetic Biology is formulating the design principles to engineer affordable, scalable, predictable and robust functions in biological systems. In addition to efficient transfer of evolved traits from one organism to another, Synthetic Biology offers a new and radical approach to bottom-up engineering of sensors, actuators, dynamical controllers and the biological chassis they are embedded in. Because it abstracts much of the mechanistic details underlying biological component behavior, Synthetic Biology methods and resources can be readily used by interdisciplinary teams to tackle complex problems. In addition, the advent of robust new methods for the assembly of large genetic circuits enables teaching Biology and Bioengineering in a learning-by-making fashion for diverse backgrounds at the graduate, undergraduate and high school levels. Synthetic Biology offers unique opportunities to empower interdisciplinary training, research and industrial development in Chile for a technology that promises a significant role in this century's economy.

  7. Synthetic biology: advancing biological frontiers by building synthetic systems

    OpenAIRE

    Chen, Yvonne Yu-Hsuan; Galloway, Kate E; Smolke, Christina D.

    2012-01-01

    Advances in synthetic biology are contributing to diverse research areas, from basic biology to biomanufacturing and disease therapy. We discuss the theoretical foundation, applications, and potential of this emerging field.

  8. Synthetic biology and genetic causation.

    Science.gov (United States)

    Oftedal, Gry; Parkkinen, Veli-Pekka

    2013-06-01

    Synthetic biology research is often described in terms of programming cells through the introduction of synthetic genes. Genetic material is seemingly attributed with a high level of causal responsibility. We discuss genetic causation in synthetic biology and distinguish three gene concepts differing in their assumptions of genetic control. We argue that synthetic biology generally employs a difference-making approach to establishing genetic causes, and that this approach does not commit to a specific notion of genetic program or genetic control. Still, we suggest that a strong program concept of genetic material can be used as a successful heuristic in certain areas of synthetic biology. Its application requires control of causal context, and may stand in need of a modular decomposition of the target system. We relate different modularity concepts to the discussion of genetic causation and point to possible advantages of and important limitations to seeking modularity in synthetic biology systems.

  9. The Ethics of Synthetic Biology

    DEFF Research Database (Denmark)

    Christiansen, Andreas

    The dissertation analyses and discusses a number of ethical issues that have been raised in connection with the development of synthetic biology. Synthetic biology is a set of new techniques for DNA-level design and construction of living beings with useful properties. The dissertation especially...

  10. Synthetic biology: ethical ramifications 2009.

    Science.gov (United States)

    Rabinow, Paul; Bennett, Gaymon

    2009-12-01

    During 2007 and 2008 synthetic biology moved from the manifesto stage to research programs. As of 2009, synthetic biology is ramifying; to ramify means to produce differentiated trajectories from previous determinations. From its inception, most of the players in synthetic biology agreed on the need for (a) rationalized design and construction of new biological parts, devices, and systems as well as (b) the re-design of natural biological systems for specified purposes, and that (c) the versatility of designed biological systems makes them suitable to address such challenges as renewable energy, the production of inexpensive drugs, and environmental remediation, as well as providing a catalyst for further growth of biotechnology. What is understood by these goals, however, is diverse. Those assorted understandings are currently contributing to different ramifications of synthetic biology. The Berkeley Human Practices Lab, led by Paul Rabinow, is currently devoting its efforts to documenting and analyzing these ramifications as they emerge.

  11. Synthetic biology and metabolic engineering.

    Science.gov (United States)

    Stephanopoulos, Gregory

    2012-11-16

    Metabolic engineering emerged 20 years ago as the discipline occupied with the directed modification of metabolic pathways for the microbial synthesis of various products. As such, it deals with the engineering (design, construction, and optimization) of native as well as non-natural routes of product synthesis, aided in this task by the availability of synthetic DNA, the core enabling technology of synthetic biology. The two fields, however, only partially overlap in their interest in pathway engineering. While fabrication of biobricks, synthetic cells, genetic circuits, and nonlinear cell dynamics, along with pathway engineering, have occupied researchers in the field of synthetic biology, the sum total of these areas does not constitute a coherent definition of synthetic biology with a distinct intellectual foundation and well-defined areas of application. This paper reviews the origins of the two fields and advances two distinct paradigms for each of them: that of unit operations for metabolic engineering and electronic circuits for synthetic biology. In this context, metabolic engineering is about engineering cell factories for the biological manufacturing of chemical and pharmaceutical products, whereas the main focus of synthetic biology is fundamental biological research facilitated by the use of synthetic DNA and genetic circuits.

  12. Synthetic biology for therapeutic applications.

    Science.gov (United States)

    Abil, Zhanar; Xiong, Xiong; Zhao, Huimin

    2015-02-02

    Synthetic biology is a relatively new field with the key aim of designing and constructing biological systems with novel functionalities. Today, synthetic biology devices are making their first steps in contributing new solutions to a number of biomedical challenges, such as emerging bacterial antibiotic resistance and cancer therapy. This review discusses some synthetic biology approaches and applications that were recently used in disease mechanism investigation and disease modeling, drug discovery and production, as well as vaccine development and treatment of infectious diseases, cancer, and metabolic disorders.

  13. Artificial intelligence and synthetic biology: A tri-temporal contribution.

    Science.gov (United States)

    Bianchini, Francesco

    2016-10-01

    Artificial intelligence can make numerous contributions to synthetic biology. I would like to suggest three that are related to the past, present and future of artificial intelligence. From the past, works in biology and artificial systems by Turing and von Neumann prove highly interesting to explore within the new framework of synthetic biology, especially with regard to the notions of self-modification and self-replication and their links to emergence and the bottom-up approach. The current epistemological inquiry into emergence and research on swarm intelligence, superorganisms and biologically inspired cognitive architecture may lead to new achievements on the possibilities of synthetic biology in explaining cognitive processes. Finally, the present-day discussion on the future of artificial intelligence and the rise of superintelligence may point to some research trends for the future of synthetic biology and help to better define the boundary of notions such as "life", "cognition", "artificial" and "natural", as well as their interconnections in theoretical synthetic biology.

  14. The Ethics of Synthetic Biology

    DEFF Research Database (Denmark)

    Christiansen, Andreas

    The dissertation analyses and discusses a number of ethical issues that have been raised in connection with the development of synthetic biology. Synthetic biology is a set of new techniques for DNA-level design and construction of living beings with useful properties. The dissertation especially......) popular responsesto them succeed, and whether the objections are ultimately persuasive.2. Given that synthetic biology is a new technology, there is a certain degree of uncertainty about its ultimate effects, and many perceive the technology as risky. I discuss two common approaches in risk regulation...

  15. Synthetic biology as red herring.

    Science.gov (United States)

    Preston, Beth

    2013-12-01

    It has become commonplace to say that with the advent of technologies like synthetic biology the line between artifacts and living organisms, policed by metaphysicians since antiquity, is beginning to blur. But that line began to blur 10,000 years ago when plants and animals were first domesticated; and has been thoroughly blurred at least since agriculture became the dominant human subsistence pattern many millennia ago. Synthetic biology is ultimately only a late and unexceptional offshoot of this prehistoric development. From this perspective, then, synthetic biology is a red herring, distracting us from more thorough philosophical consideration of the most truly revolutionary human practice-agriculture. In the first section of this paper I will make this case with regard to ontology, arguing that synthetic biology crosses no ontological lines that were not crossed already in the Neolithic. In the second section I will construct a parallel case with regard to cognition, arguing that synthetic biology as biological engineering represents no cognitive advance over what was required for domestication and the new agricultural subsistence pattern it grounds. In the final section I will make the case with regard to human existence, arguing that synthetic biology, even if wildly successful, is not in a position to cause significant existential change in what it is to be human over and above the massive existential change caused by the transition to agriculture. I conclude that a longer historical perspective casts new light on some important issues in philosophy of technology and environmental philosophy.

  16. Microfluidic Technologies for Synthetic Biology

    Directory of Open Access Journals (Sweden)

    Sung Kuk Lee

    2011-06-01

    Full Text Available Microfluidic technologies have shown powerful abilities for reducing cost, time, and labor, and at the same time, for increasing accuracy, throughput, and performance in the analysis of biological and biochemical samples compared with the conventional, macroscale instruments. Synthetic biology is an emerging field of biology and has drawn much attraction due to its potential to create novel, functional biological parts and systems for special purposes. Since it is believed that the development of synthetic biology can be accelerated through the use of microfluidic technology, in this review work we focus our discussion on the latest microfluidic technologies that can provide unprecedented means in synthetic biology for dynamic profiling of gene expression/regulation with high resolution, highly sensitive on-chip and off-chip detection of metabolites, and whole-cell analysis.

  17. Synthetic Biology for Specialty Chemicals.

    Science.gov (United States)

    Markham, Kelly A; Alper, Hal S

    2015-01-01

    In this review, we address recent advances in the field of synthetic biology and describe how those tools have been applied to produce a wide variety of chemicals in microorganisms. Here we classify the expansion of the synthetic biology toolbox into three different categories based on their primary function in strain engineering-for design, for construction, and for optimization. Next, focusing on recent years, we look at how chemicals have been produced using these new synthetic biology tools. Advances in producing fuels are briefly described, followed by a more thorough treatment of commodity chemicals, specialty chemicals, pharmaceuticals, and nutraceuticals. Throughout this review, an emphasis is placed on how synthetic biology tools are applied to strain engineering. Finally, we discuss organism and host strain diversity and provide a future outlook in the field.

  18. Top Down Chemistry Versus Bottom up Chemistry

    Science.gov (United States)

    Oka, Takeshi; Witt, Adolf N.

    2016-06-01

    The idea of interstellar top down chemistry (TDC), in which molecules are produced from decomposition of larger molecules and dust in contrast to ordinary bottom up chemistry (BUC) in which molecules are produced synthetically from smaller molecules and atoms in the ISM, has been proposed in the chemistry of PAH and carbon chain molecules both for diffusea,c and dense cloudsb,d. A simple and natural idea, it must have occurred to many people and has been in the air for sometime. The validity of this hypothesis is apparent for diffuse clouds in view of the observed low abundance of small molecules and its rapid decrease with molecular size on the one hand and the high column densities of large carbon molecules demonstrated by the many intense diffuse interstellar bands (DIBs) on the other. Recent identification of C60^+ as the carrier of 5 near infrared DIBs with a high column density of 2×1013 cm-2 by Maier and others confirms the TDC. This means that the large molecules and dust produced in the high density high temperature environment of circumstellar envelopes are sufficiently stable to survive decompositions due to stellar UV radiaiton, cosmic rays, C-shocks etc. for a long time (≥ 10^7 year) of their migration to diffuse clouds and seems to disagree with the consensus in the field of interstellar grains. The stability of molecules and aggregates in the diffuse interstellar medium will be discussed. Duley, W. W. 2006, Faraday Discuss. 133, 415 Zhen,J., Castellanos, P., Paardekooper, D. M., Linnartz, H., Tielens, A. G. G. M. 2014, ApJL, 797, L30 Huang, J., Oka, T. 2015, Mol. Phys. 113, 2159 Guzmán, V. V., Pety, J., Goicoechea, J. R., Gerin, M., Roueff, E., Gratier, P., Öberg, K. I. 2015, ApJL, 800, L33 L. Ziurys has sent us many papers beginning Ziurys, L. M. 2006, PNAS 103, 12274 indicating she had long been a proponent of the idea. Campbell, E. K., Holz, M., Maier, J. P., Gerlich, D., Walker, G. A. H., Bohlender, D, 2016, ApJ, in press Draine, B. T. 2003

  19. Bottom-up organic integrated circuits

    NARCIS (Netherlands)

    Smits, Edsger C. P.; Mathijssen, Simon G. J.; van Hal, Paul A.; Setayesh, Sepas; Geuns, Thomas C. T.; Mutsaers, Kees A. H. A.; Cantatore, Eugenio; Wondergem, Harry J.; Werzer, Oliver; Resel, Roland; Kemerink, Martijn; Kirchmeyer, Stephan; Muzafarov, Aziz M.; Ponomarenko, Sergei A.; de Boer, Bert; Blom, Paul W. M.; de Leeuw, Dago M.

    2008-01-01

    Self- assembly - the autonomous organization of components into patterns and structures(1) - is a promising technology for the mass production of organic electronics. Making integrated circuits using a bottom- up approach involving self- assembling molecules was proposed(2) in the 1970s. The basic b

  20. US Competitiveness in Synthetic Biology.

    Science.gov (United States)

    Gronvall, Gigi Kwik

    2015-01-01

    Synthetic biology is an emerging technical field that aims to make biology easier to engineer; the field has applications in strategically important sectors for the US economy. While the United States currently leads in synthetic biology R&D, other nations are heavily investing in order to boost their economies, which will inevitably diminish the US leadership position. This outcome is not entirely negative--additional investments will expand markets--but it is critical that the US government take steps to remain competitive: There are applications from which the US population and economy may benefit; there are specific applications with importance for national defense; and US technical leadership will ensure that US experts have a leading role in synthetic biology governance, regulation, and oversight. Measures to increase competitiveness in S&T generally are broadly applicable for synthetic biology and should be pursued. However, the US government will also need to take action on fundamental issues that will affect the field's development, such as countering anti-GMO (genetically modified organism) sentiments and anti-GMO legislation. The United States should maintain its regulatory approach so that it is the product that is regulated, not the method used to create a product. At the same time, the United States needs to ensure that the regulatory framework is updated so that synthetic biology products do not fall into regulatory gaps. Finally, the United States needs to pay close attention to how synthetic biology applications may be governed internationally, such as through the Nagoya Protocol of the Convention on Biological Diversity, so that beneficial applications may be realized.

  1. US Competitiveness in Synthetic Biology

    Science.gov (United States)

    2015-01-01

    Synthetic biology is an emerging technical field that aims to make biology easier to engineer; the field has applications in strategically important sectors for the US economy. While the United States currently leads in synthetic biology R&D, other nations are heavily investing in order to boost their economies, which will inevitably diminish the US leadership position. This outcome is not entirely negative—additional investments will expand markets—but it is critical that the US government take steps to remain competitive: There are applications from which the US population and economy may benefit; there are specific applications with importance for national defense; and US technical leadership will ensure that US experts have a leading role in synthetic biology governance, regulation, and oversight. Measures to increase competitiveness in S&T generally are broadly applicable for synthetic biology and should be pursued. However, the US government will also need to take action on fundamental issues that will affect the field's development, such as countering anti-GMO (genetically modified organism) sentiments and anti-GMO legislation. The United States should maintain its regulatory approach so that it is the product that is regulated, not the method used to create a product. At the same time, the United States needs to ensure that the regulatory framework is updated so that synthetic biology products do not fall into regulatory gaps. Finally, the United States needs to pay close attention to how synthetic biology applications may be governed internationally, such as through the Nagoya Protocol of the Convention on Biological Diversity, so that beneficial applications may be realized. PMID:26690379

  2. Digital 'faces' of synthetic biology.

    Science.gov (United States)

    Friedrich, Kathrin

    2013-06-01

    In silicio design plays a fundamental role in the endeavour to synthesise biological systems. In particular, computer-aided design software enables users to manage the complexity of biological entities that is connected to their construction and reconfiguration. The software's graphical user interface bridges the gap between the machine-readable data on the algorithmic subface of the computer and its human-amenable surface represented by standardised diagrammatic elements. Notations like the Systems Biology Graphical Notation (SBGN), together with interactive operations such as drag & drop, allow the user to visually design and simulate synthetic systems as 'bio-algorithmic signs'. Finally, the digital programming process should be extended to the wet lab to manufacture the designed synthetic biological systems. By exploring the different 'faces' of synthetic biology, I argue that in particular computer-aided design (CAD) is pushing the idea to automatically produce de novo objects. Multifaceted software processes serve mutually aesthetic, epistemic and performative purposes by simultaneously black-boxing and bridging different data sources, experimental operations and community-wide standards. So far, synthetic biology is mainly a product of digital media technologies that structurally mimic the epistemological challenge to take both qualitative as well as quantitative aspects of biological systems into account in order to understand and produce new and functional entities.

  3. Synthetic biology: insights into biological computation.

    Science.gov (United States)

    Manzoni, Romilde; Urrios, Arturo; Velazquez-Garcia, Silvia; de Nadal, Eulàlia; Posas, Francesc

    2016-04-18

    Organisms have evolved a broad array of complex signaling mechanisms that allow them to survive in a wide range of environmental conditions. They are able to sense external inputs and produce an output response by computing the information. Synthetic biology attempts to rationally engineer biological systems in order to perform desired functions. Our increasing understanding of biological systems guides this rational design, while the huge background in electronics for building circuits defines the methodology. In this context, biocomputation is the branch of synthetic biology aimed at implementing artificial computational devices using engineered biological motifs as building blocks. Biocomputational devices are defined as biological systems that are able to integrate inputs and return outputs following pre-determined rules. Over the last decade the number of available synthetic engineered devices has increased exponentially; simple and complex circuits have been built in bacteria, yeast and mammalian cells. These devices can manage and store information, take decisions based on past and present inputs, and even convert a transient signal into a sustained response. The field is experiencing a fast growth and every day it is easier to implement more complex biological functions. This is mainly due to advances in in vitro DNA synthesis, new genome editing tools, novel molecular cloning techniques, continuously growing part libraries as well as other technological advances. This allows that digital computation can now be engineered and implemented in biological systems. Simple logic gates can be implemented and connected to perform novel desired functions or to better understand and redesign biological processes. Synthetic biological digital circuits could lead to new therapeutic approaches, as well as new and efficient ways to produce complex molecules such as antibiotics, bioplastics or biofuels. Biological computation not only provides possible biomedical and

  4. Programming languages for synthetic biology.

    Science.gov (United States)

    Umesh, P; Naveen, F; Rao, Chanchala Uma Maheswara; Nair, Achuthsankar S

    2010-12-01

    In the backdrop of accelerated efforts for creating synthetic organisms, the nature and scope of an ideal programming language for scripting synthetic organism in-silico has been receiving increasing attention. A few programming languages for synthetic biology capable of defining, constructing, networking, editing and delivering genome scale models of cellular processes have been recently attempted. All these represent important points in a spectrum of possibilities. This paper introduces Kera, a state of the art programming language for synthetic biology which is arguably ahead of similar languages or tools such as GEC, Antimony and GenoCAD. Kera is a full-fledged object oriented programming language which is tempered by biopart rule library named Samhita which captures the knowledge regarding the interaction of genome components and catalytic molecules. Prominent feature of the language are demonstrated through a toy example and the road map for the future development of Kera is also presented.

  5. Where Synthetic Biology Meets ET

    Science.gov (United States)

    Rothschild, Lynn J.

    2016-01-01

    Synthetic biology - the design and construction of new biological parts and systems and the redesign of existing ones for useful purposes - has the potential to transform fields from pharmaceuticals to fuels. Our lab has focused on the potential of synthetic biology to revolutionize all three major parts of astrobiology: Where do we come from? Where are we going? and Are we alone? For the first and third, synthetic biology is allowing us to answer whether the evolutionary narrative that has played out on planet earth is likely to have been unique or universal. For example, in our lab we are re-evolving the biosynthetic pathways of amino acids in order to understand potential capabilities of an early organism with a limited repertoire of amino acids and developing techniques for the recovery of metals from spent electronics on other planetary bodies. And what about the limits for life? Can we create organisms that expand the envelope for life? In the future synthetic biology will play an increasing role in human activities both on earth, in fields as diverse as human health and the industrial production of novel bio-composites. Beyond earth, we will rely increasingly on biologically-provided life support, as we have throughout our evolutionary history. In order to do this, the field will build on two of the great contributions of astrobiology: studies of the origin of life and life in extreme environments.

  6. Synthetic biology and its promises

    Directory of Open Access Journals (Sweden)

    José Manuel De Cózar Escalante

    2016-12-01

    Full Text Available Synthetic biology is a new science and emerging technology, or rather a technoscience, which converges with others such as nanotechnology, information technology, robotics, artificial intelligence and neuroscience. All have common features that could have highly concerning social and environmental impacts. With its ambitious goals of controlling complexity, redesigning and creating new living entities, synthetic biology perfectly exemplifies the new bioeconomic reality. This requires expanding the focus of the discussion beyond the limited comparative analysis of risks and benefits, to address uncertainties, reassign responsibilities and initiate a thorough social assessment of what is at stake.

  7. The synthetic biology open language.

    Science.gov (United States)

    Myers, Chris; Clancy, Kevin; Misirli, Goksel; Oberortner, Ernst; Pocock, Matthew; Quinn, Jacqueline; Roehner, Nicholas; Sauro, Herbert M

    2015-01-01

    The design and construction of engineered organisms is an emerging new discipline called synthetic biology and holds considerable promise as a new technological platform. The design of biologically engineered systems is however nontrivial, requiring contributions from a wide array of disciplines. One particular issue that confronts synthetic biologists is the ability to unambiguously describe novel designs such that they can be reengineered by a third-party. For this reason, the synthetic biology open language (SBOL) was developed as a community wide standard for formally representing biological designs. A design created by one engineering team can be transmitted electronically to another who can then use this design to reproduce the experimental results. The development and the community of the SBOL standard started in 2008 and has since grown in use with now over 80 participants, including international, academic, and industrial interests. SBOL has stimulated the development of repositories and software tools to help synthetic biologists in their design efforts. This chapter summarizes the latest developments and future of the SBOL standard and its supporting infrastructure.

  8. Synthetic Biological Engineering of Photosynthesis

    Science.gov (United States)

    2015-11-16

    photosynthesis into artificial metabolic pathways. During the course of the granting period, we also made significant progress on understanding the...compartmentalization of carbon fixation and flux in relationship to photosynthesis and obtained 1. REPORT DATE (DD-MM-YYYY) 4. TITLE AND SUBTITLE...2014 Approved for Public Release; Distribution Unlimited Final Report: Synthetic Biological Engineering of Photosynthesis The views, opinions and/or

  9. Control theory meets synthetic biology.

    Science.gov (United States)

    Del Vecchio, Domitilla; Dy, Aaron J; Qian, Yili

    2016-07-01

    The past several years have witnessed an increased presence of control theoretic concepts in synthetic biology. This review presents an organized summary of how these control design concepts have been applied to tackle a variety of problems faced when building synthetic biomolecular circuits in living cells. In particular, we describe success stories that demonstrate how simple or more elaborate control design methods can be used to make the behaviour of synthetic genetic circuits within a single cell or across a cell population more reliable, predictable and robust to perturbations. The description especially highlights technical challenges that uniquely arise from the need to implement control designs within a new hardware setting, along with implemented or proposed solutions. Some engineering solutions employing complex feedback control schemes are also described, which, however, still require a deeper theoretical analysis of stability, performance and robustness properties. Overall, this paper should help synthetic biologists become familiar with feedback control concepts as they can be used in their application area. At the same time, it should provide some domain knowledge to control theorists who wish to enter the rising and exciting field of synthetic biology.

  10. Design Automation in Synthetic Biology.

    Science.gov (United States)

    Appleton, Evan; Madsen, Curtis; Roehner, Nicholas; Densmore, Douglas

    2017-04-03

    Design automation refers to a category of software tools for designing systems that work together in a workflow for designing, building, testing, and analyzing systems with a target behavior. In synthetic biology, these tools are called bio-design automation (BDA) tools. In this review, we discuss the BDA tools areas-specify, design, build, test, and learn-and introduce the existing software tools designed to solve problems in these areas. We then detail the functionality of some of these tools and show how they can be used together to create the desired behavior of two types of modern synthetic genetic regulatory networks.

  11. Bottom-up holographic approach to QCD

    Energy Technology Data Exchange (ETDEWEB)

    Afonin, S. S. [V. A. Fock Department of Theoretical Physics, Saint Petersburg State University, 1 ul. Ulyanovskaya, 198504 (Russian Federation)

    2016-01-22

    One of the most known result of the string theory consists in the idea that some strongly coupled gauge theories may have a dual description in terms of a higher dimensional weakly coupled gravitational theory — the so-called AdS/CFT correspondence or gauge/gravity correspondence. The attempts to apply this idea to the real QCD are often referred to as “holographic QCD” or “AdS/QCD approach”. One of directions in this field is to start from the real QCD and guess a tentative dual higher dimensional weakly coupled field model following the principles of gauge/gravity correspondence. The ensuing phenomenology can be then developed and compared with experimental data and with various theoretical results. Such a bottom-up holographic approach turned out to be unexpectedly successful in many cases. In the given short review, the technical aspects of the bottom-up holographic approach to QCD are explained placing the main emphasis on the soft wall model.

  12. Bottom-up holographic approach to QCD

    Science.gov (United States)

    Afonin, S. S.

    2016-01-01

    One of the most known result of the string theory consists in the idea that some strongly coupled gauge theories may have a dual description in terms of a higher dimensional weakly coupled gravitational theory — the so-called AdS/CFT correspondence or gauge/gravity correspondence. The attempts to apply this idea to the real QCD are often referred to as "holographic QCD" or "AdS/QCD approach". One of directions in this field is to start from the real QCD and guess a tentative dual higher dimensional weakly coupled field model following the principles of gauge/gravity correspondence. The ensuing phenomenology can be then developed and compared with experimental data and with various theoretical results. Such a bottom-up holographic approach turned out to be unexpectedly successful in many cases. In the given short review, the technical aspects of the bottom-up holographic approach to QCD are explained placing the main emphasis on the soft wall model.

  13. Engineering life through Synthetic Biology.

    Science.gov (United States)

    Chopra, Paras; Kamma, Akhil

    2006-01-01

    Synthetic Biology is a field involving synthesis of novel biological systems which are not generally found in nature. It has brought a new paradigm in science as it has enabled scientists to create life from the scratch, hence helping better understand the principles of biology. The viability of living organisms that use unnatural molecules is also being explored. Unconventional projects such as DNA playing tic-tac-toe, bacterial photographic film, etc. are taking biology to its extremes. The field holds a promise for mass production of cheap drugs and programming bacteria to seek-and-destroy tumors in the body. However, the complexity of biological systems make the field a challenging one. In addition to this, there are other major technical and ethical challenges which need to be addressed before the field realizes its true potential.

  14. Synthetic biology character and impact

    CERN Document Server

    Pade, Christian; Wigger, Henning; Gleich, Arnim

    2015-01-01

    Synthetic Biology is already an object of intensive debate. However, to a great extent the discussion to date has been concerned with fundamental ethical, religious and philosophical questions. By contrast, based on an investigation of the field’s scientific and technological character, this book focuses on new functionalities provided by synthetic biology and explores the associated opportunities and risks. Following an introduction to the subject and a discussion of the most central paradigms and methodologies, the book provides an overview of the structure of this field of science and technology. It informs the reader about the current stage of development, as well as topical problems and potential opportunities in important fields of application. But not only the science itself is in focus. In order to investigate its broader impact, ecological as well as ethical implications will be considered, paving the way for a discussion of responsibilities in the context of a field at a transitional crossroads be...

  15. Meeting Report: Synthetic Biology Jamboree for Undergraduates

    Science.gov (United States)

    Campbell, A. Malcolm

    2005-01-01

    The field of synthetic biology (the name is derived from an analogy to synthetic chemistry) has recognized itself as a "field" only since about 2002. Synthetic biology has gotten some high-profile attention recently, but most people are not aware the field even exists. Synthetic biologists apply engineering principles to genomic circuits to…

  16. Programmable chemical reaction networks: emulating regulatory functions in living cells using a bottom-up approach.

    Science.gov (United States)

    van Roekel, Hendrik W H; Rosier, Bas J H M; Meijer, Lenny H H; Hilbers, Peter A J; Markvoort, Albert J; Huck, Wilhelm T S; de Greef, Tom F A

    2015-11-07

    Living cells are able to produce a wide variety of biological responses when subjected to biochemical stimuli. It has become apparent that these biological responses are regulated by complex chemical reaction networks (CRNs). Unravelling the function of these circuits is a key topic of both systems biology and synthetic biology. Recent progress at the interface of chemistry and biology together with the realisation that current experimental tools are insufficient to quantitatively understand the molecular logic of pathways inside living cells has triggered renewed interest in the bottom-up development of CRNs. This builds upon earlier work of physical chemists who extensively studied inorganic CRNs and showed how a system of chemical reactions can give rise to complex spatiotemporal responses such as oscillations and pattern formation. Using purified biochemical components, in vitro synthetic biologists have started to engineer simplified model systems with the goal of mimicking biological responses of intracellular circuits. Emulation and reconstruction of system-level properties of intracellular networks using simplified circuits are able to reveal key design principles and molecular programs that underlie the biological function of interest. In this Tutorial Review, we present an accessible overview of this emerging field starting with key studies on inorganic CRNs followed by a discussion of recent work involving purified biochemical components. Finally, we review recent work showing the versatility of programmable biochemical reaction networks (BRNs) in analytical and diagnostic applications.

  17. Synthetic Biology Guides Biofuel Production

    Directory of Open Access Journals (Sweden)

    Michael R. Connor

    2010-01-01

    Full Text Available The advancement of microbial processes for the production of renewable liquid fuels has increased with concerns about the current fuel economy. The development of advanced biofuels in particular has risen to address some of the shortcomings of ethanol. These advanced fuels have chemical properties similar to petroleum-based liquid fuels, thus removing the need for engine modification or infrastructure redesign. While the productivity and titers of each of these processes remains to be improved, progress in synthetic biology has provided tools to guide the engineering of these processes through present and future challenges.

  18. Bottom-up assembly of metallic germanium.

    Science.gov (United States)

    Scappucci, Giordano; Klesse, Wolfgang M; Yeoh, LaReine A; Carter, Damien J; Warschkow, Oliver; Marks, Nigel A; Jaeger, David L; Capellini, Giovanni; Simmons, Michelle Y; Hamilton, Alexander R

    2015-08-10

    Extending chip performance beyond current limits of miniaturisation requires new materials and functionalities that integrate well with the silicon platform. Germanium fits these requirements and has been proposed as a high-mobility channel material, a light emitting medium in silicon-integrated lasers, and a plasmonic conductor for bio-sensing. Common to these diverse applications is the need for homogeneous, high electron densities in three-dimensions (3D). Here we use a bottom-up approach to demonstrate the 3D assembly of atomically sharp doping profiles in germanium by a repeated stacking of two-dimensional (2D) high-density phosphorus layers. This produces high-density (10(19) to 10(20) cm(-3)) low-resistivity (10(-4)Ω · cm) metallic germanium of precisely defined thickness, beyond the capabilities of diffusion-based doping technologies. We demonstrate that free electrons from distinct 2D dopant layers coalesce into a homogeneous 3D conductor using anisotropic quantum interference measurements, atom probe tomography, and density functional theory.

  19. A framework for assessing inter-individual variability in pharmacokinetics using virtual human populations and integrating general knowledge of physical chemistry, biology, anatomy, physiology and genetics: A tale of 'bottom-up' vs 'top-down' recognition of covariates.

    Science.gov (United States)

    Jamei, Masoud; Dickinson, Gemma L; Rostami-Hodjegan, Amin

    2009-01-01

    An increasing number of failures in clinical stages of drug development have been related to the effects of candidate drugs in a sub-group of patients rather than the 'average' person. Expectation of extreme effects or lack of therapeutic effects in some subgroups following administration of similar doses requires a full understanding of the issue of variability and the importance of identifying covariates that determine the exposure to the drug candidates in each individual. In any drug development program the earlier these covariates are known the better. An important component of the drive to decrease this failure rate in drug development involves attempts to use physiologically-based pharmacokinetics 'bottom-up' modeling and simulation to optimize molecular features with respect to the absorption, distribution, metabolism and elimination (ADME) processes. The key element of this approach is the separation of information on the system (i.e. human body) from that of the drug (e.g. physicochemical characteristics determining permeability through membranes, partitioning to tissues, binding to plasma proteins or affinities toward certain enzymes and transporter proteins) and the study design (e.g. dose, route and frequency of administration, concomitant drugs and food). In this review, the classical 'top-down' approach in covariate recognition is compared with the 'bottom-up' paradigm. The determinants and sources of inter-individual variability in different stages of drug absorption, distribution, metabolism and excretion are discussed in detail. Further, the commonly known tools for simulating ADME properties are introduced.

  20. Synthetic Biology in Health and Disease

    NARCIS (Netherlands)

    Passel, van M.W.J.; Lam, C.M.C.; Martins dos Santos, V.A.P.; Suarez Diez, M.

    2014-01-01

    Synthetic biology draws on the understanding from genetics, biology, chemistry, physics, engineering, and computational sciences to (re-)design and (re-)engineer biological functions. Here we address how synthetic biology can be possibly deployed to promote health and tackle disease. We discuss how

  1. BitCube: A Bottom-Up Cubing Engineering

    Science.gov (United States)

    Ferro, Alfredo; Giugno, Rosalba; Puglisi, Piera Laura; Pulvirenti, Alfredo

    Enhancing on line analytical processing through efficient cube computation plays a key role in Data Warehouse management. Hashing, grouping and mining techniques are commonly used to improve cube pre-computation. BitCube, a fast cubing method which uses bitmaps as inverted indexes for grouping, is presented. It horizontally partitions data according to the values of one dimension and for each resulting fragment it performs grouping following bottom-up criteria. BitCube allows also partial materialization based on iceberg conditions to treat large datasets for which a full cube pre-computation is too expensive. Space requirement of bitmaps is optimized by applying an adaption of the WAH compression technique. Experimental analysis, on both synthetic and real datasets, shows that BitCube outperforms previous algorithms for full cube computation and results comparable on iceberg cubing.

  2. Towards developing algal synthetic biology.

    Science.gov (United States)

    Scaife, Mark Aden; Smith, Alison Gail

    2016-06-15

    The genetic, physiological and metabolic diversity of microalgae has driven fundamental research into photosynthesis, flagella structure and function, and eukaryotic evolution. Within the last 10 years these organisms have also been investigated as potential biotechnology platforms, for example to produce high value compounds such as long chain polyunsaturated fatty acids, pigments and antioxidants, and for biodiesel precursors, in particular triacylglycerols (TAGs). Transformation protocols, molecular tools and genome sequences are available for a number of model species including the green alga Chlamydomonas reinhardtii and the diatom Phaeodactylum tricornutum, although for both species there are bottlenecks to be overcome to allow rapid and predictable genetic manipulation. One approach to do this would be to apply the principles of synthetic biology to microalgae, namely the cycle of Design-Build-Test, which requires more robust, predictable and high throughput methods. In this mini-review we highlight recent progress in the areas of improving transgene expression, genome editing, identification and design of standard genetic elements (parts), and the use of microfluidics to increase throughput. We suggest that combining these approaches will provide the means to establish algal synthetic biology, and that application of standard parts and workflows will avoid parallel development and capitalize on lessons learned from other systems.

  3. Synthetic biology - the state of play.

    Science.gov (United States)

    Kitney, Richard; Freemont, Paul

    2012-07-16

    Just over two years ago there was an article in Nature entitled "Five Hard Truths for Synthetic Biology". Since then, the field has moved on considerably. A number of economic commentators have shown that synthetic biology very significant industrial potential. This paper addresses key issues in relation to the state of play regarding synthetic biology. It first considers the current background to synthetic biology, whether it is a legitimate field and how it relates to foundational biological sciences. The fact that synthetic biology is a translational field is discussed and placed in the context of the industrial translation process. An important aspect of synthetic biology is platform technology, this topic is also discussed in some detail. Finally, examples of application areas are described.

  4. Rational design of modular circuits for gene transcription: A test of the bottom-up approach

    Directory of Open Access Journals (Sweden)

    Giordano Emanuele

    2010-11-01

    Full Text Available Abstract Background Most of synthetic circuits developed so far have been designed by an ad hoc approach, using a small number of components (i.e. LacI, TetR and a trial and error strategy. We are at the point where an increasing number of modular, inter-changeable and well-characterized components is needed to expand the construction of synthetic devices and to allow a rational approach to the design. Results We used interchangeable modular biological parts to create a set of novel synthetic devices for controlling gene transcription, and we developed a mathematical model of the modular circuits. Model parameters were identified by experimental measurements from a subset of modular combinations. The model revealed an unexpected feature of the lactose repressor system, i.e. a residual binding affinity for the operator site by induced lactose repressor molecules. Once this residual affinity was taken into account, the model properly reproduced the experimental data from the training set. The parameters identified in the training set allowed the prediction of the behavior of networks not included in the identification procedure. Conclusions This study provides new quantitative evidences that the use of independent and well-characterized biological parts and mathematical modeling, what is called a bottom-up approach to the construction of gene networks, can allow the design of new and different devices re-using the same modular parts.

  5. Microbial synthetic biology for human therapeutics.

    Science.gov (United States)

    Jain, Aastha; Bhatia, Pooja; Chugh, Archana

    2012-06-01

    The emerging field of synthetic biology holds tremendous potential for developing novel drugs to treat various human conditions. The current study discusses the scope of synthetic biology for human therapeutics via microbial approach. In this context, synthetic biology aims at designing, engineering and building new microbial synthetic cells that do not pre-exist in nature as well as re-engineer existing microbes for synthesis of therapeutic products. It is expected that the construction of novel microbial genetic circuitry for human therapeutics will greatly benefit from the data generated by 'omics' approaches and multidisciplinary nature of synthetic biology. Development of novel antimicrobial drugs and vaccines by engineering microbial systems are a promising area of research in the field of synthetic biology for human theragnostics. Expression of plant based medicinal compounds in the microbial system using synthetic biology tools is another avenue dealt in the present study. Additionally, the study suggest that the traditional medicinal knowledge can do value addition for developing novel drugs in the microbial systems using synthetic biology tools. The presented work envisions the success of synthetic biology for human therapeutics via microbial approach in a holistic manner. Keeping this in view, various legal and socio-ethical concerns emerging from the use of synthetic biology via microbial approach such as patenting, biosafety and biosecurity issues have been touched upon in the later sections.

  6. Synthetic biology: a utilitarian perspective.

    Science.gov (United States)

    Smith, Kevin

    2013-10-01

    I examine the positive and negative features of synthetic biology ('SynBio') from a utilitarian ethical perspective. The potential beneficial outcomes from SynBio in the context of medicine are substantial; however it is not presently possible to predict precise outcomes due to the nascent state of the field. Potential negative outcomes from SynBio also exist, including iatrogenesis and bioterrorism; however it is not yet possible to quantify these risks. I argue that the application of a 'precautionary' approach to SynBio is ethically fraught, as is the notion that SynBio-associated knowledge ought to be restricted. I conclude that utilitarians ought to support a broadly laissez-faire stance in respect of SynBio.

  7. Synthetic biology: from mainstream to counterculture.

    Science.gov (United States)

    Sleator, Roy D

    2016-09-01

    Existing at the interface of science and engineering, synthetic biology represents a new and emerging field of mainstream biology. However, there also exists a counterculture of Do-It-Yourself biologists, citizen scientists, who have made significant inroads, particularly in the design and development of new tools and techniques. Herein, I review the development and convergence of synthetic biology's mainstream and countercultures.

  8. Synergistic Synthetic Biology: Units in Concert.

    Science.gov (United States)

    Trosset, Jean-Yves; Carbonell, Pablo

    2013-01-01

    Synthetic biology aims at translating the methods and strategies from engineering into biology in order to streamline the design and construction of biological devices through standardized parts. Modular synthetic biology devices are designed by means of an adequate elimination of cross-talk that makes circuits orthogonal and specific. To that end, synthetic constructs need to be adequately optimized through in silico modeling by choosing the right complement of genetic parts and by experimental tuning through directed evolution and craftsmanship. In this review, we consider an additional and complementary tool available to the synthetic biologist for innovative design and successful construction of desired circuit functionalities: biological synergies. Synergy is a prevalent emergent property in biological systems that arises from the concerted action of multiple factors producing an amplification or cancelation effect compared with individual actions alone. Synergies appear in domains as diverse as those involved in chemical and protein activity, polypharmacology, and metabolic pathway complementarity. In conventional synthetic biology designs, synergistic cross-talk between parts and modules is generally attenuated in order to verify their orthogonality. Synergistic interactions, however, can induce emergent behavior that might prove useful for synthetic biology applications, like in functional circuit design, multi-drug treatment, or in sensing and delivery devices. Synergistic design principles are therefore complementary to those coming from orthogonal design and may provide added value to synthetic biology applications. The appropriate modeling, characterization, and design of synergies between biological parts and units will allow the discovery of yet unforeseeable, novel synthetic biology applications.

  9. Knowledge-making distinctions in synthetic biology.

    Science.gov (United States)

    O'Malley, Maureen A; Powell, Alexander; Davies, Jonathan F; Calvert, Jane

    2008-01-01

    Synthetic biology is an increasingly high-profile area of research that can be understood as encompassing three broad approaches towards the synthesis of living systems: DNA-based device construction, genome-driven cell engineering and protocell creation. Each approach is characterized by different aims, methods and constructs, in addition to a range of positions on intellectual property and regulatory regimes. We identify subtle but important differences between the schools in relation to their treatments of genetic determinism, cellular context and complexity. These distinctions tie into two broader issues that define synthetic biology: the relationships between biology and engineering, and between synthesis and analysis. These themes also illuminate synthetic biology's connections to genetic and other forms of biological engineering, as well as to systems biology. We suggest that all these knowledge-making distinctions in synthetic biology raise fundamental questions about the nature of biological investigation and its relationship to the construction of biological components and systems.

  10. Synthetic biology: programming cells for biomedical applications.

    Science.gov (United States)

    Hörner, Maximilian; Reischmann, Nadine; Weber, Wilfried

    2012-01-01

    The emerging field of synthetic biology is a novel biological discipline at the interface between traditional biology, chemistry, and engineering sciences. Synthetic biology aims at the rational design of complex synthetic biological devices and systems with desired properties by combining compatible, modular biological parts in a systematic manner. While the first engineered systems were mainly proof-of-principle studies to demonstrate the power of the modular engineering approach of synthetic biology, subsequent systems focus on applications in the health, environmental, and energy sectors. This review describes recent approaches for biomedical applications that were developed along the synthetic biology design hierarchy, at the level of individual parts, of devices, and of complex multicellular systems. It describes how synthetic biological parts can be used for the synthesis of drug-delivery tools, how synthetic biological devices can facilitate the discovery of novel drugs, and how multicellular synthetic ecosystems can give insight into population dynamics of parasites and hosts. These examples demonstrate how this new discipline could contribute to novel solutions in the biopharmaceutical industry.

  11. Word selection affects perceptions of synthetic biology.

    Science.gov (United States)

    Pearson, Brianna; Snell, Sam; Bye-Nagel, Kyri; Tonidandel, Scott; Heyer, Laurie J; Campbell, A Malcolm

    2011-07-21

    Members of the synthetic biology community have discussed the significance of word selection when describing synthetic biology to the general public. In particular, many leaders proposed the word "create" was laden with negative connotations. We found that word choice and framing does affect public perception of synthetic biology. In a controlled experiment, participants perceived synthetic biology more negatively when "create" was used to describe the field compared to "construct" (p = 0.008). Contrary to popular opinion among synthetic biologists, however, low religiosity individuals were more influenced negatively by the framing manipulation than high religiosity people. Our results suggest that synthetic biologists directly influence public perception of their field through avoidance of the word "create".

  12. Word selection affects perceptions of synthetic biology

    Directory of Open Access Journals (Sweden)

    Tonidandel Scott

    2011-07-01

    Full Text Available Abstract Members of the synthetic biology community have discussed the significance of word selection when describing synthetic biology to the general public. In particular, many leaders proposed the word "create" was laden with negative connotations. We found that word choice and framing does affect public perception of synthetic biology. In a controlled experiment, participants perceived synthetic biology more negatively when "create" was used to describe the field compared to "construct" (p = 0.008. Contrary to popular opinion among synthetic biologists, however, low religiosity individuals were more influenced negatively by the framing manipulation than high religiosity people. Our results suggest that synthetic biologists directly influence public perception of their field through avoidance of the word "create".

  13. Grand challenges in space synthetic biology.

    Science.gov (United States)

    Menezes, Amor A; Montague, Michael G; Cumbers, John; Hogan, John A; Arkin, Adam P

    2015-12-06

    Space synthetic biology is a branch of biotechnology dedicated to engineering biological systems for space exploration, industry and science. There is significant public and private interest in designing robust and reliable organisms that can assist on long-duration astronaut missions. Recent work has also demonstrated that such synthetic biology is a feasible payload minimization and life support approach as well. This article identifies the challenges and opportunities that lie ahead in the field of space synthetic biology, while highlighting relevant progress. It also outlines anticipated broader benefits from this field, because space engineering advances will drive technological innovation on Earth.

  14. Enabling plant synthetic biology through genome engineering.

    Science.gov (United States)

    Baltes, Nicholas J; Voytas, Daniel F

    2015-02-01

    Synthetic biology seeks to create new biological systems, including user-designed plants and plant cells. These systems can be employed for a variety of purposes, ranging from producing compounds of industrial or therapeutic value, to reducing crop losses by altering cellular responses to pathogens or climate change. To realize the full potential of plant synthetic biology, techniques are required that provide control over the genetic code - enabling targeted modifications to DNA sequences within living plant cells. Such control is now within reach owing to recent advances in the use of sequence-specific nucleases to precisely engineer genomes. We discuss here the enormous potential provided by genome engineering for plant synthetic biology.

  15. Synthetic biology: mapping the scientific landscape.

    Science.gov (United States)

    Oldham, Paul; Hall, Stephen; Burton, Geoff

    2012-01-01

    This article uses data from Thomson Reuters Web of Science to map and analyse the scientific landscape for synthetic biology. The article draws on recent advances in data visualisation and analytics with the aim of informing upcoming international policy debates on the governance of synthetic biology by the Subsidiary Body on Scientific, Technical and Technological Advice (SBSTTA) of the United Nations Convention on Biological Diversity. We use mapping techniques to identify how synthetic biology can best be understood and the range of institutions, researchers and funding agencies involved. Debates under the Convention are likely to focus on a possible moratorium on the field release of synthetic organisms, cells or genomes. Based on the empirical evidence we propose that guidance could be provided to funding agencies to respect the letter and spirit of the Convention on Biological Diversity in making research investments. Building on the recommendations of the United States Presidential Commission for the Study of Bioethical Issues we demonstrate that it is possible to promote independent and transparent monitoring of developments in synthetic biology using modern information tools. In particular, public and policy understanding and engagement with synthetic biology can be enhanced through the use of online interactive tools. As a step forward in this process we make existing data on the scientific literature on synthetic biology available in an online interactive workbook so that researchers, policy makers and civil society can explore the data and draw conclusions for themselves.

  16. Synthetic biology: mapping the scientific landscape.

    Directory of Open Access Journals (Sweden)

    Paul Oldham

    Full Text Available This article uses data from Thomson Reuters Web of Science to map and analyse the scientific landscape for synthetic biology. The article draws on recent advances in data visualisation and analytics with the aim of informing upcoming international policy debates on the governance of synthetic biology by the Subsidiary Body on Scientific, Technical and Technological Advice (SBSTTA of the United Nations Convention on Biological Diversity. We use mapping techniques to identify how synthetic biology can best be understood and the range of institutions, researchers and funding agencies involved. Debates under the Convention are likely to focus on a possible moratorium on the field release of synthetic organisms, cells or genomes. Based on the empirical evidence we propose that guidance could be provided to funding agencies to respect the letter and spirit of the Convention on Biological Diversity in making research investments. Building on the recommendations of the United States Presidential Commission for the Study of Bioethical Issues we demonstrate that it is possible to promote independent and transparent monitoring of developments in synthetic biology using modern information tools. In particular, public and policy understanding and engagement with synthetic biology can be enhanced through the use of online interactive tools. As a step forward in this process we make existing data on the scientific literature on synthetic biology available in an online interactive workbook so that researchers, policy makers and civil society can explore the data and draw conclusions for themselves.

  17. Bottom-up GGM algorithm for constructing multiple layered hierarchical gene regulatory networks

    Science.gov (United States)

    Multilayered hierarchical gene regulatory networks (ML-hGRNs) are very important for understanding genetics regulation of biological pathways. However, there are currently no computational algorithms available for directly building ML-hGRNs that regulate biological pathways. A bottom-up graphic Gaus...

  18. Grand challenges in space synthetic biology

    OpenAIRE

    Menezes, Amor A.; Montague, Michael G.; Cumbers, John; Hogan, John A.; Arkin, Adam P.

    2015-01-01

    Space synthetic biology is a branch of biotechnology dedicated to engineering biological systems for space exploration, industry and science. There is significant public and private interest in designing robust and reliable organisms that can assist on long-duration astronaut missions. Recent work has also demonstrated that such synthetic biology is a feasible payload minimization and life support approach as well. This article identifies the challenges and opportunities that lie ahead in the...

  19. Synthetic Biology: game changer in intelectual property

    Directory of Open Access Journals (Sweden)

    Laurens Landeweerd

    2016-12-01

    Full Text Available Synthetic biology can be considered a game changer that plays an important role in the current NBIC, or BINC convergence of nano-, bio-, info and cognitive sciences. Although most synthetic biology experts are unaware of it, the field appeals to the imagination in its adherence to targets that were usually associated with premodern alchemist science. This paper elaborates several aspects of synthetic biology as well as its consequences for long held notions of intellectual property and the ontological categories of scientific discovery on the one hand and engineering on the other, the distinction between natural and artificial, the grown and the made.

  20. Engineering microbes with synthetic biology frameworks.

    Science.gov (United States)

    Leonard, Effendi; Nielsen, David; Solomon, Kevin; Prather, Kristala Jones

    2008-12-01

    Typically, the outcome of biologically engineered unit operations cannot be controlled a priori due to the incorporation of ad hoc design into complex natural systems. To mitigate this problem, synthetic biology presents a systematic approach to standardizing biological components for the purpose of increasing their programmability and robustness when assembled with the aim to achieve novel biological functions. A complex engineered biological system using only standardized biological components is yet to exist. Nevertheless, current attempts to create and to implement modular, standardized biological components pave the way for the future creation of highly predictable artificial biological systems. Although synthetic biology frameworks can be applied to any biological engineering endeavor, this article will focus on providing a brief overview of advances in the field and its recent utilization for the engineering of microbes.

  1. Biological Applications of Synthetic Nanomachines

    Science.gov (United States)

    Kagan, Daniel Robert

    The field of synthetic nano/microscale propulsion devices has been rapidly expanding because of their ability to possess many key features necessary for bioanalytical applications on biological microchip devices and targeted in vivo delivery. Past studies focused on developing powerful and easily controllable motors by investigating different propulsion schemes (e.g. electrophoretic, bubble release, magnetically propelled) for use in physiological environments. These engineering advancements and the nanomotors inherit capabilities have allowed for their use in three research areas: motion-based biosensing, cellular and biomolecular isolation, and targeted drug delivery. The first research area investigates a unique speed increase of electrophoretically propelled nanomotors when in the presence of silver ions. Au/Pt nanomotors propel by the electrocatalytic decomposition of H2O2 fuel. While most metal ions resulted in a decrease in speed to near Brownian levels, Ag+ has shown a steady increase in speed from 10microm/s to 52microm/s over the micro-molar range. This phenomenon was exploited by tagging nucleic acid detector probes with Ag nanoparticles when conducting simple sandwich assays. This resulted in a cheap, fast, and sensitive, motion-based readout of the concentration-dependent DNA target present on the sandwich assay. The second area of research involved the bioisolation of nucleic acids, protein, bacteria, and cancer cells by bubble-based microrockets. These microrockets contain a platinum interior to catalyze peroxide fuel and can be easily functionalized with antibodies and nucleic acid capture probes to isolate target biomolecules. The motion of these micro-isolation devices creates convection for faster isolation and can be used to transport the biomolecules to a clean environment. The third area of research is focused on targeted drug delivery by various propulsion methods. The ability of nanomotors to transport PLGA and liposome drug vesicles to

  2. Bottom-up Initiatives for Photovoltaic: Incentives and Barriers

    Directory of Open Access Journals (Sweden)

    Kathrin Reinsberger

    2014-06-01

    Full Text Available When facing the challenge of restructuring the energy system, bottom-up initiatives can aid the diffusion of decentralized and clean energy technologies. We focused here on a bottom-up initiative of citizen-funded and citizen-operated photovoltaic power plants. The project follows a case study-based approach and examines two different community initiatives. The aim is to investigate the potential incentives and barriers relating to participation or non-participation in predefined community PV projects. Qualitative, as well as quantitative empirical research was used to examine the key factors in the further development of bottom-up initiatives as contributors to a general energy transition.

  3. The 'atom-splitting' moment of synthetic biology: Nuclear physics and synthetic biology share common features

    OpenAIRE

    Valentine, Alex J; Kleinert, Aleysia; Verdier, Jerome

    2012-01-01

    Synthetic biology and nuclear physics share many commonalities in terms of public perception and funding. Synthetic biologists could learn valuable lessons from the history of the atomic bomb and nuclear power.

  4. Standardization for natural product synthetic biology.

    Science.gov (United States)

    Zhao, Huimin; Medema, Marnix H

    2016-08-27

    Standardization is one of the foundational features of modern-day engineering, and the use of standardized parts and processes is a key element that distinguishes bona fide synthetic biology from traditional genetic engineering. Here, we discuss the role of standardization in natural product synthetic biology, focusing on standardization of data on biosynthetic pathways and gene clusters, as well as the role of standardization in the process of biosynthetic gene cluster engineering.

  5. Systems and synthetic biology as emerging technosciences

    Directory of Open Access Journals (Sweden)

    Karen Kastenhofer

    2016-12-01

    Full Text Available Systems and synthetic biology can be understood as emerging technosciences. Both are characteristically shaped by promises and visions, a certain logic and function of labelling, specific forms of social organisation, an embedding in specific regimes of funding and innovation as well as a characteristic matrix of orientations within research practice. This characteristic constitution of systems and synthetic biology has fundamental consequences for scientific practice, its analysis and its governance.

  6. [Progress in synthetic biology of "973 Funding Program" in China].

    Science.gov (United States)

    Chen, Guoqiang; Wang, Ying

    2015-06-01

    This paper reviews progresses made in China from 2011 in areas of "Synthetic Biology" supported by State Basic Research 973 Program. Till the end of 2014, 9 "synthetic biology" projects have been initiated with emphasis on "microbial manufactures" with the 973 Funding Program. Combined with the very recent launch of one project on "mammalian cell synthetic biology" and another on "plant synthetic biology", Chinese "synthetic biology" research reflects its focus on "manufactures" while not giving up efforts on "synthetic biology" of complex systems.

  7. Nanoelectronics: Thermoelectric Phenomena in «Bottom-Up» Approach

    Directory of Open Access Journals (Sweden)

    Yu.A. Kruglyak

    2014-04-01

    Full Text Available Thermoelectric phenomena of Seebeck and Peltier, quality indicators and thermoelectric optimization, ballistic and diffusive phonon heat current are discussed in the frame of the «bottom-up» approach of modern nanoelectronics.

  8. Biomedical synthetic biology: an overview for physicians.

    Science.gov (United States)

    Keret, Ophir

    2013-06-01

    Synthetic bioiogy is a ,relatively new fieild of bologlcal research and development that focases on the engineering of genetic molecular machlnes wIth a specific predefined function. Plainly put the newly engineered organism functions as a machine. It can process information. manufature, heal and even diagnose. We just have to engineer It to do so. The famous quote "Biology Is the nanotechnology that works" is currently being put to the test on a worldwide scale. The application of these machines Is theoretically boundless. In laboratories worldwide synthetic biology technologies are being rationally designed to assist in diagnosis or disrupt disease mechnisms. In the not too distant future they are expected to reach the clinical setting. This new field should be distinguished from classic genetic engineering. The latter researches naturalfy found DNA segments via cloning. It is weakly associated with engineering. Synthetic biology focuses on the engineering of molecular biological machines for the benefit of mankind. This is done via synthetic (computer printed) DNA sequences, man-designed or altered in silico. In this article I will briefly introduce synthetic biology, elaborate on the BiobrickFoundation as an independent fast-growing synthetic biology-sharing movement, and report on selected developing applications for medicine.

  9. Informing biological design by integration of systems and synthetic biology.

    Science.gov (United States)

    Smolke, Christina D; Silver, Pamela A

    2011-03-18

    Synthetic biology aims to make the engineering of biology faster and more predictable. In contrast, systems biology focuses on the interaction of myriad components and how these give rise to the dynamic and complex behavior of biological systems. Here, we examine the synergies between these two fields.

  10. The Synthetic Biology Open Language (SBOL) provides a community standard for communicating designs in synthetic biology.

    Science.gov (United States)

    Galdzicki, Michal; Clancy, Kevin P; Oberortner, Ernst; Pocock, Matthew; Quinn, Jacqueline Y; Rodriguez, Cesar A; Roehner, Nicholas; Wilson, Mandy L; Adam, Laura; Anderson, J Christopher; Bartley, Bryan A; Beal, Jacob; Chandran, Deepak; Chen, Joanna; Densmore, Douglas; Endy, Drew; Grünberg, Raik; Hallinan, Jennifer; Hillson, Nathan J; Johnson, Jeffrey D; Kuchinsky, Allan; Lux, Matthew; Misirli, Goksel; Peccoud, Jean; Plahar, Hector A; Sirin, Evren; Stan, Guy-Bart; Villalobos, Alan; Wipat, Anil; Gennari, John H; Myers, Chris J; Sauro, Herbert M

    2014-06-01

    The re-use of previously validated designs is critical to the evolution of synthetic biology from a research discipline to an engineering practice. Here we describe the Synthetic Biology Open Language (SBOL), a proposed data standard for exchanging designs within the synthetic biology community. SBOL represents synthetic biology designs in a community-driven, formalized format for exchange between software tools, research groups and commercial service providers. The SBOL Developers Group has implemented SBOL as an XML/RDF serialization and provides software libraries and specification documentation to help developers implement SBOL in their own software. We describe early successes, including a demonstration of the utility of SBOL for information exchange between several different software tools and repositories from both academic and industrial partners. As a community-driven standard, SBOL will be updated as synthetic biology evolves to provide specific capabilities for different aspects of the synthetic biology workflow.

  11. Bridging the gap between systems biology and synthetic biology.

    Science.gov (United States)

    Liu, Di; Hoynes-O'Connor, Allison; Zhang, Fuzhong

    2013-01-01

    Systems biology is an inter-disciplinary science that studies the complex interactions and the collective behavior of a cell or an organism. Synthetic biology, as a technological subject, combines biological science and engineering, allowing the design and manipulation of a system for certain applications. Both systems and synthetic biology have played important roles in the recent development of microbial platforms for energy, materials, and environmental applications. More importantly, systems biology provides the knowledge necessary for the development of synthetic biology tools, which in turn facilitates the manipulation and understanding of complex biological systems. Thus, the combination of systems and synthetic biology has huge potential for studying and engineering microbes, especially to perform advanced tasks, such as producing biofuels. Although there have been very few studies in integrating systems and synthetic biology, existing examples have demonstrated great power in extending microbiological capabilities. This review focuses on recent efforts in microbiological genomics, transcriptomics, proteomics, and metabolomics, aiming to fill the gap between systems and synthetic biology.

  12. Mammalian synthetic biology: emerging medical applications.

    Science.gov (United States)

    Kis, Zoltán; Pereira, Hugo Sant'Ana; Homma, Takayuki; Pedrigi, Ryan M; Krams, Rob

    2015-05-06

    In this review, we discuss new emerging medical applications of the rapidly evolving field of mammalian synthetic biology. We start with simple mammalian synthetic biological components and move towards more complex and therapy-oriented gene circuits. A comprehensive list of ON-OFF switches, categorized into transcriptional, post-transcriptional, translational and post-translational, is presented in the first sections. Subsequently, Boolean logic gates, synthetic mammalian oscillators and toggle switches will be described. Several synthetic gene networks are further reviewed in the medical applications section, including cancer therapy gene circuits, immuno-regulatory networks, among others. The final sections focus on the applicability of synthetic gene networks to drug discovery, drug delivery, receptor-activating gene circuits and mammalian biomanufacturing processes.

