WorldWideScience

Sample records for bottom-up synthetic biology

  1. Bottom-up synthetic biology: engineering in a tinkerer's world.

    Science.gov (United States)

    Schwille, Petra

    2011-09-02

    How synthetic can "synthetic biology" be? A literal interpretation of the name of this new life science discipline invokes expectations of the systematic construction of biological systems with cells being built module by module--from the bottom up. But can this possibly be achieved, taking into account the enormous complexity and redundancy of living systems, which distinguish them quite remarkably from design features that characterize human inventions? There are several recent developments in biology, in tight conjunction with quantitative disciplines, that may bring this literal perspective into the realm of the possible. However, such bottom-up engineering requires tools that were originally designed by nature's greatest tinkerer: evolution.

  2. Bottom-up synthetic biology: modular design for making artificial platelets

    Science.gov (United States)

    Majumder, Sagardip; Liu, Allen P.

    2018-01-01

    Engineering artificial cells to mimic one or multiple fundamental cell biological functions is an emerging area of synthetic biology. Reconstituting functional modules from biological components in vitro is a challenging yet an important essence of bottom-up synthetic biology. Here we describe the concept of building artificial platelets using bottom-up synthetic biology and the four functional modules that together could enable such an ambitious effort.

  3. 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. © 2016 The Author(s).

  4. 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Sequential bottom-up assembly of mechanically stabilized synthetic cells by microfluidics

    Science.gov (United States)

    Weiss, Marian; Frohnmayer, Johannes Patrick; Benk, Lucia Theresa; Haller, Barbara; Janiesch, Jan-Willi; Heitkamp, Thomas; Börsch, Michael; Lira, Rafael B.; Dimova, Rumiana; Lipowsky, Reinhard; Bodenschatz, Eberhard; Baret, Jean-Christophe; Vidakovic-Koch, Tanja; Sundmacher, Kai; Platzman, Ilia; Spatz, Joachim P.

    2018-01-01

    Compartments for the spatially and temporally controlled assembly of biological processes are essential towards cellular life. Synthetic mimics of cellular compartments based on lipid-based protocells lack the mechanical and chemical stability to allow their manipulation into a complex and fully functional synthetic cell. Here, we present a high-throughput microfluidic method to generate stable, defined sized liposomes termed `droplet-stabilized giant unilamellar vesicles (dsGUVs)’. The enhanced stability of dsGUVs enables the sequential loading of these compartments with biomolecules, namely purified transmembrane and cytoskeleton proteins by microfluidic pico-injection technology. This constitutes an experimental demonstration of a successful bottom-up assembly of a compartment with contents that would not self-assemble to full functionality when simply mixed together. Following assembly, the stabilizing oil phase and droplet shells are removed to release functional self-supporting protocells to an aqueous phase, enabling them to interact with physiologically relevant matrices.

  6. Sequential bottom-up assembly of mechanically stabilized synthetic cells by microfluidics.

    Science.gov (United States)

    Weiss, Marian; Frohnmayer, Johannes Patrick; Benk, Lucia Theresa; Haller, Barbara; Janiesch, Jan-Willi; Heitkamp, Thomas; Börsch, Michael; Lira, Rafael B; Dimova, Rumiana; Lipowsky, Reinhard; Bodenschatz, Eberhard; Baret, Jean-Christophe; Vidakovic-Koch, Tanja; Sundmacher, Kai; Platzman, Ilia; Spatz, Joachim P

    2017-10-16

    Compartments for the spatially and temporally controlled assembly of biological processes are essential towards cellular life. Synthetic mimics of cellular compartments based on lipid-based protocells lack the mechanical and chemical stability to allow their manipulation into a complex and fully functional synthetic cell. Here, we present a high-throughput microfluidic method to generate stable, defined sized liposomes termed 'droplet-stabilized giant unilamellar vesicles (dsGUVs)'. The enhanced stability of dsGUVs enables the sequential loading of these compartments with biomolecules, namely purified transmembrane and cytoskeleton proteins by microfluidic pico-injection technology. This constitutes an experimental demonstration of a successful bottom-up assembly of a compartment with contents that would not self-assemble to full functionality when simply mixed together. Following assembly, the stabilizing oil phase and droplet shells are removed to release functional self-supporting protocells to an aqueous phase, enabling them to interact with physiologically relevant matrices.

  7. New, national bottom-up estimate for tree-based biological ...

    Science.gov (United States)

    Nitrogen is a limiting nutrient in many ecosystems, but is also a chief pollutant from human activity. Quantifying human impacts on the nitrogen cycle and investigating natural ecosystem nitrogen cycling both require an understanding of the magnitude of nitrogen inputs from biological nitrogen fixation (BNF). A bottom-up approach to estimating BNF—scaling rates up from measurements to broader scales—is attractive because it is rooted in actual BNF measurements. However, bottom-up approaches have been hindered by scaling difficulties, and a recent top-down approach suggested that the previous bottom-up estimate was much too large. Here, we used a bottom-up approach for tree-based BNF, overcoming scaling difficulties with the systematic, immense (>70,000 N-fixing trees) Forest Inventory and Analysis (FIA) database. We employed two approaches to estimate species-specific BNF rates: published ecosystem-scale rates (kg N ha-1 yr-1) and published estimates of the percent of N derived from the atmosphere (%Ndfa) combined with FIA-derived growth rates. Species-specific rates can vary for a variety of reasons, so for each approach we examined how different assumptions influenced our results. Specifically, we allowed BNF rates to vary with stand age, N-fixer density, and canopy position (since N-fixation is known to require substantial light).Our estimates from this bottom-up technique are several orders of magnitude lower than previous estimates indicating

  8. Cognition from the bottom up: on biological inspiration, body morphology, and soft materials.

    Science.gov (United States)

    Pfeifer, Rolf; Iida, Fumiya; Lungarella, Max

    2014-08-01

    Traditionally, in cognitive science the emphasis is on studying cognition from a computational point of view. Studies in biologically inspired robotics and embodied intelligence, however, provide strong evidence that cognition cannot be analyzed and understood by looking at computational processes alone, but that physical system-environment interaction needs to be taken into account. In this opinion article, we review recent progress in cognitive developmental science and robotics, and expand the notion of embodiment to include soft materials and body morphology in the big picture. We argue that we need to build our understanding of cognition from the bottom up; that is, all the way from how our body is physically constructed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. 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.

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

    Science.gov (United States)

    Pasotti, Lorenzo; Politi, Nicolò; Zucca, Susanna; Cusella De Angelis, Maria Gabriella; Magni, Paolo

    2012-01-01

    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. 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. 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 provides a significant contribution to the

  11. 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

  12. Synthetic biology: integrated gene circuits.

    Science.gov (United States)

    Nandagopal, Nagarajan; Elowitz, Michael B

    2011-09-02

    A major goal of synthetic biology is to develop a deeper understanding of biological design principles from the bottom up, by building circuits and studying their behavior in cells. Investigators initially sought to design circuits "from scratch" that functioned as independently as possible from the underlying cellular system. More recently, researchers have begun to develop a new generation of synthetic circuits that integrate more closely with endogenous cellular processes. These approaches are providing fundamental insights into the regulatory architecture, dynamics, and evolution of genetic circuits and enabling new levels of control across diverse biological systems.

  13. Synthetic Biology-The Synthesis of Biology.

    Science.gov (United States)

    Ausländer, Simon; Ausländer, David; Fussenegger, Martin

    2017-06-01

    Synthetic biology concerns the engineering of man-made living biomachines from standardized components that can perform predefined functions in a (self-)controlled manner. Different research strategies and interdisciplinary efforts are pursued to implement engineering principles to biology. The "top-down" strategy exploits nature's incredible diversity of existing, natural parts to construct synthetic compositions of genetic, metabolic, or signaling networks with predictable and controllable properties. This mainly application-driven approach results in living factories that produce drugs, biofuels, biomaterials, and fine chemicals, and results in living pills that are based on engineered cells with the capacity to autonomously detect and treat disease states in vivo. In contrast, the "bottom-up" strategy seeks to be independent of existing living systems by designing biological systems from scratch and synthesizing artificial biological entities not found in nature. This more knowledge-driven approach investigates the reconstruction of minimal biological systems that are capable of performing basic biological phenomena, such as self-organization, self-replication, and self-sustainability. Moreover, the syntheses of artificial biological units, such as synthetic nucleotides or amino acids, and their implementation into polymers inside living cells currently set the boundaries between natural and artificial biological systems. In particular, the in vitro design, synthesis, and transfer of complete genomes into host cells point to the future of synthetic biology: the creation of designer cells with tailored desirable properties for biomedicine and biotechnology. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. 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.

  15. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Models for synthetic biology

    Directory of Open Access Journals (Sweden)

    Kaznessis Yiannis N

    2007-11-01

    Full Text Available Abstract Synthetic biological engineering is emerging from biology as a distinct discipline based on quantification. The technologies propelling synthetic biology are not new, nor is the concept of designing novel biological molecules. What is new is the emphasis on system behavior. The objective is the design and construction of new biological devices and systems to deliver useful applications. Numerous synthetic gene circuits have been created in the past decade, including bistable switches, oscillators, and logic gates, and possible applications abound, including biofuels, detectors for biochemical and chemical weapons, disease diagnosis, and gene therapies. More than fifty years after the discovery of the molecular structure of DNA, molecular biology is mature enough for real quantification that is useful for biological engineering applications, similar to the revolution in modeling in chemistry in the 1950s. With the excitement that synthetic biology is generating, the engineering and biological science communities appear remarkably willing to cross disciplinary boundaries toward a common goal.

  17. Nanoelectronics from the bottom up.

    Science.gov (United States)

    Lu, Wei; Lieber, Charles M

    2007-11-01

    Electronics obtained through the bottom-up approach of molecular-level control of material composition and structure may lead to devices and fabrication strategies not possible with top-down methods. This review presents a brief summary of bottom-up and hybrid bottom-up/top-down strategies for nanoelectronics with an emphasis on memories based on the crossbar motif. First, we will discuss representative electromechanical and resistance-change memory devices based on carbon nanotube and core-shell nanowire structures, respectively. These device structures show robust switching, promising performance metrics and the potential for terabit-scale density. Second, we will review architectures being developed for circuit-level integration, hybrid crossbar/CMOS circuits and array-based systems, including experimental demonstrations of key concepts such lithography-independent, chemically coded stochastic demultipluxers. Finally, bottom-up fabrication approaches, including the opportunity for assembly of three-dimensional, vertically integrated multifunctional circuits, will be critically discussed.

  18. 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.…

  19. Creating biological nanomaterials using synthetic biology.

    Science.gov (United States)

    Rice, MaryJoe K; Ruder, Warren C

    2014-02-01

    Synthetic biology is a new discipline that combines science and engineering approaches to precisely control biological networks. These signaling networks are especially important in fields such as biomedicine and biochemical engineering. Additionally, biological networks can also be critical to the production of naturally occurring biological nanomaterials, and as a result, synthetic biology holds tremendous potential in creating new materials. This review introduces the field of synthetic biology, discusses how biological systems naturally produce materials, and then presents examples and strategies for incorporating synthetic biology approaches in the development of new materials. In particular, strategies for using synthetic biology to produce both organic and inorganic nanomaterials are discussed. Ultimately, synthetic biology holds the potential to dramatically impact biological materials science with significant potential applications in medical systems.

  20. 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.

  1. Space Synthetic Biology Project

    Science.gov (United States)

    Howard, David; Roman, Monsi; Mansell, James (Matt)

    2015-01-01

    Synthetic biology is an effort to make genetic engineering more useful by standardizing sections of genetic code. By standardizing genetic components, biological engineering will become much more similar to traditional fields of engineering, in which well-defined components and subsystems are readily available in markets. Specifications of the behavior of those components and subsystems can be used to model a system which incorporates them. Then, the behavior of the novel system can be simulated and optimized. Finally, the components and subsystems can be purchased and assembled to create the optimized system, which most often will exhibit behavior similar to that indicated by the model. The Space Synthetic Biology project began in 2012 as a multi-Center effort. The purpose of this project was to harness Synthetic Biology principals to enable NASA's missions. A central target for application was to Environmental Control & Life Support (ECLS). Engineers from NASA Marshall Space Flight Center's (MSFC's) ECLS Systems Development Branch (ES62) were brought into the project to contribute expertise in operational ECLS systems. Project lead scientists chose to pursue the development of bioelectrochemical technologies to spacecraft life support. Therefore, the ECLS element of the project became essentially an effort to develop a bioelectrochemical ECLS subsystem. Bioelectrochemical systems exploit the ability of many microorganisms to drive their metabolisms by direct or indirect utilization of electrical potential gradients. Whereas many microorganisms are capable of deriving the energy required for the processes of interest (such as carbon dioxide (CO2) fixation) from sunlight, it is believed that subsystems utilizing electrotrophs will exhibit smaller mass, volume, and power requirements than those that derive their energy from sunlight. In the first 2 years of the project, MSFC personnel conducted modeling, simulation, and conceptual design efforts to assist the

  2. Evolutionary synthetic biology.

    Science.gov (United States)

    Peisajovich, Sergio G

    2012-06-15

    Signaling networks process vast amounts of environmental information to generate specific cellular responses. As cellular environments change, signaling networks adapt accordingly. Here, I will discuss how the integration of synthetic biology and directed evolution approaches is shedding light on the molecular mechanisms that guide the evolution of signaling networks. In particular, I will review studies that demonstrate how different types of mutations, from the replacement of individual amino acids to the shuffling of modular domains, lead to markedly different evolutionary trajectories and consequently to diverse network rewiring. Moreover, I will argue that intrinsic evolutionary properties of signaling proteins, such as the robustness of wild type functions, the promiscuous nature of evolutionary intermediates, and the modular decoupling between binding and catalysis, play important roles in the evolution of signaling networks. Finally, I will argue that rapid advances in our ability to synthesize DNA will radically alter how we study signaling network evolution at the genome-wide level.

  3. Synthetic biology and occupational risk.

    Science.gov (United States)

    Howard, John; Murashov, Vladimir; Schulte, Paul

    2017-03-01

    Synthetic biology is an emerging interdisciplinary field of biotechnology that involves applying the principles of engineering and chemical design to biological systems. Biosafety professionals have done an excellent job in addressing research laboratory safety as synthetic biology and gene editing have emerged from the larger field of biotechnology. Despite these efforts, risks posed by synthetic biology are of increasing concern as research procedures scale up to industrial processes in the larger bioeconomy. A greater number and variety of workers will be exposed to commercial synthetic biology risks in the future, including risks to a variety of workers from the use of lentiviral vectors as gene transfer devices. There is a need to review and enhance current protection measures in the field of synthetic biology, whether in experimental laboratories where new advances are being researched, in health care settings where treatments using viral vectors as gene delivery systems are increasingly being used, or in the industrial bioeconomy. Enhanced worker protection measures should include increased injury and illness surveillance of the synthetic biology workforce; proactive risk assessment and management of synthetic biology products; research on the relative effectiveness of extrinsic and intrinsic biocontainment methods; specific safety guidance for synthetic biology industrial processes; determination of appropriate medical mitigation measures for lentiviral vector exposure incidents; and greater awareness and involvement in synthetic biology safety by the general occupational safety and health community as well as by government occupational safety and health research and regulatory agencies.

  4. Finding Hope in Synthetic Biology.

    Science.gov (United States)

    Takala, Tuija

    2017-04-01

    For some, synthetic biology represents great hope in offering possible solutions to many of the world's biggest problems, from hunger to sustainable development. Others remain fearful of the harmful uses, such as bioweapons, that synthetic biology can lend itself to, and most hold that issues of biosafety are of utmost importance. In this article, I will evaluate these points of view and conclude that although the biggest promises of synthetic biology are unlikely to become reality, and the probability of accidents is fairly substantial, synthetic biology could still be seen to benefit humanity by enhancing our ethical understanding and by offering a boost to world economy.

  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. Copyright © 2015 Académie des sciences. Published by Elsevier SAS. All rights reserved.

  6. 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.

  7. 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. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. 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...

  9. Chemical synthesis using synthetic biology.

    Science.gov (United States)

    Carothers, James M; Goler, Jonathan A; Keasling, Jay D

    2009-08-01

    An immense array of naturally occurring biological systems have evolved that convert simple substrates into the products that cells need for growth and persistence. Through the careful application of metabolic engineering and synthetic biology, this biotransformation potential can be harnessed to produce chemicals that address unmet clinical and industrial needs. Developing the capacity to utilize biology to perform chemistry is a matter of increasing control over both the function of synthetic biological systems and the engineering of those systems. Recent efforts have improved general techniques and yielded successes in the use of synthetic biology for the production of drugs, bulk chemicals, and fuels in microbial platform hosts. Synthetic promoter systems and novel RNA-based, or riboregulator, mechanisms give more control over gene expression. Improved methods for isolating, engineering, and evolving enzymes give more control over substrate and product specificity and better catalysis inside the cell. New computational tools and methods for high-throughput system assembly and analysis may lead to more rapid forward engineering. We highlight research that reduces reliance upon natural biological components and point to future work that may enable more rational design and assembly of synthetic biological systems for synthetic chemistry.

  10. Synthetic biology advancing clinical applications.

    Science.gov (United States)

    Folcher, Marc; Fussenegger, Martin

    2012-08-01

    The 'omics' era, with its identification of genetic and protein components, has combined with systems biology, which provided insights into network structures, to set the stage for synthetic biology, an emerging interdisciplinary life science that uses engineering principles. By capitalizing on an iterative design cycle that involves molecular and computational biology tools to assemble functional designer devices from a comprehensive catalogue of standardized biological components with predictable functions, synthetic biology has significantly advanced our understanding of complex control dynamics that program living systems. Such insights, collected over the past decade, are priming a variety of synthetic biology-inspired biomedical applications that have the potential to revolutionize drug discovery and production technologies, as well as treatment strategies for infectious diseases and metabolic disorders. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. 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.

  12. 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.

  13. 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. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Synthetic biology, metaphors and responsibility.

    Science.gov (United States)

    McLeod, Carmen; Nerlich, Brigitte

    2017-08-29

    Metaphors are not just decorative rhetorical devices that make speech pretty. They are fundamental tools for thinking about the world and acting on the world. The language we use to make a better world matters; words matter; metaphors matter. Words have consequences - ethical, social and legal ones, as well as political and economic ones. They need to be used 'responsibly'. They also need to be studied carefully - this is what we want to do through this editorial and the related thematic collection. In the context of synthetic biology, natural and social scientists have become increasingly interested in metaphors, a wave of interest that we want to exploit and amplify. We want to build on emerging articles and books on synthetic biology, metaphors of life and the ethical and moral implications of such metaphors. This editorial provides a brief introduction to synthetic biology and responsible innovation, as well as a comprehensive review of literature on the social, cultural and ethical impacts of metaphor use in genomics and synthetic biology. Our aim is to stimulate an interdisciplinary and international discussion on the impact that metaphors can have on science, policy and publics in the context of synthetic biology.

  15. 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.

  16. 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

  17. 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.

  18. Droplet microfluidics for synthetic biology.

    Science.gov (United States)

    Gach, Philip C; Iwai, Kosuke; Kim, Peter W; Hillson, Nathan J; Singh, Anup K

    2017-10-11

    Synthetic biology is an interdisciplinary field that aims to engineer biological systems for useful purposes. Organism engineering often requires the optimization of individual genes and/or entire biological pathways (consisting of multiple genes). Advances in DNA sequencing and synthesis have recently begun to enable the possibility of evaluating thousands of gene variants and hundreds of thousands of gene combinations. However, such large-scale optimization experiments remain cost-prohibitive to researchers following traditional molecular biology practices, which are frequently labor-intensive and suffer from poor reproducibility. Liquid handling robotics may reduce labor and improve reproducibility, but are themselves expensive and thus inaccessible to most researchers. Microfluidic platforms offer a lower entry price point alternative to robotics, and maintain high throughput and reproducibility while further reducing operating costs through diminished reagent volume requirements. Droplet microfluidics have shown exceptional promise for synthetic biology experiments, including DNA assembly, transformation/transfection, culturing, cell sorting, phenotypic assays, artificial cells and genetic circuits.

  19. 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.

  20. Police reform from the bottom up

    African Journals Online (AJOL)

    The title of this volume, Police reform from the bottom up, is bound to create expectations amongst those concerned with the challenges confronting institutional change in public police agencies. It is an interest shared by police scholars and practitioners across the usual North-South divide. Few police agencies today can ...

  1. Synthetic biology: putting synthesis into biology.

    Science.gov (United States)

    Liang, Jing; Luo, Yunzi; Zhao, Huimin

    2011-01-01

    The ability to manipulate living organisms is at the heart of a range of emerging technologies that serve to address important and current problems in environment, energy, and health. However, with all its complexity and interconnectivity, biology has for many years been recalcitrant to engineering manipulations. The recent advances in synthesis, analysis, and modeling methods have finally provided the tools necessary to manipulate living systems in meaningful ways and have led to the coining of a field named synthetic biology. The scope of synthetic biology is as complicated as life itself--encompassing many branches of science and across many scales of application. New DNA synthesis and assembly techniques have made routine customization of very large DNA molecules. This in turn has allowed the incorporation of multiple genes and pathways. By coupling these with techniques that allow for the modeling and design of protein functions, scientists have now gained the tools to create completely novel biological machineries. Even the ultimate biological machinery--a self-replicating organism--is being pursued at this moment. The aim of this article is to dissect and organize these various components of synthetic biology into a coherent picture.

  2. Investigating bottom-up auditory attention

    Directory of Open Access Journals (Sweden)

    Emine Merve Kaya

    2014-05-01

    Full Text Available Bottom-up attention is a sensory-driven selection mechanism that directs perception towards a subset of the stimulus that is considered salient, or attention-grabbing. Most studies of bottom-up auditory attention have adapted frameworks similar to visual attention models whereby local or global contrast is a central concept in defining salient elements in a scene. In the current study, we take a more fundamental approach to modeling auditory attention; providing the first examination of the space of auditory saliency spanning pitch, intensity and timbre; and shedding light on complex interactions among these features. Informed by psychoacoustic results, we develop a computational model of auditory saliency implementing a novel attentional framework, guided by processes hypothesized to take place in the auditory pathway. In particular, the model tests the hypothesis that perception tracks the evolution of sound events in a multidimensional feature space, and flags any deviation from background statistics as salient. Predictions from the model corroborate the relationship between bottom-up auditory attention and statistical inference, and argues for a potential role of predictive coding as mechanism for saliency detection in acoustic scenes.

  3. 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...

  4. 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. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

  5. Mammalian Synthetic Biology: Engineering Biological Systems.

    Science.gov (United States)

    Black, Joshua B; Perez-Pinera, Pablo; Gersbach, Charles A

    2017-06-21

    The programming of new functions into mammalian cells has tremendous application in research and medicine. Continued improvements in the capacity to sequence and synthesize DNA have rapidly increased our understanding of mechanisms of gene function and regulation on a genome-wide scale and have expanded the set of genetic components available for programming cell biology. The invention of new research tools, including targetable DNA-binding systems such as CRISPR/Cas9 and sensor-actuator devices that can recognize and respond to diverse chemical, mechanical, and optical inputs, has enabled precise control of complex cellular behaviors at unprecedented spatial and temporal resolution. These tools have been critical for the expansion of synthetic biology techniques from prokaryotic and lower eukaryotic hosts to mammalian systems. Recent progress in the development of genome and epigenome editing tools and in the engineering of designer cells with programmable genetic circuits is expanding approaches to prevent, diagnose, and treat disease and to establish personalized theranostic strategies for next-generation medicines. This review summarizes the development of these enabling technologies and their application to transforming mammalian synthetic biology into a distinct field in research and medicine.

  6. 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.

  7. Synthetic Biology Guides Biofuel Production

    Science.gov (United States)

    Connor, Michael R.; Atsumi, Shota

    2010-01-01

    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. PMID:20827393

  8. Synthetic biology: Emerging bioengineering in Indonesia

    Science.gov (United States)

    Suhandono, Sony

    2017-05-01

    The development of synthetic biology will shape the new era of science and technology. It is an emerging bioengineering technique involving genetic engineering which can alter the phenotype and behavior of the cell or the new product. Synthetic biology may produce biomaterials, drugs, vaccines, biosensors, and even a recombinant secondary metabolite used in herbal and complementary medicine, such as artemisinin, a malaria drug which is usually extracted from the plant Artemisia annua. The power of synthetic biology has encouraged scientists in Indonesia, and is still in early development. This paper also covers some research from an Indonesian research institute in synthetic biology such as observing the production of bio surfactants and the enhanced production of artemisinin using a transient expression system. Synthetic biology development in Indonesia may also be related to the iGEM competition, a large synthetic biology research competition which was attended by several universities in Indonesia. The application of synthetic biology for drug discovery will be discussed.

  9. 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.

  10. Synthetic biology of antimicrobial discovery.

    Science.gov (United States)

    Zakeri, Bijan; Lu, Timothy K

    2013-07-19

    Antibiotic discovery has a storied history. From the discovery of penicillin by Sir Alexander Fleming to the relentless quest for antibiotics by Selman Waksman, the stories have become like folklore used to inspire future generations of scientists. However, recent discovery pipelines have run dry at a time when multidrug-resistant pathogens are on the rise. Nature has proven to be a valuable reservoir of antimicrobial agents, which are primarily produced by modularized biochemical pathways. Such modularization is well suited to remodeling by an interdisciplinary approach that spans science and engineering. Herein, we discuss the biological engineering of small molecules, peptides, and non-traditional antimicrobials and provide an overview of the growing applicability of synthetic biology to antimicrobials discovery.

  11. 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

  12. A computational study of liposome logic: towards cellular computing from the bottom up.

    Science.gov (United States)

    Smaldon, James; Romero-Campero, Francisco J; Fernández Trillo, Francisco; Gheorghe, Marian; Alexander, Cameron; Krasnogor, Natalio

    2010-09-01

    In this paper we propose a new bottom-up approach to cellular computing, in which computational chemical processes are encapsulated within liposomes. This "liposome logic" approach (also called vesicle computing) makes use of supra-molecular chemistry constructs, e.g. protocells, chells, etc. as minimal cellular platforms to which logical functionality can be added. Modeling and simulations feature prominently in "top-down" synthetic biology, particularly in the specification, design and implementation of logic circuits through bacterial genome reengineering. The second contribution in this paper is the demonstration of a novel set of tools for the specification, modelling and analysis of "bottom-up" liposome logic. In particular, simulation and modelling techniques are used to analyse some example liposome logic designs, ranging from relatively simple NOT gates and NAND gates to SR-Latches, D Flip-Flops all the way to 3 bit ripple counters. The approach we propose consists of specifying, by means of P systems, gene regulatory network-like systems operating inside proto-membranes. This P systems specification can be automatically translated and executed through a multiscaled pipeline composed of dissipative particle dynamics (DPD) simulator and Gillespie's stochastic simulation algorithm (SSA). Finally, model selection and analysis can be performed through a model checking phase. This is the first paper we are aware of that brings to bear formal specifications, DPD, SSA and model checking to the problem of modeling target computational functionality in protocells. Potential chemical routes for the laboratory implementation of these simulations are also discussed thus for the first time suggesting a potentially realistic physiochemical implementation for membrane computing from the bottom-up.

  13. 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. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  14. The benefits of bottom-up design

    Science.gov (United States)

    Mcfarland, Gregory

    1986-01-01

    An inconsistency is examined in generic top-down design methods and standards employed in the implementation of reliable software. Many design approaches adopt top-down ordering when defining the structure, interfaces, and processing of a system. However, strict adherence to a top-down sequencing does not permit accurate description of a system's error handling functions. The design of the system response to errors is becoming critical as the reliability requirements of systems increase. How top-down methods such as object oriented design and structured design do not adequately address the issues of error handling is described, and it is suggested using a bottom-up substep within these methods to eliminate the problem.

  15. Synthetic biology: an emerging engineering discipline.

    Science.gov (United States)

    Cheng, Allen A; Lu, Timothy K

    2012-01-01

    Over the past decade, synthetic biology has emerged as an engineering discipline for biological systems. Compared with other substrates, biology poses a unique set of engineering challenges resulting from an incomplete understanding of natural biological systems and tools for manipulating them. To address these challenges, synthetic biology is advancing from developing proof-of-concept designs to focusing on core platforms for rational and high-throughput biological engineering. These platforms span the entire biological design cycle, including DNA construction, parts libraries, computational design tools, and interfaces for manipulating and probing synthetic circuits. The development of these enabling technologies requires an engineering mindset to be applied to biology, with an emphasis on generalizable techniques in addition to application-specific designs. This review aims to discuss the progress and challenges in synthetic biology and to illustrate areas where synthetic biology may impact biomedical engineering and human health.

  16. 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.

  17. Bottom-up grammar analysis : a functional formulation

    NARCIS (Netherlands)

    Jeuring, J.T.; Swierstra, D.

    1994-01-01

    This paper discusses bottom-up grammar analysis problems such as te EMPTY problem and the FIRST problem. It defines a general class of bottom-up grammar analysis problems, and from this definition it derives a functional program for performing bottom-up grammar analysis. The derivation is purely

  18. Repurposing ribosomes for synthetic biology.

    Science.gov (United States)

    Liu, Yi; Kim, Do Soon; Jewett, Michael C

    2017-10-01

    The translation system is the cell's factory for protein biosynthesis, stitching together hundreds to thousands of amino acids into proteins, which are required for the structure, function, and regulation of living systems. The extraordinary synthetic capability of this system, which includes the ribosome and its associated factors required for polymerization, has driven extensive efforts to harness it for societal use in areas as diverse as energy, materials, and medicine. A powerful example is recombinant protein production, which has impacted the lives of patients through the synthesis of biopharmaceuticals such as insulin. In nature, however, only limited sets of monomers are utilized, thereby resulting in limited sets of biopolymers (i.e., proteins). Expanding nature's repertoire of ribosomal monomers could yield new classes of enzymes, therapeutics, materials, and chemicals with diverse, genetically encoded chemistry. Here, we discuss recent progress towards engineering ribosomes both in vivo and in vitro. These fundamental and technical breakthroughs open doors for advanced applications in biotechnology and synthetic biology. Copyright © 2017 Elsevier Ltd. All rights reserved.

  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. Synergistic Synthetic Biology: Units In Concert

    Directory of Open Access Journals (Sweden)

    Jean-Yves eTrosset

    2013-10-01

    Full Text Available 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 cancellation 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, multidrug 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.

  1. Bottoms Up. [report on the Defense Department

    Energy Technology Data Exchange (ETDEWEB)

    Isaacs, J.

    1993-11-01

    The [open quotes]Bottoms Up Review[close quotes] was the Pentagon's ongoing reevaluation of the dangers faced by the United States and the forces needed to deal with those dangers. Its purpose was [open quotes]to define the strategy, force structure, modernization programs, industrial base, and infrastucture needed to meet new dangers and seize new opportunities.[close quotes] The report was released in early September. Washington's reaction to the review (generally silence) and the review's major shortcomings are discussed is this article. The central shortfall of the review is the disconnection between the latest military plan and the security threats faced by the United States. As an example of the disconnection, the Pentagon's fiscal 1994 budget request allots less than one percent of the $263 billion budget request to destroy nuclear weapons in the former Soviet Union, to fund peacekeeping operations, to support economic conversion, and to counter proliferation, although these problems are among those slated as among the most important when listed in the review.

  2. Disease, dysfunction, and synthetic biology.

    Science.gov (United States)

    Holm, Sune

    2014-08-01

    Theorists analyzing the concept of disease on the basis of the notion of dysfunction consider disease to be dysfunction requiring. More specifically, dysfunction-requiring theories of disease claim that for an individual to be diseased certain biological facts about it must be the case. Disease is not wholly a matter of evaluative attitudes. In this paper, I consider the dysfunction-requiring component of Wakefield's hybrid account of disease in light of the artifactual organisms envisioned by current research in synthetic biology. In particular, I argue that the possibility of artifactual organisms and the case of oncomice and other bred or genetically modified strains of organism constitute a significant objection to Wakefield's etiological account of the dysfunction requirement. I then develop a new alternative understanding of the dysfunction requirement that builds on the organizational theory of function. I conclude that my suggestion is superior to Wakefield's theory because it (a) can accommodate both artifactual and naturally evolved organisms, (b) avoids the possibility of there being a conflict between what an organismic part is supposed to do and the health of the organism, and (c) provides a nonarbitrary and practical way of determining whether dysfunction occurs. © The Author 2014. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. 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.

  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. 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".

  6. 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".

  7. 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. PMID:22539946

  8. Bottom-up grammar analysis : a functional formulation

    OpenAIRE

    Jeuring, J.T.; Swierstra, D.

    1994-01-01

    This paper discusses bottom-up grammar analysis problems such as te EMPTY problem and the FIRST problem. It defines a general class of bottom-up grammar analysis problems, and from this definition it derives a functional program for performing bottom-up grammar analysis. The derivation is purely calculational, using theorems from lattice therory, the Bird-Meertens calculus, and laws for list-comprehensions. Sufficient conditions guaranteeing the existence of a solution emerge as a byproduct o...

  9. Mammalian synthetic biology for studying the cell

    OpenAIRE

    Mathur, Melina; Xiang, Joy S.; Smolke, Christina D.

    2017-01-01

    Synthetic biology is advancing the design of genetic devices that enable the study of cellular and molecular biology in mammalian cells. These genetic devices use diverse regulatory mechanisms to both examine cellular processes and achieve precise and dynamic control of cellular phenotype. Synthetic biology tools provide novel functionality to complement the examination of natural cell systems, including engineered molecules with specific activities and model systems that mimic complex regula...

  10. 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.

  11. Defining the Synthetic Biology Supply Chain

    Energy Technology Data Exchange (ETDEWEB)

    Frazar, Sarah L.; Hund, Gretchen E.; Bonheyo, George T.; Diggans, James; Bartholomew, Rachel A.; Gehrig, Lindsey; Greaves, Mark

    2017-08-01

    In this article, a team of experts in synthetic biology, data analytics, and national security describe the overall supply chain surrounding synthetic biology. The team analyzes selected interactions within that network to better understand the risks raised by synthetic biology and identifies opportunities for risk mitigation. To introduce the concept, the article will briefly describe how an understanding of supply chains has been important in promoting nuclear nonproliferation objectives. The article concludes by assessing the structure and networks identified in the supply chains to reveal potential opportunities for future biodefense research and development; options for additional information exchange; and means to interdict, detect, or deter suspicious activity.

  12. Philosophy of Systems and Synthetic Biology

    DEFF Research Database (Denmark)

    Green, Sara

    2017-01-01

    philosophically interesting for their own sake. By pursuing ambitious aims such as the development of multiscale computational models and synthetic life forms, they uncover new ground for philosophical analysis. Systems and synthetic biology raise fundamental questions about how far research can be taken through...

  13. Network Reverse Engineering Approach in Synthetic Biology

    Science.gov (United States)

    Zhang, Haoqian; Liu, Ao; Lu, Yuheng; Sheng, Ying; Wu, Qianzhu; Yin, Zhenzhen; Chen, Yiwei; Liu, Zairan; Pan, Heng; Ouyang, Qi

    2013-12-01

    Synthetic biology is a new branch of interdisciplinary science that has been developed in recent years. The main purpose of synthetic biology is to apply successful principles that have been developed in electronic and chemical engineering to develop basic biological functional modules, and through rational design, develop man-made biological systems that have predicted useful functions. Here, we discuss an important principle in rational design of functional biological circuits: the reverse engineering design. We will use a research project that was conducted at Peking University for the International Genetic Engineering Machine Competition (iGEM) to illustrate the principle: synthesis a cell which has a semi-log dose-response to the environment. Through this work we try to demonstrate the potential application of network engineering in synthetic biology.

  14. Bottom-up attention orienting in young children with autism.

    Science.gov (United States)

    Amso, Dima; Haas, Sara; Tenenbaum, Elena; Markant, Julie; Sheinkopf, Stephen J

    2014-03-01

    We examined the impact of simultaneous bottom-up visual influences and meaningful social stimuli on attention orienting in young children with autism spectrum disorders (ASDs). Relative to typically-developing age and sex matched participants, children with ASDs were more influenced by bottom-up visual scene information regardless of whether social stimuli and bottom-up scene properties were congruent or competing. This initial reliance on bottom-up strategies correlated with severity of social impairment as well as receptive language impairments. These data provide support for the idea that there is enhanced reliance on bottom-up attention strategies in ASDs, and that this may have a negative impact on social and language development.

  15. Standardization for natural product synthetic biology

    OpenAIRE

    Zhao, Huimin; Marnix H Medema

    2016-01-01

    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.

  16. Synthetic Biology: Applications Come of Age

    OpenAIRE

    Khalil, Ahmad S.; Collins, James J.

    2010-01-01

    Synthetic biology is bringing together engineers and biologists to design and build novel biomolecular components, networks and pathways, and to use these constructs to rewire and reprogram organisms. These re-engineered organisms will change our lives in the coming years, leading to cheaper drugs, “green” means to fuel our cars, and targeted therapies to attack “superbugs” and diseases such as cancer. The de novo engineering of genetic circuits, biological modules, and synthetic pathways is ...

  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. 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. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. Synthetic biology through biomolecular design and engineering.

    Science.gov (United States)

    Channon, Kevin; Bromley, Elizabeth H C; Woolfson, Derek N

    2008-08-01

    Synthetic biology is a rapidly growing field that has emerged in a global, multidisciplinary effort among biologists, chemists, engineers, physicists, and mathematicians. Broadly, the field has two complementary goals: To improve understanding of biological systems through mimicry and to produce bio-orthogonal systems with new functions. Here we review the area specifically with reference to the concept of synthetic biology space, that is, a hierarchy of components for, and approaches to generating new synthetic and functional systems to test, advance, and apply our understanding of biological systems. In keeping with this issue of Current Opinion in Structural Biology, we focus largely on the design and engineering of biomolecule-based components and systems.

  20. Mammalian synthetic biology for studying the cell.

    Science.gov (United States)

    Mathur, Melina; Xiang, Joy S; Smolke, Christina D

    2017-01-02

    Synthetic biology is advancing the design of genetic devices that enable the study of cellular and molecular biology in mammalian cells. These genetic devices use diverse regulatory mechanisms to both examine cellular processes and achieve precise and dynamic control of cellular phenotype. Synthetic biology tools provide novel functionality to complement the examination of natural cell systems, including engineered molecules with specific activities and model systems that mimic complex regulatory processes. Continued development of quantitative standards and computational tools will expand capacities to probe cellular mechanisms with genetic devices to achieve a more comprehensive understanding of the cell. In this study, we review synthetic biology tools that are being applied to effectively investigate diverse cellular processes, regulatory networks, and multicellular interactions. We also discuss current challenges and future developments in the field that may transform the types of investigation possible in cell biology. © 2017 Mathur et al.

  1. 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. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

  2. Synthetic biology between technoscience and thing knowledge.

    Science.gov (United States)

    Gelfert, Axel

    2013-06-01

    Synthetic biology presents a challenge to traditional accounts of biology: Whereas traditional biology emphasizes the evolvability, variability, and heterogeneity of living organisms, synthetic biology envisions a future of homogeneous, humanly engineered biological systems that may be combined in modular fashion. The present paper approaches this challenge from the perspective of the epistemology of technoscience. In particular, it is argued that synthetic-biological artifacts lend themselves to an analysis in terms of what has been called 'thing knowledge'. As such, they should neither be regarded as the simple outcome of applying theoretical knowledge and engineering principles to specific technological problems, nor should they be treated as mere sources of new evidence in the general pursuit of scientific understanding. Instead, synthetic-biological artifacts should be viewed as partly autonomous research objects which, qua their material-biological constitution, embody knowledge about the natural world-knowledge that, in turn, can be accessed via continuous experimental interrogation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. 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...

  4. 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.

  5. 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...

  6. 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. 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...... 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...... not yet benefited from such approaches. In this perspective, we review the synthetic biology approaches that have been applied to date and speculate on possible short to medium term and "blue sky" aspirations for synthetic biology, particularly in clinical and environmental toxicology. Finally, we point...

  8. Building biological foundries for next-generation synthetic biology.

    Science.gov (United States)

    Chao, Ran; Yuan, YongBo; Zhao, HuiMin

    2015-07-01

    Synthetic biology is an interdisciplinary field that takes top-down approaches to understand and engineer biological systems through design-build-test cycles. A number of advances in this relatively young field have greatly accelerated such engineering cycles. Specifically, various innovative tools were developed for in silico biosystems design, DNA de novo synthesis and assembly, construct verification, as well as metabolite analysis, which have laid a solid foundation for building biological foundries for rapid prototyping of improved or novel biosystems. This review summarizes the state-of-the-art technologies for synthetic biology and discusses the challenges to establish such biological foundries.

  9. 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. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Stability of leadership in bottom-up hierarchical organizations

    OpenAIRE

    Galam, Serge

    2007-01-01

    The stability of a leadership against a growing internal opposition is studied in bottom-up hierarchical organizations. Using a very simple model with bottom-up majority rule voting, the dynamics of power distribution at the various hierarchical levels is calculated within a probabilistic framework. Given a leadership at the top, the opposition weight from the hierarchy bottom is shown to fall off quickly while climbing up the hierarchy. It reaches zero after only a few hierarchical levels. I...

  11. [Applications of synthetic biology in materials science].

    Science.gov (United States)

    Zhao, Tianxin; Zhong, Chao

    2017-03-25

    Materials are the basis for human being survival and social development. To keep abreast with the increasing needs from all aspects of human society, there are huge needs in the development of advanced materials as well as high-efficiency but low-cost manufacturing strategies that are both sustainable and tunable. Synthetic biology, a new engineering principle taking gene regulation and engineering design as the core, greatly promotes the development of life sciences. This discipline has also contributed to the development of material sciences and will continuously bring new ideas to future new material design. In this paper, we review recent advances in applications of synthetic biology in material sciences, with the focus on how synthetic biology could enable synthesis of new polymeric biomaterials and inorganic materials, phage display and directed evolution of proteins relevant to materials development, living functional materials, engineered bacteria-regulated artificial photosynthesis system as well as applications of gene circuits for material sciences.

  12. CSBB: synthetic biology research at Newcastle University.

    Science.gov (United States)

    Goñi-Moreno, Angel; Wipat, Anil; Krasnogor, Natalio

    2017-06-15

    The Centre for Synthetic Biology and the Bioeconomy (CSBB) brings together a far-reaching multidisciplinary community across all Newcastle University's faculties - Medical Sciences, Science, Agriculture and Engineering, and Humanities, Arts and Social Sciences. The CSBB focuses on many different areas of Synthetic Biology, including bioprocessing, computational design and in vivo computation, as well as improving understanding of basic molecular machinery. Such breadth is supported by major national and international research funding, a range of industrial partners in the North East of England and beyond, as well as a large number of doctoral and post-doctoral researchers. The CSBB trains the next generation of scientists through a 1-year MSc in Synthetic Biology. © 2017 The Author(s).

  13. Engineering reduced evolutionary potential for synthetic biology.

    Science.gov (United States)

    Renda, Brian A; Hammerling, Michael J; Barrick, Jeffrey E

    2014-07-01

    The field of synthetic biology seeks to engineer reliable and predictable behaviors in organisms from collections of standardized genetic parts. However, unlike other types of machines, genetically encoded biological systems are prone to changes in their designed sequences due to mutations in their DNA sequences after these devices are constructed and deployed. Thus, biological engineering efforts can be confounded by undesired evolution that rapidly breaks the functions of parts and systems, particularly when they are costly to the host cell to maintain. Here, we explain the fundamental properties that determine the evolvability of biological systems. Then, we use this framework to review current efforts to engineer the DNA sequences that encode synthetic biology devices and the genomes of their microbial hosts to reduce their ability to evolve and therefore increase their genetic reliability so that they maintain their intended functions over longer timescales.

  14. Semiconductor nanowires and nanowire heterostructures: Nanoscience from the bottom up

    Science.gov (United States)

    Zhong, Zhaohui

    2005-07-01

    Nanoscale science and technology involves interdisciplinary research at the interface of chemistry, physics, biology, and engineering sciences. By developing and following a unique intellectual path---the bottom-up paradigm of nanoscale science and technology---it is possible to assemble integrated nanoscale systems with novel functionalities beyond the conventional lithography limit. In this thesis, I present research efforts focused on fundamental aspects of this bottom-up paradigm using semiconductor nanowires (NWs) and nanowire heterostructures as nanoscale building blocks. We first present studies conducted on one of the most important semiconductor materials, silicon nanowires (SiNWs). SiNWs are rationally synthesized via a metal cluster-catalyzed vapor-liquid-solid (VLS) growth mechanism. Room temperature electrical transport studies carried out on SiNW field effect transistors (FETs) show exceptional device performance; estimated hole mobilities in p-SiNWs are significantly higher than bulk silicon at similar doping levels. Furthermore, low temperature transport studies on molecular scale SiNWs reveal phase coherent single charge transport through discrete single particle quantum levels with length scales up to several hundred nanometers. Finally, we show that SiNWs can be assembled into functional nanoelectronic devices. We then discuss two types of nanowire heterostructures: modulation doped silicon nanowires, and branched and hyper-branched nanowire structures. All key properties of modulation doped nanowires can be controlled during the synthesis, including the number, size and periodicity of the differentially doped regions. Their potential applications are also discussed. Moreover, branched and hyper-branched nanowire structures are synthesized via a multi-step nanocluster-catalyzed VLS approach, with branch density controlled by the nanocluster catalyst concentration. Lastly, we describe the realization of complementary doping in gallium nitride

  15. Synthetic biology approaches to engineer T cells.

    Science.gov (United States)

    Wu, Chia-Yung; Rupp, Levi J; Roybal, Kole T; Lim, Wendell A

    2015-08-01

    There is rapidly growing interest in learning how to engineer immune cells, such as T lymphocytes, because of the potential of these engineered cells to be used for therapeutic applications such as the recognition and killing of cancer cells. At the same time, our knowhow and capability to logically engineer cellular behavior is growing rapidly with the development of synthetic biology. Here we describe how synthetic biology approaches are being used to rationally alter the behavior of T cells to optimize them for therapeutic functions. We also describe future developments that will be important in order to construct safe and precise T cell therapeutics. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Synthetic biology of microbes synthesizing polyhydroxyalkanoates (PHA

    Directory of Open Access Journals (Sweden)

    Guo-Qiang Chen

    2016-12-01

    Full Text Available Microbial polyhydroxyalkanoates (PHA have been produced as bioplastics for various purposes. Under the support of China National Basic Research 973 Project, we developed synthetic biology methods to diversify the PHA structures into homo-, random, block polymers with improved properties to better meet various application requirements. At the same time, various pathways were assembled to produce various PHA from glucose as a simple carbon source. At the end, Halomonas bacteria were reconstructed to produce PHA in changing morphology for low cost production under unsterile and continuous conditions. The synthetic biology will advance the PHA into a bio- and material industry.

  17. Synthetic biology: applications come of age.

    Science.gov (United States)

    Khalil, Ahmad S; Collins, James J

    2010-05-01

    Synthetic biology is bringing together engineers and biologists to design and build novel biomolecular components, networks and pathways, and to use these constructs to rewire and reprogram organisms. These re-engineered organisms will change our lives over the coming years, leading to cheaper drugs, 'green' means to fuel our cars and targeted therapies for attacking 'superbugs' and diseases, such as cancer. The de novo engineering of genetic circuits, biological modules and synthetic pathways is beginning to address these crucial problems and is being used in related practical applications.

  18. 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.

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

    Science.gov (United States)

    Wang, Li; Sun, Yujing; Li, Zhuang; Wu, Aiguo; Wei, Gang

    2016-01-01

    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. PMID:28787853

  20. 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.

  1. Integrated Bottom-Up and Top-Down Proteomics of Patient-Derived Breast Tumor Xenografts.

    Science.gov (United States)

    Ntai, Ioanna; LeDuc, Richard D; Fellers, Ryan T; Erdmann-Gilmore, Petra; Davies, Sherri R; Rumsey, Jeanne; Early, Bryan P; Thomas, Paul M; Li, Shunqiang; Compton, Philip D; Ellis, Matthew J C; Ruggles, Kelly V; Fenyö, David; Boja, Emily S; Rodriguez, Henry; Townsend, R Reid; Kelleher, Neil L

    2016-01-01

    Bottom-up proteomics relies on the use of proteases and is the method of choice for identifying thousands of protein groups in complex samples. Top-down proteomics has been shown to be robust for direct analysis of small proteins and offers a solution to the "peptide-to-protein" inference problem inherent with bottom-up approaches. Here, we describe the first large-scale integration of genomic, bottom-up and top-down proteomic data for the comparative analysis of patient-derived mouse xenograft models of basal and luminal B human breast cancer, WHIM2 and WHIM16, respectively. Using these well-characterized xenograft models established by the National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium, we compared and contrasted the performance of bottom-up and top-down proteomics to detect cancer-specific aberrations at the peptide and proteoform levels and to measure differential expression of proteins and proteoforms. Bottom-up proteomic analysis of the tumor xenografts detected almost 10 times as many coding nucleotide polymorphisms and peptides resulting from novel splice junctions than top-down. For proteins in the range of 0-30 kDa, where quantitation was performed using both approaches, bottom-up proteomics quantified 3,519 protein groups from 49,185 peptides, while top-down proteomics quantified 982 proteoforms mapping to 358 proteins. Examples of both concordant and discordant quantitation were found in a ∼60:40 ratio, providing a unique opportunity for top-down to fill in missing information. The two techniques showed complementary performance, with bottom-up yielding eight times more identifications of 0-30 kDa proteins in xenograft proteomes, but failing to detect differences in certain posttranslational modifications (PTMs), such as phosphorylation pattern changes of alpha-endosulfine. This work illustrates the potency of a combined bottom-up and top-down proteomics approach to deepen our knowledge of cancer biology, especially when

  2. Synthetic Biology to Engineer Bacteriophage Genomes.

    Science.gov (United States)

    Rita Costa, Ana; Milho, Catarina; Azeredo, Joana; Pires, Diana Priscila

    2018-01-01

    Recent advances in the synthetic biology field have enabled the development of new molecular biology techniques used to build specialized bacteriophages with new functionalities. Bacteriophages have been engineered towards a wide range of applications including pathogen control and detection, targeted drug delivery, or even assembly of new materials.In this chapter, two strategies that have been successfully used to genetically engineer bacteriophage genomes are addressed: a yeast-based platform and bacteriophage recombineering of electroporated DNA.

  3. Synthetic biology expands chemical control of microorganisms

    OpenAIRE

    Ford, Tyler J.; Silver, Pamela A.

    2015-01-01

    The tools of synthetic biology allow researchers to change the ways engineered organisms respond to chemical stimuli. Decades of basic biology research and new efforts in computational protein and RNA design have led to the development of small molecule sensors that can be used to alter organism function. These new functions leap beyond the natural propensities of the engineered organisms. They can range from simple fluorescence or growth reporting to pathogen killing, and can involve metabol...

  4. Standardization for natural product synthetic biology

    NARCIS (Netherlands)

    Zhao, Huimin; Medema, Marnix H.

    2016-01-01

    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

  5. Synthetic biology advances for pharmaceutical production

    OpenAIRE

    Breitling, Rainer; Takano, Eriko

    2015-01-01

    Synthetic biology enables a new generation of microbial engineering for the biotechnological production of pharmaceuticals and other high-value chemicals. This review presents an overview of recent advances in the field, describing new computational and experimental tools for the discovery, optimization and production of bioactive molecules, and outlining progress towards the application of these tools to pharmaceutical production systems.

  6. Synthetic biology, patenting, health and global justice

    NARCIS (Netherlands)

    Belt, van den H.

    2013-01-01

    The legal and moral issues that synthetic biology (SB) and its medical applications are likely to raise with regard to intellectual property (IP) and patenting are best approached through the lens of a theoretical framework highlighting the ‘‘co-construction’’ or ‘‘co-evolution’’ of patent law and

  7. 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.

  8. Agent-based modelling in synthetic biology.

    Science.gov (United States)

    Gorochowski, Thomas E

    2016-11-30

    Biological systems exhibit complex behaviours that emerge at many different levels of organization. These span the regulation of gene expression within single cells to the use of quorum sensing to co-ordinate the action of entire bacterial colonies. Synthetic biology aims to make the engineering of biology easier, offering an opportunity to control natural systems and develop new synthetic systems with useful prescribed behaviours. However, in many cases, it is not understood how individual cells should be programmed to ensure the emergence of a required collective behaviour. Agent-based modelling aims to tackle this problem, offering a framework in which to simulate such systems and explore cellular design rules. In this article, I review the use of agent-based models in synthetic biology, outline the available computational tools, and provide details on recently engineered biological systems that are amenable to this approach. I further highlight the challenges facing this methodology and some of the potential future directions. © 2016 The Author(s).

  9. Synthetic biology expands chemical control of microorganisms.

    Science.gov (United States)

    Ford, Tyler J; Silver, Pamela A

    2015-10-01

    The tools of synthetic biology allow researchers to change the ways engineered organisms respond to chemical stimuli. Decades of basic biology research and new efforts in computational protein and RNA design have led to the development of small molecule sensors that can be used to alter organism function. These new functions leap beyond the natural propensities of the engineered organisms. They can range from simple fluorescence or growth reporting to pathogen killing, and can involve metabolic coordination among multiple cells or organisms. Herein, we discuss how synthetic biology alters microorganisms' responses to chemical stimuli resulting in the development of microbes as toxicity sensors, disease treatments, and chemical factories. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. 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.

  11. 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. Copyright© by the Spanish Society for Microbiology and Institute for Catalan Studies.

  12. Compositional generative mapping for tree-structured data--part I: bottom-up probabilistic modeling of trees.

    Science.gov (United States)

    Bacciu, Davide; Micheli, Alessio; Sperduti, Alessandro

    2012-12-01

    We introduce a novel compositional (recursive) probabilistic model for trees that defines an approximated bottom-up generative process from the leaves to the root of a tree. The proposed model defines contextual state transitions from the joint configuration of the children to the parent nodes. We argue that the bottom-up context postulates different probabilistic assumptions with respect to a top-down approach, leading to different representational capabilities. We discuss classes of applications that are best suited to a bottom-up approach. In particular, the bottom-up context is shown to better correlate and model the co-occurrence of substructures among the child subtrees of internal nodes. A mixed memory approximation is introduced to factorize the joint children-to-parent state transition matrix as a mixture of pairwise transitions. The proposed approach is the first practical bottom-up generative model for tree-structured data that maintains the same computational class of its top-down counterpart. Comparative experimental analyses exploiting synthetic and real-world datasets show that the proposed model can deal with deep structures better than a top-down generative model. The model is also shown to better capture structural information from real-world data comprising trees with a large out-degree. The proposed bottom-up model can be used as a fundamental building block for the development of other new powerful models.

  13. 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.

  14. Consequentialism and the Synthetic Biology Problem.

    Science.gov (United States)

    Heavey, Patrick

    2017-04-01

    This article analyzes the ethics of synthetic biology (synbio) from a consequentialist perspective, examining potential effects on food and agriculture, and on medicine, fuel, and the advancement of science. The issues of biosafety and biosecurity are also examined. A consequentialist analysis offers an essential road map to policymakers and regulators as to how to deal with synbio. Additionally, the article discusses the limitations of consequentialism as a tool for analysing synbioethics. Is it possible to predict, with any degree of plausibility, what the consequences of synthetic biology will be in 50 years, or in 100, or in 500? Synbio may take humanity to a place of radical departure from what is known or knowable.

  15. Nanowire nanoelectronics assembled from the bottom-up

    Science.gov (United States)

    Duan, Xiangfeng

    2002-01-01

    In this thesis, a new paradigm for "bottom-up" assembly of nanoelectronics using nanowires (NWs) as building blocks has been defined. Three critical problems at the heart of device fabrication and integration will be addressed. First, we describe a general catalytic growth approach for the synthesis of a broad range of single crystal NWs of group III--V, II--VI and IV--IV binary and ternary alloy semiconductors with precisely controlled chemical composition, physical dimension, electronic and optical properties. In this approach, nanoclusters serve as catalytic sites confining and directing the growth of crystalline NWs through a vapor-liquid-solid growth mechanism. A key feature of this method is that the catalyst material and synthetic conditions can be rationally determined from phase diagram data and/or knowledge of chemical reactivity, and thus enables rational design and predictable syntheses. Moreover, catalytic nanocluster size and growth time can be used to precisely define the diameter and length of the NWs, and dopants can be flexibly introduced into the reactant to control the electronic properties. Second, we have performed a series of studies to characterize the physical properties of this new class of NW materials and utilized them for novel device fabrication. Photoluminescence studies show individual NWs exhibit strong quantum confined emission. Electrical transport studies demonstrate that these NWs can be doped as either n- or p-type material with carrier mobility comparable or larger than the bulk materials. The unique optical and electronic properties suggest that the NWs are of high quality and readily enable us to construct a variety of conceptually or fundamentally new types of nanoscale devices, including single NW field-effect transistors (FETs), crossed NW p-n junctions, crossed NW FETs, molecule-gated NW switching/memory devices, crossed NW light emitting diodes (LEDs), NW optical waveguide and optical cavity, highly polarization

  16. Synthetic biology advances for pharmaceutical production.

    Science.gov (United States)

    Breitling, Rainer; Takano, Eriko

    2015-12-01

    Synthetic biology enables a new generation of microbial engineering for the biotechnological production of pharmaceuticals and other high-value chemicals. This review presents an overview of recent advances in the field, describing new computational and experimental tools for the discovery, optimization and production of bioactive molecules, and outlining progress towards the application of these tools to pharmaceutical production systems. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Planning from the bottom up : Democratic decentralisation in action

    NARCIS (Netherlands)

    Pal, A.

    2010-01-01

    This research highlights the gap between the official rhetoric and the political reality of democratic decentralisation and bottom-up planning using an indepth study of the metropolitan planning process in Kolkata, India. The key question that I address here is: how do elected officials at different

  18. Fostering Rural Social Organizations: A Bottom-Up Paradigm In ...

    African Journals Online (AJOL)

    This paper therefore examines rural social organizations in bottom-up paradigm in sustainable rural transformation in Nigeria. In an attempt to justify the continued involvement of rural social organizations in rural transformation, the paper takes an overview on the short and long term strategies adopted so far by rural social ...

  19. 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.

  20. Top-Down Beta Enhances Bottom-Up Gamma.

    Science.gov (United States)

    Richter, Craig G; Thompson, William H; Bosman, Conrado A; Fries, Pascal

    2017-07-12

    Several recent studies have demonstrated that the bottom-up signaling of a visual stimulus is subserved by interareal gamma-band synchronization, whereas top-down influences are mediated by alpha-beta band synchronization. These processes may implement top-down control of stimulus processing if top-down and bottom-up mediating rhythms are coupled via cross-frequency interaction. To test this possibility, we investigated Granger-causal influences among awake macaque primary visual area V1, higher visual area V4, and parietal control area 7a during attentional task performance. Top-down 7a-to-V1 beta-band influences enhanced visually driven V1-to-V4 gamma-band influences. This enhancement was spatially specific and largest when beta-band activity preceded gamma-band activity by ∼0.1 s, suggesting a causal effect of top-down processes on bottom-up processes. We propose that this cross-frequency interaction mechanistically subserves the attentional control of stimulus selection.SIGNIFICANCE STATEMENT Contemporary research indicates that the alpha-beta frequency band underlies top-down control, whereas the gamma-band mediates bottom-up stimulus processing. This arrangement inspires an attractive hypothesis, which posits that top-down beta-band influences directly modulate bottom-up gamma band influences via cross-frequency interaction. We evaluate this hypothesis determining that beta-band top-down influences from parietal area 7a to visual area V1 are correlated with bottom-up gamma frequency influences from V1 to area V4, in a spatially specific manner, and that this correlation is maximal when top-down activity precedes bottom-up activity. These results show that for top-down processes such as spatial attention, elevated top-down beta-band influences directly enhance feedforward stimulus-induced gamma-band processing, leading to enhancement of the selected stimulus. Copyright © 2017 Richter, Thompson et al.

  1. 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 production pathways to a wide variety of chemicals generated by microorganisms. The selection and enhancement of microbiological strains through the practice of strain engineering enables targets of design, construction, and optimization. This news column aspires to cover recent literature relating to the development and understanding of clean technology.

  2. Computational design tools for synthetic biology.

    Science.gov (United States)

    Marchisio, Mario A; Stelling, Jörg

    2009-08-01

    Computer-aided design, pervasive in other engineering disciplines, is currently developing in synthetic biology. Concepts for standardization and hierarchies of parts, devices and systems provide a basis for efficient engineering in biology. Recently developed computational tools, for instance, enable rational (and graphical) composition of genetic circuits from standard parts, and subsequent simulation for testing the predicted functions in silico. The computational design of DNA and proteins with predetermined quantitative functions has made similar advances. The biggest challenge, however, is the integration of tools and methods into powerful and intuitively usable workflows-and the field is only starting to address it.

  3. From DNA nanotechnology to synthetic biology.

    Science.gov (United States)

    Jungmann, Ralf; Renner, Stephan; Simmel, Friedrich C

    2008-04-01

    Attempts to construct artificial systems from biological molecules such as DNA and RNA by self-assembly are compatible with the recent development of synthetic biology. Genetic mechanisms can be used to produce or control artificial structures made from DNA and RNA, and these structures can in turn be used as artificial gene regulatory elements, in vitro as well as in vivo. Artificial biochemical circuits can be incorporated into cell-like reaction compartments, which opens up the possibility to operate them permanently out of equilibrium. In small systems, stochastic effects become noticeable and will have to be accounted for in the design of future systems.

  4. Synthetic biology for pharmaceutical drug discovery

    Directory of Open Access Journals (Sweden)

    Trosset JY

    2015-12-01

    Full Text Available Jean-Yves Trosset,1 Pablo Carbonell2,3 1Bioinformation Research Laboratory, Sup’Biotech, Villejuif, France; 2Faculty of Life Sciences, SYNBIOCHEM Centre, Manchester Institute of Biotechnology, University of Manchester, Manchester, UK; 3Department of Experimental and Health Sciences (DCEXS, Research Programme on Biomedical Informatics (GRIB, Hospital del Mar Medical Research Institute (IMIM, Universitat Pompeu Fabra (UPF, Barcelona, Spain Abstract: 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. Keywords: metabolic engineering, plant synthetic biology, natural products, synthetic quorum sensing, drug resistance

  5. 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 the...

  6. Combining bottom-up and top-down

    Energy Technology Data Exchange (ETDEWEB)

    Boehringer, Christoph [Department of Economics, University of Oldenburg, Oldenburg (Germany); Centre for European Economic Research (ZEW), Mannheim (Germany); Rutherford, Thomas F. [Ann Arbor, Michigan (United States)

    2008-03-15

    We motivate the formulation of market equilibrium as a mixed complementarity problem which explicitly represents weak inequalities and complementarity between decision variables and equilibrium conditions. The complementarity format permits an energy-economy model to combine technological detail of a bottom-up energy system with a second-best characterization of the over-all economy. Our primary objective is pedagogic. We first lay out the complementarity features of economic equilibrium and demonstrate how we can integrate bottom-up activity analysis into a top-down representation of the broader economy. We then provide a stylized numerical example of an integrated model - within both static and dynamic settings. Finally, we present illustrative applications to three themes figuring prominently on the energy policy agenda of many industrialized countries: nuclear phase-out, green quotas, and environmental tax reforms. (author)

  7. Peat accumulation in kettle holes: bottom up or top down?

    OpenAIRE

    G. Gaudig; Couwenberg, J; Joosten, H.

    2006-01-01

    Rapid peat formation in kettle hole-shaped basins may take place either a) by peat forming downwards (top down) from a floating mat under stable water level conditions (terrestrialisation), or b) by peat forming upwards (bottom up) as humus colloids seal off the basin, causing the water level to rise progressively (“kettle hole mire mechanism”). The latter mechanism has hardly been considered in the international literature. The floating-mat mechanism must lead to concave peat isochrones thro...

  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. Trophic control of mesopredators in terrestrial ecosystems: top-down or bottom-up?

    Science.gov (United States)

    Elmhagen, Bodil; Rushton, Stephen P

    2007-03-01

    It has been argued that widespread extinctions of top predators have changed terrestrial ecosystem structures through mesopredator release, where increased abundances of medium-sized predators have detrimental effects on prey communities. This top-down concept has received much attention within conservation biology, but few studies have demonstrated the phenomenon. The concept has been criticized since alternative explanations involving bottom-up impacts from bioclimatic effects on ecosystem productivity and from anthropogenic habitat change are rarely considered. We analyse the response of a mesopredator (the red fox) to declines in top predators (wolf and Eurasian lynx) and agricultural expansion over 90 years in Sweden, taking bioclimatic effects into account. We show a top-down mesopredator release effect, but ecosystem productivity determined its strength. The impacts of agricultural activity were mediated by their effects on top predator populations. Thus, both top-down and bottom-up processes need to be understood for effective preservation of biodiversity in anthropogenically transformed ecosystems.

  10. Biological Dual-Use Research and Synthetic Biology of Yeast.

    Science.gov (United States)

    Cirigliano, Angela; Cenciarelli, Orlando; Malizia, Andrea; Bellecci, Carlo; Gaudio, Pasquale; Lioj, Michele; Rinaldi, Teresa

    2017-04-01

    In recent years, the publication of the studies on the transmissibility in mammals of the H5N1 influenza virus and synthetic genomes has triggered heated and concerned debate within the community of scientists on biological dual-use research; these papers have raised the awareness that, in some cases, fundamental research could be directed to harmful experiments, with the purpose of developing a weapon that could be used by a bioterrorist. Here is presented an overview regarding the dual-use concept and its related international agreements which underlines the work of the Australia Group (AG) Export Control Regime. It is hoped that the principles and activities of the AG, that focuses on export control of chemical and biological dual-use materials, will spread and become well known to academic researchers in different countries, as they exchange biological materials (i.e. plasmids, strains, antibodies, nucleic acids) and scientific papers. To this extent, and with the aim of drawing the attention of the scientific community that works with yeast to the so called Dual-Use Research of Concern, this article reports case studies on biological dual-use research and discusses a synthetic biology applied to the yeast Saccharomyces cerevisiae, namely the construction of the first eukaryotic synthetic chromosome of yeast and the use of yeast cells as a factory to produce opiates. Since this organism is considered harmless and is not included in any list of biological agents, yeast researchers should take simple actions in the future to avoid the sharing of strains and advanced technology with suspicious individuals.

  11. Mapping the Emergence of Synthetic Biology.

    Directory of Open Access Journals (Sweden)

    Benjamin Raimbault

    Full Text Available 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.

  12. Mapping the Emergence of Synthetic Biology.

    Science.gov (United States)

    Raimbault, Benjamin; Cointet, Jean-Philippe; Joly, Pierre-Benoît

    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.

  13. 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...

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

    Science.gov (United States)

    Gilad, Assaf A; Shapiro, Mikhail G

    2017-06-01

    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.

  15. [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.

  16. 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. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. 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. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  18. Top down, bottom up structured programming and program structuring

    Science.gov (United States)

    Hamilton, M.; Zeldin, S.

    1972-01-01

    New design and programming techniques for shuttle software. Based on previous Apollo experience, recommendations are made to apply top-down structured programming techniques to shuttle software. New software verification techniques for large software systems are recommended. HAL, the higher order language selected for the shuttle flight code, is discussed and found to be adequate for implementing these techniques. Recommendations are made to apply the workable combination of top-down, bottom-up methods in the management of shuttle software. Program structuring is discussed relevant to both programming and management techniques.

  19. Bottom-up silicon nanowire-based thermoelectric microgenerators

    Science.gov (United States)

    Dávila, D.; Huber, R.; Hierold, C.

    2015-12-01

    In this work, bottom-up intrinsic crystalline Si nanowire arrays in combination with top-down microfabrication techniques and a vertical device architecture have been proposed to develop an all-silicon nanostructured thermoelectric generator. To fabricate this device, a suitable vertical integration of Si NWs on patterned microstructures, which define the thermoelectric legs of the generator, has been achieved by bonding top and bottom silicon structures through nanowires. The process has been proven to be a feasible approach that employs a regrowth process of the nanowires for bonding purposes.

  20. Bottom-up effects on attention capture and choice

    DEFF Research Database (Denmark)

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

    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...... 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...

  1. 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.

  2. ICT-ENABLED BOTTOM-UP ARCHITECTURAL DESIGN

    Directory of Open Access Journals (Sweden)

    Burak Pak

    2016-04-01

    Full Text Available This paper aims at discussing the potentials of bottom-up design practices in relation to the latest developments in Information and Communication Technologies (ICT by making an in-depth review of inaugural cases. The first part of the study involves a literature study and the elaboration of basic strategies from the case study. The second part reframes the existing ICT tools and strategies and elaborates on their potentials to support the modes of participation performed in these cases. As a result, by distilling the created knowledge, the study reveals the potentials of novel modes of ICT-enabled design participation which exploit a set of collective action tools to support sustainable ways of self-organization and bottom-up design. The final part explains the relevance of these with solid examples and presents a hypothetical case for future implementation. The paper concludes with a brief reflection on the implications of the findings for the future of architectural design education.

  3. Athena: Modular CAM/CAD Software for Synthetic Biology

    OpenAIRE

    Chandran, Deepak; Bergmann, Frank T; Sauro, Herbert M.