  13. Bottom-Up Synthesis and Sensor Applications of Biomimetic Nanostructures

    Directory of Open Access Journals (Sweden)

    Li Wang

    2016-01-01

    Full Text Available The combination of nanotechnology, biology, and bioengineering greatly improved the developments of nanomaterials with unique functions and properties. Biomolecules as the nanoscale building blocks play very important roles for the final formation of functional nanostructures. Many kinds of novel nanostructures have been created by using the bioinspired self-assembly and subsequent binding with various nanoparticles. In this review, we summarized the studies on the fabrications and sensor applications of biomimetic nanostructures. The strategies for creating different bottom-up nanostructures by using biomolecules like DNA, protein, peptide, and virus, as well as microorganisms like bacteria and plant leaf are introduced. In addition, the potential applications of the synthesized biomimetic nanostructures for colorimetry, fluorescence, surface plasmon resonance, surface-enhanced Raman scattering, electrical resistance, electrochemistry, and quartz crystal microbalance sensors are presented. This review will promote the understanding of relationships between biomolecules/microorganisms and functional nanomaterials in one way, and in another way it will guide the design and synthesis of biomimetic nanomaterials with unique properties in the future.

  14. Synthetic biology and the technicity of biofuels.

    Science.gov (United States)

    Mackenzie, Adrian

    2013-06-01

    The principal existing real-world application of synthetic biology is biofuels. Several 'next generation biofuel' companies-Synthetic Genomics, Amyris and Joule Unlimited Technologies-claim to be using synthetic biology to make biofuels. The irony of this is that highly advanced science and engineering serves the very mundane and familiar realm of transport. Despite their rather prosaic nature, biofuels could offer an interesting way to highlight the novelty of synthetic biology from several angles at once. Drawing on the French philosopher of technology and biology Gilbert Simondon, we can understand biofuels as technical objects whose genesis involves processes of concretisation that negotiate between heterogeneous geographical, biological, technical, scientific and commercial realities. Simondon's notion of technicity, the degree of concretisation of a technical object, usefully conceptualises this relationality. Viewed in terms of technicity, we might understand better how technical entities, elements, and ensembles are coming into being in the name of synthetic biology. The broader argument here is that when we seek to identify the newness of disciplines, their newness might be less epistemic and more logistic.

  15. News: Synthetic biology leading to specialty chemicals

    Science.gov (United States)

    Synthetic biology can combine the disciplines of biology, engineering, and chemistry productively to form molecules of great scientific and commercial value. Recent advances in the new field are explored for their connection to new tools that have been used to elucidate productio...

  16. Realizing the potential of synthetic biology.

    Science.gov (United States)

    Church, George M; Elowitz, Michael B; Smolke, Christina D; Voigt, Christopher A; Weiss, Ron

    2014-04-01

    Synthetic biology, despite still being in its infancy, is increasingly providing valuable information for applications in the clinic, the biotechnology industry and in basic molecular research. Both its unique potential and the challenges it presents have brought together the expertise of an eclectic group of scientists, from cell biologists to engineers. In this Viewpoint article, five experts discuss their views on the future of synthetic biology, on its main achievements in basic and applied science, and on the bioethical issues that are associated with the design of new biological systems.

  17. Synthetic biology and biosecurity: challenging the "myths".

    Science.gov (United States)

    Jefferson, Catherine; Lentzos, Filippa; Marris, Claire

    2014-01-01

    Synthetic biology, a field that aims to "make biology easier to engineer," is routinely described as leading to an increase in the "dual-use" threat, i.e., the potential for the same scientific research to be "used" for peaceful purposes or "misused" for warfare or terrorism. Fears have been expressed that the "de-skilling" of biology, combined with online access to the genomic DNA sequences of pathogenic organisms and the reduction in price for DNA synthesis, will make biology increasingly accessible to people operating outside well-equipped professional research laboratories, including people with malevolent intentions. The emergence of do-it-yourself (DIY) biology communities and of the student iGEM competition has come to epitomize this supposed trend toward greater ease of access and the associated potential threat from rogue actors. In this article, we identify five "myths" that permeate discussions about synthetic biology and biosecurity, and argue that they embody misleading assumptions about both synthetic biology and bioterrorism. We demonstrate how these myths are challenged by more realistic understandings of the scientific research currently being conducted in both professional and DIY laboratories, and by an analysis of historical cases of bioterrorism. We show that the importance of tacit knowledge is commonly overlooked in the dominant narrative: the focus is on access to biological materials and digital information, rather than on human practices and institutional dimensions. As a result, public discourse on synthetic biology and biosecurity tends to portray speculative scenarios about the future as realities in the present or the near future, when this is not warranted. We suggest that these "myths" play an important role in defining synthetic biology as a "promissory" field of research and as an "emerging technology" in need of governance.

  18. Chemical synthetic biology: a mini-review

    Directory of Open Access Journals (Sweden)

    Cristiano eChiarabelli

    2013-09-01

    Full Text Available Chemical synthetic biology (CSB is a branch of synthetic biology (SB oriented towards the synthesis of chemical structures alternative to those present in nature. Whereas SB combines biology and engineering with the aim of synthesizing biological structures or life forms that do not exist in nature – often based on genome manipulation, CSB uses and assembles biological parts, synthetic or not, to create new and alternative structures. A short epistemological note will introduce the theoretical concepts related to these fields, whereas the text will be largely devoted to introduce and comment two main projects of CSB, carried out in our laboratory in the recent years.The Never Born Biopolymers (NBB project deals with the construction and the screening of RNA and peptide sequences that are not present in nature, whereas the Minimal Cell project focuses on the construction of semi-synthetic compartments (usually liposomes containing the minimal and sufficient number of components to perform the basic function of a biological cell.These two topics are extremely important for both the general understanding of biology in terms of function, organization and development, and for applied biotechnology.

  19. WISB: Warwick Integrative Synthetic Biology Centre.

    Science.gov (United States)

    McCarthy, John

    2016-06-15

    Synthetic biology promises to create high-impact solutions to challenges in the areas of biotechnology, human/animal health, the environment, energy, materials and food security. Equally, synthetic biologists create tools and strategies that have the potential to help us answer important fundamental questions in biology. Warwick Integrative Synthetic Biology (WISB) pursues both of these mutually complementary 'build to apply' and 'build to understand' approaches. This is reflected in our research structure, in which a core theme on predictive biosystems engineering develops underpinning understanding as well as next-generation experimental/theoretical tools, and these are then incorporated into three applied themes in which we engineer biosynthetic pathways, microbial communities and microbial effector systems in plants. WISB takes a comprehensive approach to training, education and outreach. For example, WISB is a partner in the EPSRC/BBSRC-funded U.K. Doctoral Training Centre in synthetic biology, we have developed a new undergraduate module in the subject, and we have established five WISB Research Career Development Fellowships to support young group leaders. Research in Ethical, Legal and Societal Aspects (ELSA) of synthetic biology is embedded in our centre activities. WISB has been highly proactive in building an international research and training network that includes partners in Barcelona, Boston, Copenhagen, Madrid, Marburg, São Paulo, Tartu and Valencia.

  20. Cell-free biology: exploiting the interface between synthetic biology and synthetic chemistry.

    Science.gov (United States)

    Harris, D Calvin; Jewett, Michael C

    2012-10-01

    Just as synthetic organic chemistry once revolutionized the ability of chemists to build molecules (including those that did not exist in nature) following a basic set of design rules, cell-free synthetic biology is beginning to provide an improved toolbox and faster process for not only harnessing but also expanding the chemistry of life. At the interface between chemistry and biology, research in cell-free synthetic systems is proceeding in two different directions: using synthetic biology for synthetic chemistry and using synthetic chemistry to reprogram or mimic biology. In the coming years, the impact of advances inspired by these approaches will make possible the synthesis of nonbiological polymers having new backbone compositions, new chemical properties, new structures, and new functions.

  1. On a Bottom-Up Approach to Scientific Discovery

    Science.gov (United States)

    Huang, Xiang

    2014-03-01

    Two popular models of scientific discovery, abduction and the inference to the best explanation (IBE), presuppose that the reason for accepting a hypothetical explanation A comes from the epistemic and/or explanatory force manifested in the fact that observed fact C is an inferred consequence of A. However, not all discoveries take this top-down procedure from A to C, in which the result of discovery A implies the observed fact C. I contend that discovery can be modeled as a bottom-up procedure based on inductive and analogical rules that lead us to infer from C to A. I take the theory of Dignaga, an Indian medieval logician, as a model of this bottom-up approach. My argument has three panels: 1) this bottom-up approach applies to both commonsense and scientific discovery without the assumption that C has to be an inferred consequence of A; 2) this bottom-up approach helps us get around problems that crop up in applying abduction and/or IBE, which means that scientific discovery need not to be modeled exclusively by top-down approaches; and 3) the existence of the bottom-up approach requires a pluralist attitude towards modeling of scientific discovery.

  2. Tunable promoters in synthetic and systems biology

    DEFF Research Database (Denmark)

    Dehli, Tore; Solem, Christian; Jensen, Peter Ruhdal

    2012-01-01

    in synthetic biology. A number of tools exist to manipulate the steps in between gene sequence and functional protein in living cells, but out of these the most straight-forward approach is to alter the gene expression level by manipulating the promoter sequence. Some of the promoter tuning tools available......Synthetic and systems biologists need standardized, modular and orthogonal tools yielding predictable functions in vivo. In systems biology such tools are needed to quantitatively analyze the behavior of biological systems while the efficient engineering of artificial gene networks is central...... for accomplishing such altered gene expression levels are discussed here along with examples of their use, and ideas for new tools are described. The road ahead looks very promising for synthetic and systems biologists as tools to achieve just about anything in terms of tuning and timing multiple gene expression...

  3. A plea for Global Health Action bottom-up

    Directory of Open Access Journals (Sweden)

    Ulrich Laaser

    2016-10-01

    Full Text Available This opinion piece focuses on global health action by hands-on bottom-up practice: Initiation of an organizational framework and securing financial efficiency are – however - essential, both clearly a domain of well trained public health professionals. Examples of action are cited in the four main areas of global threats: planetary climate change, global divides and inequity, global insecurity and violent conflicts, global instability and financial crises. In conclusion a stable health systems policy framework would greatly enhance success. However, such organisational framework dries out if not linked to public debates channelling fresh thoughts and controversial proposals: the structural stabilisation is essential but has to serve not to dominate bottom-up activities. In other words a horizontal management is required, a balanced equilibrium between bottom-up initiative and top-down support. Last not least rewarding voluntary and charity work by public acknowledgement is essential.

  4. Synthetic Biology: legal context and public policies

    Directory of Open Access Journals (Sweden)

    Vicente Bellver Capella

    2016-12-01

    Full Text Available The paper considers three questions with the goal of improving the proposals about the governance and regulation of Synthetic Biology. First, it looks at the relationship between some of the breakthroughs in this field and the public interest in the matter. Second, it is mentioned the international regulation on this topic and particularly the principles that inform and should inform this matter. Third, a critical consideration on the reports devoted to the ethical and social aspects of Synthetic Biology is included.

  5. Synthetic Biology: Applications in the Food Sector.

    Science.gov (United States)

    Tyagi, Ashish; Kumar, Ashwani; Aparna, S V; Mallappa, Rashmi H; Grover, Sunita; Batish, Virender Kumar

    2016-08-17

    Synthetic biology also termed as "genomic alchemy" represents a powerful area of science that is based on the convergence of biological sciences with systems engineering. It has been fittingly described as "moving from reading the genetic code to writing it" as it focuses on building, modeling, designing and fabricating novel biological systems using customized gene components that result in artificially created genetic circuitry. The scientifically compelling idea of the technological manipulation of life has been advocated since long time. Realization of this idea has gained momentum with development of high speed automation and the falling cost of gene sequencing and synthesis following the completion of the human genome project. Synthetic biology will certainly be instrumental in shaping the development of varying areas ranging from biomedicine, biopharmaceuticals, chemical production, food and dairy quality monitoring, packaging, and storage of food and dairy products, bioremediation and bioenergy production, etc. However, potential dangers of using synthetic life forms have to be acknowledged and adoption of policies by the scientific community to ensure safe practice while making important advancements in the ever expanding field of synthetic biology is to be fully supported and implemented.

  6. Prospects for applying synthetic biology to toxicology

    DEFF Research Database (Denmark)

    Behrendorff, James Bruce Yarnton H; Gillam, Elizabeth M.J.

    2017-01-01

    The 30 years since the inception of Chemical Research in Toxicology, game-changing advances in chemical and molecular biology, the fundamental disciplines underpinning molecular toxicology, have been made. While these have led to important advances in the study of mechanisms by which chemicals...... damage cells and systems, there has been less focus on applying these advances to prediction, detection, and mitigation of toxicity. Over the last ∼15 years, synthetic biology, the repurposing of biological "parts" in systems engineered for useful ends, has been explored in other areas of the biomedical...... and life sciences, for such applications as detecting metabolites, drug discovery and delivery, investigating disease mechanisms, improving medical treatment, and producing useful chemicals. These examples provide models for the application of synthetic biology to toxicology, which, for the most part, has...

  7. An integrated top-down and bottom-up strategy for characterization protein isoforms and modifications

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Si; Tolic, Nikola; Tian, Zhixin; Robinson, Errol W.; Pasa-Tolic, Ljiljana

    2011-04-15

    Bottom-up and top-down strategies are two commonly used methods for mass spectrometry (MS) based protein identification; each method has its own advantages and disadvantages. In this chapter, we describe an integrated top-down and bottom-up approach facilitated by concurrent liquid chromatography-mass spectrometry (LC-MS) analysis and fraction collection for comprehensive high-throughput intact protein profiling. The approach employs a high resolution reversed phase (RP) LC separation coupled with LC eluent fraction collection and concurrent on-line MS with a high field (12 Tesla) Fourier-transform ion cyclotron resonance (FTICR) mass spectrometer. Protein elusion profiles and tentative modified protein identification are made using detected intact protein mass in conjunction with bottom-up protein identifications from the enzymatic digestion and analysis of corresponding LC fractions. Specific proteins of biological interest are incorporated into a target ion list for subsequent off-line gas-phase fragmentation that uses an aliquot of the original collected LC fraction, an aliquot of which was also used for bottom-up analysis.

  8. Bottom up approaches to defining future climate mitigation commitments

    NARCIS (Netherlands)

    Elzen MGJ den; Berk MM; KMD

    2005-01-01

    Dit rapport beschrijft de resultaten van een aantal in de literatuur geopperde alternatieve, bottom-up benaderingen om verplichtingen vorm te geven,i.e. technologie en performance standaards, technologie onderzoek en ontwikkelingsafspraken, sectorale verplichtingen, S-CDM (Sectoraal CDM) en SD-P

  9. Bottom up approaches to defining future climate mitigation commitments

    NARCIS (Netherlands)

    Elzen MGJ den; Berk MM; KMD

    2005-01-01

    This report analyses a number of alternative, bottom-up approaches, i.e. technology and performance standards; technology Research and Development agreements, sectoral targets (national /transnational), sector based CDM, and sustainable development policies and measures (SD-PAMs). Included are tech

  10. A bottom-up approach to MEDLINE indexing recommendations

    DEFF Research Database (Denmark)

    Jimeno-Yepes, Antonio; Wilkowski, Bartlomiej; Mork, James/G

    2011-01-01

    MEDLINE indexing performed by the US National Library of Medicine staff describes the essence of a biomedical publication in about 14 Medical Subject Headings (MeSH). Since 2002, this task is assisted by the Medical Text Indexer (MTI) program. We present a bottom-up approach to MEDLINE indexing...

  11. Bottom-Up Analysis of Single-Case Research Designs

    Science.gov (United States)

    Parker, Richard I.; Vannest, Kimberly J.

    2012-01-01

    This paper defines and promotes the qualities of a "bottom-up" approach to single-case research (SCR) data analysis. Although "top-down" models, for example, multi-level or hierarchical linear models, are gaining momentum and have much to offer, interventionists should be cautious about analyses that are not easily understood, are not governed by…

  12. Reading Nature from a "Bottom-Up" Perspective

    Science.gov (United States)

    Magntorn, Ola; Hellden, Gustav

    2007-01-01

    This paper reports on a study of ecology teaching and learning in a Swedish primary school class (age 10-11 yrs). A teaching sequence was designed to help students read nature in a river ecosystem. The teaching sequence had a "bottom up" approach, taking as its starting point a common key organism--the freshwater shrimp. From this species and its…

  13. Identifying robust communities and multi-community nodes by combining top-down and bottom-up approaches to clustering.

    Science.gov (United States)

    Gaiteri, Chris; Chen, Mingming; Szymanski, Boleslaw; Kuzmin, Konstantin; Xie, Jierui; Lee, Changkyu; Blanche, Timothy; Chaibub Neto, Elias; Huang, Su-Chun; Grabowski, Thomas; Madhyastha, Tara; Komashko, Vitalina

    2015-11-09

    Biological functions are carried out by groups of interacting molecules, cells or tissues, known as communities. Membership in these communities may overlap when biological components are involved in multiple functions. However, traditional clustering methods detect non-overlapping communities. These detected communities may also be unstable and difficult to replicate, because traditional methods are sensitive to noise and parameter settings. These aspects of traditional clustering methods limit our ability to detect biological communities, and therefore our ability to understand biological functions. To address these limitations and detect robust overlapping biological communities, we propose an unorthodox clustering method called SpeakEasy which identifies communities using top-down and bottom-up approaches simultaneously. Specifically, nodes join communities based on their local connections, as well as global information about the network structure. This method can quantify the stability of each community, automatically identify the number of communities, and quickly cluster networks with hundreds of thousands of nodes. SpeakEasy shows top performance on synthetic clustering benchmarks and accurately identifies meaningful biological communities in a range of datasets, including: gene microarrays, protein interactions, sorted cell populations, electrophysiology and fMRI brain imaging.

  14. Micro/nanofabricated environments for synthetic biology.

    Science.gov (United States)

    Collier, C Patrick; Simpson, Michael L

    2011-08-01

    A better understanding of how confinement, crowding and reduced dimensionality modulate reactivity and reaction dynamics will aid in the rational and systematic discovery of functionality in complex biological systems. Artificial microfabricated and nanofabricated structures have helped elucidate the effects of nanoscale spatial confinement and segregation on biological behavior, particularly when integrated with microfluidics, through precise control in both space and time of diffusible signals and binding interactions. Examples of nanostructured interfaces for synthetic biology include the development of cell-like compartments for encapsulating biochemical reactions, nanostructured environments for fundamental studies of diffusion, molecular transport and biochemical reaction kinetics, and regulation of biomolecular interactions as functions of microfabricated and nanofabricated topological constraints.

  15. Toward total synthesis of cell function: Reconstituting cell dynamics with synthetic biology.

    Science.gov (United States)

    Kim, Allen K; DeRose, Robert; Ueno, Tasuku; Lin, Benjamin; Komatsu, Toru; Nakamura, Hideki; Inoue, Takanari

    2016-02-09

    Biological phenomena, such as cellular differentiation and phagocytosis, are fundamental processes that enable cells to fulfill important physiological roles in multicellular organisms. In the field of synthetic biology, the study of these behaviors relies on the use of a broad range of molecular tools that enable the real-time manipulation and measurement of key components in the underlying signaling pathways. This Review will focus on a subset of synthetic biology tools known as bottom-up techniques, which use technologies such as optogenetics and chemically induced dimerization to reconstitute cellular behavior in cells. These techniques have been crucial not only in revealing causal relationships within signaling networks but also in identifying the minimal signaling components that are necessary for a given cellular function. We discuss studies that used these systems in a broad range of cellular and molecular phenomena, including the time-dependent modulation of protein activity in cellular proliferation and differentiation, the reconstitution of phagocytosis, the reconstitution of chemotaxis, and the regulation of actin reorganization. Finally, we discuss the potential contribution of synthetic biology to medicine.

  16. The Next Generation of Synthetic Biology Chassis: Moving Synthetic Biology from the Laboratory to the Field

    Science.gov (United States)

    2016-09-26

    Bryn L Adams 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) US Army Research...and molecular biology as scientific fields. It is therefore not surprising that synthetic biology (SB) was built upon E. coli and continues to...dominate the field. However, scientific capabilities have advanced from simple gene mutations to the insertion of rationally designed, complex synthetic

  17. Synthetic biology: Novel approaches for microbiology.

    Science.gov (United States)

    Padilla-Vaca, Felipe; Anaya-Velázquez, Fernando; Franco, Bernardo

    2015-06-01

    In the past twenty years, molecular genetics has created powerful tools for genetic manipulation of living organisms. Whole genome sequencing has provided necessary information to assess knowledge on gene function and protein networks. In addition, new tools permit to modify organisms to perform desired tasks. Gene function analysis is speed up by novel approaches that couple both high throughput data generation and mining. Synthetic biology is an emerging field that uses tools for generating novel gene networks, whole genome synthesis and engineering. New applications in biotechnological, pharmaceutical and biomedical research are envisioned for synthetic biology. In recent years these new strategies have opened up the possibilities to study gene and genome editing, creation of novel tools for functional studies in virus, parasites and pathogenic bacteria. There is also the possibility to re-design organisms to generate vaccine subunits or produce new pharmaceuticals to combat multi-drug resistant pathogens. In this review we provide our opinion on the applicability of synthetic biology strategies for functional studies of pathogenic organisms and some applications such as genome editing and gene network studies to further comprehend virulence factors and determinants in pathogenic organisms. We also discuss what we consider important ethical issues for this field of molecular biology, especially for potential misuse of the new technologies.

  18. Bottom-up effects on attention capture and choice

    DEFF Research Database (Denmark)

    Peschel, Anne; Orquin, Jacob Lund; Mueller Loose, Simone

    Attention processes and decision making are accepted to be closely linked together because only information that is attended to can be incorporated in the decision process. Little is known however, to which extent bottom-up processes of attention affect stimulus selection and therefore...... the information available to form a decision. Does changing one visual cue in the stimulus set affect attention towards this cue and what does that mean for the choice outcome? To address this, we conducted a combined eye tracking and choice experiment in a consumer choice setting with visual shelf simulations...... of different product categories. Surface size and visual saliency of a product label were manipulated to determine bottom-up effects on attention and choice. Results show a strong and significant increase in attention in terms of fixation likelihood towards product labels which are larger and more visually...

  19. Synthetic Biology and the Imperative of Enhancement

    Directory of Open Access Journals (Sweden)

    Antonio Diéguez

    2016-12-01

    Full Text Available Synthetic Biology has a huge capacity for the transformation of living beings, including for the transformation of the human genome in a future perhaps not too distant. There are, thus, clear connections between this potential to biological transformation and the aspirations of the supporters of human bioenhancement. The construction of completely synthetic genomes could eventually change in a definitive and irreversible way the central aspects of the human life, and it could give risen even to a new organism as different of our species as we are different of big apes. This paper discusses the main arguments offered in this debate, and points out some of the most problematic assumptions in recent proposals concerning human bioenhancement.

  20. Biologic and synthetic skin substitutes: An overview

    Directory of Open Access Journals (Sweden)

    Halim Ahmad

    2010-10-01

    Full Text Available The current trend of burn wound care has shifted to more holistic approach of improvement in the long-term form and function of the healed burn wounds and quality of life. This has demanded the emergence of various skin substitutes in the management of acute burn injury as well as post burn reconstructions. Skin substitutes have important roles in the treatment of deep dermal and full thickness wounds of various aetiologies. At present, there is no ideal substitute in the market. Skin substitutes can be divided into two main classes, namely, biological and synthetic substitutes. The biological skin substitutes have a more intact extracellular matrix structure, while the synthetic skin substitutes can be synthesised on demand and can be modulated for specific purposes. Each class has its advantages and disadvantages. The biological skin substitutes may allow the construction of a more natural new dermis and allow excellent re-epithelialisation characteristics due to the presence of a basement membrane. Synthetic skin substitutes demonstrate the advantages of increase control over scaffold composition. The ultimate goal is to achieve an ideal skin substitute that provides an effective and scar-free wound healing.

  1. Synthetic biology approaches to fluorinated polyketides.

    Science.gov (United States)

    Thuronyi, Benjamin W; Chang, Michelle C Y

    2015-03-17

    The catalytic diversity of living systems offers a broad range of opportunities for developing new methods to produce small molecule targets such as fuels, materials, and pharmaceuticals. In addition to providing cost-effective and renewable methods for large-scale commercial processes, the exploration of the unusual chemical phenotypes found in living organisms can also enable the expansion of chemical space for discovery of novel function by combining orthogonal attributes from both synthetic and biological chemistry. In this context, we have focused on the development of new fluorine chemistry using synthetic biology approaches. While fluorine has become an important feature in compounds of synthetic origin, the scope of biological fluorine chemistry in living systems is limited, with fewer than 20 organofluorine natural products identified to date. In order to expand the diversity of biosynthetically accessible organofluorines, we have begun to develop methods for the site-selective introduction of fluorine into complex natural products by engineering biosynthetic machinery to incorporate fluorinated building blocks. To gain insight into how both enzyme active sites and metabolic pathways can be evolved to manage and select for fluorinated compounds, we have studied one of the only characterized natural hosts for organofluorine biosynthesis, the soil microbe Streptomyces cattleya. This information provides a template for designing engineered organofluorine enzymes, pathways, and hosts and has allowed us to initiate construction of enzymatic and cellular pathways for the production of fluorinated polyketides.

  2. 75 FR 52752 - Request for Comments on Synthetic Biology

    Science.gov (United States)

    2010-08-27

    ... HUMAN SERVICES Request for Comments on Synthetic Biology AGENCY: Department of Health and Human Services... public comment on the emerging science of synthetic biology, including its potential applications and... synthetic biology. The President asked the Commission to address this topic on May 20, 2010, following...

  3. Synthetic biology for CO2 fixation.

    Science.gov (United States)

    Gong, Fuyu; Cai, Zhen; Li, Yin

    2016-11-01

    Recycling of carbon dioxide (CO2) into fuels and chemicals is a potential approach to reduce CO2 emission and fossil-fuel consumption. Autotrophic microbes can utilize energy from light, hydrogen, or sulfur to assimilate atmospheric CO2 into organic compounds at ambient temperature and pressure. This provides a feasible way for biological production of fuels and chemicals from CO2 under normal conditions. Recently great progress has been made in this research area, and dozens of CO2-derived fuels and chemicals have been reported to be synthesized by autotrophic microbes. This is accompanied by investigations into natural CO2-fixation pathways and the rapid development of new technologies in synthetic biology. This review first summarizes the six natural CO2-fixation pathways reported to date, followed by an overview of recent progress in the design and engineering of CO2-fixation pathways as well as energy supply patterns using the concept and tools of synthetic biology. Finally, we will discuss future prospects in biological fixation of CO2.

  4. A Bottom-Up Approach to SUSY Analyses

    Energy Technology Data Exchange (ETDEWEB)

    Horn, Claus; /SLAC

    2009-08-03

    This paper proposes a new way to perform event generation and analysis in searches for new physics at the LHC. An abstract notation is used to describe the new particles on a level which better corresponds to detector resolution of LHC experiments. In this way the SUSY discovery space can be decomposed into a small number of eigenmodes each with only a few parameters, which allows to investigate the SUSY parameter space in a model-independent way. By focusing on the experimental observables for each process investigated the Bottom-Up Approach allows to systematically study the boarders of the experimental efficiencies and thus to extend the sensitivity for new physics.

  5. A Bottom-Up Approach to SUSY Analyses

    Energy Technology Data Exchange (ETDEWEB)

    Horn, Claus; /SLAC

    2011-11-11

    This paper proposes a new way to do event generation and analysis in searches for new physics at the LHC. An abstract notation is used to describe the new particles on a level which better corresponds to detector resolution of LHC experiments. In this way the SUSY discovery space can be decomposed into a small number of eigenmodes each with only a few parameters, which allows to investigate the SUSY parameter space in a model-independent way. By focusing on the experimental observables for each process investigated the Bottom-Up Approach allows to systematically study the boarders of the experimental efficiencies and thus to extend the sensitivity for new physics.

  6. Recent progress in backreacted bottom-up holographic QCD

    Energy Technology Data Exchange (ETDEWEB)

    Järvinen, Matti [Laboratoire de Physique Théorique, École Normale Supérieure, 24 rue Lhomond, 75231 Paris Cedex 05 (France)

    2016-01-22

    Recent progress in constructing holographic models for QCD is discussed, concentrating on the bottom-up models which implement holographically the renormalization group flow of QCD. The dynamics of gluons can be modeled by using a string-inspired model termed improved holographic QCD, and flavor can be added by introducing space filling branes in this model. The flavor fully backreacts to the glue in the Veneziano limit, giving rise to a class of models which are called V-QCD. The phase diagrams and spectra of V-QCD are in good agreement with results for QCD obtained by other methods.

  7. Increased performance in a bottom-up designed robot by experimentally guided redesign

    DEFF Research Database (Denmark)

    Larsen, Jørgen Christian

    2013-01-01

    the bottom-up, mode-free approach, the authors used the robotic construction kit, LocoKit. This construction kit allows researchers to construct legged robots, without having a mathematical model beforehand. The authors used no specific mathematical model to design the robot, but instead used intuition...... and took inspiration from biology. The results were afterwards compared with results gained from biology, to see if the robot has some of the key elements the authors were looking for. Findings – With the use of LocoKit as the experimental platform, combined with known experimental measurement methods from...

  8. Pareto Optimal Design for Synthetic Biology.

    Science.gov (United States)

    Patanè, Andrea; Santoro, Andrea; Costanza, Jole; Carapezza, Giovanni; Nicosia, Giuseppe

    2015-08-01

    Recent advances in synthetic biology call for robust, flexible and efficient in silico optimization methodologies. We present a Pareto design approach for the bi-level optimization problem associated to the overproduction of specific metabolites in Escherichia coli. Our method efficiently explores the high dimensional genetic manipulation space, finding a number of trade-offs between synthetic and biological objectives, hence furnishing a deeper biological insight to the addressed problem and important results for industrial purposes. We demonstrate the computational capabilities of our Pareto-oriented approach comparing it with state-of-the-art heuristics in the overproduction problems of i) 1,4-butanediol, ii) myristoyl-CoA, i ii) malonyl-CoA , iv) acetate and v) succinate. We show that our algorithms are able to gracefully adapt and scale to more complex models and more biologically-relevant simulations of the genetic manipulations allowed. The Results obtained for 1,4-butanediol overproduction significantly outperform results previously obtained, in terms of 1,4-butanediol to biomass formation ratio and knock-out costs. In particular overproduction percentage is of +662.7%, from 1.425 mmolh⁻¹gDW⁻¹ (wild type) to 10.869 mmolh⁻¹gDW⁻¹, with a knockout cost of 6. Whereas, Pareto-optimal designs we have found in fatty acid optimizations strictly dominate the ones obtained by the other methodologies, e.g., biomass and myristoyl-CoA exportation improvement of +21.43% (0.17 h⁻¹) and +5.19% (1.62 mmolh⁻¹gDW⁻¹), respectively. Furthermore CPU time required by our heuristic approach is more than halved. Finally we implement pathway oriented sensitivity analysis, epsilon-dominance analysis and robustness analysis to enhance our biological understanding of the problem and to improve the optimization algorithm capabilities.

  9. Using synthetic biology to increase nitrogenase activity

    OpenAIRE

    Li, Xin-Xin; Liu, Qi; Liu, Xiao-Meng; Shi, Hao-Wen; Chen, San-feng

    2016-01-01

    Background Nitrogen fixation has been established in protokaryotic model Escherichia coli by transferring a minimal nif gene cluster composed of 9 genes (nifB, nifH, nifD, nifK, nifE, nifN, nifX, hesA and nifV) from Paenibacillus sp. WLY78. However, the nitrogenase activity in the recombinant E. coli 78-7 is only 10 % of that observed in wild-type Paenibacillus. Thus, it is necessary to increase nitrogenase activity through synthetic biology. Results In order to increase nitrogenase activity ...

  10. Synthetic biology ethics: a deontological assessment.

    Science.gov (United States)

    Heavey, Patrick

    2013-10-01

    In this article I discuss the ethics of synthetic biology from a broadly deontological perspective, evaluating its morality in terms of the integrity of nature, the dignity of life and the relationship between God and his creation. Most ethical analyses to date have been largely consequentialist in nature; they reveal a dual use dilemma, showing that synbio has potential for great good and great evil, possibly more so than any step humanity has taken before. A deontological analysis may help to resolve this dilemma, by evaluating whether synbio is right or wrong in itself. I also assess whether deontology alone is a sufficient methodological paradigm for the proper evaluation of synbio ethics.

  11. Synthetic biology for pharmaceutical drug discovery.

    Science.gov (United States)

    Trosset, Jean-Yves; Carbonell, Pablo

    2015-01-01

    Synthetic biology (SB) is an emerging discipline, which is slowly reorienting the field of drug discovery. For thousands of years, living organisms such as plants were the major source of human medicines. The difficulty in resynthesizing natural products, however, often turned pharmaceutical industries away from this rich source for human medicine. More recently, progress on transformation through genetic manipulation of biosynthetic units in microorganisms has opened the possibility of in-depth exploration of the large chemical space of natural products derivatives. Success of SB in drug synthesis culminated with the bioproduction of artemisinin by microorganisms, a tour de force in protein and metabolic engineering. Today, synthetic cells are not only used as biofactories but also used as cell-based screening platforms for both target-based and phenotypic-based approaches. Engineered genetic circuits in synthetic cells are also used to decipher disease mechanisms or drug mechanism of actions and to study cell-cell communication within bacteria consortia. This review presents latest developments of SB in the field of drug discovery, including some challenging issues such as drug resistance and drug toxicity.

  12. Inverse Magnetic Catalysis in Bottom-Up Holographic QCD

    CERN Document Server

    Evans, Nick; Scott, Marc

    2016-01-01

    We explore the effect of magnetic field on chiral condensation in QCD via a simple bottom up holographic model which inputs QCD dynamics through the running of the anomalous dimension of the quark bilinear. Bottom up holography is a form of effective field theory and we use it to explore the dependence on the coefficients of the two lowest order terms linking the magnetic field and the quark condensate. In the massless theory, we identify a region of parameter space where magnetic catalysis occurs at zero temperature but inverse magnetic catalysis at temperatures of order the thermal phase transition. The model shows similar non-monotonic behaviour in the condensate with B at intermediate T as the lattice data. This behaviour is due to the separation of the meson melting and chiral transitions in the holographic framework. The introduction of quark mass raises the scale of B where inverse catalysis takes over from catalysis until the inverse catalysis lies outside the regime of validity of the effective descr...

  13. [New synthetic and biologic treatments for spondylarthritis].

    Science.gov (United States)

    Zufferey, Pascal

    2016-03-09

    The only biological treatments recognized and reimbursed for spondylarthritis in Switzerland are anti TNF. Other effective agents in rheumatoid arthritis were found to be of little use in this indication. Fortunately, in recent years appeared biological molecules blocking cytokines involved in new pathways of inflammation in particular that of IL7. They have been very effective against psoriasis and have a high potential in psoriatic arthritis and spondylarthritis. In parallel, synthetic small molecules capable of modulating the production of intracellular cytokines begin to be marketed. They also are potentially active in the same rheumatic diseases. The purpose of this article is to review these new drugs, in particular to review the progress of their development and commercialization status.

  14. Mapping the Emergence of Synthetic Biology

    Science.gov (United States)

    2016-01-01

    In this paper, we apply an original scientometric analyses to a corpus comprising synthetic biology (SynBio) publications in Thomson Reuters Web of Science to characterize the emergence of this new scientific field. Three results were drawn from this empirical investigation. First, despite the exponential growth of publications, the study of population level statistics (newcomers proportion, collaboration network structure) shows that SynBio has entered a stabilization process since 2010. Second, the mapping of textual and citational networks shows that SynBio is characterized by high heterogeneity and four different approaches: the central approach, where biobrick engineering is the most widespread; genome engineering; protocell creation; and metabolic engineering. We suggest that synthetic biology acts as an umbrella term allowing for the mobilization of resources, and also serves to relate scientific content and promises of applications. Third, we observed a strong intertwinement between epistemic and socio-economic dynamics. Measuring scientific production and impact and using structural analysis data, we identified a core set of mostly American scientists. Biographical analysis shows that these central and influential scientists act as “boundary spanners,” meaning that their importance to the field lies not only in their academic contributions, but also in their capacity to interact with other social spaces that are outside the academic sphere. PMID:27611324

  15. Synthetic biology analysed tools for discussion and evaluation

    CERN Document Server

    2016-01-01

    Synthetic biology is a dynamic, young, ambitious, attractive, and heterogeneous scientific discipline. It is constantly developing and changing, which makes societal evaluation of this emerging new science a challenging task, prone to misunderstandings. Synthetic biology is difficult to capture, and confusion arises not only regarding which part of synthetic biology the discussion is about, but also with respect to the underlying concepts in use. This book offers a useful toolbox to approach this complex and fragmented field. It provides a biological access to the discussion using a 'layer' model that describes the connectivity of synthetic or semisynthetic organisms and cells to the realm of natural organisms derived by evolution. Instead of directly reviewing the field as a whole, firstly our book addresses the characteristic features of synthetic biology that are relevant to the societal discussion. Some of these features apply only to parts of synthetic biology, whereas others are relevant to synthetic bi...

  16. Synthetic biology and therapeutic strategies for the degenerating brain

    OpenAIRE

    Agustín-Pavón, Carmen; Isalan, Mark

    2014-01-01

    Synthetic biology is an emerging engineering discipline that attempts to design and rewire biological components, so as to achieve new functions in a robust and predictable manner. The new tools and strategies provided by synthetic biology have the potential to improve therapeutics for neurodegenerative diseases. In particular, synthetic biology will help design small molecules, proteins, gene networks, and vectors to target disease-related genes. Ultimately, new intelligent delivery systems ...

  17. Nanobiotechnology: synthetic biology meets materials science.

    Science.gov (United States)

    Jewett, Michael C; Patolsky, Fernando

    2013-08-01

    Nanotechnology, the area of science focused on the control of matter in the nanometer scale, allows ground-breaking changes of the fundamental properties of matter that are often radically different compared to those exhibited by the bulk counterparts. In view of the fact that dimensionality plays a key role in determining the qualities of matter, the realization of the great potential of nanotechnology has opened the door to other disciplines such as life sciences and medicine, where the merging between them offers exciting new applications, along with basic science research. The application of nanotechnology in life sciences, nanobiotechnology, is now having a profound impact on biological circuit design, bioproduction systems, synthetic biology, medical diagnostics, disease therapy and drug delivery. This special issue is dedicated to the overview of how we are learning to control biopolymers and biological machines at the molecular- and nanoscale. In addition, it covers far-reaching progress in the design and synthesis of nanoscale materials, thus enabling the construction of integrated systems in which the component blocks are comparable in size to the chemical and biological entities under investigation.

  18. Molecular Imaging in Synthetic Biology, and Synthetic Biology in Molecular Imaging.

    Science.gov (United States)

    Gilad, Assaf A; Shapiro, Mikhail G

    2017-02-17

    Biomedical synthetic biology is an emerging field in which cells are engineered at the genetic level to carry out novel functions with relevance to biomedical and industrial applications. This approach promises new treatments, imaging tools, and diagnostics for diseases ranging from gastrointestinal inflammatory syndromes to cancer, diabetes, and neurodegeneration. As these cellular technologies undergo pre-clinical and clinical development, it is becoming essential to monitor their location and function in vivo, necessitating appropriate molecular imaging strategies, and therefore, we have created an interest group within the World Molecular Imaging Society focusing on synthetic biology and reporter gene technologies. Here, we highlight recent advances in biomedical synthetic biology, including bacterial therapy, immunotherapy, and regenerative medicine. We then discuss emerging molecular imaging approaches to facilitate in vivo applications, focusing on reporter genes for noninvasive modalities such as magnetic resonance, ultrasound, photoacoustic imaging, bioluminescence, and radionuclear imaging. Because reporter genes can be incorporated directly into engineered genetic circuits, they are particularly well suited to imaging synthetic biological constructs, and developing them provides opportunities for creative molecular and genetic engineering.

  19. [How to be prudent with synthetic biology. Synthetic Biology and the precautionary principle].

    Science.gov (United States)

    Rodríguez López, Blanca

    2014-01-01

    Synthetic biology is a new discipline that is twofold: firstly it offers the promise to pay benefits that can alleviate some of the ills that plague mankind; On the other hand, like all technologies, holds risks. Given these, the most critical and concerned about the risks, invoke the application of the precautionary principle, common in cases where an activity or new technology creates risks to the environment and/or human health, but far from universally accepted happens to be currently one of the most controversial principles. In this paper the question of the risks and benefits of synthetic biology and the relevance of applying the precautionary principle are analyzed. To do this we proceed as follows. The first part focuses on synthetic biology. At first, this discipline is characterized, with special attention to what is novel compared to the known as "genetic engineering". In the second stage both the benefits and the risks associated with it are discussed. The first part concludes with a review of the efforts currently being made to control or minimize the risks. The second part aims to analyze the precautionary principle and its possible relevance to the case of Synthetic Biology. At first, the different versions and interpretations of the principle and the various criticisms of which has been the subject are reviewed. Finally, after discarding the Precautionary Principle as an useful tool, it is seen as more appropriate some recent proposals to treat technologies that take into account not only risks but also their benefits.

  20. Pressurized Pepsin Digestion in Proteomics: An Automatable Alternative to Trypsin for Integrated Top-down Bottom-up Proteomics

    Energy Technology Data Exchange (ETDEWEB)

    Lopez-Ferrer, Daniel; Petritis, Konstantinos; Robinson, Errol W.; Hixson, Kim K.; Tian, Zhixin; Lee, Jung Hwa; Lee, Sang-Won; Tolic, Nikola; Weitz, Karl K.; Belov, Mikhail E.; Smith, Richard D.; Pasa-Tolic, Ljiljana

    2011-02-01

    Integrated top-down bottom-up proteomics combined with online digestion has great potential to improve the characterization of protein isoforms in biological systems and is amendable to highthroughput proteomics experiments. Bottom-up proteomics ultimately provides the peptide sequences derived from the tandem MS analyses of peptides after the proteome has been digested. Top-down proteomics conversely entails the MS analyses of intact proteins for more effective characterization of genetic variations and/or post-translational modifications (PTMs). Herein, we describe recent efforts towards efficient integration of bottom-up and top-down LCMS based proteomic strategies. Since most proteomic platforms (i.e. LC systems) operate in acidic environments, we exploited the compatibility of the pepsin (i.e. the enzyme’s natural acidic activity) for the integration of bottom-up and top-down proteomics. Pressure enhanced pepsin digestions were successfully performed and characterized with several standard proteins in either an offline mode using a Barocycler or an online mode using a modified high pressure LC system referred to as a fast online digestion system (FOLDS). FOLDS was tested using pepsin and a whole microbial proteome, and the results compared against traditional trypsin digestions on the same platform. Additionally, FOLDS was integrated with a RePlay configuration to demonstrate an ultra-rapid integrated bottom-up top-down proteomic strategy employing a standard mixture of proteins and a monkey pox virus proteome.

  1. The emerging age of cell-free synthetic biology.

    Science.gov (United States)

    Smith, Mark Thomas; Wilding, Kristen M; Hunt, Jeremy M; Bennett, Anthony M; Bundy, Bradley C

    2014-08-25

    The engineering of and mastery over biological parts has catalyzed the emergence of synthetic biology. This field has grown exponentially in the past decade. As increasingly more applications of synthetic biology are pursued, more challenges are encountered, such as delivering genetic material into cells and optimizing genetic circuits in vivo. An in vitro or cell-free approach to synthetic biology simplifies and avoids many of the pitfalls of in vivo synthetic biology. In this review, we describe some of the innate features that make cell-free systems compelling platforms for synthetic biology and discuss emerging improvements of cell-free technologies. We also select and highlight recent and emerging applications of cell-free synthetic biology.

  2. Network benchmarking: a happy marriage between systems and synthetic biology.

    Science.gov (United States)

    Minty, Jeremy J; Varedi K, S Marjan; Nina Lin, Xiaoxia

    2009-03-27

    In their new Cell paper, Cantone et al. (2009) present exciting results on constructing and utilizing a small synthetic gene regulatory network in yeast that draws from two rapidly developing fields of systems and synthetic biology.

  3. Contextualised ICT4D: a Bottom-Up Approach

    DEFF Research Database (Denmark)

    Lund, Henrik Hautop; Sutinen, Erkki

    2010-01-01

    . In a certain way, this agenda can be understood as a topdown approach which transfers technology in a hierarchical way to actual users. Complementary to the traditional approach, a bottom-up approach starts by identifying communities that are ready to participate in a process to use technology to transform......The term ICT4D refers to the opportunities of Information and Communication Technology (ICT) as an agent of development. Much of the research in the field is based on evaluating the feasibility of existing technologies, mostly of Western or Asian origin, in the context of developing countries...... their own strengths to new levels by designing appropriate technologies with experts of technology and design. The bottomup approach requires a new kind of ICT education at the undergraduate level. An example of the development of a contextualized IT degree program at Tumaini University in Tanzania shows...

  4. A bottom-up approach to MEDLINE indexing recommendations.

    Science.gov (United States)

    Jimeno-Yepes, Antonio; Wilkowski, Bartłomiej; Mork, James G; Van Lenten, Elizabeth; Fushman, Dina Demner; Aronson, Alan R

    2011-01-01

    MEDLINE indexing performed by the US National Library of Medicine staff describes the essence of a biomedical publication in about 14 Medical Subject Headings (MeSH). Since 2002, this task is assisted by the Medical Text Indexer (MTI) program. We present a bottom-up approach to MEDLINE indexing in which the abstract is searched for indicators for a specific MeSH recommendation in a two-step process. Supervised machine learning combined with triage rules improves sensitivity of recommendations while keeping the number of recommended terms relatively small. Improvement in recommendations observed in this work warrants further exploration of this approach to MTI recommendations on a larger set of MeSH headings.

  5. Bottom-up fabrication of graphene nanostructures on Ru(1010).

    Science.gov (United States)

    Song, Junjie; Zhang, Han-jie; Cai, Yiliang; Zhang, Yuxi; Bao, Shining; He, Pimo

    2016-02-01

    Investigations on the bottom-up fabrication of graphene nanostructures with 10, 10'-dibromo-9, 9'-bianthryl (DBBA) as a precursor on Ru(1010) were carried out using scanning tunnelling microscopy (STM) and density functional theory (DFT) calculations. Upon annealing the sample at submonolayer DBBA coverage, N = 7 graphene nanoribbons (GNRs) aligned along the [1210] direction form. Higher DBBA coverage and higher annealing temperature lead to the merging of GNRs into ribbon-like graphene nanoflakes with multiple orientations. These nanoflakes show different Moiré patterns, and their structures were determined by DFT simulations. The results showed that GNRs possess growth preference on the Ru(1010) substrate with a rectangular unit cell, and GNRs with armchair and zigzag boundaries are obtainable. Further DFT calculations suggest that the interaction between graphene and the substrate controls the orientations of the graphene overlayer and the growth of graphene on Ru(1010).

  6. Making the results of bottom-up energy savings comparable

    Directory of Open Access Journals (Sweden)

    Moser Simon

    2012-01-01

    Full Text Available The Energy Service Directive (ESD has pushed forward the issue of energy savings calculations without clarifying the methodological basis. Savings achieved in the Member States are calculated with rather non-transparent and hardly comparable Bottom-up (BU methods. This paper develops the idea of parallel evaluation tracks separating the Member States’ issue of ESD verification and comparable savings calculations. Comparability is ensured by developing a standardised BU calculation kernel for different energy efficiency improvement (EEI actions which simultaneously depicts the different calculation options in a structured way (e.g. baseline definition, system boundaries, double counting. Due to the heterogeneity of BU calculations the approach requires a central database where Member States feed in input data on BU actions according to a predefined structure. The paper demonstrates the proposed approach including a concrete example of application.

  7. Bottom-Up Discrete Symmetries for Cabibbo Mixing

    CERN Document Server

    Varzielas, Ivo de Medeiros; Talbert, Jim

    2016-01-01

    We perform a bottom-up search for discrete non-Abelian symmetries capable of quantizing the Cabibbo angle that parameterizes CKM mixing. Given a particular Abelian symmetry structure in the up and down sectors, we construct representations of the associated residual generators which explicitly depend on the degrees of freedom present in our effective mixing matrix. We then discretize those degrees of freedom and utilize the Groups, Algorithms, Programming (GAP) package to close the associated finite groups. This short study is performed in the context of recent results indicating that, without resorting to special model-dependent corrections, no small-order finite group can simultaneously predict all four parameters of the three-generation CKM matrix and that only groups of $\\mathcal{O}(10^{2})$ can predict the analogous parameters of the leptonic PMNS matrix, regardless of whether neutrinos are Dirac or Majorana particles. Therefore a natural model of flavour might instead incorporate small(er) finite groups...

  8. Synthetic Biology in the Biotech Patent Landscape

    Directory of Open Access Journals (Sweden)

    Viviana García-llerena

    2016-12-01

    Full Text Available Recently, the intended positive effects of the current patent system in biotechnological research have been widely questioned. As part of this review, it is discussed here one of the foundations of the model. The assumption of the indispensability of patents is examined through the analysis of their expected benefits; namely, that patents are suitable to ensure access to information, access to and use of inventions and, finally, that they should promote both creativity and research. Applied to synthetic biology, in spite of newly discovered techniques and promising products, this approach reveals that this discipline also encounters similar issues. However, it also offers a new vision of intellectual property rights and their effects on research, which is based on a different conception of the commons and its relationship with private ownership of intangible assets in the knowledge economy.

  9. Synthetic biology: applying biological circuits beyond novel therapies.

    Science.gov (United States)

    Dobrin, Anton; Saxena, Pratik; Fussenegger, Martin

    2016-04-18

    Synthetic biology, an engineering, circuit-driven approach to biology, has developed whole new classes of therapeutics. Unfortunately, these advances have thus far been undercapitalized upon by basic researchers. As discussed herein, using synthetic circuits, one can undertake exhaustive investigations of the endogenous circuitry found in nature, develop novel detectors and better temporally and spatially controlled inducers. One could detect changes in DNA, RNA, protein or even transient signaling events, in cell-based systems, in live mice, and in humans. Synthetic biology has also developed inducible systems that can be induced chemically, optically or using radio waves. This induction has been re-wired to lead to changes in gene expression, RNA stability and splicing, protein stability and splicing, and signaling via endogenous pathways. Beyond simple detectors and inducible systems, one can combine these modalities and develop novel signal integration circuits that can react to a very precise pre-programmed set of conditions or even to multiple sets of precise conditions. In this review, we highlight some tools that were developed in which these circuits were combined such that the detection of a particular event automatically triggered a specific output. Furthermore, using novel circuit-design strategies, circuits have been developed that can integrate multiple inputs together in Boolean logic gates composed of up to 6 inputs. We highlight the tools available and what has been developed thus far, and highlight how some clinical tools can be very useful in basic science. Most of the systems that are presented can be integrated together; and the possibilities far exceed the number of currently developed strategies.

  10. Bottom-up processing and low temperature transport properties of polycrystalline SnSe

    Energy Technology Data Exchange (ETDEWEB)

    Ge, Zhen-Hua; Wei, Kaya; Lewis, Hutton [Department of Physics, University of South Florida, Tampa, FL 33620 (United States); Martin, Joshua [Materials Measurement Science Division, National Institute of Standards and Technology, Gaithersburg, MD 20899 (United States); Nolas, George S., E-mail: gnolas@usf.edu [Department of Physics, University of South Florida, Tampa, FL 33620 (United States)

    2015-05-15

    A hydrothermal approach was employed to efficiently synthesize SnSe nanorods. The nanorods were consolidated into polycrystalline SnSe by spark plasma sintering for low temperature electrical and thermal properties characterization. The low temperature transport properties indicate semiconducting behavior with a typical dielectric temperature dependence of the thermal conductivity. The transport properties are discussed in light of the recent interest in this material for thermoelectric applications. The nanorod growth mechanism is also discussed in detail. - Graphical abstract: SnSe nanorods were synthesized by a simple hydrothermal method through a bottom-up approach. Micron sized flower-like crystals changed to nanorods with increasing hydrothermal temperature. Low temperature transport properties of polycrystalline SnSe, after SPS densification, were reported for the first time. This bottom-up synthetic approach can be used to produce phase-pure dense polycrystalline materials for thermoelectrics applications. - Highlights: • SnSe nanorods were synthesized by a simple and efficient hydrothermal approach. • The role of temperature, time and NaOH content was investigated. • SPS densification allowed for low temperature transport properties measurements. • Transport measurements indicate semiconducting behavior.

  11. Exploring Synthetic and Systems Biology at the University of Edinburgh.

    Science.gov (United States)

    Fletcher, Liz; Rosser, Susan; Elfick, Alistair

    2016-06-15

    The Centre for Synthetic and Systems Biology ('SynthSys') was originally established in 2007 as the Centre for Integrative Systems Biology, funded by the Biotechnology and Biological Sciences Research Council (BBSRC) and the Engineering and Physical Sciences Research Council (EPSRC). Today, SynthSys embraces an extensive multidisciplinary community of more than 200 researchers from across the University with a common interest in synthetic and systems biology. Our research is broad and deep, addressing a diversity of scientific questions, with wide ranging impact. We bring together the power of synthetic biology and systems approaches to focus on three core thematic areas: industrial biotechnology, agriculture and the environment, and medicine and healthcare. In October 2015, we opened a newly refurbished building as a physical hub for our new U.K. Centre for Mammalian Synthetic Biology funded by the BBSRC/EPSRC/MRC as part of the U.K. Research Councils' Synthetic Biology for Growth programme.

  12. Integration of microfluidics into the synthetic biology design flow.

    Science.gov (United States)

    Huang, Haiyao; Densmore, Douglas

    2014-09-21

    One goal of synthetic biology is to design and build genetic circuits in living cells for a range of applications. Major challenges in these efforts include increasing the scalability and robustness of engineered biological systems and streamlining and automating the synthetic biology workflow of specification-design-assembly-verification. We present here a summary of the advances in microfluidic technology, particularly microfluidic large scale integration, that can be used to address the challenges facing each step of the synthetic biology workflow. Microfluidic technologies allow precise control over the flow of biological content within microscale devices, and thus may provide more reliable and scalable construction of synthetic biological systems. The integration of microfluidics and synthetic biology has the capability to produce rapid prototyping platforms for characterization of genetic devices, testing of biotherapeutics, and development of biosensors.

  13. Synthetic biology: a challenge to mechanical explanations in biology?

    Science.gov (United States)

    Morange, Michel

    2012-01-01

    In their plans to modify organisms, synthetic biologists have contrasted engineering and tinkering. By drawing this contrast between their endeavors and what has happened during the evolution of organisms by natural selection, they underline the novelty of their projects and justify their ambitions. Synthetic biologists are at odds with a long tradition that has considered organisms as "perfect machines." This tradition had already been questioned by Stephen Jay Gould in the 1970s and received a major blow with the comparison made by François Jacob between organisms and the results of "bricolage" (tinkering). These contrasts between engineering and tinkering, synthetic biology and evolution, have no raison d'être. Machines built by humans are increasingly inspired by observations made on organisms. This is not a simple reversal of the previous trend-the mechanical conception of organisms-in which the characteristics of the latter were explained by comparison with human-built machines. Relations between organisms and machines have always been complex and ambiguous.

  14. Developments in the tools and methodologies of synthetic biology

    Directory of Open Access Journals (Sweden)

    Richard eKelwick

    2014-11-01

    Full Text Available Synthetic biology is principally concerned with the rational design and engineering of biologically based parts, devices or systems. However, biological systems are generally complex and unpredictable and are therefore intrinsically difficult to engineer. In order to address these fundamental challenges, synthetic biology is aiming to unify a ‘body of knowledge’ from several foundational scientific fields, within the context of a set of engineering principles. This shift in perspective is enabling synthetic biologists to address complexity, such that robust biological systems can be designed, assembled and tested as part of a biological design cycle. The design cycle takes a forward-design approach in which a biological system is specified, modeled, analyzed, assembled and its functionality tested. At each stage of the design cycle an expanding repertoire of tools is being developed. In this review we highlight several of these tools in terms of their applications and benefits to the synthetic biology community.

  15. BUEES:a bottom-up event extraction system

    Institute of Scientific and Technical Information of China (English)

    Xiao DING; Bing QIN; Ting LIU

    2015-01-01

    Traditional event extraction systems focus mainly on event type identifi cation and event participant extraction based on pre-specifi ed event type paradigms and manually annotated corpora. However, different domains have different event type paradigms. When transferring to a new domain, we have to build a new event type paradigm and annotate a new corpus from scratch. This kind of conventional event extraction system requires massive human effort, and hence prevents event extraction from being widely applicable. In this paper, we present BUEES, a bottom-up event extraction system, which extracts events from the web in a completely unsupervised way. The system automatically builds an event type paradigm in the input corpus, and then proceeds to extract a large number of instance patterns of these events. Subsequently, the system extracts event arguments according to these patterns. By conducting a series of experiments, we demonstrate the good performance of BUEES and compare it to a state-of-the-art Chinese event extraction system, i.e., a supervised event extraction system. Experimental results show that BUEES performs comparably (5% higher F-measure in event type identifi cation and 3% higher F-measure in event argument extraction), but without any human effort.

  16. Top down and bottom up engineering of bone.

    Science.gov (United States)

    Knothe Tate, Melissa L

    2011-01-11

    The goal of this retrospective article is to place the body of my lab's multiscale mechanobiology work in context of top-down and bottom-up engineering of bone. We have used biosystems engineering, computational modeling and novel experimental approaches to understand bone physiology, in health and disease, and across time (in utero, postnatal growth, maturity, aging and death, as well as evolution) and length scales (a single bone like a femur, m; a sample of bone tissue, mm-cm; a cell and its local environment, μm; down to the length scale of the cell's own skeleton, the cytoskeleton, nm). First we introduce the concept of flow in bone and the three calibers of porosity through which fluid flows. Then we describe, in the context of organ-tissue, tissue-cell and cell-molecule length scales, both multiscale computational models and experimental methods to predict flow in bone and to understand the flow of fluid as a means to deliver chemical and mechanical cues in bone. Addressing a number of studies in the context of multiple length and time scales, the importance of appropriate boundary conditions, site specific material parameters, permeability measures and even micro-nanoanatomically correct geometries are discussed in context of model predictions and their value for understanding multiscale mechanobiology of bone. Insights from these multiscale computational modeling and experimental methods are providing us with a means to predict, engineer and manufacture bone tissue in the laboratory and in the human body.

  17. Single-molecule spectroscopy for plastic electronics: materials analysis from the bottom-up.

    Science.gov (United States)

    Lupton, John M

    2010-04-18

    pi-conjugated polymers find a range of applications in electronic devices. These materials are generally highly disordered in terms of chain length and chain conformation, besides being influenced by a variety of chemical and physical defects. Although this characteristic can be of benefit in certain device applications, disorder severely complicates materials analysis. Accurate analytical techniques are, however, crucial to optimising synthetic procedures and assessing overall material purity. Fortunately, single-molecule spectroscopic techniques have emerged as an unlikely but uniquely powerful approach to unraveling intrinsic material properties from the bottom up. Building on the success of such techniques in the life sciences, single-molecule spectroscopy is finding increasing applicability in materials science, effectively enabling the dissection of the bulk down to the level of the individual molecular constituent. This article reviews recent progress in single molecule spectroscopy of conjugated polymers as used in organic electronics.

  18. Scientific Opinion on Risk Assessment of Synthetic Biology.

    Science.gov (United States)

    Epstein, Michelle M; Vermeire, Theo

    2016-08-01

    In 2013, three Scientific Committees of the European Commission (EC) drafted Scientific Opinions on synthetic biology that provide an operational definition and address risk assessment methodology, safety aspects, environmental risks, knowledge gaps, and research priorities. These Opinions contribute to the international discussions on the risk governance for synthetic biology developments.

  19. Misconceptions of Synthetic Biology: Lessons from an Interdisciplinary Summer School

    DEFF Research Database (Denmark)

    Verseux, Cyprien; G Acevedo-Rocha, Carlos; Chizzolini, Fabio;

    2016-01-01

    In 2014, an international group of scholars from various fields analysed the "societal dimensions" of synthetic biology in an interdisciplinary summer school. Here, we report and discuss the biologists' observations on the general perception of synthetic biology by non-biologists who took part in...

  20. From noise to synthetic nucleoli: can synthetic biology achieve new insights?

    Science.gov (United States)

    Ciechonska, Marta; Grob, Alice; Isalan, Mark

    2016-04-18

    Synthetic biology aims to re-organise and control biological components to make functional devices. Along the way, the iterative process of designing and testing gene circuits has the potential to yield many insights into the functioning of the underlying chassis of cells. Thus, synthetic biology is converging with disciplines such as systems biology and even classical cell biology, to give a new level of predictability to gene expression, cell metabolism and cellular signalling networks. This review gives an overview of the contributions that synthetic biology has made in understanding gene expression, in terms of cell heterogeneity (noise), the coupling of growth and energy usage to expression, and spatiotemporal considerations. We mainly compare progress in bacterial and mammalian systems, which have some of the most-developed engineering frameworks. Overall, one view of synthetic biology can be neatly summarised as "creating in order to understand."

  1. Building Models from the Bottom Up: The HOBBES Project

    Science.gov (United States)

    Medellin-Azuara, J.; Sandoval Solis, S.; Lund, J. R.; Chu, W.

    2013-12-01

    Water problems are often bigger than technical and data challenges associated in representing a water system using a model. Controversy and complexity is inherent when water is to be allocated among different uses making difficult to maintain coherent and productive discussions on addressing water problems. Quantification of a water supply system through models has proven to be helpful to improve understanding, explore and develop adaptable solutions to water problems. However, models often become too large and complex and become hostages of endless discussions of the assumptions, their algorithms and their limitations. Data management organization and documentation keep model flexible and useful over time. The UC Davis HOBBES project is a new approach, building models from the bottom up. Reversing the traditional model development, where data are arranged around a model algorithm, in Hobbes the data structure, organization and documentation are established first, followed by application of simulation or optimization modeling algorithms for a particular problem at hand. The HOBBES project establishes standards for storing, documenting and sharing datasets on California water system. This allows models to be developed and modified more easily and transparently, with greater comparability. Elements in the database have a spatial definition and can aggregate several infrastructural elements into detailed to coarse representations of the water system. Elements in the database represent reservoirs, groundwater basins, pumping stations, hydropower and water treatment facilities, demand areas and conveyance infrastructure statewide. These elements also host time series, economic and other information from hydrologic, economic, climate and other models. This presentation provides an overview of the project HOBBES project, its applications and prospects for California and elsewhere. The HOBBES Project

  2. Ecological perspectives on synthetic biology: insights from microbial population biology

    Science.gov (United States)

    Escalante, Ana E.; Rebolleda-Gómez, María; Benítez, Mariana; Travisano, Michael

    2015-01-01

    The metabolic capabilities of microbes are the basis for many major biotechnological advances, exploiting microbial diversity by selection or engineering of single strains. However, there are limits to the advances that can be achieved with single strains, and attention has turned toward the metabolic potential of consortia and the field of synthetic ecology. The main challenge for the synthetic ecology is that consortia are frequently unstable, largely because evolution by constituent members affects their interactions, which are the basis of collective metabolic functionality. Current practices in modeling consortia largely consider interactions as fixed circuits of chemical reactions, which greatly increases their tractability. This simplification comes at the cost of essential biological realism, stripping out the ecological context in which the metabolic actions occur and the potential for evolutionary change. In other words, evolutionary stability is not engineered into the system. This realization highlights the necessity to better identify the key components that influence the stable coexistence of microorganisms. Inclusion of ecological and evolutionary principles, in addition to biophysical variables and stoichiometric modeling of metabolism, is critical for microbial consortia design. This review aims to bring ecological and evolutionary concepts to the discussion on the stability of microbial consortia. In particular, we focus on the combined effect of spatial structure (connectivity of molecules and cells within the system) and ecological interactions (reciprocal and non-reciprocal) on the persistence of microbial consortia. We discuss exemplary cases to illustrate these ideas from published studies in evolutionary biology and biotechnology. We conclude by making clear the relevance of incorporating evolutionary and ecological principles to the design of microbial consortia, as a way of achieving evolutionarily stable and sustainable systems. PMID

  3. The development of synthetic biology: a patent analysis.

    Science.gov (United States)

    van Doren, Davy; Koenigstein, Stefan; Reiss, Thomas

    2013-12-01

    In the past decades, synthetic biology has gained interest regarding research and development efforts within the biotechnology domain. However, it is unclear to what extent synthetic biology has matured already into being commercially exploitable. By means of a patent analysis, this study shows that there is an increasing trend regarding synthetic biology related patent applications. The majority of retrieved patents relates to innovations facilitating the realisation of synthetic biology through improved understanding of biological systems. In addition, there is increased activity concerning the development of synthetic biology based applications. When looking at potential application areas, the majority of synthetic biology patents seems most relevant for the medical, energy and industrial sector. Furthermore, the analysis shows that most activity has been carried out by the USA, with Japan and a number of European countries considerably trailing behind. In addition, both universities and companies are major patent applicant actor types. The results presented here form a starting point for follow-up studies concerning the identification of drivers explaining the observed patent application trends in synthetic biology.

  4. Applications of synthetic carbohydrates to chemical biology.

    Science.gov (United States)

    Lepenies, Bernd; Yin, Jian; Seeberger, Peter H

    2010-06-01

    Access to synthetic carbohydrates is an urgent need for the development of carbohydrate-based drugs, vaccines, adjuvants as well as novel drug delivery systems. Besides traditional synthesis in solution, synthetic carbohydrates have been generated by chemoenzymatic methods as well as automated solid-phase synthesis. Synthetic oligosaccharides have proven to be useful for identifying ligands of carbohydrate-binding proteins such as C-type lectins and siglecs using glycan arrays. Furthermore, glyconanoparticles and glycodendrimers have been used for specific targeting of lectins of the immune system such as selectins, DC-SIGN, and CD22. This review focuses on how diverse carbohydrate structures can be synthetically derived and highlights the benefit of synthetic carbohydrates for glycobiology.

  5. Atomically Precise Bottom-up Fabrication of Graphene Nanoribbons

    Science.gov (United States)

    Cai, Jinming

    2011-03-01

    Graphene nanoribbons (GNRs) -- narrow stripes of graphene -- are predicted to exhibit remarkable properties making them suitable for future electronic applications. Contrary to their two-dimensional (2D) parent material graphene, which exhibits semimetallic behavior, GNRs with widths smaller than 10 nm are predicted to be semiconductors due to quantum confinement and edge effects. Despite significant advances in GNR fabrication using chemical, sonochemical and lithographic methods as well as recent reports on the successful unzipping of carbon nanotubes into GNRs, the production of sub-10 nm GNRs with chemical precision remains a major challenge. In this talk, we will present a simple GNR fabrication method that allows for the production of atomically precise GNRs of different topologies and widths. Our bottom-up approach consists in the surface-assisted coupling of suitably designed molecular precursors into linear polyphenylenes and their subsequent cyclodehydrogenation, and results in GNRs whose topology, width and edge periphery are defined by the precursor monomers. By means of STM and Raman characterization, we demonstrate that this fabrication process allows for the atomically precise fabrication of complex GNR topologies. Furthermore, we have developed a reliable procedure to transfer GNRs fabricated on metal surfaces onto other substrates. It will for example be shown that millimeter sized sheets of crosslinked GNRs can be transferred onto silicon wafers, making them available for further processing, e.g. by lithography, prototype device fabrication and characterization. Coauthors: Pascal Ruffieux, Rached Jaafar, Marco Bieri, Thomas Braun, and Stephan Blankenburg, Empa, Swiss Federal Laboratories for Materials Science and Technology, 3602 Thun and 8600 Dübendorf, Switzerland; Matthias Muoth, ETH Zurich, Department of Mechanical and Process Engineering, 8092 Zurich, Switzerland; Ari P. Seitsonen, University of Zurich, Physical Chemistry Institute, 8057

  6. Recent applications of synthetic biology tools for yeast metabolic engineering

    DEFF Research Database (Denmark)

    Jensen, Michael Krogh; Keasling, Jay

    2015-01-01

    to engineer microbial chemical factories has steadily decreased, improvement is still needed. Through the development of synthetic biology tools for key microbial hosts, it should be possible to further decrease the development times and improve the reliability of the resulting microorganism. Together...... with continuous decreases in price and improvements in DNA synthesis, assembly and sequencing, synthetic biology tools will rationalize time-consuming strain engineering, improve control of metabolic fluxes, and diversify screening assays for cellular metabolism. This review outlines some recently developed...... synthetic biology tools and their application to improve production of chemicals and fuels in yeast. Finally, we provide a perspective for the challenges that lie ahead....

  7. Synthetic biology and intellectual property rights: six recommendations.

    Science.gov (United States)

    Minssen, Timo; Rutz, Berthold; van Zimmeren, Esther

    2015-02-01

    On 26th November 2013, the Danish Agency for Science, Technology and Innovation organized an expert meeting on "Synthetic Biology & Intellectual Property Rights" in Copenhagen sponsored by the European Research Area Network in Synthetic Biology (ERASynBio). The meeting brought together ten experts from different countries with a variety of professional backgrounds to discuss emerging challenges and opportunities at the interface of synthetic biology and intellectual property rights. The aim of this article is to provide a summary of the major issues and recommendations discussed during the meeting.

  8. Bottom-up capacity building for data providers in RITMARE

    Science.gov (United States)

    Pepe, Monica; Basoni, Anna; Bastianini, Mauro; Fugazza, Cristiano; Menegon, Stefano; Oggioni, Alessandro; Pavesi, Fabio; Sarretta, Alessandro; Carrara, Paola

    2014-05-01

    RITMARE is a Flagship Project by the Italian Ministry of Research, coordinated by the National Research Council (CNR). It aims at the interdisciplinary integration of Italian marine research. Sub-project 7 shall create an interoperable infrastructure for the project, capable of interconnecting the whole community of researchers involved. It will allow coordinating and sharing of data, processes, and information produced by the other sub-projects [1]. Spatial Data Infrastructures (SDIs) allow for interoperable sharing among heterogeneous, distributed spatial content providers. The INSPIRE Directive [2] regulates the development of a pan-european SDI despite the great variety of national approaches in managing spatial data. However, six years after its adoption, its growth is still hampered by technological, cultural, and methodological gaps. In particular, in the research sector, actors may not be prone to comply with INSPIRE (or feel not compelled to) because they are too concentrated on domain-specific activities or hindered by technological issues. Indeed, the available technologies and tools for enabling standard-based discovery and access services are far from being user-friendly and requires time-consuming activities, such as metadata creation. Moreover, the INSPIRE implementation guidelines do not accommodate an essential component in environmental research, that is, in situ observations. In order to overcome most of the aforementioned issues and to enable researchers to actively give their contribution in the creation of the project infrastructure, a bottom-up approach has been adopted: a software suite has been developed, called Starter Kit, which is offered to research data production units, so that they can become autonomous, independent nodes of data provision. The Starter Kit enables the provision of geospatial resources, either geodata (e.g., maps and layers) or observations pulled from sensors, which are made accessible according to the OGC standards

  9. Misconceptions of Synthetic Biology: Lessons from an Interdisciplinary Summer School

    Science.gov (United States)

    Verseux, Cyprien; Acevedo-Rocha, Carlos G.; Chizzolini, Fabio; Rothschild, Lynn J.

    2016-01-01

    In 2014, an international group of scholars from various fields analysed the "societal dimensions" of synthetic biology in an interdisciplinary summer school. Here, we report and discuss the biologists' observations on the general perception of synthetic biology by non-biologists who took part in this event. Most attendees mainly associated synthetic biology with contributions from the best-known public figures of the field, rarely mentioning other scientists. Media extrapolations of those contributions appeared to have created unrealistic expectations and irrelevant fears that were widely disconnected from the current research in synthetic biology. Another observation was that when debating developments in synthetic biology, semantics strongly mattered: depending on the terms used to present an application of synthetic biology, attendees reacted in radically different ways. For example, using the term "GMOs" (genetically modified organisms) rather than the term "genetic engineering" led to very different reactions. Stimulating debates also happened with participants having unanticipated points of view, for instance biocentrist ethicists who argued that engineered microbes should not be used for human purposes. Another communication challenge emerged from the connotations and inaccuracies surrounding the word "life", which impaired constructive debates, thus leading to misconceptions about the abilities of scientists to engineer or even create living organisms. Finally, it appeared that synthetic biologists tend to overestimate the knowledge of non-biologists, further affecting communication. The motivation and ability of synthetic biologists to communicate their work outside their research field needs to be fostered, notably towards policymakers who need a more accurate and technical understanding of the field to make informed decisions. Interdisciplinary events gathering scholars working in and around synthetic biology are an effective tool in addressing those

  10. Synthetic Biology with Cytochromes P450 Using Photosynthetic Chassis

    DEFF Research Database (Denmark)

    Gnanasekaran, Thiyagarajan

    Synthetic biology is a rapidly growing engineering discipline in biology. It aims at building novel biological systems that do not exist in nature by selecting the interchangeable standardized biological parts that are already available in the nature, and assembling them in a specific order. Today......, this modern field of synthetic biology is completely dependent on the nature of the chassis - the host organisms - for its endeavor. Of all the chassis, photosynthetic organisms such as cyanobacteria and plants gains special attention due to the remarkable amount of sunlight that is striking the Earth......’s atmosphere and anthropogenic carbon dioxide (CO2) increase in the atmosphere. Hence, tapping into photosynthesis for synthetic biology endeavor is very rational, and for future, it has a huge potential for the industrial production of fuels and high value bioactive compounds in a sustainable way. Most...

  11. Semi-synthetic artemisinin: a model for the use of synthetic biology in pharmaceutical development.

    Science.gov (United States)

    Paddon, Chris J; Keasling, Jay D

    2014-05-01

    Recent developments in synthetic biology, combined with continued progress in systems biology and metabolic engineering, have enabled the engineering of microorganisms to produce heterologous molecules in a manner that was previously unfeasible. The successful synthesis and recent entry of semi-synthetic artemisinin into commercial production is the first demonstration of the potential of synthetic biology for the development and production of pharmaceutical agents. In this Review, we describe the metabolic engineering and synthetic biology approaches that were used to develop this important antimalarial drug precursor. This not only demonstrates the incredible potential of the available technologies but also illuminates how lessons learned from this work could be applied to the production of other pharmaceutical agents.

  12. Playing God? Synthetic biology as a theological and ethical challenge

    OpenAIRE

    2009-01-01

    In the ethical debate over synthetic biology the formula “playing god” is widely used in order to attack this new branch of biotechnology. The article analyses, contextualizes and criticises this usage with respect to the theological concepts of creation, sin and humans as created in the image of God. Against the background of these theological understandings an ethical corridor of how to responsibly cope with the societal challenges of synthetic biology is presented.

  13. Playing God? Synthetic biology as a theological and ethical challenge.

    Science.gov (United States)

    Dabrock, Peter

    2009-12-01

    In the ethical debate over synthetic biology the formula "playing god" is widely used in order to attack this new branch of biotechnology. The article analyses, contextualizes and criticises this usage with respect to the theological concepts of creation, sin and humans as created in the image of God. Against the background of these theological understandings an ethical corridor of how to responsibly cope with the societal challenges of synthetic biology is presented.

  14. Synthetic biology of cyanobacteria: unique challenges and opportunities

    OpenAIRE

    Berla, Bertram M.; Saha, Rajib; Immethun, Cheryl M.; Maranas, Costas D.; Moon, Tae Seok; Pakrasi, Himadri B.

    2013-01-01

    Photosynthetic organisms, and especially cyanobacteria, hold great promise as sources of renewably-produced fuels, bulk and specialty chemicals, and nutritional products. Synthetic biology tools can help unlock cyanobacteria's potential for these functions, but unfortunately tool development for these organisms has lagged behind that for S. cerevisiae and E. coli. While these organisms may in many cases be more difficult to work with as “chassis” strains for synthetic biology than certain het...

  15. The Role of Synthetic Biology in NASA's Missions

    Science.gov (United States)

    Rothschild, Lynn J.

    2016-01-01

    The time has come to for NASA to exploit synthetic biology in pursuit of its missions, including aeronautics, earth science, astrobiology and most notably, human exploration. Conversely, NASA advances the fundamental technology of synthetic biology as no one else can because of its unique expertise in the origin of life and life in extreme environments, including the potential for alternate life forms. This enables unique, creative "game changing" advances. NASA's requirement for minimizing upmass in flight will also drive the field toward miniaturization and automation. These drivers will greatly increase the utility of synthetic biology solutions for military, health in remote areas and commercial purposes. To this end, we have begun a program at NASA to explore the use of synthetic biology in NASA's missions, particular space exploration. As part of this program, we began hosting an iGEM team of undergraduates drawn from Brown and Stanford Universities to conduct synthetic biology research at NASA Ames Research Center. The 2011 team (http://2011.igem.org/Team:Brown-Stanford) produced an award-winning project on using synthetic biology as a basis for a human Mars settlement.

  16. Exploring the potential of metallic nanoparticles within synthetic biology.

    Science.gov (United States)

    Edmundson, Matthew C; Capeness, Michael; Horsfall, Louise

    2014-12-25

    The fields of metallic nanoparticle study and synthetic biology have a great deal to offer one another. Metallic nanoparticles as a class of material have many useful properties. Their small size allows for more points of contact than would be the case with a similar bulk compound, making nanoparticles excellent candidates for catalysts or for when increased levels of binding are required. Some nanoparticles have unique optical qualities, making them well suited as sensors, while others display para-magnetism, useful in medical imaging, especially by magnetic resonance imaging (MRI). Many of these metallic nanoparticles could be used in creating tools for synthetic biology, and conversely the use of synthetic biology could itself be utilised to create nanoparticle tools. Examples given here include the potential use of quantum dots (QDs) and gold nanoparticles as sensing mechanisms in synthetic biology, and the use of synthetic biology to create nanoparticle-sensing devices based on current methods of detecting metals and metalloids such as arsenate. There are a number of organisms which are able to produce a range of metallic nanoparticles naturally, such as species of the fungus Phoma which produces anti-microbial silver nanoparticles. The biological synthesis of nanoparticles may have many advantages over their more traditional industrial synthesis. If the proteins involved in biological nanoparticle synthesis can be put into a suitable bacterial chassis then they might be manipulated and the pathways engineered in order to produce more valuable nanoparticles.

  17. Charge transport in bottom-up inorganic-organic and quantum-coherent nanostructures

    NARCIS (Netherlands)

    Makarenko, Ksenia Sergeevna

    2015-01-01

    This thesis is based on results obtained from experiments designed for a consistent study of charge transport in bottom-up inorganic-organic and quantum-coherent nanostructures. New unconventional ways to build elements of electrical circuits (like dielectrophoresis, wedging transfer and bottom-up f

  18. Synthetic Biology Open Language (SBOL) Version 2.0.0.

    Science.gov (United States)

    Bartley, Bryan; Beal, Jacob; Clancy, Kevin; Misirli, Goksel; Roehner, Nicholas; Oberortner, Ernst; Pocock, Matthew; Bissell, Michael; Madsen, Curtis; Nguyen, Tramy; Zhang, Zhen; Gennari, John H; Myers, Chris; Wipat, Anil; Sauro, Herbert

    2015-09-04

    Synthetic biology builds upon the techniques and successes of genetics, molecular biology, and metabolic engineering by applying engineering principles to the design of biological systems. The field still faces substantial challenges, including long development times, high rates of failure, and poor reproducibility. One method to ameliorate these problems would be to improve the exchange of information about designed systems between laboratories. The Synthetic Biology Open Language (SBOL) has been developed as a standard to support the specification and exchange of biological design information in synthetic biology, filling a need not satisfied by other pre-existing standards. This document details version 2.0 of SBOL, introducing a standardized format for the electronic exchange of information on the structural and functional aspects of biological designs. The standard has been designed to support the explicit and unambiguous description of biological designs by means of a well defined data model. The standard also includes rules and best practices on how to use this data model and populate it with relevant design details. The publication of this specification is intended to make these capabilities more widely accessible to potential developers and users in the synthetic biology community and beyond.

  19. Using synthetic biology to make cells tomorrow's test tubes.

    Science.gov (United States)

    Garcia, Hernan G; Brewster, Robert C; Phillips, Rob

    2016-04-18

    The main tenet of physical biology is that biological phenomena can be subject to the same quantitative and predictive understanding that physics has afforded in the context of inanimate matter. However, the inherent complexity of many of these biological processes often leads to the derivation of complex theoretical descriptions containing a plethora of unknown parameters. Such complex descriptions pose a conceptual challenge to the establishment of a solid basis for predictive biology. In this article, we present various exciting examples of how synthetic biology can be used to simplify biological systems and distill these phenomena down to their essential features as a means to enable their theoretical description. Here, synthetic biology goes beyond previous efforts to engineer nature and becomes a tool to bend nature to understand it. We discuss various recent and classic experiments featuring applications of this synthetic approach to the elucidation of problems ranging from bacteriophage infection, to transcriptional regulation in bacteria and in developing embryos, to evolution. In all of these examples, synthetic biology provides the opportunity to turn cells into the equivalent of a test tube, where biological phenomena can be reconstituted and our theoretical understanding put to test with the same ease that these same phenomena can be studied in the in vitro setting.

  20. Biomedically relevant circuit-design strategies in mammalian synthetic biology.

    Science.gov (United States)

    Bacchus, William; Aubel, Dominique; Fussenegger, Martin

    2013-01-01

    The development and progress in synthetic biology has been remarkable. Although still in its infancy, synthetic biology has achieved much during the past decade. Improvements in genetic circuit design have increased the potential for clinical applicability of synthetic biology research. What began as simple transcriptional gene switches has rapidly developed into a variety of complex regulatory circuits based on the transcriptional, translational and post-translational regulation. Instead of compounds with potential pharmacologic side effects, the inducer molecules now used are metabolites of the human body and even members of native cell signaling pathways. In this review, we address recent progress in mammalian synthetic biology circuit design and focus on how novel designs push synthetic biology toward clinical implementation. Groundbreaking research on the implementation of optogenetics and intercellular communications is addressed, as particularly optogenetics provides unprecedented opportunities for clinical application. Along with an increase in synthetic network complexity, multicellular systems are now being used to provide a platform for next-generation circuit design.

  1. The PLOS ONE synthetic biology collection: six years and counting.

    Science.gov (United States)

    Peccoud, Jean; Isalan, Mark

    2012-01-01

    Since it was launched in 2006, PLOS ONE has published over fifty articles illustrating the many facets of the emerging field of synthetic biology. This article reviews these publications by organizing them into broad categories focused on DNA synthesis and assembly techniques, the development of libraries of biological parts, the use of synthetic biology in protein engineering applications, and the engineering of gene regulatory networks and metabolic pathways. Finally, we review articles that describe enabling technologies such as software and modeling, along with new instrumentation. In order to increase the visibility of this body of work, the papers have been assembled into the PLOS ONE Synthetic Biology Collection (www.ploscollections.org/synbio). Many of the innovative features of the PLOS ONE web site will help make this collection a resource that will support a lively dialogue between readers and authors of PLOS ONE synthetic biology papers. The content of the collection will be updated periodically by including relevant articles as they are published by the journal. Thus, we hope that this collection will continue to meet the publishing needs of the synthetic biology community.

  2. Synthetic Biology: Knowledge Accessed by Everyone (Open Sources)

    Science.gov (United States)

    Sánchez Reyes, Patricia Margarita

    2016-01-01

    Using the principles of biology, along with engineering and with the help of computer, scientists manage to copy. DNA sequences from nature and use them to create new organisms. DNA is created through engineering and computer science managing to create life inside a laboratory. We cannot dismiss the role that synthetic biology could lead in…

  3. Cell-free synthetic biology for environmental sensing and remediation.

    Science.gov (United States)

    Karig, David K

    2017-02-19

    The fields of biosensing and bioremediation leverage the phenomenal array of sensing and metabolic capabilities offered by natural microbes. Synthetic biology provides tools for transforming these fields through complex integration of natural and novel biological components to achieve sophisticated sensing, regulation, and metabolic function. However, the majority of synthetic biology efforts are conducted in living cells, and concerns over releasing genetically modified organisms constitute a key barrier to environmental applications. Cell-free protein expression systems offer a path towards leveraging synthetic biology, while preventing the spread of engineered organisms in nature. Recent efforts in the areas of cell-free approaches for sensing, regulation, and metabolic pathway implementation, as well as for preserving and deploying cell-free expression components, embody key steps towards realizing the potential of cell-free systems for environmental sensing and remediation.

  4. Aesthetics in synthesis and synthetic biology.

    Science.gov (United States)

    Benner, Steven A

    2012-12-01

    Physicists frequently allow aesthetics to guide their science. Chemists sometimes do. Biologists rarely do. They have encountered too frequently the consequences of the Darwinian 'hack'. The biological parts delivered by Darwinian processes are rarely simple, efficient, or elegant solutions to the biological problems that they address. Nevertheless, as humans, we seek to find aesthetics within our activities. In general, however, it is hard to distinguish what we say is beautiful from what is, in reality, utilitarian.

  5. Industrial systems biology and its impact on synthetic biology of yeast cell factories

    DEFF Research Database (Denmark)

    Fletcher, Eugene; Krivoruchko, Anastasia; Nielsen, Jens

    2016-01-01

    Engineering industrial cell factories to effectively yield a desired product while dealing with industrially relevant stresses is usually the most challenging step in the development of industrial production of chemicals using microbial fermentation processes. Using synthetic biology tools......, microbial cell factories such as Saccharomyces cerevisiae can be engineered to express synthetic pathways for the production of fuels, biopharmaceuticals, fragrances, and food flavors. However, directing fluxes through these synthetic pathways towards the desired product can be demanding due to complex...... regulation or poor gene expression. Systems biology, which applies computational tools and mathematical modeling to understand complex biological networks, can be used to guide synthetic biology design. Here, we present our perspective on how systems biology can impact synthetic biology towards the goal...

  6. Industrial systems biology and its impact on synthetic biology of yeast cell factories.

    Science.gov (United States)

    Fletcher, Eugene; Krivoruchko, Anastasia; Nielsen, Jens

    2016-06-01

    Engineering industrial cell factories to effectively yield a desired product while dealing with industrially relevant stresses is usually the most challenging step in the development of industrial production of chemicals using microbial fermentation processes. Using synthetic biology tools, microbial cell factories such as Saccharomyces cerevisiae can be engineered to express synthetic pathways for the production of fuels, biopharmaceuticals, fragrances, and food flavors. However, directing fluxes through these synthetic pathways towards the desired product can be demanding due to complex regulation or poor gene expression. Systems biology, which applies computational tools and mathematical modeling to understand complex biological networks, can be used to guide synthetic biology design. Here, we present our perspective on how systems biology can impact synthetic biology towards the goal of developing improved yeast cell factories. Biotechnol. Bioeng. 2016;113: 1164-1170. © 2015 Wiley Periodicals, Inc.

  7. Aspects of the political economy of development and synthetic biology.

    Science.gov (United States)

    Wellhausen, Rachel; Mukunda, Gautam

    2009-12-01

    What implications might synthetic biology's potential as a wholly new method of production have for the world economy, particularly developing countries? Theories of political economy predict that synthetic biology can shift terms of trade and displace producers in developing countries. Governments, however, retain the ability to mitigate negative changes through social safety nets and to foster adaptation to some changes through research, education and investment. We consider the effects the synthetic production of otherwise naturally derived molecules are likely to have on trade and investment, particularly in developing countries. Both rubber in Malaysia and indigo dyes in India provide historical examples of natural molecules that faced market dislocations from synthetic competitors. Natural rubber was able to maintain significant market share, while natural indigo vanished from world markets. These cases demonstrate the two extremes of the impact synthetic biology might have on naturally derived products. If developing countries can cushion the pain of technological changes by providing producers support as they retool or exit, the harmful effects of synthetic biology can be mitigated while its benefits can still be captured.

  8. Synthetic biology and biosecurity: challenging the ‘myths’

    Directory of Open Access Journals (Sweden)

    Catherine eJefferson

    2014-08-01

    Full Text Available Synthetic biology, a field that aims to ‘make biology easier to engineer’, is routinely described as leading to an increase in the ‘dual use’ threat, i.e. the potential for the same piece of scientific research to be ‘used’ for peaceful purposes or ‘misused’ for warfare or terrorism. Fears have been expressed that the ‘de-skilling’ of biology, combined with online access to the genomic DNA sequences of pathogenic organisms and the reduction in price for DNA synthesis, will make biology increasingly accessible to people operating outside well-equipped professional research laboratories, including people with malevolent intentions. The emergence of DIY biology communities and of the student iGEM competition has come to epitomize this supposed trend towards greater ease of access and the associated potential threat from rogue actors. In this article, we identify 5 ‘myths’ that permeate discussions about synthetic biology and biosecurity, and argue that they embody misleading assumptions about both synthetic biology and bioterrorism. We demonstrate how these myths are challenged by more realistic understandings of the scientific research currently being conducted in both professional and DIY laboratories, and by an analysis of historical cases of bioterrorism. We show that the importance of tacit knowledge is commonly overlooked in the dominant narrative: the focus is on access to biological materials and digital information, rather than on human practices and institutional dimensions. As a result, public discourse on synthetic biology and biosecurity tends to portray speculative scenarios about the future as realities in the present or the near future, when this is not warranted. We suggest that these ‘myths’ play an important role in defining synthetic biology as a ‘promissory’ field of research and as an ‘emerging technology’ in need of governance.

  9. [Application of microelectronics CAD tools to synthetic biology].

    Science.gov (United States)

    Madec, Morgan; Haiech, Jacques; Rosati, Élise; Rezgui, Abir; Gendrault, Yves; Lallement, Christophe

    2017-02-01

    Synthetic biology is an emerging science that aims to create new biological functions that do not exist in nature, based on the knowledge acquired in life science over the last century. Since the beginning of this century, several projects in synthetic biology have emerged. The complexity of the developed artificial bio-functions is relatively low so that empirical design methods could be used for the design process. Nevertheless, with the increasing complexity of biological circuits, this is no longer the case and a large number of computer aided design softwares have been developed in the past few years. These tools include languages for the behavioral description and the mathematical modelling of biological systems, simulators at different levels of abstraction, libraries of biological devices and circuit design automation algorithms. All of these tools already exist in other fields of engineering sciences, particularly in microelectronics. This is the approach that is put forward in this paper.

  10. Systems Biology and Synthetic Biology: A New Epoch for Toxicology Research

    OpenAIRE

    Mark T. Mc Auley; Hyunok Choi; Kathleen Mooney; Emily Paul; Miller, Veronica M.

    2015-01-01

    Systems biology and synthetic biology are emerging disciplines which are becoming increasingly utilised in several areas of bioscience. Toxicology is beginning to benefit from systems biology and we suggest in the future that is will also benefit from synthetic biology. Thus, a new era is on the horizon. This review illustrates how a suite of innovative techniques and tools can be applied to understanding complex health and toxicology issues. We review limitations confronted by the traditiona...

  11. Synthetic Biology of Cyanobacteria: Unique Challenges and Opportunities

    Directory of Open Access Journals (Sweden)

    Bertram M Berla

    2013-08-01

    Full Text Available Photosynthetic organisms, and especially cyanobacteria, hold great promise as sources of renewably-produced fuels, bulk and specialty chemicals, and nutritional products. Synthetic biology tools can help unlock cyanobacteria’s potential for these functions, but unfortunately tool development for these organisms has lagged behind that for S. cerevisiae and E. coli. While these organisms may in many cases be more difficult to work with as ‘chassis’ strains for synthetic biology than certain heterotrophs, the unique advantages of autotrophs in biotechnology applications as well as the scientific importance of improved understanding of photosynthesis warrant the development of these systems into something akin to a ‘green E. coli’. In this review, we highlight unique challenges and opportunities for development of synthetic biology approaches in cyanobacteria. We review classical and recently developed methods for constructing targeted mutants in various cyanobacterial strains, and offer perspective on what genetic tools might most greatly expand the ability to engineer new functions in such strains. Similarly, we review what genetic parts are most needed for the development of cyanobacterial synthetic biology. Finally, we highlight recent methods to construct genome-scale models of cyanobacterial metabolism and to use those models to measure properties of autotrophic metabolism. Throughout this paper, we discuss some of the unique challenges of a diurnal, autotrophic lifestyle along with how the development of synthetic biology and biotechnology in cyanobacteria must fit within those constraints.

  12. Varieties of noise: analogical reasoning in synthetic biology.

    Science.gov (United States)

    Knuuttila, Tarja; Loettgers, Andrea

    2014-12-01

    The picture of synthetic biology as a kind of engineering science has largely created the public understanding of this novel field, covering both its promises and risks. In this paper, we will argue that the actual situation is more nuanced and complex. Synthetic biology is a highly interdisciplinary field of research located at the interface of physics, chemistry, biology, and computational science. All of these fields provide concepts, metaphors, mathematical tools, and models, which are typically utilized by synthetic biologists by drawing analogies between the different fields of inquiry. We will study analogical reasoning in synthetic biology through the emergence of the functional meaning of noise, which marks an important shift in how engineering concepts are employed in this field. The notion of noise serves also to highlight the differences between the two branches of synthetic biology: the basic science-oriented branch and the engineering-oriented branch, which differ from each other in the way they draw analogies to various other fields of study. Moreover, we show that fixing the mapping between a source domain and the target domain seems not to be the goal of analogical reasoning in actual scientific practice.

  13. Synthetic Biology: A Unifying View and Review Using Analog Circuits.

    Science.gov (United States)

    Teo, Jonathan J Y; Woo, Sung Sik; Sarpeshkar, Rahul

    2015-08-01

    We review the field of synthetic biology from an analog circuits and analog computation perspective, focusing on circuits that have been built in living cells. This perspective is well suited to pictorially, symbolically, and quantitatively representing the nonlinear, dynamic, and stochastic (noisy) ordinary and partial differential equations that rigorously describe the molecular circuits of synthetic biology. This perspective enables us to construct a canonical analog circuit schematic that helps unify and review the operation of many fundamental circuits that have been built in synthetic biology at the DNA, RNA, protein, and small-molecule levels over nearly two decades. We review 17 circuits in the literature as particular examples of feedforward and feedback analog circuits that arise from special topological cases of the canonical analog circuit schematic. Digital circuit operation of these circuits represents a special case of saturated analog circuit behavior and is automatically incorporated as well. Many issues that have prevented synthetic biology from scaling are naturally represented in analog circuit schematics. Furthermore, the deep similarity between the Boltzmann thermodynamic equations that describe noisy electronic current flow in subthreshold transistors and noisy molecular flux in biochemical reactions has helped map analog circuit motifs in electronics to analog circuit motifs in cells and vice versa via a `cytomorphic' approach. Thus, a body of knowledge in analog electronic circuit design, analysis, simulation, and implementation may also be useful in the robust and efficient design of molecular circuits in synthetic biology, helping it to scale to more complex circuits in the future.

  14. Synthetic biology of cyanobacteria: unique challenges and opportunities.

    Science.gov (United States)

    Berla, Bertram M; Saha, Rajib; Immethun, Cheryl M; Maranas, Costas D; Moon, Tae Seok; Pakrasi, Himadri B

    2013-01-01

    Photosynthetic organisms, and especially cyanobacteria, hold great promise as sources of renewably-produced fuels, bulk and specialty chemicals, and nutritional products. Synthetic biology tools can help unlock cyanobacteria's potential for these functions, but unfortunately tool development for these organisms has lagged behind that for S. cerevisiae and E. coli. While these organisms may in many cases be more difficult to work with as "chassis" strains for synthetic biology than certain heterotrophs, the unique advantages of autotrophs in biotechnology applications as well as the scientific importance of improved understanding of photosynthesis warrant the development of these systems into something akin to a "green E. coli." In this review, we highlight unique challenges and opportunities for development of synthetic biology approaches in cyanobacteria. We review classical and recently developed methods for constructing targeted mutants in various cyanobacterial strains, and offer perspective on what genetic tools might most greatly expand the ability to engineer new functions in such strains. Similarly, we review what genetic parts are most needed for the development of cyanobacterial synthetic biology. Finally, we highlight recent methods to construct genome-scale models of cyanobacterial metabolism and to use those models to measure properties of autotrophic metabolism. Throughout this paper, we discuss some of the unique challenges of a diurnal, autotrophic lifestyle along with how the development of synthetic biology and biotechnology in cyanobacteria must fit within those constraints.

  15. A Converter from the Systems Biology Markup Language to the Synthetic Biology Open Language.

    Science.gov (United States)

    Nguyen, Tramy; Roehner, Nicholas; Zundel, Zach; Myers, Chris J

    2016-06-17

    Standards are important to synthetic biology because they enable exchange and reproducibility of genetic designs. This paper describes a procedure for converting between two standards: the Systems Biology Markup Language (SBML) and the Synthetic Biology Open Language (SBOL). SBML is a standard for behavioral models of biological systems at the molecular level. SBOL describes structural and basic qualitative behavioral aspects of a biological design. Converting SBML to SBOL enables a consistent connection between behavioral and structural information for a biological design. The conversion process described in this paper leverages Systems Biology Ontology (SBO) annotations to enable inference of a designs qualitative function.

  16. Opportunities for synthetic biology in antibiotics: expanding glycopeptide chemical diversity.

    Science.gov (United States)

    Thaker, Maulik N; Wright, Gerard D

    2015-03-20

    Synthetic biology offers a new path for the exploitation and improvement of natural products to address the growing crisis in antibiotic resistance. All antibiotics in clinical use are facing eventual obsolesce as a result of the evolution and dissemination of resistance mechanisms, yet there are few new drug leads forthcoming from the pharmaceutical sector. Natural products of microbial origin have proven over the past 70 years to be the wellspring of antimicrobial drugs. Harnessing synthetic biology thinking and strategies can provide new molecules and expand chemical diversity of known antibiotic scaffolds to provide much needed new drug leads. The glycopeptide antibiotics offer paradigmatic scaffolds suitable for such an approach. We review these strategies here using the glycopeptides as an example and demonstrate how synthetic biology can expand antibiotic chemical diversity to help address the growing resistance crisis.

  17. Synthetic biology and the moral significance of artificial life

    DEFF Research Database (Denmark)

    Christiansen, Andreas

    2016-01-01

    I discuss the moral significance of artificial life within synthetic biology via a discussion of Douglas, Powell and Savulescu's paper 'Is the creation of artificial life morally significant’. I argue that the definitions of 'artificial life’ and of 'moral significance’ are too narrow. Douglas......, Powell and Savulescu's definition of artificial life does not capture all core projects of synthetic biology or the ethical concerns that have been voiced, and their definition of moral significance fails to take into account the possibility that creating artificial life is conditionally acceptable....... Finally, I show how several important objections to synthetic biology are plausibly understood as arguing that creating artificial life in a wide sense is only conditionally acceptable....

  18. Mapping practices of project management – merging top-down and bottom-up perspectives

    DEFF Research Database (Denmark)

    Thuesen, Christian

    2015-01-01

    This paper presents a new methodology for studying different accounts of project management practices based on network mapping and analysis. Drawing upon network mapping and visualization as an analytical strategy top-down and bottom-up accounts of project management practice are analysed...... and compared. The analysis initially reveals a substantial difference between the top-down and bottom-up accounts of practice. Furthermore it identifies a soft side of project management that is central in the bottom-up account but absent from the top-down. Finally, the study shows that network mapping...... is a promising strategy for visualizing and analysing different accounts of project management practices....

  19. Anticipation: beyond synthetic biology and cognitive robotics

    OpenAIRE

    Slawomir J. Nasuto; Hayashi, Yoshikatsu

    2016-01-01

    The aim of this paper is to propose that current robotic technologies cannot have intentional states any more than is feasible within the sensorimotor variant of embodied cognition. It argues that anticipation is an emerging concept that can provide a bridge between both the deepest philosophical theories about the nature of life and cognition and the empirical biological and cognitive sciences steeped in reductionist and Newtonian conceptions of causality. The paper advocates that in order t...

  20. Anticipation: Beyond synthetic biology and cognitive robotics.

    Science.gov (United States)

    Nasuto, Slawomir J; Hayashi, Yoshikatsu

    2016-10-01

    The aim of this paper is to propose that current robotic technologies cannot have intentional states any more than is feasible within the sensorimotor variant of embodied cognition. It argues that anticipation is an emerging concept that can provide a bridge between both the deepest philosophical theories about the nature of life and cognition and the empirical biological and cognitive sciences steeped in reductionist and Newtonian conceptions of causality. The paper advocates that in order to move forward, cognitive robotics needs to embrace new platforms and a conceptual framework that will enable it to pursue, in a meaningful way, questions about autonomy and purposeful behaviour. We suggest that hybrid systems, part robotic and part cultures of neurones, offer experimental platforms where different dimensions of enactivism (sensorimotor, constitutive foundations of biological autonomy, including anticipation), and their relative contributions to cognition, can be investigated in an integrated way. A careful progression, mindful to the deep philosophical concerns but also respecting empirical evidence, will ultimately lead towards unifying theoretical and empirical biological sciences and may offer advancement where reductionist sciences have been so far faltering.

  1. Selection platforms for directed evolution in synthetic biology.

    Science.gov (United States)

    Tizei, Pedro A G; Csibra, Eszter; Torres, Leticia; Pinheiro, Vitor B

    2016-08-15

    Life on Earth is incredibly diverse. Yet, underneath that diversity, there are a number of constants and highly conserved processes: all life is based on DNA and RNA; the genetic code is universal; biology is limited to a small subset of potential chemistries. A vast amount of knowledge has been accrued through describing and characterizing enzymes, biological processes and organisms. Nevertheless, much remains to be understood about the natural world. One of the goals in Synthetic Biology is to recapitulate biological complexity from simple systems made from biological molecules-gaining a deeper understanding of life in the process. Directed evolution is a powerful tool in Synthetic Biology, able to bypass gaps in knowledge and capable of engineering even the most highly conserved biological processes. It encompasses a range of methodologies to create variation in a population and to select individual variants with the desired function-be it a ligand, enzyme, pathway or even whole organisms. Here, we present some of the basic frameworks that underpin all evolution platforms and review some of the recent contributions from directed evolution to synthetic biology, in particular methods that have been used to engineer the Central Dogma and the genetic code.

  2. A Computational Strategy to Analyze Label-Free Temporal Bottom-up Proteomics Data

    Energy Technology Data Exchange (ETDEWEB)

    Du, Xiuxia; Callister, Stephen J.; Manes, Nathan P.; Adkins, Joshua N.; Alexandridis, Roxana A.; Zeng, Xiaohua; Roh, Jung Hyeob; Smith, William E.; Donohue, Timothy J.; Kaplan, Samuel; Smith, Richard D.; Lipton, Mary S.

    2008-07-01

    Motivation: Biological systems are in a continual state of flux, which necessitates an understanding of the dynamic nature of protein abundances. The study of protein abundance dynamics has become feasible with recent improvements in mass spectrometry-based quantitative proteomics. However, a number of challenges still re-main related to how best to extract biological information from dy-namic proteomics data; for example, challenges related to extrane-ous variability, missing abundance values, and the identification of significant temporal patterns. Results: This article describes a strategy that addresses the afore-mentioned issues for the analysis of temporal bottom-up proteomics data. The core strategy for the data analysis algorithms and subse-quent data interpretation was formulated to take advantage of the temporal properties of the data. The analysis procedure presented herein was applied to data from a Rhodobacter sphaeroides 2.4.1 time-course study. The results were in close agreement with existing knowledge about R. sphaeroides, therefore demonstrating the utility of this analytical strategy.

  3. Toward metabolic engineering in the context of system biology and synthetic biology: advances and prospects.

    Science.gov (United States)

    Liu, Yanfeng; Shin, Hyun-dong; Li, Jianghua; Liu, Long

    2015-02-01

    Metabolic engineering facilitates the rational development of recombinant bacterial strains for metabolite overproduction. Building on enormous advances in system biology and synthetic biology, novel strategies have been established for multivariate optimization of metabolic networks in ensemble, spatial, and dynamic manners such as modular pathway engineering, compartmentalization metabolic engineering, and metabolic engineering guided by genome-scale metabolic models, in vitro reconstitution, and systems and synthetic biology. Herein, we summarize recent advances in novel metabolic engineering strategies. Combined with advancing kinetic models and synthetic biology tools, more efficient new strategies for improving cellular properties can be established and applied for industrially important biochemical production.

  4. Synthetic biology for microbial production of lipid-based biofuels.

    Science.gov (United States)

    d'Espaux, Leo; Mendez-Perez, Daniel; Li, Rachel; Keasling, Jay D

    2015-12-01

    The risks of maintaining current CO2 emission trends have led to interest in producing biofuels using engineered microbes. Microbial biofuels reduce emissions because CO2 produced by fuel combustion is offset by CO2 captured by growing biomass, which is later used as feedstock for biofuel fermentation. Hydrocarbons found in petroleum fuels share striking similarity with biological lipids. Here we review synthetic metabolic pathways based on fatty acid and isoprenoid metabolism to produce alkanes and other molecules suitable as biofuels. We further discuss engineering strategies to optimize engineered biosynthetic routes, as well as the potential of synthetic biology for sustainable manufacturing.

  5. Regenesis how synthetic biology will reinvent nature and ourselves

    CERN Document Server

    Church, George M

    2012-01-01

    Imagine a future in which human beings have become immune to all viruses, in which bacteria can custom-produce everyday items, like a drinking cup, or generate enough electricity to end oil dependency. Building a house would entail no more work than planting a seed in the ground. These scenarios may seem far-fetched, but pioneering geneticist George Church and science writer Ed Regis show that synthetic biology is bringing us ever closer to making such visions a reality. In "Regenesis," Church and Regis explorethe possibilities--and perils--of the emerging field of synthetic biology. Synthetic biology, in which living organisms are selectively altered by modifying substantial portions of their genomes, allows for the creation of entirely new species of organisms. Until now, nature has been the exclusive arbiter of life, death, and evolution; with synthetic biology, we now have the potential to write our own biological future. Indeed, as Church and Regis show, it even enables us to revisit crucial points in th...

  6. Synthetic Nanopores: Biological Analogues and Nanofluidic Devices

    Science.gov (United States)

    Davenport, Matthew W.

    Nanoscopic pores in biological systems -- cells, for example -- are responsible for regulating the transport of ionic and molecular species between physiologically distinct compartments maintained by thin plasma membranes. These biological pores are proteinaceous structures: long, contorted chains of chemical building blocks called amino acids. Protein pores have evolved to span a staggering range of shapes, sizes and chemical properties, each crucial to a pore's unique functionality. Protein pores have extremely well-defined jobs. For instance, pores called ion channels only transport ions. Within this family, there are pores designated to selectively transport specific ions, such as sodium channels for sodium, chloride channels for chloride and so on. Further subdivisions exist within each type of ion channel, resulting in a pantheon of specialized proteins pores. Specificity and selectivity are bestowed upon a pore through its unique incorporation and arrangement of its amino acids, which in turn have their own unique chemical and physical properties. With hundreds of task-specific pores, deciphering the precise relationship between form and function in these protein channels is a critical, but daunting task. In this thesis, we examine an alternative for probing the fundamental mechanisms responsible for transport on the nanoscale. Solid-state membranes offer well-defined structural surrogates to directly address the science underlying pore functionality. Numerous protein pores rely on electronic interactions, size exclusion principles and hydrophobic effects to fulfill their duties, regardless of their amino acid sequence. Substituting an engineered and well-characterized pore, we strive to achieve and, thus, understand the hallmarks of biological pore function: analyte recognition and selective transport. While we restrict our study to only two readily available membrane materials -- one a polymer and the other a ceramic -- nanofabrication techniques give us

  7. Painful faces-induced attentional blink modulated by top-down and bottom-up mechanisms

    OpenAIRE

    2015-01-01

    Pain-related stimuli can capture attention in an automatic (bottom-up) or intentional (top-down) fashion. Previous studies have examined attentional capture by pain-related information using spatial attention paradigms that involve mainly a bottom-up mechanism. In the current study, we investigated the pain information–induced attentional blink (AB) using a rapid serial visual presentation (RSVP) task, and compared the effects of task-irrelevant and task-relevant pain distractors. Relationshi...

  8. TinkerCell: modular CAD tool for synthetic biology

    Directory of Open Access Journals (Sweden)

    Bergmann Frank T

    2009-10-01

    Full Text Available Abstract Background Synthetic biology brings together concepts and techniques from engineering and biology. In this field, computer-aided design (CAD is necessary in order to bridge the gap between computational modeling and biological data. Using a CAD application, it would be possible to construct models using available biological "parts" and directly generate the DNA sequence that represents the model, thus increasing the efficiency of design and construction of synthetic networks. Results An application named TinkerCell has been developed in order to serve as a CAD tool for synthetic biology. TinkerCell is a visual modeling tool that supports a hierarchy of biological parts. Each part in this hierarchy consists of a set of attributes that define the part, such as sequence or rate constants. Models that are constructed using these parts can be analyzed using various third-party C and Python programs that are hosted by TinkerCell via an extensive C and Python application programming interface (API. TinkerCell supports the notion of a module, which are networks with interfaces. Such modules can be connected to each other, forming larger modular networks. TinkerCell is a free and open-source project under the Berkeley Software Distribution license. Downloads, documentation, and tutorials are available at http://www.tinkercell.com. Conclusion An ideal CAD application for engineering biological systems would provide features such as: building and simulating networks, analyzing robustness of networks, and searching databases for components that meet the design criteria. At the current state of synthetic biology, there are no established methods for measuring robustness or identifying components that fit a design. The same is true for databases of biological parts. TinkerCell's flexible modeling framework allows it to cope with changes in the field. Such changes may involve the way parts are characterized or the way synthetic networks are modeled

  9. Synthetic biology of minimal living cells: primitive cell models and semi-synthetic cells.

    Science.gov (United States)

    Stano, Pasquale

    2010-09-01

    This article summarizes a contribution presented at the ESF 2009 Synthetic Biology focused on the concept of the minimal requirement for life and on the issue of constructive (synthetic) approaches in biological research. The attempts to define minimal life within the framework of autopoietic theory are firstly described, and a short report on the development of autopoietic chemical systems based on fatty acid vesicles, which are relevant as primitive cell models is given. These studies can be used as a starting point for the construction of more complex systems, firstly being inspired by possible origins of life scenarioes (and therefore by considering primitive functions), then by considering an approach based on modern biomacromolecular-encoded functions. At this aim, semi-synthetic minimal cells are defined as those man-made vesicle-based systems that are composed of the minimal number of genes, proteins, biomolecules and which can be defined as living. Recent achievements on minimal sized semi-synthetic cells are then discussed, and the kind of information obtained is recognized as being distinctively derived by a constructive approach. Synthetic biology is therefore a fundamental tool for gaining basic knowledge about biosystems, and it should not be confined at all to the engineering side.

  10. Identifying robust clusters and multi-community nodes by combining top-down and bottom-up approaches to clustering

    CERN Document Server

    Gaiteri, Chris; Szymanski, Boleslaw; Kuzmin, Konstantin; Xie, Jierui; Lee, Changkyu; Blanche, Timothy; Neto, Elias Chaibub; Huang, Su-Chun; Grabowski, Thomas; Madhyastha, Tara; Komashko, Vitalina

    2015-01-01

    Biological functions are often realized by groups of interacting molecules or cells. Membership in these groups may overlap when molecules or cells are reused in multiple functions. Traditional clustering methods assign each component to one group. Noisy measurements are common in high-throughput biological datasets. These two limitations reduce our ability to accurately define clusters in biological datasets and to interpret their biological functions. To address these limitations, we designed an algorithm called SpeakEasy, which detects overlapping or non-overlapping communities in biological networks. Input to SpeakEasy can be physical networks, such as molecular interactions, or inferred networks, such as gene coexpression networks. The networks can be directed or undirected, and may contain negative links. SpeakEasy combines traditional bottom-up and top-down approaches to clustering, by creating competition between clusters. Nodes that oscillate between multiple clusters in this competition are classifi...

  11. Reinvigorating natural product combinatorial biosynthesis with synthetic biology.

    Science.gov (United States)

    Kim, Eunji; Moore, Bradley S; Yoon, Yeo Joon

    2015-09-01

    Natural products continue to play a pivotal role in drug-discovery efforts and in the understanding if human health. The ability to extend nature's chemistry through combinatorial biosynthesis--altering functional groups, regiochemistry and scaffold backbones through the manipulation of biosynthetic enzymes--offers unique opportunities to create natural product analogs. Incorporating emerging synthetic biology techniques has the potential to further accelerate the refinement of combinatorial biosynthesis as a robust platform for the diversification of natural chemical drug leads. Two decades after the field originated, we discuss the current limitations, the realities and the state of the art of combinatorial biosynthesis, including the engineering of substrate specificity of biosynthetic enzymes and the development of heterologous expression systems for biosynthetic pathways. We also propose a new perspective for the combinatorial biosynthesis of natural products that could reinvigorate drug discovery by using synthetic biology in combination with synthetic chemistry.

  12. Chemical master equation closure for computer-aided synthetic biology.

    Science.gov (United States)

    Smadbeck, Patrick; Kaznessis, Yiannis N

    2015-01-01

    With inexpensive DNA synthesis technologies, we can now construct biological systems by quickly piecing together DNA sequences. Synthetic biology is the promising discipline that focuses on the construction of these new biological systems. Synthetic biology is an engineering discipline, and as such, it can benefit from mathematical modeling. This chapter focuses on mathematical models of biological systems. These models take the form of chemical reaction networks. The importance of stochasticity is discussed and methods to simulate stochastic reaction networks are reviewed. A closure scheme solution is also presented for the master equation of chemical reaction networks. The master equation is a complete model of randomly evolving molecular populations. Because of its ambitious character, the master equation remained unsolved for all but the simplest of molecular interaction networks for over 70 years. With the first complete solution of chemical master equations, a wide range of experimental observations of biomolecular interactions may be mathematically conceptualized. We anticipate that models based on the closure scheme described herein may assist in rationally designing synthetic biological systems.

  13. Controlling the Biological Effects of Spermine Using a Synthetic Receptor

    NARCIS (Netherlands)

    Vial, Laurent; Ludlow, R. Frederick; Leclaire, Julien; Pérez-Fernández, Ruth; Otto, Sijbren

    2006-01-01

    Polyamines play an important role in biology, yet their exact function in many processes is poorly understood. Artificial host molecules capable of sequestering polyamines could be useful tools for studying their cellular function. However, designing synthetic receptors with affinities sufficient to

  14. Plant synthetic biology: a new platform for industrial biotechnology.

    Science.gov (United States)

    Fesenko, Elena; Edwards, Robert

    2014-05-01

    Thirty years after the production of the first generation of genetically modified plants we are now set to move into a new era of recombinant crop technology through the application of synthetic biology to engineer new and complex input and output traits. The use of synthetic biology technologies will represent more than incremental additions of transgenes, but rather the directed design of completely new metabolic pathways, physiological traits, and developmental control strategies. The need to enhance our ability to improve crops through new engineering capability is now increasingly pressing as we turn to plants not just for food, but as a source of renewable feedstocks for industry. These accelerating and diversifying demands for new output traits coincide with a need to reduce inputs and improve agricultural sustainability. Faced with such challenges, existing technologies will need to be supplemented with new and far-more-directed approaches to turn valuable resources more efficiently into usable agricultural products. While these objectives are challenging enough, the use of synthetic biology in crop improvement will face public acceptance issues as a legacy of genetically modified technologies in many countries. Here we review some of the potential benefits of adopting synthetic biology approaches in improving plant input and output traits for their use as industrial chemical feedstocks, as linked to the rapidly developing biorefining industry. Several promising technologies and biotechnological targets are identified along with some of the key regulatory and societal challenges in the safe and acceptable introduction of such technology.

  15. Synthetic Biology and the Argument from Continuity with Established Technologies

    DEFF Research Database (Denmark)

    Christiansen, Andreas

    2015-01-01

    ) that it ignores the distinction between what reasons we have and what we should do all things considered. I then illustrate the Continuity Argument and its problems in the case where human manipulation of organisms’ genetic makeup is a suggested reason for finding synthetic biology problematic. Finally, I suggest...

  16. Policy on synthetic biology: deliberation, probability, and the precautionary paradox.

    Science.gov (United States)

    Wareham, Christopher; Nardini, Cecilia

    2015-02-01

    Synthetic biology is a cutting-edge area of research that holds the promise of unprecedented health benefits. However, in tandem with these large prospective benefits, synthetic biology projects entail a risk of catastrophic consequences whose severity may exceed that of most ordinary human undertakings. This is due to the peculiar nature of synthetic biology as a 'threshold technology' which opens doors to opportunities and applications that are essentially unpredictable. Fears about these potentially unstoppable consequences have led to declarations from civil society groups calling for the use of a precautionary principle to regulate the field. Moreover, the principle is prevalent in law and international agreements. Despite widespread political recognition of a need for caution, the precautionary principle has been extensively criticized as a guide for regulatory policy. We examine a central objection to the principle: that its application entails crippling inaction and incoherence, since whatever action one takes there is always a chance that some highly improbable cataclysm will occur. In response to this difficulty, which we call the 'precautionary paradox,' we outline a deliberative means for arriving at threshold of probability below which potential dangers can be disregarded. In addition, we describe a Bayesian mechanism with which to assign probabilities to harmful outcomes. We argue that these steps resolve the paradox. The rehabilitated PP can thus provide a viable policy option to confront the uncharted waters of synthetic biology research.

  17. Toward the First Data Acquisition Standard in Synthetic Biology.

    Science.gov (United States)

    Sainz de Murieta, Iñaki; Bultelle, Matthieu; Kitney, Richard I

    2016-08-19

    This paper describes the development of a new data acquisition standard for synthetic biology. This comprises the creation of a methodology that is designed to capture all the data, metadata, and protocol information associated with biopart characterization experiments. The new standard, called DICOM-SB, is based on the highly successful Digital Imaging and Communications in Medicine (DICOM) standard in medicine. A data model is described which has been specifically developed for synthetic biology. The model is a modular, extensible data model for the experimental process, which can optimize data storage for large amounts of data. DICOM-SB also includes services orientated toward the automatic exchange of data and information between modalities and repositories. DICOM-SB has been developed in the context of systematic design in synthetic biology, which is based on the engineering principles of modularity, standardization, and characterization. The systematic design approach utilizes the design, build, test, and learn design cycle paradigm. DICOM-SB has been designed to be compatible with and complementary to other standards in synthetic biology, including SBOL. In this regard, the software provides effective interoperability. The new standard has been tested by experiments and data exchange between Nanyang Technological University in Singapore and Imperial College London.

  18. Systems biology as an integrated platform for bioinformatics, systems synthetic biology, and systems metabolic engineering.

    Science.gov (United States)

    Chen, Bor-Sen; Wu, Chia-Chou

    2013-10-11

    Systems biology aims at achieving a system-level understanding of living organisms and applying this knowledge to various fields such as synthetic biology, metabolic engineering, and medicine. System-level understanding of living organisms can be derived from insight into: (i) system structure and the mechanism of biological networks such as gene regulation, protein interactions, signaling, and metabolic pathways; (ii) system dynamics of biological networks, which provides an understanding of stability, robustness, and transduction ability through system identification, and through system analysis methods; (iii) system control methods at different levels of biological networks, which provide an understanding of systematic mechanisms to robustly control system states, minimize malfunctions, and provide potential therapeutic targets in disease treatment; (iv) systematic design methods for the modification and construction of biological networks with desired behaviors, which provide system design principles and system simulations for synthetic biology designs and systems metabolic engineering. This review describes current developments in systems biology, systems synthetic biology, and systems metabolic engineering for engineering and biology researchers. We also discuss challenges and future prospects for systems biology and the concept of systems biology as an integrated platform for bioinformatics, systems synthetic biology, and systems metabolic engineering.

  19. Systems Biology as an Integrated Platform for Bioinformatics, Systems Synthetic Biology, and Systems Metabolic Engineering

    Directory of Open Access Journals (Sweden)

    Bor-Sen Chen

    2013-10-01

    Full Text Available Systems biology aims at achieving a system-level understanding of living organisms and applying this knowledge to various fields such as synthetic biology, metabolic engineering, and medicine. System-level understanding of living organisms can be derived from insight into: (i system structure and the mechanism of biological networks such as gene regulation, protein interactions, signaling, and metabolic pathways; (ii system dynamics of biological networks, which provides an understanding of stability, robustness, and transduction ability through system identification, and through system analysis methods; (iii system control methods at different levels of biological networks, which provide an understanding of systematic mechanisms to robustly control system states, minimize malfunctions, and provide potential therapeutic targets in disease treatment; (iv systematic design methods for the modification and construction of biological networks with desired behaviors, which provide system design principles and system simulations for synthetic biology designs and systems metabolic engineering. This review describes current developments in systems biology, systems synthetic biology, and systems metabolic engineering for engineering and biology researchers. We also discuss challenges and future prospects for systems biology and the concept of systems biology as an integrated platform for bioinformatics, systems synthetic biology, and systems metabolic engineering.