    2009-01-01

    Synthetic biology is the engineering of cellular networks. It combines principles of engineering and the knowledge of biological networks to program the behavior of cells. Computational modeling techniques in conjunction with molecular biology techniques have been successful in constructing biological devices such as switches, oscillators, and gates. The ambition of synthetic biology is to construct complex systems from such fundamental devices, much in the same way electronic circuits are bu...

  4. Synthetic biology and its regulation in the European Union.

    Science.gov (United States)

    Buhk, Hans-Jörg

    2014-12-25

    The term synthetic biology is used increasingly, but without a clear definition. Most of the recent research carried out in this field is genetic engineering, as defined by current GMO-legislation in the EU. Synthetic biology has developed its own language. In vitro synthesis of DNA also carries the label synthetic biology. It is important to analyze whether present and future activities of synthetic biology are within the scope of existing EU-legislation. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. 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...... 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 issues....... 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...

  6. 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.

  7. 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.

  8. Synthetic Biology: Engineering Living Systems from Biophysical Principles.

    Science.gov (United States)

    Bartley, Bryan A; Kim, Kyung; Medley, J Kyle; Sauro, Herbert M

    2017-03-28

    Synthetic biology was founded as a biophysical discipline that sought explanations for the origins of life from chemical and physical first principles. Modern synthetic biology has been reinvented as an engineering discipline to design new organisms as well as to better understand fundamental biological mechanisms. However, success is still largely limited to the laboratory and transformative applications of synthetic biology are still in their infancy. Here, we review six principles of living systems and how they compare and contrast with engineered systems. We cite specific examples from the synthetic biology literature that illustrate these principles and speculate on their implications for further study. To fully realize the promise of synthetic biology, we must be aware of life's unique properties. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  9. Developments in the Tools and Methodologies of Synthetic Biology

    Science.gov (United States)

    Kelwick, Richard; MacDonald, James T.; Webb, Alexander J.; Freemont, Paul

    2014-01-01

    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. PMID:25505788

  10. 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.

  11. 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.

  12. Planning from the bottom up. San Diego Regional Comprehensive Plan

    Directory of Open Access Journals (Sweden)

    Inés Sánchez de Madariaga

    2013-02-01

    Full Text Available Las ciudades contemporáneas se extienden cada vez más lejos en el territorio, de hecho, son ciudades que tienen espacios diferenciados, especializados y separados, para la vivienda y para la actividad económica, para el ocio y para el comercio, que se conectan entre sí a través de redes de transporte rodado. Este artículo pretende contribuir al conocimiento de estas experiencias recientes de control de la dispersión a través del caso de la Región de San Diego. El caso de San Diego reviste especial interés porque se trata de una experiencia de planificación bottom-up, es decir, de abajo arriba, y, como tal, sirve para ilustrar los mínimos posibles.

  13. Cell-free synthetic biology: Engineering in an open world

    OpenAIRE

    Lu, Yuan

    2017-01-01

    Cell-free synthetic biology emerges as a powerful and flexible enabling technology that can engineer biological parts and systems for life science applications without using living cells. It provides simpler and faster engineering solutions with an unprecedented freedom of design in an open environment than cell system. This review focuses on recent developments of cell-free synthetic biology on biological engineering fields at molecular and cellular levels, including protein engineering, met...

  14. Ethical perception of synthetic biology | Amin | African Journal of ...

    African Journals Online (AJOL)

    Modern biotechnology has moved forward by the introduction of the synthetic biology technique. By using synthetic biology, it is possible to construct mice genes in the laboratory and replace the need for the genes to be split out from the original animal. The purpose of this paper is to examine how the public in the Klang ...

  15. Bottom-up discrete symmetries for Cabibbo mixing

    Energy Technology Data Exchange (ETDEWEB)

    De Medeiros Varzielas, Ivo [Southampton Univ. (United Kingdom). School of Physics and Astronomy; Rasmussen, Rasmus W. [Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany); Talbert, Jim [Oxford Univ. (United Kingdom). Rudolf Peierls Centre for Theoretical Physics

    2016-05-15

    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 O(10{sup 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 whose predictions for fermionic mixing are corrected via other mechanisms.

  16. Bottom-up nanotechnology: the human nephron filter.

    Science.gov (United States)

    Nissenson, Allen R

    2009-01-01

    Over one million patients worldwide have end-stage renal disease and require dialysis or kidney transplantation. Despite the availability of these forms of renal replacement therapy for nearly four decades, mortality and morbidity are high and patients often have a poor quality of life. We have developed a human nephron filter (HNF) utilizing bottom-up nanotechnology that would eventually make feasible a continuously functioning, wearable or implantable artificial kidney. The device consists of two membranes operating in series within one device cartridge. The first membrane mimics the function of the glomerulus, using convective transport to generate a plasma ultra filtrate, which contains all solutes approaching the molecular weight of albumin. The second membrane mimics the function of the renal tubules, selectively reclaiming designated solutes to maintain body homeostasis. No dialysis solution is used in this device. The HNF has been computer modeled, and operating 12 hour per day, 7 days per week the HNF provides the equivalent of 30 ml/min glomerular filtration rate (compared to half that amount for conventional thrice-weekly hemodialysis). The HNF system, by eliminating dialysate and utilizing a novel membrane system created through applied nanotechnology, represents a breakthrough in renal replacement therapy based on the functioning of native kidneys. The enhanced solute removal and wearable design should substantially improve patient outcomes and quality of life.

  17. Bottom-up Visual Integration in the Medial Parietal Lobe.

    Science.gov (United States)

    Pflugshaupt, Tobias; Nösberger, Myriam; Gutbrod, Klemens; Weber, Konrad P; Linnebank, Michael; Brugger, Peter

    2016-03-01

    Largely based on findings from functional neuroimaging studies, the medial parietal lobe is known to contribute to internally directed cognitive processes such as visual imagery or episodic memory. Here, we present 2 patients with behavioral impairments that extend this view. Both had chronic unilateral lesions of nearly the entire medial parietal lobe, but in opposite hemispheres. Routine neuropsychological examination conducted >4 years after the onset of brain damage showed little deficits of minor severity. In contrast, both patients reported persistent unusual visual impairment. A comprehensive series of tachistoscopic experiments with lateralized stimulus presentation and comparison with healthy participants revealed partial visual hemiagnosia for stimuli presented to their contralesional hemifield, applying inferential single-case statistics to evaluate deficits and dissociations. Double dissociations were found in 4 experiments during which participants had to integrate more than one visual element, either through comparison or formation of a global gestalt. Against the background of recent neuroimaging findings, we conclude that of all medial parietal structures, the precuneus is the most likely candidate for a crucial involvement in such bottom-up visual integration. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  18. Peat accumulation in kettle holes: bottom up or top down?

    Directory of Open Access Journals (Sweden)

    G. Gaudig

    2006-12-01

    Full Text Available Rapid peat formation in kettle hole-shaped basins may take place either a by peat forming downwards (top down from a floating mat under stable water level conditions (terrestrialisation, or b by peat forming upwards (bottom up as humus colloids seal off the basin, causing the water level to rise progressively (“kettle hole mire mechanism”. The latter mechanism has hardly been considered in the international literature. The floating-mat mechanism must lead to concave peat isochrones throughout the basin, whereas the kettle hole mire mechanism will yield surface-parallel isochrones. Peat isochrones were studied in three mires occupying kettle hole-shaped basins in north-eastern Germany by comparing pollen samples from the mineral soil–peat interface at different distances from the centre of each mire with the pollen assemblage profile of a central peat core. All three mires appeared to have largely surface-parallel isochrones and must have developed by the kettle hole mire mechanism. In one mire, this mechanism alternated and took place in combination with terrestrialisation following karst subsidence. The fact that evidence of the kettle hole mire mechanism was found at all of the sites investigated indicates that it may be a common peat forming mechanism in kettle hole-shaped basins worldwide.

  19. Systems Approaches for Synthetic Biology: A Pathway Toward Mammalian Design

    Directory of Open Access Journals (Sweden)

    Rahul eRekhi

    2013-10-01

    Full Text Available We review methods of understanding cellular interactions through computation in order to guide the synthetic design of mammalian cells for translational applications, such as regenerative medicine and cancer therapies. In doing so, we argue that the challenges of engineering mammalian cells provide a prime opportunity to leverage advances in computational systems biology. We support this claim systematically, by addressing each of the principal challenges to existing synthetic bioengineering approaches—stochasticity, complexity, and scale—with specific methods and paradigms in systems biology. Moreover, we characterize a key set of diverse computational techniques, including agent-based modeling, Bayesian network analysis, graph theory, and Gillespie simulations, with specific utility towards synthetic biology. Lastly, we examine the mammalian applications of synthetic biology for medicine and health, and how computational systems biology can aid in the continued development of these applications.

  20. 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. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. 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. Copyright © 2010 Elsevier Ltd. All rights reserved.

  2. Bottom-Up Syntheses and Characterization of One Dimensional Nanomaterials

    Science.gov (United States)

    Yeh, Yao-Wen

    Nanomaterials, materials having at least one dimension below 100 nm, have been creating exciting opportunities for fundamental quantum confinement studies and applications in electronic devices and energy technologies. One obvious and important aspect of nanomaterials is their production. Although nanostructures can be obtained by top-down reductive e-beam lithography and focused ion beam processes, further development of these processes is needed before these techniques can become practical routes to large scale production. On the other hand, bottom-up syntheses, with advantages in material diversity, throughput, and the potential for large volume production, may provide an alternative strategy for creating nanostructures. In this work, we explore syntheses of one dimensional nanostructures based on hydrothermal and arc discharge methods. The first project presented in this thesis involves syntheses of technologically important nanomaterials and their potential application in energy harvesting. In particular, it was demonstrated that single crystal ferroelectric lead magnesium niobate lead titanate (PMN-PT) nanowires can be synthesized by a hydrothermal route. The chemical composition of the synthesized nanowires is near the rhombohedral-monoclinic boundary of PMN-PT, which leads to a high piezoelectric coefficient of 381 pm/V. Finally, the potential use of PMN-PT nanowires in energy harvesting applications was also demonstrated. The second part of this thesis involves the synthesis of carbon and boron nitride nanotubes by dc arc discharges. In particular, we investigated how local plasma related properties affected the synthesis of carbon nanostructures. Finally, we investigated the anodic nature of the arc and how a dc arc discharge can be applied to synthesize boron nitride nanotubes.

  3. 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

  4. 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...

  5. 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......Defenders of synthetic biology commonly make reference to the fact that established technologies, such as domestication or selective breeding, share some of the features of synthetic biology that critics argue make it ethically problematic. In this chapter, I reconstruct such references...... as instances of a type of argument which I dub the Continuity Argument. Roughly, the Continuity Argument seeks to show that if we are not disposed to reject the established technology, then features that this technology share with synthetic biology cannot provide reasons to find it ethically problematic. I...

  6. Computational design approaches and tools for synthetic biology.

    Science.gov (United States)

    MacDonald, James T; Barnes, Chris; Kitney, Richard I; Freemont, Paul S; Stan, Guy-Bart V

    2011-02-01

    A proliferation of new computational methods and software tools for synthetic biology design has emerged in recent years but the field has not yet reached the stage where the design and construction of novel synthetic biology systems has become routine. To a large degree this is due to the inherent complexity of biological systems. However, advances in biotechnology and our scientific understanding have already enabled a number of significant achievements in this area. A key concept in engineering is the ability to assemble simpler standardised modules into systems of increasing complexity but it has yet to be adequately addressed how this approach can be applied to biological systems. In particular, the use of computer aided design tools is common in other engineering disciplines and it should eventually become centrally important to the field of synthetic biology if the challenge of dealing with the stochasticity and complexity of biological systems can be overcome.

  7. Synthetic Biology in the Driving Seat of the Bioeconomy.

    Science.gov (United States)

    Flores Bueso, Yensi; Tangney, Mark

    2017-05-01

    Synthetic biology is revolutionising the biotech industry and is increasingly applied in previously unthought-of markets. Here, we discuss the importance of this industry to the bioeconomy and two of its key factors: the synthetic biology approach to research and development (R&D), and the unique nature of the carefully designed, stakeholder-inclusive, community-directed evolution of the field. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. 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...

  9. Applying Synthetic Biology Principles to Increase Biocellulose (BC) Production

    Science.gov (United States)

    2017-01-31

    to interrogate known promoter systems and putative promoters identified in the genome of G. xylinus. • Apply the tools of synthetic biology to...to apply the tools and techniques of synthetic biology to create a biocatalyst for the production of high purity biocellulose (BC), and to develop a...Inducible promoter systems for Gluconacetobacter spp. were identified which should allow control ofbiocellulose production. 2) A method to use

  10. Synthetic biology looks good on paper.

    Science.gov (United States)

    Lopatkin, Allison J; You, Lingchong

    2014-11-06

    Tremendous progress has been made in the design and implementation of synthetic gene circuits, but real-world applications of such circuits have been limited. Cell-free circuits embedded on paper developed by Pardee et al. promise to deliver specific and rapid diagnostics on a low-cost, highly scalable platform.

  11. 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.

  12. Towards a whole-cell modeling approach for synthetic biology

    Science.gov (United States)

    Purcell, Oliver; Jain, Bonny; Karr, Jonathan R.; Covert, Markus W.; Lu, Timothy K.

    2013-06-01

    Despite rapid advances over the last decade, synthetic biology lacks the predictive tools needed to enable rational design. Unlike established engineering disciplines, the engineering of synthetic gene circuits still relies heavily on experimental trial-and-error, a time-consuming and inefficient process that slows down the biological design cycle. This reliance on experimental tuning is because current modeling approaches are unable to make reliable predictions about the in vivo behavior of synthetic circuits. A major reason for this lack of predictability is that current models view circuits in isolation, ignoring the vast number of complex cellular processes that impinge on the dynamics of the synthetic circuit and vice versa. To address this problem, we present a modeling approach for the design of synthetic circuits in the context of cellular networks. Using the recently published whole-cell model of Mycoplasma genitalium, we examined the effect of adding genes into the host genome. We also investigated how codon usage correlates with gene expression and find agreement with existing experimental results. Finally, we successfully implemented a synthetic Goodwin oscillator in the whole-cell model. We provide an updated software framework for the whole-cell model that lays the foundation for the integration of whole-cell models with synthetic gene circuit models. This software framework is made freely available to the community to enable future extensions. We envision that this approach will be critical to transforming the field of synthetic biology into a rational and predictive engineering discipline.

  13. Yeast synthetic biology toolbox and applications for biofuel production.

    Science.gov (United States)

    Tsai, Ching-Sung; Kwak, Suryang; Turner, Timothy L; Jin, Yong-Su

    2015-02-01

    Yeasts are efficient biofuel producers with numerous advantages outcompeting bacterial counterparts. While most synthetic biology tools have been developed and customized for bacteria especially for Escherichia coli, yeast synthetic biological tools have been exploited for improving yeast to produce fuels and chemicals from renewable biomass. Here we review the current status of synthetic biological tools and their applications for biofuel production, focusing on the model strain Saccharomyces cerevisiae We describe assembly techniques that have been developed for constructing genes, pathways, and genomes in yeast. Moreover, we discuss synthetic parts for allowing precise control of gene expression at both transcriptional and translational levels. Applications of these synthetic biological approaches have led to identification of effective gene targets that are responsible for desirable traits, such as cellulosic sugar utilization, advanced biofuel production, and enhanced tolerance against toxic products for biofuel production from renewable biomass. Although an array of synthetic biology tools and devices are available, we observed some gaps existing in tool development to achieve industrial utilization. Looking forward, future tool development should focus on industrial cultivation conditions utilizing industrial strains. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.

  14. 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.

  15. Bottom-up effects of climate on fish populations: data from the Continuous Plankton Recorder

    DEFF Research Database (Denmark)

    Pitois, S.G.; Lynam, C.P.; Jansen, Teunis

    2012-01-01

    a unique opportunity to investigate long-term changes over decadal scales in the abundance and distribution of fish larvae in relation to physical and biological factors. A principal component analysis (PCA) using 7 biotic and abiotic parameters is applied to investigate the impact of environmental changes...... in the plankton ecosystem, while the larvae of migratory species such as Atlantic mackerel responded more to hydrographic changes. Climate variability seems more likely to influence fish populations through bottom-up control via a cascading effect from changes in the North Atlantic Oscillation (NAO) impacting...... on the hydro dynamic features of the North Sea, in turn impacting on the plankton available as prey for fish larvae. The responses and adaptability of fish larvae to changing environmental conditions, parti cularly to changes in prey availability, are complex and species-specific. This complexity is enhanced...

  16. Opportunities for yeast metabolic engineering: Lessons from synthetic biology.

    Science.gov (United States)

    Krivoruchko, Anastasia; Siewers, Verena; Nielsen, Jens

    2011-03-01

    Constant progress in genetic engineering has given rise to a number of promising areas of research that facilitated the expansion of industrial biotechnology. The field of metabolic engineering, which utilizes genetic tools to manipulate microbial metabolism to enhance the production of compounds of interest, has had a particularly strong impact by providing new platforms for chemical production. Recent developments in synthetic biology promise to expand the metabolic engineering toolbox further by creating novel biological components for pathway design. The present review addresses some of the recent advances in synthetic biology and how these have the potential to affect metabolic engineering in the yeast Saccharomyces cerevisiae. While S. cerevisiae for years has been a robust industrial organism and the target of multiple metabolic engineering trials, its potential for synthetic biology has remained relatively unexplored and further research in this field could strongly contribute to industrial biotechnology. This review also addresses are general considerations for pathway design, ranging from individual components to regulatory systems, overall pathway considerations and whole-organism engineering, with an emphasis on potential contributions of synthetic biology to these areas. Some examples of applications for yeast synthetic biology and metabolic engineering are also discussed. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. 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…

  18. 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

  19. The second wave of synthetic biology: from modules to systems.

    Science.gov (United States)

    Purnick, Priscilla E M; Weiss, Ron

    2009-06-01

    Synthetic biology is a research field that combines the investigative nature of biology with the constructive nature of engineering. Efforts in synthetic biology have largely focused on the creation and perfection of genetic devices and small modules that are constructed from these devices. But to view cells as true 'programmable' entities, it is now essential to develop effective strategies for assembling devices and modules into intricate, customizable larger scale systems. The ability to create such systems will result in innovative approaches to a wide range of applications, such as bioremediation, sustainable energy production and biomedical therapies.

  20. A standard-enabled workflow for synthetic biology

    KAUST Repository

    Myers, Chris J.

    2017-06-15

    A synthetic biology workflow is composed of data repositories that provide information about genetic parts, sequence-level design tools to compose these parts into circuits, visualization tools to depict these designs, genetic design tools to select parts to create systems, and modeling and simulation tools to evaluate alternative design choices. Data standards enable the ready exchange of information within such a workflow, allowing repositories and tools to be connected from a diversity of sources. The present paper describes one such workflow that utilizes, among others, the Synthetic Biology Open Language (SBOL) to describe genetic designs, the Systems Biology Markup Language to model these designs, and SBOL Visual to visualize these designs. We describe how a standard-enabled workflow can be used to produce types of design information, including multiple repositories and software tools exchanging information using a variety of data standards. Recently, the ACS Synthetic Biology journal has recommended the use of SBOL in their publications.

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

    Science.gov (United States)

    Karig, David K

    2017-06-01

    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. Copyright © 2017 The Author. Published by Elsevier Ltd.. All rights reserved.

  2. 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. © 2015 Wiley Periodicals, Inc.

  3. 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...

  4. 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.

  5. 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.

  6. Cell-free synthetic biology for in vitro prototype engineering.

    Science.gov (United States)

    Moore, Simon J; MacDonald, James T; Freemont, Paul S

    2017-06-15

    Cell-free transcription-translation is an expanding field in synthetic biology as a rapid prototyping platform for blueprinting the design of synthetic biological devices. Exemplar efforts include translation of prototype designs into medical test kits for on-site identification of viruses (Zika and Ebola), while gene circuit cascades can be tested, debugged and re-designed within rapid turnover times. Coupled with mathematical modelling, this discipline lends itself towards the precision engineering of new synthetic life. The next stages of cell-free look set to unlock new microbial hosts that remain slow to engineer and unsuited to rapid iterative design cycles. It is hoped that the development of such systems will provide new tools to aid the transition from cell-free prototype designs to functioning synthetic genetic circuits and engineered natural product pathways in living cells. © 2017 The Author(s).

  7. Chemical communication between synthetic and natural cells: a possible experimental design

    OpenAIRE

    Livia Leoni; Pasquale Stano; Francesca D'Angelo; Marco Messina; Luisa Damiano; Giordano Rampioni

    2013-01-01

    The bottom-up construction of synthetic cells is one of the most intriguing and interesting research arenas in synthetic biology. Synthetic cells are built by encapsulating biomolecules inside lipid vesicles (liposomes), allowing the synthesis of one or more functional proteins. Thanks to the in situ synthesized proteins, synthetic cells become able to perform several biomolecular functions, which can be exploited for a large variety of applications. This paves the way to several advanced use...

  8. Improvement of Synthetic Biology Tools for DNA Editing

    DEFF Research Database (Denmark)

    Cavaleiro, Mafalda

    The unpredictability and complexity of biological systems limit the development of economically efficient bio-based production processes that rely on renewable carbon sources and are essential for biosustainability and environmental protection. Synthetic biology (synbio) aims at making biology ea...... of gene circuits, synthesis of whole genomes and natural product discovery. In line with this, it is also described in this thesis how discovery of new cytochromes P450 (CYPs) from marine bacteria could benefit industrial processes....

  9. 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. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. A survey of enabling technologies in synthetic biology.

    Science.gov (United States)

    Kahl, Linda J; Endy, Drew

    2013-05-10

    Realizing constructive applications of synthetic biology requires continued development of enabling technologies as well as policies and practices to ensure these technologies remain accessible for research. Broadly defined, enabling technologies for synthetic biology include any reagent or method that, alone or in combination with associated technologies, provides the means to generate any new research tool or application. Because applications of synthetic biology likely will embody multiple patented inventions, it will be important to create structures for managing intellectual property rights that best promote continued innovation. Monitoring the enabling technologies of synthetic biology will facilitate the systematic investigation of property rights coupled to these technologies and help shape policies and practices that impact the use, regulation, patenting, and licensing of these technologies. We conducted a survey among a self-identifying community of practitioners engaged in synthetic biology research to obtain their opinions and experiences with technologies that support the engineering of biological systems. Technologies widely used and considered enabling by survey participants included public and private registries of biological parts, standard methods for physical assembly of DNA constructs, genomic databases, software tools for search, alignment, analysis, and editing of DNA sequences, and commercial services for DNA synthesis and sequencing. Standards and methods supporting measurement, functional composition, and data exchange were less widely used though still considered enabling by a subset of survey participants. The set of enabling technologies compiled from this survey provide insight into the many and varied technologies that support innovation in synthetic biology. Many of these technologies are widely accessible for use, either by virtue of being in the public domain or through legal tools such as non-exclusive licensing. Access to some

  11. Controlled polymer synthesis--from biomimicry towards synthetic biology.

    Science.gov (United States)

    Pasparakis, George; Krasnogor, Natalio; Cronin, Leroy; Davis, Benjamin G; Alexander, Cameron

    2010-01-01

    The controlled assembly of synthetic polymer structures is now possible with an unprecedented range of functional groups and molecular architectures. In this critical review we consider how the ability to create artificial materials over lengthscales ranging from a few nm to several microns is generating systems that not only begin to mimic those in nature but also may lead to exciting applications in synthetic biology (139 references).

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

    NARCIS (Netherlands)

    Makarenko, K.S.

    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

  13. Spatial bottom-up controls on fire likelihood vary across western North America

    Science.gov (United States)

    Sean A. Parks; Marc-Andre Parisien; Carol Miller

    2012-01-01

    The unique nature of landscapes has challenged our ability to make generalizations about the effects of bottom-up controls on fire regimes. For four geographically distinct fire-prone landscapes in western North America, we used a consistent simulation approach to quantify the influence of three key bottom-up factors, ignitions, fuels, and topography, on spatial...

  14. 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....

  15. 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.

  16. Synthetic Biology: Tools to Design, Build, and Optimize Cellular Processes

    Science.gov (United States)

    Young, Eric; Alper, Hal

    2010-01-01

    The general central dogma frames the emergent properties of life, which make biology both necessary and difficult to engineer. In a process engineering paradigm, each biological process stream and process unit is heavily influenced by regulatory interactions and interactions with the surrounding environment. Synthetic biology is developing the tools and methods that will increase control over these interactions, eventually resulting in an integrative synthetic biology that will allow ground-up cellular optimization. In this review, we attempt to contextualize the areas of synthetic biology into three tiers: (1) the process units and associated streams of the central dogma, (2) the intrinsic regulatory mechanisms, and (3) the extrinsic physical and chemical environment. Efforts at each of these three tiers attempt to control cellular systems and take advantage of emerging tools and approaches. Ultimately, it will be possible to integrate these approaches and realize the vision of integrative synthetic biology when cells are completely rewired for biotechnological goals. This review will highlight progress towards this goal as well as areas requiring further research. PMID:20150964

  17. Synthetic Biology: Tools to Design, Build, and Optimize Cellular Processes

    Directory of Open Access Journals (Sweden)

    Eric Young

    2010-01-01

    Full Text Available The general central dogma frames the emergent properties of life, which make biology both necessary and difficult to engineer. In a process engineering paradigm, each biological process stream and process unit is heavily influenced by regulatory interactions and interactions with the surrounding environment. Synthetic biology is developing the tools and methods that will increase control over these interactions, eventually resulting in an integrative synthetic biology that will allow ground-up cellular optimization. In this review, we attempt to contextualize the areas of synthetic biology into three tiers: (1 the process units and associated streams of the central dogma, (2 the intrinsic regulatory mechanisms, and (3 the extrinsic physical and chemical environment. Efforts at each of these three tiers attempt to control cellular systems and take advantage of emerging tools and approaches. Ultimately, it will be possible to integrate these approaches and realize the vision of integrative synthetic biology when cells are completely rewired for biotechnological goals. This review will highlight progress towards this goal as well as areas requiring further research.

  18. 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. © 2016 The Author(s).

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

    Energy Technology Data Exchange (ETDEWEB)

    d' Espaux, L; Mendez-Perez, D; Li, R; Keasling, JD

    2015-10-23

    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 in this paper we review synthetic metabolic pathways based on fatty acid and isoprenoid metabolism to produce alkanes and other molecules suitable as biofuels. Lastly, we further discuss engineering strategies to optimize engineered biosynthetic routes, as well as the potential of synthetic biology for sustainable manufacturing.

  20. 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. Published by Elsevier Ltd.

  1. 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.

  2. Autonomy and Fear of Synthetic Biology: How Can Patients' Autonomy Be Enhanced in the Field of Synthetic Biology? A Qualitative Study with Stable Patients.

    OpenAIRE

    Rakic Milenko; Wienand Isabelle; Shaw David; Nast Rebecca; Elger Bernice S

    2017-01-01

    We analyzed stable patients' views regarding synthetic biology in general the medical application of synthetic biology and their potential participation in trials of synthetic biology in particular. The aim of the study was to find out whether patients' views and preferences change after receiving more detailed information about synthetic biology and its clinical applications. The qualitative study was carried out with a purposive sample of 36 stable patients who suffered from diabetes or gou...

  3. Nonlinear dimensionality reduction methods for synthetic biology biobricks' visualization.

    Science.gov (United States)

    Yang, Jiaoyun; Wang, Haipeng; Ding, Huitong; An, Ning; Alterovitz, Gil

    2017-01-19

    Visualizing data by dimensionality reduction is an important strategy in Bioinformatics, which could help to discover hidden data properties and detect data quality issues, e.g. data noise, inappropriately labeled data, etc. As crowdsourcing-based synthetic biology databases face similar data quality issues, we propose to visualize biobricks to tackle them. However, existing dimensionality reduction methods could not be directly applied on biobricks datasets. Hereby, we use normalized edit distance to enhance dimensionality reduction methods, including Isomap and Laplacian Eigenmaps. By extracting biobricks from synthetic biology database Registry of Standard Biological Parts, six combinations of various types of biobricks are tested. The visualization graphs illustrate discriminated biobricks and inappropriately labeled biobricks. Clustering algorithm K-means is adopted to quantify the reduction results. The average clustering accuracy for Isomap and Laplacian Eigenmaps are 0.857 and 0.844, respectively. Besides, Laplacian Eigenmaps is 5 times faster than Isomap, and its visualization graph is more concentrated to discriminate biobricks. By combining normalized edit distance with Isomap and Laplacian Eigenmaps, synthetic biology biobircks are successfully visualized in two dimensional space. Various types of biobricks could be discriminated and inappropriately labeled biobricks could be determined, which could help to assess crowdsourcing-based synthetic biology databases' quality, and make biobricks selection.

  4. 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...

  5. Living GenoChemetics by hyphenating synthetic biology and synthetic chemistry in vivo.

    Science.gov (United States)

    Sharma, Sunil V; Tong, Xiaoxue; Pubill-Ulldemolins, Cristina; Cartmell, Christopher; Bogosyan, Emma J A; Rackham, Emma J; Marelli, Enrico; Hamed, Refaat B; Goss, Rebecca J M

    2017-08-09

    Marrying synthetic biology with synthetic chemistry provides a powerful approach toward natural product diversification, combining the best of both worlds: expediency and synthetic capability of biogenic pathways and chemical diversity enabled by organic synthesis. Biosynthetic pathway engineering can be employed to insert a chemically orthogonal tag into a complex natural scaffold affording the possibility of site-selective modification without employing protecting group strategies. Here we show that, by installing a sufficiently reactive handle (e.g., a C-Br bond) and developing compatible mild aqueous chemistries, synchronous biosynthesis of the tagged metabolite and its subsequent chemical modification in living culture can be achieved. This approach can potentially enable many new applications: for example, assay of directed evolution of enzymes catalyzing halo-metabolite biosynthesis in living cells or generating and following the fate of tagged metabolites and biomolecules in living systems. We report synthetic biological access to new-to-nature bromo-metabolites and the concomitant biorthogonal cross-coupling of halo-metabolites in living cultures.Coupling synthetic biology and chemical reactions in cells is a challenging task. The authors engineer bacteria capable of generating bromo-metabolites, develop a mild Suzuki-Miyaura cross-coupling reaction compatible with cell growth and carry out the cross-coupling chemistry in live cell cultures.

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

    OpenAIRE

    Li Wang; Yujing Sun; Zhuang Li; Aiguo Wu; Gang Wei

    2016-01-01

    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 app...

  7. Cell-free synthetic biology: Engineering in an open world.

    Science.gov (United States)

    Lu, Yuan

    2017-03-01

    Cell-free synthetic biology emerges as a powerful and flexible enabling technology that can engineer biological parts and systems for life science applications without using living cells. It provides simpler and faster engineering solutions with an unprecedented freedom of design in an open environment than cell system. This review focuses on recent developments of cell-free synthetic biology on biological engineering fields at molecular and cellular levels, including protein engineering, metabolic engineering, and artificial cell engineering. In cell-free protein engineering, the direct control of reaction conditions in cell-free system allows for easy synthesis of complex proteins, toxic proteins, membrane proteins, and novel proteins with unnatural amino acids. Cell-free systems offer the ability to design metabolic pathways towards the production of desired products. Buildup of artificial cells based on cell-free systems will improve our understanding of life and use them for environmental and biomedical applications.

  8. Cell-free synthetic biology: Engineering in an open world

    Directory of Open Access Journals (Sweden)

    Yuan Lu

    2017-03-01

    Full Text Available Cell-free synthetic biology emerges as a powerful and flexible enabling technology that can engineer biological parts and systems for life science applications without using living cells. It provides simpler and faster engineering solutions with an unprecedented freedom of design in an open environment than cell system. This review focuses on recent developments of cell-free synthetic biology on biological engineering fields at molecular and cellular levels, including protein engineering, metabolic engineering, and artificial cell engineering. In cell-free protein engineering, the direct control of reaction conditions in cell-free system allows for easy synthesis of complex proteins, toxic proteins, membrane proteins, and novel proteins with unnatural amino acids. Cell-free systems offer the ability to design metabolic pathways towards the production of desired products. Buildup of artificial cells based on cell-free systems will improve our understanding of life and use them for environmental and biomedical applications.

  9. TinkerCell: modular CAD tool for synthetic biology.

    Science.gov (United States)

    Chandran, Deepak; Bergmann, Frank T; Sauro, Herbert M

    2009-10-29

    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. 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. 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 and analyzed computationally. TinkerCell can readily accept

  10. 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

  11. Recent development on synthetic biological devices treating bladder cancer

    OpenAIRE

    Chen, Zhicong; He, Anbang; Liu, Yuchen; Huang, Weiren; Cai, Zhiming

    2016-01-01

    Synthetic biology is an emerging field focusing on engineering genetic devices and biomolecular systems for a variety of applications from basic biology to biotechnology and medicine. Thanks to the tremendous advances in genomics and the chemical synthesis of DNA in the past decade, scientists are now able to engineer genetic devices and circuits for cancer research and intervention, which offer promising therapeutic strategies for cancer treatment. In this article, we provide a systemic revi...

  12. Bacterial Genome Engineering and Synthetic Biology: Combating Pathogens

    Science.gov (United States)

    2016-11-04

    distribution is unlimited. UNCLASSIFIED 2 infections. Key advances in genetic engineering approaches can successfully aid in targeting and editing...engineering and SB methods such as recombineering , clustered regularly interspaced short palindromic repeats (CRISPR), and bacterial cell-cell... recombineering , targetron. Background Recent advancements in synthetic biology (SB) have enabled the development of novel genome engineering tools for the

  13. 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.

  14. Where to start? Bottom-up attention improves working memory by determining encoding order.

    Science.gov (United States)

    Ravizza, Susan M; Uitvlugt, Mitchell G; Hazeltine, Eliot

    2016-12-01

    The present study aimed to characterize the mechanism by which working memory is enhanced for items that capture attention because of their novelty or saliency-that is, via bottom-up attention. The first experiment replicated previous research by corroborating that bottom-up attention directed to an item is sufficient for enhancing working memory and, moreover, generalized the effect to the domain of verbal working memory. The subsequent 3 experiments sought to determine how bottom-up attention affects working memory. We considered 2 hypotheses: (1) Bottom-up attention enhances the encoded representation of the stimulus, similar to how voluntary attention functions, or (2) It affects the order of encoding by shifting priority onto the attended stimulus. By manipulating how stimuli were presented (simultaneous/sequential display) and whether the cue predicted the tested items, we found evidence that bottom-up attention improves working memory performance via the order of encoding hypothesis. This finding was observed across change detection and free recall paradigms. In contrast, voluntary attention improved working memory regardless of encoding order and showed greater effects on working memory. We conclude that when multiple information sources compete, bottom-up attention prioritizes the location at which encoding should begin. When encoding order is set, bottom-up attention has little or no benefit to working memory. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  15. Interactions of top-down and bottom-up mechanisms in human visual cortex.