  20. A 'bottom-up' approach to aetiological research in autism spectrum disorders

    Directory of Open Access Journals (Sweden)

    Lisa Marie Unwin

    2013-09-01

    Full Text Available Autism Spectrum Disorders (ASD are currently diagnosed in the presence of impairments in social interaction and communication, and a restricted range of activities and interests. However, there is considerable variability in the behaviours of different individuals with an ASD diagnosis. The heterogeneity spans the entire range of IQ and language abilities, as well as other behavioural, communicative and social functions. While any psychiatric condition is likely to incorporate a degree of heterogeneity, the variability in the nature and severity of behaviours observed in ASD is thought to exceed that of other disorders. The current paper aims to provide a model for future research into ASD subgroups. In doing so, we examined whether two proposed risk factors – low birth weight (LBW, and in-utero exposure to selective serotonin reuptake inhibitors (SSRIs – are associated with greater behavioural homogeneity. Using data from the Western Australian Autism Biological Registry, this study found that LBW and maternal SSRI use during pregnancy were associated with greater sleep disturbances and a greater number of gastrointestinal complaints in children with ASD, respectively. The findings from this ‘proof of principle’ paper provide support for this 'bottom-up' approach as a feasible method for creating homogenous groups.

  1. Bottoms Up

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    China’s high-end liquor is becoming a luxury item and a favorite among collectors spring Festival, the most important festival for the Chinese, is a time for celebration—and what would a celebration be without bottles of holi-

  2. Cooperativity to increase Turing pattern space for synthetic biology.

    Science.gov (United States)

    Diambra, Luis; Senthivel, Vivek Raj; Menendez, Diego Barcena; Isalan, Mark

    2015-02-20

    It is hard to bridge the gap between mathematical formulations and biological implementations of Turing patterns, yet this is necessary for both understanding and engineering these networks with synthetic biology approaches. Here, we model a reaction-diffusion system with two morphogens in a monostable regime, inspired by components that we recently described in a synthetic biology study in mammalian cells.1 The model employs a single promoter to express both the activator and inhibitor genes and produces Turing patterns over large regions of parameter space, using biologically interpretable Hill function reactions. We applied a stability analysis and identified rules for choosing biologically tunable parameter relationships to increase the likelihood of successful patterning. We show how to control Turing pattern sizes and time evolution by manipulating the values for production and degradation relationships. More importantly, our analysis predicts that steep dose-response functions arising from cooperativity are mandatory for Turing patterns. Greater steepness increases parameter space and even reduces the requirement for differential diffusion between activator and inhibitor. These results demonstrate some of the limitations of linear scenarios for reaction-diffusion systems and will help to guide projects to engineer synthetic Turing patterns.

  3. Synthetic Biology and Human Health: Potential Applications for Spaceflight

    Science.gov (United States)

    Karouia, Fathi; Carr, Christopher; Cai, Yizhi; Chen, Y.; Grenon, Marlene; Larios-Sanz, Maia; Jones, Jeffrey A.; Santos, Orlando

    2011-01-01

    Human space travelers experience a unique environment that affects homeostasis and physiologic adaptation. Spaceflight-related changes have been reported in the musculo-skeletal, cardiovascular, neurovestibular, endocrine, and immune systems. The spacecraft environment further subjects the traveler to noise and gravitational forces, as well as airborne chemical, microbiological contaminants, and radiation exposure. As humans prepare for longer duration missions effective countermeasures must be developed, verified, and implemented to ensure mission success. Over the past ten years, synthetic biology has opened new avenues for research and development in areas such as biological control, biomaterials, sustainable energy production, bioremediation, and biomedical therapies. The latter in particular is of great interest to the implementation of long-duration human spaceflight capabilities. This article discusses the effects of spaceflight on humans, and reviews current capabilities and potential needs associated with the health of the astronauts where synthetic biology could play an important role in the pursuit of space exploration.

  4. Life by design: Philosophical perspectives on synthetic biology

    OpenAIRE

    Bensaude Vincent Bernadette

    2015-01-01

    Biology is Technology”, this title of a book authored by bioengineer Rob Carlson captures the essence of synthetic biology. This novel research field is in the hands of engineers, who are in charge of redesigning life or designing new forms of life for specific purposes. In the aftermath of “the century of the gene” (Evelyn Fox Keller, Cambridge Mass, Harvard University Press, 2002) he comes the century of “life by design”. As the emergence of molecular biology allowed reading the code of li...

  5. Synthetic biology devices for in vitro and in vivo diagnostics.

    Science.gov (United States)

    Slomovic, Shimyn; Pardee, Keith; Collins, James J

    2015-11-24

    There is a growing need to enhance our capabilities in medical and environmental diagnostics. Synthetic biologists have begun to focus their biomolecular engineering approaches toward this goal, offering promising results that could lead to the development of new classes of inexpensive, rapidly deployable diagnostics. Many conventional diagnostics rely on antibody-based platforms that, although exquisitely sensitive, are slow and costly to generate and cannot readily confront rapidly emerging pathogens or be applied to orphan diseases. Synthetic biology, with its rational and short design-to-production cycles, has the potential to overcome many of these limitations. Synthetic biology devices, such as engineered gene circuits, bring new capabilities to molecular diagnostics, expanding the molecular detection palette, creating dynamic sensors, and untethering reactions from laboratory equipment. The field is also beginning to move toward in vivo diagnostics, which could provide near real-time surveillance of multiple pathological conditions. Here, we describe current efforts in synthetic biology, focusing on the translation of promising technologies into pragmatic diagnostic tools and platforms.

  6. Integrating ethical analysis "into the DNA" of synthetic biology.

    Science.gov (United States)

    Heavey, Patrick

    2015-02-01

    Current ethical analysis tends to evaluate synthetic biology at an overview level. Synthetic biology, however, is an umbrella term that covers a variety of areas of research. These areas contain, in turn, a hierarchy of different research fields. This abstraction hierarchy-the term is borrowed from engineering-permits synthetic biologists to specialise to a very high degree. Though synthetic biology per se may create profound ethical challenges, much of the day-to-day research does not. Yet seemingly innocuous research could lead to ethically problematic results. For example, Dolly the sheep resulted from a long series of research steps, none of which presented any ethical problems. The atomic bomb was developed as a result of Einstein's uncontentions theoretical research that proved the equivalence of matter and energy. Therefore it would seem wise for ethicists to evaluate synbio research across its subfields and through its abstraction hierarchies, comparing and inter-relating the various areas of research. In addition, it would be useful if journals that publish synbio papers require an ethical statement from authors, as standard practice, so as to encourage scientists to constantly engage with ethical issues in their work. Also, this would allow an ethical snapshot of the state of the research at any given time to exist, allowing for accurate evaluation by scientists and ethicists, regulators and policymakers.

  7. Synthetic toxicology: where engineering meets biology and toxicology.

    Science.gov (United States)

    Schmidt, Markus; Pei, Lei

    2011-03-01

    This article examines the implications of synthetic biology (SB) for toxicological sciences. Starting with a working definition of SB, we describe its current subfields, namely, DNA synthesis, the engineering of DNA-based biological circuits, minimal genome research, attempts to construct protocells and synthetic cells, and efforts to diversify the biochemistry of life through xenobiology. Based on the most important techniques, tools, and expected applications in SB, we describe the ramifications of SB for toxicology under the label of synthetic toxicology. We differentiate between cases where SB offers opportunities for toxicology and where SB poses challenges for toxicology. Among the opportunities, we identified the assistance of SB to construct novel toxicity testing platforms, define new toxicity-pathway assays, explore the potential of SB to improve in vivo biotransformation of toxins, present novel biosensors developed by SB for environmental toxicology, discuss cell-free protein synthesis of toxins, reflect on the contribution to toxic use reduction, and the democratization of toxicology through do-it-yourself biology. Among the identified challenges for toxicology, we identify synthetic toxins and novel xenobiotics, biosecurity and dual-use considerations, the potential bridging of toxic substances and infectious agents, and do-it-yourself toxin production.

  8. Synthetic, biological and composite scaffolds for abdominal wall reconstruction.

    Science.gov (United States)

    Meintjes, Jennifer; Yan, Sheng; Zhou, Lin; Zheng, Shusen; Zheng, Minghao

    2011-03-01

    The reconstruction of abdominal wall defects remains a huge surgical challenge. Tension-free repair is proven to be superior to suture repair in abdominal wall reconstruction. Scaffolds are essential for tension-free repair. They are used to bridge a defect or reinforce the abdominal wall. A huge variety of scaffolds are now commercially available. Most of the synthetic scaffolds are composed of polypropylene. They provide strong tissue reinforcement, but cause a foreign body reaction, which can result in serious complications. Absorbable synthetic scaffolds, such as Dexon™ (polyglycolic acid) and Vicryl™ (polyglactin 910), are not suitable for abdominal wall reconstruction as they usually require subsequent surgeries to repair recurrent hernias. Composite scaffolds combine the strength of nonabsorbable synthetic scaffolds with the antiadhesive properties of the absorbable scaffold, but require long-term follow-up. Biological scaffolds, such as Permacol™, Surgisis(®) and Alloderm(®), are derived from acellular mammalian tissues. Non-cross-linked biological scaffolds show excellent biocompatibility and degrade slowly over time. However, remnant DNA has been found in several products and the degradation leads to recurrence. Randomized controlled trials with long-term follow-up studies are lacking for all of the available scaffolds, particularly those derived from animal tissue. This article provides an overview of the different types of scaffolds available, and presents the key clinical studies of the commercially available synthetic, composite and biological scaffolds for abdominal wall reconstruction.

  9. Integrating biological redesign: where synthetic biology came from and where it needs to go.

    Science.gov (United States)

    Way, Jeffrey C; Collins, James J; Keasling, Jay D; Silver, Pamela A

    2014-03-27

    Synthetic biology seeks to extend approaches from engineering and computation to redesign of biology, with goals such as generating new chemicals, improving human health, and addressing environmental issues. Early on, several guiding principles of synthetic biology were articulated, including design according to specification, separation of design from fabrication, use of standardized biological parts and organisms, and abstraction. We review the utility of these principles over the past decade in light of the field's accomplishments in building complex systems based on microbial transcription and metabolism and describe the progress in mammalian cell engineering.

  10. Controlling the biological effects of spermine using a synthetic receptor.

    Science.gov (United States)

    Vial, Laurent; Ludlow, R Frederick; Leclaire, Julien; Pérez-Fernandez, Ruth; Otto, Sijbren

    2006-08-09

    Polyamines play an important role in biology, yet their exact function in many processes is poorly understood. Artificial host molecules capable of sequestering polyamines could be useful tools for studying their cellular function. However, designing synthetic receptors with affinities sufficient to compete with biological polyamine receptors remains a huge challenge. Binding affinities of synthetic hosts are typically separated by a gap of several orders of magnitude from those of biomolecules. We now report that a dynamic combinatorial selection approach can deliver a synthetic receptor that bridges this gap. The selected receptor binds spermine with a dissociation constant of 22 nM, sufficient to remove it from its natural host DNA and reverse some of the biological effects of spermine on the nucleic acid. In low concentrations, spermine induces the formation of left-handed DNA, but upon addition of our receptor, the DNA reverts back to its right-handed form. NMR studies and computer simulations suggest that the spermine complex has the form of a pseudo-rotaxane. The spermine receptor is a promising lead for the development of therapeutics or molecular probes for elucidating spermine's role in cell biology.

  11. Specifications of Standards in Systems and Synthetic Biology.

    Science.gov (United States)

    Schreiber, Falk; Bader, Gary D; Golebiewski, Martin; Hucka, Michael; Kormeier, Benjamin; Le Novère, Nicolas; Myers, Chris; Nickerson, David; Sommer, Björn; Waltemath, Dagmar; Weise, Stephan

    2015-09-04

    Standards shape our everyday life. From nuts and bolts to electronic devices and technological processes, standardised products and processes are all around us. Standards have technological and economic benefits, such as making information exchange, production, and services more efficient. However, novel, innovative areas often either lack proper standards, or documents about standards in these areas are not available from a centralised platform or formal body (such as the International Standardisation Organisation). Systems and synthetic biology is a relatively novel area, and it is only in the last decade that the standardisation of data, information, and models related to systems and synthetic biology has become a community-wide effort. Several open standards have been established and are under continuous development as a community initiative. COMBINE, the ‘COmputational Modeling in BIology’ NEtwork has been established as an umbrella initiative to coordinate and promote the development of the various community standards and formats for computational models. There are yearly two meeting, HARMONY (Hackathons on Resources for Modeling in Biology), Hackathon-type meetings with a focus on development of the support for standards, and COMBINE forums, workshop-style events with oral presentations, discussion, poster, and breakout sessions for further developing the standards. For more information see http://co.mbine.org/. So far the different standards were published and made accessible through the standards’ web- pages or preprint services. The aim of this special issue is to provide a single, easily accessible and citable platform for the publication of standards in systems and synthetic biology. This special issue is intended to serve as a central access point to standards and related initiatives in systems and synthetic biology, it will be published annually to provide an opportunity for standard development groups to communicate updated specifications.

  12. Synthetic biology: regulating industry uses of new biotechnologies.

    Science.gov (United States)

    Erickson, Brent; Singh, Rina; Winters, Paul

    2011-09-02

    In our view, synthetic biology is an extension of the continuum of genetic science that has been used safely for more than 40 years by the biotechnology industry in the development of commercial products. Examples of synthetic biology use by biotechnology companies illustrate the potential to substantially reduce research and development time and to increase speed to market. Improvements in the speed and cost of DNA synthesis are enabling scientists to design modified bacterial chromosomes that can be used in the production of renewable chemicals, biofuels, bioproducts, renewable specialty chemicals, pharmaceutical intermediates, fine chemicals, food ingredients, and health care products. Regulatory options should support innovation and commercial development of new products while protecting the public from potential harms.

  13. Application of synthetic biology in cyanobacteria and algae

    Directory of Open Access Journals (Sweden)

    Bo eWang

    2012-09-01

    Full Text Available Cyanobacteria and algae are becoming increasingly attractive cell factories for producing renewable biofuels and chemicals due to their ability to capture solar energy and CO2 and their relatively simple genetic background for genetic manipulation. Increasing research efforts from the synthetic biology approach have been made in recent years to modify cyanobacteria and algae for various biotechnological applications. In the article, we critically review recent progresses in developing genetic tools for characterizing or manipulating cyanobacteria and algae, the applications of genetically modified strains for synthesizing renewable products such as biofuels and chemicals. In addition, the emergent challenges in the development and application of synthetic biology for cyanobacteria and algae are also discussed.

  14. Self-assembled nanostructured resistive switching memory devices fabricated by templated bottom-up growth.

    Science.gov (United States)

    Song, Ji-Min; Lee, Jang-Sik

    2016-01-07

    Metal-oxide-based resistive switching memory device has been studied intensively due to its potential to satisfy the requirements of next-generation memory devices. Active research has been done on the materials and device structures of resistive switching memory devices that meet the requirements of high density, fast switching speed, and reliable data storage. In this study, resistive switching memory devices were fabricated with nano-template-assisted bottom up growth. The electrochemical deposition was adopted to achieve the bottom-up growth of nickel nanodot electrodes. Nickel oxide layer was formed by oxygen plasma treatment of nickel nanodots at low temperature. The structures of fabricated nanoscale memory devices were analyzed with scanning electron microscope and atomic force microscope (AFM). The electrical characteristics of the devices were directly measured using conductive AFM. This work demonstrates the fabrication of resistive switching memory devices using self-assembled nanoscale masks and nanomateirals growth from bottom-up electrochemical deposition.

  15. Synthetic Biology: Engineering, Evolution and Design (SEED) Conference 2014

    Energy Technology Data Exchange (ETDEWEB)

    Voigt, Christopher [Massachusetts Institute of Technology

    2014-07-01

    SEED2014 focused on advances in the science and technology emerging from the field of synthetic biology. We broadly define this as technologies that accelerate the process of genetic engineering. It highlighted new tool development, as well as the application of these tools to diverse problems in biotechnology, including therapeutics, industrial chemicals and fuels, natural products, and agriculture. Systems spanned from in vitro experiments and viruses, through diverse bacteria, to eukaryotes (yeast, mammalian cells, plants).

  16. Synthetic Biology: Life, Jim, but Not As We Know It

    Science.gov (United States)

    Hallinan, Jennifer

    Frankenstein, Mary Shelley's classic tale of horror, warns of the perils of hubris: of the terrible fate that awaits when Man plays God and attempts to create life. Molecular biologists are clearly not listening. Not content with merely inserting the occasional gene into the genome of an existing organism. they are developing a whole new field, Synthetic Biology, which aims to engineer from first principles organisms with desirable, controllable qualities.

  17. Cyclization of the N-Terminal X-Asn-Gly Motif during Sample Preparation for Bottom-Up Proteomics

    DEFF Research Database (Denmark)

    Zhang, Xumin; Højrup, Peter

    2010-01-01

    We, herein, report a novel -17 Da peptide modification corresponding to an N-terminal cyclization of peptides possessing the N-terminal motif of X-Asn-Gly. The cyclization occurs spontaneously during sample preparation for bottom-up proteomics studies. Distinct from the two well-known N......-terminal cyclizations, cyclization of N-terminal glutamine and S-carbamoylmethylcysteine, it is dependent on pH instead of [NH(4)(+)]. The data set from our recent study on large-scale N(α)-modified peptides revealed a sequence requirement for the cyclization event similar to the well-known deamidation of Asn to iso......Asp and Asp. Detailed analysis using synthetic peptides confirmed that the cyclization forms between the N-terminus and its neighboring Asn residue, and the reaction shares the same succinimide intermediate with the Asn deamidation event. As a result, we, here, propose a molecular mechanism for this specific...

  18. Synthetic biology: engineering Escherichia coli to see light.

    Science.gov (United States)

    Levskaya, Anselm; Chevalier, Aaron A; Tabor, Jeffrey J; Simpson, Zachary Booth; Lavery, Laura A; Levy, Matthew; Davidson, Eric A; Scouras, Alexander; Ellington, Andrew D; Marcotte, Edward M; Voigt, Christopher A

    2005-11-24

    We have designed a bacterial system that is switched between different states by red light. The system consists of a synthetic sensor kinase that allows a lawn of bacteria to function as a biological film, such that the projection of a pattern of light on to the bacteria produces a high-definition (about 100 megapixels per square inch), two-dimensional chemical image. This spatial control of bacterial gene expression could be used to 'print' complex biological materials, for example, and to investigate signalling pathways through precise spatial and temporal control of their phosphorylation steps.

  19. Beware of metaphors: chasses and orthogonality in synthetic biology.

    Science.gov (United States)

    de Lorenzo, Víctor

    2011-01-01

    Every descriptive language is not only metaphoric and interpretative, but it is also developed (or adopted) ad hoc to fulfill a certain agenda. Even the hardcore scientific languages of mathematics and physics are not entirely neutral--let alone the much softer terminology of biology. We use metaphors all the time in science and that is useful as long as they serve their purpose well and we are aware of them. But it is a serious mistake to identify uncritically the thing and the metaphors employed to bring the thing to mind. I address here two of the most sparkling metaphors brought about by synthetic biology: chassis and orthogonality--the first borrowed instance from engineering of vehicles, and the second from computer terminology (itself borrowed from mathematics). For the sake of simplicity the discussion is limited to the connotation of these two concepts in the prokaryotic realm. The power of such metaphors from describing the state of affairs in synthetic biology and for setting a vigorous research and technology schedule is analyzed. Awareness of the meta-languages and allegories that are being adopted by the SB community should help to frame other controversial concepts such as artificial cells or synthetic life.

  20. Synthetic membranes and membrane processes with counterparts in biological systems

    Science.gov (United States)

    Matson, Stephen L.

    1996-02-01

    Conventional synthetic membranes, fashioned for the most part from rather unremarkable polymeric materials, are essentially passive structures that achieve various industrial and biomedical separations through simple and selective membrane permeation processes. Indeed, simplicity of membrane material, structure, and function has long been perceived as a virtue of membranes relative to other separation processes with which they compete. The passive membrane separation processes -- exemplified by micro- and ultrafiltration, dialysis, reverse osmosis, and gas permeation -- differ from one another primarily in terms of membrane morphology or structure (e.g., porous, gel-type, and nonporous) and the permeant transport mechanism and driving force (e.g., diffusion, convection, and 'solution/diffusion'). The passive membrane separation processes have in common the fact that interaction between permeant and membrane material is typically weak and physicochemical in nature; indeed, it is frequently an objective of membrane materials design to minimize interaction between permeant and membrane polymer, since such strategies can minimize membrane fouling. As a consequence, conventional membrane processes often provide only modest separation factors or permselectivities; that is, they are more useful in performing 'group separations' (i.e., the separation of different classes of material) than they are in fractionating species within a given class. It has long been recognized within the community of membrane technologists that biological membrane structures and their components are extraordinarily sophisticated and powerful as compared to their synthetic counterparts. Moreover, biomembranes and related biological systems have been 'designed' according to a very different paradigm -- one that frequently maximizes and capitalizes on extraordinarily strong and biochemically specific interactions between components of the membrane and species interacting with them. Thus, in recent

  1. pClone: Synthetic Biology Tool Makes Promoter Research Accessible to Beginning Biology Students

    Science.gov (United States)

    Campbell, A. Malcolm; Eckdahl, Todd; Cronk, Brian; Andresen, Corinne; Frederick, Paul; Huckuntod, Samantha; Shinneman, Claire; Wacker, Annie; Yuan, Jason

    2014-01-01

    The "Vision and Change" report recommended genuine research experiences for undergraduate biology students. Authentic research improves science education, increases the number of scientifically literate citizens, and encourages students to pursue research. Synthetic biology is well suited for undergraduate research and is a growing area…

  2. 合成生物学发展现状与前景%Progress and perspective of synthetic biology

    Institute of Scientific and Technical Information of China (English)

    熊燕; 陈大明; 杨琛; 赵国屏

    2011-01-01

    合成生物学是综合了科学与工程的一个崭新的生物学研究领域,为生命现象及其运动规律的解析提供了一种采用“自下而上”合成策略的正向工程学的研究思路和方法手段,在经济和社会发展中具有巨大的应用开发潜力.近年来,DNA合成与系统生物学技术的发展使生命系统复杂基因回路的设计、合成与组装逐步成为可能,并应用于生物基化学品、生物燃料、医药中间体、保健产品的生产和环境保护等领域.但是,合成生物学的研究仍然面临科学、技术和伦理的挑战,只有积极地应对这些问题,在加大研究开发支持力度的同时,做好必要的风险监管,才能真正把握合成生物学发展带来的历史机遇.%Synthetic biology is an emerging field of biological research that combines science and engineering to study the mechanism of life and for a variety of technological applications. Research in synthetic biology has primarily focused on developing an engineering dogma for bottom-up design and synthesis of biological circuits from standardized parts and modules followed by optimizing their operation on well-characterized chassis, in vivo or in vitro. Recent progress in synthetic biology, such as significant improvements in efficient DNA/gene synthesis and ever increasing knowledge of biological systems via genomic and functional genomic analysis enables scientists to design and construct increasingly complex genetic devices and circuits, to synthesize and assembly bacterial genomes, and to develop artificially modified biological systems to produce renewable chemicals, biofuels, pharmaceutical intermediates, health care products and new tools for environment protection. However, neither the scientific complexity nor the technological uncertainty of the research has been thoroughly studied. In addition, the legal and ethical concerns of its social and humanitarian impact is largely yet to be addressed. Proper

  3. Optimal Environmental Conditions and Anomalous Ecosystem Responses: Constraining Bottom-up Controls of Phytoplankton Biomass in the California Current System

    Science.gov (United States)

    Jacox, Michael G.; Hazen, Elliott L.; Bograd, Steven J.

    2016-06-01

    In Eastern Boundary Current systems, wind-driven upwelling drives nutrient-rich water to the ocean surface, making these regions among the most productive on Earth. Regulation of productivity by changing wind and/or nutrient conditions can dramatically impact ecosystem functioning, though the mechanisms are not well understood beyond broad-scale relationships. Here, we explore bottom-up controls during the California Current System (CCS) upwelling season by quantifying the dependence of phytoplankton biomass (as indicated by satellite chlorophyll estimates) on two key environmental parameters: subsurface nitrate concentration and surface wind stress. In general, moderate winds and high nitrate concentrations yield maximal biomass near shore, while offshore biomass is positively correlated with subsurface nitrate concentration. However, due to nonlinear interactions between the influences of wind and nitrate, bottom-up control of phytoplankton cannot be described by either one alone, nor by a combined metric such as nitrate flux. We quantify optimal environmental conditions for phytoplankton, defined as the wind/nitrate space that maximizes chlorophyll concentration, and present a framework for evaluating ecosystem change relative to environmental drivers. The utility of this framework is demonstrated by (i) elucidating anomalous CCS responses in 1998-1999, 2002, and 2005, and (ii) providing a basis for assessing potential biological impacts of projected climate change.

  4. Optimal Environmental Conditions and Anomalous Ecosystem Responses: Constraining Bottom-up Controls of Phytoplankton Biomass in the California Current System.

    Science.gov (United States)

    Jacox, Michael G; Hazen, Elliott L; Bograd, Steven J

    2016-06-09

    In Eastern Boundary Current systems, wind-driven upwelling drives nutrient-rich water to the ocean surface, making these regions among the most productive on Earth. Regulation of productivity by changing wind and/or nutrient conditions can dramatically impact ecosystem functioning, though the mechanisms are not well understood beyond broad-scale relationships. Here, we explore bottom-up controls during the California Current System (CCS) upwelling season by quantifying the dependence of phytoplankton biomass (as indicated by satellite chlorophyll estimates) on two key environmental parameters: subsurface nitrate concentration and surface wind stress. In general, moderate winds and high nitrate concentrations yield maximal biomass near shore, while offshore biomass is positively correlated with subsurface nitrate concentration. However, due to nonlinear interactions between the influences of wind and nitrate, bottom-up control of phytoplankton cannot be described by either one alone, nor by a combined metric such as nitrate flux. We quantify optimal environmental conditions for phytoplankton, defined as the wind/nitrate space that maximizes chlorophyll concentration, and present a framework for evaluating ecosystem change relative to environmental drivers. The utility of this framework is demonstrated by (i) elucidating anomalous CCS responses in 1998-1999, 2002, and 2005, and (ii) providing a basis for assessing potential biological impacts of projected climate change.

  5. Ethical and regulatory challenges posed by synthetic biology.

    Science.gov (United States)

    Rager-Zisman, Bracha

    2012-01-01

    Synthetic biology is a relatively new science with tremendous potential to change how we view and know the life sciences, but like many developing technologies, it has provoked ethical concerns from the scientific community and the public and confronts demands for new regulatory measures. The concerns raised involve the danger of "dual use," in which results for improving human well-being and the environment may be misappropriated for bioterror. To counteract these dangers, many governments, but the United States and Israel in particular, have introduced new laws and redoubled measures for biosafety and biosecurity. In the United States, the recent H5N1 results achieved by two groups of NIH-funded investigators highlighted the dilemma of balancing the risk of dual-use research and the freedom of science. In Israel, concern for unconventional terrorism is long-standing, and the country is constantly engaged in improving biosecurity and biodefense measures. In 2008, the Israeli parliament passed the Regulation of Research into Biological Disease Agents Law, a legislative framework for safeguarding research into biological disease agents. This article summarizes and analyzes the current state of affairs in the United States and Israel, ethical attitudes, and regulatory responses to synthetic biology.

  6. Top-down model estimates, bottom-up inventories, and future projections of global natural and anthropogenic emissions of nitrous oxide

    Science.gov (United States)

    Davidson, E. A.; Kanter, D.

    2013-12-01

    Nitrous oxide (N2O) is the third most abundantly emitted greenhouse gas and the largest remaining emitted ozone depleting substance. It is a product of nitrifying and denitrifying bacteria in soils, sediments and water bodies. Humans began to disrupt the N cycle in the preindustrial era as they expanded agricultural land, used fire for land clearing and management, and cultivated leguminous crops that carry out biological N fixation. This disruption accelerated after the industrial revolution, especially as the use of synthetic N fertilizers became common after 1950. Here we present findings from a new United Nations Environment Programme report, in which we constrain estimates of the anthropogenic and natural emissions of N2O and consider scenarios for future emissions. Inventory-based estimates of natural emissions from terrestrial, marine and atmospheric sources range from 10 to 12 Tg N2O-N/yr. Similar values can be derived for global N2O emissions that were predominantly natural before the industrial revolution. While there was inter-decadal variability, there was little or no consistent trend in atmospheric N2O concentrations between 1730 and 1850, allowing us to assume near steady state. Assuming an atmospheric lifetime of 120 years, the 'top-down' estimate of pre-industrial emissions of 11 Tg N2O-N/yr is consistent with the bottom-up inventories for natural emissions, although the former includes some modest pre-industrial anthropogenic effects (probably large inherent uncertainties in both approaches, it is encouraging that the bottom-up (6.0) and top-down (5.3) estimates are within 12% of each other and their uncertainty ranges overlap. N2O is inescapably linked to food production and food security. Future agricultural emissions will be determined by population, dietary habits, and agricultural N use efficiency. Without deliberate and effective mitigation policies, anthropogenic N2O emissions will likely double by 2050 and continue to increase thereafter

  7. Oriented bottom-up growth of armchair graphene nanoribbons on germanium

    Science.gov (United States)

    Arnold, Michael Scott; Jacobberger, Robert Michael

    2016-03-15

    Graphene nanoribbon arrays, methods of growing graphene nanoribbon arrays and electronic and photonic devices incorporating the graphene nanoribbon arrays are provided. The graphene nanoribbons in the arrays are formed using a scalable, bottom-up, chemical vapor deposition (CVD) technique in which the (001) facet of the germanium is used to orient the graphene nanoribbon crystals along the [110] directions of the germanium.

  8. Bottom-Up Molecular Tunneling Junctions Formed by Self-Assembly

    NARCIS (Netherlands)

    Zhang, Yanxi; Zhao, Zhiyuan; Fracasso, Davide; Chiechi, Ryan C

    2014-01-01

    This Minireview focuses on bottom-up molecular tunneling junctions - a fundamental component of molecular electronics - that are formed by self-assembly. These junctions are part of devices that, in part, fabricate themselves, and therefore, are particularly dependent on the chemistry of the molecul

  9. Coupling 2D Finite Element Models and Circuit Equations Using a Bottom-Up Methodology

    Science.gov (United States)

    2002-11-01

    EQUATIONS USING A BOTTOM-UP METHODOLOGY E. G6mezl, J. Roger-Folch2 , A. Gabald6nt and A. Molina’ ’Dpto. de Ingenieria Eldctrica. Universidad Polit...de Ingenieria Elictrica. ETSII. Universidad Politdcnica de Valencia. PO Box 22012, 46071. Valencia, Spain. E-mail: iroger adie.upv.es ABSTRACT The

  10. A Bottom-Up Approach for Implementing Electronic Portfolios in a Teacher Education Program

    Science.gov (United States)

    An, Heejung; Wilder, Hilary

    2010-01-01

    In an effort to generate a bottom-up approach for the program-wide implementation of electronic portfolios, this article first reports on the ways in which teacher candidates perceived the benefits and setbacks of this experience, after an initial course. Second, this article reports on whether and how the teacher candidates continued to develop…

  11. Achieving Campus Sustainability: Top-Down, Bottom-Up, or Neither?

    Science.gov (United States)

    Brinkhurst, Marena; Rose, Peter; Maurice, Gillian; Ackerman, Josef Daniel

    2011-01-01

    Purpose: The dynamics of organizational change related to environmental sustainability on university campuses are examined in this article. Whereas case studies of campus sustainability efforts tend to classify leadership as either "top-down" or "bottom-up", this classification neglects consideration of the leadership roles of…

  12. Managing Bottom up Strategizing : Collective Sensemaking of Strategic Issues in a Dutch Bank

    NARCIS (Netherlands)

    van der Steen, Martijn

    2016-01-01

    This paper discusses a bottom-up approach to strategizing in two member banks of a Dutch cooperative bank. In both banks, through a collective process of sensemaking, organisational participants evaluated their day-to-day experiences in order to identify strategic issues. The potential benefits of s

  13. Co-financing of bottom-up approaches towards Broadband Infrastructure Development

    DEFF Research Database (Denmark)

    Williams, Idongesit

    2016-01-01

    Bottom – up Broadband infrastructure development facilitated by the civil societies and social enterprises are on the increase. However, the problem plaguing the development of these bottom-up approaches in developing countries is the financial capacity to expand their small networks into larger...

  14. Computational versus psychophysical bottom-up image saliency: A comparative evaluation study

    NARCIS (Netherlands)

    Toet, A.

    2011-01-01

    The predictions of 13 computational bottom-up saliency models and a newly introduced Multiscale Contrast Conspicuity (MCC) metric are compared with human visual conspicuity measurements. The agreement between human visual conspicuity estimates and model saliency predictions is quantified through the

  15. Top-Down and Bottom-Up Approaches in Engineering 1 T Phase Molybdenum Disulfide (MoS2 ): Towards Highly Catalytically Active Materials.

    Science.gov (United States)

    Chua, Chun Kiang; Loo, Adeline Huiling; Pumera, Martin

    2016-09-26

    The metallic 1 T phase of MoS2 has been widely identified to be responsible for the improved performances of MoS2 in applications including hydrogen evolution reactions and electrochemical supercapacitors. To this aim, various synthetic methods have been reported to obtain 1 T phase-rich MoS2 . Here, the aim is to evaluate the efficiencies of the bottom-up (hydrothermal reaction) and top-down (chemical exfoliation) approaches in producing 1 T phase MoS2 . It is established in this study that the 1 T phase MoS2 produced through the bottom-up approach contains a high proportion of 1 T phase and demonstrates excellent electrochemical and electrical properties. Its performance in the hydrogen evolution reaction and electrochemical supercapacitors also surpassed that of 1 T phase MoS2 produced through a top-down approach.

  16. The fusion of biology, computer science, and engineering: towards efficient and successful synthetic biology.

    Science.gov (United States)

    Linshiz, Gregory; Goldberg, Alex; Konry, Tania; Hillson, Nathan J

    2012-01-01

    Synthetic biology is a nascent field that emerged in earnest only around the turn of the millennium. It aims to engineer new biological systems and impart new biological functionality, often through genetic modifications. The design and construction of new biological systems is a complex, multistep process, requiring multidisciplinary collaborative efforts from "fusion" scientists who have formal training in computer science or engineering, as well as hands-on biological expertise. The public has high expectations for synthetic biology and eagerly anticipates the development of solutions to the major challenges facing humanity. This article discusses laboratory practices and the conduct of research in synthetic biology. It argues that the fusion science approach, which integrates biology with computer science and engineering best practices, including standardization, process optimization, computer-aided design and laboratory automation, miniaturization, and systematic management, will increase the predictability and reproducibility of experiments and lead to breakthroughs in the construction of new biological systems. The article also discusses several successful fusion projects, including the development of software tools for DNA construction design automation, recursive DNA construction, and the development of integrated microfluidics systems.

  17. Materials Manufactured from 3D Printed Synthetic Biology Arrays

    Science.gov (United States)

    Gentry, Diana; Micks, Ashley

    2013-01-01

    Many complex, biologically-derived materials have extremely useful properties (think wood or silk), but are unsuitable for space-related applications due to production, manufacturing, or processing limitations. Large-scale ecosystem-based production, such as raising and harvesting trees for wood, is impractical in a self-contained habitat such as a space station or potential Mars colony. Manufacturing requirements, such as the specialized equipment needed to harvest and process cotton, add too much upmass for current launch technology. Cells in nature are already highly specialized for making complex biological materials on a micro scale. We envision combining these strengths with the recently emergent technologies of synthetic biology and 3D printing to create 3D-structured arrays of cells that are bioengineered to secrete different materials in a specified three-dimensional pattern.

  18. Synthetic metabolism: engineering biology at the protein and pathway scales.

    Science.gov (United States)

    Martin, Collin H; Nielsen, David R; Solomon, Kevin V; Prather, Kristala L Jones

    2009-03-27

    Biocatalysis has become a powerful tool for the synthesis of high-value compounds, particularly so in the case of highly functionalized and/or stereoactive products. Nature has supplied thousands of enzymes and assembled them into numerous metabolic pathways. Although these native pathways can be use to produce natural bioproducts, there are many valuable and useful compounds that have no known natural biochemical route. Consequently, there is a need for both unnatural metabolic pathways and novel enzymatic activities upon which these pathways can be built. Here, we review the theoretical and experimental strategies for engineering synthetic metabolic pathways at the protein and pathway scales, and highlight the challenges that this subfield of synthetic biology currently faces.

  19. Liver Transplantation Utilizing Mixed Biologic and Synthetic Arterial Conduits

    Directory of Open Access Journals (Sweden)

    Marcio F. Chedid

    2016-01-01

    Full Text Available Arterial conduits are necessary in nearly 5% of all liver transplants and are usually constructed utilizing segments of donor iliac artery. However, available segments of donor iliac artery may not be lengthy enough or may not possess enough quality to enable its inclusion in the conduit. Although there are few reports of arterial conduits constructed solely utilizing prosthetic material, no previous reports of conduits composed of a segment of donor iliac artery and prosthetic material (mixed biologic and synthetic arterial conduits were found in the medial literature to date. Two cases reporting successful outcomes after creation of mixed biologic and prosthetic arterial conduits are outlined in this report. Reason for creation of conduits was complete intimal dissection of the recipient’s hepatic artery in both cases. In both cases, available segments of donor iliac artery were not lengthy enough to bridge infrarenal aorta to porta hepatis. Both patients have patent conduits and normally functioning liver allografts, respectively, at 4 and 31 months after transplant. Mixed biologic and synthetic arterial conduits constitute a viable technical option and may offer potential advantages over fully prosthetic arterial conduits.

  20. 3rd congress on applied synthetic biology in Europe (Costa da Caparica, Portugal, February 2016).

    Science.gov (United States)

    Cueva, Miguel

    2017-03-25

    The third meeting organised by the European Federation of Biotechnology (EFB) on advances in Applied Synthetic Biotechnology in Europe (ASBE) was held in Costa da Caparica, Portugal, in February 2016. Abundant novel applications in synthetic biology were described in the six sessions of the meeting, which was divided into technology and tools for synthetic biology (I, II and III), bionanoscience, biosynthetic pathways and enzyme synthetic biology, and metabolic engineering and chemical manufacturing. The meeting presented numerous methods for the development of novel synthetic strains, synthetic biological tools and synthetic biology applications. With the aid of synthetic biology, production costs of chemicals, metabolites and food products are expected to decrease, by generating sustainable biochemical production of such resources. Also, such synthetic biological advances could be applied for medical purposes, as in pharmaceuticals and for biosensors. Recurrent, linked themes throughout the meeting were the shortage of resources, the world's transition into a bioeconomy, and how synthetic biology is helping tackle these issues through cutting-edge technologies. While there are still limitations in synthetic biology research, innovation is propelling the development of technology, the standardisation of synthetic biological tools and the use of suitable host organisms. These developments are laying a foundation to providing a future where cutting-edge research could generate potential solutions to society's pressing issues, thus incentivising a transition into a bioeconomy.

  1. Bottom-up/top-down high resolution, high throughput lithography using vertically assembled block bottle brush polymers

    Science.gov (United States)

    Trefonas, Peter; Thackeray, James W.; Sun, Guorong; Cho, Sangho; Clark, Corrie; Verkhoturov, Stanislav V.; Eller, Michael J.; Li, Ang; Pavía-Jiménez, Adriana; Schweikert, Emile A.; Wooley, Karen L.

    2013-03-01

    We describe a novel deterministic bottom-up / top-down approach to sub-30 nm photolithography using a film composed of assembled block brush polymers of highly uniform composition and chain length. The polymer architecture consists of a rigid backbone of polymerized norbornene, each linked to flexible short side brush chains. The resultant `bottle brush' topology has a cylindrical shape with short brush chains arranged concentrically around the backbone, in which the cylinder radius is determined by the number of monomers within the brush fragment, while the cylinder length is determined by the degree of backbone polymerization. The modularity of the synthetic system allows a wide diversity of lithographically useful monomers, sequencing, dimension and property variation. Sequential grafting of pre-synthesized blocks allows for facile formation of either concentric or lengthwise block copolymers. Placement of brush chains of different compositions along different regions of the cylinder, along with variation of the relative concentric and lengthwise dimensions, provides mechanisms to align and control placement of the cylinders. These polymers are compatible with photoacid generators (PAGs) and crosslinker functionality. Our results are consistent with a model that the bottle brush polymers assemble (bottom-up) in the film to yield a `forest' of vertically arranged cylindrical block brush polymers, with the film thickness determined by the coherence lengths of the cylinders. Subsequent imaging via electron beam (EB or ebeam) or optical radiation yields a (top-down) mechanism for acid catalyzed crosslinking of adjacent cylinders. Uncrosslinked cylinders are removed in developer to yield negative photoresist patterns. Exposure doses are very low and throughputs are amenable to the requirements of Extreme Ultraviolet (EUV) lithography. The limiting resolution with ebeam exposure is potentially about two cylinder diameters width (< 8 nm), with the smallest observed

  2. Bottom-up/top-down, high-resolution, high-throughput lithography using vertically assembled block bottle brush polymers

    Science.gov (United States)

    Trefonas, Peter; Thackeray, James W.; Sun, Guorong; Cho, Sangho; Clark, Corrie; Verkhoturov, Stanislav V.; Eller, Michael J.; Li, Ang; Pavia-Sanders, Adriana; Schweikert, Emile A.; Wooley, Karen L.

    2013-10-01

    We describe a novel deterministic bottom-up/top-down approach to sub-30-nm photolithography using a film composed of assembled block brush polymers of highly uniform composition and chain length. The polymer architecture consists of a rigid backbone of polymerized norbornene, each linked to flexible short side brush chains. The resultant bottle brush topology has a cylindrical shape with short brush chains arranged concentrically around the backbone, in which the cylinder radius is determined by the number of monomers within the brush fragment, while the cylinder length is determined by the degree of backbone polymerization. The modularity of the synthetic system allows a wide diversity of lithographically useful monomers, sequencing, dimension, and property variation. Sequential grafting of presynthesized blocks allows for facile formation of either concentric or lengthwise block copolymers. Placement of brush chains of different compositions along different regions of the cylinder, along with variation of the relative concentric and lengthwise dimensions, provides mechanisms to align and control placement of the cylinders. These polymers are compatible with photoacid generators and crosslinker functionality. Our results are consistent with a model that the bottle brush polymers assemble (bottom-up) in the film to yield a forest of vertically arranged cylindrical block brush polymers, with the film thickness determined by the coherence lengths of the cylinders. Subsequent imaging via electron beam (e-beam) or optical radiation yields a (top-down) mechanism for acid catalyzed crosslinking of adjacent cylinders. Uncrosslinked cylinders are removed in developer to yield negative photoresist patterns. Exposure doses are very low and throughputs are amenable to the requirements of extreme ultraviolet lithography. The limiting resolution with e-beam exposure is potentially about two cylinder diameters width (<8 nm), with the smallest observed patterns approaching 10 nm.

  3. Synthetic biology routes to bio-artificial intelligence.

    Science.gov (United States)

    Nesbeth, Darren N; Zaikin, Alexey; Saka, Yasushi; Romano, M Carmen; Giuraniuc, Claudiu V; Kanakov, Oleg; Laptyeva, Tetyana

    2016-11-30

    The design of synthetic gene networks (SGNs) has advanced to the extent that novel genetic circuits are now being tested for their ability to recapitulate archetypal learning behaviours first defined in the fields of machine and animal learning. Here, we discuss the biological implementation of a perceptron algorithm for linear classification of input data. An expansion of this biological design that encompasses cellular 'teachers' and 'students' is also examined. We also discuss implementation of Pavlovian associative learning using SGNs and present an example of such a scheme and in silico simulation of its performance. In addition to designed SGNs, we also consider the option to establish conditions in which a population of SGNs can evolve diversity in order to better contend with complex input data. Finally, we compare recent ethical concerns in the field of artificial intelligence (AI) and the future challenges raised by bio-artificial intelligence (BI).

  4. Cell-free synthetic biology: thinking outside the cell.

    Science.gov (United States)

    Hodgman, C Eric; Jewett, Michael C

    2012-05-01

    Cell-free synthetic biology is emerging as a powerful approach aimed to understand, harness, and expand the capabilities of natural biological systems without using intact cells. Cell-free systems bypass cell walls and remove genetic regulation to enable direct access to the inner workings of the cell. The unprecedented level of control and freedom of design, relative to in vivo systems, has inspired the rapid development of engineering foundations for cell-free systems in recent years. These efforts have led to programmed circuits, spatially organized pathways, co-activated catalytic ensembles, rational optimization of synthetic multi-enzyme pathways, and linear scalability from the micro-liter to the 100-liter scale. It is now clear that cell-free systems offer a versatile test-bed for understanding why nature's designs work the way they do and also for enabling biosynthetic routes to novel chemicals, sustainable fuels, and new classes of tunable materials. While challenges remain, the emergence of cell-free systems is poised to open the way to novel products that until now have been impractical, if not impossible, to produce by other means.

  5. A Versatile Microfluidic Device for Automating Synthetic Biology.

    Science.gov (United States)

    Shih, Steve C C; Goyal, Garima; Kim, Peter W; Koutsoubelis, Nicolas; Keasling, Jay D; Adams, Paul D; Hillson, Nathan J; Singh, Anup K

    2015-10-16

    New microbes are being engineered that contain the genetic circuitry, metabolic pathways, and other cellular functions required for a wide range of applications such as producing biofuels, biobased chemicals, and pharmaceuticals. Although currently available tools are useful in improving the synthetic biology process, further improvements in physical automation would help to lower the barrier of entry into this field. We present an innovative microfluidic platform for assembling DNA fragments with 10× lower volumes (compared to that of current microfluidic platforms) and with integrated region-specific temperature control and on-chip transformation. Integration of these steps minimizes the loss of reagents and products compared to that with conventional methods, which require multiple pipetting steps. For assembling DNA fragments, we implemented three commonly used DNA assembly protocols on our microfluidic device: Golden Gate assembly, Gibson assembly, and yeast assembly (i.e., TAR cloning, DNA Assembler). We demonstrate the utility of these methods by assembling two combinatorial libraries of 16 plasmids each. Each DNA plasmid is transformed into Escherichia coli or Saccharomyces cerevisiae using on-chip electroporation and further sequenced to verify the assembly. We anticipate that this platform will enable new research that can integrate this automated microfluidic platform to generate large combinatorial libraries of plasmids and will help to expedite the overall synthetic biology process.

  6. Basic science through engineering? Synthetic modeling and the idea of biology-inspired engineering.

    Science.gov (United States)

    Knuuttila, Tarja; Loettgers, Andrea

    2013-06-01

    Synthetic biology is often understood in terms of the pursuit for well-characterized biological parts to create synthetic wholes. Accordingly, it has typically been conceived of as an engineering dominated and application oriented field. We argue that the relationship of synthetic biology to engineering is far more nuanced than that and involves a sophisticated epistemic dimension, as shown by the recent practice of synthetic modeling. Synthetic models are engineered genetic networks that are implanted in a natural cell environment. Their construction is typically combined with experiments on model organisms as well as mathematical modeling and simulation. What is especially interesting about this combinational modeling practice is that, apart from greater integration between these different epistemic activities, it has also led to the questioning of some central assumptions and notions on which synthetic biology is based. As a result synthetic biology is in the process of becoming more "biology inspired."

  7. Systems Biology and Synthetic Biology: A New Epoch for Toxicology Research

    Directory of Open Access Journals (Sweden)

    Mark T. Mc Auley

    2015-01-01

    Full Text Available Systems biology and synthetic biology are emerging disciplines which are becoming increasingly utilised in several areas of bioscience. Toxicology is beginning to benefit from systems biology and we suggest in the future that is will also benefit from synthetic biology. Thus, a new era is on the horizon. This review illustrates how a suite of innovative techniques and tools can be applied to understanding complex health and toxicology issues. We review limitations confronted by the traditional computational approaches to toxicology and epidemiology research, using polycyclic aromatic hydrocarbons (PAHs and their effects on adverse birth outcomes as an illustrative example. We introduce how systems toxicology (and their subdisciplines, genomic, proteomic, and metabolomic toxicology will help to overcome such limitations. In particular, we discuss the advantages and disadvantages of mathematical frameworks that computationally represent biological systems. Finally, we discuss the nascent discipline of synthetic biology and highlight relevant toxicological centred applications of this technique, including improvements in personalised medicine. We conclude this review by presenting a number of opportunities and challenges that could shape the future of these rapidly evolving disciplines.

  8. A Bottom up Initiative: Meditation & Mindfulness 'Eastern' Practices in the "Western" Academia

    DEFF Research Database (Denmark)

    Singla, Rashmi

    The process of globalisation has also influenced the curriculum of Psychology discipline in the Nordic countries to some extent. There are new sub disciplines and themes in the contemporary courses which have been brought about by both top down as well as bottom up initiative. This paper covers...... a case of bottom up initiative, where the students themselves have demanded inclusion of non- conventional psychosocial interventions illustrated by meditation and mindfulness as Eastern psychological practices, thus filling the gap related to the existential, spiritual approaches. The western...... psychological hegemony has made such transformations difficult and contentious in some universities in Denmark, whereas others are more open towards an integrated form of knowledge originating from different geographical contexts. The initiative taken by the psychology students in Århus University, the specific...

  9. Mindfulness meditation associated with alterations in bottom-up processing: psychophysiological evidence for reduced reactivity.

    Science.gov (United States)

    van den Hurk, Paul A M; Janssen, Barbara H; Giommi, Fabio; Barendregt, Henk P; Gielen, Stan C

    2010-11-01

    Mental training by meditation has been related to changes in high-level cognitive functions that involve top-down processing. The aim of this study was to investigate whether the practice of meditation is also related to alterations in low-level, bottom-up processing. Therefore, intersensory facilitation (IF) effects in a group of mindfulness meditators (MM) were compared to IF effects in an age- and gender-matched control group. Smaller and even absent IF effects were found in the MM group, which suggests that changes in bottom-up processing are associated with MM. Furthermore, reduced interference of a visual warning stimulus with the IF effects was found, which suggests an improved allocation of attentional resources in mindfulness meditators, even across modalities.

  10. Bottom-up mining of XML query patterns to improve XML querying

    Institute of Scientific and Technical Information of China (English)

    Yi-jun BEI; Gang CHEN; Jin-xiang DONG; Ke CHEN

    2008-01-01

    Querying XML data is a computationally expensive process due to the complex nature of both the XML data and the XML queries. In this paper we propose an approach to expedite XML query processing by caching the results of frequent queries. We discover frequent query patterns from user-issued queries using an efficient bottom-up mining approach called VBUXMiner. VBUXMiner consists of two main steps. First, all queries are merged into a summary structure named "compressed global tree guide" (CGTG). Second, a bottom-up traversal scheme based on the CGTG is employed to generate frequent query patterns. We use the frequent query patterns in a cache mechanism to improve the XML query performance. Experimental results show that our proposed mining approach outperforms the previous mining algorithms for XML queries, such as XQPMinerTID and FastXMiner, and that by caching the results of frequent query patterns, XML query performance can be dramatically improved.

  11. Scaled CMOS Reliability and Considerations for Spacecraft Systems: Bottom-Up and Top-Down Perspective

    Science.gov (United States)

    White, Mark

    2012-01-01

    New space missions will increasingly rely on more advanced technologies because of system requirements for higher performance, particularly in instruments and high-speed processing. Component-level reliability challenges with scaled CMOS in spacecraft systems from a bottom-up perspective have been presented. Fundamental Front-end and Back-end processing reliability issues with more aggressively scaled parts have been discussed. Effective thermal management from system-level to the componentlevel (top-down) is a key element in overall design of reliable systems. Thermal management in space systems must consider a wide range of issues, including thermal loading of many different components, and frequent temperature cycling of some systems. Both perspectives (top-down and bottom-up) play a large role in robust, reliable spacecraft system design.

  12. A balance of bottom-up and top-down in linking climate policies

    Science.gov (United States)

    Green, Jessica F.; Sterner, Thomas; Wagner, Gernot

    2014-12-01

    Top-down climate negotiations embodied by the Kyoto Protocol have all but stalled, chiefly because of disagreements over targets and objections to financial transfers. To avoid those problems, many have shifted their focus to linkage of bottom-up climate policies such as regional carbon markets. This approach is appealing, but we identify four obstacles to successful linkage: different levels of ambition; competing domestic policy objectives; objections to financial transfers; and the difficulty of close regulatory coordination. Even with a more decentralized approach, overcoming the 'global warming gridlock' of the intergovernmental negotiations will require close international coordination. We demonstrate how a balance of bottom-up and top-down elements can create a path toward an effective global climate architecture.

  13. The generation of myricetin-nicotinamide nanococrystals by top down and bottom up technologies

    Science.gov (United States)

    Liu, Mingyu; Hong, Chao; Li, Guowen; Ma, Ping; Xie, Yan

    2016-09-01

    Myricetin-nicotinamide (MYR-NIC) nanococrystal preparation methods were developed and optimized using both top down and bottom up approaches. The grinding (top down) method successfully achieved nanococrystals, but there were some micrometer range particles and aggregation. The key consideration of the grinding technology was to control the milling time to determine a balance between the particle size and distribution. In contrast, a modified bottom up approach based on a solution method in conjunction with sonochemistry resulted in a uniform MYR-NIC nanococrystal that was confirmed by powder x-ray diffraction, scanning electron microscopy, dynamic light scattering, and differential scanning calorimeter, and the particle dissolution rate and amount were significantly greater than that of MYR-NIC cocrystal. Notably, this was a simple method without the addition of any non-solvent. We anticipate our findings will provide some guidance for future nanococrystal preparation as well as its application in both chemical and pharmaceutical area.

  14. Bottom-up laboratory testing of the DKIST Visible Broadband Imager (VBI)

    Science.gov (United States)

    Ferayorni, Andrew; Beard, Andrew; Cole, Wes; Gregory, Scott; Wöeger, Friedrich

    2016-08-01

    The Daniel K. Inouye Solar Telescope (DKIST) is a 4-meter solar observatory under construction at Haleakala, Hawaii [1]. The Visible Broadband Imager (VBI) is a first light instrument that will record images at the highest possible spatial and temporal resolution of the DKIST at a number of scientifically important wavelengths [2]. The VBI is a pathfinder for DKIST instrumentation and a test bed for developing processes and procedures in the areas of unit, systems integration, and user acceptance testing. These test procedures have been developed and repeatedly executed during VBI construction in the lab as part of a "test early and test often" philosophy aimed at identifying and resolving issues early thus saving cost during integration test and commissioning on summit. The VBI team recently completed a bottom up end-to-end system test of the instrument in the lab that allowed the instrument's functionality, performance, and usability to be validated against documented system requirements. The bottom up testing approach includes four levels of testing, each introducing another layer in the control hierarchy that is tested before moving to the next level. First the instrument mechanisms are tested for positioning accuracy and repeatability using a laboratory position-sensing detector (PSD). Second the real-time motion controls are used to drive the mechanisms to verify speed and timing synchronization requirements are being met. Next the high-level software is introduced and the instrument is driven through a series of end-to-end tests that exercise the mechanisms, cameras, and simulated data processing. Finally, user acceptance testing is performed on operational and engineering use cases through the use of the instrument engineering graphical user interface (GUI). In this paper we present the VBI bottom up test plan, procedures, example test cases and tools used, as well as results from test execution in the laboratory. We will also discuss the benefits realized

  15. A constraint-based bottom-up counterpart to definite clause grammars

    DEFF Research Database (Denmark)

    Christiansen, Henning

    2004-01-01

    A new grammar formalism, CHR Grammars (CHRG), is proposed that provides a constraint-solving approach to language analysis, built on top of the programming language of Constraint Handling Rules in the same way as Definite Clause Grammars (DCG) on Prolog. CHRG works bottom-up and adds the following......, integrity constraints, operators a la assumption grammars, and to incorporate other constraint solvers. (iv)~Context-sensitive rules that apply for disambiguation, coordination in natural language and tagger-like rules....

  16. Bottom-Up Cost Analysis of a High Concentration PV Module

    Energy Technology Data Exchange (ETDEWEB)

    Horowitz, Kelsey A. W.; Woodhouse, Michael; Lee, Hohyun; Smestad, Greg P.

    2016-03-31

    We present a bottom-up model of III-V multi-junction cells, as well as a high concentration PV (HCPV) module. We calculate $0.59/W(DC) manufacturing costs for our model HCPV module design with today's capabilities, and find that reducing cell costs and increasing module efficiency offer the most promising paths for future cost reductions. Cell costs could be significantly reduced via substrate reuse and improved manufacturing yields.

  17. Identifying prognostic features by bottom-up approach and correlating to drug repositioning.

    Directory of Open Access Journals (Sweden)

    Wei Li

    Full Text Available Traditionally top-down method was used to identify prognostic features in cancer research. That is to say, differentially expressed genes usually in cancer versus normal were identified to see if they possess survival prediction power. The problem is that prognostic features identified from one set of patient samples can rarely be transferred to other datasets. We apply bottom-up approach in this study: survival correlated or clinical stage correlated genes were selected first and prioritized by their network topology additionally, then a small set of features can be used as a prognostic signature.Gene expression profiles of a cohort of 221 hepatocellular carcinoma (HCC patients were used as a training set, 'bottom-up' approach was applied to discover gene-expression signatures associated with survival in both tumor and adjacent non-tumor tissues, and compared with 'top-down' approach. The results were validated in a second cohort of 82 patients which was used as a testing set.Two sets of gene signatures separately identified in tumor and adjacent non-tumor tissues by bottom-up approach were developed in the training cohort. These two signatures were associated with overall survival times of HCC patients and the robustness of each was validated in the testing set, and each predictive performance was better than gene expression signatures reported previously. Moreover, genes in these two prognosis signature gave some indications for drug-repositioning on HCC. Some approved drugs targeting these markers have the alternative indications on hepatocellular carcinoma.Using the bottom-up approach, we have developed two prognostic gene signatures with a limited number of genes that associated with overall survival times of patients with HCC. Furthermore, prognostic markers in these two signatures have the potential to be therapeutic targets.

  18. Facilitating a research culture in an academic library: top down and bottom up approaches

    OpenAIRE

    Pickton, Miggie

    2016-01-01

    Purpose:\\ud The purpose of this paper is to consider why and how a research culture might be established in an academic library and to describe and evaluate efforts to achieve this at the University of Northampton. \\ud Design/methodology/approach:\\ud Contextualised within current literature on this topic, the paper examines the top down and bottom up approaches taken to facilitate practitioner research in one academic library. \\ud Findings:\\ud The approaches taken have led to a significant in...

  19. On the interactions between top-down anticipation and bottom-up regression

    Directory of Open Access Journals (Sweden)

    Jun Tani

    2007-11-01

    Full Text Available This paper discusses the importance of anticipation and regression in modeling cognitive behavior. The meanings of these cognitive functions are explained by describing our proposed neural network model which has been implemented on a set of cognitive robotics experiments. The reviews of these experiments suggest that the essences of embodied cognition may reside in the phenomena of the break-down between the top-down anticipation and the bottom-up regression and in its recovery process.

  20. The Application of Bottom-up and Top-down Processing in L2 Listening Comprehension

    Institute of Scientific and Technical Information of China (English)

    温颖茜

    2008-01-01

    Listening comprehension is one of the four basic skills for language learning and is also one of the most difficult tasks L2 learners ever experienced.L2 listening comprehemion is a cognitvive process,in which listeners use both bottom-up andtop-downprocessing to comprehend the auraltext.Thepaper focmes on the applicationof the two approaches in L2 lis-tening comprehemiom

  1. External Costs of Road, Rail and Air Transport - a Bottom-Up Approach

    OpenAIRE

    Weinreich, Sigurd; Rennings, Klaus; Schlomann, Barbara; Geßner, Christian; Engel, Thomas

    1998-01-01

    This paper aims to describe the calculation of environmental and health externalities caused by air pollutants, accidents and noise from different transport modes (road, rail, air) on the route Frankfurt-Milan. The investigation is part of the QUITS project (QUITS = Quality Indicators for Transport Systems), commissioned by the European Commission DG VII. The evaluation of the external costs is based on a bottom-up approach. The calculation involves four stages: emissions, dispersion, impacts...