    Science.gov (United States)

    McMains, Stephanie; Kastner, Sabine

    2011-01-12

    Multiple stimuli present in the visual field at the same time compete for neural representation by mutually suppressing their evoked activity throughout visual cortex, providing a neural correlate for the limited processing capacity of the visual system. Competitive interactions among stimuli can be counteracted by top-down, goal-directed mechanisms such as attention, and by bottom-up, stimulus-driven mechanisms. Because these two processes cooperate in everyday life to bias processing toward behaviorally relevant or particularly salient stimuli, it has proven difficult to study interactions between top-down and bottom-up mechanisms. Here, we used an experimental paradigm in which we first isolated the effects of a bottom-up influence on neural competition by parametrically varying the degree of perceptual grouping in displays that were not attended. Second, we probed the effects of directed attention on the competitive interactions induced with the parametric design. We found that the amount of attentional modulation varied linearly with the degree of competition left unresolved by bottom-up processes, such that attentional modulation was greatest when neural competition was little influenced by bottom-up mechanisms and smallest when competition was strongly influenced by bottom-up mechanisms. These findings suggest that the strength of attentional modulation in the visual system is constrained by the degree to which competitive interactions have been resolved by bottom-up processes related to the segmentation of scenes into candidate objects.

  16. 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.

  17. Synthetic Biology Open Language (SBOL) Version 2.1.0.

    Science.gov (United States)

    Beal, Jacob; Cox, Robert Sidney; Grünberg, Raik; McLaughlin, James; Nguyen, Tramy; Bartley, Bryan; Bissell, Michael; Choi, Kiri; Clancy, Kevin; Macklin, Chris; Madsen, Curtis; Misirli, Goksel; Oberortner, Ernst; Pocock, Matthew; Roehner, Nicholas; Samineni, Meher; Zhang, Michael; Zhang, Zhen; Zundel, Zach; Gennari, John; Myers, Chris; Sauro, Herbert; Wipat, Anil

    2016-12-18

    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 2.1 of SBOL that builds upon version 2.0 published in last year’s JIB special issue. In particular, SBOL 2.1 includes improved rules for what constitutes a valid SBOL document, new role fields to simplify the expression of sequence features and how components are used in context, and new best practices descriptions to improve the exchange of basic sequence topology information and the description of genetic design provenance, as well as miscellaneous other minor improvements.

  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

    2013-01-01

    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. PMID:24709875

  19. 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.

  20. Learning affects top down and bottom up modulation of eye movements in decision making

    DEFF Research Database (Denmark)

    Orquin, Jacob Lund; Bagger, Martin; Mueller Loose, Simone

    2013-01-01

    it in a broader framework of top down and bottom up processes and derive the predictions that repeated decisions increase top down control of attention capture which in turn leads to a reduction in bottom up attention capture. To test our hypotheses we conducted a repeated discrete choice experiment with three...... different information presentation formats. We thereby operationalized top down and bottom up control as the effect of individual utility levels and presentation formats on attention capture on a trial-by-trial basis. The experiment revealed an increase in top down control of eye movements over time...

  1. Autonomy and Fear of Synthetic Biology: How Can Patients' Autonomy Be Enhanced in the Field of Synthetic Biology? A Qualitative Study with Stable Patients.

    Science.gov (United States)

    Rakic, Milenko; Wienand, Isabelle; Shaw, David; Nast, Rebecca; Elger, Bernice S

    2017-04-01

    We analyzed stable patients' views regarding synthetic biology in general, the medical application of synthetic biology, and their potential participation in trials of synthetic biology in particular. The aim of the study was to find out whether patients' views and preferences change after receiving more detailed information about synthetic biology and its clinical applications. The qualitative study was carried out with a purposive sample of 36 stable patients, who suffered from diabetes or gout. Interviews were transcribed verbatim, translated and fully anonymized. Thematic analysis was applied in order to examine stable patients' attitudes towards synthetic biology, its medical application, and their participation in trials. When patients were asked about synthetic biology in general, most of them were anxious that something uncontrollable could be created. After a concrete example of possible future treatment options, patients started to see synthetic biology in a more positive way. Our study constitutes an important first empirical insight into stable patients' views on synthetic biology and into the kind of fears triggered by the term "synthetic biology." Our results show that clear and concrete information can change patients' initial negative feelings towards synthetic biology. Information should thus be transmitted with great accuracy and transparency in order to reduce irrational fears of patients and to minimize the risk that researchers present facts too positively for the purposes of persuading patients to participate in clinical trials. Potential participants need to be adequately informed in order to be able to autonomously decide whether to participate in human subject research involving synthetic biology.

  2. Synthetic Biology: Rational Pathway Design for Regenerative Medicine.

    Science.gov (United States)

    Davies, Jamie A

    2016-01-01

    Rational pathway design is the invention of an optimally efficient route from one state (e.g. chemical structure, state of differentiation, physiological state) to another, based on knowledge of biological processes: it contrasts with the use of natural pathways that have evolved by natural selection. Synthetic biology is a hybrid discipline of biology and engineering that offers a means for rationally designed pathways to be realized in living cells. Several areas of regenerative medicine could benefit from rational pathway design, including derivation of patient-specific stem cells, directed differentiation of stem cells, replicating physiological function in an alternative cell type, construction of custom interface tissues and building fail-safe systems into transplanted tissues. Synthetic biological approaches offer the potential for construction of these, for example controllable ex vivo stem cell niches, genetic networks for direct transdifferentiation from adult fibroblast to restricted stem cell without going via induced pluripotent stem cells, signalling pathways for realizing physiological regulation in alternative cell types, morphological modules for producing self-constructing novel 'tissues' and 'kill-switches' for therapeutically applied stem cells. Given the potential of this approach, a closer convergence of the regenerative medicine and synthetic biology research fields seems timely. © 2015 S. Karger AG, Basel.

  3. 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.

  4. Renewable Energy from Synthetic Biology (LBNL Science at the Theater)

    Energy Technology Data Exchange (ETDEWEB)

    Keasling, Jay

    2007-06-04

    Jay Keasling, co-leader of Berkeley Lab's Helios Project, is a groundbreaking researcher in the new scientific field of synthetic biology. In Helios, he directs the biology program, incorporating a range of approaches to increasing the efficacy and economy of plants and cellulose-degrading microbes to make solar-based fuels. He is a UC Berkeley professor of Chemical and Bioengineering, and founder of Amyris Biotechnologies, a company that was honored as a Technology Pioneer for 2006 by the World Economic Forum. Keasling has succeeded in using synthetic biology to develop a yeast-based production scheme for precursors of the antimalarial drug artemisinin in work funded by the Bill & Melinda Gates Foundation.

  5. Plant synthetic biology for molecular engineering of signalling and development.

    Science.gov (United States)

    Nemhauser, Jennifer L; Torii, Keiko U

    2016-03-02

    Molecular genetic studies of model plants in the past few decades have identified many key genes and pathways controlling development, metabolism and environmental responses. Recent technological and informatics advances have led to unprecedented volumes of data that may uncover underlying principles of plants as biological systems. The newly emerged discipline of synthetic biology and related molecular engineering approaches is built on this strong foundation. Today, plant regulatory pathways can be reconstituted in heterologous organisms to identify and manipulate parameters influencing signalling outputs. Moreover, regulatory circuits that include receptors, ligands, signal transduction components, epigenetic machinery and molecular motors can be engineered and introduced into plants to create novel traits in a predictive manner. Here, we provide a brief history of plant synthetic biology and significant recent examples of this approach, focusing on how knowledge generated by the reference plant Arabidopsis thaliana has contributed to the rapid rise of this new discipline, and discuss potential future directions.

  6. 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.

  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. Scaling Reversible Adhesion in Synthetic and Biological Systems

    Science.gov (United States)

    Bartlett, Michael; Irschick, Duncan; Crosby, Alfred

    2013-03-01

    High capacity, easy release polymer adhesives, as demonstrated by a gecko's toe, present unique opportunities for synthetic design. However, without a framework that connects biological and synthetic adhesives from basic nanoscopic features to macroscopic systems, synthetic mimics have failed to perform favorably at large length scales. Starting from an energy balance, we develop a scaling approach to understand unstable interfacial fracture over multiple length scales. The simple theory reveals that reversibly adhesive polymers do not rely upon fibrillar features but require contradicting attributes: maximum compliance normal to the substrate and minimum compliance in the loading direction. We use this counterintuitive criterion to create reversible, easy release adhesives at macroscopic sizes (100 cm2) with unprecedented force capacities on the order of 3000 N. Importantly, we achieve this without fibrillar features, supporting our predictions and emphasizing the importance of subsurface anatomy in biological adhesive systems. Our theory describes adhesive force capacity as a function of material properties and geometry and is supported by over 1000 experiments, spanning both synthetic and biological adhesives, with agreement over 14 orders of magnitude in adhesive force.

  9. 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.

  10. Multifunctional biomaterial coatings: synthetic challenges and biological activity.

    Science.gov (United States)

    Pagel, Mareen; Beck-Sickinger, Annette G

    2017-01-01

    A controlled interaction of materials with their surrounding biological environment is of great interest in many fields. Multifunctional coatings aim to provide simultaneous modulation of several biological signals. They can consist of various combinations of bioactive, and bioinert components as well as of reporter molecules to improve cell-material contacts, prevent infections or to analyze biochemical events on the surface. However, specific immobilization and particular assembly of various active molecules are challenging. Herein, an overview of multifunctional coatings for biomaterials is given, focusing on synthetic strategies and the biological benefits by displaying several motifs.

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

    DEFF Research Database (Denmark)

    Singla, Rashmi

    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...

  12. Naval Force Sizing: Zero-Based or ’Bottoms-Up’ Method

    Science.gov (United States)

    1979-06-01

    25 III "BOTTOMS-UP" - WHAT IS IT? .......... . 25 Caveats ...... ................ 28 IV RISK ....... ................... . 29...acterized by a "count the bodies" philosophy. They argue that, 30 through quantitative methods to reduce measurement uncertainty, a strong clase can

  13. From exclusion to inclusion in public innovation support?: Innovative practices in bottom-up networks

    National Research Council Canada - National Science Library

    Lindberg, Malin

    2014-01-01

    ... – such as women, services industries and service innovations – could be acknowledged by the use of a bottom-up approach in innovation research in a way that helps make public innovation support more inclusive...

  14. Evaluation of Top-down and Bottom-up Leadership Development Programs in a Finnish Company

    OpenAIRE

    Kati Skarp; Keijo Varis; Juha Kettunen

    2017-01-01

    The purpose of this paper is to examine and evaluate the top-down and bottom-up leadership development programs focused on human capital that improve the performance of a company. This study reports on the external top-down leadership development program supported by a consulting company and the internal participatory action research of the bottom-up program. The sickness rate and the lost time incident failure rate decreased and the ideas produced for cost savings improved, leading to increa...

  15. What is Bottom-Up and What is Top-Down in Predictive Coding?

    Science.gov (United States)

    Rauss, Karsten; Pourtois, Gilles

    2013-01-01

    Everyone knows what bottom-up is, and how it is different from top-down. At least one is tempted to think so, given that both terms are ubiquitously used, but only rarely defined in the psychology and neuroscience literature. In this review, we highlight the problems and limitations of our current understanding of bottom-up and top-down processes, and we propose a reformulation of this distinction in terms of predictive coding. PMID:23730295

  16. Supporting Frequent Updates in R-Trees: A Bottom-Up Approach

    DEFF Research Database (Denmark)

    Lee, Mong Li; Hsu, Wynne; Jensen, Christian Søndergaard

    2004-01-01

    to improve update performance. It has different levels of reorganization - ranging from global to local - during updates, avoiding expensive top-down updates. A compact main-memory summary structure that allows direct access to the R-tree index nodes is used together with efficient bottom-up algorithms....... Empirical studies indicate that the bottom-up strategy outperforms the traditional top-down technique, leads to indices with better query performance, achieves higher throughput, and is scalable....

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

    OpenAIRE

    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 t...

  18. A standard-enabled workflow for synthetic biology.

    Science.gov (United States)

    Myers, Chris J; Beal, Jacob; Gorochowski, Thomas E; Kuwahara, Hiroyuki; Madsen, Curtis; McLaughlin, James Alastair; Mısırlı, Göksel; Nguyen, Tramy; Oberortner, Ernst; Samineni, Meher; Wipat, Anil; Zhang, Michael; Zundel, Zach

    2017-06-15

    A synthetic biology workflow is composed of data repositories that provide information about genetic parts, sequence-level design tools to compose these parts into circuits, visualization tools to depict these designs, genetic design tools to select parts to create systems, and modeling and simulation tools to evaluate alternative design choices. Data standards enable the ready exchange of information within such a workflow, allowing repositories and tools to be connected from a diversity of sources. The present paper describes one such workflow that utilizes, among others, the Synthetic Biology Open Language (SBOL) to describe genetic designs, the Systems Biology Markup Language to model these designs, and SBOL Visual to visualize these designs. We describe how a standard-enabled workflow can be used to produce types of design information, including multiple repositories and software tools exchanging information using a variety of data standards. Recently, the ACS Synthetic Biology journal has recommended the use of SBOL in their publications. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  19. [System biology and synthetic biology modify drug discovery and development].

    Science.gov (United States)

    Haiech, Jacques; Ranjeva, Raoul; Kilhoffer, Marie-Claude

    2012-02-01

    Life Sciences are built on observations. Right now, a more systemic approach allowing to integrate the different organizational levels in Biology is emerging. Such an approach uses a set of technologies and strategies allowing to build models that appear to be more and more predictive (omics, bioinformatics, integrative biology, computational biology…). Those models accelerate the rational development of new therapies avoiding an engineering based only on trials and errors. This approach both holistic and predictive radically modifies the discovery and development modalities used today in health industries. Moreover, because of the apparition of new jobs at the interface of disciplines, of private and public sectors and of life sciences and engineering sciences, this implies to rethink the training programs in both their contents and their pedagogical tools. © 2012 médecine/sciences – Inserm / SRMS.

  20. Bottom-up vs. top-down effects on terrestrial insect herbivores: a meta-analysis.

    Science.gov (United States)

    Vidal, Mayra C; Murphy, Shannon M

    2018-01-01

    Primary consumers are under strong selection from resource ('bottom-up') and consumer ('top-down') controls, but the relative importance of these selective forces is unknown. We performed a meta-analysis to compare the strength of top-down and bottom-up forces on consumer fitness, considering multiple predictors that can modulate these effects: diet breadth, feeding guild, habitat/environment, type of bottom-up effects, type of top-down effects and how consumer fitness effects are measured. We focused our analyses on the most diverse group of primary consumers, herbivorous insects, and found that in general top-down forces were stronger than bottom-up forces. Notably, chewing, sucking and gall-making herbivores were more affected by top-down than bottom-up forces, top-down forces were stronger than bottom-up in both natural and controlled (cultivated) environments, and parasitoids and predators had equally strong top-down effects on insect herbivores. Future studies should broaden the scope of focal consumers, particularly in understudied terrestrial systems, guilds, taxonomic groups and top-down controls (e.g. pathogens), and test for more complex indirect community interactions. Our results demonstrate the surprising strength of forces exerted by natural enemies on herbivorous insects, and thus the necessity of using a tri-trophic approach when studying insect-plant interactions. © 2017 John Wiley & Sons Ltd/CNRS.

  1. 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. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. 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.

  3. Post-translational tools expand the scope of synthetic biology.

    Science.gov (United States)

    Olson, Evan J; Tabor, Jeffrey J

    2012-08-01

    Synthetic biology is improving our understanding of and ability to control living organisms. To date, most progress has been made by engineering gene expression. However, computational and genetically encoded tools that allow protein activity and protein-protein interactions to be controlled on their natural time and length scales are emerging. These technologies provide a basis for the construction of post-translational circuits, which are capable of fast, robust and highly spatially resolved signal processing. When combined with their transcriptional and translational counterparts, synthetic post-translational circuits will allow better analysis and control of otherwise intractable biological processes such as cellular differentiation and the growth of tissues. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. The metaphysical lessons of synthetic biology and neuroscience.

    Science.gov (United States)

    Baertschi, Bernard

    2015-01-01

    In this paper, I examine some important metaphysical lessons that are often presented as derived from two new scientific disciplines: synthetic biology and neuroscience. I analyse four of them: the nature of life, the existence of a soul (the mind-body problem), personhood, and free will. Many caveats are in order, and each 'advance' or each case should be assessed for itself. I conclude that a main lesson can nevertheless be learned: in conjunction with modern science, neuroscience and synthetic biology allow us to enrich old metaphysical debates, to deepen and even renew them. In particular, it becomes less and less plausible to consider life, mind, person, and agency as non-natural or non-physical entities. Copyright © 2015 Académie des sciences. Published by Elsevier SAS. All rights reserved.

  5. Top-down network analysis to drive bottom-up modeling of physiological processes.

    Science.gov (United States)

    Poirel, Christopher L; Rodrigues, Richard R; Chen, Katherine C; Tyson, John J; Murali, T M

    2013-05-01

    Top-down analyses in systems biology can automatically find correlations among genes and proteins in large-scale datasets. However, it is often difficult to design experiments from these results. In contrast, bottom-up approaches painstakingly craft detailed models that can be simulated computationally to suggest wet lab experiments. However, developing the models is a manual process that can take many years. These approaches have largely been developed independently. We present LINKER, an efficient and automated data-driven method that can analyze molecular interactomes to propose extensions to models that can be simulated. LINKER combines teleporting random walks and k-shortest path computations to discover connections from a source protein to a set of proteins collectively involved in a particular cellular process. We evaluate the efficacy of LINKER by applying it to a well-known dynamic model of the cell division cycle in Saccharomyces cerevisiae. Compared to other state-of-the-art methods, subnetworks computed by LINKER are heavily enriched in Gene Ontology (GO) terms relevant to the cell cycle. Finally, we highlight how networks computed by LINKER elucidate the role of a protein kinase (Cdc5) in the mitotic exit network of a dynamic model of the cell cycle.

  6. 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.

  7. 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.

  8. Synthetic biology, the bioeconomy, and a societal quandary.

    Science.gov (United States)

    Philp, Jim C; Ritchie, Rachael J; Allan, Jacqueline E M

    2013-05-01

    Opinions on what synthetic biology actually is range from a natural extension of genetic engineering to a new manufacturing paradigm. It offers, for the first time in the life sciences, rational design and engineering standardisation. It could address problems across a broad spectrum of human concerns, including energy and food security, and health of growing and aging populations. It also offers great scope for public resistance to its introduction to daily life. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Synthetic Biology and Ethics: Past, Present, and Future.

    Science.gov (United States)

    Häyry, Matti

    2017-04-01

    This article explores the ethical issues that have been identified in emerging technologies, from early genetic engineering to synthetic biology. The scientific advances in the field form a continuum, and some ethical considerations can be raised time and again when new developments occur. An underlying concern is the cumulative effect of scientific advances and ensuing technological innovation that can change our understanding of life and humanity.

  10. 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).

  11. Synthetic biology and the prospects for responsible innovation.

    Science.gov (United States)

    Macnaghten, Phil; Owen, Richard; Jackson, Roland

    2016-11-30

    In this article we provide a short review of the debate on responsible innovation and its intersection with synthetic biology, focusing on initiatives we have witnessed and been involved with in the UK. First, we describe the ways in which responsibility in science has been reconfigured institutionally, from an internal focus on the provision of objective and reliable knowledge, to a more external view that embraces the ways in which it has an impact on society. Secondly, we introduce a framework for responsible innovation as a (partial) response to this shift, highlighting its constituent dimensions and the capacities and competencies that are needed to put it into practice. Thirdly, we chart the development of social science research on synthetic biology, addressing its evolution from an 'ethical, legal and social implications' (ELSI) frame to a responsible innovation frame. Fourthly, we review findings from UK social science research with the synthetic biology community setting out challenges for productive collaboration. And finally, we conclude with suggestions on the need for changes in institutional governance. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  12. 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…

  13. Generating Systems Biology Markup Language Models from the Synthetic Biology Open Language.

    Science.gov (United States)

    Roehner, Nicholas; Zhang, Zhen; Nguyen, Tramy; Myers, Chris J

    2015-08-21

    In the context of synthetic biology, model generation is the automated process of constructing biochemical models based on genetic designs. This paper discusses the use cases for model generation in genetic design automation (GDA) software tools and introduces the foundational concepts of standards and model annotation that make this process useful. Finally, this paper presents an implementation of model generation in the GDA software tool iBioSim and provides an example of generating a Systems Biology Markup Language (SBML) model from a design of a 4-input AND sensor written in the Synthetic Biology Open Language (SBOL).

  14. Synthetic Biology: A Bridge between Artificial and Natural Cells.

    Science.gov (United States)

    Ding, Yunfeng; Wu, Fan; Tan, Cheemeng

    2014-12-19

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

  15. Transcription control engineering and applications in synthetic biology

    Directory of Open Access Journals (Sweden)

    Michael D. Engstrom

    2017-09-01

    Full Text Available In synthetic biology, researchers assemble biological components in new ways to produce systems with practical applications. One of these practical applications is control of the flow of genetic information (from nucleic acid to protein, a.k.a. gene regulation. Regulation is critical for optimizing protein (and therefore activity levels and the subsequent levels of metabolites and other cellular properties. The central dogma of molecular biology posits that information flow commences with transcription, and accordingly, regulatory tools targeting transcription have received the most attention in synthetic biology. In this mini-review, we highlight many past successes and summarize the lessons learned in developing tools for controlling transcription. In particular, we focus on engineering studies where promoters and transcription terminators (cis-factors were directly engineered and/or isolated from DNA libraries. We also review several well-characterized transcription regulators (trans-factors, giving examples of how cis- and trans-acting factors have been combined to create digital and analogue switches for regulating transcription in response to various signals. Last, we provide examples of how engineered transcription control systems have been used in metabolic engineering and more complicated genetic circuits. While most of our mini-review focuses on the well-characterized bacterium Escherichia coli, we also provide several examples of the use of transcription control engineering in non-model organisms. Similar approaches have been applied outside the bacterial kingdom indicating that the lessons learned from bacterial studies may be generalized for other organisms.

  16. Kappa rule-based modeling in synthetic biology.

    Science.gov (United States)

    Wilson-Kanamori, John; Danos, Vincent; Thomson, Ty; Honorato-Zimmer, Ricardo

    2015-01-01

    Rule-based modeling, an alternative to traditional reaction-based modeling, allows us to intuitively specify biological interactions while abstracting from the underlying combinatorial complexity. One such rule-based modeling formalism is Kappa, which we introduce to readers in this chapter. We discuss the application of Kappa to three modeling scenarios in synthetic biology: a unidirectional switch based on nitrosylase induction in Saccharomyces cerevisiae, the repressilator in Escherichia coli formed from BioBrick parts, and a light-mediated extension to said repressilator developed by the University of Edinburgh team during iGEM 2010. The second and third scenarios in particular form a case-based introduction to the Kappa BioBrick Framework, allowing us to systematically address the modeling of devices and circuits based on BioBrick parts in Kappa. Through the use of these examples, we highlight the ease with which Kappa can model biological interactions both at the genetic and the protein-protein interaction level, resulting in detailed stochastic models accounting naturally for transcriptional and translational resource usage. We also hope to impart the intuitively modular nature of the modeling processes involved, supported by the introduction of visual representations of Kappa models. Concluding, we explore future endeavors aimed at making modeling of synthetic biology more user-friendly and accessible, taking advantage of the strengths of rule-based modeling in Kappa.

  17. Bottom-up and top-down emotion generation: implications for emotion regulation.

    Science.gov (United States)

    McRae, Kateri; Misra, Supriya; Prasad, Aditya K; Pereira, Sean C; Gross, James J

    2012-03-01

    Emotion regulation plays a crucial role in adaptive functioning and mounting evidence suggests that some emotion regulation strategies are often more effective than others. However, little attention has been paid to the different ways emotions can be generated: from the 'bottom-up' (in response to inherently emotional perceptual properties of the stimulus) or 'top-down' (in response to cognitive evaluations). Based on a process priming principle, we hypothesized that mode of emotion generation would interact with subsequent emotion regulation. Specifically, we predicted that top-down emotions would be more successfully regulated by a top-down regulation strategy than bottom-up emotions. To test this hypothesis, we induced bottom-up and top-down emotions, and asked participants to decrease the negative impact of these emotions using cognitive reappraisal. We observed the predicted interaction between generation and regulation in two measures of emotional responding. As measured by self-reported affect, cognitive reappraisal was more successful on top-down generated emotions than bottom-up generated emotions. Neurally, reappraisal of bottom-up generated emotions resulted in a paradoxical increase of amygdala activity. This interaction between mode of emotion generation and subsequent regulation should be taken into account when comparing of the efficacy of different types of emotion regulation, as well as when reappraisal is used to treat different types of clinical disorders. © The Author (2011). Published by Oxford University Press.

  18. Combined contributions of feedforward and feedback inputs to bottom-up attention.

    Science.gov (United States)

    Khorsand, Peyman; Moore, Tirin; Soltani, Alireza

    2015-01-01

    In order to deal with a large amount of information carried by visual inputs entering the brain at any given point in time, the brain swiftly uses the same inputs to enhance processing in one part of visual field at the expense of the others. These processes, collectively called bottom-up attentional selection, are assumed to solely rely on feedforward processing of the external inputs, as it is implied by the nomenclature. Nevertheless, evidence from recent experimental and modeling studies points to the role of feedback in bottom-up attention. Here, we review behavioral and neural evidence that feedback inputs are important for the formation of signals that could guide attentional selection based on exogenous inputs. Moreover, we review results from a modeling study elucidating mechanisms underlying the emergence of these signals in successive layers of neural populations and how they depend on feedback from higher visual areas. We use these results to interpret and discuss more recent findings that can further unravel feedforward and feedback neural mechanisms underlying bottom-up attention. We argue that while it is descriptively useful to separate feedforward and feedback processes underlying bottom-up attention, these processes cannot be mechanistically separated into two successive stages as they occur at almost the same time and affect neural activity within the same brain areas using similar neural mechanisms. Therefore, understanding the interaction and integration of feedforward and feedback inputs is crucial for better understanding of bottom-up attention.

  19. Erasing Borders: A Brief Chronicle of Early Synthetic Biology.

    Science.gov (United States)

    Peretó, Juli

    2016-12-01

    Synthetic Biology is currently presented as an emergent field involving the application of engineering principles to living matter. However, the scientific pursuit of making life in a laboratory is not new and has been the ultimate, if somewhat distant, aim of the origin-of-life research program for many years. Actually, over a century ago, the idea that the synthesis of life was indispensable to fully understand its nature already appealed to material scientists and evolutionists alike. Jacques Loeb proposed a research program from an engineering standpoint, following a synthetic method (experimental abiogenesis) and based on his mechanist vision of living beings, which he considered true chemical machines. Early synthetic biology endeavors, such as the premature experiments by Alfonso L. Herrera in Mexico, Stéphane Leduc in France, and John B. Burke in United Kingdom, were easily ridiculed on both scientific and ideological grounds. However, in retrospect, all those attempts should be considered as legitimate and sincere anti-vitalistic efforts to cross the apparent border between inert and living matter.

  20. Suture, synthetic, or biologic in contaminated ventral hernia repair.

    Science.gov (United States)

    Bondre, Ioana L; Holihan, Julie L; Askenasy, Erik P; Greenberg, Jacob A; Keith, Jerrod N; Martindale, Robert G; Roth, J Scott; Liang, Mike K

    2016-02-01

    Data are lacking to support the choice between suture, synthetic mesh, or biologic matrix in contaminated ventral hernia repair (VHR). We hypothesize that in contaminated VHR, suture repair is associated with the lowest rate of surgical site infection (SSI). A multicenter database of all open VHR performed at from 2010-2011 was reviewed. All patients with follow-up of 1 mo and longer were included. The primary outcome was SSI as defined by the Centers for Disease Control and Prevention. The secondary outcome was hernia recurrence (assessed clinically or radiographically). Multivariate analysis (stepwise regression for SSI and Cox proportional hazard model for recurrence) was performed. A total of 761 VHR were reviewed for a median (range) follow-up of 15 (1-50) mo: there were 291(38%) suture, 303 (40%) low-density and/or mid-density synthetic mesh, and 167(22%) biologic matrix repair. On univariate analysis, there were differences in the three groups including ethnicity, ASA, body mass index, institution, diabetes, primary versus incisional hernia, wound class, hernia size, prior VHR, fascial release, skin flaps, and acute repair. The unadjusted outcomes for SSI (15.1%; 17.8%; 21.0%; P = 0.280) and recurrence (17.8%; 13.5%; 21.5%; P = 0.074) were not statistically different between groups. On multivariate analysis, biologic matrix was associated with a nonsignificant reduction in both SSI and recurrences, whereas synthetic mesh associated with fewer recurrences compared to suture (hazard ratio = 0.60; P = 0.015) and nonsignificant increase in SSI. Interval estimates favored biologic matrix repair in contaminated VHR; however, these results were not statistically significant. In the absence of higher level evidence, surgeons should carefully balance risk, cost, and benefits in managing contaminated ventral hernia repair. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Temperature regulation of marine heterotrophic prokaryotes increases latitudinally as a breach between bottom-up and top-down controls.

    Science.gov (United States)

    Morán, Xosé Anxelu G; Gasol, Josep M; Pernice, Massimo C; Mangot, Jean-François; Massana, Ramon; Lara, Elena; Vaqué, Dolors; Duarte, Carlos M

    2017-09-01

    Planktonic heterotrophic prokaryotes make up the largest living biomass and process most organic matter in the ocean. Determining when and where the biomass and activity of heterotrophic prokaryotes are controlled by resource availability (bottom-up), predation and viral lysis (top-down) or temperature will help in future carbon cycling predictions. We conducted an extensive survey across subtropical and tropical waters of the Atlantic, Indian and Pacific Oceans during the Malaspina 2010 Global Circumnavigation Expedition and assessed indices for these three types of controls at 109 stations (mostly from the surface to 4,000 m depth). Temperature control was approached by the apparent activation energy in eV (ranging from 0.46 to 3.41), bottom-up control by the slope of the log-log relationship between biomass and production rate (ranging from -0.12 to 1.09) and top-down control by an index that considers the relative abundances of heterotrophic nanoflagellates and viruses (ranging from 0.82 to 4.83). We conclude that temperature becomes dominant (i.e. activation energy >1.5 eV) within a narrow window of intermediate values of bottom-up (0.3-0.6) and top-down 0.8-1.2) controls. A pervasive latitudinal pattern of decreasing temperature regulation towards the Equator, regardless of the oceanic basin, suggests that the impact of global warming on marine microbes and their biogeochemical function will be more intense at higher latitudes. Our analysis predicts that 1°C ocean warming will result in increased biomass of heterotrophic prokaryoplankton only in waters with <26°C of mean annual surface temperature. © 2017 The Authors. Global Change Biology Published by John Wiley & Sons Ltd.

  2. 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.

  3. Automated Design Framework for Synthetic Biology Exploiting Pareto Optimality.

    Science.gov (United States)

    Otero-Muras, Irene; Banga, Julio R

    2017-07-21

    In this work we consider Pareto optimality for automated design in synthetic biology. We present a generalized framework based on a mixed-integer dynamic optimization formulation that, given design specifications, allows the computation of Pareto optimal sets of designs, that is, the set of best trade-offs for the metrics of interest. We show how this framework can be used for (i) forward design, that is, finding the Pareto optimal set of synthetic designs for implementation, and (ii) reverse design, that is, analyzing and inferring motifs and/or design principles of gene regulatory networks from the Pareto set of optimal circuits. Finally, we illustrate the capabilities and performance of this framework considering four case studies. In the first problem we consider the forward design of an oscillator. In the remaining problems, we illustrate how to apply the reverse design approach to find motifs for stripe formation, rapid adaption, and fold-change detection, respectively.

  4. 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.

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

    Science.gov (United States)

    2016-09-26

    domesticated, laboratory organisms, primarily utilizing Escherichia coli (E. coli) and Saccharomyces cerevisiae . These organisms were pervasive in molecular...from extreme environments including air dust, desert soil, and cold environments and requires only minimal media for growth . This highly robust organism...biology and genetic engineering because they were highly adapted to laboratory conditions, where rapid growth rates and abundant protein production

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

    DEFF Research Database (Denmark)

    Larsen, Jørgen Christian

    2013-01-01

    Purpose – Using a bottom-up, model-free approach when building robots is often seen as a less scientific way, compared to a top-down model-based approach, because the results are not easily generalizable to other systems. The authors, however, hypothesize that this problem may be addressed by using...... solid experimental methods. The purpose of this paper is to show how well-known experimental methods from bio-mechanics are used to measure and locate weaknesses in a bottom-up, model-free implementation of a quadruped walker and come up with a better solution. Design/methodology/approach – To study...... 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...

  7. Engineering plant metabolism into microbes: from systems biology to synthetic biology.

    Science.gov (United States)

    Xu, Peng; Bhan, Namita; Koffas, Mattheos A G

    2013-04-01

    Plant metabolism represents an enormous repository of compounds that are of pharmaceutical and biotechnological importance. Engineering plant metabolism into microbes will provide sustainable solutions to produce pharmaceutical and fuel molecules that could one day replace substantial portions of the current fossil-fuel based economy. Metabolic engineering entails targeted manipulation of biosynthetic pathways to maximize yields of desired products. Recent advances in Systems Biology and the emergence of Synthetic Biology have accelerated our ability to design, construct and optimize cell factories for metabolic engineering applications. Progress in predicting and modeling genome-scale metabolic networks, versatile gene assembly platforms and delicate synthetic pathway optimization strategies has provided us exciting opportunities to exploit the full potential of cell metabolism. In this review, we will discuss how systems and synthetic biology tools can be integrated to create tailor-made cell factories for efficient production of natural products and fuel molecules in microorganisms. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. Top-down and bottom-up neurodynamic evidence in patients with tinnitus.