  2. Catalyst-Free Bottom-Up Synthesis of Few-Layer Hexagonal Boron Nitride Nanosheets

    Directory of Open Access Journals (Sweden)

    Shena M. Stanley

    2015-01-01

    Full Text Available A novel catalyst-free methodology has been developed to prepare few-layer hexagonal boron nitride nanosheets using a bottom-up process. Scanning electron microscopy and transmission electron microscopy (both high and low resolution exhibit evidence of less than ten layers of nanosheets with uniform dimension. X-ray diffraction pattern and other additional characterization techniques prove crystallinity and purity of the product.

  3. Bottom-up graphene-nanoribbon fabrication reveals chiral edges and enantioselectivity.

    Science.gov (United States)

    Han, Patrick; Akagi, Kazuto; Federici Canova, Filippo; Mutoh, Hirotaka; Shiraki, Susumu; Iwaya, Katsuya; Weiss, Paul S; Asao, Naoki; Hitosugi, Taro

    2014-09-23

    We produce precise chiral-edge graphene nanoribbons on Cu{111} using self-assembly and surface-directed chemical reactions. We show that, using specific properties of the substrate, we can change the edge conformation of the nanoribbons, segregate their adsorption chiralities, and restrict their growth directions at low surface coverage. By elucidating the molecular-assembly mechanism, we demonstrate that our method constitutes an alternative bottom-up strategy toward synthesizing defect-free zigzag-edge graphene nanoribbons.

  4. Piezoresistive characterization of bottom-up, n-type silicon microwires undergoing bend deformation

    Energy Technology Data Exchange (ETDEWEB)

    McClarty, Megan M.; Oliver, Derek R., E-mail: Michael.Freund@umanitoba.ca, E-mail: Derek.Oliver@umanitoba.ca [Department of Electrical and Computer Engineering, University of Manitoba, Winnipeg R3T 5V6 (Canada); Bruce, Jared P.; Freund, Michael S., E-mail: Michael.Freund@umanitoba.ca, E-mail: Derek.Oliver@umanitoba.ca [Department of Chemistry, University of Manitoba, Winnipeg R3T 2N2 (Canada)

    2015-01-12

    The piezoresistance of silicon has been studied over the past few decades in order to characterize the material's unique electromechanical properties and investigate their wider applicability. While bulk and top-down (etched) micro- and nano-wires have been studied extensively, less work exists regarding bottom-up grown microwires. A facile method is presented for characterizing the piezoresistance of released, phosphorus-doped silicon microwires that have been grown, bottom-up, via a chemical vapour deposition, vapour-liquid-solid process. The method uses conductive tungsten probes to simultaneously make electrical measurements via direct ohmic contact and apply mechanical strain via bend deformation. These microwires display piezoresistive coefficients within an order of magnitude of those expected for bulk n-type silicon; however, they show an anomalous response at degenerate doping concentrations (∼10{sup 20 }cm{sup −3}) when compared to lower doping concentrations (∼10{sup 17 }cm{sup −3}), with a stronger piezoresistive coefficient exhibited for the more highly doped wires. This response is postulated to be due to the different growth mechanism of bottom-up microwires as compared to top-down.

  5. A Bottom-up Trend in Research of Management of Technology

    Directory of Open Access Journals (Sweden)

    Yoko Ishino

    2014-12-01

    Full Text Available Management of Technology (MOT is defined as an academic discipline of management that enables organizations to manage their technological fundamentals to create competitive advantage. MOT covers a wide range of contents including administrative strategy, R&D management, manufacturing management, technology transfer, production control, marketing, accounting, finance, business ethics, and others. For each topic, researchers have conducted their MOT research at various levels. However, a practical and pragmatic side of MOT surely affects its research trends. Finding changes of MOT research trends, or the chronological transitions of principal subjects, can help understand the key concepts of current MOT. This paper studied a bottom-up trend in research fields in MOT by applying a text-mining method to the conference proceedings of IAMOT (International Association for Management of Technology. First, focusing on only nouns found several keywords, which more frequently emerge over time in the IAMOT proceedings. Then, expanding the scope into other parts of speech viewed the keywords in a natural context. Finally, it was found that the use of an important keyword has qualitatively and quantitatively extended over time. In conclusion, a bottom-up trend in MOT research was detected and the effects of the social situation on the trend were discussed.Keywords: Management of Technology; Text Mining; Research Trend; Bottom-up Trend; Patent

  6. A bottom-up approach of stochastic demand allocation in water quality modelling

    Directory of Open Access Journals (Sweden)

    E. J. M. Blokker

    2010-01-01

    Full Text Available An "all pipes" hydraulic model of a DMA-sized drinking water distribution system was constructed with two types of demand allocations. One is constructed with the conventional top-down approach, i.e. a demand multiplier pattern from the booster station is allocated to all demand nodes with a correction factor to account for the average water demand on that node. The other is constructed with a bottom-up approach of demand allocation, i.e., each individual home is represented by one demand node with its own stochastic water demand pattern.

    The stochastic water demand patterns are constructed with an end-use model on a per second basis and per individual home. The flow entering the test area was measured and a tracer test with sodium chloride was performed to measure travel times. The two models were evaluated on the predicted sum of demands and travel times, compared with what was measured in the test area.

    The new bottom-up approach performs at least as well as the conventional top-down approach with respect to total demand and travel times, without the need for any flow measurements or calibration measurements. The bottom-up approach leads to a stochastic method of hydraulic modelling and gives insight into the variability of travel times as an added feature beyond the conventional way of modelling.

  7. Synthetic biology and its alternatives. Descartes, Kant and the idea of engineering biological machines.

    Science.gov (United States)

    Kogge, Werner; Richter, Michael

    2013-06-01

    The engineering-based approach of synthetic biology is characterized by an assumption that 'engineering by design' enables the construction of 'living machines'. These 'machines', as biological machines, are expected to display certain properties of life, such as adapting to changing environments and acting in a situated way. This paper proposes that a tension exists between the expectations placed on biological artefacts and the notion of producing such systems by means of engineering; this tension makes it seem implausible that biological systems, especially those with properties characteristic of living beings, can in fact be produced using the specific methods of engineering. We do not claim that engineering techniques have nothing to contribute to the biotechnological construction of biological artefacts. However, drawing on Descartes's and Kant's thinking on the relationship between the organism and the machine, we show that it is considerably more plausible to assume that distinctively biological artefacts emerge within a paradigm different from the paradigm of the Cartesian machine that underlies the engineering approach. We close by calling for increased attention to be paid to approaches within molecular biology and chemistry that rest on conceptions different from those of synthetic biology's engineering paradigm.

  8. Towards synthetic biological approaches to resource utilization on space missions.

    Science.gov (United States)

    Menezes, Amor A; Cumbers, John; Hogan, John A; Arkin, Adam P

    2015-01-06

    This paper demonstrates the significant utility of deploying non-traditional biological techniques to harness available volatiles and waste resources on manned missions to explore the Moon and Mars. Compared with anticipated non-biological approaches, it is determined that for 916 day Martian missions: 205 days of high-quality methane and oxygen Mars bioproduction with Methanobacterium thermoautotrophicum can reduce the mass of a Martian fuel-manufacture plant by 56%; 496 days of biomass generation with Arthrospira platensis and Arthrospira maxima on Mars can decrease the shipped wet-food mixed-menu mass for a Mars stay and a one-way voyage by 38%; 202 days of Mars polyhydroxybutyrate synthesis with Cupriavidus necator can lower the shipped mass to three-dimensional print a 120 m(3) six-person habitat by 85% and a few days of acetaminophen production with engineered Synechocystis sp. PCC 6803 can completely replenish expired or irradiated stocks of the pharmaceutical, thereby providing independence from unmanned resupply spacecraft that take up to 210 days to arrive. Analogous outcomes are included for lunar missions. Because of the benign assumptions involved, the results provide a glimpse of the intriguing potential of 'space synthetic biology', and help focus related efforts for immediate, near-term impact.

  9. Biochemistry-directed hollow porous microspheres: bottom-up self-assembled polyanion-based cathodes for sodium ion batteries.

    Science.gov (United States)

    Lin, Bo; Li, Qiufeng; Liu, Baodong; Zhang, Sen; Deng, Chao

    2016-04-21

    Biochemistry-directed synthesis of functional nanomaterials has attracted great interest in energy storage, catalysis and other applications. The unique ability of biological systems to guide molecule self-assembling facilitates the construction of distinctive architectures with desirable physicochemical characteristics. Herein, we report a biochemistry-directed "bottom-up" approach to construct hollow porous microspheres of polyanion materials for sodium ion batteries. Two kinds of polyanions, i.e. Na3V2(PO4)3 and Na3.12Fe2.44(P2O7)2, are employed as cases in this study. The microalgae cell realizes the formation of a spherical "bottom" bio-precursor. Its tiny core is subjected to destruction and its tough shell tends to carbonize upon calcination, resulting in the hollow porous microspheres for the "top" product. The nanoscale crystals of the polyanion materials are tightly enwrapped by the highly-conductive framework in the hollow microsphere, resulting in the hierarchical nano-microstructure. The whole formation process is disclosed as a "bottom-up" mechanism. Moreover, the biochemistry-directed self-assembly process is confirmed to play a crucial role in the construction of the final architecture. Taking advantage of the well-defined hollow-microsphere architecture, the abundant interior voids and the highly-conductive framework, polyanion materials show favourable sodium-intercalation kinetics. Both materials are capable of high-rate long-term cycling. After five hundred cycles at 20 C and 10 C, Na3V2(PO4)3 and Na(3.12)Fe2.44(P2O7)2 retain 96.2% and 93.1% of the initial capacity, respectively. Therefore, the biochemistry-directed technique provides a low-cost, highly-efficient and widely applicable strategy to produce high-performance polyanion-based cathodes for sodium ion batteries.

  10. Top-down vs. bottom-up control on vegetation composition in a tidal marsh depends on scale

    NARCIS (Netherlands)

    Elschot, Kelly; Vermeulen, Anke; Vandenbruwaene, Wouter; Bakker, Jan P.; Bouma, Tjeerd J.; Stahl, Julia; Castelijns, Henk; Temmerman, Stijn

    2017-01-01

    The relative impact of top-down control by herbivores and bottom-up control by environmental conditions on vegetation is a subject of debate in ecology. In this study, we hypothesize that top-down control by goose foraging and bottom-up control by sediment accretion on vegetation composition with

  11. BoB: Best of Both in Compiler Construction Bottom-up Parsing with Top-down Semantic Evaluation

    Directory of Open Access Journals (Sweden)

    Wolfgang Dichler

    Full Text Available Compilers typically use either a top-down or a bottom-up strategy for parsing as well as semantic evaluation. Both strategies have advantages and disadvantages: bottom-up parsing supports LR(k grammars but is limited to S- or LR-attribution while top-dow ...

  12. Bottom-Up or Top-Down: English as a Foreign Language Vocabulary Instruction for Chinese University Students

    Science.gov (United States)

    Moskovsky, Christo; Jiang, Guowu; Libert, Alan; Fagan, Seamus

    2015-01-01

    Whereas there has been some research on the role of bottom-up and top-down processing in the learning of a second or foreign language, very little attention has been given to bottom-up and top-down instructional approaches to language teaching. The research reported here used a quasi-experimental design to assess the relative effectiveness of two…

  13. Engineering molecular circuits using synthetic biology in mammalian cells.

    Science.gov (United States)

    Wieland, Markus; Fussenegger, Martin

    2012-01-01

    Synthetic biology has made significant leaps over the past decade, and it now enables rational and predictable reprogramming of cells to conduct complex physiological activities. The bases for cellular reprogramming are mainly genetic control components affecting gene expression. A huge variety of these modules, ranging from engineered fusion proteins regulating transcription to artificial RNA devices affecting translation, is available, and they often feature a highly modular scaffold. First endeavors to combine these modules have led to autoregulated expression systems and genetic cascades. Analogous to the rational engineering of electronic circuits, the existing repertoire of artificial regulatory elements has further enabled the ambitious reprogramming of cells to perform Boolean calculations or to mimic the oscillation of circadian clocks. Cells harboring synthetic gene circuits are not limited to cell culture, as they have been successfully implanted in animals to obtain tailor-made therapeutics that have made it possible to restore urea or glucose homeostasis as well as to offer an innovative approach to artificial insemination.

  14. Testing of Synthetic Biological Membranes for Forward Osmosis Applications

    Science.gov (United States)

    Parodi, Jurek; Mangado, Jaione Romero; Stefanson, Ofir; Flynn, Michael; Mancinelli, Rocco; Kawashima, Brian; Trieu, Serena; Brozell, Adrian; Rosenberg, Kevan

    2016-01-01

    Commercially available forward osmosis membranes have been extensively tested for human space flight wastewater treatment. Despite the improvements achieved in the last decades, there is still a challenge to produce reliable membranes with anti-fouling properties, chemical resistance, and high flux and selectivity. Synthetic biological membranes that mimic the ones present in nature, which underwent millions of years of evolution, represent a potential solution for further development and progress in membrane technology. Biomimetic forward osmosis membranes based on a polymeric support filter and coated with surfactant multilayers have been engineered to investigate how different manufacturing processes impact the performance and structure of the membrane. However, initial results of the first generation prototype membranes tests reveal a high scatter in the data, due to the current testing apparatus set up. The testing apparatus has been upgraded to improve data collection, reduce errors, and to allow higher control of the testing process.

  15. Can the natural diversity of quorum sensing advance synthetic biology?

    Directory of Open Access Journals (Sweden)

    Rene Michele Davis

    2015-03-01

    Full Text Available Quorum-sensing networks enable bacteria to sense and respond to chemical signals produced by neighboring bacteria. They are widespread: over one hundred morphologically and genetically distinct species of eubacteria are known to use quorum sensing to control gene expression. This diversity suggests the potential to use natural protein variants to engineer parallel, input-specific, cell-cell communication pathways. However, only three distinct signaling pathways, Lux, Las, and Rhl, have been adapted for and broadly used in engineered systems. The paucity of unique quorum-sensing systems and their propensity for crosstalk limits the usefulness of our current quorum-sensing toolkit. This review discusses the need for more signaling pathways, roadblocks to using multiple pathways in parallel, and strategies for expanding the quorum-sensing toolbox for synthetic biology.

  16. The appeasement of Doug: a synthetic approach to enhancer biology.

    Science.gov (United States)

    Vincent, Ben J; Estrada, Javier; DePace, Angela H

    2016-04-18

    Genetic approaches have been instrumental in dissecting developmental enhancers by characterizing their transcription factor binding sites. Though some enhancers have been well-studied in this regard, we cannot currently build developmental enhancers from scratch. Reconstitution experiments can provide important complementary tests of our understanding of enhancer function, but these experiments are exceedingly rare in the literature, possibly due to the difficulty of publishing negative results. In this perspective, we argue that the time is right for a synthetic approach to enhancer biology. Focusing primarily on Drosophila enhancers as examples, we review classic and modern methods for dissecting enhancer function as well as computational tools for enhancer design. We include our own negative results from attempts to reconstitute the stripe 2 enhancer from the even-skipped locus and discuss possible ways forward. We believe that with a communal effort in open data sharing, we can make substantial progress toward a complete understanding of enhancer function.

  17. Ortholog prediction of the Aspergillus genus applicable for synthetic biology

    DEFF Research Database (Denmark)

    Rasmussen, Jane Lind Nybo; Vesth, Tammi Camilla; Theobald, Sebastian

    The Aspergillus genus contains leading industrial microorganisms, excelling in producing bioactive compounds and enzymes. Using synthetic biology and bioinformatics, we aim to re-engineer these organisms for applications within human health, pharmaceuticals, environmental engineering, and food...... production. In this project, we compare the genomes of +300 species from the Aspergillus genus to generate a high-resolution pan-genomic map, representing genetic diversity spanning ~200 million years. We are identifying genes specific to species and clades to allow for guilt-by-association-based mapping......-directional hits. The result is orthologous protein families describing the genomic and functional features of individual species, clades and the core/pan genome of Aspergillus; and applicable to genotype-to-phenotype analyses in other microbial genera....

  18. Challenges for the European governance of synthetic biology for human health

    NARCIS (Netherlands)

    Stemerding, D.; Douglas, C.

    2014-01-01

    Synthetic biology is a series of scientific and technological practices involved in the application of engineering principles to the design and production of predictable and robust biological systems. While policy discussions abound in this area, emerging technologies like synthetic biology present

  19. [Application of synthetic biology to sustainable utilization of Chinese materia medica resources].

    Science.gov (United States)

    Huang, Lu-Qi; Gao, Wei; Zhou, Yong-Jin

    2014-01-01

    Bioactive natural products are the material bases of Chinese materia medica resources. With successful applications of synthetic biology strategies to the researches and productions of taxol, artemisinin and tanshinone, etc, the potential ability of synthetic biology in the sustainable utilization of Chinese materia medica resources has been attracted by many researchers. This paper reviews the development of synthetic biology, the opportunities of sustainable utilization of Chinese materia medica resources, and the progress of synthetic biology applied to the researches of bioactive natural products. Furthermore, this paper also analyzes how to apply synthetic biology to sustainable utilization of Chinese materia medica resources and what the crucial factors are. Production of bioactive natural products with synthetic biology strategies will become a significant approach for the sustainable utilization of Chinese materia medica resources.

  20. PGASO: A synthetic biology tool for engineering a cellulolytic yeast

    Directory of Open Access Journals (Sweden)

    Chang Jui-Jen

    2012-07-01

    Full Text Available Abstract Background To achieve an economical cellulosic ethanol production, a host that can do both cellulosic saccharification and ethanol fermentation is desirable. However, to engineer a non-cellulolytic yeast to be such a host requires synthetic biology techniques to transform multiple enzyme genes into its genome. Results A technique, named Promoter-based Gene Assembly and Simultaneous Overexpression (PGASO, that employs overlapping oligonucleotides for recombinatorial assembly of gene cassettes with individual promoters, was developed. PGASO was applied to engineer Kluyveromycesmarxianus KY3, which is a thermo- and toxin-tolerant yeast. We obtained a recombinant strain, called KR5, that is capable of simultaneously expressing exoglucanase and endoglucanase (both of Trichodermareesei, a beta-glucosidase (from a cow rumen fungus, a neomycin phosphotransferase, and a green fluorescent protein. High transformation efficiency and accuracy were achieved as ~63% of the transformants was confirmed to be correct. KR5 can utilize beta-glycan, cellobiose or CMC as the sole carbon source for growth and can directly convert cellobiose and beta-glycan to ethanol. Conclusions This study provides the first example of multi-gene assembly in a single step in a yeast species other than Saccharomyces cerevisiae. We successfully engineered a yeast host with a five-gene cassette assembly and the new host is capable of co-expressing three types of cellulase genes. Our study shows that PGASO is an efficient tool for simultaneous expression of multiple enzymes in the kefir yeast KY3 and that KY3 can serve as a host for developing synthetic biology tools.

  1. Does Life without Past have any Future? The Neglect of Evolution in Synthetic Biology

    Directory of Open Access Journals (Sweden)

    Laura Nuño De La Rosa

    2016-12-01

    Full Text Available Synthetic biology has a singular relation to evolutionary theory. On the one hand, synthetic biology is founded on an engineering interpretation of evolution. On the other hand, bioengineers aspire to free themselves from evolution by building organisms ‘from scratch’ that behave in a predictable way. In this article, I will examine the main properties of the synthetic characterisation of bioartifacts, namely their characterisation as (1 modular and (2 computable systems which are (3 the product of design. I will argue that synthetic biology is founded on a conception of organisms and their relation with their historical legacy which has been deeply challenged by contemporary evolutionary biology.

  2. METABOLIC MODELLING IN THE DEVELOPMENT OF CELL FACTORIES BY SYNTHETIC BIOLOGY

    Directory of Open Access Journals (Sweden)

    Paula Jouhten

    2012-10-01

    Full Text Available Cell factories are commonly microbial organisms utilized for bioconversion of renewable resources to bulk or high value chemicals. Introduction of novel production pathways in chassis strains is the core of the development of cell factories by synthetic biology. Synthetic biology aims to create novel biological functions and systems not found in nature by combining biology with engineering. The workflow of the development of novel cell factories with synthetic biology is ideally linear which will be attainable with the quantitative engineering approach, high-quality predictive models, and libraries of well-characterized parts. Different types of metabolic models, mathematical representations of metabolism and its components, enzymes and metabolites, are useful in particular phases of the synthetic biology workflow. In this minireview, the role of metabolic modelling in synthetic biology will be discussed with a review of current status of compatible methods and models for the in silico design and quantitative evaluation of a cell factory.

  3. Synthetic Biology and the Search for Extraterrestrial Life

    Science.gov (United States)

    Rothschild, L. J.; Fujishima, K.

    2014-03-01

    "Are we alone?" is one of the primary questions of astrobiology, and whose answer defines our significance in the universe. Unfortunately, this quest is hindered by the fact that we have only one confirmed example of life, that of earth. While this is enormously helpful in helping to define the minimum envelope for life, it strains credulity to imagine that life, if it arose multiple times, has not taken other routes. To help fill this gap, our lab has begun using synthetic biology - the design and construction of new biological parts and systems and the redesign of existing ones for useful purposes - as an enabling technology. One theme, the "Hell Cell" project, focuses on creating artificial extremophiles in order to push the limits for Earth life, and to understand how difficult it is for life to evolve into extreme niches. In another project, we are reevolving biotic functions using only the most thermodynamically stable amino acids in order to understand potential capabilities of an early organism with a limited repertoire of amino acids. This should lead to a more universal theory of the origin of life based on materials found commonly in meteorites and other pre-biotic settings.

  4. Synthetic Biology as an Enabling Technology for Space Exploration

    Science.gov (United States)

    Rothschild, Lynn J.

    2016-01-01

    Human exploration off planet is severely limited by the cost of launching materials into space and by re-supply. Thus materials brought from Earth must be light, stable and reliable at destination. Using traditional approaches, a lunar or Mars base would require either transporting a hefty store of metals or heavy manufacturing equipment and construction materials for in situ extraction; both would severely limit any other mission objectives. Long-term human space presence requires periodic replenishment, adding a massive cost overhead. Even robotic missions often sacrifice science goals for heavy radiation and thermal protection. Biology has the potential to solve these problems because life can replicate and repair itself, and perform a wide variety of chemical reactions including making food, fuel and materials. Synthetic biology enhances and expands life's evolved repertoire. Using organisms as feedstock, additive manufacturing through bioprinting will make possible the dream of producing bespoke tools, food, smart fabrics and even replacement organs on demand. This new approach and the resulting novel products will enable human exploration and settlement on Mars, while providing new manufacturing approaches for life on Earth.

  5. Synthetic Biology and the Search for Extraterrestrial Life

    Science.gov (United States)

    Rothschild, Lynn J.

    2015-01-01

    "Are we alone?" is one of the primary questions of astrobiology, and whose answer defines our significance in the universe. Unfortunately, this quest is hindered by the fact that we have only one confirmed example of life, that of earth. While this is enormously helpful in helping to define the minimum envelope for life, it strains credulity to imagine that life, if it arose multiple times, has not taken other routes. To help fill this gap, our lab has begun using synthetic biology - the design and construction of new biological parts and systems and the redesign of existing ones for useful purposes - as an enabling technology. One theme, the "Hell Cell" project, focuses on creating artificial extremophiles in order to push the limits for Earth life, and to understand how difficult it is for life to evolve into extreme niches. In another project, we are re-evolving biotic functions using only the most thermodynamically stable amino acids in order to understand potential capabilities of an early organism with a limited repertoire of amino acids.

  6. Visual anticipation biases conscious perception but not bottom-up visual processing

    Directory of Open Access Journals (Sweden)

    Paul F.M.J. Verschure

    2015-01-01

    Full Text Available Theories of consciousness can be grouped with respect to their stance on embodiment, sensori-motor contingencies, prediction and integration. In this list prediction plays a key role and it is not clear which aspects of prediction are most prominent in the conscious scene. An evolving view on the brain is that it can be seen as a prediction machine that optimizes its ability to predict states of the world and the self through the top-down propagation of predictions and the bottom-up presentation of prediction errors. There are competing views though on whether prediction or prediction errors dominate the conscious scene. Yet, due to the lack of efficient indirect measures, the dynamic effects of prediction on perception, decision making and consciousness have been difficult to assess and to model. We propose a novel mathematical framework and psychophysical paradigm that allows us to assess both the hierarchical structuring of perceptual consciousness, its content and the impact of predictions and / or errors on the conscious scene. Using a displacement detection task combined with reverse correlation we reveal signatures of the usage of prediction at three different levels of perception: bottom-up early saccades, top-down driven late saccades and conscious decisions. Our results suggest that the brain employs multiple parallel mechanisms at different levels of information processing to restrict the sensory field using predictions. We observe that cognitive load has a quantifiable effect on this dissociation of the bottom-up sensory and top-down predictive processes. We propose a probabilistic data association model from dynamical systems theory to model this predictive bias in different information processing levels.

  7. Visual anticipation biases conscious decision making but not bottom-up visual processing.

    Science.gov (United States)

    Mathews, Zenon; Cetnarski, Ryszard; Verschure, Paul F M J

    2014-01-01

    Prediction plays a key role in control of attention but it is not clear which aspects of prediction are most prominent in conscious experience. An evolving view on the brain is that it can be seen as a prediction machine that optimizes its ability to predict states of the world and the self through the top-down propagation of predictions and the bottom-up presentation of prediction errors. There are competing views though on whether prediction or prediction errors dominate the formation of conscious experience. Yet, the dynamic effects of prediction on perception, decision making and consciousness have been difficult to assess and to model. We propose a novel mathematical framework and a psychophysical paradigm that allows us to assess both the hierarchical structuring of perceptual consciousness, its content and the impact of predictions and/or errors on conscious experience, attention and decision-making. Using a displacement detection task combined with reverse correlation, we reveal signatures of the usage of prediction at three different levels of perceptual processing: bottom-up fast saccades, top-down driven slow saccades and consciousnes decisions. Our results suggest that the brain employs multiple parallel mechanism at different levels of perceptual processing in order to shape effective sensory consciousness within a predicted perceptual scene. We further observe that bottom-up sensory and top-down predictive processes can be dissociated through cognitive load. We propose a probabilistic data association model from dynamical systems theory to model the predictive multi-scale bias in perceptual processing that we observe and its role in the formation of conscious experience. We propose that these results support the hypothesis that consciousness provides a time-delayed description of a task that is used to prospectively optimize real time control structures, rather than being engaged in the real-time control of behavior itself.

  8. Bottom-up metamaterials with an isotropic magnetic response in the visible

    Science.gov (United States)

    Mühlig, Stefan; Dintinger, José; Cunningham, Alastair; Scharf, Toralf; Bürgi, Thomas; Rockstuhl, Carsten; Lederer, Falk

    A theoretical framework to analyze the optical properties of amorphous metamaterials made from meta-atoms which are amenable for a fabrication with bottom-up technologies is introduced. The achievement of an isotropic magnetic resonance in the visible is investigated by suggesting suitable designs for the meta-atoms. Furthermore, two meta-atoms are discussed in detail that were fabricated by self-assembling plasmonic nanoparticles using techniques from the field of colloidal nanochemistry. The metamaterials are experimentally characterized by spectroscopic means and the excitation of the magnetic dipole moment is clearly revealed. Advantages and disadvantages of metamaterials made from such meta-atoms are discussed.

  9. First-principles study on bottom-up fabrication process of atomically precise graphene nanoribbons

    Science.gov (United States)

    Kaneko, Tomoaki; Tajima, Nobuo; Ohno, Takahisa

    2016-06-01

    We investigate the energetics of a polyanthracene formation in the bottom-up fabrication of atomically precise graphene nanoribbons on Au(111) using first-principles calculations based on the density functional theory. We show that the structure of precursor molecules plays a decisive role in the C-C coupling reaction. The reaction energy of the dimerization of anthracene dimers is a larger negative value than that of the dimerization of anthracene monomers, suggesting that the precursor molecule used in experiments has a favorable structure for graphene nanoribbon fabrication.

  10. Toward the atomic structure of the nuclear pore complex: when top down meets bottom up.

    Science.gov (United States)

    Hoelz, André; Glavy, Joseph S; Beck, Martin

    2016-07-01

    Elucidating the structure of the nuclear pore complex (NPC) is a prerequisite for understanding the molecular mechanism of nucleocytoplasmic transport. However, owing to its sheer size and flexibility, the NPC is unapproachable by classical structure determination techniques and requires a joint effort of complementary methods. Whereas bottom-up approaches rely on biochemical interaction studies and crystal-structure determination of NPC components, top-down approaches attempt to determine the structure of the intact NPC in situ. Recently, both approaches have converged, thereby bridging the resolution gap from the higher-order scaffold structure to near-atomic resolution and opening the door for structure-guided experimental interrogations of NPC function.

  11. Scaled CMOS Reliability and Considerations for Spacecraft Systems : Bottom-Up and Top-Down Perspectives

    Science.gov (United States)

    White, Mark

    2012-01-01

    The recently launched Mars Science Laboratory (MSL) flagship mission, named Curiosity, is the most complex rover ever built by NASA and is scheduled to touch down on the red planet in August, 2012 in Gale Crater. The rover and its instruments will have to endure the harsh environments of the surface of Mars to fulfill its main science objectives. Such complex systems require reliable microelectronic components coupled with adequate component and system-level design margins. Reliability aspects of these elements of the spacecraft system are presented from bottom- up and top-down perspectives.

  12. Unsupervised tattoo segmentation combining bottom-up and top-down cues

    Science.gov (United States)

    Allen, Josef D.; Zhao, Nan; Yuan, Jiangbo; Liu, Xiuwen

    2011-06-01

    Tattoo segmentation is challenging due to the complexity and large variance in tattoo structures. We have developed a segmentation algorithm for finding tattoos in an image. Our basic idea is split-merge: split each tattoo image into clusters through a bottom-up process, learn to merge the clusters containing skin and then distinguish tattoo from the other skin via top-down prior in the image itself. Tattoo segmentation with unknown number of clusters is transferred to a figureground segmentation. We have applied our segmentation algorithm on a tattoo dataset and the results have shown that our tattoo segmentation system is efficient and suitable for further tattoo classification and retrieval purpose.

  13. Towards nano-organic chemistry: perspectives for a bottom-up approach to the synthesis of low-dimensional carbon nanostructures

    Science.gov (United States)

    Mercuri, Francesco; Baldoni, Matteo; Sgamellotti, Antonio

    2012-01-01

    Low-dimensional carbon nanostructures, such as nanotubes and graphenes, represent one of the most promising classes of materials, in view of their potential use in nanotechnology. However, their exploitation in applications is often hindered by difficulties in their synthesis and purification. Despite the huge efforts by the research community, the production of nanostructured carbon materials with controlled properties is still beyond reach. Nonetheless, this step is nowadays mandatory for significant progresses in the realization of advanced applications and devices based on low-dimensional carbon nanostructures. Although promising alternative routes for the fabrication of nanostructured carbon materials have recently been proposed, a comprehensive understanding of the key factors governing the bottom-up assembly of simple precursors to form complex systems with tailored properties is still at its early stages. In this paper, following a survey of recent experimental efforts in the bottom-up synthesis of carbon nanostructures, we attempt to clarify generalized criteria for the design of suitable precursors that can be used as building blocks in the production of complex systems based on sp2 carbon atoms and discuss potential synthetic strategies. In particular, the approaches presented in this feature article are based on the application of concepts borrowed from traditional organic chemistry, such as valence-bond theory and Clar sextet theory, and on their extension to the case of complex carbon nanomaterials. We also present and discuss a validation of these approaches through first-principle calculations on prototypical systems. Detailed studies on the processes involved in the bottom-up fabrication of low-dimensional carbon nanostructures are expected to pave the way for the design and optimization of precursors and efficient synthetic routes, thus allowing the development of novel materials with controlled morphology and properties that can be used in

  14. Computational approaches to metabolic engineering utilizing systems biology and synthetic biology.

    Science.gov (United States)

    Fong, Stephen S

    2014-08-01

    Metabolic engineering modifies cellular function to address various biochemical applications. Underlying metabolic engineering efforts are a host of tools and knowledge that are integrated to enable successful outcomes. Concurrent development of computational and experimental tools has enabled different approaches to metabolic engineering. One approach is to leverage knowledge and computational tools to prospectively predict designs to achieve the desired outcome. An alternative approach is to utilize combinatorial experimental tools to empirically explore the range of cellular function and to screen for desired traits. This mini-review focuses on computational systems biology and synthetic biology tools that can be used in combination for prospective in silico strain design.

  15. Applications of cell-free protein synthesis in synthetic biology: Interfacing bio-machinery with synthetic environments.

    Science.gov (United States)

    Lee, Kyung-Ho; Kim, Dong-Myung

    2013-11-01

    Synthetic biology is built on the synthesis, engineering, and assembly of biological parts. Proteins are the first components considered for the construction of systems with designed biological functions because proteins carry out most of the biological functions and chemical reactions inside cells. Protein synthesis is considered to comprise the most basic levels of the hierarchical structure of synthetic biology. Cell-free protein synthesis has emerged as a powerful technology that can potentially transform the concept of bioprocesses. With the ability to harness the synthetic power of biology without many of the constraints of cell-based systems, cell-free protein synthesis enables the rapid creation of protein molecules from diverse sources of genetic information. Cell-free protein synthesis is virtually free from the intrinsic constraints of cell-based methods and offers greater flexibility in system design and manipulability of biological synthetic machinery. Among its potential applications, cell-free protein synthesis can be combined with various man-made devices for rapid functional analysis of genomic sequences. This review covers recent efforts to integrate cell-free protein synthesis with various reaction devices and analytical platforms.

  16. Automated Urban Travel Interpretation: A Bottom-up Approach for Trajectory Segmentation.

    Science.gov (United States)

    Das, Rahul Deb; Winter, Stephan

    2016-11-23

    Understanding travel behavior is critical for an effective urban planning as well as for enabling various context-aware service provisions to support mobility as a service (MaaS). Both applications rely on the sensor traces generated by travellers' smartphones. These traces can be used to interpret travel modes, both for generating automated travel diaries as well as for real-time travel mode detection. Current approaches segment a trajectory by certain criteria, e.g., drop in speed. However, these criteria are heuristic, and, thus, existing approaches are subjective and involve significant vagueness and uncertainty in activity transitions in space and time. Also, segmentation approaches are not suited for real time interpretation of open-ended segments, and cannot cope with the frequent gaps in the location traces. In order to address all these challenges a novel, state based bottom-up approach is proposed. This approach assumes a fixed atomic segment of a homogeneous state, instead of an event-based segment, and a progressive iteration until a new state is found. The research investigates how an atomic state-based approach can be developed in such a way that can work in real time, near-real time and offline mode and in different environmental conditions with their varying quality of sensor traces. The results show the proposed bottom-up model outperforms the existing event-based segmentation models in terms of adaptivity, flexibility, accuracy and richness in information delivery pertinent to automated travel behavior interpretation.

  17. Top-down (Prior Knowledge) and Bottom-up (Perceptual Modality) Influences on Spontaneous Interpersonal Synchronization.

    Science.gov (United States)

    Gipson, Christina L; Gorman, Jamie C; Hessler, Eric E

    2016-04-01

    Coordination with others is such a fundamental part of human activity that it can happen unintentionally. This unintentional coordination can manifest as synchronization and is observed in physical and human systems alike. We investigated the role of top-down influences (prior knowledge of the perceptual modality their partner is using) and bottom-up factors (perceptual modality combination) on spontaneous interpersonal synchronization. We examine this phenomena with respect to two different theoretical perspectives that differently emphasize top-down and bottom-up factors in interpersonal synchronization: joint-action/shared cognition theories and ecological-interactive theories. In an empirical study twelve dyads performed a finger oscillation task while attending to each other's movements through either visual, auditory, or visual and auditory perceptual modalities. Half of the participants were given prior knowledge of their partner's perceptual capabilities for coordinating across these different perceptual modality combinations. We found that the effect of top-down influence depends on the perceptual modality combination between two individuals. When people used the same perceptual modalities, top-down influence resulted in less synchronization and when people used different perceptual modalities, top-down influence resulted in more synchronization. Furthermore, persistence in the change in behavior as a result of having perceptual information about each other ('social memory') was stronger when this top-down influence was present.

  18. Sex differences in mental rotation: top-down versus bottom-up processing.

    Science.gov (United States)

    Butler, Tracy; Imperato-McGinley, Julianne; Pan, Hong; Voyer, Daniel; Cordero, Juan; Zhu, Yuan-Shan; Stern, Emily; Silbersweig, David

    2006-08-01

    Functional MRI during performance of a validated mental rotation task was used to assess a neurobiological basis for sex differences in visuospatial processing. Between-sex group analysis demonstrated greater activity in women than in men in dorsalmedial prefrontal and other high-order heteromodal association cortices, suggesting women performed mental rotation in an effortful, "top-down" fashion. In contrast, men activated primary sensory cortices as well as regions involved in implicit learning (basal ganglia) and mental imagery (precuneus), consistent with a more automatic, "bottom-up" strategy. Functional connectivity analysis in association with a measure of behavioral performance showed that, in men (but not women), accurate performance was associated with deactivation of parieto-insular vestibular cortex (PIVC) as part of a visual-vestibular network. Automatic evocation by men to a greater extent than women of this network during mental rotation may represent an effective, unconscious, bottom-up neural strategy which could reasonably account for men's traditional visuospatial performance advantage.

  19. A combined bottom-up/top-down approach to prepare a sterile injectable nanosuspension.

    Science.gov (United States)

    Hu, Xi; Chen, Xi; Zhang, Ling; Lin, Xia; Zhang, Yu; Tang, Xing; Wang, Yanjiao

    2014-09-10

    To prepare a uniform nanosuspension of strongly hydrophobic riboflavin laurate (RFL) allowing sterile filtration, physical modification (bottom-up) was combined with high-pressure homogenization (top-down) method. Unlike other bottom-up approaches, physical modification with surfactants (TPGS and PL-100) by lyophilization controlled crystallization and compensated for the poor wettability of RFL. On one hand, crystal growth and aggregation during freezing was restricted by a stabilizer-layer adsorbed on the drug surface by hydrophobic interaction. On the other hand, subsequent crystallization of drug in the sublimation process was limited to the interstitial spaces between solvent crystals. After lyophilization, modified drug with a smaller particle size and better wettability was obtained. When adding surfactant solution, water molecules passed between the hydrophilic groups of surface active molecules and activated the polymer chains allowing them to stretch into water. The coarse suspension was crushed into a nanosuspension (MP=162 nm) by high-pressure homogenization. For long term stability, lyophilization was applied again to solidify the nanosuspension (sorbitol as cryoprotectant). A slight crystal growth to about 600 nm was obtained to allow slow release for a sustained effect after muscular administration. Moreover, no paw-licking responses and very slight muscular inflammation demonstrated the excellent biocompatibility of this long-acting RFL injection.

  20. A bottom-up model to describe consumers’ preferences towards late season peaches

    Energy Technology Data Exchange (ETDEWEB)

    Groot, E.; Albisu, L.M.

    2015-07-01

    Peaches are consumed in Mediterranean countries since ancient times. Nowadays there are few areas in Europe that produce peaches with Protected Designation of Origin (PDO), and the Calanda area is one of them. The aim of this work is to describe consumers’ preferences towards late season PDO Calanda peaches in the city of Zaragoza, Spain, by a bottom-up model. The bottom-up model proves greater amount of information than top-down models. In this approach it is estimated one utility function per consumer. Thus, it is not necessary to make assumptions about preference distributions and correlations across respondents. It was observed that preference distributions were neither normal nor independently distributed. If those preferences were estimated by top-down models, conclusions would be biased. This paper also explores a new way to describe preferences through individual utility functions. Results show that the largest behavioural group gathered origin sensitive consumers. Their utility increased if the peaches were produced in the Calanda area and, especially, when peaches had the PDO Calanda brand. In sequence, the second most valuable attribute for consumers was the price. Peach size and packaging were not so important on purchase choice decision. Nevertheless, it is advisable to avoid trading smallest size peaches (weighting around 160 g/fruit). Traders also have to be careful by using active packaging. It was found that a group of consumers disliked this kind of product, probably, because they perceived it as less natural. (Author)

  1. Top-down and bottom-up forces interact at thermal range extremes on American lobster.

    Science.gov (United States)

    Boudreau, Stephanie A; Anderson, Sean C; Worm, Boris

    2015-05-01

    Exploited marine populations are thought to be regulated by the effects of fishing, species interactions and climate. Yet, it is unclear how these forces interact and vary across a species' range. We conducted a meta-analysis of American lobster (Homarus americanus) abundance data throughout the entirety of the species' range, testing competing hypotheses about bottom-up (climate, temperature) vs. top-down (predation, fishing) regulation along a strong thermal gradient. Our results suggest an interaction between predation and thermal range - predation effects dominated at the cold and warm extremes, but not at the centre of the species' range. Similarly, there was consistent support for a positive climate effect on lobster recruitment at warm range extremes. In contrast, fishing effort followed, rather than led changes in lobster abundance over time. Our analysis suggests that the relative effects of top-down and bottom-up forcing in regulating marine populations may intensify at thermal range boundaries and weaken at the core of a species' range.

  2. Painful faces-induced attentional blink modulated by top-down and bottom-up mechanisms

    Directory of Open Access Journals (Sweden)

    Chun eZheng

    2015-06-01

    Full Text Available Pain-related stimuli can capture attention in an automatic (bottom-up or intentional (top-down fashion. Previous studies have examined attentional capture by pain-related information using spatial attention paradigms that involve mainly a bottom-up mechanism. In the current study, we investigated the pain information–induced attentional blink (AB using a rapid serial visual presentation (RSVP task, and compared the effects of task-irrelevant and task-relevant pain distractors. Relationships between accuracy of target identification and individual traits (i.e., empathy and catastrophizing thinking about pain were also examined. The results demonstrated that task-relevant painful faces had a significant pain information–induced AB effect, whereas task-irrelevant faces a near-significant trend of this effect, supporting the notion that pain-related stimuli can influence the temporal dynamics of attention. Furthermore, we found a significant negative correlation between response accuracy and pain catastrophizing score in task-relevant trials. These findings suggest that active scanning of environmental information related to pain produces greater deficits in cognition than does unintentional attention toward pain, which may represent the different ways in which healthy individuals and patients with chronic pain process pain-relevant information. These results may provide insight into the understanding of maladaptive attentional processing in patients with chronic pain.

  3. Painful faces-induced attentional blink modulated by top-down and bottom-up mechanisms.

    Science.gov (United States)

    Zheng, Chun; Wang, Jin-Yan; Luo, Fei

    2015-01-01

    Pain-related stimuli can capture attention in an automatic (bottom-up) or intentional (top-down) fashion. Previous studies have examined attentional capture by pain-related information using spatial attention paradigms that involve mainly a bottom-up mechanism. In the current study, we investigated the pain information-induced attentional blink (AB) using a rapid serial visual presentation (RSVP) task, and compared the effects of task-irrelevant and task-relevant pain distractors. Relationships between accuracy of target identification and individual traits (i.e., empathy and catastrophizing thinking about pain) were also examined. The results demonstrated that task-relevant painful faces had a significant pain information-induced AB effect, whereas task-irrelevant faces showed a near-significant trend of this effect, supporting the notion that pain-related stimuli can influence the temporal dynamics of attention. Furthermore, we found a significant negative correlation between response accuracy and pain catastrophizing score in task-relevant trials. These findings suggest that active scanning of environmental information related to pain produces greater deficits in cognition than does unintentional attention toward pain, which may represent the different ways in which healthy individuals and patients with chronic pain process pain-relevant information. These results may provide insight into the understanding of maladaptive attentional processing in patients with chronic pain.

  4. Top-down and bottom-up definitions of human failure events in human reliability analysis

    Energy Technology Data Exchange (ETDEWEB)

    Boring, Ronald Laurids [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2014-10-01

    In the probabilistic risk assessments (PRAs) used in the nuclear industry, human failure events (HFEs) are determined as a subset of hardware failures, namely those hardware failures that could be triggered by human action or inaction. This approach is top-down, starting with hardware faults and deducing human contributions to those faults. Elsewhere, more traditionally human factors driven approaches would tend to look at opportunities for human errors first in a task analysis and then identify which of those errors is risk significant. The intersection of top-down and bottom-up approaches to defining HFEs has not been carefully studied. Ideally, both approaches should arrive at the same set of HFEs. This question is crucial, however, as human reliability analysis (HRA) methods are generalized to new domains like oil and gas. The HFEs used in nuclear PRAs tend to be top-down—defined as a subset of the PRA—whereas the HFEs used in petroleum quantitative risk assessments (QRAs) often tend to be bottom-up—derived from a task analysis conducted by human factors experts. The marriage of these approaches is necessary in order to ensure that HRA methods developed for top-down HFEs are also sufficient for bottom-up applications.

  5. A bottom-up approach for the synthesis of highly ordered fullerene-intercalated graphene hybrids

    Directory of Open Access Journals (Sweden)

    Dimitrios eGournis

    2015-02-01

    Full Text Available Much of the research effort on graphene focuses on its use as a building block for the development of new hybrid nanostructures with well-defined dimensions and properties suitable for applications such as gas storage, heterogeneous catalysis, gas/liquid separations, nanosensing and biomedicine. Towards this aim, here we describe a new bottom-up approach, which combines self-assembly with the Langmuir Schaefer deposition technique to synthesize graphene-based layered hybrid materials hosting fullerene molecules within the interlayer space. Our film preparation consists in a bottom-up layer-by-layer process that proceeds via the formation of a hybrid organo-graphene oxide Langmuir film. The structure and composition of these hybrid fullerene-containing thin multilayers deposited on hydrophobic substrates were characterized by a combination of X-ray diffraction, Raman and X-ray photoelectron spectroscopies, atomic force microscopy and conductivity measurements. The latter revealed that the presence of C60 within the interlayer spacing leads to an increase in electrical conductivity of the hybrid material as compared to the organo-graphene matrix alone.

  6. Enabling a next generation of synthetic biology community organization and leadership.

    Science.gov (United States)

    Palmer, Megan J; Jewett, Michael C

    2014-03-21

    Synthetic biology seeks to make engineering of complex biological functions more efficient, reliable, and predictable. Advancing the process of engineering biology requires community organization and leadership. As synthetic biology matures into a globally significant enterprise, the community needs to enable a next generation of leaders to organize the field's responsible advancement. We discuss key points raised at a community meeting on these issues at SB6.0--the Sixth International Meeting on Synthetic Biology--and highlight opportunities to carry forward the conversation.

  7. Synthetic biology and molecular genetics in non-conventional yeasts: Current tools and future advances.

    Science.gov (United States)

    Wagner, James M; Alper, Hal S

    2016-04-01

    Coupling the tools of synthetic biology with traditional molecular genetic techniques can enable the rapid prototyping and optimization of yeast strains. While the era of yeast synthetic biology began in the well-characterized model organism Saccharomyces cerevisiae, it is swiftly expanding to include non-conventional yeast production systems such as Hansenula polymorpha, Kluyveromyces lactis, Pichia pastoris, and Yarrowia lipolytica. These yeasts already have roles in the manufacture of vaccines, therapeutic proteins, food additives, and biorenewable chemicals, but recent synthetic biology advances have the potential to greatly expand and diversify their impact on biotechnology. In this review, we summarize the development of synthetic biological tools (including promoters and terminators) and enabling molecular genetics approaches that have been applied in these four promising alternative biomanufacturing platforms. An emphasis is placed on synthetic parts and genome editing tools. Finally, we discuss examples of synthetic tools developed in other organisms that can be adapted or optimized for these hosts in the near future.

  8. Polymersomes: A Synthetic Biological Approach to Encapsulation and Delivery

    Science.gov (United States)

    Massignani, Marzia; Lomas, Hannah; Battaglia, Giuseppe

    Compartmentalization, i.e. the ability to create controlled volumes and separate molecules one from another is possibly the most important requisite for complex manipulations. Indeed, compartmentalization has been the first step to isolate the building blocks of life and ensure the dynamic nature that today makes the complexity of any living system. For decades scientists have tried using many synthetic approaches to imitate such ability and one the most successful comes from mimicking the biological component responsible for the compartmentalization: the phospholipid. We are now able to synthesize macromolecular analogues of the phospholipid using advanced co-polymerization techniques. Copolymers that comprise hydrophilic and hydrophobic components (i.e. amphiphilic) can be designed to self assemble into membrane enclosed structures. The simplest of those is represented by a sac resulting from the enclosure of a membrane into a sphere: the vesicle. Vesicles made of amphiphilic copolymers are commonly known as polymersomes and are now one of the most important nanotechnological tool for many applications spanning from drug delivery, gene therapy, medical imaging, electronics and nanoreactors. Herein we review the molecular properties, the fabrication processes and the most important applications of polymersomes.

  9. Improving microalgae for biotechnology--From genetics to synthetic biology.

    Science.gov (United States)

    Hlavova, Monika; Turoczy, Zoltan; Bisova, Katerina

    2015-11-01

    Microalgae have traditionally been used in many biotechnological applications, where each new application required a different species or strain expressing the required properties; the challenge therefore is to isolate or develop, characterize and optimize species or strains that can express more than one specific property. In agriculture, breeding of natural variants has been successfully used for centuries to improve production traits in many existing plant and animal species. With the discovery of the concepts of classical genetics, these new ideas have been extensively used in selective breeding. However, many biotechnologically relevant algae do not possess the sexual characteristics required for traditional breeding/crossing, although they can be modified by chemical and physical mutagens. The resulting mutants are not considered as genetically modified organisms (GMOs) and their cultivation is therefore not limited by legislation. On the other hand, mutants prepared by random or specific insertion of foreign DNA are considered to be GMOs. This review will compare the effects of two genetic approaches on model algal species and will summarize their advantages in basic research. Furthermore, we will discuss the potential of mutagenesis to improve microalgae as a biotechnological resource, to accelerate the process from specific strain isolation to growth optimization, and discuss the production of new products. Finally, we will explore the potential of algae in synthetic biology.

  10. Synthetic cannabinoids pharmacokinetics and detection methods in biological matrices.

    Science.gov (United States)

    Castaneto, Marisol S; Wohlfarth, Ariane; Desrosiers, Nathalie A; Hartman, Rebecca L; Gorelick, David A; Huestis, Marilyn A

    2015-05-01

    Synthetic cannabinoids (SC), originally developed as research tools, are now highly abused novel psychoactive substances. We present a comprehensive systematic review covering in vivo and in vitro animal and human pharmacokinetics and analytical methods for identifying SC and their metabolites in biological matrices. Of two main phases of SC research, the first investigated therapeutic applications, and the second abuse-related issues. Administration studies showed high lipophilicity and distribution into brain and fat tissue. Metabolite profiling studies, mostly with human liver microsomes and human hepatocytes, structurally elucidated metabolites and identified suitable SC markers. In general, SC underwent hydroxylation at various molecular sites, defluorination of fluorinated analogs and phase II metabolites were almost exclusively glucuronides. Analytical methods are critical for documenting intake, with different strategies applied to adequately address the continuous emergence of new compounds. Immunoassays have different cross-reactivities for different SC classes, but cannot keep pace with changing analyte targets. Gas chromatography and liquid chromatography mass spectrometry assays - first for a few, then numerous analytes - are available but constrained by reference standard availability, and must be continuously updated and revalidated. In blood and oral fluid, parent compounds are frequently present, albeit in low concentrations; for urinary detection, metabolites must be identified and interpretation is complex due to shared metabolic pathways. A new approach is non-targeted HRMS screening that is more flexible and permits retrospective data analysis. We suggest that streamlined assessment of new SC's pharmacokinetics and advanced HRMS screening provide a promising strategy to maintain relevant assays.

  11. From bricolage to BioBricks™: Synthetic biology and rational design.

    Science.gov (United States)

    Lewens, Tim

    2013-12-01

    Synthetic biology is often described as a project that applies rational design methods to the organic world. Although humans have influenced organic lineages in many ways, it is nonetheless reasonable to place synthetic biology towards one end of a continuum between purely 'blind' processes of organic modification at one extreme, and wholly rational, design-led processes at the other. An example from evolutionary electronics illustrates some of the constraints imposed by the rational design methodology itself. These constraints reinforce the limitations of the synthetic biology ideal, limitations that are often freely acknowledged by synthetic biology's own practitioners. The synthetic biology methodology reflects a series of constraints imposed on finite human designers who wish, as far as is practicable, to communicate with each other and to intervene in nature in reasonably targeted and well-understood ways. This is better understood as indicative of an underlying awareness of human limitations, rather than as expressive of an objectionable impulse to mastery over nature.

  12. Beyond patchwork precaution in the dual-use governance of synthetic biology.

    Science.gov (United States)

    Kelle, Alexander

    2013-09-01

    The emergence of synthetic biology holds the potential of a major breakthrough in the life sciences by transforming biology into a predictive science. The dual-use characteristics of similar breakthroughs during the twentieth century have led to the application of benignly intended research in e.g. virology, bacteriology and aerobiology in offensive biological weapons programmes. Against this background the article raises the question whether the precautionary governance of synthetic biology can aid in preventing this techno-science witnessing the same fate? In order to address this question, this paper proceeds in four steps: it firstly introduces the emerging techno-science of synthetic biology and presents some of its potential beneficial applications. It secondly analyses contributions to the bioethical discourse on synthetic biology as well as precautionary reasoning and its application to life science research in general and synthetic biology more specifically. The paper then identifies manifestations of a moderate precautionary principle in the emerging synthetic biology dual-use governance discourse. Using a dual-use governance matrix as heuristic device to analyse some of the proposed measures, it concludes that the identified measures can best be described as "patchwork precaution" and that a more systematic approach to construct a web of dual-use precaution for synthetic biology is needed in order to guard more effectively against the field's future misuse for harmful applications.

  13. A bottom up approach for engineering catchments through sustainable runoff management

    Science.gov (United States)

    Wilkinson, M.; Quinn, P. F.; Jonczyk, J.; Burke, S.

    2010-12-01

    There is no doubt that our catchments are under great stress. There have been many accounts around the world of severe flood events and water quality issues within channels. As a result of these, ecological habitats in rivers are also under pressure. Within the United Kingdom, all these issues have been identified as key target areas for policy. Traditionally this has been managed by a policy driven top down approach which is usually ineffective. A one ‘size fits all’ attitude often does not work. This paper presents a case study in northern England whereby a bottom up approach is applied to multipurpose managing of catchments at the source (in the order of 1-10km2). This includes simultaneous tackling of water quality, flooding and ecological issues by creating sustainable runoff management solutions such as storage ponds, wetlands, beaver dams and willow riparian features. In order to identify the prevailing issues in a specific catchment, full and transparent stakeholder engagement is essential, with everybody who has a vested interest in the catchment being involved from the beginning. These problems can then be dealt with through the use of a novel catchment management toolkit, which is transferable to similar scale catchments. However, evidence collected on the ground also allows for upscaling of the toolkit. The process gathers the scientific evidence about the effectiveness of existing or new measures, which can really change the catchment functions. Still, we need to get better at communicating the science to policy makers and policy therefore must facilitate a bottom up approach to land and water management. We show a test site for this approach in the Belford burn catchment (6km2), northern England. This catchment has problems with flooding and water quality. Increased sediment loads are affecting the nearby estuary which is an important ecological zone and numerous floods have affected the local village. A catchment engineering toolkit has been

  14. Bottom-up communication. Identifying opportunities and limitations through an exploratory field-based evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, C.; Irvine, K.N. [Institute of Energy and Sustainable Development, De Montfort University, Leicester, LE1 9BH (United Kingdom)

    2013-02-15

    Communication to promote behaviours like energy saving can use significant resources. What is less clear is the comparative value of different approaches available to communicators. While it is generally agreed that 'bottom-up' approaches, where individuals are actively involved rather than passive, are preferable to 'top-down' authority-led projects, there is a dearth of evidence that verifies why this should be. Additionally, while the literature has examined the mechanics of the different approaches, there has been less attention paid to the associated psychological implications. This paper reports on an exploratory comparative study that examined the effects of six distinct communication activities. The activities used different communication approaches, some participative and others more top-down informational. Two theories, from behavioural studies and communication, were used to identify key variables for consideration in this field-based evaluation. The evaluation aimed to assess not just which activity might be most successful, as this has limited generalisability, but to also gain insight into what psychological impacts might contribute to success. Analysis found support for the general hypothesis that bottom-up approaches have more impact on behaviour change than top-down. The study also identified that, in this instance, the difference in reported behaviour across the activities related partly to the extent to which intentions to change behaviour were implemented. One possible explanation for the difference in reported behaviour change across the activities is that a bottom-up approach may offer a supportive environment where participants can discuss progress with like-minded individuals. A further possible explanation is that despite controlling for intention at an individual level, the pre-existence of strong intentions may have an effect on group success. These suggestive findings point toward the critical need for additional and larger-scale studies

  15. Humans strengthen bottom-up effects and weaken trophic cascades in a terrestrial food web.

    Directory of Open Access Journals (Sweden)

    Tyler B Muhly

    Full Text Available Ongoing debate about whether food webs are primarily regulated by predators or by primary plant productivity, cast as top-down and bottom-up effects, respectively, may becoming superfluous. Given that most of the world's ecosystems are human dominated we broadened this dichotomy by considering human effects in a terrestrial food-web. We studied a multiple human-use landscape in southwest Alberta, Canada, as opposed to protected areas where previous terrestrial food-web studies have been conducted. We used structural equation models (SEMs to assess the strength and direction of relationships between the density and distribution of: (1 humans, measured using a density index; (2 wolves (Canis lupus, elk (Cervus elapahus and domestic cattle (Bos taurus, measured using resource selection functions, and; (3 forage quality, quantity and utilization (measured at vegetation sampling plots. Relationships were evaluated by taking advantage of temporal and spatial variation in human density, including day versus night, and two landscapes with the highest and lowest human density in the study area. Here we show that forage-mediated effects of humans had primacy over predator-mediated effects in the food web. In our parsimonious SEM, occurrence of humans was most correlated with occurrence of forage (β = 0.637, p<0.0001. Elk and cattle distribution were correlated with forage (elk day: β = 0.400, p<0.0001; elk night: β = 0.369, p<0.0001; cattle day: β = 0.403, p<0.0001; cattle, night: β = 0.436, p<0.0001, and the distribution of elk or cattle and wolves were positively correlated during daytime (elk: β = 0.293, p <0.0001, cattle: β = 0.303, p<0.0001 and nighttime (elk: β = 0.460, p<0.0001, cattle: β = 0.482, p<0.0001. Our results contrast with research conducted in protected areas that suggested human effects in the food web are primarily predator-mediated. Instead, human influence on vegetation may strengthen

  16. Synthetic biology and therapeutic strategies for the degenerating brain: Synthetic biology approaches can transform classical cell and gene therapies, to provide new cures for neurodegenerative diseases.

    Science.gov (United States)

    Agustín-Pavón, Carmen; Isalan, Mark

    2014-10-01

    Synthetic biology is an emerging engineering discipline that attempts to design and rewire biological components, so as to achieve new functions in a robust and predictable manner. The new tools and strategies provided by synthetic biology have the potential to improve therapeutics for neurodegenerative diseases. In particular, synthetic biology will help design small molecules, proteins, gene networks, and vectors to target disease-related genes. Ultimately, new intelligent delivery systems will provide targeted and sustained therapeutic benefits. New treatments will arise from combining 'protect and repair' strategies: the use of drug treatments, the promotion of neurotrophic factor synthesis, and gene targeting. Going beyond RNAi and artificial transcription factors, site-specific genome modification is likely to play an increasing role, especially with newly available gene editing tools such as CRISPR/Cas9 systems. Taken together, these advances will help develop safe and long-term therapies for many brain diseases in human patients.