    Science.gov (United States)

    Hong, Sung Kwang; Park, Sejik; Ahn, Min-Hee; Min, Byoung-Kyong

    2016-12-01

    Although a peripheral auditory (bottom-up) deficit is an essential prerequisite for the generation of tinnitus, central cognitive (top-down) impairment has also been shown to be an inherent neuropathological mechanism. Using an auditory oddball paradigm (for top-down analyses) and a passive listening paradigm (for bottom-up analyses) while recording electroencephalograms (EEGs), we investigated whether top-down or bottom-up components were more critical in the neuropathology of tinnitus, independent of peripheral hearing loss. We observed significantly reduced P300 amplitudes (reflecting fundamental cognitive processes such as attention) and evoked theta power (reflecting top-down regulation in memory systems) for target stimuli at the tinnitus frequency of patients with tinnitus but without hearing loss. The contingent negative variation (reflecting top-down expectation of a subsequent event prior to stimulation) and N100 (reflecting auditory bottom-up selective attention) were different between the healthy and patient groups. Interestingly, when tinnitus patients were divided into two subgroups based on their P300 amplitudes, their P170 and N200 components, and annoyance and distress indices to their tinnitus sound were different. EEG theta-band power and its Granger causal neurodynamic results consistently support a double dissociation of these two groups in both top-down and bottom-up tasks. Directed cortical connectivity corroborates that the tinnitus network involves the anterior cingulate and the parahippocampal areas, where higher-order top-down control is generated. Together, our observations provide neurophysiological and neurodynamic evidence revealing a differential engagement of top-down impairment along with deficits in bottom-up processing in patients with tinnitus but without hearing loss. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  9. Event-Related Potentials of Bottom-Up and Top-Down Processing of Emotional Faces.

    Science.gov (United States)

    Moradi, Afsane; Mehrinejad, Seyed Abolghasem; Ghadiri, Mohammad; Rezaei, Farzin

    2017-01-01

    Emotional stimulus is processed automatically in a bottom-up way or can be processed voluntarily in a top-down way. Imaging studies have indicated that bottom-up and top-down processing are mediated through different neural systems. However, temporal differentiation of top-down versus bottom-up processing of facial emotional expressions has remained to be clarified. The present study aimed to explore the time course of these processes as indexed by the emotion-specific P100 and late positive potential (LPP) event-related potential (ERP) components in a group of healthy women. Fourteen female students of Alzahra University, Tehran, Iran aged 18-30 years, voluntarily participated in the study. The subjects completed 2 overt and covert emotional tasks during ERP acquisition. The results indicated that fearful expressions significantly produced greater P100 amplitude compared to other expressions. Moreover, the P100 findings showed an interaction between emotion and processing conditions. Further analysis indicated that within the overt condition, fearful expressions elicited more P100 amplitude compared to other emotional expressions. Also, overt conditions created significantly more LPP latencies and amplitudes compared to covert conditions. Based on the results, early perceptual processing of fearful face expressions is enhanced in top-down way compared to bottom-up way. It also suggests that P100 may reflect an attentional bias toward fearful emotions. However, no such differentiation was observed within later processing stages of face expressions, as indexed by the ERP LPP component, in a top-down versus bottom-up way. Overall, this study provides a basis for further exploring of bottom-up and top-down processes underlying emotion and may be typically helpful for investigating the temporal characteristics associated with impaired emotional processing in psychiatric disorders.

  10. 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.

  11. Societal impact of synthetic biology: responsible research and innovation (RRI).

    Science.gov (United States)

    Gregorowius, Daniel; Deplazes-Zemp, Anna

    2016-11-30

    Synthetic biology is an emerging field at the interface between biology and engineering, which has generated many expectations for beneficial biomedical and biotechnological applications. At the same time, however, it has also raised concerns about risks or the aim of producing new forms of living organisms. Researchers from different disciplines as well as policymakers and the general public have expressed the need for a form of technology assessment that not only deals with technical aspects, but also includes societal and ethical issues. A recent and very influential model of technology assessment that tries to implement these aims is known as RRI (Responsible Research and Innovation). In this paper, we introduce this model and its historical precursor strategies. Based on the societal and ethical issues which are presented in the current literature, we discuss challenges and opportunities of applying the RRI model for the assessment of synthetic biology. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  12. 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. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Supporting Frequent Updates in R-Trees: A Bottom-Up Approach

    DEFF Research Database (Denmark)

    Lee, Mong Li; Hsu, Wynne; Jensen, Christian Søndergaard

    2003-01-01

    and aims to improve update performance. It has different levels of reorganization—ranging from global to local—during updates, avoiding expensive top-down updates. A compact main-memory summary structure that allows direct access to the R-tree index nodes is used together with efficient bottom......-up algorithms. Empirical studies show that the bottom-up strategy outperforms the traditional top-down technique, leads to indices with better query performance, achieves higher throughput, and is scalable....

  14. Fast and Bottom-Up Object Detection and Segmentation using Gestalt Principles

    OpenAIRE

    Kootstra G.; Kragic D.

    2011-01-01

    In many scenarios, domestic robot will regularly encounter unknown objects. In such cases, top-down knowledge about the object for detection, recognition, and classification cannot be used. To learn about the object, or to be able to grasp it, bottom-up object segmentation is an important competence for the robot. Also when there is top-down knowledge, prior segmentation of the object can improve recognition and classification. In this paper, we focus on the problem of bottom-up detection and...

  15. Integrated Assessment of Energy Policies: A Decomposition of Top-Down and Bottom-Up

    Energy Technology Data Exchange (ETDEWEB)

    Boehringer, Christoph (Univ. of Oldenburg (Germany)); Rutherford, Thomas F. (ETH Zuerich (Switzerland))

    2008-01-15

    The formulation of market equilibrium problems as mixed complementarity problems (MCP) permits integration of bottom-up programming models of the energy system into top-down general equilibrium models of the overall economy. Yet, in practise the MCP approach loses analytical tractability of income effects, when the energy system includes upper and lowrbounds on many decision variables . We therefore advocate the use of complementarity methods to solve only the top-down economic equilibrium model and employ quadratic programming to solve the underlying bottom-up energy supply model. A simple iterative procedure reconciles the equilibrium prices and quantities between both models.

  16. Nature versus design: synthetic biology or how to build a biological non-machine.

    Science.gov (United States)

    Porcar, M; Peretó, J

    2016-04-18

    The engineering ideal of synthetic biology presupposes that organisms are composed of standard, interchangeable parts with a predictive behaviour. In one word, organisms are literally recognized as machines. Yet living objects are the result of evolutionary processes without any purposiveness, not of a design by external agents. Biological components show massive overlapping and functional degeneracy, standard-free complexity, intrinsic variation and context dependent performances. However, although organisms are not full-fledged machines, synthetic biologists may still be eager for machine-like behaviours from artificially modified biosystems.

  17. Nitrogen and water inputs to tomato plant do not trigger bottom-up effects on a leafminer parasitoid through host and non-host exposures.

    Science.gov (United States)

    Dong, Yong-Cheng; Han, Peng; Niu, Chang-Ying; Zappalà, Lucia; Amiens-Desneux, Edwige; Bearez, Philippe; Lavoir, Anne-Violette; Biondi, Antonio; Desneux, Nicolas

    2017-10-02

    Bottom-up and top-down forces are major components of biological control against pests in an agro-ecosystem. Understanding the multi-trophic interactions between plants and secondary consumers would help optimize pest control strategies. We manipulated nitrogen and/or water inputs to tomato plants (Solanum lycopersicum) to test whether these manipulations could trigger bottom-up effects on the parasitoid Necremnus tutae via host (Tuta absoluta) and/or non-host (Bemisia tabaci) exposures, and compared the control efficacy of N. tutae on T. absoluta in the presence and absence of B. tabaci. The results showed no cascading effects of plant nitrogen and/or water inputs on N. tutae via either host or non-host exposure. The bottom-up force was mitigated by chewing or sap-feeding insect consumers at the second energy level. By contrast, the top-down force on T. absoluta from parasitoids was enhanced by an additionally provided non-host, which could produce alternative food sources extending N. tutae longevity and enhancing the fitness of its offspring. Our results provided evidence for the combination of bottom-up and top-down approaches in tomato integrated pest management programs. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  18. Bottom-up and top-down solid-state NMR approaches for bacterial biofilm matrix composition

    Science.gov (United States)

    Cegelski, Lynette

    2015-04-01

    The genomics and proteomics revolutions have been enormously successful in providing crucial "parts lists" for biological systems. Yet, formidable challenges exist in generating complete descriptions of how the parts function and assemble into macromolecular complexes and whole-cell assemblies. Bacterial biofilms are complex multicellular bacterial communities protected by a slime-like extracellular matrix that confers protection to environmental stress and enhances resistance to antibiotics and host defenses. As a non-crystalline, insoluble, heterogeneous assembly, the biofilm extracellular matrix poses a challenge to compositional analysis by conventional methods. In this perspective, bottom-up and top-down solid-state NMR approaches are described for defining chemical composition in complex macrosystems. The "sum-of-the-parts" bottom-up approach was introduced to examine the amyloid-integrated biofilms formed by Escherichia coli and permitted the first determination of the composition of the intact extracellular matrix from a bacterial biofilm. An alternative top-down approach was developed to define composition in Vibrio cholerae biofilms and relied on an extensive panel of NMR measurements to tease out specific carbon pools from a single sample of the intact extracellular matrix. These two approaches are widely applicable to other heterogeneous assemblies. For bacterial biofilms, quantitative parameters of matrix composition are needed to understand how biofilms are assembled, to improve the development of biofilm inhibitors, and to dissect inhibitor modes of action. Solid-state NMR approaches will also be invaluable in obtaining parameters of matrix architecture.

  19. Mimicking biological stress–strain behaviour with synthetic elastomers

    Science.gov (United States)

    Vatankhah-Varnosfaderani, Mohammad; Daniel, William F. M.; Everhart, Matthew H.; Pandya, Ashish A.; Liang, Heyi; Matyjaszewski, Krzysztof; Dobrynin, Andrey V.; Sheiko, Sergei S.

    2017-09-01

    Despite the versatility of synthetic chemistry, certain combinations of mechanical softness, strength, and toughness can be difficult to achieve in a single material. These combinations are, however, commonplace in biological tissues, and are therefore needed for applications such as medical implants, tissue engineering, soft robotics, and wearable electronics. Present materials synthesis strategies are predominantly Edisonian, involving the empirical mixing of assorted monomers, crosslinking schemes, and occluded swelling agents, but this approach yields limited property control. Here we present a general strategy for mimicking the mechanical behaviour of biological materials by precisely encoding their stress–strain curves in solvent-free brush- and comb-like polymer networks (elastomers). The code consists of three independent architectural parameters—network strand length, side-chain length and grafting density. Using prototypical poly(dimethylsiloxane) elastomers, we illustrate how this parametric triplet enables the replication of the strain-stiffening characteristics of jellyfish, lung, and arterial tissues.

  20. Engineering the robustness of industrial microbes through synthetic biology.

    Science.gov (United States)

    Zhu, Linjiang; Zhu, Yan; Zhang, Yanping; Li, Yin

    2012-02-01

    Microbial fermentations and bioconversions play a central role in the production of pharmaceuticals, enzymes and chemicals. To meet the demands of industrial production, it is desirable that microbes maintain a maximized carbon flux towards target metabolites regardless of fluctuations in intracellular or extracellular environments. This requires cellular systems that maintain functional stability and dynamic homeostasis in a given physiological state, or manipulate transitions between different physiological states. Stable maintenance or smooth transition can be achieved through engineering of dynamic controllability, modular and hierarchical organization, or functional redundancy, three key features of biological robustness in a cellular system. This review summarizes how synthetic biology can be used to improve the robustness of industrial microbes. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Learning from biology: synthetic lipoproteins for drug delivery.

    Science.gov (United States)

    Huang, Huang; Cruz, William; Chen, Juan; Zheng, Gang

    2015-01-01

    Synthetic lipoproteins represent a relevant tool for targeted delivery of biological/chemical agents (chemotherapeutics, siRNAs, photosensitizers, and imaging contrast agents) into various cell types. These nanoparticles offer a number of advantages for drugs delivery over their native counterparts while retaining their natural characteristics and biological functions. Their ultra-small size (lipoprotein receptors, i.e., low-density lipoprotein receptor (LDLR) and Scavenger receptor class B member 1 (SRB1) that are found in a number of pathological conditions (e.g., cancer, atherosclerosis), make them superior delivery strategies when compared with other nanoparticle systems. We review the various approaches that have been developed for the generation of synthetic lipoproteins and their respective applications in vitro and in vivo. More specifically, we summarize the approaches employed to address the limitation on use of reconstituted lipoproteins by means of natural or recombinant apolipoproteins, as well as apolipoprotein mimetic molecules. Finally, we provide an overview of the advantages and disadvantages of these approaches and discuss future perspectives for clinical translation of these nanoparticles. © 2014 Wiley Periodicals, Inc.

  2. Is there anything unique in the ethics of synthetic biology?

    Science.gov (United States)

    Heyd, David

    2012-01-01

    Synthetic biology does not create any ethical dilemmas that have not already been raised in the development of practices such as genetic screening, genetic engineering, and other interventions in the evolutionary processes. The issue is, nevertheless, ethically serious. Two different angles are examined: the philosophical legitimacy of human intervention in the shaping of human nature, and the more pragmatic (though by no means less important) question of the risks involved in such a novel line of research. As for the first, the claim made here is that in principle there is no constraint in human intervention in the world, since ultimately the source of any value lies in human interests, welfare, and values. This is an approach that is opposite to Habermas's. As for the practical problem of risk, research in synthetic biology calls for particular caution, since in at least the first stages of a new research or program, there is no social regulation, and society is wholly dependent on the scientist's ethical integrity.

  3. Research Translation and Emerging Health Technologies: Synthetic Biology and Beyond.

    Science.gov (United States)

    Chan, Sarah

    2016-12-09

    New health technologies are rapidly emerging from various areas of bioscience research, such as gene editing, regenerative medicine and synthetic biology. These technologies raise promising medical possibilities but also a range of ethical considerations. Apart from the issues involved in considering whether novel health technologies can or should become part of mainstream medical treatment once established, the process of research translation to develop such therapies itself entails particular ethical concerns. In this paper I use synthetic biology as an example of a new and largely unexplored area of health technology to consider the ways in which novel health technologies are likely to emerge and the ethical challenges these will present. I argue that such developments require us to rethink conventional attitudes towards clinical research, the roles of doctors/researchers and patients/participants with respect to research, and the relationship between science and society; and that a broader framework is required to address the plurality of stakeholder roles and interests involved in the development of treatments based on novel technologies.

  4. 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 com...

  5. Bottom-up processes influence the demography and life-cycle phenology of Hawaiian bird communities

    Science.gov (United States)

    Jared D. Wolfe; C. John Ralph; Andrew Wiegardt

    2017-01-01

    Changes in climate can indirectly regulate populations at higher trophic levels by influencing the availability of food resources in the lower reaches of the food web. As such, species that rely on fruit and nectar food resources may be particularly sensitive to these bottom-up perturbations due to the strength of their trophic linkages with climatically-...

  6. 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…

  7. Multistable Perception: When Bottom-Up and Top-Down Coincide

    Science.gov (United States)

    Kornmeier, Jurgen; Hein, Christine Maira; Bach, Michael

    2009-01-01

    During prolonged observation of an ambiguous figure sudden perceptual reversals occur, while the stimulus itself stays unchanged. There is a vivid debate about whether bottom-up or top-down mechanisms underlie this phenomenon. In the present study, we investigated the interrelation of two experimental factors: volitional control and discontinuous…

  8. Lexical Quality and Reading Skill: Bottom-Up and Top-Down Contributions to Sentence Processing

    Science.gov (United States)

    Hersch, Jolyn; Andrews, Sally

    2012-01-01

    This research investigated whether spelling ability, an index of precise lexical representations, predicts the balance between bottom-up and top-down processing in online sentence processing among skilled readers, over and above contributions of reading ability, vocabulary, and working memory. The results showed that the combination of superior…

  9. 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...

  10. Bottom-up and top-down emotion generation: implications for emotion regulation

    Science.gov (United States)

    Misra, Supriya; Prasad, Aditya K.; Pereira, Sean C.; Gross, James J.

    2012-01-01

    Emotion regulation plays a crucial role in adaptive functioning and mounting evidence suggests that some emotion regulation strategies are often more effective than others. However, little attention has been paid to the different ways emotions can be generated: from the ‘bottom-up’ (in response to inherently emotional perceptual properties of the stimulus) or ‘top-down’ (in response to cognitive evaluations). Based on a process priming principle, we hypothesized that mode of emotion generation would interact with subsequent emotion regulation. Specifically, we predicted that top-down emotions would be more successfully regulated by a top-down regulation strategy than bottom-up emotions. To test this hypothesis, we induced bottom-up and top-down emotions, and asked participants to decrease the negative impact of these emotions using cognitive reappraisal. We observed the predicted interaction between generation and regulation in two measures of emotional responding. As measured by self-reported affect, cognitive reappraisal was more successful on top-down generated emotions than bottom-up generated emotions. Neurally, reappraisal of bottom-up generated emotions resulted in a paradoxical increase of amygdala activity. This interaction between mode of emotion generation and subsequent regulation should be taken into account when comparing of the efficacy of different types of emotion regulation, as well as when reappraisal is used to treat different types of clinical disorders. PMID:21296865

  11. Comparing Top-Down with Bottom-Up Approaches: Teaching Data Modeling

    Science.gov (United States)

    Kung, Hsiang-Jui; Kung, LeeAnn; Gardiner, Adrian

    2013-01-01

    Conceptual database design is a difficult task for novice database designers, such as students, and is also therefore particularly challenging for database educators to teach. In the teaching of database design, two general approaches are frequently emphasized: top-down and bottom-up. In this paper, we present an empirical comparison of students'…

  12. Bottom-up and Top-down: An alternate classification of LD authoring approaches

    NARCIS (Netherlands)

    Sodhi, Tim; Miao, Yongwu; Brouns, Francis; Koper, Rob

    2007-01-01

    Sodhi, T., Miao, Y., Brouns, F., & Koper, E. J. R. (2007). Bottom-up and Top-down: An alternate classification of LD authoring approaches. Paper presented at the TENCompetence Open Workshop on Current research on IMS Learning Design and Lifelong Competence Development Infrastructures. June, 21-22,

  13. 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...

  14. Bottom-up and top-down tree transformations - a comparison

    NARCIS (Netherlands)

    Engelfriet, Joost

    1975-01-01

    The top-down and bottom-up tree transducer are incomparable with respect to their transformation power. The difference between them is mainly caused by the different order in which they use the facilities of copying and nondeterminism. One can however define certain simple tree transformations,

  15. 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

  16. Bottom-up control of water hyacinth weevil populations: Do the plants regulate the insects?

    Science.gov (United States)

    A key measure of dietary sufficiency relates to an insect’s reproductive ability so oögenesis, a nutrient-limited process, can be subject to bottom-up regulation. We hypothesized that aquatic nutrient flux seasonally affects ovarian development thereby controlling population growth of two specialis...

  17. Iodine versus Bromine Functionalization for Bottom-Up Graphene Nanoribbon Growth

    DEFF Research Database (Denmark)

    Bronner, Christopher; Marangoni, Tomas; Rizzo, Daniel J.

    2017-01-01

    Deterministic bottom-up approaches for synthesizing atomically well-defined graphene nanoribbons (GNRs) largely rely on the surface-catalyzed activation of selected labile bonds in a molecular precursor followed by step-growth polymerization and cyclodehydrogenation. While the majority of success...

  18. Teacher-Led Professional Development: A Proposal for a Bottom-up Structure Approach

    Science.gov (United States)

    Macias, Angela

    2017-01-01

    This article uses current research recommendations for teacher-led professional development as well as qualitative data from a set of grassroots conferences to propose a new model for bottom-up teacher-led professional development. This article argues that by providing a neutral space and recruiting expertise of local experts, a public sphere can…

  19. Who Should Be at the Top of Bottom-Up Development?

    OpenAIRE

    Rao, Vijayendra; Joshi, Shareen

    2017-01-01

    It is widely acknowledged that top-down support is essential for bottom-up participatory projects to be effectively implemented at scale. However, which level of government, national or sub-national, should be given the responsibility to implement such projects is an open question, with wide variations in practice. This paper analyzes qualitative and quantitative data from a natural experi...

  20. Ways toward a European Vocational Education and Training Space: A "Bottom-Up" Approach

    Science.gov (United States)

    Blings, Jessica; Spottl, Georg

    2008-01-01

    Purpose: This paper seeks to concentrate on bottom-up approaches in order to promote a European vocational education and training (VET) concept. The overall aim of this article is to demonstrate that sophisticated approaches still have a chance of becoming common practice in European countries. Design/methodology/approach: The centre of the…

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

    DEFF Research Database (Denmark)

    Williams, Idongesit

    2016-01-01

    networks –leading to the demise of some of these initiatives. This paper proposes co-financing of these networks as a means of sustaining the bottom-up Broadband network. The argument of this paper is anchored on two of developing country cases. One in India and the other in Ghana. One survived...

  2. 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.

  3. Comparison between bottom-up and top-down approaches in the estimation of measurement uncertainty.

    Science.gov (United States)

    Lee, Jun Hyung; Choi, Jee-Hye; Youn, Jae Saeng; Cha, Young Joo; Song, Woonheung; Park, Ae Ja

    2015-06-01

    Measurement uncertainty is a metrological concept to quantify the variability of measurement results. There are two approaches to estimate measurement uncertainty. In this study, we sought to provide practical and detailed examples of the two approaches and compare the bottom-up and top-down approaches to estimating measurement uncertainty. We estimated measurement uncertainty of the concentration of glucose according to CLSI EP29-A guideline. Two different approaches were used. First, we performed a bottom-up approach. We identified the sources of uncertainty and made an uncertainty budget and assessed the measurement functions. We determined the uncertainties of each element and combined them. Second, we performed a top-down approach using internal quality control (IQC) data for 6 months. Then, we estimated and corrected systematic bias using certified reference material of glucose (NIST SRM 965b). The expanded uncertainties at the low glucose concentration (5.57 mmol/L) by the bottom-up approach and top-down approaches were ±0.18 mmol/L and ±0.17 mmol/L, respectively (all k=2). Those at the high glucose concentration (12.77 mmol/L) by the bottom-up and top-down approaches were ±0.34 mmol/L and ±0.36 mmol/L, respectively (all k=2). We presented practical and detailed examples for estimating measurement uncertainty by the two approaches. The uncertainties by the bottom-up approach were quite similar to those by the top-down approach. Thus, we demonstrated that the two approaches were approximately equivalent and interchangeable and concluded that clinical laboratories could determine measurement uncertainty by the simpler top-down approach.

  4. Assessment of discrepancies between bottom-up and regional emission inventories in Norwegian urban areas

    Science.gov (United States)

    López-Aparicio, Susana; Guevara, Marc; Thunis, Philippe; Cuvelier, Kees; Tarrasón, Leonor

    2017-04-01

    This study shows the capabilities of a benchmarking system to identify inconsistencies in emission inventories, and to evaluate the reason behind discrepancies as a mean to improve both bottom-up and downscaled emission inventories. Fine scale bottom-up emission inventories for seven urban areas in Norway are compared with three regional emission inventories, EC4MACS, TNO_MACC-II and TNO_MACC-III, downscaled to the same areas. The comparison shows discrepancies in nitrogen oxides (NOx) and particulate matter (PM2.5 and PM10) when evaluating both total and sectorial emissions. The three regional emission inventories underestimate NOx and PM10 traffic emissions by approximately 20-80% and 50-90%, respectively. The main reasons for the underestimation of PM10 emissions from traffic in the regional inventories are related to non-exhaust emissions due to resuspension, which are included in the bottom-up emission inventories but are missing in the official national emissions, and therefore in the downscaled regional inventories. The benchmarking indicates that the most probable reason behind the underestimation of NOx traffic emissions by the regional inventories is the activity data. The fine scale NOx traffic emissions from bottom-up inventories are based on the actual traffic volume at the road link and are much higher than the NOx emissions downscaled from national estimates based on fuel sales and based on population for the urban areas. We have identified important discrepancies in PM2.5 emissions from wood burning for residential heating among all the inventories. These discrepancies are associated with the assumptions made for the allocation of emissions. In the EC4MACs inventory, such assumptions imply high underestimation of PM2.5 emissions from the residential combustion sector in urban areas, which ranges from 40 to 90% compared with the bottom-up inventories. The study shows that in three of the seven Norwegian cities there is need for further improvement of

  5. 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 period 2000-2007. Based on a review of bottom-up inventories, we estimate total net anthropogenic N2O emissions of 6.0 Tg N2O-N/yr (5.4-8.4 Tg N2O-N/yr). Estimates (and ranges) by sector (in Tg N2O-N/yr) are: agriculture 4.1 Tg (3.8-6.8); biomass burning 0.7 (0.5-1.7); energy and transport 0.7 (0.5-1.2); industry 0.7 (0.3-1.1); and other 0.5 (0.2 - 0.8). Tropical deforestation has reduced emissions by 0.7 (0.5 - 1.0). Given the large inherent uncertainties in both approaches, it is encouraging that the

  6. 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. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Learning from nature - novel synthetic biology approaches for biomaterial design.

    Science.gov (United States)

    Bryksin, Anton V; Brown, Ashley C; Baksh, Michael M; Finn, M G; Barker, Thomas H

    2014-04-01

    Many biomaterials constructed today are complex chemical structures that incorporate biologically active components derived from nature, but the field can still be said to be in its infancy. The need for materials that bring sophisticated properties of structure, dynamics and function to medical and non-medical applications will only grow. Increasing appreciation of the functionality of biological systems has caused biomaterials researchers to consider nature for design inspiration, and many examples exist of the use of biomolecular motifs. Yet evolution, nature's only engine for the creation of new designs, has been largely ignored by the biomaterials community. Molecular evolution is an emerging tool that enables one to apply nature's engineering principles to non-natural situations using variation and selection. The purpose of this review is to highlight the most recent advances in the use of molecular evolution in synthetic biology applications for biomaterial engineering, and to discuss some of the areas in which this approach may be successfully applied in the future. Copyright © 2014 Acta Materialia Inc. All rights reserved.

  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. 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.

  10. Carnosic acid biosynthesis elucidated by a synthetic biology platform

    Science.gov (United States)

    Ignea, Codruta; Athanasakoglou, Anastasia; Ioannou, Efstathia; Georgantea, Panagiota; Trikka, Fotini A.; Loupassaki, Sofia; Roussis, Vassilios; Makris, Antonios M.

    2016-01-01

    Synthetic biology approaches achieving the reconstruction of specific plant natural product biosynthetic pathways in dedicated microbial “chassis” have provided access to important industrial compounds (e.g., artemisinin, resveratrol, vanillin). However, the potential of such production systems to facilitate elucidation of plant biosynthetic pathways has been underexplored. Here we report on the application of a modular terpene production platform in the characterization of the biosynthetic pathway leading to the potent antioxidant carnosic acid and related diterpenes in Salvia pomifera and Rosmarinus officinalis. Four cytochrome P450 enzymes are identified (CYP76AH24, CYP71BE52, CYP76AK6, and CYP76AK8), the combined activities of which account for all of the oxidation events leading to the biosynthesis of the major diterpenes produced in these plants. This approach develops yeast as an efficient tool to harness the biotechnological potential of the numerous sequencing datasets that are increasingly becoming available through transcriptomic or genomic studies. PMID:26976595

  11. 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.

  12. 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.

  13. Plant glyco-biotechnology on the way to synthetic biology

    Directory of Open Access Journals (Sweden)

    Andreas eLoos

    2014-10-01

    Full Text Available Plants are increasingly being used for the production of recombinant proteins. One reason is that plants are highly amenable for glycan engineering processes and allow the production of therapeutic proteins with increased efficacies due to optimized glycosylation profiles. Removal and insertion of glycosylation reactions by knock-out/knock-down approaches and introduction of glycosylation enzymes have paved the way for the humanization of the plant glycosylation pathway. The insertion of heterologous enzymes at exactly the right stage of the existing glycosylation pathway has turned out to be of utmost importance for optimal results. To enable such precise targeting chimeric enzymes have been constructed. In this short review we will exemplify the importance of correct targeting of glycosyltransferases, we will give an overview of the targeting mechanism of glycosyltransferases, describe chimeric enzymes used in plant N-glycosylation engineering and illustrate how plant glycoengineering builds on the tools offered by synthetic biology to construct such chimeric enzymes.

  14. 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.

  15. Engineering Therapeutic T Cells: From Synthetic Biology to Clinical Trials.

    Science.gov (United States)

    Esensten, Jonathan H; Bluestone, Jeffrey A; Lim, Wendell A

    2017-01-24

    Engineered T cells are currently in clinical trials to treat patients with cancer, solid organ transplants, and autoimmune diseases. However, the field is still in its infancy. The design, and manufacturing, of T cell therapies is not standardized and is performed mostly in academic settings by competing groups. Reliable methods to define dose and pharmacokinetics of T cell therapies need to be developed. As of mid-2016, there are no US Food and Drug Administration (FDA)-approved T cell therapeutics on the market, and FDA regulations are only slowly adapting to the new technologies. Further development of engineered T cell therapies requires advances in immunology, synthetic biology, manufacturing processes, and government regulation. In this review, we outline some of these challenges and discuss the contributions that pathologists can make to this emerging field.

  16. Agricultural ammonia emissions in China: reconciling bottom-up and top-down estimates

    Directory of Open Access Journals (Sweden)

    L. Zhang

    2018-01-01

    Full Text Available Current estimates of agricultural ammonia (NH3 emissions in China differ by more than a factor of 2, hindering our understanding of their environmental consequences. Here we apply both bottom-up statistical and top-down inversion methods to quantify NH3 emissions from agriculture in China for the year 2008. We first assimilate satellite observations of NH3 column concentration from the Tropospheric Emission Spectrometer (TES using the GEOS-Chem adjoint model to optimize Chinese anthropogenic NH3 emissions at the 1∕2°  ×  2∕3° horizontal resolution for March–October 2008. Optimized emissions show a strong summer peak, with emissions about 50 % higher in summer than spring and fall, which is underestimated in current bottom-up NH3 emission estimates. To reconcile the latter with the top-down results, we revisit the processes of agricultural NH3 emissions and develop an improved bottom-up inventory of Chinese NH3 emissions from fertilizer application and livestock waste at the 1∕2°  ×  2∕3° resolution. Our bottom-up emission inventory includes more detailed information on crop-specific fertilizer application practices and better accounts for meteorological modulation of NH3 emission factors in China. We find that annual anthropogenic NH3 emissions are 11.7 Tg for 2008, with 5.05 Tg from fertilizer application and 5.31 Tg from livestock waste. The two sources together account for 88 % of total anthropogenic NH3 emissions in China. Our bottom-up emission estimates also show a distinct seasonality peaking in summer, consistent with top-down results from the satellite-based inversion. Further evaluations using surface network measurements show that the model driven by our bottom-up emissions reproduces the observed spatial and seasonal variations of NH3 gas concentrations and ammonium (NH4+ wet deposition fluxes over China well, providing additional credibility to the improvements we have made to our

  17. Agricultural ammonia emissions in China: reconciling bottom-up and top-down estimates

    Science.gov (United States)

    Zhang, Lin; Chen, Youfan; Zhao, Yuanhong; Henze, Daven K.; Zhu, Liye; Song, Yu; Paulot, Fabien; Liu, Xuejun; Pan, Yuepeng; Lin, Yi; Huang, Binxiang

    2018-01-01

    Current estimates of agricultural ammonia (NH3) emissions in China differ by more than a factor of 2, hindering our understanding of their environmental consequences. Here we apply both bottom-up statistical and top-down inversion methods to quantify NH3 emissions from agriculture in China for the year 2008. We first assimilate satellite observations of NH3 column concentration from the Tropospheric Emission Spectrometer (TES) using the GEOS-Chem adjoint model to optimize Chinese anthropogenic NH3 emissions at the 1/2° × 2/3° horizontal resolution for March-October 2008. Optimized emissions show a strong summer peak, with emissions about 50 % higher in summer than spring and fall, which is underestimated in current bottom-up NH3 emission estimates. To reconcile the latter with the top-down results, we revisit the processes of agricultural NH3 emissions and develop an improved bottom-up inventory of Chinese NH3 emissions from fertilizer application and livestock waste at the 1/2° × 2/3° resolution. Our bottom-up emission inventory includes more detailed information on crop-specific fertilizer application practices and better accounts for meteorological modulation of NH3 emission factors in China. We find that annual anthropogenic NH3 emissions are 11.7 Tg for 2008, with 5.05 Tg from fertilizer application and 5.31 Tg from livestock waste. The two sources together account for 88 % of total anthropogenic NH3 emissions in China. Our bottom-up emission estimates also show a distinct seasonality peaking in summer, consistent with top-down results from the satellite-based inversion. Further evaluations using surface network measurements show that the model driven by our bottom-up emissions reproduces the observed spatial and seasonal variations of NH3 gas concentrations and ammonium (NH4+) wet deposition fluxes over China well, providing additional credibility to the improvements we have made to our agricultural NH3 emission inventory.

  18. 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.

  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. 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

  1. An exploration of synthetic biology: A preliminary Christian ethical assessment of the advantages and disadvantages of synthetic biology

    Directory of Open Access Journals (Sweden)

    Riaan A.L. Rheeder

    2014-02-01

    Full Text Available On 20 May 2010, the Venter Institute in America announced that they have fully synthesised the genome of the organism Mycoplasma mycoides whilst in vitro by using a computer connected to a machine that synthesises genes. Thereafter, the genome was placed back into the casing of another organism (Mycoplasma capricolum and it was reported that the synthesised organism and the genome functioned normally. This synthesised organism was reconstructed to function as a minute little factory with the aim of producing and secreting fuel and medicine − something that is not the natural function of this organism. There are certain potential dangers inherent in this kind of technology. Scientists fear that this technology may contaminate or infect humans, animals or the environment, and that it can as such be extremely harmful, or even lead to the destruction of humans. Other scientists are concerned that terrorists can use this technology to kill innocent citizens. Some ethicists are of the opinion that the consequences of synthetic biology is currently unpredictable and that it is therefore risky. In opposition to the potential dangers, one has to mention that synthetic biology indeed can result in far-reaching positive outcomes such as the manufacturing of biofuel and medication. Most scientists and ethicists are of the opinion that the potential dangers involved in synthetic biology should be evaluated in light of the fact that genetic manipulation has not caused any biological devastation over the last 30 years. From a Christian point of departure, the opinion is currently that synthetic biology is not an irresponsible science and technology.’n Verkenning van sintetiese biologie: ’n Voorlopige Christelik-etiese beoordeling van die voor- en nadele van sintetiese biologie. Op 20 Mei 2010 het die Venter-instituut (in Amerika aangekondig dat hulle die genoom van die organisme Mycoplasma mycoides ten volle in vitro gesintetiseer het (deur middel van

  2. DESIGN OF GENETIC ELEMENTS AND SOFTWARE TOOLS FOR PLANT SYNTHETIC BIOLOGY

    OpenAIRE

    Vázquez Vilar, Marta

    2016-01-01

    [EN] Synthetic Biology is an emerging interdisciplinary field that aims to apply the engineering principles of modularity, abstraction and standardization to genetic engineering. The nascent branch of Synthetic Biology devoted to plants, Plant Synthetic Biology (PSB), offers new breeding possibilities for crops, potentially leading to enhanced resistance, higher yield, or increased nutritional quality. To this end, the molecular tools in the PSB toolbox need to be adapted accordingly, to beco...