  17. Enhancing bottom-up and top-down proteomic measurements with ion mobility separations.

    Science.gov (United States)

    Baker, Erin Shammel; Burnum-Johnson, Kristin E; Ibrahim, Yehia M; Orton, Daniel J; Monroe, Matthew E; Kelly, Ryan T; Moore, Ronald J; Zhang, Xing; Théberge, Roger; Costello, Catherine E; Smith, Richard D

    2015-08-01

    Proteomic measurements with greater throughput, sensitivity, and structural information are essential for improving both in-depth characterization of complex mixtures and targeted studies. While LC separation coupled with MS (LC-MS) measurements have provided information on thousands of proteins in different sample types, the introduction of a separation stage that provides further component resolution and rapid structural information has many benefits in proteomic analyses. Technical advances in ion transmission and data acquisition have made ion mobility separations an opportune technology to be easily and effectively incorporated into LC-MS proteomic measurements for enhancing their information content. Herein, we report on applications illustrating increased sensitivity, throughput, and structural information by utilizing IMS-MS and LC-IMS-MS measurements for both bottom-up and top-down proteomics measurements.

  18. A bottom-up perspective on leadership of collaborative innovation in the public sector

    DEFF Research Database (Denmark)

    Hansen, Jesper Rohr

    . A crucial condition for success is iterative leadership adaptation. In conclusion, the thesis finds that specialized professionals are indeed able to develop politically viable, innovative and collaborative solutions to wicked problems; and that such professionals are able to transform themselves......The thesis investigates how new forms of public leadership can contribute to solving complex problems in today’s welfare societies through innovation. A bottom-up type of leadership for collaborative innovation addressing wicked problems is theorised, displaying a social constructive process...... approach to leadership; a theoretical model emphasises that leadership emerges through social processes of recognition. Leadership is recognised by utilising the uncertainty of a wicked problem and innovation to influence collaborators’ sensemaking processes. The empirical setting is the City of Copenhagen...

  19. Bottom-up synthesis of chiral covalent organic frameworks and their bound capillaries for chiral separation.

    Science.gov (United States)

    Qian, Hai-Long; Yang, Cheng-Xiong; Yan, Xiu-Ping

    2016-07-12

    Covalent organic frameworks (COFs) are a novel class of porous materials, and offer great potential for various applications. However, the applications of COFs in chiral separation and chiral catalysis are largely underexplored due to the very limited chiral COFs available and their challenging synthesis. Here we show a bottom-up strategy to construct chiral COFs and an in situ growth approach to fabricate chiral COF-bound capillary columns for chiral gas chromatography. We incorporate the chiral centres into one of the organic ligands for the synthesis of the chiral COFs. We subsequently in situ prepare the COF-bound capillary columns. The prepared chiral COFs and their bound capillary columns give high resolution for the separation of enantiomers with excellent repeatability and reproducibility. The proposed strategy provides a promising platform for the synthesis of chiral COFs and their chiral separation application.

  20. Bottom-Up Meets Top-Down: Patchy Hybrid Nonwovens as an Efficient Catalysis Platform.

    Science.gov (United States)

    Schöbel, Judith; Burgard, Matthias; Hils, Christian; Dersch, Roland; Dulle, Martin; Volk, Kirsten; Karg, Matthias; Greiner, Andreas; Schmalz, Holger

    2017-01-02

    Heterogeneous catalysis with supported nanoparticles (NPs) is a highly active field of research. However, the efficient stabilization of NPs without deteriorating their catalytic activity is challenging. By combining top-down (coaxial electrospinning) and bottom-up (crystallization-driven self-assembly) approaches, we prepared patchy nonwovens with functional, nanometer-sized patches on the surface. These patches can selectively bind and efficiently stabilize gold nanoparticles (AuNPs). The use of these AuNP-loaded patchy nonwovens in the alcoholysis of dimethylphenylsilane led to full conversion under comparably mild conditions and in short reaction times. The absence of gold leaching or a slowing down of the reaction even after ten subsequent cycles manifests the excellent reusability of this catalyst system. The flexibility of the presented approach allows for easy transfer to other nonwoven supports and catalytically active NPs, which promises broad applicability.

  1. Bottom-up fabrication of zwitterionic polymer brushes on intraocular lens for improved biocompatibility

    Science.gov (United States)

    Han, Yuemei; Xu, Xu; Tang, Junmei; Shen, Chenghui; Lin, Quankui; Chen, Hao

    2017-01-01

    Intraocular lens (IOL) is an efficient implantable device commonly used for treating cataracts. However, bioadhesion of bacteria or residual lens epithelial cells on the IOL surface after surgery causes postoperative complications, such as endophthalmitis or posterior capsular opacification, and leads to loss of sight again. In the present study, zwitterionic polymer brushes were fabricated on the IOL surface via bottom-up grafting procedure. The attenuated total reflection-Fourier transform infrared and contact angle measurements indicated successful surface modification, as well as excellent hydrophilicity. The coating of hydrophilic zwitterionic polymer effectively decreased the bioadhesion of lens epithelial cells or bacteria. In vivo intraocular implantation results showed good in vivo biocompatibility of zwitterionic IOL and its effectiveness against postoperative complications. PMID:28053528

  2. Bottom-up and top-down controls on picoplankton in the East China Sea

    Science.gov (United States)

    Guo, C.; Liu, H.; Zheng, L.; Song, S.; Chen, B.; Huang, B.

    2013-05-01

    Dynamics of picoplankton population distribution in the East China Sea (ECS), a marginal sea in the western North Pacific Ocean, were studied during two "CHOICE-C" cruises in August 2009 (summer) and January 2010 (winter). Dilution experiments were conducted during the two cruises to investigate the growth and grazing among picophytoplantkon populations. Picoplankton accounted for an average of ~29% (2% to 88%) of community carbon biomass in the ECS on average, with lower percentages in plume region than in shelf and kuroshio regions. Averaged growth rates (μ) for Prochlorococcus (Pro), Synechococcus (Syn) and picoeukaryotes (peuk) were 0.36, 0.89, 0.90 d-1, respectively, in summer, and 0.46, 0.58, 0.56 d-1, respectively, in winter. Seawater salinity and nutrient availability exerted significant controls on picoplankton growth rate. Averaged grazing mortality (m) were 0.46, 0.63, 0.68 d-1 in summer, and 0.22, 0.32, 0.22 d-1 in winter for Pro, Syn and peuk respectively. The three populations demonstrated very different distribution patterns regionally and seasonally affected by both bottom-up and top-down controls. In summer, Pro, Syn and peuk were dominant in Kuroshio, transitional and plume regions respectively. Protist grazing consumed 84%, 78%, 73% and 45%, 47%, 57% of production for Pro, Syn and peuk in summer and winter respectively, suggesting more significant top-down controls in summer. In winter, all three populations tended to distribute in offshore regions, although the area of coverage was different (peuk > Syn > Pro). Bottom-up factors can explain as much as 91.5%, 82% and 81.2% of Pro, Syn and peuk abundance variance in winter, while only 59.1% and 43.7% for Pro and peuk in summer. Regionally, Yangtze River discharge plays a significant role in affecting the intensity of top-down control, indicated by significant and negative association between salinity and grazing mortality of all three populations and higher grazing mortality to growth rate ratio

  3. Bottom-up and top-down controls on picoplankton in the East China Sea

    Directory of Open Access Journals (Sweden)

    C. Guo

    2013-05-01

    Full Text Available Dynamics of picoplankton population distribution in the East China Sea (ECS, a marginal sea in the western North Pacific Ocean, were studied during two "CHOICE-C" cruises in August 2009 (summer and January 2010 (winter. Dilution experiments were conducted during the two cruises to investigate the growth and grazing among picophytoplantkon populations. Picoplankton accounted for an average of ~29% (2% to 88% of community carbon biomass in the ECS on average, with lower percentages in plume region than in shelf and kuroshio regions. Averaged growth rates (μ for Prochlorococcus (Pro, Synechococcus (Syn and picoeukaryotes (peuk were 0.36, 0.89, 0.90 d−1, respectively, in summer, and 0.46, 0.58, 0.56 d−1, respectively, in winter. Seawater salinity and nutrient availability exerted significant controls on picoplankton growth rate. Averaged grazing mortality (m were 0.46, 0.63, 0.68 d−1 in summer, and 0.22, 0.32, 0.22 d−1 in winter for Pro, Syn and peuk respectively. The three populations demonstrated very different distribution patterns regionally and seasonally affected by both bottom-up and top-down controls. In summer, Pro, Syn and peuk were dominant in Kuroshio, transitional and plume regions respectively. Protist grazing consumed 84%, 78%, 73% and 45%, 47%, 57% of production for Pro, Syn and peuk in summer and winter respectively, suggesting more significant top-down controls in summer. In winter, all three populations tended to distribute in offshore regions, although the area of coverage was different (peuk > Syn > Pro. Bottom-up factors can explain as much as 91.5%, 82% and 81.2% of Pro, Syn and peuk abundance variance in winter, while only 59.1% and 43.7% for Pro and peuk in summer. Regionally, Yangtze River discharge plays a significant role in affecting the intensity of top-down control, indicated by significant and negative association between salinity and grazing mortality of all three populations and higher grazing mortality to

  4. Collective Inclusioning: A Grounded Theory of a Bottom-Up Approach to Innovation and Leading

    Directory of Open Access Journals (Sweden)

    Michal Lysek

    2016-06-01

    Full Text Available This paper is a grounded theory study of how leaders (e.g., entrepreneurs, managers, etc. engage people in challenging undertakings (e.g., innovation that require everyone’s commitment to such a degree that they would have to go beyond what could be reasonably expected in order to succeed. Company leaders sometimes wonder why their employees no longer show the same responsibility towards their work, and why they are more concerned with internal politics than solving customer problems. It is because company leaders no longer apply collective inclusioning to the same extent as they did in the past. Collective inclusioning can be applied in four ways by convincing, afinitizing, goal congruencing, and engaging. It can lead to fostering strong units of people for taking on challenging undertakings. Collective inclusioning is a complementing theory to other strategic management and leading theories. It offers a new perspective on how to implement a bottom-up approach to innovation.

  5. Bottom-up synthesis of chiral covalent organic frameworks and their bound capillaries for chiral separation

    Science.gov (United States)

    Qian, Hai-Long; Yang, Cheng-Xiong; Yan, Xiu-Ping

    2016-07-01

    Covalent organic frameworks (COFs) are a novel class of porous materials, and offer great potential for various applications. However, the applications of COFs in chiral separation and chiral catalysis are largely underexplored due to the very limited chiral COFs available and their challenging synthesis. Here we show a bottom-up strategy to construct chiral COFs and an in situ growth approach to fabricate chiral COF-bound capillary columns for chiral gas chromatography. We incorporate the chiral centres into one of the organic ligands for the synthesis of the chiral COFs. We subsequently in situ prepare the COF-bound capillary columns. The prepared chiral COFs and their bound capillary columns give high resolution for the separation of enantiomers with excellent repeatability and reproducibility. The proposed strategy provides a promising platform for the synthesis of chiral COFs and their chiral separation application.

  6. Differential recolonization of Atlantic intertidal habitats after disturbance reveals potential bottom-up community regulation

    Science.gov (United States)

    Petzold, Willy; Scrosati, Ricardo A.

    2014-01-01

    In the spring of 2014, abundant sea ice that drifted out of the Gulf of St. Lawrence caused extensive disturbance in rocky intertidal habitats on the northern Atlantic coast of mainland Nova Scotia, Canada. To monitor recovery of intertidal communities, we surveyed two wave-exposed locations in the early summer of 2014. Barnacle recruitment and the abundance of predatory dogwhelks were low at one location (Tor Bay Provincial Park) but more than 20 times higher at the other location (Whitehead). Satellite data indicated that the abundance of coastal phytoplankton (the main food source for barnacle larvae) was consistently higher at Whitehead just before the barnacle recruitment season, when barnacle larvae were in the water column. These observations suggest bottom-up forcing of intertidal communities. The underlying mechanisms and their intensity along the NW Atlantic coast could be investigated through studies done at local and regional scales. PMID:26213609

  7. Ion mobility tandem mass spectrometry enhances performance of bottom-up proteomics.

    Science.gov (United States)

    Helm, Dominic; Vissers, Johannes P C; Hughes, Christopher J; Hahne, Hannes; Ruprecht, Benjamin; Pachl, Fiona; Grzyb, Arkadiusz; Richardson, Keith; Wildgoose, Jason; Maier, Stefan K; Marx, Harald; Wilhelm, Mathias; Becher, Isabelle; Lemeer, Simone; Bantscheff, Marcus; Langridge, James I; Kuster, Bernhard

    2014-12-01

    One of the limiting factors in determining the sensitivity of tandem mass spectrometry using hybrid quadrupole orthogonal acceleration time-of-flight instruments is the duty cycle of the orthogonal ion injection system. As a consequence, only a fraction of the generated fragment ion beam is collected by the time-of-flight analyzer. Here we describe a method utilizing postfragmentation ion mobility spectrometry of peptide fragment ions in conjunction with mobility time synchronized orthogonal ion injection leading to a substantially improved duty cycle and a concomitant improvement in sensitivity of up to 10-fold for bottom-up proteomic experiments. This enabled the identification of 7500 human proteins within 1 day and 8600 phosphorylation sites within 5 h of LC-MS/MS time. The method also proved powerful for multiplexed quantification experiments using tandem mass tags exemplified by the chemoproteomic interaction analysis of histone deacetylases with Trichostatin A.

  8. Strain Response of Hot-Mix Asphalt Overlays for Bottom-Up Reflective Cracking

    CERN Document Server

    Ghauch, Ziad G

    2011-01-01

    This paper examines the strain response of typical HMA overlays above jointed PCC slabs prone to bottom-up reflective cracking. The occurrence of reflective cracking under the combined effect of traffic and environmental loading significantly reduces the design life of the HMA overlays and can lead to its premature failure. In this context, viscoelastic material properties combined with cyclic vehicle loadings and pavement temperature distribution were implemented in a series of FE models in order to study the evolution of horizontal tensile and shear strains at the bottom of the HMA overlay. The effect of several design parameters, such as subbase and subgrade moduli, vehicle speed, overlay thickness, and temperature condition, on the horizontal and shear strain response was investigated. Results obtained show that the rate of horizontal and shear strain increase at the bottom of the HMA overlay drop with higher vehicle speed, higher subgrade modulus, and higher subbase modulus. Moreover, the rate of horizon...

  9. Unsupervised Tattoo Segmentation Combining Bottom-Up and Top-Down Cues

    Energy Technology Data Exchange (ETDEWEB)

    Allen, Josef D [ORNL

    2011-01-01

    Tattoo segmentation is challenging due to the complexity and large variance in tattoo structures. We have developed a segmentation algorithm for nding tattoos in an image. Our basic idea is split-merge: split each tattoo image into clusters through a bottom-up process, learn to merge the clusters containing skin and then distinguish tattoo from the other skin via top-down prior in the image itself. Tattoo segmentation with unknown number of clusters is transferred to a gure-ground segmentation. We have applied our segmentation algorithm on a tattoo dataset and the results have shown that our tattoo segmentation system is e cient and suitable for further tattoo classi cation and retrieval purpose.

  10. The ideological divide and climate change opinion: "top-down" and "bottom-up" approaches.

    Science.gov (United States)

    Jacquet, Jennifer; Dietrich, Monica; Jost, John T

    2014-01-01

    The United States wields disproportionate global influence in terms of carbon dioxide emissions and international climate policy. This makes it an especially important context in which to examine the interplay among social, psychological, and political factors in shaping attitudes and behaviors related to climate change. In this article, we review the emerging literature addressing the liberal-conservative divide in the U.S. with respect to thought, communication, and action concerning climate change. Because of its theoretical and practical significance, we focus on the motivational basis for skepticism and inaction on the part of some, including "top-down" institutional forces, such as corporate strategy, and "bottom-up" psychological factors, such as ego, group, and system justification. Although more research is needed to elucidate fully the social, cognitive, and motivational bases of environmental attitudes and behavior, a great deal has been learned in just a few years by focusing on specific ideological factors in addition to general psychological principles.

  11. Differential recolonization of Atlantic intertidal habitats after disturbance reveals potential bottom-up community regulation.

    Science.gov (United States)

    Petzold, Willy; Scrosati, Ricardo A

    2014-01-01

    In the spring of 2014, abundant sea ice that drifted out of the Gulf of St. Lawrence caused extensive disturbance in rocky intertidal habitats on the northern Atlantic coast of mainland Nova Scotia, Canada. To monitor recovery of intertidal communities, we surveyed two wave-exposed locations in the early summer of 2014. Barnacle recruitment and the abundance of predatory dogwhelks were low at one location (Tor Bay Provincial Park) but more than 20 times higher at the other location (Whitehead). Satellite data indicated that the abundance of coastal phytoplankton (the main food source for barnacle larvae) was consistently higher at Whitehead just before the barnacle recruitment season, when barnacle larvae were in the water column. These observations suggest bottom-up forcing of intertidal communities. The underlying mechanisms and their intensity along the NW Atlantic coast could be investigated through studies done at local and regional scales.

  12. Bottom-up effects of a no-take zone on endangered penguin demographics.

    Science.gov (United States)

    Sherley, Richard B; Winker, Henning; Altwegg, Res; van der Lingen, Carl D; Votier, Stephen C; Crawford, Robert J M

    2015-07-01

    Marine no-take zones can have positive impacts for target species and are increasingly important management tools. However, whether they indirectly benefit higher order predators remains unclear. The endangered African penguin (Spheniscus demersus) depends on commercially exploited forage fish. We examined how chick survival responded to an experimental 3-year fishery closure around Robben Island, South Africa, controlling for variation in prey biomass and fishery catches. Chick survival increased by 18% when the closure was initiated, which alone led to a predicted 27% higher population compared with continued fishing. However, the modelled population continued to decline, probably because of high adult mortality linked to poor prey availability over larger spatial scales. Our results illustrate that small no-take zones can have bottom-up benefits for highly mobile marine predators, but are only one component of holistic, ecosystem-based management regimes.

  13. Comparing top-down and bottom-up costing approaches for economic evaluation within social welfare.

    Science.gov (United States)

    Olsson, Tina M

    2011-10-01

    This study compares two approaches to the estimation of social welfare intervention costs: one "top-down" and the other "bottom-up" for a group of social welfare clients with severe problem behavior participating in a randomized trial. Intervention costs ranging over a two-year period were compared by intervention category (foster care placement, institutional placement, mentorship services, individual support services and structured support services), estimation method (price, micro costing, average cost) and treatment group (intervention, control). Analyses are based upon 2007 costs for 156 individuals receiving 404 interventions. Overall, both approaches were found to produce reliable estimates of intervention costs at the group level but not at the individual level. As choice of approach can greatly impact the estimate of mean difference, adjustment based on estimation approach should be incorporated into sensitivity analyses. Analysts must take care in assessing the purpose and perspective of the analysis when choosing a costing approach for use within economic evaluation.

  14. Bottom-Up Cost Analysis of a High Concentration PV Module; NREL (National Renewable Energy Laboratory)

    Energy Technology Data Exchange (ETDEWEB)

    Horowitz, K.; Woodhouse, M.; Lee, H.; Smestad, G.

    2015-04-13

    We present a bottom-up model of III-V multi-junction cells, as well as a high concentration PV (HCPV) module. We calculate $0.65/Wp(DC) manufacturing costs for our model HCPV module design with today’s capabilities, and find that reducing cell costs and increasing module efficiency offer the promising pathways for future cost reductions. Cell costs could be significantly reduced via an increase in manufacturing scale, substrate reuse, and improved manufacturing yields. We also identify several other significant drivers of HCPV module costs, including the Fresnel lens primary optic, module housing, thermal management, and the receiver board. These costs could potentially be lowered by employing innovative module designs.

  15. Integration of top-down and bottom-up information for audio organization and retrieval

    DEFF Research Database (Denmark)

    Jensen, Bjørn Sand

    The increasing availability of digital audio and music calls for methods and systems to analyse and organize these digital objects. This thesis investigates three elements related to such systems focusing on the ability to represent and elicit the user's view on the multimedia object and the system...... sources based on latent Dirichlet allocation (LDA). The model is used to integrate bottom-up features (reflecting timbre, loudness, tempo and chroma), meta-data aspects (lyrics) and top-down aspects, namely user generated open vocabulary tags. The model and representation is evaluated on the auxiliary...... task of genre and style classification. Eliciting the subjective representation and opinion of users is an important aspect in building personalized systems. The thesis contributes with a setup for modelling and elicitation of preference and other cognitive aspects with focus on audio applications...

  16. Highly directional bottom-up 3D nanoantenna for visible light.

    Science.gov (United States)

    Tong, L; Pakizeh, T; Feuz, L; Dmitriev, A

    2013-01-01

    Controlling light at the nanoscale is of fundamental importance and is essential for applications ranging from optical sensing and metrology to information processing, communications, and quantum optics. Considerable efforts are currently directed towards optical nanoantennas that directionally convert light into strongly localized energy and vice versa. Here we present highly directional 3D nanoantenna operating with visible light. We demonstrate a simple bottom-up approach to produce macroscopic arrays of such nanoantennas and present a way to address their functionality via interaction with quantum dots (QDs), properly embedded in the structure of the nanoantenna. The ease and accessibility of this structurally robust optical antenna device prompts its use as an affordable test bed for concepts in nano-optics and nanophotonics applications.

  17. Bottom-Up Engineering of Well-Defined 3D Microtissues Using Microplatforms and Biomedical Applications.

    Science.gov (United States)

    Lee, Geon Hui; Lee, Jae Seo; Wang, Xiaohong; Lee, Sang Hoon

    2016-01-07

    During the last decades, the engineering of well-defined 3D tissues has attracted great attention because it provides in vivo mimicking environment and can be a building block for the engineering of bioartificial organs. In this Review, diverse engineering methods of 3D tissues using microscale devices are introduced. Recent progress of microtechnologies has enabled the development of microplatforms for bottom-up assembly of diverse shaped 3D tissues consisting of various cells. Micro hanging-drop plates, microfluidic chips, and arrayed microwells are the typical examples. The encapsulation of cells in hydrogel microspheres and microfibers allows the engineering of 3D microtissues with diverse shapes. Applications of 3D microtissues in biomedical fields are described, and the future direction of microplatform-based engineering of 3D micro-tissues is discussed.

  18. Implementing collaborative improvement - top-down, bottom-up or both?

    DEFF Research Database (Denmark)

    Kaltoft, Rasmus; Boer, Harry; Caniato, Federico

    2007-01-01

    , the study identifies three different implementation approaches. The bottom-up learning-by-doing approach starts at a practical level, with simple improvement activities, and aims at gradually developing a wide range of CoI knowledge, skills and initiatives. The top-down directive approach starts......The research presented in this article was aimed at increasing the current understanding of the process of developing Collaborative Improvement (CoI) in Extended Manufacturing Enterprises (EME). Based on action research in three EMEs involving a total of 13 companies from five European countries...... with aligning the partners' CoI objectives and an assessment of their collaboration and CoI maturity in order to provide a common platform before actually starting improvement activities. The laissez-faire approach builds on shared goals/vision, meetings on equal terms and joint work, in a non-directive and non...

  19. Reconciling Top Down and Bottom Up Approaches to Understand Land Carbon Cycle Variability

    Science.gov (United States)

    Collatz, G. J.; Gurney, K. R.; Denning, A. S.; Randerson, J. T.; van der Werf, G. R.

    2004-12-01

    Cycle Variability Two fundamentally different approaches for estimating global carbon sources and sinks have been used over the past 15 years. The so-called "Top-down" approach involves analysis of atmospheric composition and often includes inversions of atmospheric transport. Bottom-up approaches, on the other hand, involve using carbon cycle process models driven by various observational data. Reconciling the results of these two approaches can provide powerful constraints on each but is challenging because of the large uncertainties in atmospheric measurements and transport and in our understanding of the processes controlling biogeochemical cycling of carbon. Recently, the Atmospheric Carbon Inversion Intercomparison (TransCom 3) completed mean seasonal cycle and interannual variability inversions using 12 transport models. Their results include predictions of biogeochemically driven net carbon fluxes with associated uncertainties for the globe divided into 22 regions, half of which are land regions. The cyclo-stationary inversions predicted the mean seasonal cycle as well as the mean sink/source of each region. The interannual inversions predicted the interannual variability in the sources and sinks for each region between 1980 and 2000. This study describes an analysis of the processes controlling biogeochemically driven net carbon fluxes over the seasonal cycle for each of the Transcom land regions. The processes considered are those included in the CASA biogeochemical model. The seasonally variable model inputs include NDVI, temperature, precipitation and solar radiation and burned area. The contributions of NPP, heterotrophic respiration and fire season to the seasonal cycle are evaluated for each of the 11 TransCom 3 land regions. We prescribed plausible scenarios in the biogeochemical model to evaluate the mechanisms responsible for the size and seasonality of the mean annual carbon sinks reported by TransCom 3. Initial results will also be presented for

  20. Bottom-Up Energy Analysis System (BUENAS). An international appliance efficiency policy tool

    Energy Technology Data Exchange (ETDEWEB)

    McNeil, M.A.; Letschert, V.E.; De la Rue du Can, S.; Ke, Jing [Lawrence Berkeley National Laboratory LBNL, 1 Cyclotron Rd, Berkeley, CA (United States)

    2013-02-15

    The Bottom-Up Energy Analysis System (BUENAS) calculates potential energy and greenhouse gas emission impacts of efficiency policies for lighting, heating, ventilation, and air conditioning, appliances, and industrial equipment through 2030. The model includes 16 end use categories and covers 11 individual countries plus the European Union. BUENAS is a bottom-up stock accounting model that predicts energy consumption for each type of equipment in each country according to engineering-based estimates of annual unit energy consumption, scaled by projections of equipment stock. Energy demand in each scenario is determined by equipment stock, usage, intensity, and efficiency. When available, BUENAS uses sales forecasts taken from country studies to project equipment stock. Otherwise, BUENAS uses an econometric model of household appliance uptake developed by the authors. Once the business as usual scenario is established, a high-efficiency policy scenario is constructed that includes an improvement in the efficiency of equipment installed in 2015 or later. Policy case efficiency targets represent current 'best practice' and include standards already established in a major economy or well-defined levels known to enjoy a significant market share in a major economy. BUENAS calculates energy savings according to the difference in energy demand in the two scenarios. Greenhouse gas emission mitigation is then calculated using a forecast of electricity carbon factor. We find that mitigation of 1075 mt annual CO2 emissions is possible by 2030 from adopting current best practices of appliance efficiency policies. This represents a 17 % reduction in emissions in the business as usual case in that year.

  1. Achieving social-ecological fit through bottom-up collaborative governance: an empirical investigation

    Directory of Open Access Journals (Sweden)

    Angela M. Guerrero

    2015-12-01

    Full Text Available Significant benefits can arise from collaborative forms of governance that foster self-organization and flexibility. Likewise, governance systems that fit with the extent and complexity of the system under management are considered essential to our ability to solve environmental problems. However, from an empirical perspective the fundamental question of whether self-organized (bottom-up collaborative forms of governance are able to accomplish adequate fit is unresolved. We used new theory and methodological approaches underpinned by interdisciplinary network analysis to address this gap by investigating three governance challenges that relate to the problem of fit: shared management of ecological resources, management of interconnected ecological resources, and cross-scale management. We first identified a set of social-ecological network configurations that represent the hypothesized ways in which collaborative arrangements can contribute to addressing these challenges. Using social and ecological data from a large-scale biodiversity conservation initiative in Australia, we empirically determined how well the observed patterns of stakeholder interactions reflect these network configurations. We found that stakeholders collaborate to manage individual parcels of native vegetation, but not for the management of interconnected parcels. In addition, our data show that the collaborative arrangements enable management across different scales (local, regional, supraregional. Our study provides empirical support for the ability of collaborative forms of governance to address the problem of fit, but also suggests that in some cases the establishment of bottom-up collaborative arrangements would likely benefit from specific guidance to facilitate the establishment of collaborations that better align with the ways ecological resources are interconnected across the landscape. In our case study region, this would improve the capacity of stakeholders to

  2. A bottom-up approach of stochastic demand allocation in water quality modelling

    Directory of Open Access Journals (Sweden)

    E. J. M. Blokker

    2010-04-01

    Full Text Available An "all pipes" hydraulic model of a drinking water distribution system was constructed with two types of demand allocations. One is constructed with the conventional top-down approach, i.e. a demand multiplier pattern from the booster station is allocated to all demand nodes with a correction factor to account for the average water demand on that node. The other is constructed with a bottom-up approach of demand allocation, i.e., each individual home is represented by one demand node with its own stochastic water demand pattern. This was done for a drinking water distribution system of approximately 10 km of mains and serving ca. 1000 homes. The system was tested in a real life situation.

    The stochastic water demand patterns were constructed with the end-use model SIMDEUM on a per second basis and per individual home. Before applying the demand patterns in a network model, some temporal aggregation was done. The flow entering the test area was measured and a tracer test with sodium chloride was performed to determine travel times. The two models were validated on the total sum of demands and on travel times.

    The study showed that the bottom-up approach leads to realistic water demand patterns and travel times, without the need for any flow measurements or calibration. In the periphery of the drinking water distribution system it is not possible to calibrate models on pressure, because head losses are too low. The study shows that in the periphery it is also difficult to calibrate on water quality (e.g. with tracer measurements, as a consequence of the high variability between days. The stochastic approach of hydraulic modelling gives insight into the variability of travel times as an added feature beyond the conventional way of modelling.

  3. Preferential effect of isoflurane on top-down versus bottom-up pathways in sensory cortex

    Directory of Open Access Journals (Sweden)

    Aeyal eRaz

    2014-10-01

    Full Text Available The mechanism of loss of consciousness (LOC under anesthesia is unknown. Because consciousness depends on activity in the cortico-thalamic network, anesthetic actions on this network are likely critical for LOC. Competing theories stress the importance of anesthetic actions on bottom-up ‘core’ thalamo-cortical (TC versus top-down cortico-cortical (CC and matrix TC connections. We tested these models using laminar recordings in rat auditory cortex in-vivo and murine brain slices. We selectively activated bottom-up vs. top-down afferent pathways using sensory stimuli in vivo and electrical stimulation in brain slices, and compared effects of isoflurane on responses evoked via the two pathways. Auditory stimuli in vivo and core TC afferent stimulation in brain slices evoked short latency current sinks in middle layers, consistent with activation of core TC afferents. By contrast, visual stimuli in vivo and stimulation of CC and matrix TC afferents in brain slices evoked responses mainly in superficial and deep layers, consistent with projection patterns of top-down afferents that carry visual information to auditory cortex. Responses to auditory stimuli in vivo and core TC afferents in brain slices were significantly less affected by isoflurane compared to responses triggered by visual stimuli in vivo and CC/matrix TC afferents in slices. At a just-hypnotic dose in vivo, auditory responses were enhanced by isoflurane, whereas visual responses were dramatically reduced. At a comparable concentration in slices, isoflurane suppressed both core TC and CC/matrix TC responses, but the effect on the latter responses was far greater than on core TC responses, indicating that at least part of the differential effects observed in vivo were due to local actions of isoflurane in auditory cortex. These data support a model in which disruption of top-down connectivity contributes to anesthesia-induced LOC, and have implications for understanding the neural

  4. Life by design: Philosophical perspectives on synthetic biology

    Directory of Open Access Journals (Sweden)

    Bensaude Vincent Bernadette

    2015-01-01

    This paper outlines a number of distinctive features of this emerging field in the constellation of bionanotechnologies. It then insists on the variety of research agendas and strategies gathered under the umbrella “synthetic biology”. While redesigning life is the central goal, synthetic biologists do not develop a uniform view of living organisms.

  5. A comparative 'bottom up' proteomics strategy for the site-specific identification and quantification of protein modifications by electrophilic lipids.

    Science.gov (United States)

    Han, Bingnan; Hare, Michael; Wickramasekara, Samanthi; Fang, Yi; Maier, Claudia S

    2012-10-22

    We report a mass spectrometry-based comparative "bottom up" proteomics approach that combines d(0)/d(4)-succinic anhydride labeling with commercially available hydrazine (Hz)-functionalized beads (Affi-gel Hz beads) for detection, identification and relative quantification of site-specific oxylipid modifications in biological matrices. We evaluated and applied this robust and simple method for the quantitative analysis of oxylipid protein conjugates in cardiac mitochondrial proteome samples isolated from 3- and 24-month-old rat hearts. The use of d(0)/d(4)-succinic anhydride labeling, Hz-bead based affinity enrichment, nanoLC fractionation and MALDI-ToF/ToF tandem mass spectrometry yielded relative quantification of oxylipid conjugates with residue-specific modification information. Conjugation of acrolein (ACR), 4-hydroxy-2-hexenal (HHE), 4-hydroxy-2-nonenal (HNE) and 4-oxo-2-noneal (ONE) to cysteine, histidine and lysine residues were identified. HHE conjugates were the predominant subset of Michael-type adducts detected in this study. The HHE conjugates showed higher levels in mitochondrial preparations from young heart congruent with previous findings by others that the n-3/n-6 PUFA ratio is higher in young heart mitochondrial membranes. Although this study focuses on protein adducts of reactive oxylipids, the method might be equally applicable to protein carbonyl modifications caused by metal catalyzed oxidation reactions.

  6. A bottom-up approach to derive the closure relation for modelling hydrological fluxes at the watershed scale

    Science.gov (United States)

    Vannametee, Ekkamol; Karssenberg, Derek; Hendriks, Martin; Bierkens, Marc

    2014-05-01

    Physically-based hydrological modelling could be considered as an ideal approach for predictions in ungauged basins because observable catchment characteristics can be used to parameterize the model, avoiding model calibration using discharge data, which are not available. Lumped physically-based modelling at the watershed scale is possible with the Representative Elementary Watershed (REW) approach. A key to successful application of this approach is to find a reliable way of developing closure relations to calculate fluxes from different hydrological compartments in the REWs. Here, we present a bottom-up approach as a generic framework to identify the closure relations for particular hydrological processes that are scale-independent and can be directly parameterized using the local-scale observable REW characteristics. The approach is illustrated using the Hortonian runoff as an example. This approach starts from developing a physically-based high-resolution model describing the Hortonian runoff mechanism based on physically-based infiltration theory and runoff generation processes at a local scale. This physically-based model is used to generate a synthetic discharge data set of hypothetical rainfall events and HRUs (6×105 scenarios) as a surrogate for real-world observations. The Hortonian runoff closure relation is developed as a lumped process-based model, consisting of the Green-Ampt equation, a time-lagged linear reservoir model, and three scale-transfer parameters representing the processes within REWs. These scale-transfer parameters are identified by calibrating the closure relations against the synthetic discharge data set for each scenario run, which are, in turn, empirically related to their corresponding observable REW properties and rainstorm characteristics. This results in a parameter library, which allows direct estimation of scaling parameter for arbitrary REWs based on their local-scale observable properties and rainfall characteristics

  7. 2nd Congress on applied synthetic biology in Europe (Málaga, Spain, November 2013).

    Science.gov (United States)

    Vetter, Beatrice V; Pantidos, Nikolaos; Edmundson, Matthew

    2014-05-25

    The second meeting organised by the EFB on the advances of applied synthetic biology in Europe was held in Málaga, Spain in November 2013. The potential for the broad application of synthetic biology was reflected in the five sessions of this meeting: synthetic biology for healthcare applications, tools and technologies for synthetic biology, production of recombinant proteins, synthetic plant biology, and biofuels and other small molecules. Outcomes from the meeting were that synthetic biology offers methods for rapid development of new strains that will result in decreased production costs, sustainable chemical production and new medical applications. Additionally, it also introduced novel ways to produce sustainable energy and biofuels, to find new alternatives for bioremediation and resource recovery, and environmentally friendly foodstuff production. All the above-mentioned advances could enable biotechnology to solve some of the major problems of Society. However, while there are still limitations in terms of lacking tools, standardisation and suitable host organisms, this meeting has laid a foundation providing cutting-edge concepts and techniques to ultimately convert the potential of synthetic biology into practice.

  8. Communicating Synthetic Biology: from the lab via the media to the broader public.

    Science.gov (United States)

    Kronberger, Nicole; Holtz, Peter; Kerbe, Wolfgang; Strasser, Ewald; Wagner, Wolfgang

    2009-12-01

    We present insights from a study on communicating Synthetic Biology conducted in 2008. Scientists were invited to write press releases on their work; the resulting texts were passed on to four journalists from major Austrian newspapers and magazines. The journalists in turn wrote articles that were used as stimulus material for eight group discussions with select members of the Austrian public. The results show that, from the lab via the media to the general public, communication is characterized by two important tendencies: first, communication becomes increasingly focused on concrete applications of Synthetic Biology; and second, biotechnology represents an important benchmark against which Synthetic Biology is being evaluated.

  9. Recent progress in development of synthetic biology platforms and metabolic engineering of Corynebacterium glutamicum.

    Science.gov (United States)

    Woo, Han Min; Park, Jin-Byung

    2014-06-20

    The paradigm of synthetic biology has been evolving, along with relevant engineering, to achieve designed bio-systems. Synthetic biology has reached the point where it is possible to develop microbial strains to produce desired chemicals. Recent advances in this field have promoted metabolic engineering of Corynebacterium glutamicum as an amino-acid producer for use in intelligent microbial-cell factories. Here, we review recent advances that address C. glutamicum as a potential model organism for synthetic biology, and evaluate their industrial applications. Finally, we highlight the perspective of developing C. glutamicum as a step toward advanced microbial-cell factories that could produce valuable chemicals from renewable resources.

  10. A Powerful Toolkit for Synthetic Biology: Over 3.8 Billion Years of Evolution

    Science.gov (United States)

    Rothschild, Lynn J.

    2010-01-01

    The combination of evolutionary with engineering principles will enhance synthetic biology. Conversely, synthetic biology has the potential to enrich evolutionary biology by explaining why some adaptive space is empty, on Earth or elsewhere. Synthetic biology, the design and construction of artificial biological systems, substitutes bio-engineering for evolution, which is seen as an obstacle. But because evolution has produced the complexity and diversity of life, it provides a proven toolkit of genetic materials and principles available to synthetic biology. Evolution operates on the population level, with the populations composed of unique individuals that are historical entities. The source of genetic novelty includes mutation, gene regulation, sex, symbiosis, and interspecies gene transfer. At a phenotypic level, variation derives from regulatory control, replication and diversification of components, compartmentalization, sexual selection and speciation, among others. Variation is limited by physical constraints such as diffusion, and chemical constraints such as reaction rates and membrane fluidity. While some of these tools of evolution are currently in use in synthetic biology, all ought to be examined for utility. A hybrid approach of synthetic biology coupled with fine-tuning through evolution is suggested

  11. Biochemistry-directed hollow porous microspheres: bottom-up self-assembled polyanion-based cathodes for sodium ion batteries

    Science.gov (United States)

    Lin, Bo; Li, Qiufeng; Liu, Baodong; Zhang, Sen; Deng, Chao

    2016-04-01

    Biochemistry-directed synthesis of functional nanomaterials has attracted great interest in energy storage, catalysis and other applications. The unique ability of biological systems to guide molecule self-assembling facilitates the construction of distinctive architectures with desirable physicochemical characteristics. Herein, we report a biochemistry-directed ``bottom-up'' approach to construct hollow porous microspheres of polyanion materials for sodium ion batteries. Two kinds of polyanions, i.e. Na3V2(PO4)3 and Na3.12Fe2.44(P2O7)2, are employed as cases in this study. The microalgae cell realizes the formation of a spherical ``bottom'' bio-precursor. Its tiny core is subjected to destruction and its tough shell tends to carbonize upon calcination, resulting in the hollow porous microspheres for the ``top'' product. The nanoscale crystals of the polyanion materials are tightly enwrapped by the highly-conductive framework in the hollow microsphere, resulting in the hierarchical nano-microstructure. The whole formation process is disclosed as a ``bottom-up'' mechanism. Moreover, the biochemistry-directed self-assembly process is confirmed to play a crucial role in the construction of the final architecture. Taking advantage of the well-defined hollow-microsphere architecture, the abundant interior voids and the highly-conductive framework, polyanion materials show favourable sodium-intercalation kinetics. Both materials are capable of high-rate long-term cycling. After five hundred cycles at 20 C and 10 C, Na3V2(PO4)3 and Na3.12Fe2.44(P2O7)2 retain 96.2% and 93.1% of the initial capacity, respectively. Therefore, the biochemistry-directed technique provides a low-cost, highly-efficient and widely applicable strategy to produce high-performance polyanion-based cathodes for sodium ion batteries.Biochemistry-directed synthesis of functional nanomaterials has attracted great interest in energy storage, catalysis and other applications. The unique ability of

  12. On Beyond Star Trek, the Role of Synthetic Biology in Nasa's Missions

    Science.gov (United States)

    Rothschild, Lynn J.

    2016-01-01

    The time has come to for NASA to exploit the nascent field of synthetic biology in pursuit of its mission, including aeronautics, earth science, astrobiology and notably, human exploration. Conversely, NASA advances the fundamental technology of synthetic biology as no one else can because of its unique expertise in the origin of life and life in extreme environments, including the potential for alternate life forms. This enables unique, creative "game changing" advances. NASA's requirement for minimizing upmass in flight will also drive the field toward miniaturization and automation. These drivers will greatly increase the utility of synthetic biology solutions for military, health in remote areas and commercial purposes. To this end, we have begun a program at NASA to explore the use of synthetic biology in NASA's missions, particularly space exploration. As part of this program, we began hosting an iGEM team of undergraduates drawn from Brown and Stanford Universities to conduct synthetic biology research at NASA Ames Research Center. The 2011 team (http://2011.igem.org/Team:Brown-Stanford) produced an award-winning project on using synthetic biology as a basis for a human Mars settlement and the 2012 team has expanded the use of synthetic biology to estimate the potential for life in the clouds of other planets (http://2012.igem.org/Team:Stanford-Brown; http://www.calacademy.org/sciencetoday/igem-competition/). More recent projects from the Stanford-Brown team have expanded our ideas of how synthetic biology can aid NASA's missions from "Synthetic BioCommunication" (http://2013.igem.org/Team:Stanford-Brown) to a "Biodegradable UAS (drone)" in collaboration with Spelman College (http://2014.igem.org/Team:StanfordBrownSpelman#SBS%20iGEM) and most recently, "Self-Folding Origami" (http://2015.igem.org/Team:Stanford-Brown), the winner of the 2015 award for Manufacturing.

  13. The Defence of Artificial Life by Synthetic Biology From Ethical and Social Aspects.

    Science.gov (United States)

    Chen, Yiyi; Yin, Zhou; Shao, Zhexin; Xie, Qiong

    2015-07-01

    Synthetic biology opens up exciting new opportunities for research and industry. Although the work of synthetic biologists presents many beneficial applications, it also raises potentially serious ethical concerns. Therefore, clear ideas must be formed regarding its ethical and social implications, e.g., public perception, safety, security, intellectual property rights and so on. In this review, the authors identified four issues relevant to synthetic biology and discussed associated ethical and practical implications. By weighing these perspectives of all sides, this paper clarifies the point that synthetic biology, as an emerging discipline with many anticipated benefits and positive impacts on society, can acquire moral support and ethical defence. Therefore, synthetic biologists should not be shackled with heavy ethical chains, but we must ensure that research is conducted under strict control and effective supervisory methods.

  14. Regime shift from phytoplankton to macrophyte dominance in a large river: Top-down versus bottom-up effects

    Energy Technology Data Exchange (ETDEWEB)

    Ibanez, Carles, E-mail: carles.ibanez@irta.cat [IRTA Aquatic Ecosystems, Carretera Poble Nou, Km 5.5, 43540 St. Carles de la Rapita, Catalonia (Spain); Alcaraz, Carles; Caiola, Nuno; Rovira, Albert; Trobajo, Rosa [IRTA Aquatic Ecosystems, Carretera Poble Nou, Km 5.5, 43540 St. Carles de la Rapita, Catalonia (Spain); Alonso, Miguel [United Research Services S.L., Urgell 143, 08036 Barcelona, Catalonia (Spain); Duran, Concha [Confederacion Hidrografica del Ebro, Sagasta 24-26, 50071 Zaragoza, Aragon (Spain); Jimenez, Pere J. [Grup Natura Freixe, Major 56, 43750 Flix, Catalonia (Spain); Munne, Antoni [Agencia Catalana de l' Aigua, Provenca 204-208, 08036 Barcelona, Catalonia (Spain); Prat, Narcis [Departament d' Ecologia, Universitat de Barcelona, Diagonal 645, 08028 Barcelona Catalonia (Spain)

    2012-02-01

    The lower Ebro River (Catalonia, Spain) has recently undergone a regime shift from a phytoplankton-dominated to a macrophyte-dominated system. This shift is well known in shallow lakes but apparently it has never been documented in rivers. Two initial hypotheses to explain the collapse of the phytoplankton were considered: a) the diminution of nutrients (bottom-up); b) the filtering effect due to the colonization of the zebra mussel (top-down). Data on water quality, hydrology and biological communities (phytoplankton, macrophytes and zebra mussel) was obtained both from existing data sets and new surveys. Results clearly indicate that the decrease in phosphorus is the main cause of a dramatic decrease in chlorophyll and large increase in water transparency, triggering the subsequent colonization of macrophytes in the river bed. A Generalized Linear Model analysis showed that the decrease in dissolved phosphorus had a relative importance 14 times higher than the increase in zebra mussel density to explain the variation of total chlorophyll. We suggest that the described changes in the lower Ebro River can be considered a novel ecosystem shift. This shift is triggering remarkable changes in the biological communities beyond the decrease of phytoplankton and the proliferation of macrophytes, such as massive colonization of Simulidae (black fly) and other changes in the benthic invertebrate communities that are currently investigated. - Highlights: Black-Right-Pointing-Pointer We show a regime shift in a large river from phytoplankton to macrophyte dominance. Black-Right-Pointing-Pointer Two main hypotheses are considered: nutrient decrease and zebra mussel grazing. Black-Right-Pointing-Pointer Phosphorus depletion is found to be the main cause of the phytoplankton decline. Black-Right-Pointing-Pointer We conclude that oligotrophication triggered the colonization of macrophytes. Black-Right-Pointing-Pointer This new regime shift in a river is similar to that described

  15. Quantifying the uncertainties of a bottom-up emission inventory of anthropogenic atmospheric pollutants in China

    Science.gov (United States)

    Zhao, Y.; Nielsen, C. P.; Lei, Y.; McElroy, M. B.; Hao, J.

    2011-03-01

    The uncertainties of a national, bottom-up inventory of Chinese emissions of anthropogenic SO2, NOx, and particulate matter (PM) of different size classes and carbonaceous species are comprehensively quantified, for the first time, using Monte Carlo simulation. The inventory is structured by seven dominant sectors: coal-fired electric power, cement, iron and steel, other industry (boiler combustion), other industry (non-combustion processes), transportation, and residential. For each parameter related to emission factors or activity-level calculations, the uncertainties, represented as probability distributions, are either statistically fitted using results of domestic field tests or, when these are lacking, estimated based on foreign or other domestic data. The uncertainties (i.e., 95% confidence intervals around the central estimates) of Chinese emissions of SO2, NOx, total PM, PM10, PM2.5, black carbon (BC), and organic carbon (OC) in 2005 are estimated to be -14%~13%, -13%~37%, -11%~38%, -14%~45%, -17%~54%, -25%~136%, and -40%~121%, respectively. Variations at activity levels (e.g., energy consumption or industrial production) are not the main source of emission uncertainties. Due to narrow classification of source types, large sample sizes, and relatively high data quality, the coal-fired power sector is estimated to have the smallest emission uncertainties for all species except BC and OC. Due to poorer source classifications and a wider range of estimated emission factors, considerable uncertainties of NOx and PM emissions from cement production and boiler combustion in other industries are found. The probability distributions of emission factors for biomass burning, the largest source of BC and OC, are fitted based on very limited domestic field measurements, and special caution should thus be taken interpreting these emission uncertainties. Although Monte Carlo simulation yields narrowed estimates of uncertainties compared to previous bottom-up emission

  16. A bottom-up approach to estimating cost elements of REDD+ pilot projects in Tanzania

    Directory of Open Access Journals (Sweden)

    Merger Eduard

    2012-08-01

    Full Text Available Abstract Background Several previous global REDD+ cost studies have been conducted, demonstrating that payments for maintaining forest carbon stocks have significant potential to be a cost-effective mechanism for climate change mitigation. These studies have mostly followed highly aggregated top-down approaches without estimating the full range of REDD+ costs elements, thus underestimating the actual costs of REDD+. Based on three REDD+ pilot projects in Tanzania, representing an area of 327,825 ha, this study explicitly adopts a bottom-up approach to data assessment. By estimating opportunity, implementation, transaction and institutional costs of REDD+ we develop a practical and replicable methodological framework to consistently assess REDD+ cost elements. Results Based on historical land use change patterns, current region-specific economic conditions and carbon stocks, project-specific opportunity costs ranged between US$ -7.8 and 28.8 tCOxxxx for deforestation and forest degradation drivers such as agriculture, fuel wood production, unsustainable timber extraction and pasture expansion. The mean opportunity costs for the three projects ranged between US$ 10.1 – 12.5 tCO2. Implementation costs comprised between 89% and 95% of total project costs (excluding opportunity costs ranging between US$ 4.5 - 12.2 tCO2 for a period of 30 years. Transaction costs for measurement, reporting, verification (MRV, and other carbon market related compliance costs comprised a minor share, between US$ 0.21 - 1.46 tCO2. Similarly, the institutional costs comprised around 1% of total REDD+ costs in a range of US$ 0.06 – 0.11 tCO2. Conclusions The use of bottom-up approaches to estimate REDD+ economics by considering regional variations in economic conditions and carbon stocks has been shown to be an appropriate approach to provide policy and decision-makers robust economic information on REDD+. The assessment of opportunity costs is a crucial first step to

  17. A methodology to annotate systems biology markup language models with the synthetic biology open language.

    Science.gov (United States)

    Roehner, Nicholas; Myers, Chris J

    2014-02-21

    Recently, we have begun to witness the potential of synthetic biology, noted here in the form of bacteria and yeast that have been genetically engineered to produce biofuels, manufacture drug precursors, and even invade tumor cells. The success of these projects, however, has often failed in translation and application to new projects, a problem exacerbated by a lack of engineering standards that combine descriptions of the structure and function of DNA. To address this need, this paper describes a methodology to connect the systems biology markup language (SBML) to the synthetic biology open language (SBOL), existing standards that describe biochemical models and DNA components, respectively. Our methodology involves first annotating SBML model elements such as species and reactions with SBOL DNA components. A graph is then constructed from the model, with vertices corresponding to elements within the model and edges corresponding to the cause-and-effect relationships between these elements. Lastly, the graph is traversed to assemble the annotating DNA components into a composite DNA component, which is used to annotate the model itself and can be referenced by other composite models and DNA components. In this way, our methodology can be used to build up a hierarchical library of models annotated with DNA components. Such a library is a useful input to any future genetic technology mapping algorithm that would automate the process of composing DNA components to satisfy a behavioral specification. Our methodology for SBML-to-SBOL annotation is implemented in the latest version of our genetic design automation (GDA) software tool, iBioSim.

  18. Emotional face expression modulates occipital-frontal effective connectivity during memory formation in a bottom-up fashion.

    Science.gov (United States)

    Xiu, Daiming; Geiger, Maximilian J; Klaver, Peter

    2015-01-01

    This study investigated the role of bottom-up and top-down neural mechanisms in the processing of emotional face expression during memory formation. Functional brain imaging data was acquired during incidental learning of positive ("happy"), neutral and negative ("angry" or "fearful") faces. Dynamic Causal Modeling (DCM) was applied on the functional magnetic resonance imaging (fMRI) data to characterize effective connectivity within a brain network involving face perception (inferior occipital gyrus and fusiform gyrus) and successful memory formation related areas (hippocampus, superior parietal lobule, amygdala, and orbitofrontal cortex). The bottom-up models assumed processing of emotional face expression along feed forward pathways to the orbitofrontal cortex. The top-down models assumed that the orbitofrontal cortex processed emotional valence and mediated connections to the hippocampus. A subsequent recognition memory test showed an effect of negative emotion on the response bias, but not on memory performance. Our DCM findings showed that the bottom-up model family of effective connectivity best explained the data across all subjects and specified that emotion affected most bottom-up connections to the orbitofrontal cortex, especially from the occipital visual cortex and superior parietal lobule. Of those pathways to the orbitofrontal cortex the connection from the inferior occipital gyrus correlated with memory performance independently of valence. We suggest that bottom-up neural mechanisms support effects of emotional face expression and memory formation in a parallel and partially overlapping fashion.

  19. Emotional face expression modulates occipital-frontal effective connectivity during memory formation in a bottom-up fashion

    Directory of Open Access Journals (Sweden)

    Daiming eXiu

    2015-04-01

    Full Text Available This study investigated the role of bottom-up and top-down neural mechanisms in the processing of emotional face expression during memory formation. Functional brain imaging data was acquired during incidental learning of positive (‘happy’, neutral and negative (‘angry’ or ‘fearful’ faces. Dynamic Causal Modeling (DCM was applied on the fMRI data to characterize effective connectivity within a brain network involving face perception (inferior occipital gyrus and fusiform gyrus and successful memory formation related areas (hippocampus, superior parietal lobule, amygdala and orbitofrontal cortex. The bottom-up models assumed processing of emotional face expression along feed forward pathways to the orbitofrontal cortex. The top-down models assumed that the orbitofrontal cortex processed emotional valence and mediated connections to the hippocampus. A subsequent recognition memory test showed an effect of negative emotion on the response bias, but not on memory performance. Our DCM findings showed that the bottom-up model family of effective connectivity best explained the data across all subjects and specified that emotion affected most bottom-up connections to the orbitofrontal cortex, especially from the occipital visual cortex and superior parietal lobule. Of those pathways to the orbitofrontal cortex the connection from the inferior occipital gyrus correlated with memory performance independently of valence. We suggest that bottom-up neural mechanisms support effects of emotional face expression and memory formation in a parallel and partially overlapping fashion.

  20. Using Synthetic Biological Parts and Microbioreactors to Explore the Protein Expression Characteristics of Escherichia coli

    NARCIS (Netherlands)

    Gorochowski, Thomas E.; van den Berg, Eric; Kerkman, Richard; Roubos, Johannes A.; Bovenberg, Roel A. L.

    2014-01-01

    Synthetic biology has developed numerous parts for the precise control of protein expression. However, relatively little is known about the burden these place on a host, or their reliability under varying environmental conditions. To address this, we made use of synthetic transcriptional and transla

  1. Organism, machine, artifact: The conceptual and normative challenges of synthetic biology.

    Science.gov (United States)

    Holm, Sune; Powell, Russell

    2013-12-01

    Synthetic biology is an emerging discipline that aims to apply rational engineering principles in the design and creation of organisms that are exquisitely tailored to human ends. The creation of artificial life raises conceptual, methodological and normative challenges that are ripe for philosophical investigation. This special issue examines the defining concepts and methods of synthetic biology, details the contours of the organism-artifact distinction, situates the products of synthetic biology vis-à-vis this conceptual typology and against historical human manipulation of the living world, and explores the normative implications of these conclusions. In addressing the challenges posed by emerging biotechnologies, new light can be thrown on old problems in the philosophy of biology, such as the nature of the organism, the structure of biological teleology, the utility of engineering metaphors and methods in biological science, and humankind's relationship to nature.

  2. Web-based software tool for constraint-based design specification of synthetic biological systems.

    Science.gov (United States)

    Oberortner, Ernst; Densmore, Douglas

    2015-06-19

    miniEugene provides computational support for solving combinatorial design problems, enabling users to specify and enumerate designs for novel biological systems based on sets of biological constraints. This technical note presents a brief tutorial for biologists and software engineers in the field of synthetic biology on how to use miniEugene. After reading this technical note, users should know which biological constraints are available in miniEugene, understand the syntax and semantics of these constraints, and be able to follow a step-by-step guide to specify the design of a classical synthetic biological system-the genetic toggle switch.1 We also provide links and references to more information on the miniEugene web application and the integration of the miniEugene software library into sophisticated Computer-Aided Design (CAD) tools for synthetic biology ( www.eugenecad.org ).

  3. Blueprints for green biotech: development and application of standards for plant synthetic biology.

    Science.gov (United States)

    Patron, Nicola J

    2016-06-15

    Synthetic biology aims to apply engineering principles to the design and modification of biological systems and to the construction of biological parts and devices. The ability to programme cells by providing new instructions written in DNA is a foundational technology of the field. Large-scale de novo DNA synthesis has accelerated synthetic biology by offering custom-made molecules at ever decreasing costs. However, for large fragments and for experiments in which libraries of DNA sequences are assembled in different combinations, assembly in the laboratory is still desirable. Biological assembly standards allow DNA parts, even those from multiple laboratories and experiments, to be assembled together using the same reagents and protocols. The adoption of such standards for plant synthetic biology has been cohesive for the plant science community, facilitating the application of genome editing technologies to plant systems and streamlining progress in large-scale, multi-laboratory bioengineering projects.

  4. Playing God or just unnatural? Religious beliefs and approval of synthetic biology.

    Science.gov (United States)

    Dragojlovic, Nicolas; Einsiedel, Edna

    2013-10-01

    Using evidence from a 2010 survey of 32 European publics, this article argues that belief in God increases disapproval for synthetic biology through two different mechanisms, depending on the strength of the individual's belief. Among weak believers, belief in God appears to be associated with the increased availability and accessibility of the idea that genetic manipulation interferes with nature. Strong believers, in contrast, appear to also engage in an explicitly theological evaluation of synthetic biology, with opposition to synthetic biology resulting from the perception that the creation of new types of organisms encroaches on a domain of activity (creation) that has traditionally been considered to be a divine prerogative. Overall, our findings suggest that value predispositions can influence public attitudes towards synthetic biology even when individuals engage in explicit deliberation about the technology in question.

  5. Synthetic biology and conservation of nature: wicked problems and wicked solutions.

    Science.gov (United States)

    Redford, Kent H; Adams, William; Mace, Georgina M

    2013-01-01

    So far, conservation scientists have paid little attention to synthetic biology; this is unfortunate as the technology is likely to transform the operating space within which conservation functions, and therefore the prospects for maintaining biodiversity into the future.

  6. A priority paper for the societal and ethical aspects of synthetic biology.

    Science.gov (United States)

    Schmidt, Markus; Ganguli-Mitra, Agomoni; Torgersen, Helge; Kelle, Alexander; Deplazes, Anna; Biller-Andorno, Nikola

    2009-12-01

    As synthetic biology develops into a promising science and engineering field, we need to have clear ideas and priorities regarding its safety, security, ethical and public dialogue implications. Based on an extensive literature search, interviews with scientists, social scientists, a 4 week long public e-forum, and consultation with several stakeholders from science, industry and civil society organisations, we compiled a list of priority topics regarding societal issues of synthetic biology for the years ahead. The points presented here are intended to encourage all stakeholders to engage in the prioritisation of these issues and to participate in a continuous dialogue, with the ultimate goal of providing a basis for a multi-stakeholder governance in synthetic biology. Here we show possible ways to solve the challenges to synthetic biology in the field of safety, security, ethics and the science-public interface.

  7. Bottom-Up Abstract Modelling of Optical Networks-on-Chip: From Physical to Architectural Layer

    Directory of Open Access Journals (Sweden)

    Alberto Parini

    2012-01-01

    Full Text Available This work presents a bottom-up abstraction procedure based on the design-flow FDTD + SystemC suitable for the modelling of optical Networks-on-Chip. In this procedure, a complex network is decomposed into elementary switching elements whose input-output behavior is described by means of scattering parameters models. The parameters of each elementary block are then determined through 2D-FDTD simulation, and the resulting analytical models are exported within functional blocks in SystemC environment. The inherent modularity and scalability of the S-matrix formalism are preserved inside SystemC, thus allowing the incremental composition and successive characterization of complex topologies typically out of reach for full-vectorial electromagnetic simulators. The consistency of the outlined approach is verified, in the first instance, by performing a SystemC analysis of a four-input, four-output ports switch and making a comparison with the results of 2D-FDTD simulations of the same device. Finally, a further complex network encompassing 160 microrings is investigated, the losses over each routing path are calculated, and the minimum amount of power needed to guarantee an assigned BER is determined. This work is a basic step in the direction of an automatic technology-aware network-level simulation framework capable of assembling complex optical switching fabrics, while at the same time assessing the practical feasibility and effectiveness at the physical/technological level.

  8. Bottom-Up, Wet Chemical Technique for the Continuous Synthesis of Inorganic Nanoparticles

    Directory of Open Access Journals (Sweden)

    Annika Betke

    2014-01-01

    Full Text Available Continuous wet chemical approaches for the production of inorganic nanoparticles are important for large scale production of nanoparticles. Here we describe a bottom-up, wet chemical method applying a microjet reactor. This technique allows the separation between nucleation and growth in a continuous reactor environment. Zinc oxide (ZnO, magnetite (Fe3O4, as well as brushite (CaHPO4·2H2O, particles with a small particle size distribution can be obtained continuously by using the rapid mixing of two precursor solutions and the fast removal of the nuclei from the reaction environment. The final particles were characterized by FT-IR, TGA, DLS, XRD and SEM techniques. Systematic studies on the influence of the different process parameters, such as flow rate and process temperature, show that the particle size can be influenced. Zinc oxide was obtained with particle sizes between 44 nm and 102 nm. The obtained magnetite particles have particle sizes in the range of 46 nm to 132 nm. Brushite behaves differently; the obtained particles were shaped like small plates with edge lengths between 100 nm and 500 nm.

  9. Two Paths to Transforming Markets through Public Sector EnergyEfficiency: Bottom Up versus Top Down

    Energy Technology Data Exchange (ETDEWEB)

    Van Wie McGrory, Laura; Coleman, Philip; Fridley, David; Harris,Jeffrey; Villasenor Franco, Edgar

    2006-05-10

    The evolution of government purchasing initiatives in Mexicoand China, part of the PEPS (Promoting an Energy-efficient Public Sector)program, demonstrates the need for flexibility in designingenergy-efficiency strategies in the public sector. Several years ofpursuing a top-down (federally led) strategy in Mexico produced fewresults, and it was not until the program was restructured in 2004 tofocus on municipal-level purchasing that the program gained momentum.Today, a new partnership with the Mexican federal government is leadingto an intergovernmental initiative with strong support at the federallevel. By contrast, the PEPS purchasing initiative in China wassuccessfully initiated and led at the central government level withstrategic support from international experts. The very different successtrajectories in these two countries provide valuable lessons fordesigning country-specific public sector energy-efficiency initiatives.Enabling conditions for any successful public sector purchasinginitiative include the existence of mandatory energy-efficiencyperformance standards, an effective energy-efficiency endorsementlabeling program, an immediate need for energy conservation, a simplepilot phase (focusing on a limited number of strategically chosenproducts), and specialized technical assistance. Top-down purchasingprograms are likely to be more successful where there is high-levelpolitical endorsement and a national procurement law in place, supportedby a network of trained purchasers. Bottom-up (municipally led)purchasing programs require that municipalities have the authority to settheir own purchasing policies, and also benefit from existing networks ofcities, supported by motivated municipal leaders and trained purchasingofficials.

  10. Spinodal nanotechnology as a new class of bottom-up one and applications

    Science.gov (United States)

    Katayama-Yoshida, Hiroshi; Fukushima, Tetsuya; Kizaki, Hidetoshi; Oshitani, Masamune; Sato, Kazunori

    2010-03-01

    We discuss the nano-materials design of spinodal nano-decomposition as a new class of bottom-up nanotechnology by combining ab initio calculations and kinetic Monte Carlo simulations. We include all the complexity in the fabrication process of spinodal nano-decomposition (Konbu- and Dairiseki-phase) into advanced materials design with inhomogeneous materials. We compare the theoretical predictions with available experiments, such as (i)semiconductor nano-spintronics in dilute magnetic semiconductors, (ii)colossal thermoelectric-power responses of spincaloritronics, (iii)self-repaired nano-catalysis in La(Fe,Pd)O3, (iv)high-efficiency solar-cells, (v)high-efficiency light-emitting diode and Lasers. (1) K. Sato, et al., Reviews of Modern Physics, in printing (2009). (2) H. Katayama-Yoshida, et al.,Handbook of Spintronic Semiconductors, (Pan Stanford Pub.), p.1-79, (2009). (3) H. Katayama-Yoshida, et al.,Semiconductors and Semimetals, 82,433 (2008). (4) H. Katayama-Yoshida, et al.,Jpn. J. Appl. Phys. 46, L777 (2007). (5) H. Kizaki, et al.,Applied Physics Express 1, 104001, (2008).

  11. The Early Anthropogenic Hypothesis: Top-Down and Bottom-up Evidence

    Science.gov (United States)

    Ruddiman, W. F.

    2014-12-01

    Two complementary lines of evidence support the early anthropogenic hypothesis. Top-down evidence comes from comparing Holocene greenhouse-gas trends with those during equivalent intervals of previous interglaciations. The increases in CO2 and CH4 during the late Holocene are anomalous compared to the decreasing trends in a stacked average of previous interglaciations, thereby supporting an anthropogenic origin. During interglacial stage 19, the closest Holocene insolation analog, CO2 fell to 245 ppm by the time equivalent to the present, in contrast to the observed pre-industrial rise to 280-285 ppm. The 245-ppm level measured in stage 19 falls at the top of the natural range predicted by the original anthropogenic hypothesis of Ruddiman (2003). Bottom-up evidence comes from a growing list of archeological and other compilations showing major early anthropogenic transformations of Earth's surface. Key examples include: efforts by Dorian Fuller and colleagues mapping the spread of irrigated rice agriculture across southern Asia and its effects on CH4 emissions prior to the industrial era; an additional effort by Fuller showing the spread of methane-emitting domesticated livestock across Asia and Africa (coincident with the spread of fertile crescent livestock across Europe); historical compilations by Jed Kaplan and colleagues documenting very high early per-capita forest clearance in Europe, thus underpinning simulations of extensive pre-industrial clearance and large CO2 emissions; and wide-ranging studies by Erle Ellis and colleagues of early anthropogenic land transformations in China and elsewhere.

  12. A "bottom up" governance framework for developing Australia's marine Spatial Data Infrastructure (SDI

    Directory of Open Access Journals (Sweden)

    K T Finney

    2007-07-01

    Full Text Available Spatial Data Infrastructures (SDIs have been developing in some countries for over 10 years but still suffer from having a relatively small installed base. Most SDIs will soon converge around a service-oriented-architecture (SOA using IT standards promulgated primarily by the Open Geospatial Consortium (OGC and ISO Technical Committee 211. There are very few examples of these types of architected SDIs in action, and as a result little detailed information exists on suitable governance models. This paper discusses the governance issues that are posed by SOA-based SDIs, particularly those issues surrounding standards and services management, with reference to an Australian marine case study and the general literature. A generalised governance framework is then postulated using an idealised use case model which is applicable for "bottom-up," community-based initiatives. This model incorporates guiding principles and motivational and self-regulation instruments that are characteristically found in successful open source development activities. It is argued that harnessing an open development model, using a voluntary workforce, could rapidly increase the size of the SDI installed base and importantly defray infrastructure build costs.

  13. A Bottom-Up Approach for Automatically Grouping Sensor Data Layers by their Observed Property

    Directory of Open Access Journals (Sweden)

    Steve H.L. Liang

    2013-01-01

    Full Text Available The Sensor Web is a growing phenomenon where an increasing number of sensors are collecting data in the physical world, to be made available over the Internet. To help realize the Sensor Web, the Open Geospatial Consortium (OGC has developed open standards to standardize the communication protocols for sharing sensor data. Spatial Data Infrastructures (SDIs are systems that have been developed to access, process, and visualize geospatial data from heterogeneous sources, and SDIs can be designed specifically for the Sensor Web. However, there are problems with interoperability associated with a lack of standardized naming, even with data collected using the same open standard. The objective of this research is to automatically group similar sensor data layers. We propose a methodology to automatically group similar sensor data layers based on the phenomenon they measure. Our methodology is based on a unique bottom-up approach that uses text processing, approximate string matching, and semantic string matching of data layers. We use WordNet as a lexical database to compute word pair similarities and derive a set-based dissimilarity function using those scores. Two approaches are taken to group data layers: mapping is defined between all the data layers, and clustering is performed to group similar data layers. We evaluate the results of our methodology.

  14. Preparation of hydrocortisone nanosuspension through a bottom-up nanoprecipitation technique using microfluidic reactors.

    Science.gov (United States)

    Ali, Hany S M; York, Peter; Blagden, Nicholas

    2009-06-22

    In this work, the possibility of bottom-up creation of a relatively stable aqueous hydrocortisone nanosuspension using microfluidic reactors was examined. The first part of the work involved a study of the parameters of the microfluidic precipitation process that affect the size of generated drug particles. These parameters included flow rates of drug solution and antisolvent, microfluidic channel diameters, microreactors inlet angles and drug concentrations. The experimental results revealed that hydrocortisone nano-sized dispersions in the range of 80-450 nm were obtained and the mean particle size could be changed by modifying the experimental parameters and design of microreactors. The second part of the work studied the possibility of preparing a hydrocortisone nanosuspension using microfluidic reactors. The nano-sized particles generated from a microreactor were rapidly introduced into an aqueous solution of stabilizers stirred at high speed with a propeller mixer. A tangential flow filtration system was then used to concentrate the prepared nanosuspension. The nanosuspension produced was then characterized using photon correlation spectroscopy (PCS), Zeta potential measurement, transmission electron microscopy (TEM), differential scanning calorimetry (DSC) and X-ray analysis. Results showed that a narrow sized nanosuspension composed of amorphous spherical particles with a mean particle size of 500+/-64 nm, a polydispersity index of 0.21+/-0.026 and a zeta potential of -18+/-2.84 mV was obtained. Physical stability studies showed that the hydrocortisone nanosuspension remained homogeneous with slight increase in mean particle size and polydispersity index over a 3-month period.

  15. Ursgal, Universal Python Module Combining Common Bottom-Up Proteomics Tools for Large-Scale Analysis.

    Science.gov (United States)

    Kremer, Lukas P M; Leufken, Johannes; Oyunchimeg, Purevdulam; Schulze, Stefan; Fufezan, Christian

    2016-03-04

    Proteomics data integration has become a broad field with a variety of programs offering innovative algorithms to analyze increasing amounts of data. Unfortunately, this software diversity leads to many problems as soon as the data is analyzed using more than one algorithm for the same task. Although it was shown that the combination of multiple peptide identification algorithms yields more robust results, it is only recently that unified approaches are emerging; however, workflows that, for example, aim to optimize search parameters or that employ cascaded style searches can only be made accessible if data analysis becomes not only unified but also and most importantly scriptable. Here we introduce Ursgal, a Python interface to many commonly used bottom-up proteomics tools and to additional auxiliary programs. Complex workflows can thus be composed using the Python scripting language using a few lines of code. Ursgal is easily extensible, and we have made several database search engines (X!Tandem, OMSSA, MS-GF+, Myrimatch, MS Amanda), statistical postprocessing algorithms (qvality, Percolator), and one algorithm that combines statistically postprocessed outputs from multiple search engines ("combined FDR") accessible as an interface in Python. Furthermore, we have implemented a new algorithm ("combined PEP") that combines multiple search engines employing elements of "combined FDR", PeptideShaker, and Bayes' theorem.

  16. Sustainability and Uncertainty: Bottom-Up and Top-Down Approaches

    Directory of Open Access Journals (Sweden)

    K. Klint Jensen

    2010-04-01

    Full Text Available The widely used concept of sustainability is seldom precisely defined, and its clarification involves making up one’s mind about a range of difficult questions. One line of research (bottom-up takes sustaining a system over time as its starting point and then infers prescriptions from this requirement. Another line (top-down takes an economical interpretation of the Brundtland Commission’s suggestion that the present generation’s needsatisfaction should not compromise the need-satisfaction of future generations as its starting point. It then measures sustainability at the level of society and infers prescriptions from this requirement. These two approaches may conflict, and in this conflict the top-down approach has the upper hand, ethically speaking. However, the implicit goal in the top-down approach of justice between generations needs to be refined in several dimensions. But even given a clarified ethical goal, disagreements can arise. At present we do not know what substitutions will be possible in the future. This uncertainty clearly affects the prescriptions that follow from the measure of sustainability. Consequently, decisions about how to make future agriculture sustainable are decisions under uncertainty. There might be different judgments on likelihoods; but even given some set of probabilities, there might be disagreement on the right level of precaution in face of the uncertainty.

  17. Top-down and bottom-up analysis of commercial enoxaparins.

    Science.gov (United States)

    Liu, Xinyue; St Ange, Kalib; Lin, Lei; Zhang, Fuming; Chi, Lianli; Linhardt, Robert J

    2017-01-13

    A strategy for the comprehensive analysis of low molecular weight (LMW) heparins is described that relies on using an integrated top-down and bottom-up approach. Liquid chromatography-mass spectrometry, an essential component of this approach, is rapid, robust, and amenable to automated processing and interpretation. Nuclear magnetic resonance spectroscopy provides complementary top-down information on the chirality of the uronic acid residues comprising a low molecular weight heparin. Using our integrated approach four different low molecular weight heparins prepared from porcine heparin through chemical β-eliminative cleavage were comprehensively analyzed. Lovenox™ and Clexane™, the innovator versions of enoxaparin marketed in the US and Europe, respectively, and two generic enoxaparins, from Sandoz and Teva, were analyzed. The results which were supported by analysis of variation (ANOVA), while showing remarkable similarities between different versions of the product and good lot-to-lot consistency of each product, also detects subtle differences that may result from differences in their manufacturing processes or differences in the source (or parent) porcine heparin from which each product is prepared.

  18. Um Modelo de inovação bottom up: Museu de Favela (MUF

    Directory of Open Access Journals (Sweden)

    Natália Nakano

    2013-12-01

    Full Text Available Este artigo tem como objetivo apresentar, descrever e discutir o modelo de inovação do primeiro museu territorial ao ar livre, concebido em uma favela no Rio de Janeiro, o Museu de Favela (MUF. Nele são introduzidos os conceitos de favela, e diferenciados museu tradicional e os ecomuseus, a fim de contextualizar o universo do MUF. Discute-se o conceito de coleção de um museu territorial ao ar livre e como se dá o trabalho de curadoria nesse contexto, bem como os tipos de interação possíveis com a diversidade de indivíduos atendidos por um museu como o MUF. Discute-se ainda o papel dessa nova tipologia museológica na sociedade, a partir de entidades criadas pela inovação do tipo bottom up realizada pela iniciativa do MUF dentro da nova museologia de ação. Conclui-se com considerações a respeito da mudança de foco do papel desempenhado pelo MUF como agente de desenvolvimento social e cultural.

  19. Visionmaker NYC: A bottom-up approach to finding shared socioeconomic pathways in New York City

    Science.gov (United States)

    Sanderson, E. W.; Fisher, K.; Giampieri, M.; Barr, J.; Meixler, M.; Allred, S. B.; Bunting-Howarth, K. E.; DuBois, B.; Parris, A. S.

    2015-12-01

    Visionmaker NYC is a free, public participatory, bottom-up web application to develop and share climate mitigation and adaptation strategies for New York City neighborhoods. The goal is to develop shared socioeconomic pathways by allowing a broad swath of community members - from schoolchildren to architects and developers to the general public - to input their concepts for a desired future. Visions are comprised of climate scenarios, lifestyle choices, and ecosystem arrangements, where ecosystems are broadly defined to include built ecosystems (e.g. apartment buildings, single family homes, etc.), transportation infrastructure (e.g. highways, connector roads, sidewalks), and natural land cover types (e.g. wetlands, forests, estuary.) Metrics of water flows, carbon cycling, biodiversity patterns, and population are estimated for the user's vision, for the same neighborhood today, and for that neighborhood as it existed in the pre-development state, based on the Welikia Project (welikia.org.) Users can keep visions private, share them with self-defined groups of other users, or distribute them publicly. Users can also propose "challenges" - specific desired states of metrics for specific parts of the city - and others can post visions in response. Visionmaker contributes by combining scenario planning, scientific modelling, and social media to create new, wide-open possibilities for discussion, collaboration, and imagination regarding future, shared socioeconomic pathways.

  20. Bottom-up simulations of methane and ethane emissions from global oil and gas systems 1980 to 2012

    Science.gov (United States)

    Höglund-Isaksson, Lena

    2017-02-01

    Existing bottom-up emission inventories of methane from global oil and gas systems do not satisfactorily explain year-on-year variation in atmospheric methane estimated by top-down models. Using a novel bottom-up approach this study quantifies and attributes methane and ethane emissions from global oil and gas production from 1980 to 2012. Country-specific information on associated gas flows from published sources are combined with inter-annual variations in observed flaring of associated gas from satellite images from 1994 to 2010, to arrive at country-specific annual estimates of methane and ethane emissions from flows of associated gas. Results confirm trends from top-down models and indicate considerably higher methane and ethane emissions from oil production than previously shown in bottom-up inventories for this time period.

  1. Bottom-up synthesis of ordered metal/oxide/metal nanodots on substrates for nanoscale resistive switching memory

    Science.gov (United States)

    Han, Un-Bin; Lee, Jang-Sik

    2016-01-01

    The bottom-up approach using self-assembled materials/processes is thought to be a promising solution for next-generation device fabrication, but it is often found to be not feasible for use in real device fabrication. Here, we report a feasible and versatile way to fabricate high-density, nanoscale memory devices by direct bottom-up filling of memory elements. An ordered array of metal/oxide/metal (copper/copper oxide/copper) nanodots was synthesized with a uniform size and thickness defined by self-organized nanotemplate mask by sequential electrochemical deposition (ECD) of each layer. The fabricated memory devices showed bipolar resistive switching behaviors confirmed by conductive atomic force microscopy. This study demonstrates that ECD with bottom-up growth has great potential to fabricate high-density nanoelectronic devices beyond the scaling limit of top-down device fabrication processes. PMID:27157385

  2. Promoting microbiology education through the iGEM synthetic biology competition.

    Science.gov (United States)

    Kelwick, Richard; Bowater, Laura; Yeoman, Kay H; Bowater, Richard P

    2015-08-01

    Synthetic biology has developed rapidly in the 21st century. It covers a range of scientific disciplines that incorporate principles from engineering to take advantage of and improve biological systems, often applied to specific problems. Methods important in this subject area include the systematic design and testing of biological systems and, here, we describe how synthetic biology projects frequently develop microbiology skills and education. Synthetic biology research has huge potential in biotechnology and medicine, which brings important ethical and moral issues to address, offering learning opportunities about the wider impact of microbiological research. Synthetic biology projects have developed into wide-ranging training and educational experiences through iGEM, the International Genetically Engineered Machines competition. Elements of the competition are judged against specific criteria and teams can win medals and prizes across several categories. Collaboration is an important element of iGEM, and all DNA constructs synthesized by iGEM teams are made available to all researchers through the Registry for Standard Biological Parts. An overview of microbiological developments in the iGEM competition is provided. This review is targeted at educators that focus on microbiology and synthetic biology, but will also be of value to undergraduate and postgraduate students with an interest in this exciting subject area.

  3. 3-Substituted-7-(diethylamino)coumarins as molecular scaffolds for the bottom-up self-assembly of solids with extensive π-stacking

    Science.gov (United States)

    Arcos-Ramos, Rafael; Maldonado-Domínguez, Mauricio; Ordóñez-Hernández, Javier; Romero-Ávila, Margarita; Farfán, Norberto; Carreón-Castro, María del Pilar

    2017-02-01

    In this study, a set of molecular crystals derived from 3-substituted-7-(diethylamino)-2H-chromen-2-ones 1-8 were studied to sample the aggregation of coumarins into ordered solids. Crystals of parent compound 1a and its brominated derivative 2 were obtained and solved in the P-1 and C2/c space groups, respectively. All the crystalline coumarins studied display extensive π-stacking in the solid-state. Theoretical valence-conduction band gaps for derivatives 3b and 5 are close to crystalline rubrene, highlighting the importance of cooperativity and periodicity of π-stacking, in organic semiconductors; given their synthetic accessibility, electronic tunability and self-assembly via stacking, dipolar and H-bonding interactions, these systems arise as candidates for the bottom-up construction of organic crystals with extensive π-stacking and high polarizability.

  4. The Comparative Effect of Top-down Processing and Bottom-up Processing through TBLT on Extrovert and Introvert EFL

    Directory of Open Access Journals (Sweden)

    Pezhman Nourzad Haradasht

    2013-09-01

    Full Text Available This research seeks to examine the effect of two models of reading comprehension, namely top-down and bottom-up processing, on the reading comprehension of extrovert and introvert EFL learners’ reading comprehension. To do this, 120 learners out of a total number of 170 intermediate learners being educated at Iran Mehr English Language School were selected all taking a PET (Preliminary English Test first for homogenization prior to the study. They also answered the Eysenck Personality Inventory (EPI which in turn categorized them into two subgroups within each reading models consisting of introverts and extroverts. All in all, there were four subgroups: 30 introverts and 30 extroverts undergoing the top-down processing treatment, and 30 introverts and 30 extroverts experiencing the bottom-up processing treatment. The aforementioned PET was administered as the post test of the study after each group was exposed to the treatment for 18 sessions in six weeks. After the instructions finished, the mean scores of all four groups on this post test were computed and a two-way ANOVA was run to test all the four hypotheses raise in this study. the results showed that while learners generally benefitted more from the bottom-up processing setting compared  to the top-down processing one, the extrovert group was better off receiving top-down instruction. Furthermore, introverts outperformed extroverts in bottom-up group; yet between the two personalities subgroups in the top-down setting no difference was seen. A predictable pattern of benefitting from teaching procedures could not be drawn for introverts as in both top-down and bottom-up settings, they benefitted more than extroverts. Keywords: Reading comprehension, top-down processing, bottom-up processing, extrovert, introvert

  5. Evidence of bottom-up control of marine productivity in the Mediterranean Sea during the last 50 years

    Science.gov (United States)

    Macías, Diego; Garcia-Gorriz, Elisa; Piroddi, Chiara; Stips, Adolf

    2014-05-01

    The temporal dynamics of biogeochemical variables derived from a coupled 3D hydrodynamic-biogeochemical model of the entire Mediterranean Sea is evaluated during the last 50 years (1960 - 2010). Realistic atmospheric forcing and river discharge are used to force the dynamics of the coupled model system. The time evolutions of primary and secondary productions in the entire basin are assessed against available independent data on fisheries yields and catches per unit effort for the same time period. Concordant patterns are found in the time-series of all biological variables (from the model and from fisheries statistics), with low values at the beginning of the series, a later increase with maximum values reached at the end of the 1990's and a posterior stabilization or a small decline. Spectral analysis of the annual biological time-series reveals coincident low-frequency signals in all of them; the first, more energetic signal, peaks at 2000 while the second one (less energetic) presents maximum values at around 1982. Almost identical low-frequency signals are found in the nutrient loads of the main rivers of the basin and in the integrated (0-100 meters) mean nutrient concentrations in the marine ecosystem. Nitrate concentration shows an increasing trend up to 1998 with a later stabilization or a slight decline to present day values. This nitrate evolution seems to be driving the first low-frequency signal found in the biological time series. Phosphate, on the other hand, shows maximum concentrations around 1982 and a posterior sharp decline. This nutrient seems to be responsible for the second low-frequency signal observed in the biological time-series. Our analysis shows that the control of marine productivity (from plankton to fish) in the Mediterranean basin seem to be principally mediated through bottom-up processes that could be traced back to the characteristics of riverine discharges. Other types of control could not be excluded from our analysis (e

  6. Synthetic biology approaches in cancer immunotherapy, genetic network engineering, and genome editing.

    Science.gov (United States)

    Chakravarti, Deboki; Cho, Jang Hwan; Weinberg, Benjamin H; Wong, Nicole M; Wong, Wilson W

    2016-04-18

    Investigations into cells and their contents have provided evolving insight into the emergence of complex biological behaviors. Capitalizing on this knowledge, synthetic biology seeks to manipulate the cellular machinery towards novel purposes, extending discoveries from basic science to new applications. While these developments have demonstrated the potential of building with biological parts, the complexity of cells can pose numerous challenges. In this review, we will highlight the broad and vital role that the synthetic biology approach has played in applying fundamental biological discoveries in receptors, genetic circuits, and genome-editing systems towards translation in the fields of immunotherapy, biosensors, disease models and gene therapy. These examples are evidence of the strength of synthetic approaches, while also illustrating considerations that must be addressed when developing systems around living cells.

  7. Advances in Synthetic Biology%合成生物学技术研究进展

    Institute of Scientific and Technical Information of China (English)

    吕永坤; 堵国成; 陈坚; 周景文

    2015-01-01

    Synthetic biology is an applied discipline that introduces engineering into biology. The aim of synthetic biology is to standardize and modularize biological parts. It can also be applied in the basic researches,such as the research of life origin. This review gives a detailed introduction to the synthetic biology,especially the new methods and applications.%合成生物学是一门将生物学工程化的应用学科,目的在于将生命元件标准化和模块化;也可用于生命起源等基础理论研究。对合成生物学进行了较为详细地介绍,主要综述了合成生物学领域新出现的方法及应用。

  8. Synthetic biology in space: considering the broad societal and ethical implications

    Science.gov (United States)

    Race, Margaret S.; Moses, Jacob; McKay, Christopher; Venkateswaran, Kasthuri J.

    2012-02-01

    Although the field of synthetic biology is still in its infancy, there are expectations for great advances in the coming decades, both on Earth and potentially in space. Promising applications for long duration space missions include a variety of biologically engineered products and biologically aided processes and technologies, which will undoubtedly be scrutinized for risks and benefits in the broad context of ethical, legal and social realms. By comparing and contrasting features of Earth-based and space-applied synthetic biology, it is possible to identify the likely similarities and differences, and to identify possible challenges ahead for space applications that will require additional research, both in the short and long terms. Using an analytical framework associated with synthetic biology and new technologies on Earth, this paper analyses the kinds of issues and concerns ahead, and identifies those areas where space applications may require additional examination. In general, while Earth- and space-based synthetic biology share many commonalities, space applications have additional challenges such as those raised by space microbiology and environmental factors, legal complications, planetary protection, lack of decision-making infrastructure(s), long duration human missions, terraforming and the possible discovery of extraterrestrial (ET) life. For synthetic biology, the way forward offers many exciting opportunities, but is not without legitimate concerns - for life, environments and society, both on Earth and beyond.

  9. Quantifying the uncertainties of a bottom-up emission inventory of anthropogenic atmospheric pollutants in China

    Directory of Open Access Journals (Sweden)

    Y. Zhao

    2010-11-01

    Full Text Available The uncertainties of a national, bottom-up inventory of Chinese emissions of anthropogenic SO2, NOx, and particulate matter (PM of different size classes and carbonaceous species are comprehensively quantified, for the first time, using Monte Carlo simulation. The inventory is structured by seven dominant sectors: coal-fired electric power, cement, iron and steel, other industry (boiler combustion, other industry (non-combustion processes, transportation, and residential. For each parameter related to emission factors or activity-level calculations, the uncertainties, represented as probability distributions, are either statistically fitted using results of domestic field tests or, when these are lacking, estimated based on foreign or other domestic data. The uncertainties (i.e., 95% confidence intervals around the central estimates of Chinese emissions of SO2, NOx, total PM, PM10, PM2.5, black carbon (BC, and organic carbon (OC in 2005 are estimated to be −14%~12%, −10%~36%, −10%~36%, −12%~42% −16%~52%, −23%~130%, and −37%~117%, respectively. Variations at activity levels (e.g., energy consumption or industrial production are not the main source of emission uncertainties. Due to narrow classification of source types, large sample sizes, and relatively high data quality, the coal-fired power sector is estimated to have the smallest emission uncertainties for all species except BC and OC. Due to poorer source classifications and a wider range of estimated emission factors, considerable uncertainties of NOx and PM emissions from cement production and boiler combustion in other industries are found. The probability distributions of emission factors for biomass burning, the largest source of BC and OC, are fitted based on very limited domestic field measurements, and special caution should thus be taken interpreting these emission uncertainties. Although Monte

  10. Adaptive genetic variation mediates bottom-up and top-down control in an aquatic ecosystem

    Science.gov (United States)

    Rudman, Seth M.; Rodriguez-Cabal, Mariano A.; Stier, Adrian; Sato, Takuya; Heavyside, Julian; El-Sabaawi, Rana W.; Crutsinger, Gregory M.

    2015-01-01

    Research in eco-evolutionary dynamics and community genetics has demonstrated that variation within a species can have strong impacts on associated communities and ecosystem processes. Yet, these studies have centred around individual focal species and at single trophic levels, ignoring the role of phenotypic variation in multiple taxa within an ecosystem. Given the ubiquitous nature of local adaptation, and thus intraspecific variation, we sought to understand how combinations of intraspecific variation in multiple species within an ecosystem impacts its ecology. Using two species that co-occur and demonstrate adaptation to their natal environments, black cottonwood (Populus trichocarpa) and three-spined stickleback (Gasterosteus aculeatus), we investigated the effects of intraspecific phenotypic variation on both top-down and bottom-up forces using a large-scale aquatic mesocosm experiment. Black cottonwood genotypes exhibit genetic variation in their productivity and consequently their leaf litter subsidies to the aquatic system, which mediates the strength of top-down effects from stickleback on prey abundances. Abundances of four common invertebrate prey species and available phosphorous, the most critically limiting nutrient in freshwater systems, are dictated by the interaction between genetic variation in cottonwood productivity and stickleback morphology. These interactive effects fit with ecological theory on the relationship between productivity and top-down control and are comparable in strength to the effects of predator addition. Our results illustrate that intraspecific variation, which can evolve rapidly, is an under-appreciated driver of community structure and ecosystem function, demonstrating that a multi-trophic perspective is essential to understanding the role of evolution in structuring ecological patterns. PMID:26203004

  11. Mechanisms underlying the basal forebrain enhancement of top-down and bottom-up attention.

    Science.gov (United States)

    Avery, Michael C; Dutt, Nikil; Krichmar, Jeffrey L

    2014-03-01

    Both attentional signals from frontal cortex and neuromodulatory signals from basal forebrain (BF) have been shown to influence information processing in the primary visual cortex (V1). These two systems exert complementary effects on their targets, including increasing firing rates and decreasing interneuronal correlations. Interestingly, experimental research suggests that the cholinergic system is important for increasing V1's sensitivity to both sensory and attentional information. To see how the BF and top-down attention act together to modulate sensory input, we developed a spiking neural network model of V1 and thalamus that incorporated cholinergic neuromodulation and top-down attention. In our model, activation of the BF had a broad effect that decreases the efficacy of top-down projections and increased the reliance of bottom-up sensory input. In contrast, we demonstrated how local release of acetylcholine in the visual cortex, which was triggered through top-down gluatmatergic projections, could enhance top-down attention with high spatial specificity. Our model matched experimental data showing that the BF and top-down attention decrease interneuronal correlations and increase between-trial reliability. We found that decreases in correlations were primarily between excitatory-inhibitory pairs rather than excitatory-excitatory pairs and suggest that excitatory-inhibitory decorrelation is necessary for maintaining low levels of excitatory-excitatory correlations. Increased inhibitory drive via release of acetylcholine in V1 may then act as a buffer, absorbing increases in excitatory-excitatory correlations that occur with attention and BF stimulation. These findings will lead to a better understanding of the mechanisms underyling the BF's interactions with attention signals and influences on correlations.

  12. Bottom-up model of self-organized criticality on networks.

    Science.gov (United States)

    Noël, Pierre-André; Brummitt, Charles D; D'Souza, Raissa M

    2014-01-01

    The Bak-Tang-Wiesenfeld (BTW) sandpile process is an archetypal, stylized model of complex systems with a critical point as an attractor of their dynamics. This phenomenon, called self-organized criticality, appears to occur ubiquitously in both nature and technology. Initially introduced on the two-dimensional lattice, the BTW process has been studied on network structures with great analytical successes in the estimation of macroscopic quantities, such as the exponents of asymptotically power-law distributions. In this article, we take a microscopic perspective and study the inner workings of the process through both numerical and rigorous analysis. Our simulations reveal fundamental flaws in the assumptions of past phenomenological models, the same models that allowed accurate macroscopic predictions; we mathematically justify why universality may explain these past successes. Next, starting from scratch, we obtain microscopic understanding that enables mechanistic models; such models can, for example, distinguish a cascade's area from its size. In the special case of a 3-regular network, we use self-consistency arguments to obtain a zero-parameter mechanistic (bottom-up) approximation that reproduces nontrivial correlations observed in simulations and that allows the study of the BTW process on networks in regimes otherwise prohibitively costly to investigate. We then generalize some of these results to configuration model networks and explain how one could continue the generalization. The numerous tools and methods presented herein are known to enable studying the effects of controlling the BTW process and other self-organizing systems. More broadly, our use of multitype branching processes to capture information bouncing back and forth in a network could inspire analogous models of systems in which consequences spread in a bidirectional fashion.

  13. Bottom-up control of geomagnetic secular variation by the Earth's inner core.

    Science.gov (United States)

    Aubert, Julien; Finlay, Christopher C; Fournier, Alexandre

    2013-10-10

    Temporal changes in the Earth's magnetic field, known as geomagnetic secular variation, occur most prominently at low latitudes in the Atlantic hemisphere (that is, from -90 degrees east to 90 degrees east), whereas in the Pacific hemisphere there is comparatively little activity. This is a consequence of the geographical localization of intense, westward drifting, equatorial magnetic flux patches at the core surface. Despite successes in explaining the morphology of the geomagnetic field, numerical models of the geodynamo have so far failed to account systematically for this striking pattern of geomagnetic secular variation. Here we show that it can be reproduced provided that two mechanisms relying on the inner core are jointly considered. First, gravitational coupling aligns the inner core with the mantle, forcing the flow of liquid metal in the outer core into a giant, westward drifting, sheet-like gyre. The resulting shear concentrates azimuthal magnetic flux at low latitudes close to the core-mantle boundary, where it is expelled by core convection and subsequently transported westward. Second, differential inner-core growth, fastest below Indonesia, causes an asymmetric buoyancy release in the outer core which in turn distorts the gyre, forcing it to become eccentric, in agreement with recent core flow inversions. This bottom-up heterogeneous driving of core convection dominates top-down driving from mantle thermal heterogeneities, and localizes magnetic variations in a longitudinal sector centred beneath the Atlantic, where the eccentric gyre reaches the core surface. To match the observed pattern of geomagnetic secular variation, the solid material forming the inner core must now be in a state of differential growth rather than one of growth and melting induced by convective translation.

  14. Do top-down or bottom-up forces determine Stephanitis pyrioides abundance in urban landscapes?

    Science.gov (United States)

    Shrewsbury, Paula M; Raupp, Michael J

    2006-02-01

    This study examined the influence of habitat structural complexity on the collective effects of top-down and bottom-up forces on herbivore abundance in urban landscapes. The persistence and varying complexity of urban landscapes set them apart from ephemeral agroecosystems and natural habitats where the majority of studies have been conducted. Using surveys and manipulative experiments. We explicitly tested the effect of natural enemies (enemies hypothesis), host plant quality, and herbivore movement on the abundance of the specialist insect herbivore, Stephanitis pyrioides, in landscapes of varying structural complexity. This herbivore was extremely abundant in simple landscapes and rare in complex ones. Natural enemies were the major force influencing abundance of S. pyrioides across habitat types. Generalist predators, particularly the spider Anyphaena celer, were more abundant in complex landscapes. Predator abundance was related to greater abundance of alternative prey in those landscapes. Stephanitis pyrioides survival was lower in complex habitats when exposed to endemic natural enemy populations. Laboratory feeding trials confirmed the more abundant predators consumed S. pyrioides. Host plant quality was not a strong force influencing patterns of S. pyrioides abundance. When predators were excluded, adult S. pyrioides survival was greater on azaleas grown in complex habitats, in opposition to the observed pattern of abundance. Similarly, complexity did not affect S. pyrioides immigration and emigration rates. The complexity of urban landscapes affects the strength of top-down forces on herbivorous insect populations by influencing alternative prey and generalist predator abundance. It is possible that habitats can be manipulated to promote the suppressive effects of generalist predators.

  15. Can synthetic pesticides be replaced with biologically-based alternatives?--an industry perspective.

    Science.gov (United States)

    Froyd, J D

    1997-09-01

    Agricultural chemical companies have invested in the discovery and development of biological pesticides to complement synthetic pesticides for the control of insects, diseases, and weeds on agronomic and horticultural crops. For plant disease control, companies envisage biological fungicides entering markets where they have the best chance of performing and which are most receptive to using biological control methods. Fewer regulatory requirements can mean faster registration for a biological than a synthetic pesticide. However, industry's requirements for competitive performance, effective formulations, and economic production can mean significant investments in time and money for a biological pesticide, although total investment may be less than for a synthetic pesticide. One biocontrol project in which industry has invested is baculoviruses for insect control. Insect baculoviruses, genetically modified to kill insects faster than wild-type viruses, are attractive biocontrol agents because their selectivity to insect pests and safety to beneficial insects and mammals enable them to compete with synthetic insecticides. Industry is looking for similar biocontrol opportunities in disease control. Biocontrol agents for seedling disease, root rot, and postharvest disease control have been registered by the EPA and are trying to compete with synthetic fungicides for market share. To date, effective biocontrol agents have not been identified for the control of serious foliar diseases, such as grape downy mildew, potato late blight, wheat powdery mildew, and apple scab. Farmers must rely on synthetic fungicides and agronomic methods to control these diseases for the foreseeable future.

  16. Biologically Inspired Waveform Diversity for Synthetic Autonomous Navigation Sensing

    Science.gov (United States)

    2009-11-01

    Autonomous Navigation Sensing UNCLASSIFIED/UNLIMITED (g) Long duration broadband calls are presently described only for the Malagasy sucker -footed bat...approach [12]. Target size was found not to affect call intensity during approach to targets of varying size in M. daubentonii [12]. In synthetic sensing...between target strength and frequency was developed for spheres by Lord Rayleigh over a century ago, the theoretical relationship between prey size and

  17. Synthetic biology and regulatory networks: where metabolic systems biology meets control engineering.

    Science.gov (United States)

    He, Fei; Murabito, Ettore; Westerhoff, Hans V

    2016-04-01

    Metabolic pathways can be engineered to maximize the synthesis of various products of interest. With the advent of computational systems biology, this endeavour is usually carried out through in silico theoretical studies with the aim to guide and complement further in vitro and in vivo experimental efforts. Clearly, what counts is the result in vivo, not only in terms of maximal productivity but also robustness against environmental perturbations. Engineering an organism towards an increased production flux, however, often compromises that robustness. In this contribution, we review and investigate how various analytical approaches used in metabolic engineering and synthetic biology are related to concepts developed by systems and control engineering. While trade-offs between production optimality and cellular robustness have already been studied diagnostically and statically, the dynamics also matter. Integration of the dynamic design aspects of control engineering with the more diagnostic aspects of metabolic, hierarchical control and regulation analysis is leading to the new, conceptual and operational framework required for the design of robust and productive dynamic pathways.

  18. Deciphering the language between biological and synthetic materials

    Directory of Open Access Journals (Sweden)

    Paolo Antonio Netti

    2014-06-01

    Full Text Available Chemical signals propagating through aqueous environment are at the basis of the language utilized by living systems to exchange information. In the last years, molecular biology has partly disclosed the grammar and the syntax of this complex language revealing the fascinating world of molecular communication that is the foundation of biological development.

  19. Pre-stimulus activity predicts the winner of top-down vs. bottom-up attentional selection.

    Directory of Open Access Journals (Sweden)

    Ali Mazaheri

    Full Text Available Our ability to process visual information is fundamentally limited. This leads to competition between sensory information that is relevant for top-down goals and sensory information that is perceptually salient, but task-irrelevant. The aim of the present study was to identify, from EEG recordings, pre-stimulus and pre-saccadic neural activity that could predict whether top-down or bottom-up processes would win the competition for attention on a trial-by-trial basis. We employed a visual search paradigm in which a lateralized low contrast target appeared alone, or with a low (i.e., non-salient or high contrast (i.e., salient distractor. Trials with a salient distractor were of primary interest due to the strong competition between top-down knowledge and bottom-up attentional capture. Our results demonstrated that 1 in the 1-sec pre-stimulus interval, frontal alpha (8-12 Hz activity was higher on trials where the salient distractor captured attention and the first saccade (bottom-up win; and 2 there was a transient pre-saccadic increase in posterior-parietal alpha (7-8 Hz activity on trials where the first saccade went to the target (top-down win. We propose that the high frontal alpha reflects a disengagement of attentional control whereas the transient posterior alpha time-locked to the saccade indicates sensory inhibition of the salient distractor and suppression of bottom-up oculomotor capture.

  20. Pre-stimulus activity predicts the winner of top-down vs. bottom-up attentional selection.

    Science.gov (United States)

    Mazaheri, Ali; DiQuattro, Nicholas E; Bengson, Jesse; Geng, Joy J

    2011-02-28

    Our ability to process visual information is fundamentally limited. This leads to competition between sensory information that is relevant for top-down goals and sensory information that is perceptually salient, but task-irrelevant. The aim of the present study was to identify, from EEG recordings, pre-stimulus and pre-saccadic neural activity that could predict whether top-down or bottom-up processes would win the competition for attention on a trial-by-trial basis. We employed a visual search paradigm in which a lateralized low contrast target appeared alone, or with a low (i.e., non-salient) or high contrast (i.e., salient) distractor. Trials with a salient distractor were of primary interest due to the strong competition between top-down knowledge and bottom-up attentional capture. Our results demonstrated that 1) in the 1-sec pre-stimulus interval, frontal alpha (8-12 Hz) activity was higher on trials where the salient distractor captured attention and the first saccade (bottom-up win); and 2) there was a transient pre-saccadic increase in posterior-parietal alpha (7-8 Hz) activity on trials where the first saccade went to the target (top-down win). We propose that the high frontal alpha reflects a disengagement of attentional control whereas the transient posterior alpha time-locked to the saccade indicates sensory inhibition of the salient distractor and suppression of bottom-up oculomotor capture.

  1. Engineered Micro-Objects as Scaffolding Elements in Cellular Building Blocks for Bottom-Up Tissue Engineering Approaches

    NARCIS (Netherlands)

    Leferink, A.M.; Schipper, D.; Arts, E.; Vrij, E.J.; Rivron, N.C.; Karperien, H.B.J.; Mittmann, K.; Blitterswijk, van C.A.; Moroni, L.; Truckenmuller, R.K.

    2014-01-01

    A material-based bottom-up approach is proposed towards an assembly of cells and engineered micro-objects at the macroscale. We show how shape, size and wettability of engineered micro-objects play an important role in the behavior of cells on these objects. This approach can, among other applicatio

  2. Evaluating the Resilience of the Bottom-up Method used to Detect and Benchmark the Smartness of University Campuses

    DEFF Research Database (Denmark)

    Giovannella, Carlo; Andone, Diana; Dascalu, Mihai

    2016-01-01

    A new method to perform a bottom-up extraction and benchmark of the perceived multilevel smartness of complex ecosystems has been recently described and applied to territories and learning ecosystems like university campuses and schools. In this paper we study the resilience of our method...

  3. Assessing the Gap Between Top-down and Bottom-up Measured Methane Emissions in Indianapolis, IN.

    Science.gov (United States)

    Prasad, K.; Lamb, B. K.; Cambaliza, M. O. L.; Shepson, P. B.; Stirm, B. H.; Salmon, O. E.; Lavoie, T. N.; Lauvaux, T.; Ferrara, T.; Howard, T.; Edburg, S. L.; Whetstone, J. R.

    2014-12-01

    Releases of methane (CH4) from the natural gas supply chain in the United States account for approximately 30% of the total US CH4 emissions. However, there continues to be large questions regarding the accuracy of current emission inventories for methane emissions from natural gas usage. In this paper, we describe results from top-down and bottom-up measurements of methane emissions from the large isolated city of Indianapolis. The top-down results are based on aircraft mass balance and tower based inverse modeling methods, while the bottom-up results are based on direct component sampling at metering and regulating stations, surface enclosure measurements of surveyed pipeline leaks, and tracer/modeling methods for other urban sources. Mobile mapping of methane urban concentrations was also used to identify significant sources and to show an urban-wide low level enhancement of methane levels. The residual difference between top-down and bottom-up measured emissions is large and cannot be fully explained in terms of the uncertainties in top-down and bottom-up emission measurements and estimates. Thus, the residual appears to be, at least partly, attributed to a significant wide-spread diffusive source. Analyses are included to estimate the size and nature of this diffusive source.

  4. Using classic methods in a networked manner: seeing volunteered spatial information in a bottom-up fashion

    NARCIS (Netherlands)

    Carton, L.J.; Ache, P.M.

    2014-01-01

    Using new social media and ICT infrastructures for self-organization, more and more citizen networks and business sectors organize themselves voluntarily around sustainability themes. The paper traces and evaluates one emerging innovation in such bottom-up, networked form of sustainable governance

  5. Evaluating the Resilience of the Bottom-up Method used to Detect and Benchmark the Smartness of University Campuses

    NARCIS (Netherlands)

    Giovannella, Carlo; Andone, Diana; Dascalu, Mihai; Popescu, Elvira; Rehm, Matthias; Mealha, Oscar

    2017-01-01

    A new method to perform a bottom-up extraction and benchmark of the perceived multilevel smartness of complex ecosystems has been recently described and applied to territories and learning ecosystems like university campuses and schools. In this paper we study the resilience of our method by co

  6. Citizenship Policy from the Bottom-Up: The Linguistic and Semiotic Landscape of a Naturalization Field Office

    Science.gov (United States)

    Loring, Ariel

    2015-01-01

    This article follows a bottom-up approach to language policy (Ramanathan, 2005; Wodak, 2006) in an analysis of citizenship in policy and practice. It compares representations of citizenship in and around a regional branch of the United States Citizenship and Immigration Services (USCIS), with a focus on citizenship swearing-in ceremonies for…

  7. Proceedings of Synthetic Biology: Engineering, Evolution and Design (SEED) Conference 2015

    Energy Technology Data Exchange (ETDEWEB)

    Silver, Pamela [Harvard Univ., Cambridge, MA (United States); SEED 2015 Conference Chair; Flach, Evan [American Institute of Chemical Engineers; SEED 2015 Conference Organizer

    2016-10-27

    Synthetic Biology is an emerging discipline that seeks to accelerate the process of engineering biology. As such, the tools are broadly applicable to application areas, including chemicals and biofuels, materials, medicine and agriculture. A characteristic of the field is to look holistically at cellular design, from sensing and genetic circuitry to the manipulation of cellular processes and actuators, to controlling metabolism, to programming multicellular behaviors. Further, the types of cells that are manipulated are broad, from in vitro systems to microbes and fungi to mammalian and plant cells and living animals. Many of the projects in synthetic biology seek to move biochemical functions across organisms. The field is highly interdisciplinary with faculty and students spread across departments that focus on engineering (biological, chemical, electrical, mechanical, civil, computer science) and basic science (biology and systems biology, chemistry, physics). While there have been many one-off workshops and meeting on synthetic biology, the 2014 Synthetic Biology: Engineering, Evolution and Design (SEED) was the first of an annual conference series that serves as a reliable place to pull together the involved disciplines in order to organize and exchange advances in the science and technology in the field. Further, the SEED conferences have a strong focus on industry, with many companies represented and actively participating. A number of these companies have started major efforts in synthetic biology including large companies (e.g., Pfizer, Novartis, Dow, Dupont, BP, Total), smaller companies have recently gone public (e.g., Amyris, Gevo, Intrexon), and many start-ups (e.g., Teslagen, Refactored Materials, Pivot, Genomatica). There are a number of loosely affiliated Synthetic Biology Centers, including ones at MIT, Boston University, UCSD, UCSF, UC-Berkeley, Imperial College, Oxford, and ETH. SEED 2015 will serve as the primary meeting at which international

  8. A Unique Model Platform for C4 Plant Systems and Synthetic Biology

    Science.gov (United States)

    2015-12-10

    agrobacterium mediated transformation 15. SUBJECT TERMS 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT Same as Report (SAR) 18. NUMBER OF...successful agrobacterium mediated transformation 15. SUBJECT TERMS synthetic biology, Systems Biology 16. SECURITY CLASSIFICATION OF...were obtained suggesting successful agrobacterium mediated transformation. Introduction: C4 plants such as sugarcane, maize and sorghum are more

  9. Experiential Engineering through iGEM--An Undergraduate Summer Competition in Synthetic Biology

    Science.gov (United States)

    Mitchell, Rudolph; Dori, Yehudit Judy; Kuldell, Natalie H.

    2011-01-01

    Unlike students in other engineering disciplines, undergraduates in biological engineering typically have limited opportunity to develop design competencies, and even fewer chances to implement their designed projects. The international Genetically Engineered Machines (iGEM) competition is a student Synthetic Biology competition that, in 2009,…

  10. Ambivalences of creating life societal and philosophical dimensions of synthetic biology

    CERN Document Server

    Engelhard, Margret; Toepfer, Georg

    2016-01-01

    "Synthetic biology" is the label of a new technoscientific field with many different facets and agendas. One common aim is to "create life", primarily by using engineering principles to design and modify biological systems for human use. In a wider context, the topic has become one of the big cases in the legitimization processes associated with the political agenda to solve global problems with the aid of (bio-)technological innovation. Conceptual-level and meta-level analyses are needed: we should sort out conceptual ambiguities to agree on what we talk about, and we need to spell out agendas to see the disagreements clearly. The book is based on the interdisciplinary summer school "Analyzing the societal dimensions of synthetic biology", which took place in Berlin in September 2014. The contributions address controversial discussions around the philosophical examination, public perception, moral evaluation and governance of synthetic biology.

  11. Intellectual property rights in synthetic biology: an anti-thesis to open access to research?

    Science.gov (United States)

    Saukshmya, Trichi; Chugh, Archana

    2010-12-01

    Synthetic Biology is a surging area of contemporary life science based research that is rapidly evolving by virtue of its multidisciplinary composition and applications. Biology never before has seen such a gold rush and demonstrated potential for knowledge based economy. The area of synthetic biology is in a nascent and tender stage, however issues pertaining to open access to research versus the monopolistic intellectual property regime (specifically patents) have already started raising concerns in the emerging bio-based economy. The present study critically analyses the comparative benefits as well as lacunas of open access to research and patenting issues. It is noteworthy that both approaches for synthetic biology development have to co-exist in order to optimally benefit the society at large.

  12. Reconciling Top-Down and Bottom-Up Estimates of Oil and Gas Methane Emissions in the Barnett Shale

    Science.gov (United States)

    Hamburg, S.

    2015-12-01

    Top-down approaches that use aircraft, tower, or satellite-based measurements of well-mixed air to quantify regional methane emissions have typically estimated higher emissions from the natural gas supply chain when compared to bottom-up inventories. A coordinated research campaign in October 2013 used simultaneous top-down and bottom-up approaches to quantify total and fossil methane emissions in the Barnett Shale region of Texas. Research teams have published individual results including aircraft mass-balance estimates of regional emissions and a bottom-up, 25-county region spatially-resolved inventory. This work synthesizes data from the campaign to directly compare top-down and bottom-up estimates. A new analytical approach uses statistical estimators to integrate facility emission rate distributions from unbiased and targeted high emission site datasets, which more rigorously incorporates the fat-tail of skewed distributions to estimate regional emissions of well pads, compressor stations, and processing plants. The updated spatially-resolved inventory was used to estimate total and fossil methane emissions from spatial domains that match seven individual aircraft mass balance flights. Source apportionment of top-down emissions between fossil and biogenic methane was corroborated with two independent analyses of methane and ethane ratios. Reconciling top-down and bottom-up estimates of fossil methane emissions leads to more accurate assessment of natural gas supply chain emission rates and the relative contribution of high emission sites. These results increase our confidence in our understanding of the climate impacts of natural gas relative to more carbon-intensive fossil fuels and the potential effectiveness of mitigation strategies.

  13. A bottom-up approach to urban metabolism: the perspective of BRIDGE

    Science.gov (United States)

    Chrysoulakis, N.; Borrego, C.; San Josè, R.; Grimmond, S. B.; Jones, M. B.; Magliulo, V.; Klostermann, J.; Santamouris, M.

    2011-12-01

    Urban metabolism considers a city as a system and usually distinguishes between energy and material flows as its components. "Metabolic" studies are usually top-down approaches that assess the inputs and outputs of food, water, energy, and pollutants from a city, or that compare the changing metabolic process of several cities. In contrast, bottom-up approaches are based on quantitative estimates of urban metabolism components at local to regional scales. Such approaches consider the urban metabolism as the 3D exchange and transformation of energy and matter between a city and its environment. The city is considered as a system and the physical flows between this system and its environment are quantitatively estimated. The transformation of landscapes from primarily agricultural and forest uses to urbanized landscapes can greatly modify energy and material exchanges and it is, therefore, an important aspect of an urban area. Here we focus on the exchanges and transformation of energy, water, carbon and pollutants. Recent advances in bio-physical sciences have led to new methods and models to estimate local scale energy, water, carbon and pollutant fluxes. However, there is often poor communication of new knowledge and its implications to end-users, such as planners, architects and engineers. The FP7 Project BRIDGE (SustainaBle uRban plannIng Decision support accountinG for urban mEtabolism) aims at bridging this gap and at illustrating the advantages of considering environmental issues in urban planning. BRIDGE does not perform a complete life cycle analysis or calculate whole system urban metabolism, but rather focuses on specific metabolism components (energy, water, carbon and pollutants). Its main goal is the development of a Decision Suport System (DSS) with the potential to select planning actions which better fit the goal of changing the metabolism of urban systems towards sustainability. BRIDGE evaluates how planning alternatives can modify the physical

  14. Cosmo Cassette: A Microfluidic Microgravity Microbial System For Synthetic Biology Unit Tests and Satellite Missions

    Science.gov (United States)

    Berliner, Aaron J.

    2013-01-01

    Although methods in the design-build-test life cycle of the synthetic biology field have grown rapidly, the expansion has been non-uniform. The design and build stages in development have seen innovations in the form of biological CAD and more efficient means for building DNA, RNA, and other biological constructs. The testing phase of the cycle remains in need of innovation. Presented will be both a theoretical abstraction of biological measurement and a practical demonstration of a microfluidics-based platform for characterizing synthetic biological phenomena. Such a platform demonstrates a design of additive manufacturing (3D printing) for construction of a microbial fuel cell (MFC) to be used in experiments carried out in space. First, the biocompatibility of the polypropylene chassis will be demonstrated. The novel MFCs will be cheaper, and faster to make and iterate through designs. The novel design will contain a manifold switchingdistribution system and an integrated in-chip set of reagent reservoirs fabricated via 3D printing. The automated nature of the 3D printing yields itself to higher resolution switching valves and leads to smaller sized payloads, lower cost, reduced power and a standardized platform for synthetic biology unit tests on Earth and in space. It will be demonstrated that the application of unit testing in synthetic biology will lead to the automatic construction and validation of desired constructs. Unit testing methodologies offer benefits of preemptive problem identification, change of facility, simplicity of integration, ease of documentation, and separation of interface from implementation, and automated design.

  15. Co-culture systems and technologies: taking synthetic biology to the next level.

    Science.gov (United States)

    Goers, Lisa; Freemont, Paul; Polizzi, Karen M

    2014-07-06

    Co-culture techniques find myriad applications in biology for studying natural or synthetic interactions between cell populations. Such techniques are of great importance in synthetic biology, as multi-species cell consortia and other natural or synthetic ecology systems are widely seen to hold enormous potential for foundational research as well as novel industrial, medical and environmental applications with many proof-of-principle studies in recent years. What is needed for co-cultures to fulfil their potential? Cell-cell interactions in co-cultures are strongly influenced by the extracellular environment, which is determined by the experimental set-up, which therefore needs to be given careful consideration. An overview of existing experimental and theoretical co-culture set-ups in synthetic biology and adjacent fields is given here, and challenges and opportunities involved in such experiments are discussed. Greater focus on foundational technology developments for co-cultures is needed for many synthetic biology systems to realize their potential in both applications and answering biological questions.

  16. High molecular weight DNA assembly in vivo for synthetic biology applications.

    Science.gov (United States)

    Juhas, Mario; Ajioka, James W

    2017-05-01

    DNA assembly is the key technology of the emerging interdisciplinary field of synthetic biology. While the assembly of smaller DNA fragments is usually performed in vitro, high molecular weight DNA molecules are assembled in vivo via homologous recombination in the host cell. Escherichia coli, Bacillus subtilis and Saccharomyces cerevisiae are the main hosts used for DNA assembly in vivo. Progress in DNA assembly over the last few years has paved the way for the construction of whole genomes. This review provides an update on recent synthetic biology advances with particular emphasis on high molecular weight DNA assembly in vivo in E. coli, B. subtilis and S. cerevisiae. Special attention is paid to the assembly of whole genomes, such as those of the first synthetic cell, synthetic yeast and minimal genomes.

  17. Synthetic biology devices and circuits for RNA-based 'smart vaccines': a propositional review.

    Science.gov (United States)

    Andries, Oliwia; Kitada, Tasuku; Bodner, Katie; Sanders, Niek N; Weiss, Ron

    2015-02-01

    Nucleic acid vaccines have been gaining attention as an alternative to the standard attenuated pathogen or protein based vaccine. However, an unrealized advantage of using such DNA or RNA based vaccination modalities is the ability to program within these nucleic acids regulatory devices that would provide an immunologist with the power to control the production of antigens and adjuvants in a desirable manner by administering small molecule drugs as chemical triggers. Advances in synthetic biology have resulted in the creation of highly predictable and modular genetic parts and devices that can be composed into synthetic gene circuits with complex behaviors. With the recent advent of modified RNA gene delivery methods and developments in the RNA replicon platform, we foresee a future in which mammalian synthetic biologists will create genetic circuits encoded exclusively on RNA. Here, we review the current repertoire of devices used in RNA synthetic biology and propose how programmable 'smart vaccines' will revolutionize the field of RNA vaccination.

  18. Overloaded and stressed: whole-cell considerations for bacterial synthetic biology.

    Science.gov (United States)

    Borkowski, Olivier; Ceroni, Francesca; Stan, Guy-Bart; Ellis, Tom

    2016-10-01

    The predictability and robustness of engineered bacteria depend on the many interactions between synthetic constructs and their host cells. Expression from synthetic constructs is an unnatural load for the host that typically reduces growth, triggers stresses and leads to decrease in performance or failure of engineered cells. Work in systems and synthetic biology has now begun to address this through new tools, methods and strategies that characterise and exploit host-construct interactions in bacteria. Focusing on work in E. coli, we review here a selection of the recent developments in this area, highlighting the emerging issues and describing the new solutions that are now making the synthetic biology community consider the cell just as much as they consider the construct.

  19. Standardization, IPRs and open innovation in synthetic biology

    DEFF Research Database (Denmark)

    Minssen, Timo; Wested, Jakob

    2015-01-01

    (ICT) to biological standards? These and further legal issues related to IP, regulation, standardization, competition law & open innovation require a careful consideration of new user-generated models and solutions. Before this background this paper seeks to describe IP and standardization aspects...

  20. Glowing Plants and Living Machines. Towards a Critique of Synthetic Biology

    Directory of Open Access Journals (Sweden)

    Martin Müller

    2016-12-01

    Full Text Available This article criticly engages with 1 synthetic biologys’ technoscientific specifica, 2 the role of biotechnical and biopolitical promises of perfectibility of‚ life itself’, and 3 the problematic notion of ‘digital biology’. Synthetic biology dismisses the idea of an already given nature: ‘life itself’ is conceptualized as a field of potentialities, with adaptable materials and flexible structures that can be used for re-engineering to ‘perfect’ nature. Bioengineers claim to create new living organisms from scratch, using genetically standardized parts and computer-based design: ‘Living machines’ which do not exist in nature are supposed to serve human purposes. Beyond its actual (and limited state of research, some voices of synthetic biology offer bold claims of socio-technical scenarios, imagined objects, and future biotechnical experiments, which take place in society rather than behind laboratory doors. With their visions, synthetic biologists are becoming engineers of future societies. Synthetic biology develops a ‘biotechnologization of collective futures’ and it is part of a technoscientific ‘promise- economy’ that aims on colonizing the future - which demands to rethink Foucaults the question of biopolitics. Crucial for synthetic biologys’ promise of ‘digital biology’ are script-centered, bio-cybernetic, and even transhumanist figures of thought that fuel new visions of ‘life and nature’ as a field of potentials and even limitless treasures that can be programmed and produced by computational procedures: ‘writing’ the code of life.