  3. Bottom-up and top-down effects on plant communities

    DEFF Research Database (Denmark)

    Souza, Lara; Zelikova, Tamara Jane; Sanders, Nate

    2016-01-01

    Top-down effects of herbivores and bottom-up effects of nutrients shape productivity and diversity across ecosystems, yet their single and combined effects on spatial and temporal beta diversity is unknown. We established a field experiment in which the abundance of insect herbivores (top-down...... affected ANPP while top-down factors influenced plant community structure. Across years, while N reduction lowered ANPP by 10%, N reduction did not alter ANPP relative to control plots. Further, N reduction lowered ANPP by 20% relative to N addition plots. On the other hand, the reduction of insect...... herbivores did not alter plant richness (α diversity) yet consistently promoted Shannon's evenness, relative to plots where insect herbivores were present. Further, insect herbivores promoted spatial-temporal β diversity. Overall, we found that the relative importance of top-down and bottom-up controls...

  4. 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.

  5. Cognitive Functions of the Posterior Parietal Cortex: Top-down and bottom-up attentional control

    Directory of Open Access Journals (Sweden)

    Sarah eShomstein

    2012-07-01

    Full Text Available Although much less is known about human parietal cortex than that of homologous monkey cortex, recent studies, employing neuroimaging and neuropsychological methods, have begun to elucidate increasingly fine-grained functional and structural distinctions.This review is focused on recent neuroimaging and neuropsychological studies elucidating the cognitive roles of dorsal and ventral regions of parietal cortex in top-down and bottom-up attentional orienting, and on the interaction between the two attentional allocation mechanisms. Evidence is reviewed arguing that regions along the dorsal areas of the parietal cortex, including the superior parietal lobule (SPL are involved in top-down attentional orienting, while ventral regions including the temporo-parietal junction (TPJ are involved in bottom-up attentional orienting.

  6. The science and applications of synthetic and systems biology: workshop summary

    National Research Council Canada - National Science Library

    Choffnes, Eileen R; Relman, David A; Pray, Leslie A

    2011-01-01

    "Many potential applications of synthetic and systems biology are relevant to the challenges associated with the detection, surveillance, and responses to emerging and re-emerging infectious diseases...

  7. BrisSynBio: a BBSRC/EPSRC-funded Synthetic Biology Research Centre.

    Science.gov (United States)

    Sedgley, Kathleen R; Race, Paul R; Woolfson, Derek N

    2016-06-15

    BrisSynBio is the Bristol-based Biotechnology and Biological Sciences Research Council (BBSRC)/Engineering and Physical Sciences Research Council (EPSRC)-funded Synthetic Biology Research Centre. It is one of six such Centres in the U.K. BrisSynBio's emphasis is on rational and predictive bimolecular modelling, design and engineering in the context of synthetic biology. It trains the next generation of synthetic biologists in these approaches, to facilitate translation of fundamental synthetic biology research to industry and the clinic, and to do this within an innovative and responsible research framework. © 2016 The Author(s).

  8. Dissociable effects of top-down and bottom-up attention during episodic encoding

    Science.gov (United States)

    Uncapher, Melina R.; Hutchinson, J. Benjamin; Wagner, Anthony D.

    2011-01-01

    It is well established that the formation of memories for life’s experiences—episodic memory—is influenced by how we attend to those experiences, yet the neural mechanisms by which attention shapes episodic encoding are still unclear. We investigated how top-down and bottom-up attention contribute to memory encoding of visual objects in humans by manipulating both types of attention during functional magnetic resonance imaging (fMRI) of episodic memory formation. We show that dorsal parietal cortex—specifically, intraparietal sulcus (IPS)—was engaged during top-down attention and was also recruited during the successful formation of episodic memories. By contrast, bottom-up attention engaged ventral parietal cortex—specifically, temporoparietal junction (TPJ)—and was also more active during encoding failure. Functional connectivity analyses revealed further dissociations in how top-down and bottom-up attention influenced encoding: while both IPS and TPJ influenced activity in perceptual cortices thought to represent the information being encoded (fusiform/lateral occipital cortex), they each exerted opposite effects on memory encoding. Specifically, during a preparatory period preceding stimulus presentation, a stronger drive from IPS was associated with a higher likelihood that the subsequently attended stimulus would be encoded. By contrast, during stimulus processing, stronger connectivity with TPJ was associated with a lower likelihood the stimulus would be successfully encoded. These findings suggest that during encoding of visual objects into episodic memory, top-down and bottom-up attention can have opposite influences on perceptual areas that subserve visual object representation, suggesting that one manner in which attention modulates memory is by altering the perceptual processing of to-be-encoded stimuli. PMID:21880922

  9. A Positive Model of Earnings Forecasts: Top Down versus Bottom Up

    OpenAIRE

    Masako N. Darrough

    2002-01-01

    This article analyzes the behavior of two groups of corporate earnings forecasters: analysts, who follow individual company fortunes, and market strategists, who predict earnings for various company aggregates. Using data for two market indices, the S&P 500 and the Dow Jones Industrial Average, we document that bottom-up forecasts are systematically more optimistic than top-down forecasts made by strategists. This difference is not driven by the difference in the forecast target. This finding...

  10. A bottom-up approach for labeling of human airway trees

    DEFF Research Database (Denmark)

    2011-01-01

    In this paper, an airway labeling algorithm that allows for gaps between the labeled branches is introduced. A bottom-up approach for arriving to an optimal set of branches and their associated labels is used in the proposed method. A K nearest neighbor based appearance model is used to different...... with simulated errors, such as missing branches and having falsely detected branches, where we showed that such errors have little or no effect on the proposed method....

  11. 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.

  12. Metabolic modelling in the development of cell factories by synthetic biology

    Directory of Open Access Journals (Sweden)

    Paula Tuulia 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.

  13. Interactions between top-down and bottom-up attention in barn owls (Tyto alba).

    Science.gov (United States)

    Lev-Ari, Tidhar; Gutfreund, Yoram

    2017-12-06

    Selective attention, the prioritization of behaviorally relevant stimuli for behavioral control, is commonly divided into two processes: bottom-up, stimulus-driven selection and top-down, task-driven selection. Here, we tested two barn owls in a visual search task that examines attentional capture of the top-down task by bottom-up mechanisms. We trained barn owls to search for a vertical Gabor patch embedded in a circular array of differently oriented Gabor distractors (top-down guided search). To track the point of gaze, a lightweight wireless video camera was mounted on the owl's head. Three experiments were conducted in which the owls were tested in the following conditions: (1) five distractors; (2) nine distractors; (3) five distractors with one distractor surrounded by a red circle; or (4) five distractors with a brief sound at the initiation of the stimulus. Search times and number of head saccades to reach the target were measured and compared between the different conditions. It was found that search time and number of saccades to the target increased when the number of distractors was larger (condition 2) and when an additional irrelevant salient stimulus, auditory or visual, was added to the scene (conditions 3 and 4). These results demonstrate that in barn owls, bottom-up attention interacts with top-down attention to shape behavior in ways similar to human attentional capture. The findings suggest similar attentional principles in taxa that have been evolutionarily separated for 300 million years.

  14. Bottom-up and top-down attention: different processes and overlapping neural systems.

    Science.gov (United States)

    Katsuki, Fumi; Constantinidis, Christos

    2014-10-01

    The brain is limited in its capacity to process all sensory stimuli present in the physical world at any point in time and relies instead on the cognitive process of attention to focus neural resources according to the contingencies of the moment. Attention can be categorized into two distinct functions: bottom-up attention, referring to attentional guidance purely by externally driven factors to stimuli that are salient because of their inherent properties relative to the background; and top-down attention, referring to internal guidance of attention based on prior knowledge, willful plans, and current goals. Over the past few years, insights on the neural circuits and mechanisms of bottom-up and top-down attention have been gained through neurophysiological experiments. Attention affects the mean neuronal firing rate as well as its variability and correlation across neurons. Although distinct processes mediate the guidance of attention based on bottom-up and top-down factors, a common neural apparatus, the frontoparietal network, is essential in both types of attentional processes. © The Author(s) 2013.

  15. 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

  16. Hierarchical time series bottom-up approach for forecast the export value in Central Java

    Science.gov (United States)

    Mahkya, D. A.; Ulama, B. S.; Suhartono

    2017-10-01

    The purpose of this study is Getting the best modeling and predicting the export value of Central Java using a Hierarchical Time Series. The export value is one variable injection in the economy of a country, meaning that if the export value of the country increases, the country’s economy will increase even more. Therefore, it is necessary appropriate modeling to predict the export value especially in Central Java. Export Value in Central Java are grouped into 21 commodities with each commodity has a different pattern. One approach that can be used time series is a hierarchical approach. Hierarchical Time Series is used Buttom-up. To Forecast the individual series at all levels using Autoregressive Integrated Moving Average (ARIMA), Radial Basis Function Neural Network (RBFNN), and Hybrid ARIMA-RBFNN. For the selection of the best models used Symmetric Mean Absolute Percentage Error (sMAPE). Results of the analysis showed that for the Export Value of Central Java, Bottom-up approach with Hybrid ARIMA-RBFNN modeling can be used for long-term predictions. As for the short and medium-term predictions, it can be used a bottom-up approach RBFNN modeling. Overall bottom-up approach with RBFNN modeling give the best result.

  17. Bottom-up effects of geologic parent material through ecological interaction webs

    Science.gov (United States)

    Bradley, R.

    2012-04-01

    Community ecologists study the interactions between species to understand what controls the distribution and abundance of different populations. Communities are thus portrayed as "interaction webs", in which different species exert reciprocal pressures on each other. In the case of one population being a resource for which another population is the consumer (i.e. food-web), reciprocal pressures are commonly referred to as "bottom-up" vs. "top-down" effects. The starting point for studying bottom-up effects is usually the vegetation (primary producers), and its end-point the decomposer community responsible for breaking down detrital matter from each trophic level. In my presentation, I will present results from three former graduate students, to argue that the starting point for studying bottom-up effects should be the geologic parent material (GPM), whose importance has often been overlooked by community ecologists. For example, our data show that GPM had a stronger effect on forest floor nutrient budgets than the identity or successional stage of the vegetation. Likewise, GPM had a strong effect on the structure of forest floor microbial communities, as well as their resistance to, and resilience from, disturbance. GPM also had a significant effect on the richness and diversity of understory plant communities from similar forest stands. Finally, we present evidence that soil fertility controls the resistance and tolerance of certain plant species to selective browsing, thereby affecting the composition of the dominant plant cover and the feeding patterns of large herbivores.

  18. 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.

  19. 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.

  20. 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). © 2016 The Author(s). This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY).

  1. Bringing together models from bottom-up and top-down approaches: an application for growth of Escherichia coli on different carbohydrates.

    Science.gov (United States)

    Kremling, Andeas

    2012-01-01

    Modeling in systems biology follows two lines: a data driven top-down approach that integrates experimental data from various "omics" technologies and a model based bottom-up approach where the model structure is given and kinetic parameters are chosen in such a way that an experimental observation can be reproduced quantitatively or qualitatively. Mathematical models are frequently used to elucidate cellular design principles in order to understand complex biochemical networks better. To show that both approaches lead to a consistent description of cellular dynamics, mathematical models from both approaches are explored. On the level of transcription factor activities a sufficient qualitative agreement is observed. Experimental data for the classical growth experiment of Escherichia coli on two carbon sources, glucose and lactose is available to set up the data driven model and to support the theoretical findings from the bottom-up approach.

  2. 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.

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

    Directory of Open Access Journals (Sweden)

    Stephen S. Fong

    2014-08-01

    Full Text Available 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.

  4. 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. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. 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…

  6. Integrating top-down and bottom-up nanomanufacturing: Design of nucleation and growth processes from electrolytes

    Science.gov (United States)

    Kitayaporn, Sathana

    2011-07-01

    The integration of self-propagating material growth (bottom-up) with tool-directed patterning (top-down) has great potential for minimizing the cost and reducing the time needed for manufacturing nanoscale products. This requires new molecules, algorithms, and growth processes. We describe a process called "orchestrated structure evolution" (OSE) in which one "seeds" specific locations and allows a material to spontaneously grow from these sites into the desired final pattern. Software-reconfigurable seed patterning is ideal for manufacturing flexibility, but direct-write tools are often slow: combining them with bottom-up growth is a strategy for reducing patterning times. Seeds are any nucleation initiator (nanoelectrodes, proteins, catalyst, etc.) that can be patterned using tools such as electron-beam lithography (EBL) or dip-pen nanolithography. Here, we explore the OSE concept using nanoelectrode seeds patterned with EBL and engineered Thioredoxin A (TrxA) as protein seeds. For the case of nanoelectrode seeds, we use electrodeposition to initiate copper and nickel growth that propagates into a continuous patterned film. We evaluate the trade-off between reduced pattern time and pattern degradation, and predict seed-scale interactions governing growth rate and composition using Voronoi diagrams and modified Green's function calculations. The work combines experiments and theory for a wide range of pattern length scales, driving forces, seed densities, compositions and geometries. For the case of protein seeds, we use ZnO-binding derivatives of TrxA to understand how proteins may serve as nucleation initiators for ZnO crystal growth. Our studies include thermodynamics prediction of zinc-compatible biological buffers, adsorption isotherms, and electrodeposition of protein-modified ZnO. We show that electrolyte engineering is a critical part of the process, and that the electrolyte stability and prevalence of key species must be matched with protein stability

  7. Dynamics of problem setting and framing in citizen discussions on synthetic biology.

    Science.gov (United States)

    Betten, Afke Wieke; Broerse, Jacqueline E W; Kupper, Frank

    2017-06-01

    Synthetic biology is an emerging scientific field where engineers and biologists design and build biological systems for various applications. Developing synthetic biology responsibly in the public interest necessitates a meaningful societal dialogue. In this article, we argue that facilitating such a dialogue requires an understanding of how people make sense of synthetic biology. We performed qualitative research to unravel the underlying dynamics of problem setting and framing in citizen discussions on synthetic biology. We found that most people are not inherently for or against synthetic biology as a technology or development in itself, but that their perspectives are framed by core values about our relationships with science and technology and that sensemaking is much dependent on the context and general feelings of (dis)content. Given that there are many assumptions focused on a more binary idea of the public's view, we emphasize the need for frame awareness and understanding in a meaningful dialogue.

  8. Artificial cell-cell communication as an emerging tool in synthetic biology applications

    National Research Council Canada - National Science Library

    Hennig, Stefan; Rödel, Gerhard; Ostermann, Kai

    2015-01-01

    .... Synthetic biology, i.e., the implementation of artificial functions within biological systems, is a promising approach towards the engineering of sophisticated, autonomous devices based on specifically functionalized cells...

  9. BSim: an agent-based tool for modeling bacterial populations in systems and synthetic biology

    National Research Council Canada - National Science Library

    Gorochowski, Thomas E; Matyjaszkiewicz, Antoni; Todd, Thomas; Oak, Neeraj; Kowalska, Kira; Reid, Stephen; Tsaneva-Atanasova, Krasimira T; Savery, Nigel J; Grierson, Claire S; di Bernardo, Mario

    2012-01-01

    .... With systems biology attempting to understand these phenomena, and synthetic biology opening up the possibility of engineering them for our own benefit, there is growing interest in how bacterial...

  10. Sucralose, a synthetic organochlorine sweetener: overview of biological issues.

    Science.gov (United States)

    Schiffman, Susan S; Rother, Kristina I

    2013-01-01

    Sucralose is a synthetic organochlorine sweetener (OC) that is a common ingredient in the world's food supply. Sucralose interacts with chemosensors in the alimentary tract that play a role in sweet taste sensation and hormone secretion. In rats, sucralose ingestion was shown to increase the expression of the efflux transporter P-glycoprotein (P-gp) and two cytochrome P-450 (CYP) isozymes in the intestine. P-gp and CYP are key components of the presystemic detoxification system involved in first-pass drug metabolism. The effect of sucralose on first-pass drug metabolism in humans, however, has not yet been determined. In rats, sucralose alters the microbial composition in the gastrointestinal tract (GIT), with relatively greater reduction in beneficial bacteria. Although early studies asserted that sucralose passes through the GIT unchanged, subsequent analysis suggested that some of the ingested sweetener is metabolized in the GIT, as indicated by multiple peaks found in thin-layer radiochromatographic profiles of methanolic fecal extracts after oral sucralose administration. The identity and safety profile of these putative sucralose metabolites are not known at this time. Sucralose and one of its hydrolysis products were found to be mutagenic at elevated concentrations in several testing methods. Cooking with sucralose at high temperatures was reported to generate chloropropanols, a potentially toxic class of compounds. Both human and rodent studies demonstrated that sucralose may alter glucose, insulin, and glucagon-like peptide 1 (GLP-1) levels. Taken together, these findings indicate that sucralose is not a biologically inert compound.

  11. Metabolomics, Standards, and Metabolic Modeling for Synthetic Biology in Plants.

    Science.gov (United States)

    Hill, Camilla Beate; Czauderna, Tobias; Klapperstück, Matthias; Roessner, Ute; Schreiber, Falk

    2015-01-01

    Life on earth depends on dynamic chemical transformations that enable cellular functions, including electron transfer reactions, as well as synthesis and degradation of biomolecules. Biochemical reactions are coordinated in metabolic pathways that interact in a complex way to allow adequate regulation. Biotechnology, food, biofuel, agricultural, and pharmaceutical industries are highly interested in metabolic engineering as an enabling technology of synthetic biology to exploit cells for the controlled production of metabolites of interest. These approaches have only recently been extended to plants due to their greater metabolic complexity (such as primary and secondary metabolism) and highly compartmentalized cellular structures and functions (including plant-specific organelles) compared with bacteria and other microorganisms. Technological advances in analytical instrumentation in combination with advances in data analysis and modeling have opened up new approaches to engineer plant metabolic pathways and allow the impact of modifications to be predicted more accurately. In this article, we review challenges in the integration and analysis of large-scale metabolic data, present an overview of current bioinformatics methods for the modeling and visualization of metabolic networks, and discuss approaches for interfacing bioinformatics approaches with metabolic models of cellular processes and flux distributions in order to predict phenotypes derived from specific genetic modifications or subjected to different environmental conditions.

  12. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. UbiGate: a synthetic biology toolbox to analyse ubiquitination.

    Science.gov (United States)

    Kowarschik, Kathrin; Hoehenwarter, Wolfgang; Marillonnet, Sylvestre; Trujillo, Marco

    2018-03-01

    Ubiquitination is mediated by an enzymatic cascade that results in the modification of substrate proteins, redefining their fate. This post-translational modification is involved in most cellular processes, yet its analysis faces manifold obstacles due to its complex and ubiquitous nature. Reconstitution of the ubiquitination cascade in bacterial systems circumvents several of these problems and was shown to faithfully recapitulate the process. Here, we present UbiGate - a synthetic biology toolbox, together with an inducible bacterial expression system - to enable the straightforward reconstitution of the ubiquitination cascades of different organisms in Escherichia coli by 'Golden Gate' cloning. This inclusive toolbox uses a hierarchical modular cloning system to assemble complex DNA molecules encoding the multiple genetic elements of the ubiquitination cascade in a predefined order, to generate polycistronic operons for expression. We demonstrate the efficiency of UbiGate in generating a variety of expression elements to reconstitute autoubiquitination by different E3 ligases and the modification of their substrates, as well as its usefulness for dissecting the process in a time- and cost-effective manner. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

  14. Synthetic biology approaches to engineering the nitrogen symbiosis in cereals.

    Science.gov (United States)

    Rogers, Christian; Oldroyd, Giles E D

    2014-05-01

    Nitrogen is abundant in the earth's atmosphere but, unlike carbon, cannot be directly assimilated by plants. The limitation this places on plant productivity has been circumvented in contemporary agriculture through the production and application of chemical fertilizers. The chemical reduction of nitrogen for this purpose consumes large amounts of energy and the reactive nitrogen released into the environment as a result of fertilizer application leads to greenhouse gas emissions, as well as widespread eutrophication of aquatic ecosystems. The environmental impacts are intensified by injudicious use of fertilizers in many parts of the world. Simultaneously, limitations in the production and supply of chemical fertilizers in other regions are leading to low agricultural productivity and malnutrition. Nitrogen can be directly fixed from the atmosphere by some bacteria and Archaea, which possess the enzyme nitrogenase. Some plant species, most notably legumes, have evolved close symbiotic associations with nitrogen-fixing bacteria. Engineering cereal crops with the capability to fix their own nitrogen could one day address the problems created by the over- and under-use of nitrogen fertilizers in agriculture. This could be achieved either by expression of a functional nitrogenase enzyme in the cells of the cereal crop or through transferring the capability to form a symbiotic association with nitrogen-fixing bacteria. While potentially transformative, these biotechnological approaches are challenging; however, with recent advances in synthetic biology they are viable long-term goals. This review discusses the possibility of these biotechnological solutions to the nitrogen problem, focusing on engineering the nitrogen symbiosis in cereals.

  15. [New materia medica project: synthetic biology based bioactive metabolites research in medicinal plant].

    Science.gov (United States)

    Wang, Yong

    2017-03-25

    In the last decade, synthetic biology research has been gradually transited from monocellular parts or devices toward more complex multicellular systems. The emerging plant synthetic biology is regarded as the "next chapter" of synthetic biology. The complex and diverse plant metabolism as the entry point, plant synthetic biology research not only helps us understand how real life is working, but also facilitates us to learn how to design and construct more complex artificial life. Bioactive compounds innovation and large-scale production are expected to be breakthrough with the redesigned plant metabolism as well. In this review, we discuss the research progress in plant synthetic biology and propose the new materia medica project to lift the level of traditional Chinese herbal medicine research.

  16. 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.

  17. Enhanced Photon Extraction from a Nanowire Quantum Dot Using a Bottom-Up Photonic Shell

    DEFF Research Database (Denmark)

    Jeannin, Mathieu; Cremel, Thibault; Häyrynen, Teppo

    2017-01-01

    Semiconductor nanowires offer the possibility to grow high-quality quantum-dot heterostructures, and, in particular, CdSe quantum dots inserted in ZnSe nanowires have demonstrated the ability to emit single photons up to room temperature. In this paper, we demonstrate a bottom-up approach...... to fabricate a photonic fiberlike structure around such nanowire quantum dots by depositing an oxide shell using atomic-layer deposition. Simulations suggest that the intensity collected in our NA=0.6 microscope objective can be increased by a factor 7 with respect to the bare nanowire case. Combining...

  18. 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.

  19. 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.

  20. Integrating Top-down and Bottom-up Cybersecurity Guidance using XML.

    Science.gov (United States)

    Lubell, Joshua

    2016-08-01

    This paper describes a markup-based approach for synthesizing disparate information sources and discusses a software implementation of the approach. The implementation makes it easier for people to use two complementary, but differently structured, guidance specifications together: the (top-down) Cybersecurity Framework and the (bottom-up) National Institute of Standards and Technology Special Publication 800-53 security control catalog. An example scenario demonstrates how the software implementation can help a security professional select the appropriate safeguards for restricting unauthorized access to an Industrial Control System. The implementation and example show the benefits of this approach and suggest its potential application to disciplines other than cybersecurity.

  1. Superconformal Bottom-Up Cobalt Deposition in High Aspect Ratio Through Silicon Vias.

    Science.gov (United States)

    Josell, D; Silva, M; Moffat, T P

    2016-01-01

    This work demonstrates void-free cobalt filling of 56 μm tall, annular Through Silicon Vias (TSVs) using a mechanism that couples suppression breakdown and surface topography to achieve controlled bottom-up deposition. The chemistry, a Watts electrolyte containing a dilute suppressing additive, and processes are described. This work extends understanding and application of the additive-derived S-shaped Negative Differential Resistance (S-NDR) mechanism, including previous demonstrations of superconformal filling of TSVs with nickel, copper, zinc and gold.

  2. Predicting Saliency and Aesthetics in Images: A Bottom-up Perspective

    OpenAIRE

    Murray, Naila

    2012-01-01

    Esta tesis investiga dos aspectos diferentes sobre cómo un observador percibe una imagen natural: (i) dónde miramos o, concretamente, qué nos atrae la atención, y (ii) qué nos gusta, e.g., si una imagen es estéticamente agradable, o no. Estas dos experiencias son objeto de crecientes esfuerzos de la investigación en visión por computador. Tanto la atención visual como la estética visual pueden ser modeladas como consecuencia de múltiples mecanismos en interacción, algunos bottom-up o involunt...

  3. Transformations Between Different Types of Unranked Bottom-Up Tree Automata

    Directory of Open Access Journals (Sweden)

    Xiaoxue Piao

    2010-08-01

    Full Text Available We consider the representational state complexity of unranked tree automata. The bottom-up computation of an unranked tree automaton may be either deterministic or nondeterministic, and further variants arise depending on whether the horizontal string languages defining the transitions are represented by a DFA or an NFA. Also, we consider for unranked tree automata the alternative syntactic definition of determinism introduced by Cristau et al. (FCT'05, Lect. Notes Comput. Sci. 3623, pp. 68-79. We establish upper and lower bounds for the state complexity of conversions between different types of unranked tree automata.

  4. Integrating Top-down and Bottom-up Cybersecurity Guidance using XML

    Science.gov (United States)

    Lubell, Joshua

    2016-01-01

    This paper describes a markup-based approach for synthesizing disparate information sources and discusses a software implementation of the approach. The implementation makes it easier for people to use two complementary, but differently structured, guidance specifications together: the (top-down) Cybersecurity Framework and the (bottom-up) National Institute of Standards and Technology Special Publication 800-53 security control catalog. An example scenario demonstrates how the software implementation can help a security professional select the appropriate safeguards for restricting unauthorized access to an Industrial Control System. The implementation and example show the benefits of this approach and suggest its potential application to disciplines other than cybersecurity. PMID:27795810

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

    Science.gov (United States)

    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 of science. We developed a laboratory module called pClone that empowers students to use advances in molecular cloning methods to discover new promoters for use by synthetic biologists. Our educational goals are consistent with Vision and Change and emphasize core concepts and competencies. pClone is a family of three plasmids that students use to clone a new transcriptional promoter or mutate a canonical promoter and measure promoter activity in Escherichia coli. We also developed the Registry of Functional Promoters, an open-access database of student promoter research results. Using pre- and posttests, we measured significant learning gains among students using pClone in introductory biology and genetics classes. Student posttest scores were significantly better than scores of students who did not use pClone. pClone is an easy and affordable mechanism for large-enrollment labs to meet the high standards of Vision and Change. PMID:26086659

  6. 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.

  7. Integrating the bottom-up and top-down approach to energy economy modelling. The case of Denmark

    DEFF Research Database (Denmark)

    Klinge Jacobsen, Henrik

    1998-01-01

    This paper presents results from an integration project covering Danish models based on bottom-up and top-down approaches to energy]economy modelling. The purpose of the project was to identify theoretical and methodological problems for integrating existing models for Denmark and to implement...... an integration of the models. The integration was established through a number of links between energy bottom-up modules and a macroeconomic model. In this integrated model it is possible to analyse both top-down instruments, such as taxes along with bottom-up instruments, such as regulation of technology...

  8. Integrating top-down/bottom-up sustainability strategies: an ethical challenge

    Directory of Open Access Journals (Sweden)

    John Cairns Jr.

    2003-02-01

    Full Text Available Sustainable use of the planet will require multiple sustainability strategies, which will range from the entire system, the entire Earth, the local or regional. Strategies starting at the highest system level are referred to as 'top-down', and strategies designed for components, local or regional, are referred to as 'bottom-up'. Doubtless, several intermediate levels will eventually be required, although the number is far from clear at this time. It is abundantly clear that both top-down and bottom-up strategies must be integrated effectively or neither will work well. Furthermore, there will be significant uncertainties at both levels of organisation, which will be reduced as evidence accumulates. However, sustainability is too complex and dynamic to reduce scientific uncertainty to a level desired by most decision makers. A great emphasis on sustain-ethics and value judgements will improve communications between those working at different organisational levels since humankind's wish to leave a habitable planet for its descendants and those of other life forms is clearly a value judgement.

  9. 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.

  10. Bottom-up and top-down computations in word- and face-selective cortex

    Science.gov (United States)

    Kay, Kendrick N; Yeatman, Jason D

    2017-01-01

    The ability to read a page of text or recognize a person's face depends on category-selective visual regions in ventral temporal cortex (VTC). To understand how these regions mediate word and face recognition, it is necessary to characterize how stimuli are represented and how this representation is used in the execution of a cognitive task. Here, we show that the response of a category-selective region in VTC can be computed as the degree to which the low-level properties of the stimulus match a category template. Moreover, we show that during execution of a task, the bottom-up representation is scaled by the intraparietal sulcus (IPS), and that the level of IPS engagement reflects the cognitive demands of the task. These results provide an account of neural processing in VTC in the form of a model that addresses both bottom-up and top-down effects and quantitatively predicts VTC responses. DOI: http://dx.doi.org/10.7554/eLife.22341.001 PMID:28226243

  11. 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.

  12. 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.

  13. 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.

  14. Ecology of Caribbean sponges: are top-down or bottom-up processes more important?

    Science.gov (United States)

    Lesser, Michael P; Slattery, Marc

    2013-01-01

    Benthic-pelagic coupling and the role of bottom-up versus top-down processes are recognized as having a major impact on the structure of marine communities. While the roles of bottom-up processes are better appreciated they are still viewed as principally affecting the outcome of top-down processes. Sponges on coral reefs are important members of the benthic community and provide a critically important functional linkage between water-column productivity and the benthos. As active suspension feeders sponges utilize the abundant autotrophic and heterotrophic picoplankton in the water column. As a result sponges across the Caribbean basin exhibit a consistent and significant pattern of greater biomass, tube extension rate, and species numbers with increasing depth. Likewise, the abundance of their food supply also increases along a depth gradient. Using experimental manipulations it has recently been reported that predation is the primary determinant of sponge community structure. Here we provide data showing that the size and growth of the sponge Callyspongia vaginalis are significantly affected by food availability. Sponges increased in size and tube extension rate with increasing depth down to 46 m, while simultaneously exposed to the full range of potential spongivores at all depths. Additionally, we point out important flaws in the experimental design used to demonstrate the role of predation and suggest that a resolution of this important question will require well-controlled, multi-factorial experiments to examine the independent and interactive effects of predation and food abundance on the ecology of sponges.

  15. Bottom-Up Gazetteers: Learning from the Implicit Semantics of Geotags

    Science.gov (United States)

    Keßler, Carsten; Maué, Patrick; Heuer, Jan Torben; Bartoschek, Thomas

    As directories of named places, gazetteers link the names to geographic footprints and place types. Most existing gazetteers are managed strictly top-down: entries can only be added or changed by the responsible toponymic authority. The covered vocabulary is therefore often limited to an administrative view on places, using only official place names. In this paper, we propose a bottom-up approach for gazetteer building based on geotagged photos harvested from the web. We discuss the building blocks of a geotag and how they relate to each other to formally define the notion of a geotag. Based on this formalization, we introduce an extraction process for gazetteer entries that captures the emergent semantics of collections of geotagged photos and provides a group-cognitive perspective on named places. Using an experimental setup based on clustering and filtering algorithms, we demonstrate how to identify place names and assign adequate geographic footprints. The results for three different place names (Soho, Camino de Santiago and Kilimanjaro), representing different geographic feature types, are evaluated and compared to the results obtained from traditional gazetteers. Finally, we sketch how our approach can be combined with other (for example, linguistic) approaches and discuss how such a bottom-up gazetteer can complement existing gazetteers.

  16. Graphene devices with bottom-up contacts by area-selective atomic layer deposition

    Science.gov (United States)

    Thissen, Nick F. W.; Vervuurt, René H. J.; Mackus, Adriaan J. M.; Mulders, Johannes J. L.; Weber, Jan-Willem; Kessels, Wilhelmus M. M.; Bol, Ageeth A.

    2017-06-01

    Graphene field-effect transistor devices were fabricated using a bottom-up and resist-free method, avoiding common compatibility issues such as contamination by resist residues. Large-area CVD graphene sheets were structured into device channels by patterning with a focused ion beam. Platinum contacts were then deposited by direct-write atomic layer deposition (ALD), which is a combination between electron beam induced deposition (EBID) and bottom-up area-selective ALD. This is a unique approach that enables nucleation of Pt ALD on graphene, and therefore these devices are the first reported graphene devices with contacts deposited by ALD. Electrical characterization of the devices confirms ambipolar transistor behaviour with typical field-effect mobilities in the range of 1000-1800 cm2 V-1 s-1. We observe clear signs of strong Pt-graphene coupling and contact induced hole doping, implying good contact properties in contrast to the conventionally weak bonding between Pt and graphene. We attribute these observations to the reduced amount of resist residue under the contacts, the improved wettability of the Pt due to the use of ALD, and the formation of a graphitic interlayer that bonds the Pt more strongly to the graphene. We conclude that direct-write ALD is a very suitable technique for metallization of graphene devices and to study the intrinsic properties of metal-graphene contacts in more detail. In addition, it offers unique opportunities to control the metal-graphene coupling strength.

  17. Selective Ru ALD as a Catalyst for Sub-Seven-Nanometer Bottom-Up Metal Interconnects.

    Science.gov (United States)

    Zyulkov, Ivan; Krishtab, Mikhail; De Gendt, Stefan; Armini, Silvia

    2017-09-13

    Integrating bottom-up area-selective building-blocks in microelectronics has a disruptive potential because of the unique capability of engineering new structures and architectures. Atomic layer deposition (ALD) is an enabling technology, yet understanding the surfaces and their modification is crucial to leverage area-selective ALD (AS-ALD) in this field. The understanding of general selectivity mechanisms and the compatibility of plasma surface modifications with existing materials and processes, both at research and production scale, will greatly facilitate AS-ALD integration in microelectronics. The use of self-assembled monolayers to inhibit the nucleation and growth of ALD films is still scarcely compatible with nanofabrication because of defectivity and downscaling limitations. Alternatively, in this Research Article, we demonstrate a straightforward H 2 plasma surface modification process capable of inhibiting Ru ALD nucleation on an amorphous carbon surface while still allowing instantaneous nucleation and linear growth on Si-containing materials. Furthermore, we demonstrate how AS-ALD enables previously inaccessible routes, such as bottom-up electroless metal deposition in a dual damascene etch-damage free low-k replacement scheme. Specifically, our approach offers a general strategy for scalable ultrafine 3D nanostructures without the burden of subtractive metal patterning and high cost chemical mechanical planarization processes.

  18. Beam-deposited platinum as versatile catalyst for bottom-up silicon nanowire synthesis

    Science.gov (United States)

    Hibst, N.; Knittel, P.; Kranz, C.; Mizaikoff, B.; Strehle, S.