  1. From Extremophiles to Star Trek, The Use of Synthetic Biology in Astrobiology

    Science.gov (United States)

    Rothschild, Lynn J.; Fujishima, Kosuke; Lima, Ivan Paulino; Gentry, Diana; Phan, Samson; Navarette, Jesica; Palmer, Jesse; Burnier, Andre

    2012-01-01

    Synthetic biology – the design and construction of new biological parts and systems and the redesign of existing ones for useful purposes – has the potential to transform fields from pharmaceuticals to fuels. Our lab has focused on the potential of synthetic biology to revolutionize all three major parts of astrobiology: Where do we come from? Where are we going? and Are we alone? For the first and third, synthetic biology is allowing us to answer whether the evolutionary narrative that has played out on planet earth is likely to have been unique or universal. For example, in our lab we are re-evolving biotic functions using only the most thermodynamically stable amino acids in order to understand potential capabilities of an early organism with a limited repertoire of amino acids. In the future synthetic biology will play an increasing role in human activities both on earth, in fields as diverse as bio-mining, human health and the industrial production of novel bio-composites. Beyond earth, we will rely increasingly on biologically-provided life support, as we have throughout our evolutionary history. In order to do this, the field will build on two of the great contributions of astrobiology: studies of the origin of life and life in extreme environments.

  2. Flow cytometry for bacteria: enabling metabolic engineering, synthetic biology and the elucidation of complex phenotypes.

    Science.gov (United States)

    Tracy, Bryan P; Gaida, Stefan M; Papoutsakis, Eleftherios T

    2010-02-01

    Flow cytometry (FC) and FC-based cell sorting have been established as critical tools in modern cell and developmental biology. Yet, their applications in bacteria, especially in the multiparametric mode, remain limited. We argue that FC technologies have the potential to greatly accelerate the analysis and development of microbial complex phenotypes through applications of metabolic engineering, synthetic biology, and evolutionary engineering. We demonstrate the importance of FC for elucidating population heterogeneity because of developmental processes or epigenetic regulation. FC can be engaged for both synthetic and analytical applications of complex phenotypes within a single species, multispecies, and microbial-library populations. Examples include methods to identify developmental microbial stages associated with productive metabolic phenotypes, select desirable promoters from a single species or metagenomic libraries, and to screen designer riboswitches for synthetic-biology applications.

  3. Synthetic Biology and the Moral Significance of Artificial Life: A Reply to Douglas, Powell and Savulescu.

    Science.gov (United States)

    Christiansen, Andreas

    2016-06-01

    I discuss the moral significance of artificial life within synthetic biology via a discussion of Douglas, Powell and Savulescu's paper 'Is the creation of artificial life morally significant'. I argue that the definitions of 'artificial life' and of 'moral significance' are too narrow. Douglas, Powell and Savulescu's definition of artificial life does not capture all core projects of synthetic biology or the ethical concerns that have been voiced, and their definition of moral significance fails to take into account the possibility that creating artificial life is conditionally acceptable. Finally, I show how several important objections to synthetic biology are plausibly understood as arguing that creating artificial life in a wide sense is only conditionally acceptable.

  4. Recent progress in synthetic biology for microbial production of C3-C10 alcohols

    Directory of Open Access Journals (Sweden)

    Edna N. Lamsen

    2012-06-01

    Full Text Available The growing need to address current energy and environmental problems has sparked an interest in developing improved biological methods to produce liquid fuels from renewable sources. While microbial ethanol production is well established, higher chain alcohols possess chemical properties that are more similar to gasoline. Unfortunately, these alcohols (except 1-butanol are not produced efficiently in natural microorganisms, and thus economical production in industrial volumes remains a challenge. Synthetic biology, however, offers additional tools to engineer synthetic pathways in user-friendly hosts to help increase titers and productivity of these advanced biofuels. This review concentrates on recent developments in synthetic biology to produce higher-chain alcohols as viable renewable replacements for traditional fuel.

  5. Synthetic biology outside the cell: linking computational tools to cell-free systems.

    Science.gov (United States)

    Lewis, Daniel D; Villarreal, Fernando D; Wu, Fan; Tan, Cheemeng

    2014-01-01

    As mathematical models become more commonly integrated into the study of biology, a common language for describing biological processes is manifesting. Many tools have emerged for the simulation of in vivo synthetic biological systems, with only a few examples of prominent work done on predicting the dynamics of cell-free synthetic systems. At the same time, experimental biologists have begun to study dynamics of in vitro systems encapsulated by amphiphilic molecules, opening the door for the development of a new generation of biomimetic systems. In this review, we explore both in vivo and in vitro models of biochemical networks with a special focus on tools that could be applied to the construction of cell-free expression systems. We believe that quantitative studies of complex cellular mechanisms and pathways in synthetic systems can yield important insights into what makes cells different from conventional chemical systems.

  6. Review of Microfluidic Photobioreactor Technology for Metabolic Engineering and Synthetic Biology of Cyanobacteria and Microalgae

    Directory of Open Access Journals (Sweden)

    Ya-Tang Yang

    2016-10-01

    Full Text Available One goal of metabolic engineering and synthetic biology for cyanobacteria and microalgae is to engineer strains that can optimally produce biofuels and commodity chemicals. However, the current workflow is slow and labor intensive with respect to assembly of genetic parts and characterization of production yields because of the slow growth rates of these organisms. Here, we review recent progress in the microfluidic photobioreactors and identify opportunities and unmet needs in metabolic engineering and synthetic biology. Because of the unprecedented experimental resolution down to the single cell level, long-term real-time monitoring capability, and high throughput with low cost, microfluidic photobioreactor technology will be an indispensible tool to speed up the development process, advance fundamental knowledge, and realize the full potential of metabolic engineering and synthetic biology for cyanobacteria and microalgae.

  7. Optimality in evolution: new insights from synthetic biology.

    Science.gov (United States)

    de Vos, Marjon G J; Poelwijk, Frank J; Tans, Sander J

    2013-08-01

    Whether organisms evolve to perform tasks optimally has intrigued biologists since Lamarck and Darwin. Optimality models have been used to study diverse properties such as shape, locomotion, and behavior. However, without access to the genetic underpinnings or the ability to manipulate biological functions, it has been difficult to understand an organism's intrinsic potential and limitations. Now, novel experiments are overcoming these technical obstacles and have begun to test optimality in more quantitative terms. With the use of simple model systems, genetic engineering, and mathematical modeling, one can independently quantify the prevailing selective pressures and optimal phenotypes. These studies have given an exciting view into the evolutionary potential and constraints of biological systems, and hold the promise to further test the limits of predicting future evolutionary change.

  8. Applications of membrane computing in systems and synthetic biology

    CERN Document Server

    Gheorghe, Marian; Pérez-Jiménez, Mario

    2014-01-01

    Membrane Computing was introduced as a computational paradigm in Natural Computing. The models introduced, called Membrane (or P) Systems, provide a coherent platform to describe and study living cells as computational systems. Membrane Systems have been investigated for their computational aspects and employed to model problems in other fields, like: Computer Science, Linguistics, Biology, Economy, Computer Graphics, Robotics, etc. Their inherent parallelism, heterogeneity and intrinsic versatility allow them to model a broad range of processes and phenomena, being also an efficient means to solve and analyze problems in a novel way. Membrane Computing has been used to model biological systems, becoming with time a thorough modeling paradigm comparable, in its modeling and predicting capabilities, to more established models in this area. This book is the result of the need to collect, in an organic way, different facets of this paradigm. The chapters of this book, together with the web pages accompanying th...

  9. Sender-receiver systems and applying information theory for quantitative synthetic biology.

    Science.gov (United States)

    Barcena Menendez, Diego; Senthivel, Vivek Raj; Isalan, Mark

    2015-02-01

    Sender-receiver (S-R) systems abound in biology, with communication systems sending information in various forms. Information theory provides a quantitative basis for analysing these processes and is being applied to study natural genetic, enzymatic and neural networks. Recent advances in synthetic biology are providing us with a wealth of artificial S-R systems, giving us quantitative control over networks with a finite number of well-characterised components. Combining the two approaches can help to predict how to maximise signalling robustness, and will allow us to make increasingly complex biological computers. Ultimately, pushing the boundaries of synthetic biology will require moving beyond engineering the flow of information and towards building more sophisticated circuits that interpret biological meaning.

  10. Sender–receiver systems and applying information theory for quantitative synthetic biology

    Science.gov (United States)

    Barcena Menendez, Diego; Senthivel, Vivek Raj; Isalan, Mark

    2015-01-01

    Sender–receiver (S–R) systems abound in biology, with communication systems sending information in various forms. Information theory provides a quantitative basis for analysing these processes and is being applied to study natural genetic, enzymatic and neural networks. Recent advances in synthetic biology are providing us with a wealth of artificial S–R systems, giving us quantitative control over networks with a finite number of well-characterised components. Combining the two approaches can help to predict how to maximise signalling robustness, and will allow us to make increasingly complex biological computers. Ultimately, pushing the boundaries of synthetic biology will require moving beyond engineering the flow of information and towards building more sophisticated circuits that interpret biological meaning. PMID:25282688

  11. Genome-scale engineering for systems and synthetic biology

    OpenAIRE

    Esvelt, Kevin Michael; Wang, Harris H.

    2013-01-01

    Genome-modification technologies enable the rational engineering and perturbation of biological systems. Historically, these methods have been limited to gene insertions or mutations at random or at a few pre-defined locations across the genome. The handful of methods capable of targeted gene editing suffered from low efficiencies, significant labor costs, or both. Recent advances have dramatically expanded our ability to engineer cells in a directed and combinatorial manner. Here, we review ...

  12. Influenza Neuraminidase Inhibitors: Synthetic Approaches, Derivatives and Biological Activity

    Directory of Open Access Journals (Sweden)

    Pedro Laborda

    2016-11-01

    Full Text Available Despite being a common viral disease, influenza has very negative consequences, causing the death of around half a million people each year. A neuraminidase located on the surface of the virus plays an important role in viral reproduction by contributing to the release of viruses from infected host cells. The treatment of influenza is mainly based on the administration of neuraminidase inhibitors. The neuraminidase inhibitors zanamivir, laninamivir, oseltamivir and peramivir have been commercialized and have been demonstrated to be potent influenza viral neuraminidase inhibitors against most influenza strains. In order to create more potent neuraminidase inhibitors and fight against the surge in resistance resulting from naturally-occurring mutations, these anti-influenza drugs have been used as templates for the development of new neuraminidase inhibitors through structure-activity relationship studies. Here, we review the synthetic routes to these commercial drugs, the modifications which have been performed on these structures and the effects of these modifications on their inhibitory activity.

  13. Kinetics of struvite precipitation in synthetic biologically treated swine wastewaters.

    Science.gov (United States)

    Capdevielle, Aurélie; Sýkorová, Eva; Béline, Fabrice; Daumer, Marie-Line

    2014-01-01

    An experimental design was set up to understand the influence of five process parameters on the kinetics of struvite precipitation in synthetic swine wastewaters. The responses studied were the kinetics of phosphorus (P) removal, the struvite precipitation rate and the dissolution rate of amorphous calcium phosphates (ACP). The kinetic study showed that the P-removal was complete in less than 1 h and was influenced positively by the added MgO. The precipitation of struvite with MgO was confirmed to follow a first-order kinetic. This study showed that ACP co-precipitated with struvite during the first 30 min. Afterwards, ACP dissolved to maintain the phosphates balance limiting the struvite growth. An initial Mg:Ca > 1.5 induced a complete dissolution of ACP in 1 h. Another experiment was conducted and it validated the results of the statistical model. This experiment also determined that 7-10 h was the best time to recover large crystals. After 10 h, the crystals were broken by stirring.

  14. New synthetic strategies towards psammaplin A, access to natural product analogues for biological evaluation.

    Science.gov (United States)

    Baud, Matthias G J; Leiser, Thomas; Meyer-Almes, Franz-Josef; Fuchter, Matthew J

    2011-02-07

    New synthetic routes towards the natural product psammaplin A were developed with the particular view to preparing diverse analogues for biological assessment. These routes utilize cheap and commercially available starting materials, and allowed access to psammaplin A analogues not accessible via currently reported methods. Preliminary biological studies revealed these compounds to be the most potent non peptidic inhibitors of the enzyme histone deacetylase 1 (HDAC1, class I) discovered so far. Interestingly, psammaplin A and our synthetic analogues show class I selectivity in vitro, an important feature for the design and synthesis of future isoform selective inhibitors.

  15. SEVA Linkers: A Versatile and Automatable DNA Backbone Exchange Standard for Synthetic Biology

    DEFF Research Database (Denmark)

    Kim, Se Hyeuk; Cavaleiro, Mafalda; Rennig, Maja

    2016-01-01

    DNA vectors serve to maintain and select recombinant DNA in cell factories, and as design complexity increases, there is a greater need for well-characterized parts and methods for their assembly. Standards in synthetic biology are top priority, but standardizing molecular cloning contrasts...... flexibility, and different researchers prefer and master different molecular technologies. Here, we describe a new, highly versatile and automatable standard “SEVA linkers” for vector exchange. SEVA linkers enable backbone swapping with 20 combinations of classical enzymatic restriction/ligation, Gibson...... to the synthetic biology community....

  16. Industry 5.0—The Relevance and Implications of Bionics and Synthetic Biology

    OpenAIRE

    Peter Sachsenmeier

    2016-01-01

    Bionics (the imitation or abstraction of the “inventions of nature) and, to an even greater extent, synthetic biology, will be as relevant to engineering development and industry as the silicon chip was over the last 50 years. Chemical industries already use so-called “white biotechnology” for new processes, new raw materials, and more sustainable use of resources. Synthetic biology is also used for the development of second-generation biofuels and for harvesting the sun's energy with the hel...

  17. GUBS, a Behavior-based Language for Open System Dedicated to Synthetic Biology

    Directory of Open Access Journals (Sweden)

    Adrien Basso-Blandin

    2012-11-01

    Full Text Available In this article, we propose a domain specific language, GUBS (Genomic Unified Behavior Specification, dedicated to the behavioral specification of synthetic biological devices, viewed as discrete open dynamical systems. GUBS is a rule-based declarative language. By contrast to a closed system, a program is always a partial description of the behavior of the system. The semantics of the language accounts the existence of some hidden non-specified actions possibly altering the behavior of the programmed device. The compilation framework follows a scheme similar to automatic theorem proving, aiming at improving synthetic biological design safety.

  18. Glutarimides: Biological activity, general synthetic methods and physicochemical properties

    Directory of Open Access Journals (Sweden)

    Popović-Đorđević Jelena B.

    2015-01-01

    Full Text Available Glutarimides, 2,6-dioxopiperidines are compounds that rarely occur in natural sources, but so far isolated ones exert widespread pharmacological activities, which makes them valuable as potential pharmacotherapeutics. Glutarimides act as androgen receptor antagonists, anti-inflammatory, anxiolytics, antibacterials, and tumor suppressing agents. Some synthetic glutarimide derivatives are already in use as immunosuppressive and sedative (e.g., thalidomide or anxiolytics (buspirone drugs. The wide applicability of this class of compounds, justify the interest of scientists to explore new pathways for its syntheses. General methods for synthesis of six-membered imide ring, are presented in this paper. These methods include: a reaction of dicarboxylic acids with ammonia or primary amine, b reactions of cyclization: amido-acids, diamides, dinitriles, nitrilo-acids, amido-nitriles, amido-esters, amidoacyl-chlorides or diacyl-chlorides, c adition of carbon-monoxide on a,b-unsaturated amides, d oxidation reactions, e Michael adition of active methylen compounds on methacrylamide or conjugated amides. Some of the described methods are used for closing glutarimide ring in syntheses of farmacological active compounds sesbanimide and aldose reductase inhibitors (ARI. Analyses of the geometry, as well as, the spectroscopic analyses (NMR and FT-IR of some glutarimides are presented because of their broad spectrum of pharmacological activity. To elucidate structures of glutarimides, geometrical parameters of newly synthesized tert-pentyl-1-benzyl-4-methyl-glutarimide-3-carboxylate (PBMG are analyzed and compared with the experimental data from X-ray analysis for glutarimide. Moreover, molecular electrostatic potential (MEP surface which is plotted over the optimized geometry to elucidate the reactivity of PBMG molecule is analyzed. The electronic properties of glutarimide derivatives are explained on the example of thalidomide. The Frontier Molecular Orbital

  19. Developing a comprehensive and comparative questionnaire for measuring personality in chimpanzees using a simultaneous top-down/bottom-up design.

    Science.gov (United States)

    Freeman, Hani D; Brosnan, Sarah F; Hopper, Lydia M; Lambeth, Susan P; Schapiro, Steven J; Gosling, Samuel D

    2013-10-01

    One effective method for measuring personality in primates is to use personality trait ratings to distill the experience of people familiar with the individual animals. Previous rating instruments were created using either top-down or bottom-up approaches. Top-down approaches, which essentially adapt instruments originally designed for use with another species, can unfortunately lead to the inclusion of traits irrelevant to chimpanzees or fail to include all relevant aspects of chimpanzee personality. Conversely, because bottom-up approaches derive traits specifically for chimpanzees, their unique items may impede comparisons with findings in other studies and other species. To address the limitations of each approach, we developed a new personality rating scale using a combined top-down/bottom-up design. Seventeen raters rated 99 chimpanzees on the new 41-item scale, with all but one item being rated reliably. Principal components analysis, using both varimax and direct oblimin rotations, identified six broad factors. Strong evidence was found for five of the factors (Reactivity/Undependability, Dominance, Openness, Extraversion, and Agreeableness). A sixth factor (Methodical) was offered provisionally until more data are collected. We validated the factors against behavioral data collected independently on the chimpanzees. The five factors demonstrated good evidence for convergent and predictive validity, thereby underscoring the robustness of the factors. Our combined top-down/bottom-up approach provides the most extensive data to date to support the universal existence of these five personality factors in chimpanzees. This framework, which facilitates cross-species comparisons, can also play a vital role in understanding the evolution of personality and can assist with husbandry and welfare efforts.

  20. Benchmarking energy scenarios for China: perspectives from top-down, economic and bottom-up, technical modelling

    DEFF Research Database (Denmark)

    This study uses a soft-linking methodology to harmonise two complex global top-down and bottom-up models with a regional China focus. The baseline follows the GDP and demographic trends of the Shared Socio-economic Pathways (SSP2) scenario, down-scaled for China, while the carbon tax scenario......-specific modelling results further. These new sub-regional China features can now be used for a more detailed analysis of China's regional developments in a global context....

  1. [Impact of synthetic biology on patent law in view of of European jurisprudence].

    Science.gov (United States)

    Bernardo Alvarez, María Angela

    2014-01-01

    The roots of synthetic biology--the redesign of biological molecules, structures and organisms--can be traced to the research developed by Jacques L. Monod and François Jacob in 1961. This field has undergone significant growth in the past ten years and its emergence has raised the question of whether the patent system is suitable to protect inventions in emergent areas as synthetic biology. The article will analyze the numerous scientific, socio-economic, ethical and legal challenges faced by synthetic biology, introducing the European Patent Law related to biotechnology as the minimum common framework and considering if more changes are needed to adequately protect the inventor rights, while taking into account the arrival of a new research culture, characterized by embracing open-innovation and open-source initiatives. The discussion will review some biotechnological patent law cases and summarize questions as whether isolated molecules of DNA are eligible for patent or the patentability of living matter, under the terms of Directive 98/44/EC. The article will finally consider the impact of synthetic biology on the European patent system.

  2. A comprehensive estimate of recent carbon sinks in China using both top-down and bottom-up approaches

    Science.gov (United States)

    Jiang, Fei; Chen, Jing; Zhou, Linxi; Ju, Weimin; Zhang, Huifang; Machida, Toshinobu; Ciais, Philippe; Peters, Wouter; Wang, Hengmao; Chen, Baozhang; Liu, Linxin; Zhang, Chunhua; Matsueda, Hidekazu; Sawa, Yousuke

    2016-04-01

    Atmospheric inversions use measurements of atmospheric CO2 gradients to constrain regional surface fluxes. Current inversions indicate a net terrestrial CO2 sink in China between 0.16 and 0.35 PgC/yr. The uncertainty of these estimates is as large as the mean because the atmospheric network historically contained only one high altitude station in China. Here, we revisit the calculation of the terrestrial CO2 flux in China, excluding emissions from fossil fuel burning and cement production, by using two inversions with three new CO2 monitoring stations in China as well as aircraft observations over Asia. We estimate a net terrestrial CO2 uptake of 0.39-0.51 PgC/yr with a mean of 0.45 PgC/yr in 2006-2009. After considering the lateral transport of carbon in air and water and international trade, the annual mean carbon sink is adjusted to 0.35 PgC/yr. To evaluate this top-down estimate, we constructed an independent bottom-up estimate based on ecosystem data, and giving a net land sink of 0.33 PgC/yr. This demonstrates closure between the top-down and bottom-up estimates. Both top-down and bottom-up estimates give a higher carbon sink than previous estimates made for the 1980s and 1990s, suggesting a trend towards increased uptake by land ecosystems in China.

  3. Sponge communities on Caribbean coral reefs are structured by factors that are top-down, not bottom-up.

    Directory of Open Access Journals (Sweden)

    Joseph R Pawlik

    Full Text Available Caribbean coral reefs have been transformed in the past few decades with the demise of reef-building corals, and sponges are now the dominant habitat-forming organisms on most reefs. Competing hypotheses propose that sponge communities are controlled primarily by predatory fishes (top-down or by the availability of picoplankton to suspension-feeding sponges (bottom-up. We tested these hypotheses on Conch Reef, off Key Largo, Florida, by placing sponges inside and outside predator-excluding cages at sites with less and more planktonic food availability (15 m vs. 30 m depth. There was no evidence of a bottom-up effect on the growth of any of 5 sponge species, and 2 of 5 species grew more when caged at the shallow site with lower food abundance. There was, however, a strong effect of predation by fishes on sponge species that lacked chemical defenses. Sponges with chemical defenses grew slower than undefended species, demonstrating a resource trade-off between growth and the production of secondary metabolites. Surveys of the benthic community on Conch Reef similarly did not support a bottom-up effect, with higher sponge cover at the shallower depth. We conclude that the structure of sponge communities on Caribbean coral reefs is primarily top-down, and predict that removal of sponge predators by overfishing will shift communities toward faster-growing, undefended species that better compete for space with threatened reef-building corals.

  4. Genome-scale engineering for systems and synthetic biology.

    Science.gov (United States)

    Esvelt, Kevin M; Wang, Harris H

    2013-01-01

    Genome-modification technologies enable the rational engineering and perturbation of biological systems. Historically, these methods have been limited to gene insertions or mutations at random or at a few pre-defined locations across the genome. The handful of methods capable of targeted gene editing suffered from low efficiencies, significant labor costs, or both. Recent advances have dramatically expanded our ability to engineer cells in a directed and combinatorial manner. Here, we review current technologies and methodologies for genome-scale engineering, discuss the prospects for extending efficient genome modification to new hosts, and explore the implications of continued advances toward the development of flexibly programmable chasses, novel biochemistries, and safer organismal and ecological engineering.

  5. Silicon Nitride: A Synthetic Mineral for Vertebrate Biology

    Science.gov (United States)

    Pezzotti, Giuseppe; McEntire, Bryan J.; Bock, Ryan; Boffelli, Marco; Zhu, Wenliang; Vitale, Eleonora; Puppulin, Leonardo; Adachi, Tetsuya; Yamamoto, Toshiro; Kanamura, Narisato; Bal, B. Sonny

    2016-08-01

    The remarkable stoichiometric flexibility of hydroxyapatite (HAp) enables the formation of a variety of charged structural sites at the material’s surface which facilitates bone remodeling due to binding of biomolecule moieties in zwitterionic fashion. In this paper, we report for the first time that an optimized biomedical grade silicon nitride (Si3N4) demonstrated cell adhesion and improved osteoconductivity comparable to highly defective, non-stoichiometric natural hydroxyapatite. Si3N4’s zwitterionic-like behavior is a function of the dualism between positive and negative charged off-stoichiometric sites (i.e., N-vacancies versus silanols groups, respectively). Lattice defects at the biomaterial’s surface greatly promote interaction with positively- and negatively-charged functional groups in biomolecules, and result in the biologically effective characteristics of silicon nitride. These findings are anticipated to be a starting point for further discoveries of therapeutic bone-graft substitute materials.

  6. Synthetic biology and biomimetic chemistry as converging technologies fostering a new generation of smart biosensors.

    Science.gov (United States)

    Scognamiglio, Viviana; Antonacci, Amina; Lambreva, Maya D; Litescu, Simona C; Rea, Giuseppina

    2015-12-15

    Biosensors are powerful tunable systems able to switch between an ON/OFF status in response to an external stimulus. This extraordinary property could be engineered by adopting synthetic biology or biomimetic chemistry to obtain tailor-made biosensors having the desired requirements of robustness, sensitivity and detection range. Recent advances in both disciplines, in fact, allow to re-design the configuration of the sensing elements - either by modifying toggle switches and gene networks, or by producing synthetic entities mimicking key properties of natural molecules. The present review considered the role of synthetic biology in sustaining biosensor technology, reporting examples from the literature and reflecting on the features that make it a useful tool for designing and constructing engineered biological systems for sensing application. Besides, a section dedicated to bioinspired synthetic molecules as powerful tools to enhance biosensor potential is reported, and treated as an extension of the concept of biomimetic chemistry, where organic synthesis is used to generate artificial molecules that mimic natural molecules. Thus, the design of synthetic molecules, such as aptamers, biomimetics, molecular imprinting polymers, peptide nucleic acids, and ribozymes were encompassed as "products" of biomimetic chemistry.

  7. RNA and RNP as Building Blocks for Nanotechnology and Synthetic Biology.

    Science.gov (United States)

    Ohno, Hirohisa; Saito, Hirohide

    2016-01-01

    Recent technologies that aimed to elucidate cellular function have revealed essential roles for RNA molecules in living systems. Our knowledge concerning functional and structural information of naturally occurring RNA and RNA-protein (RNP) complexes is increasing rapidly. RNA and RNP interaction motifs are structural units that function as building blocks to constitute variety of complex structures. RNA-central synthetic biology and nanotechnology are constructive approaches that employ the accumulated information and build synthetic RNA (RNP)-based circuits and nanostructures. Here, we describe how to design and construct synthetic RNA (RNP)-based devices and structures at the nanometer-scale for biological and future therapeutic applications. RNA/RNP nanostructures can also be utilized as the molecular scaffold to control the localization or interactions of target molecule(s). Moreover, RNA motifs recognized by RNA-binding proteins can be applied to make protein-responsive translational "switches" that can turn gene expression "on" or "off" depending on the intracellular environment. This "synthetic RNA and RNP world" will expand tools for nanotechnology and synthetic biology. In addition, these reconstructive approaches would lead to a greater understanding of building principle in naturally occurring RNA/RNP molecules and systems.

  8. Accessing Nature’s diversity through metabolic engineering and synthetic biology [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Jason R. King

    2016-03-01

    Full Text Available In this perspective, we highlight recent examples and trends in metabolic engineering and synthetic biology that demonstrate the synthetic potential of enzyme and pathway engineering for natural product discovery. In doing so, we introduce natural paradigms of secondary metabolism whereby simple carbon substrates are combined into complex molecules through “scaffold diversification”, and subsequent “derivatization” of these scaffolds is used to synthesize distinct complex natural products. We provide examples in which modern pathway engineering efforts including combinatorial biosynthesis and biological retrosynthesis can be coupled to directed enzyme evolution and rational enzyme engineering to allow access to the “privileged” chemical space of natural products in industry-proven microbes. Finally, we forecast the potential to produce natural product-like discovery platforms in biological systems that are amenable to single-step discovery, validation, and synthesis for streamlined discovery and production of biologically active agents.

  9. Synthetic Biology-Based Point-of-Care Diagnostics for Infectious Disease.

    Science.gov (United States)

    Wei, Ting-Yen; Cheng, Chao-Min

    2016-09-22

    Infectious diseases outpace all other causes of death in low-income countries, posing global health risks, laying stress on healthcare systems and societies, and taking an avoidable human toll. One solution to this crisis is early diagnosis of infectious disease, which represents a powerful way to optimize treatment, increase patient survival rate, and decrease healthcare costs. However, conventional early diagnosis methods take a long time to generate results, lack accuracy, and are known to seriously underperform with regard to fungal and viral infections. Synthetic biology offers a fast and highly accurate alternative to conventional infectious disease diagnosis. In this review, we outline obstacles to infectious disease diagnostics and discuss two emerging alternatives: synthetic viral diagnostic systems and biosensors. We argue that these synthetic biology-based approaches may overcome diagnostic obstacles in infectious disease and improve health outcomes.

  10. Microfluidics for synthetic biology: from design to execution.

    Science.gov (United States)

    Ferry, M S; Razinkov, I A; Hasty, J

    2011-01-01

    With the expanding interest in cellular responses to dynamic environments, microfluidic devices have become important experimental platforms for biological research. Microfluidic "microchemostat" devices enable precise environmental control while capturing high quality, single-cell gene expression data. For studies of population heterogeneity and gene expression noise, these abilities are crucial. Here, we describe the necessary steps for experimental microfluidics using devices created in our lab as examples. First, we discuss the rational design of microchemostats and the tools available to predict their performance. We carefully analyze the critical parts of an example device, focusing on the most important part of any microchemostat: the cell trap. Next, we present a method for generating on-chip dynamic environments using an integrated fluidic junction coupled to linear actuators. Our system relies on the simple modulation of hydrostatic pressure to alter the mixing ratio between two source reservoirs and we detail the software and hardware behind it. To expand the throughput of microchemostat experiments, we describe how to build larger, parallel versions of simpler devices. To analyze the large amounts of data, we discuss methods for automated cell tracking, focusing on the special problems presented by Saccharomyces cerevisiae cells. The manufacturing of microchemostats is described in complete detail: from the photolithographic processing of the wafer to the final bonding of the PDMS chip to glass coverslip. Finally, the procedures for conducting Escherichia coli and S. cerevisiae microchemostat experiments are addressed.

  11. Improving Synthetic Biology Communication: Recommended Practices for Visual Depiction and Digital Submission of Genetic Designs.

    Science.gov (United States)

    Hillson, Nathan J; Plahar, Hector A; Beal, Jacob; Prithviraj, Ranjini

    2016-06-17

    Research is communicated more effectively and reproducibly when articles depict genetic designs consistently and fully disclose the complete sequences of all reported constructs. ACS Synthetic Biology is now providing authors with updated guidance and piloting a new tool and publication workflow that facilitate compliance with these recommended practices and standards for visual representation and data exchange.

  12. Impact of synthetic biology and metabolic engineering on industrial production of fine chemicals

    DEFF Research Database (Denmark)

    Jullesson, David; David, Florian; Pfleger, Brian

    2015-01-01

    Industrial bio-processes for fine chemical production are increasingly relying on cell factories developed through metabolic engineering and synthetic biology. The use of high throughput techniques and automation for the design of cell factories, and especially platform strains, has played...

  13. Playing God in Frankenstein's Footsteps: Synthetic Biology and the Meaning of Life.

    Science.gov (United States)

    van den Belt, Henk

    2009-12-01

    The emergent new science of synthetic biology is challenging entrenched distinctions between, amongst others, life and non-life, the natural and the artificial, the evolved and the designed, and even the material and the informational. Whenever such culturally sanctioned boundaries are breached, researchers are inevitably accused of playing God or treading in Frankenstein's footsteps. Bioethicists, theologians and editors of scientific journals feel obliged to provide an authoritative answer to the ambiguous question of the 'meaning' of life, both as a scientific definition and as an explication with wider existential connotations. This article analyses the arguments mooted in the emerging societal debates on synthetic biology and the way its practitioners respond to criticism, mostly by assuming a defiant posture or professing humility. It explores the relationship between the 'playing God' theme and the Frankenstein motif and examines the doctrinal status of the 'playing God' argument. One particularly interesting finding is that liberal theologians generally deny the religious character of the 'playing God' argument-a response which fits in with the curious fact that this argument is used mainly by secular organizations. Synthetic biology, it is therefore maintained, does not offend so much the God of the Bible as a deified Nature. While syntheses of artificial life forms cause some vague uneasiness that life may lose its special meaning, most concerns turn out to be narrowly anthropocentric. As long as synthetic biology creates only new microbial life and does not directly affect human life, it will in all likelihood be considered acceptable.

  14. Exploiting plug-and-play synthetic biology for drug discovery and production in microorganisms

    NARCIS (Netherlands)

    Medema, Marnix H.; Breitling, Rainer; Bovenberg, Roel; Takano, Eriko

    2011-01-01

    One of the most promising applications of synthetic biology is the biosynthesis of new drugs from secondary metabolites. Here, we survey a wide range of strategies that control the activity of biosynthetic modules in the cell in space and time, and illustrate how these strategies can be used to desi

  15. Synthetic biology and global health in the age of intellectual property

    NARCIS (Netherlands)

    Belt, van den H.

    2014-01-01

    Although synthetic biology (SB) conjures up a future cornucopia of new medicines and other health applications, the antimalarial drug artemisinin is still one of the few concrete illustrations to substantiate this promise. As SB’s favorite poster child, it is atypical because it exemplifies a rather

  16. Synthetic biology and conservation of nature: wicked problems and wicked solutions.

    Directory of Open Access Journals (Sweden)

    Kent H Redford

    Full Text Available So far, conservation scientists have paid little attention to synthetic biology; this is unfortunate as the technology is likely to transform the operating space within which conservation functions, and therefore the prospects for maintaining biodiversity into the future.

  17. Playing God in Frankenstein's Footsteps: Synthetic Biology and the Meaning of Life

    NARCIS (Netherlands)

    Belt, van den H.

    2009-01-01

    The emergent new science of synthetic biology is challenging entrenched distinctions between, amongst others, life and non-life, the natural and the artificial, the evolved and the designed, and even the material and the informational. Whenever such culturally sanctioned boundaries are breached, res

  18. Engineering Nanoscale Biological Molecular Motors

    OpenAIRE

    Korosec, Chapin; Forde, Nancy R.

    2017-01-01

    Understanding the operation of biological molecular motors, nanoscale machines that transduce electrochemical energy into mechanical work, is enhanced by bottom-up strategies to synthesize novel motors.

  19. Identifying the computational requirements of an integrated top-down-bottom-up model for overt visual attention within an active vision system.

    Directory of Open Access Journals (Sweden)

    Sebastian McBride

    Full Text Available Computational visual attention systems have been constructed in order for robots and other devices to detect and locate regions of interest in their visual world. Such systems often attempt to take account of what is known of the human visual system and employ concepts, such as 'active vision', to gain various perceived advantages. However, despite the potential for gaining insights from such experiments, the computational requirements for visual attention processing are often not clearly presented from a biological perspective. This was the primary objective of this study, attained through two specific phases of investigation: 1 conceptual modeling of a top-down-bottom-up framework through critical analysis of the psychophysical and neurophysiological literature, 2 implementation and validation of the model into robotic hardware (as a representative of an active vision system. Seven computational requirements were identified: 1 transformation of retinotopic to egocentric mappings, 2 spatial memory for the purposes of medium-term inhibition of return, 3 synchronization of 'where' and 'what' information from the two visual streams, 4 convergence of top-down and bottom-up information to a centralized point of information processing, 5 a threshold function to elicit saccade action, 6 a function to represent task relevance as a ratio of excitation and inhibition, and 7 derivation of excitation and inhibition values from object-associated feature classes. The model provides further insight into the nature of data representation and transfer between brain regions associated with the vertebrate 'active' visual attention system. In particular, the model lends strong support to the functional role of the lateral intraparietal region of the brain as a primary area of information consolidation that directs putative action through the use of a 'priority map'.

  20. Identifying the computational requirements of an integrated top-down-bottom-up model for overt visual attention within an active vision system.

    Science.gov (United States)

    McBride, Sebastian; Huelse, Martin; Lee, Mark

    2013-01-01

    Computational visual attention systems have been constructed in order for robots and other devices to detect and locate regions of interest in their visual world. Such systems often attempt to take account of what is known of the human visual system and employ concepts, such as 'active vision', to gain various perceived advantages. However, despite the potential for gaining insights from such experiments, the computational requirements for visual attention processing are often not clearly presented from a biological perspective. This was the primary objective of this study, attained through two specific phases of investigation: 1) conceptual modeling of a top-down-bottom-up framework through critical analysis of the psychophysical and neurophysiological literature, 2) implementation and validation of the model into robotic hardware (as a representative of an active vision system). Seven computational requirements were identified: 1) transformation of retinotopic to egocentric mappings, 2) spatial memory for the purposes of medium-term inhibition of return, 3) synchronization of 'where' and 'what' information from the two visual streams, 4) convergence of top-down and bottom-up information to a centralized point of information processing, 5) a threshold function to elicit saccade action, 6) a function to represent task relevance as a ratio of excitation and inhibition, and 7) derivation of excitation and inhibition values from object-associated feature classes. The model provides further insight into the nature of data representation and transfer between brain regions associated with the vertebrate 'active' visual attention system. In particular, the model lends strong support to the functional role of the lateral intraparietal region of the brain as a primary area of information consolidation that directs putative action through the use of a 'priority map'.

  1. Immobilized Biofilm in Thermophilic Biohydrogen Production using Synthetic versus Biological Materials

    Directory of Open Access Journals (Sweden)

    Jaruwan Wongthanate

    2015-02-01

    Full Text Available Biohydrogen production was studied from the vermicelli processing wastewater using synthetic and biological materials as immobilizing substrate employing a mixed culture in a batch reactor operated at the initial pH 6.0 and thermophilic condition (55 ± 1ºC. Maximum cumulative hydrogen production (1,210 mL H2/L wastewater was observed at 5% (v/v addition of ring-shaped synthetic material, which was the ring-shaped hydrophobic acrylic. Regarding 5% (v/v addition of synthetic and biological materials, the maximum cumulative hydrogen production using immobilizing synthetic material of ball-shaped hydrophobic polyethylene (HBPE (1,256.5 mL H2/L wastewater was a two-fold increase of cumulative hydrogen production when compared to its production using immobilizing biological material of rope-shaped hydrophilic ramie (609.8 mL H2/L wastewater. SEM observation of immobilized biofilm on a ball-shaped HBPE or a rope-shaped hydrophilic ramie was the rod shape and gathered into group.

  2. A comparison of top-down and bottom-up approaches to benthic habitat mapping to inform offshore wind energy development

    Science.gov (United States)

    LaFrance, Monique; King, John W.; Oakley, Bryan A.; Pratt, Sheldon

    2014-07-01

    Recent interest in offshore renewable energy within the United States has amplified the need for marine spatial planning to direct management strategies and address competing user demands. To assist this effort in Rhode Island, benthic habitat classification maps were developed for two sites in offshore waters being considered for wind turbine installation. Maps characterizing and representing the distribution and extent of benthic habitats are valuable tools for improving understanding of ecosystem patterns and processes, and promoting scientifically-sound management decisions. This project presented the opportunity to conduct a comparison of the methodologies and resulting map outputs of two classification approaches, “top-down” and “bottom-up” in the two study areas. This comparison was undertaken to improve understanding of mapping methodologies and their applicability, including the bottom-up approach in offshore environments where data density tends to be lower, as well as to provide case studies for scientists and managers to consider for their own areas of interest. Such case studies can offer guidance for future work for assessing methodologies and translating them to other areas. The traditional top-down mapping approach identifies biological community patterns based on communities occurring within geologically defined habitat map units, under the concept that geologic environments contain distinct biological assemblages. Alternatively, the bottom-up approach aims to establish habitat map units centered on biological similarity and then uses statistics to identify relationships with associated environmental parameters and determine habitat boundaries. When applied to the two study areas, both mapping approaches produced habitat classes with distinct macrofaunal assemblages and each established statistically strong and significant biotic-abiotic relationships with geologic features, sediment characteristics, water depth, and/or habitat

  3. Bottom-up coarse-grained models that accurately describe the structure, pressure, and compressibility of molecular liquids

    Energy Technology Data Exchange (ETDEWEB)

    Dunn, Nicholas J. H.; Noid, W. G., E-mail: wnoid@chem.psu.edu [Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania 16802 (United States)

    2015-12-28

    The present work investigates the capability of bottom-up coarse-graining (CG) methods for accurately modeling both structural and thermodynamic properties of all-atom (AA) models for molecular liquids. In particular, we consider 1, 2, and 3-site CG models for heptane, as well as 1 and 3-site CG models for toluene. For each model, we employ the multiscale coarse-graining method to determine interaction potentials that optimally approximate the configuration dependence of the many-body potential of mean force (PMF). We employ a previously developed “pressure-matching” variational principle to determine a volume-dependent contribution to the potential, U{sub V}(V), that approximates the volume-dependence of the PMF. We demonstrate that the resulting CG models describe AA density fluctuations with qualitative, but not quantitative, accuracy. Accordingly, we develop a self-consistent approach for further optimizing U{sub V}, such that the CG models accurately reproduce the equilibrium density, compressibility, and average pressure of the AA models, although the CG models still significantly underestimate the atomic pressure fluctuations. Additionally, by comparing this array of models that accurately describe the structure and thermodynamic pressure of heptane and toluene at a range of different resolutions, we investigate the impact of bottom-up coarse-graining upon thermodynamic properties. In particular, we demonstrate that U{sub V} accounts for the reduced cohesion in the CG models. Finally, we observe that bottom-up coarse-graining introduces subtle correlations between the resolution, the cohesive energy density, and the “simplicity” of the model.

  4. Top-down vs. bottom-up control on vegetation composition in a tidal marsh depends on scale.

    Science.gov (United States)

    Elschot, Kelly; Vermeulen, Anke; Vandenbruwaene, Wouter; Bakker, Jan P; Bouma, Tjeerd J; Stahl, Julia; Castelijns, Henk; Temmerman, Stijn

    2017-01-01

    The relative impact of top-down control by herbivores and bottom-up control by environmental conditions on vegetation is a subject of debate in ecology. In this study, we hypothesize that top-down control by goose foraging and bottom-up control by sediment accretion on vegetation composition within an ecosystem can co-occur but operate at different spatial and temporal scales. We used a highly dynamic marsh system with a large population of the Greylag goose (Anser anser) to investigate the potential importance of spatial and temporal scales on these processes. At the local scale, Greylag geese grub for below-ground storage organs of the vegetation, thereby creating bare patches of a few square metres within the marsh vegetation. In our study, such activities by Greylag geese allowed them to exert top-down control by setting back vegetation succession. However, we found that the patches reverted back to the initial vegetation type within 12 years. At large spatial (i.e. several square kilometres) and temporal scales (i.e. decades), high rates of sediment accretion surpassing the rate of local sea-level rise were found to drive long-term vegetation succession and increased cover of several climax vegetation types. In summary, we conclude that the vegetation composition within this tidal marsh was primarily controlled by the bottom-up factor of sediment accretion, which operates at large spatial as well as temporal scales. Top-down control exerted by herbivores was found to be a secondary process and operated at much smaller spatial and temporal scales.

  5. Bottom-up coarse-grained models that accurately describe the structure, pressure, and compressibility of molecular liquids

    Science.gov (United States)

    Dunn, Nicholas J. H.; Noid, W. G.

    2015-12-01

    The present work investigates the capability of bottom-up coarse-graining (CG) methods for accurately modeling both structural and thermodynamic properties of all-atom (AA) models for molecular liquids. In particular, we consider 1, 2, and 3-site CG models for heptane, as well as 1 and 3-site CG models for toluene. For each model, we employ the multiscale coarse-graining method to determine interaction potentials that optimally approximate the configuration dependence of the many-body potential of mean force (PMF). We employ a previously developed "pressure-matching" variational principle to determine a volume-dependent contribution to the potential, UV(V), that approximates the volume-dependence of the PMF. We demonstrate that the resulting CG models describe AA density fluctuations with qualitative, but not quantitative, accuracy. Accordingly, we develop a self-consistent approach for further optimizing UV, such that the CG models accurately reproduce the equilibrium density, compressibility, and average pressure of the AA models, although the CG models still significantly underestimate the atomic pressure fluctuations. Additionally, by comparing this array of models that accurately describe the structure and thermodynamic pressure of heptane and toluene at a range of different resolutions, we investigate the impact of bottom-up coarse-graining upon thermodynamic properties. In particular, we demonstrate that UV accounts for the reduced cohesion in the CG models. Finally, we observe that bottom-up coarse-graining introduces subtle correlations between the resolution, the cohesive energy density, and the "simplicity" of the model.

  6. A regression approach for estimation of anthropogenic heat flux based on a bottom-up air pollutant emission database

    Science.gov (United States)

    Lee, Sang-Hyun; McKeen, Stuart A.; Sailor, David J.

    2014-10-01

    A statistical regression method is presented for estimating hourly anthropogenic heat flux (AHF) using an anthropogenic pollutant emission inventory for use in mesoscale meteorological and air-quality modeling. Based on bottom-up AHF estimated from detailed energy consumption data and anthropogenic pollutant emissions of carbon monoxide (CO) and nitrogen oxides (NOx) in the US National Emission Inventory year 2005 (NEI-2005), a robust regression relation between the AHF and the pollutant emissions is obtained for Houston. This relation is a combination of two power functions (Y = aXb) relating CO and NOx emissions to AHF, giving a determinant coefficient (R2) of 0.72. The AHF for Houston derived from the regression relation has high temporal (R = 0.91) and spatial (R = 0.83) correlations with the bottom-up AHF. Hourly AHF for the whole US in summer is estimated by applying the regression relation to the NEI-2005 summer pollutant emissions with a high spatial resolution of 4-km. The summer daily mean AHF range 10-40 W m-2 on a 4 × 4 km2 grid scale with maximum heat fluxes of 50-140 W m-2 for major US cities. The AHFs derived from the regression relations between the bottom-up AHF and either CO or NOx emissions show a small difference of less than 5% (4.7 W m-2) in city-scale daily mean AHF, and similar R2 statistics, compared to results from their combination. Thus, emissions of either species can be used to estimate AHF in the US cities. An hourly AHF inventory at 4 × 4 km2 resolution over the entire US based on the combined regression is derived and made publicly available for use in mesoscale numerical modeling.

  7. Bottom-Up Nano-heteroepitaxy of Wafer-Scale Semipolar GaN on (001) Si

    KAUST Repository

    Hus, Jui Wei

    2015-07-15

    Semipolar {101¯1} InGaN quantum wells are grown on (001) Si substrates with an Al-free buffer and wafer-scale uniformity. The novel structure is achieved by a bottom-up nano-heteroepitaxy employing self-organized ZnO nanorods as the strain-relieving layer. This ZnO nanostructure unlocks the problems encountered by the conventional AlN-based buffer, which grows slowly and contaminates the growth chamber. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. FROM A COMPARISON OF "TOP-DOWN" AND "BOTTOM-UP" APPROACHES TO THE APPLICATION OF THE "INTERACTIVE" APPROACH

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    This paper introduces three models of reading. Then it ana-lyzes the data gathered from an experiment on the comparison ofthe "top.down" and the "bottom-up" approaches and accord-ingly draws the conclusion that the former approach is helpful inimproving students’ reading comprehension while the latter isuseful in developing their writing skills as well as their knowledgeof vocabulary and sentence structure. Finally this paper presentsa procedure of the application of the "interactive approach",which proves to be productive in teaching college English inten-sive reading.

  9. [Diversity in thalamic relay neurons: evidence for "bottom-up" and "top-down" information flow in thalamocortical pathways].

    Science.gov (United States)

    Clascá, Francisco; Rubio-Garrido, Pablo; Galazo, María J; Porrero, César

    2009-01-01

    Thalamocortical (TC) pathways are still mainly understood as the gateway for ascending sensory-motor information into the cortex. However, it is now clear that a great many TC cells are involved in interactions between cortical areas via the thalamus. We review recent data, including our own, which demonstrate the generalized presence in rodent thalamus of two major TC cell types characterized, among other features, by their axon development, arborization and laminar targeting in the cortex. Such duality may allow inputs from thalamus to access cortical circuits via "bottom-up"-wired axon arbors or via "top-down"-wired axon arbors.

  10. Una implementación computacional de un modelo de atención visual Bottom-up aplicado a escenas naturales/A Computational Implementation of a Bottom-up Visual Attention Model Applied to Natural Scenes

    Directory of Open Access Journals (Sweden)

    Juan F. Ramírez Villegas

    2011-12-01

    Full Text Available El modelo de atención visual bottom-up propuesto por Itti et al., 2000 [1], ha sido un modelo popular en tanto exhibe cierta evidencia neurobiológica de la visión en primates. Este trabajo complementa el modelo computacional de este fenómeno desde la dinámica realista de una red neuronal. Asimismo, esta aproximación se basa en la existencia de mapas topográficos que representan la prominencia de los objetos del campo visual para la formación de una representación general (mapa de prominencia, esta representación es la entrada de una red neuronal dinámica con interacciones locales y globales de colaboración y competencia que convergen sobre las principales particularidades (objetos de la escena.The bottom-up visual attention model proposed by Itti et al. 2000 [1], has been a popular model since it exhibits certain neurobiological evidence of primates’ vision. This work complements the computational model of this phenomenon using a neural network with realistic dynamics. This approximation is based on several topographical maps representing the objects saliency that construct a general representation (saliency map, which is the input for a dynamic neural network, whose local and global collaborative and competitive interactions converge to the main particularities (objects presented by the visual scene as well.

  11. Engineering of a genome-reduced host: practical application of synthetic biology in the overproduction of desired secondary metabolites.

    Science.gov (United States)

    Gao, Hong; Zhuo, Ying; Ashforth, Elizabeth; Zhang, Lixin

    2010-07-01

    Synthetic biology aims to design and build new biological systems with desirable properties, providing the foundation for the biosynthesis of secondary metabolites. The most prominent representation of synthetic biology has been used in microbial engineering by recombinant DNA technology. However, there are advantages of using a deleted host, and therefore an increasing number of biotechnology studies follow similar strategies to dissect cellular networks and construct genome-reduced microbes. This review will give an overview of the strategies used for constructing and engineering reduced-genome factories by synthetic biology to improve production of secondary metabolites.

  12. The ten grand challenges of synthetic life.

    Science.gov (United States)

    Porcar, Manuel; Danchin, Antoine; de Lorenzo, Victor; Dos Santos, Vitor A; Krasnogor, Natalio; Rasmussen, Steen; Moya, Andrés

    2011-06-01

    The construction of artificial life is one of the main scientific challenges of the Synthetic Biology era. Advances in DNA synthesis and a better understanding of regulatory processes make the goal of constructing the first artificial cell a realistic possibility. This would be both a fundamental scientific milestone and a starting point of a vast range of applications, from biofuel production to drug design. However, several major issues might hamper the objective of achieving an artificial cell. From the bottom-up to the selection-based strategies, this work encompasses the ten grand challenges synthetic biologists will have to be aware of in order to cope with the task of creating life in the lab.

  13. Rewiring cells: synthetic biology as a tool to interrogate the organizational principles of living systems.

    Science.gov (United States)

    Bashor, Caleb J; Horwitz, Andrew A; Peisajovich, Sergio G; Lim, Wendell A

    2010-01-01

    The living cell is an incredibly complex entity, and the goal of predictively and quantitatively understanding its function is one of the next great challenges in biology. Much of what we know about the cell concerns its constituent parts, but to a great extent we have yet to decode how these parts are organized to yield complex physiological function. Classically, we have learned about the organization of cellular networks by disrupting them through genetic or chemical means. The emerging discipline of synthetic biology offers an additional, powerful approach to study systems. By rearranging the parts that comprise existing networks, we can gain valuable insight into the hierarchical logic of the networks and identify the modular building blocks that evolution uses to generate innovative function. In addition, by building minimal toy networks, one can systematically explore the relationship between network structure and function. Here, we outline recent work that uses synthetic biology approaches to investigate the organization and function of cellular networks, and describe a vision for a synthetic biology toolkit that could be used to interrogate the design principles of diverse systems.

  14. Systems and synthetic biology approaches to alter plant cell walls and reduce biomass recalcitrance.

    Science.gov (United States)

    Kalluri, Udaya C; Yin, Hengfu; Yang, Xiaohan; Davison, Brian H

    2014-12-01

    Fine-tuning plant cell wall properties to render plant biomass more amenable to biofuel conversion is a colossal challenge. A deep knowledge of the biosynthesis and regulation of plant cell wall and a high-precision genome engineering toolset are the two essential pillars of efforts to alter plant cell walls and reduce biomass recalcitrance. The past decade has seen a meteoric rise in use of transcriptomics and high-resolution imaging methods resulting in fresh insights into composition, structure, formation and deconstruction of plant cell walls. Subsequent gene manipulation approaches, however, commonly include ubiquitous mis-expression of a single candidate gene in a host that carries an intact copy of the native gene. The challenges posed by pleiotropic and unintended changes resulting from such an approach are moving the field towards synthetic biology approaches. Synthetic biology builds on a systems biology knowledge base and leverages high-precision tools for high-throughput assembly of multigene constructs and pathways, precision genome editing and site-specific gene stacking, silencing and/or removal. Here, we summarize the recent breakthroughs in biosynthesis and remodelling of major secondary cell wall components, assess the impediments in obtaining a systems-level understanding and explore the potential opportunities in leveraging synthetic biology approaches to reduce biomass recalcitrance.

  15. The SBOL Stack: A Platform for Storing, Publishing, and Sharing Synthetic Biology Designs.

    Science.gov (United States)

    Madsen, Curtis; McLaughlin, James Alastair; Mısırlı, Göksel; Pocock, Matthew; Flanagan, Keith; Hallinan, Jennifer; Wipat, Anil

    2016-06-17

    Recently, synthetic biologists have developed the Synthetic Biology Open Language (SBOL), a data exchange standard for descriptions of genetic parts, devices, modules, and systems. The goals of this standard are to allow scientists to exchange designs of biological parts and systems, to facilitate the storage of genetic designs in repositories, and to facilitate the description of genetic designs in publications. In order to achieve these goals, the development of an infrastructure to store, retrieve, and exchange SBOL data is necessary. To address this problem, we have developed the SBOL Stack, a Resource Description Framework (RDF) database specifically designed for the storage, integration, and publication of SBOL data. This database allows users to define a library of synthetic parts and designs as a service, to share SBOL data with collaborators, and to store designs of biological systems locally. The database also allows external data sources to be integrated by mapping them to the SBOL data model. The SBOL Stack includes two Web interfaces: the SBOL Stack API and SynBioHub. While the former is designed for developers, the latter allows users to upload new SBOL biological designs, download SBOL documents, search by keyword, and visualize SBOL data. Since the SBOL Stack is based on semantic Web technology, the inherent distributed querying functionality of RDF databases can be used to allow different SBOL stack databases to be queried simultaneously, and therefore, data can be shared between different institutes, centers, or other users.

  16. Synthetic

    Directory of Open Access Journals (Sweden)

    Anna Maria Manferdini

    2010-06-01

    Full Text Available Traditionally materials have been associated with a series of physical properties that can be used as inputs to production and manufacturing. Recently we witnessed an interest in materials considered not only as ‘true matter’, but also as new breeds where geometry, texture, tooling and finish are able to provoke new sensations when they are applied to a substance. These artificial materials can be described as synthetic because they are the outcome of various qualities that are not necessarily true to the original matter, but they are the combination of two or more parts, whether by design or by natural processes. The aim of this paper is to investigate the potential of architectural surfaces to produce effects through the invention of new breeds of artificial matter, using micro-scale details derived from Nature as an inspiration.

  17. Linking top-down and bottom-up approaches for assessing the vulnerability of a 100 % renewable energy system in Northern-Italy

    Science.gov (United States)

    Borga, Marco; Francois, Baptiste; Hingray, Benoit; Zoccatelli, Davide; Creutin, Jean-Dominique; brown, Casey

    2016-04-01

    Due to their variable and un-controllable features, integration of Variable Renewable Energies (e.g. solar-power, wind-power and hydropower, denoted as VRE) into the electricity network implies higher production variability and increased risk of not meeting demand. Two approaches are commonly used for assessing this risk and especially its evolution in a global change context (i.e. climate and societal changes); top-down and bottom-up approaches. The general idea of a top-down approach is to drive analysis of global change or of some key aspects of global change on their systems (e.g., the effects of the COP 21, of the deployment of Smart Grids, or of climate change) with chains of loosely linked simulation models within a predictive framework. The bottom-up approach aims to improve understanding of the dependencies between the vulnerability of regional systems and large-scale phenomenon from knowledge gained through detailed exploration of the response to change of the system of interest, which may reveal vulnerability thresholds, tipping points as well as potential opportunities. Brown et al. (2012) defined an analytical framework to merge these two approaches. The objective is to build, a set of Climate Response Functions (CRFs) putting in perspective i) indicators of desired states ("success") and undesired states ("failure") of a system as defined in collaboration with stakeholders 2) exhaustive exploration of the effects of uncertain forcings and imperfect system understanding on the response of the system itself to a plausible set of possible changes, implemented a with multi-dimensionally consistent "stress test" algorithm, and 3) a set "ex post" hydroclimatic and socioeconomic scenarios that provide insight into the differential effectiveness of alternative policies and serve as entry points for the provision of climate information to inform policy evaluation and choice. We adapted this approach for analyzing a 100 % renewable energy system within a region

  18. Smart city planning from a bottom-up approach: local communities' intervention for a smarter urban environment

    Science.gov (United States)

    Alverti, Maroula; Hadjimitsis, Diofantos; Kyriakidis, Phaedon; Serraos, Konstantinos

    2016-08-01

    The aim of this paper is to explore the concept of "smart" cities from the perspective of inclusive community participation and Geographical Information Systems (GIS).The concept of a smart city is critically analyzed, focusing on the power/knowledge implications of a "bottom-up" approach in planning and how GIS could encourage community participation in smart urban planning. The paper commences with a literature review of what it means for cities to be "smart". It draws supporting definitions and critical insights into smart cities with respect to the built environment and the human factor. The second part of the paper, analyzes the "bottom-up" approach in urban planning, focusing on community participation reviewing forms and expressions through good practices from European cities. The third part of the paper includes a debate on how smart urban cities policies and community participation interact and influence each other. Finally, the paper closes with a discussion of the insights that were found and offers recommendations on how this debate could be addressed by Information and Communication Technologies and GIS in particular.

  19. Climate-induced changes in bottom-up and top-down processes independently alter a marine ecosystem.

    Science.gov (United States)

    Jochum, Malte; Schneider, Florian D; Crowe, Tasman P; Brose, Ulrich; O'Gorman, Eoin J

    2012-11-05

    Climate change has complex structural impacts on coastal ecosystems. Global warming is linked to a widespread decline in body size, whereas increased flood frequency can amplify nutrient enrichment through enhanced run-off. Altered population body-size structure represents a disruption in top-down control, whereas eutrophication embodies a change in bottom-up forcing. These processes are typically studied in isolation and little is known about their potential interactive effects. Here, we present the results of an in situ experiment examining the combined effects of top-down and bottom-up forces on the structure of a coastal marine community. Reduced average body mass of the top predator (the shore crab, Carcinus maenas) and nutrient enrichment combined additively to alter mean community body mass. Nutrient enrichment increased species richness and overall density of organisms. Reduced top-predator body mass increased community biomass. Additionally, we found evidence for an allometrically induced trophic cascade. Here, the reduction in top-predator body mass enabled greater biomass of intermediate fish predators within the mesocosms. This, in turn, suppressed key micrograzers, which led to an overall increase in microalgal biomass. This response highlights the possibility for climate-induced trophic cascades, driven by altered size structure of populations, rather than species extinction.

  20. Source attribution of methane emissions from global oil and gas production: results of bottom-up simulations over three decades

    Science.gov (United States)

    Höglund-Isaksson, Lena

    2016-04-01

    Existing bottom-up emission inventories of historical methane and ethane emissions from global oil and gas systems do not well explain year-on-year variations estimated by top-down models from atmospheric measurements. This paper develops a bottom-up methodology which allows for country- and year specific source attribution of methane and ethane emissions from global oil and natural gas production for the period 1980 to 2012. The analysis rests on country-specific simulations of associated gas flows which are converted into methane and ethane emissions. The associated gas flows are constructed from country-specific information on oil and gas production and associated gas generation and recovery, and coupled with generic assumptions to bridge regional information gaps on the fractions of unrecovered associated gas that is vented instead of flared. Summing up emissions from associated gas flows with global estimates of emissions from unintended leakage and natural gas transmission and distribution, the resulting global emissions of methane and ethane from oil and gas systems are reasonably consistent with corresponding estimates from top-down models. Also revealed is that the fall of the Soviet Union in 1990 had a significant impact on methane and ethane emissions from global oil and gas systems.