    2014-10-01

    The controlled localized bottom-up synthesis of silicon nanowires on arbitrarily shaped surfaces is still a persisting challenge for functional device assembly. In order to address this issue, electron beam and focused ion beam-assisted catalyst deposition have been investigated with respect to platinum expected to form a PtSi alloy catalyst for a subsequent bottom-up nanowire synthesis. The effective implementation of pure platinum nanoparticles or thin films for silicon nanowire growth has been demonstrated recently. Beam-deposited platinum contains significant quantities of amorphous carbon due to the organic precursor and gallium ions for a focused ion beam-based deposition process. Nevertheless, silicon nanowires could be grown on various substrates regardless of the platinum purity. Additionally, p-type doping could be realized with diborane whereas n-type doping suppressed a nanowire growth. The rational utilization of this beam-assisted approach enables us to control the localized synthesis of single silicon nanowires at planar surfaces but succeeded also in single nanowire growth at the three-dimensional apex of an atomic force microscopy tip. Therefore, this catalyst deposition method appears to be a unique extension of current technologies to assemble complex nanowire-based devices.

  19. Comparing effectiveness of top-down and bottom-up strategies in containing influenza.

    Directory of Open Access Journals (Sweden)

    Achla Marathe

    Full Text Available This research compares the performance of bottom-up, self-motivated behavioral interventions with top-down interventions targeted at controlling an "Influenza-like-illness". Both types of interventions use a variant of the ring strategy. In the first case, when the fraction of a person's direct contacts who are diagnosed exceeds a threshold, that person decides to seek prophylaxis, e.g. vaccine or antivirals; in the second case, we consider two intervention protocols, denoted Block and School: when a fraction of people who are diagnosed in a Census Block (resp., School exceeds the threshold, prophylax the entire Block (resp., School. Results show that the bottom-up strategy outperforms the top-down strategies under our parameter settings. Even in situations where the Block strategy reduces the overall attack rate well, it incurs a much higher cost. These findings lend credence to the notion that if people used antivirals effectively, making them available quickly on demand to private citizens could be a very effective way to control an outbreak.

  20. Superconformal Bottom-Up Gold Deposition in High Aspect Ratio Through Silicon Vias.

    Science.gov (United States)

    Josell, D; Moffat, T P

    2017-01-01

    This work presents superconformal, bottom-up Au filling of high aspect ratio through silicon vias (TSVs) along with a predictive framework based on the coupling of suppression breakdown and surface topography. The work extends a previous study of superconformal Au deposition in lower aspect ratio TSVs. Deposition was performed in a Na3AuSO3 electrolyte containing a branched polyethyleneimine (PEI) deposition-rate suppressing additive. Voltammetric measurements using a rotating disk electrode (RDE) were used to assess the impact of the PEI suppressor concentration and transport on the rate of metal deposition, enabling the interplay between metal deposition and suppressor adsorption to be quantified. The positive feedback associated with suppression breakdown gives rise to an S-shaped negative differential resistance (S-NDR). The derived kinetics for suppressor adsorption and consumption were used in a mass conservation model to account for bottom-up filling of patterned features. Predictions, including the impact of deposition potential and additive concentration on feature filling, are shown to match experimental results for filling of TSVs. This further generalizes the utility of the additive derived S-NDR model as a predictive formalism for identifying additives capable of generating localized, void-free filling of TSVs by electrodeposition.

  1. Top-down and bottom-up processes in speech comprehension.

    Science.gov (United States)

    Zekveld, Adriana A; Heslenfeld, Dirk J; Festen, Joost M; Schoonhoven, Ruurd

    2006-10-01

    Speech comprehension includes both bottom-up and top-down processes, and imaging studies have isolated a frontal-temporal network of brain areas active during speech perception. However, the precise role of the various areas in this network during normal speech comprehension is not yet fully understood. In the present fMRI study, the signal-to-noise ratio (SNR) of spoken sentences was varied in 144 steps, and speech intelligibility was measured independently in order to study in detail its effect on the activation of brain areas involved in speech perception. Relative to noise alone, intelligible speech in noise evoked spatially extended activation in left frontal, bilateral temporal, and medial occipital brain regions. Increasing SNR led to a sigmoid-shaped increase of activation in all areas of the frontal-temporal network. The onset of the activation with respect to SNR was similar in temporal and frontal regions, but frontal activation was found to be smaller than temporal activation at the highest SNRs. Finally, only Broca's area (BA44) showed activation to unintelligible speech presented at low SNRs. These findings demonstrate distinct roles of frontal and temporal areas in speech comprehension in that temporal regions subserve bottom-up processing of speech, whereas frontal areas are more involved in top-down supplementary mechanisms.

  2. 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)

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

    Directory of Open Access Journals (Sweden)

    Etiénne Groot

    2015-12-01

    Full Text Available 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.

  4. Proteomics in Heart Failure: Top-down or Bottom-up?

    Science.gov (United States)

    Gregorich, Zachery R.; Chang, Ying-Hua; Ge, Ying

    2014-01-01

    Summary The pathophysiology of heart failure (HF) is diverse, owing to multiple etiologies and aberrations in a number of cellular processes. Therefore, it is essential to understand how defects in the molecular pathways that mediate cellular responses to internal and external stressors function as a system to drive the HF phenotype. Mass spectrometry (MS)-based proteomics strategies have great potential for advancing our understanding of disease mechanisms at the systems level because proteins are the effector molecules for all cell functions and, thus, are directly responsible for determining cell phenotype. Two MS-based proteomics strategies exist: peptide-based bottom-up and protein-based top-down proteomics—each with its own unique strengths and weaknesses for interrogating the proteome. In this review, we will discuss the advantages and disadvantages of bottom-up and top-down MS for protein identification, quantification, and the analysis of post-translational modifications, as well as highlight how both of these strategies have contributed to our understanding of the molecular and cellular mechanisms underlying HF. Additionally, the challenges associated with both proteomics approaches will be discussed and insights will be offered regarding the future of MS-based proteomics in HF research. PMID:24619480

  5. 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.

  6. 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. © 2014 The Authors. Journal of Animal Ecology © 2014 British Ecological Society.

  7. Synthetic Biology Outside the Cell: Linking Computational Tools to Cell-Free Systems

    OpenAIRE

    Daniel eLewis; Villarreal, Fernando D.; Fan eWu; Cheemeng eTan

    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...

  8. Biotechnology by Design: An Introductory Level, Project-Based, Synthetic Biology Laboratory Program for Undergraduate Students†

    OpenAIRE

    Beach, Dale L.; Alvarez, Consuelo J.

    2015-01-01

    Synthetic biology offers an ideal opportunity to promote undergraduate laboratory courses with research-style projects, immersing students in an inquiry-based program that enhances the experience of the scientific process. We designed a semester-long, project-based laboratory curriculum using synthetic biology principles to develop a novel sensory device. Students develop subject matter knowledge of molecular genetics and practical skills relevant to molecular biology, recombinant DNA techniq...

  9. Synthetic biology in the UK - An outline of plans and progress.

    Science.gov (United States)

    Clarke, L J; Kitney, R I

    2016-12-01

    Synthetic biology is capable of delivering new solutions to key challenges spanning the bioeconomy, both nationally and internationally. Recognising this significant potential and the associated need to facilitate its translation and commercialisation the UK government commissioned the production of a national Synthetic Biology Roadmap in 2011, and subsequently provided crucial support to assist its implementation. Critical infrastructural investments have been made, and important strides made towards the development of an effectively connected community of practitioners and interest groups. A number of Synthetic Biology Research Centres, DNA Synthesis Foundries, a Centre for Doctoral Training, and an Innovation Knowledge Centre have been established, creating a nationally distributed and integrated network of complementary facilities and expertise. The UK Synthetic Biology Leadership Council published a UK Synthetic Biology Strategic Plan in 2016, increasing focus on the processes of translation and commercialisation. Over 50 start-ups, SMEs and larger companies are actively engaged in synthetic biology in the UK, and inward investments are starting to flow. Together these initiatives provide an important foundation for stimulating innovation, actively contributing to international research and development partnerships, and helping deliver useful benefits from synthetic biology in response to local and global needs and challenges.

  10. Abundant Lysine Methylation and N-Terminal Acetylation in Sulfolobus islandicus Revealed by Bottom-Up and Top-Down Proteomics.

    Science.gov (United States)

    Vorontsov, Egor A; Rensen, Elena; Prangishvili, David; Krupovic, Mart; Chamot-Rooke, Julia

    2016-11-01

    Protein post-translational methylation has been reported to occur in archaea, including members of the genus Sulfolobus, but has never been characterized on a proteome-wide scale. Among important Sulfolobus proteins carrying such modification are the chromatin proteins that have been described to be methylated on lysine side chains, resembling eukaryotic histones in that aspect. To get more insight into the extent of this modification and its dynamics during the different growth steps of the thermoacidophylic archaeon S. islandicus LAL14/1, we performed a global and deep proteomic analysis using a combination of high-throughput bottom-up and top-down approaches on a single high-resolution mass spectrometer. 1,931 methylation sites on 751 proteins were found by the bottom-up analysis, with methylation sites on 526 proteins monitored throughout three cell culture growth stages: early-exponential, mid-exponential, and stationary. The top-down analysis revealed 3,978 proteoforms arising from 681 proteins, including 292 methylated proteoforms, 85 of which were comprehensively characterized. Methylated proteoforms of the five chromatin proteins (Alba1, Alba2, Cren7, Sul7d1, Sul7d2) were fully characterized by a combination of bottom-up and top-down data. The top-down analysis also revealed an increase of methylation during cell growth for two chromatin proteins, which had not been evidenced by bottom-up. These results shed new light on the ubiquitous lysine methylation throughout the S. islandicus proteome. Furthermore, we found that S. islandicus proteins are frequently acetylated at the N terminus, following the removal of the N-terminal methionine. This study highlights the great value of combining bottom-up and top-down proteomics for obtaining an unprecedented level of accuracy in detecting differentially modified intact proteoforms. The data have been deposited to the ProteomeXchange with identifiers PXD003074 and PXD004179. © 2016 by The American Society for

  11. A powerful toolkit for synthetic biology: Over 3.8 billion years of evolution.

    Science.gov (United States)

    Rothschild, Lynn J

    2010-04-01

    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.

  12. 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

  13. Top-Down and Bottom-Up Cues Based Moving Object Detection for Varied Background Video Sequences

    Directory of Open Access Journals (Sweden)

    Chirag I. Patel

    2014-01-01

    there is no need for background formulation and updates as it is background independent. Many bottom-up approaches and one combination of bottom-up and top-down approaches are proposed in the present paper. The proposed approaches seem more efficient due to inessential requirement of learning background model and due to being independent of previous video frames. Results indicate that the proposed approach works even against slight movements in the background and in various outdoor conditions.

  14. Reconciliation of top-down and bottom-up CO2 fluxes in Siberian larch forest

    Science.gov (United States)

    Takata, Kumiko; Patra, Prabir K.; Kotani, Ayumi; Mori, Junko; Belikov, Dmitry; Ichii, Kazuhito; Saeki, Tazu; Ohta, Takeshi; Saito, Kazuyuki; Ueyama, Masahito; Ito, Akihiko; Maksyutov, Shamil; Miyazaki, Shin; Burke, Eleanor J.; Ganshin, Alexander; Iijima, Yoshihiro; Ise, Takeshi; Machiya, Hirokazu; Maximov, Trofim C.; Niwa, Yosuke; O’ishi, Ryo’ta; Park, Hotaek; Sasai, Takahiro; Sato, Hisashi; Tei, Shunsuke; Zhuravlev, Ruslan; Machida, Toshinobu; Sugimoto, Atsuko; Aoki, Shuji

    2017-12-01

    Carbon dioxide (CO2) fluxes by different methods vary largely at global, regional and local scales. The net CO2 fluxes by three bottom-up methods (tower observation (TWR), biogeochemical models (GTM), and a data-driven model (SVR)), and an ensemble of atmospheric inversions (top-down method, INV) are compared in Yakutsk, Siberia for 2004–2013. The region is characterized by highly homogeneous larch forest on a flat terrain. The ecosystem around Yakutsk shows a net sink of CO2 by all the methods (means during 2004–2007 were 10.9 g C m‑2 month‑1 by TWR, 4.28 g C m‑2 month‑1 by GTM, 5.62 g C m‑2 month‑1 and 0.863 g C m‑2 month‑1 by SVR at two different scales, and 4.89 g C m‑2 month‑1 by INV). Absorption in summer (June–August) was smaller by three bottom-up methods (ranged from 88.1 to 191.8 g C m‑2 month‑1) than the top-down method (223.6 g C m‑2 month‑1). Thus the peak-to-trough amplitude of the seasonal cycle is greater for the inverse models than bottom-up methods. The monthly-mean seasonal cycles agree among the four methods within the range of inter-model variations. The interannual variability estimated by an ensemble of inverse models and a site-scale data-driven model (the max-min range was 35.8 g C m‑2 month‑1and 34.2 g C m‑2 month‑1) is more similar to that of the tower observation (42.4 g C m‑2 month‑1) than those by the biogeochemical models and the large-scale data-driven model (9.5 g C m‑2 month‑1 and 1.45 g C m‑2 month‑1). The inverse models and tower observations captured a reduction in CO2 uptake after 2008 due to unusual waterlogging.

  15. 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

  16. 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.

  17. 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.

  18. Brain dynamics of distractibility: interaction between top-down and bottom-up mechanisms of auditory attention.

    Science.gov (United States)

    Bidet-Caulet, Aurélie; Bottemanne, Laure; Fonteneau, Clara; Giard, Marie-Hélène; Bertrand, Olivier

    2015-05-01

    Attention improves the processing of specific information while other stimuli are disregarded. A good balance between bottom-up (attentional capture by unexpected salient stimuli) and top-down (selection of relevant information) mechanisms is crucial to be both task-efficient and aware of our environment. Only few studies have explored how an isolated unexpected task-irrelevant stimulus outside the attention focus can disturb the top-down attention mechanisms necessary to the good performance of the ongoing task, and how these top-down mechanisms can modulate the bottom-up mechanisms of attentional capture triggered by an unexpected event. We recorded scalp electroencephalography in 18 young adults performing a new paradigm measuring distractibility and assessing both bottom-up and top-down attention mechanisms, at the same time. Increasing task load in top-down attention was found to reduce early processing of the distracting sound, but not bottom-up attentional capture mechanisms nor the behavioral distraction cost in reaction time. Moreover, the impact of bottom-up attentional capture by distracting sounds on target processing was revealed as a delayed latency of the N100 sensory response to target sounds mirroring increased reaction times. These results provide crucial information into how bottom-up and top-down mechanisms dynamically interact and compete in the human brain, i.e. on the precarious balance between voluntary attention and distraction.

  19. Bottom-up coarse-graining of a simple graphene model: the blob picture.

    Science.gov (United States)

    Kauzlarić, David; Meier, Julia T; Español, Pep; Succi, Sauro; Greiner, Andreas; Korvink, Jan G

    2011-02-14

    The coarse-graining of a simple all-atom 2D microscopic model of graphene, in terms of "blobs" described by center of mass variables, is presented. The equations of motion of the coarse-grained variables take the form of dissipative particle dynamics (DPD). The coarse-grained conservative forces and the friction of the DPD model are obtained via a bottom-up procedure from molecular dynamics (MD) simulations. The separation of timescales for blobs of 24 and 96 carbon atoms is sufficiently pronounced for the Markovian assumption, inherent to the DPD model, to provide satisfactory results. In particular, the MD velocity autocorrelation function of the blobs is well reproduced by the DPD model, provided that the effect of friction and noise is taken into account. However, DPD cross-correlations between neighbor blobs show appreciable discrepancies with respect to the MD results. Possible extensions to mend these discrepancies are briefly outlined.

  20. Plasmonic nanoparticles for a bottom-up approach to fabricate optical metamaterials

    Science.gov (United States)

    Dintinger, José; Scharf, Toralf

    2012-03-01

    We investigate experimentally metallic nanoparticle composites fabricated by bottom-up techniques as potential candidates for optical metamaterials. Depending on the plasmonic resonances sustained by individual NPs and their nanoscale organization into larger meta-atoms, various properties might emerge. Here, the focus of our contribution is on the fabrication and optical characterization of silver NP clusters with a spherical shape. We start with the characterisation of the "bulk" dielectric constants of silver NP inks by spectroscopic ellipsometry for different nanoparticle densities (i.e from strongly diluted dispersions to solid randomly packed films). The inks are then used to prepare spherical nanoparticle clusters by an oil-in water emulsion technique. The study of their optical properties demonstrates their ability to support Mie resonances in the visible. These resonances are associated with the excitation of a magnetic dipole, which constitutes a prerequisite to the realization of metamaterials with negative permeability.

  1. Bottom-up control of geomagnetic secular variation by the Earth's inner core

    DEFF Research Database (Denmark)

    Aubert, Julien; Finlay, Chris; Fournier, Alexandre

    2013-01-01

    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 coupling5 aligns the inner core with the mantle, forcing the flow of liquid metal in the outer core into a giant, westward drifting, sheet...... release in the outer core which in turn distorts the gyre, forcing it to become eccentric, in agreement with recent core flow inversions6, 10, 11. This bottom-up heterogeneous driving of core convection dominates top-down driving from mantle thermal heterogeneities, and localizes magnetic variations....... This is a consequence of the geographical localization of intense, westward drifting, equatorial magnetic flux patches at the core surface3. Despite successes in explaining the morphology of the geomagnetic field4, numerical models of the geodynamo have so far failed to account systematically for this striking pattern...

  2. 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.

  3. Top-Down Versus Bottom-Up Nanoengineering Routes to Design Advanced Oropharmacological Products.

    Science.gov (United States)

    Singh, Ajay V; Mehta, Krunal K

    2016-01-01

    Energy intensive and chemical routes predominately govern modern dental material fabrication involving complex physicochemical approaches. Current interest in dental material design is shifting towards biomineralization method and green chemistry synthesis to support oral tissue biocompatibility and oropharmacology. This review article describes the context of biophysical approaches based on development in nanoengineering to design advance nanomaterials for clinical dentistry. We particularly focus on approaches governing surface texture and hierarchical assembly emphasis based on micro-nanoscale tooth anatomy. Further, this article provides an overview about the merit of micro-nanoscale material design techniques exchanging the traditional dental material. In this context, top-down and bottom-up approaches involving biomimetic nanoengineering route, opportunities and challenges are discussed.

  4. Top-down and bottom-up guidance in comprehension of schematic football diagrams.

    Science.gov (United States)

    Khacharem, Aïmen

    2017-06-01

    Comprehension of a narrated diagram entail complex cognitive processing as learner is challenged to extract the orally evoked information. The present experiment examined the effects of 2 different forms of attention guidance - bottom-up and top-down - on comprehension performance, cognitive load investment, and motivation to learn, using a 2 × 2 mixed design with factors "Expertise" (Expert vs. Novice) and "Condition" (no-signal, circle, segment). The results revealed an expertise reversal effect indicating that the incorporation of visual signals in diagram is effective for novice learners but partially reverses and becomes ineffective for more experienced learners (even though they invested less mental effort and reported higher level of motivation in the segmented condition). The findings suggested that the effectiveness of instructional guidance depends heavily on levels of prior knowledge.

  5. 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.

  6. 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...

  7. 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. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  8. 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. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Telecom-Wavelength Bottom-up Nanobeam Lasers on Silicon-on-Insulator.

    Science.gov (United States)

    Kim, Hyunseok; Lee, Wook-Jae; Farrell, Alan C; Balgarkashi, Akshay; Huffaker, Diana L

    2017-09-13

    Semiconductor nanowire lasers are considered promising ultracompact and energy-efficient light sources in the field of nanophotonics. Although the integration of nanowire lasers onto silicon photonic platforms is an innovative path toward chip-scale optical communications and photonic integrated circuits, operating nanowire lasers at telecom-wavelengths remains challenging. Here, we report on InGaAs nanowire array lasers on a silicon-on-insulator platform operating up to 1440 nm at room temperature. Bottom-up photonic crystal nanobeam cavities are formed by growing nanowires as ordered arrays using selective-area epitaxy, and single-mode lasing by optical pumping is demonstrated. We also show that arrays of nanobeam lasers with individually tunable wavelengths can be integrated on a single chip by the simple adjustment of the lithographically defined growth pattern. These results exemplify a practical approach toward nanowire lasers for silicon photonics.

  10. Bottom-up Synthesis of Porous NiMo Alloy for Hydrogen Evolution Reaction

    Directory of Open Access Journals (Sweden)

    Kailong Hu

    2018-01-01

    Full Text Available Bottom-up synthesis of porous NiMo alloy reduced by NiMoO4 nanofibers was systematically investigated to fabricate non-noble metal porous electrodes for hydrogen production. The different annealing temperatures of NiMoO4 nanofibers under hydrogen atmosphere reveal that the 950 °C annealing temperature is key for producing bicontinuous porous NiMo alloy without oxide phases. The porous NiMo alloy acts as a cathode in electrical water splitting, which demonstrates not only almost identical catalytic activity with commercial Pt/C in 1.0 M KOH solution, but also superb stability for 12 days at an electrode potential of −200 mV vs. reversible hydrogen electrode (RHE.

  11. Bottom-up construction of a superstructure in a porous uranium-organic crystal

    Energy Technology Data Exchange (ETDEWEB)

    Li, Peng; Vermeulen, Nicolaas A.; Malliakas, Christos D.; G?mez-Gualdr?n, Diego A.; Howarth, Ashlee J.; Mehdi, B. Layla; Dohnalkova, Alice; Browning, Nigel D.; O?Keeffe, Michael; Farha, Omar K.

    2017-04-20

    Bottom-up construction of highly intricate structures from simple building blocks remains one of the most difficult challenges in chemistry. We report a structurally complex, mesoporous uranium-based metal-organic framework (MOF) made from simple starting components. The structure comprises 10 uranium nodes and seven tricarboxylate ligands (both crystallographically nonequivalent), resulting in a 173.3-angstrom cubic unit cell enclosing 816 uranium nodes and 816 organic linkers—the largest unit cell found to date for any nonbiological material. The cuboctahedra organize into pentagonal and hexagonal prismatic secondary structures, which then form tetrahedral and diamond quaternary topologies with unprecedented complexity. This packing results in the formation of colossal icosidodecahedral and rectified hexakaidecahedral cavities with internal diameters of 5.0 nanometers and 6.2 nanometers, respectively—ultimately giving rise to the lowest-density MOF reported to date.

  12. 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...

  13. Multisegment injections improve peptide identification rates in capillary zone electrophoresis-based bottom-up proteomics.

    Science.gov (United States)

    Boley, Danielle A; Zhang, Zhenbin; Dovichi, Norman J

    2017-11-10

    While capillary zone electrophoresis (CZE) provides dramatically improved numbers of peptide identifications compared with reversed-phase chromatography for bottom-up proteomics of mass limited samples, CZE inevitably produces lower numbers of peptide identifications than RPLC for larger samples. One reason for this poorer performance is the dead time between injection of samples and subsequent appearance of the fastest moving component. This dead time is typically 25% of the separation window in CZE, but is only 5% of the separation window in gradient elution RPLC. This dead time can be eliminated in CZE by use of a multisegment injection mode where a series of samples is analyzed by injecting each sample while the preceding sample is still being separated. In this paper, we demonstrate that capillary zone electrophoresis employing sequential injections can produce a doubling in peptide identification rate with no degradation in separation efficiency. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Bottom-Up Nanofabrication of Supported Noble Metal Alloy Nanoparticle Arrays for Plasmonics

    DEFF Research Database (Denmark)

    Nugroho, Ferry A. A.; Iandolo, Beniamino; Wagner, Jakob Birkedal

    2016-01-01

    Mixing different elements at the nanoscale to obtain alloy nanostructures with fine-tuned physical and chemical properties offers appealing opportunities for nanotechnology and nanoscience. However, despite widespread successful application of alloy nanoparticles made by colloidal synthesis...... in heterogeneous catalysis, nanoalloy systems have been used very rarely in solid-state devices and nanoplasmonics-related applications. One reason is that such applications require integration in arrays on a surface with compelling demands on nanoparticle arrangement, uniformity in surface coverage......, and optimization of the surface density. These cannot be fulfilled even using state-of-the-art self -assembly strategies of colloids. As a solution, we present here a generic bottom-up nanolithography-compatible fabrication approach for large-area arrays of alloy nanoparticles on surfaces. To illustrate...

  15. Reconciling bottom-up, top-down, and direct measurements of biogenic VOC emissions

    Science.gov (United States)

    Guenther, A.; Karl, T.; Wiedinmyer, C.; Barkley, M.; Palmer, P.; Muller, J. F.; Stavrakov, T.; Millet, D.

    2007-12-01

    Biogenic Volatile Organic compound (BVOC) emissions vary considerably on spatial scales ranging from a few meters to thousands of kilometers and temporal scales ranging from seconds to years. Accurate estimates of BVOC emissions are required for many regional air quality modeling studies and global earth system investigations. We compare results from bottom-up estimates, using The Model of Emissions of Gases and Aerosols from Nature (MEGAN), with top-down estimates, based on satellite and in-situ concentration distributions, and direct flux measurements. We describe examples of both agreement and disagreement in U.S., tropical forest and other landscapes and discuss potential explanations for differences that can exceed a factor of 2. Future measurement and modeling needs are outlined and specific activities are proposed to improve efforts to reconcile these approaches and understand the controlling processes.

  16. Mesoporous ZSM-5 Zeolites in Acid Catalysis: Top-Down vs. Bottom-Up Approach

    Directory of Open Access Journals (Sweden)

    Pit Losch

    2017-07-01

    Full Text Available A top-down desilication of Al-rich ZSM-5 zeolites and a bottom-up mesopores creating method were evaluated in this study. Three liquid–solid and one gas–solid heterogeneously-catalysed reactions were chosen to establish relationships between zeolites textural properties and their catalytic behavior in acid-catalysed model reactions that are influenced by shape selectivity: Diels-Alder cyclization between isoprene and methylacrylate, Methanol-to-Olefins (MTO reaction, chlorination of iodobenzene with trichloroisocyanuric acid (TCCA, and Friedel-Crafts acylation of anisole by carboxylic acids with differing sizes. It is found amongst others that no optimal mesoporosity for all the different reactions can be easily obtained, but depending on the chosen application, a specific treatment has to be set to achieve high activity/selectivity and stability.

  17. 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.

  18. 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.

  19. Ecology of Caribbean sponges: are top-down or bottom-up processes more important?

    Directory of Open Access Journals (Sweden)

    Michael P Lesser

    Full Text Available Benthic-pelagic coupling and the role of bottom-up versus top-down processes are recognized as having a major impact on the structure of marine communities. While the roles of bottom-up processes are better appreciated they are still viewed as principally affecting the outcome of top-down processes. Sponges on coral reefs are important members of the benthic community and provide a critically important functional linkage between water-column productivity and the benthos. As active suspension feeders sponges utilize the abundant autotrophic and heterotrophic picoplankton in the water column. As a result sponges across the Caribbean basin exhibit a consistent and significant pattern of greater biomass, tube extension rate, and species numbers with increasing depth. Likewise, the abundance of their food supply also increases along a depth gradient. Using experimental manipulations it has recently been reported that predation is the primary determinant of sponge community structure. Here we provide data showing that the size and growth of the sponge Callyspongia vaginalis are significantly affected by food availability. Sponges increased in size and tube extension rate with increasing depth down to 46 m, while simultaneously exposed to the full range of potential spongivores at all depths. Additionally, we point out important flaws in the experimental design used to demonstrate the role of predation and suggest that a resolution of this important question will require well-controlled, multi-factorial experiments to examine the independent and interactive effects of predation and food abundance on the ecology of sponges.

  20. Seasonal shift from bottom-up to top-down impact in phytophagous insect populations.

    Science.gov (United States)

    Gratton, Claudio; Denno, Robert F

    2003-03-01

    Although many studies now examine how multiple factors influence the dynamics of herbivore populations, few studies explicitly attempt to document where and when each is important and how they vary and interact. In fact, how temporal variation in top-down (natural enemies) and bottom-up (host plant resources) factors affect herbivore dynamics has been suggested as a particularly important yet poorly understood feature of terrestrial food webs. In this study we examined how temporal changes in predator density (wolf spiders, sheet-web builders, and mirid egg predators) and host-plant resources (plant quality and structural complexity) influence the population dynamics of the dominant phytophagous insects on Atlantic-coast salt marshes, namely Prokelisia planthoppers (Homoptera: Delphacidae). We designed a factorial experiment in meadows of Spartina alterniflora to mimic natural variation in vegetation quality and structure by establishing two levels of plant nutrition (leaf nitrogen content) by fertilization, and two levels of habitat complexity by adding leaf litter (thatch). We then assessed seasonal changes in the strength of bottom-up (plant quality) and top-down (predator) impacts on planthopper populations. Planthopper populations responded positively to increased plant quality treatments in late summer. Despite the greater number of planthopper adults colonizing fertilized Spartina plots compared to unfertilized controls, the offspring of these colonists were much less abundant at the end of the season in fertilized plots, particularly those with thatch. The initial colonization effect was later erased because arthropod predators selectively accumulated in fertilized plots where they inflicted significant mortality on all stages of planthoppers. Predators rapidly colonized fertilized plots and reached high densities well in advance of planthopper colonization, a response we attribute to their rapid aggregation in complex-structured habitats with readily

  1. Intracellular bottom-up generation of targeted nanosensors for single-molecule imaging

    Science.gov (United States)

    Hou, Yanyan; Arai, Satoshi; Kitaguchi, Tetsuya; Suzuki, Madoka

    2016-02-01

    Organic dyes are useful tools for sensing cellular activities but unfavorable in single-molecule imaging, whereas quantum dots (QDs) are widely applied in single-molecule imaging but with few sensing applications. Here, to visualize cellular activities by monitoring the response of a single probe in living cells, we propose a bottom-up approach to generate nanoprobes where four organic dyes are conjugated to tetravalent single-chain avidin (scAVD) proteins via an intracellular click reaction. We demonstrate that the nanoprobes, exhibiting increased brightness and enhanced photostability, were detectable as single dots in living cells. The ease of intracellular targeting allowed the tracking of endoplasmic reticulum (ER) remodeling with nanometer spatial resolution. Conjugating thermosensitive dyes generated temperature-sensitive nanoprobes on ER membranes that successfully monitored local temperature changes in response to external heat pulses. Our approach is potentially a suitable tool for visualizing localized cellular activities with single probe sensitivity in living cells.Organic dyes are useful tools for sensing cellular activities but unfavorable in single-molecule imaging, whereas quantum dots (QDs) are widely applied in single-molecule imaging but with few sensing applications. Here, to visualize cellular activities by monitoring the response of a single probe in living cells, we propose a bottom-up approach to generate nanoprobes where four organic dyes are conjugated to tetravalent single-chain avidin (scAVD) proteins via an intracellular click reaction. We demonstrate that the nanoprobes, exhibiting increased brightness and enhanced photostability, were detectable as single dots in living cells. The ease of intracellular targeting allowed the tracking of endoplasmic reticulum (ER) remodeling with nanometer spatial resolution. Conjugating thermosensitive dyes generated temperature-sensitive nanoprobes on ER membranes that successfully monitored local

  2. Platform Dependencies in Bottom-up Hydrogen/Deuterium Exchange Mass Spectrometry*

    Science.gov (United States)

    Burns, Kyle M.; Rey, Martial; Baker, Charles A. H.; Schriemer, David C.

    2013-01-01

    Hydrogen-deuterium exchange mass spectrometry is an important method for protein structure-function analysis. The bottom-up approach uses protein digestion to localize deuteration to higher resolution, and the essential measurement involves centroid mass determinations on a very large set of peptides. In the course of evaluating systems for various projects, we established two (HDX-MS) platforms that consisted of a FT-MS and a high-resolution QTOF mass spectrometer, each with matched front-end fluidic systems. Digests of proteins spanning a 20–110 kDa range were deuterated to equilibrium, and figures-of-merit for a typical bottom-up (HDX-MS) experiment were compared for each platform. The Orbitrap Velos identified 64% more peptides than the 5600 QTOF, with a 42% overlap between the two systems, independent of protein size. Precision in deuterium measurements using the Orbitrap marginally exceeded that of the QTOF, depending on the Orbitrap resolution setting. However, the unique nature of FT-MS data generates situations where deuteration measurements can be inaccurate, because of destructive interference arising from mismatches in elemental mass defects. This is shown through the analysis of the peptides common to both platforms, where deuteration values can be as low as 35% of the expected values, depending on FT-MS resolution, peptide length and charge state. These findings are supported by simulations of Orbitrap transients, and highlight that caution should be exercised in deriving centroid mass values from FT transients that do not support baseline separation of the full isotopic composition. PMID:23197788

  3. 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.

  4. Synthetic biology in the UK – An outline of plans and progress

    Directory of Open Access Journals (Sweden)

    L.J. Clarke

    2016-12-01

    Together these initiatives provide an important foundation for stimulating innovation, actively contributing to international research and development partnerships, and helping deliver useful benefits from synthetic biology in response to local and global needs and challenges.

  5. Biotechnology and synthetic biology approaches for metabolic engineering of bioenergy crops

    National Research Council Canada - National Science Library

    Shih, Patrick M; Liang, Yan; Loqué, Dominique

    2016-01-01

    .... In this review, we present recent advances made in the field of plant synthetic biology, specifically in genome editing, transgene expression regulation, and bioenergy crop engineering, with a focus...

  6. Application of synthetic biology for production of chemicals in yeast Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Borodina, Irina; Li, Mingji

    2015-01-01

    Synthetic biology and metabolic engineering enable generation of novel cell factories that efficiently convert renewable feedstocks into biofuels, bulk, and fine chemicals, thus creating the basis for biosustainable economy independent on fossil resources. While over a hundred proof-of-concept ch...... computational tools for the prediction of biochemical pathways, molecular biology methods for assembly of DNA parts into pathways, and for introducing the pathways into the host, and finally approaches for optimizing performance of the introduced pathways.......Synthetic biology and metabolic engineering enable generation of novel cell factories that efficiently convert renewable feedstocks into biofuels, bulk, and fine chemicals, thus creating the basis for biosustainable economy independent on fossil resources. While over a hundred proof...... biology has the potential to bring down this cost by improving our ability to predictably engineer biological systems. This review highlights synthetic biology applications for design, assembly, and optimization of non-native biochemical pathways in baker's yeast Saccharomyces cerevisiae. We describe...

  7. 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 ).

  8. Plant and bacterial systems biology as platform for plant synthetic bio(techno)logy.

    Science.gov (United States)

    Zurbriggen, Matias D; Moor, Alina; Weber, Wilfried

    2012-07-31

    The recent implementation of various high-throughput biochemical and bioanalytical platforms for the study of biological systems has resulted in a wealth of experimental information that systems biology integrates into models and functional descriptions of organisms. The fast tempo of systems biology development is currently bringing in a revolution in the understanding of cell networks by providing with a holistic comprehension of cellular components and their interaction dynamics. This thorough description of biological systems has laid the grounds for the development of synthetic biology, a discipline applying basic principles of engineering for the rational assembly of biological modules into higher order complex biological systems with desired properties. Despite the success of this new field for the generation of biotechnological tools, it has not been yet widely applied to plant systems. This review aims at describing the current status of systems biology, its contribution to our understanding of plant metabolism, expression and regulatory networks and how synthetic biology approaches could benefit utilising plant and bacterial 'omics' as a source for the design and development of biological modules for the improvement of plant stress tolerance and crop production, among other applications. The article further describes synthetic biology strategies currently being applied to plant metabolic engineering, development of signalling pathways and synthetic organelles, and the potential of this new field for the understanding of plant cellular functioning and the generation of plant biotechnological tools. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. Across-proteome modeling of dimer structures for the bottom-up assembly of protein-protein interaction networks.

    Science.gov (United States)

    Maheshwari, Surabhi; Brylinski, Michal

    2017-05-12

    Deciphering complete networks of interactions between proteins is the key to comprehend cellular regulatory mechanisms. A significant effort has been devoted to expanding the coverage of the proteome-wide interaction space at molecular level. Although a growing body of research shows that protein docking can, in principle, be used to predict biologically relevant interactions, the accuracy of the across-proteome identification of interacting partners and the selection of near-native complex structures still need to be improved. In this study, we developed a new method to discover and model protein interactions employing an exhaustive all-to-all docking strategy. This approach integrates molecular modeling, structural bioinformatics, machine learning, and functional annotation filters in order to provide interaction data for the bottom-up assembly of protein interaction networks. Encouragingly, the success rates for dimer modeling is 57.5 and 48.7% when experimental and computer-generated monomer structures are employed, respectively. Further, our protocol correctly identifies 81% of protein-protein interactions at the expense of only 19% false positive rate. As a proof of concept, 61,913 protein-protein interactions were confidently predicted and modeled for the proteome of E. coli. Finally, we validated our method against the human immune disease pathway. Protein docking supported by evolutionary restraints and machine learning can be used to reliably identify and model biologically relevant protein assemblies at the proteome scale. Moreover, the accuracy of the identification of protein-protein interactions is improved by considering only those protein pairs co-localized in the same cellular compartment and involved in the same biological process. The modeling protocol described in this communication can be applied to detect protein-protein interactions in other organisms and pathways as well as to construct dimer structures and estimate the confidence of protein

  10. 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. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  11. From a word to a world: the current situation in the interdisciplinary field of synthetic biology

    Directory of Open Access Journals (Sweden)

    Xiaojun Hu

    2015-01-01

    Full Text Available Using a carefully designed search query, we describe the field of synthetic biology in terms of leading countries, organizations and funding sources. Besides articles we also paid some attention to patents. The USA is the leading country in this field, followed by China. There is a clear exponential growth in the field of synthetic biology over the latest 14 years. Keywords were analyzed using the notion of year-based h-indices, core gap and relative core gap. We conclude that the term “synthetic biology” hides a large world ready to be explored by interdisciplinary research.

  12. 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

  13. 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.

  14. Sucralose, A Synthetic Organochlorine Sweetener: Overview of Biological Issues

    OpenAIRE

    Schiffman, Susan S.; Rother, Kristina I.

    2013-01-01

    Sucralose is a synthetic organochlorine sweetener (OC) that is a common ingredient in the world's food supply. Sucralose interacts with chemosensors in the alimentary tract that play a role in sweet taste sensation and hormone secretion. In rats, sucralose ingestion was shown to increase the expression of the efflux transporter P-glycoprotein (P-gp) and two cytochrome P-450 (CYP) isozymes in the intestine. P-gp and CYP are key components of the presystemic detoxification system involved in fi...

  15. 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

  16. Bottom-up and top-down influences at untrained conditions determine perceptual learning specificity and transfer.

    Science.gov (United States)

    Xiong, Ying-Zi; Zhang, Jun-Yun; Yu, Cong

    2016-07-05

    Perceptual learning is often orientation and location specific, which may indicate neuronal plasticity in early visual areas. However, learning specificity diminishes with additional exposure of the transfer orientation or location via irrelevant tasks, suggesting that the specificity is related to untrained conditions, likely because neurons representing untrained conditions are neither bottom-up stimulated nor top-down attended during training. To demonstrate these top-down and bottom-up contributions, we applied a "continuous flash suppression" technique to suppress the exposure stimulus into sub-consciousness, and with additional manipulations to achieve pure bottom-up stimulation or top-down attention with the transfer condition. We found that either bottom-up or top-down influences enabled significant transfer of orientation and Vernier discrimination learning. These results suggest that learning specificity may result from under-activations of untrained visual neurons due to insufficient bottom-up stimulation and/or top-down attention during training. High-level perceptual learning thus may not functionally connect to these neurons for learning transfer.

  17. 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.

  18. Getting to the bottom of L2 listening instruction: Making a case for bottom-up activities

    Directory of Open Access Journals (Sweden)

    Joseph Siegel

    2015-12-01

    Full Text Available This paper argues for the incorporation of bottom-up activities for English as a foreign language (EFL listening. It discusses theoretical concepts and pedagogic options for addressing bottom-up aural processing in the EFL classroom as well as how and why teachers may wish to include such activities in lessons. This discussion is augmented by a small-scale classroom-based research project that investigated six activities targeting learners’ bottom-up listening abilities. Learners studying at the lower-intermediate level of a compulsory EFL university course were divided into a treatment group (n = 21 and a contrast group (n = 32. Each group listened to the same audio material and completed listening activities from an assigned textbook. The treatment group also engaged in a set of six bottom-up listening activities using the same material. This quasi-experimental study used dictation and listening proficiency tests before and after the course. Between-group comparisons of t-test results of dictation and listening proficiency tests indicated that improvements for the treatment group were probably due to the BU intervention. In addition, results from a posttreatment survey suggested that learners value explicit bottom-up listening instruction.

  19. Bottom-up and trait-mediated effects of resource quality on amphibian parasitism.

    Science.gov (United States)

    Stephens, Jeffrey P; Altman, Karie A; Berven, Keith A; Tiegs, Scott D; Raffel, Thomas R

    2017-03-01

    Leaf litter subsidies are important resources for aquatic consumers like tadpoles and snails, causing bottom-up effects on wetland ecosystems. Recent studies have shown that variation in litter nutritional quality can be as important as litter quantity in driving these bottom-up effects. Resource subsidies likely also have indirect and trait-mediated effects on predation and parasitism, but these potential effects remain largely unexplored. We generated predictions for differential effects of litter nutrition and secondary polyphenolic compounds on tadpole (Lithobates sylvatica) exposure and susceptibility to Ribeiroia ondatrae, based on ecological stoichiometry and community-ecology theory. We predicted direct and indirect effects on key traits of the tadpole host (rates of growth, development and survival), the trematode parasite (production of the cercaria infective stages) and the parasite's snail intermediate host (growth and reproduction). To test these predictions, we conducted a large-scale mesocosm experiment using a natural gradient in the concentrations of nutrients (nitrogen) and toxic secondary compounds (polyphenolics) of nine leaf litter species. To differentiate between effects on exposure vs. susceptibility to infection, we included multiple infection experiments including one with constant per capita exposure. We found that increased litter nitrogen increased tadpole survival, and also increased cercaria production by the snail intermediate hosts, causing opposing effects on tadpole per capita exposure to trematode infection. Increased litter polyphenolics slowed tadpole development, leading to increased infection by increasing both their susceptibility to infection and the length of time they were exposed to parasites. Based on these results, recent shifts in forest composition towards more nitrogen-poor litter species should decrease trematode infection in tadpoles via density- and trait-mediated effects on the snail intermediate hosts. However

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

    Science.gov (United States)

    Merger, Eduard; Held, Christian; Tennigkeit, Timm; Blomley, Tom

    2012-08-09

    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. 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. 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 provide information on the economic baseline situation of

  1. 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

  2. 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.

  3. Synthetic Nanoelectronic Probes for Biological Cells and Tissue

    Science.gov (United States)

    2013-01-01

    Research at the interface between nanoscience and biology has the potential to produce breakthroughs in fundamental science and lead to revolutionary technologies. In this review, we focus on nanoelectronic/biological interfaces. First, we discuss nanoscale field effect transistors (nanoFETs) as probes to study cellular systems, including the realization of nanoFET comparable in size to biological nanostructures involved in communication using synthesized nanowires. Second, we overview current progress in multiplexed extracellular sensing using planar nanoFET arrays. Third, we describe the design and implementation of three distinct nanoFETs used to realize the first intracellular electrical recording from single cells. Fourth, we present recent progress in merging electronic and biological systems at the 3D tissue level by using macroporous nanoelectronic scaffolds. Finally, we discuss future development in this research area, the unique challenges and opportunities, and the tremendous impact these nanoFET based technologies might have in advancing biology and medical sciences. PMID:23451719

  4. 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

  5. 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

  6. 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.

  7. Enhanced Photon Extraction from a Nanowire Quantum Dot Using a Bottom-Up Photonic Shell

    Science.gov (United States)

    Jeannin, Mathieu; Cremel, Thibault; Häyrynen, Teppo; Gregersen, Niels; Bellet-Amalric, Edith; Nogues, Gilles; Kheng, Kuntheak

    2017-11-01

    Semiconductor nanowires offer the possibility to grow high-quality quantum-dot heterostructures, and, in particular, CdSe quantum dots inserted in ZnSe nanowires have demonstrated the ability to emit single photons up to room temperature. In this paper, we demonstrate a bottom-up approach to fabricate a photonic fiberlike structure around such nanowire quantum dots by depositing an oxide shell using atomic-layer deposition. Simulations suggest that the intensity collected in our NA =0.6 microscope objective can be increased by a factor 7 with respect to the bare nanowire case. Combining microphotoluminescence, decay time measurements, and numerical simulations, we obtain a fourfold increase in the collected photoluminescence from the quantum dot. We show that this improvement is due to an increase of the quantum-dot emission rate and a redirection of the emitted light. Our ex situ fabrication technique allows a precise and reproducible fabrication on a large scale. Its improved extraction efficiency is compared to state-of-the-art top-down devices.

  8. To elute or not to elute in immunocapture bottom-up LC-MS.

    Science.gov (United States)

    Levernæs, Maren Christin Stillesby; Broughton, Marianne Nordlund; Reubsaet, Léon; Halvorsen, Trine Grønhaug

    2017-06-15

    Immunocapture-based bottom-up LC-MS is a promising technique for the quantification of low abundant proteins. Magnetic immunocapture beads provide efficient enrichment from complex samples through the highly specific interaction between the target protein and its antibody. In this article, we have performed the first thorough comparison between digestion of proteins while bound to antibody coated beads versus after elution from the beads. Two previously validated immunocapture based MS methods for the quantification of pro-gastrin releasing peptide (ProGRP) and human chorionic gonadotropin (hCG) were used as model systems. The tryptic peptide generation was shown to be protein dependent and influenced by protein folding and accessibility towards trypsin both on-beads and in the eluate. The elution of proteins bound to the beads was also shown to be incomplete. In addition, the on-beads digestion suffered from non-specific binding of the trypsin generated peptides. A combination of on-beads digestion and elution may be applied to improve both the quantitative (peak area of the signature peptides) and qualitative yield (number of missed cleavages, total number of identified peptides, coverage, signal intensity and number of zero missed cleavage peptides) of the target proteins. The quantitative yield of signature peptides was shown to be reproducible in all procedures tested. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Bottom-up Retinotopic Organization Supports Top-down Mental Imagery.

    Science.gov (United States)

    Huang, Ruey-Song; Sereno, Martin I

    2013-01-01

    Finding a path between locations is a routine task in daily life. Mental navigation is often used to plan a route to a destination that is not visible from the current location. We first used functional magnetic resonance imaging (fMRI) and surface-based averaging methods to find high-level brain regions involved in imagined navigation between locations in a building very familiar to each participant. This revealed a mental navigation network that includes the precuneus, retrosplenial cortex (RSC), parahippocampal place area (PPA), occipital place area (OPA), supplementary motor area (SMA), premotor cortex, and areas along the medial and anterior intraparietal sulcus. We then visualized retinotopic maps in the entire cortex using wide-field, natural scene stimuli in a separate set of fMRI experiments. This revealed five distinct visual streams or 'fingers' that extend anteriorly into middle temporal, superior parietal, medial parietal, retrosplenial and ventral occipitotemporal cortex. By using spherical morphing to overlap these two data sets, we showed that the mental navigation network primarily occupies areas that also contain retinotopic maps. Specifically, scene-selective regions RSC, PPA and OPA have a common emphasis on the far periphery of the upper visual field. These results suggest that bottom-up retinotopic organization may help to efficiently encode scene and location information in an eye-centered reference frame for top-down, internally generated mental navigation. This study pushes the border of visual cortex further anterior than was initially expected.

  10. Bottom-up Perspectives on Multilingual Ideologies in the EU: The Case of a Transnational NGO

    Directory of Open Access Journals (Sweden)

    Franco Zappettini

    2014-11-01

    Full Text Available This paper investigates the discursive construction of multilingualism in citizens’ discourses, aiming to fill a gap in the literature of European studies that has scarcely been concerned with language ideologies from bottom-up perspectives. In particular, we focus on the discourses of a transnational NGO to analyse how its members position themselves in relation to linguistic issues and to what extent (if so they reproduce the EU’s multilingual ideology. Deriving data from focus groups and semi-structured interviews, we contextualise our analysis against the backdrop of an increasingly ‘glocalised’ European site of struggle between global communication and linguistic justice. Using critical discourse analysis we aim to show how discourses of multilingualism are being negotiated at the grass-roots level. Our findings suggest that whilst citizens’ discourses validate an ideal promotion and preservation of linguistic diversity in the EU, they also endorse a diglossic scenario with language performing separate identity and communicative functions. We thus argue for an understanding of European multilingualism that takes into account the transnational dynamics of the European sphere.

  11. 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.

  12. Optical and electronic properties study of bottom-up graphene nanoribbons for photovoltaic applications

    Science.gov (United States)

    Villegas, Cesar E. P.; Rocha, Alexandre

    2015-03-01

    Graphene nanoribbons (GNRs), turn out to be serious contender for several optolectronic applications due to their physical properties. Recently, bottom-up methods, using the assembly of appropriate precursor molecules were shown to be an exciting pathway towards making precise nanoribbons. In particular, it has been demonstrated that so-called cove-shaped GNRs absorb light in the visible part of the spectrum, suggesting they could be used for photovoltaic applications. In solar cells, the key ingredient is the presence excitons and their subsequent diffusion along a donor material. This is influenced by the character of the different excitations taking place, as well as, the exciton binding energy. Thus, In this work we use many-body corrected density functional theory to simulate the optical properties of these nanoribbons. We elucidate the most important transitions occurring in these systems, and identify types of excitatiions that have not been previously observed in conventional nanoribbons. We also find that the exciton binding energies for all the structures we considered are in the eV range, which enhances the diffusion lengths for the particle-hole pairs. Finally, we estimate the potencial of these systems as solar cells by calculating the short-circuit current. The Authors thank FAPESP for financial support.

  13. Suspension trapping (STrap) sample preparation method for bottom-up proteomics analysis.

    Science.gov (United States)

    Zougman, Alexandre; Selby, Peter J; Banks, Rosamonde E

    2014-05-01

    Despite recent developments in bottom-up proteomics, the need still exists in a fast, uncomplicated, and robust method for comprehensive sample processing especially when applied to low protein amounts. The suspension trapping method combines the advantage of efficient SDS-based protein extraction with rapid detergent removal, reactor-type protein digestion, and peptide cleanup. Proteins are solubilized in SDS. The sample is acidified and introduced into the suspension trapping tip incorporating the depth filter and hydrophobic compartments, filled with the neutral pH methanolic solution. The instantly formed fine protein suspension is trapped in the depth filter stack-this crucial step is aimed at separating the particulate matter in space. SDS and other contaminants are removed in the flow-through, and a protease is introduced. Following the digestion, the peptides are cleaned up using the tip's hydrophobic part. The methodology allows processing of protein loads down to the low microgram/submicrogram levels. The detergent removal takes about 5 min, whereas the tryptic proteolysis of a cellular lysate is complete in as little as 30 min. We have successfully utilized the method for analysis of cellular lysates, enriched membrane preparations, and immunoprecipitates. We expect that due to its robustness and simplicity, the method will become an essential proteomics tool. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Bottom-Up Two-Dimensional Electron-Capture Dissociation Mass Spectrometry of Calmodulin

    Science.gov (United States)

    Floris, Federico; van Agthoven, Maria A.; Chiron, Lionel; Wootton, Christopher A.; Lam, Pui Yiu Yuko; Barrow, Mark P.; Delsuc, Marc-André; O'Connor, Peter B.

    2017-10-01

    Two-dimensional mass spectrometry (2D MS) is a tandem mass spectrometry technique that allows data-independent fragmentation of all precursors in a mixture without previous isolation, through modulation of the ion cyclotron frequency in the ICR-cell prior to fragmentation. Its power as an analytical technique has been proven particularly for proteomics. Recently, a comparison study between 1D and 2D MS has been performed using infrared multiphoton dissociation (IRMPD) on calmodulin (CaM), highlighting the capabilities of the technique in both top-down (TDP) and bottom-up proteomics (BUP). The goal of this work is to expand this study on CaM using electron-capture dissociation (ECD) 2D MS as a single complementary BUP experiment in order to enhance the cleavage coverage of the protein under analysis. By adding the results of the BUP 2D ECD MS to the 2D IRMPD MS analysis of CaM, the total cleavage coverage increased from 40% to 68%. [Figure not available: see fulltext.

  15. Bottom-up fabrication of graphene on Ru(0001) via molecular self-assembly

    Science.gov (United States)

    Cai, Yiliang; Zhang, Hanjie; Song, Junjie; Zhang, Yuxi; Rehman, A. U.; He, Pimo

    2015-07-01

    A bottom-up fabrication of graphene via molecular self-assembly of p-Terphenyl on Ru(0001) has been investigated by scanning tunneling microcopy and density functional theory. Upon annealing of the sample at 450 °C, the intermediate stage is observed, in which the adsorbed p-Terphenyl molecules and graphitized flakes converted from the molecules coexist, implying the onset of dehydrogenation of p-Terphenyl. At the annealing temperature of 480 °C, the graphitized flakes start to convert into graphene. An adsoption energy of 5.99 eV is calculated for an individual p-Terphenyl molecule on Ru(0001), denoting a strong interaction between the adsorbate and substrate. The intermolecular interaction brings an extra adsorption energy of 0.28 eV for each molecule in the di-molecule adsorption system. During the conversion process from adsorbed molecule into graphene, the intermolecular interaction leads to the increase of the dehydrogenation barrier from 1.52 to 1.64 eV.

  16. 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.

  17. Bottom-up synthesis of nitrogen-doped graphene sheets for ultrafast lithium storage.

    Science.gov (United States)

    Tian, Lei-Lei; Wei, Xian-Yong; Zhuang, Quan-Chao; Jiang, Chen-Hui; Wu, Chao; Ma, Guang-Yao; Zhao, Xing; Zong, Zhi-Min; Sun, Shi-Gang

    2014-06-07

    A facile bottom-up strategy was developed to fabricate nitrogen-doped graphene sheets (NGSs) from glucose using a sacrificial template synthesis method. Three main types of nitrogen dopants (pyridinic, pyrrolic and graphitic nitrogens) were introduced into the graphene lattice, and an inimitable microporous structure of NGS with a high specific surface area of 504 m(2) g(-1) was obtained. Particularly, with hybrid features of lithium ion batteries and Faradic capacitors at a low rate and features of Faradic capacitors at a high rate, the NGS presents a superior lithium storage performance. During electrochemical cycling, the NGS electrode afforded an enhanced reversible capacity of 832.4 mA h g(-1) at 100 mA g(-1) and an excellent cycling stability of 750.7 mA h g(-1) after 108 discharge-charge cycles. Furthermore, an astonishing rate capability of 333 mA h g(-1) at 10,000 mA g(-1) and a high rate cycle performance of 280.6 mA h g(-1) even after 1200 cycles were also achieved, highlighting the significance of nitrogen doping on the maximum utilization of graphene-based materials for advanced lithium storage.

  18. The path to next generation biofuels: successes and challenges in the era of synthetic biology

    Science.gov (United States)

    2010-01-01

    Volatility of oil prices along with major concerns about climate change, oil supply security and depleting reserves have sparked renewed interest in the production of fuels from renewable resources. Recent advances in synthetic biology provide new tools for metabolic engineers to direct their strategies and construct optimal biocatalysts for the sustainable production of biofuels. Metabolic engineering and synthetic biology efforts entailing the engineering of native and de novo pathways for conversion of biomass constituents to short-chain alcohols and advanced biofuels are herewith reviewed. In the foreseeable future, formal integration of functional genomics and systems biology with synthetic biology and metabolic engineering will undoubtedly support the discovery, characterization, and engineering of new metabolic routes and more efficient microbial systems for the production of biofuels. PMID:20089184

  19. 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.

  20. Synthetic Approaches and Biological Activities of 4-Hydroxycoumarin Derivatives

    Directory of Open Access Journals (Sweden)

    Oee-Sook Park

    2009-11-01

    Full Text Available The main purpose of this review is to summarize recent chemical syntheses and structural modifications of 4-hydroxycoumarin and its derivatives, of interest due to their characteristic conjugated molecular architecture and biological activities.

  1. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Biologically inspired synthetic gecko adhesive from hard polymer microfiber arrays

    Science.gov (United States)

    Lee, Jongho

    Inspiration from nature and development of nano/micro-technology suggest new types of smart adhesives. Gecko's fast wall-climbing and upside-down-walking even on contaminated surfaces inspire the development of easily attachable and easily releasable, durable, self-cleaning synthetic adhesives. Advances in nano/micro-technology enable the fabrication of gecko-like nano/micro-structures. However, producing structures that exhibit a close resemblance to those of gecko is still challenging. This thesis explores achieving the key properties of the natural gecko adhesive with relatively simple nano/micro-structures consisting of synthetic materials. Hard material, comparable to the natural gecko structures, was used, and the surface geometry was modified to achieve novel adhesion properties. Important properties of the fabricated microfiber arrays were characterized and compared with the natural gecko adhesives using a custom-made force sensor apparatus. The high-aspect-ratio of the microfiber arrays showed similar novel properties, including easiness in attachment and release, durability, self-cleaning capability, and directional dependence of adhesion/friction properties, similar to natural gecko surfaces.

  3. 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.

  4. Synthetic Versus Biological Mesh-Related Erosion After Laparoscopic Ventral Mesh Rectopexy: A Systematic Review.

    Science.gov (United States)

    Balla, Andrea; Quaresima, Silvia; Smolarek, Sebastian; Shalaby, Mostafa; Missori, Giulia; Sileri, Pierpaolo

    2017-04-01

    This review reports the incidence of mesh-related erosion after ventral mesh rectopexy to determine whether any difference exists in the erosion rate between synthetic and biological mesh. A systematic search of the MEDLINE and the Ovid databases was conducted to identify suitable articles published between 2004 and 2015. The search strategy capture terms were laparoscopic ventral mesh rectopexy, laparoscopic anterior rectopexy, robotic ventral rectopexy, and robotic anterior rectopexy. Eight studies (3,956 patients) were included in this review. Of those patients, 3,517 patients underwent laparoscopic ventral rectopexy (LVR) using synthetic mesh and 439 using biological mesh. Sixty-six erosions were observed with synthetic mesh (26 rectal, 32 vaginal, 8 recto-vaginal fistulae) and one (perineal erosion) with biological mesh. The synthetic and the biological mesh-related erosion rates were 1.87% and 0.22%, respectively. The time between rectopexy and diagnosis of mesh erosion ranged from 1.7 to 124 months. No mesh-related mortalities were reported. The incidence of mesh-related erosion after LVR is low and is more common after the placement of synthetic mesh. The use of biological mesh for LVR seems to be a safer option; however, large, multicenter, randomized, control trials with long follow-ups are required if a definitive answer is to be obtained.

  5. 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.

  6. Synthetic Biology Platform for Sensing and Integrating Endogenous Transcriptional Inputs in Mammalian Cells.

    Science.gov (United States)

    Angelici, Bartolomeo; Mailand, Erik; Haefliger, Benjamin; Benenson, Yaakov

    2016-08-30

    One of the goals of synthetic biology is to develop programmable artificial gene networks that can transduce multiple endogenous molecular cues to precisely control cell behavior. Realizing this vision requires interfacing natural molecular inputs with synthetic components that generate functional molecular outputs. Interfacing synthetic circuits with endogenous mammalian transcription factors has been particularly difficult. Here, we describe a systematic approach that enables integration and transduction of multiple mammalian transcription factor inputs by a synthetic network. The approach is facilitated by a proportional amplifier sensor based on synergistic positive autoregulation. The circuits efficiently transduce endogenous transcription factor levels into RNAi, transcriptional transactivation, and site-specific recombination. They also enable AND logic between pairs of arbitrary transcription factors. The results establish a framework for developing synthetic gene networks that interface with cellular processes through transcriptional regulators. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  7. Advanced Drug Delivery Systems - a Synthetic and Biological Applied Evaluation

    DEFF Research Database (Denmark)

    Bjerg, Lise Nørkjær

    Specific delivery of drugs to diseased sites in the body is a major topic in the development of drug delivery system today. Especially, the field of cancer treatment needs improved drug delivery systems as the strong dose-limiting side effects of chemotherapy today often present a barrier...... unloading of the encapsulated drug have been tried optimized in a variety of ways. Many propose the use of small molecules, such as vitamins and peptides, for active targeting of the liposomes to overexpressed receptors on the cancerous tissue. Once located close to the diseased site a trigger mechanism...... function as the targeting moiety on the surface of the liposomes. Several examples of synthetic procedures known from the literature are presented. The chapter is completed with a study covering the conjugation efficiencies of a variety of chemical functionalities. Large differences are revealed between...

  8. Synthetic biology: lessons from engineering yeast MAPK signalling pathways.

    Science.gov (United States)

    Furukawa, Kentaro; Hohmann, Stefan

    2013-04-01

    All living cells respond to external stimuli and execute specific physiological responses through signal transduction pathways. Understanding the mechanisms controlling signalling pathways is important for diagnosing and treating diseases and for reprogramming cells with desired functions. Although many of the signalling components in the budding yeast Saccharomyces cerevisiae have been identified by genetic studies, many features concerning the dynamic control of pathway activity, cross-talk, cell-to-cell variability or robustness against perturbation are still incompletely understood. Comparing the behaviour of engineered and natural signalling pathways offers insight complementary to that achievable with standard genetic and molecular studies. Here, we review studies that aim at a deeper understanding of signalling design principles and generation of novel signalling properties by engineering the yeast mitogen-activated protein kinase (MAPK) pathways. The underlying approaches can be applied to other organisms including mammalian cells and offer opportunities for building synthetic pathways and functionalities useful in medicine and biotechnology. © 2013 Blackwell Publishing Ltd.

  9. Importance of bottom-up approach in water management - sustainable development of catchment areas in Croatia

    Science.gov (United States)

    Pavic, M.; Cosic-Flajsig, G.; Petricec, M.; Blazevic, Z.

    2012-04-01

    Association for preservation of Croatian waters and sea SLAP is a non-governmental organization (NGO) that gathers more than 150 scientist, hydrologist and civil engineers. SLAP has been established in 2006 and since then had organized many conferences and participated in projects dealing with water management. We have started our work developing plans to secure water supply to the 22 (21) villages in the rural parts of Dubrovnik (Pozega) area and trough the years we have accumulated knowledge and experience in dealing with stakeholders in hydrology and water management. Within this paper we will present importance of bottom-up approach to the stakeholders in water management in Croatia on two case studies: (1) Management of River Trebizat catchment area - irrigation of the Imotsko-Bekijsko rural parts; (2) Development of multipurpose water reservoirs at the River Orljava catchment area. Both projects were designed in the mid and late 1980's but due to the war were forgotten and on halt. River Trebizat meanders between Croatia and Bosnia and Herzegovina and acquires joint management by both countries. In 2010 and 2011 SLAP has organized conferences in both countries gathering all the relevant stakeholders from representatives of local and state governments, water management companies and development agencies to the scientist and interested NGO's. The conferences gave firm scientific background of the topic including presentation of all previous studies and measurements as well as model results but presented in manner appropriate to the stakeholders. The main result of the conference was contribution to the development of joint cross-border project sent to the EU Pre-Accession funds in December 2011 with the aim to strengthen capacities of both countries and prepare larger project dealing with management of the whole Trebizat catchment area to EU structural funds once Croatia enters EU in 2013. Similar approach was taken for the Orljava catchment in the northern

  10. 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.

  11. Bottom-up modeling approach for the quantitative estimation of parameters in pathogen-host interactions

    Directory of Open Access Journals (Sweden)

    Teresa eLehnert

    2015-06-01

    Full Text Available Opportunistic fungal pathogens can cause bloodstream infection and severe sepsis upon entering the blood stream of the host. The early immune response in human blood comprises the elimination of pathogens by antimicrobial peptides and innate immune cells, such as neutrophils or monocytes. Mathematical modeling is a predictive method to examine these complex processes and to quantify the dynamics of pathogen-host interactions. Since model parameters are often not directly accessible from experiment, their estimation is required by calibrating model predictions with experimental data. Depending on the complexity of the mathematical model, parameter estimation can be associated with excessively high computational costs in terms of run time and memory. We apply a strategy for reliable parameter estimation where different modeling approaches with increasing complexity are used that build on one another. This bottom-up modeling approach is applied to an experimental human whole-blood infection assay for Candida albicans. Aiming for the quantification of the relative impact of different routes of the immune response against this human-pathogenic fungus, we start from a non-spatial state-based model (SBM, because this level of model complexity allows estimating textit{a priori} unknown transition rates between various system states by the global optimization method simulated annealing. Building on the non-spatial SBM, an agent-based model (ABM is implemented that incorporates the migration of interacting cells in three-dimensional space. The ABM takes advantage of estimated parameters from the non-spatial SBM, leading to a decreased dimensionality of the parameter space. This space can be scanned using a local optimization approach, i.e. least-squares error estimation based on an adaptive regular grid search, to predict cell migration parameters that are not accessible in experiment.

  12. Bottom-up engineering of thermoelectric nanomaterials and devices from solution-processed nanoparticle building blocks.

    Science.gov (United States)

    Ortega, Silvia; Ibáñez, Maria; Liu, Yu; Zhang, Yu; Kovalenko, Maksym V; Cadavid, Doris; Cabot, Andreu

    2017-06-19

    The conversion of thermal energy to electricity and vice versa by means of solid state thermoelectric devices is extremely appealing. However, its cost-effectiveness is seriously hampered by the relatively high production cost and low efficiency of current thermoelectric materials and devices. To overcome present challenges and enable a successful deployment of thermoelectric systems in their wide application range, materials with significantly improved performance need to be developed. Nanostructuration can help in several ways to reach the very particular group of properties required to achieve high thermoelectric performances. Nanodomains inserted within a crystalline matrix can provide large charge carrier concentrations without strongly influencing their mobility, thus allowing to reach very high electrical conductivities. Nanostructured materials contain numerous grain boundaries that efficiently scatter mid- and long-wavelength phonons thus reducing the thermal conductivity. Furthermore, nanocrystalline domains can enhance the Seebeck coefficient by modifying the density of states and/or providing type- and energy-dependent charge carrier scattering. All these advantages can only be reached when engineering a complex type of material, nanocomposites, with exquisite control over structural and chemical parameters at multiple length scales. Since current conventional nanomaterial production technologies lack such level of control, alternative strategies need to be developed and adjusted to the specifics of the field. A particularly suitable approach to produce nanocomposites with unique level of control over their structural and compositional parameters is their bottom-up engineering from solution-processed nanoparticles. In this work, we review the state-of-the-art of this technology applied to the thermoelectric field, including the synthesis of nanoparticles of suitable materials with precisely engineered composition and surface chemistry, their combination

  13. Top-down or bottom-up: Contrasting perspectives on psychiatric diagnoses

    Directory of Open Access Journals (Sweden)

    Willem MA Verhoeven

    2008-09-01

    Full Text Available Willem MA Verhoeven1,2, Siegfried Tuinier1, Ineke van der Burgt31Vincent van Gogh Institute for Psychiatry, Venray, The Netherlands; 2Department of Psychiatry, Erasmus University Medical Centre, Rotterdam, The Netherlands; 3Department of Human Genetics, Radboud University Medical Centre, Nijmegen, The NetherlandsAbstract: Clinical psychiatry is confronted with the expanding knowledge of medical genetics. Most of the research into the genetic underpinnings of major mental disorders as described in the categorical taxonomies, however, did reveal linkage with a variety of chromosomes. This heterogeneity of results is most probably due to the assumption that the nosological categories as used in these studies are disease entities with clear boundaries. If the reverse way of looking, the so-called bottom-up approach, is applied, it becomes clear that genetic abnormalities are in most cases not associated with a single psychiatric disorder but with a certain probability to develop a variety of aspecific psychiatric symptoms. The adequacy of the categorical taxonomy, the so-called top-down approach, seems to be inversely related to the amount of empirical etiological data. This is illustrated by four rather prevalent genetic syndromes, fragile X syndrome, Prader-Willi syndrome, 22q11 deletion syndrome, and Noonan syndrome, as well as by some cases with rare chromosomal abnormalities. From these examples, it becomes clear that psychotic symptoms as well as mood, anxiety, and autistic features can be found in a great variety of different genetic syndromes. A psychiatric phenotype exists, but comprises, apart from the chance to present several psychiatric symptoms, all elements from developmental, neurocognitive, and physical characteristics.Keywords: genetic disorders, psychiatric symptoms, phenotype, mental disorders

  14. The case for refining bottom-up methane emission inventories using top-down measurements

    Science.gov (United States)

    Kelly, Bryce F. J.; Iverach, Charlotte P.; Ginty, Elisa; Bashir, Safdar; Lowry, Dave; Fisher, Rebecca E.; France, James L.; Nisbet, Euan G.

    2017-04-01

    Bottom-up global methane emission estimates are important for guiding policy development and mitigation strategies. Such inventories enable rapid and consistent proportioning of emissions by industrial sectors and land use at various scales from city to country to global. There has been limited use of top-down measurements to guide refining emission inventories. Here we compare the EDGAR gridmap data version 4.2 with over 5000 km of daytime ground level mobile atmospheric methane surveys in eastern Australia. The landscapes and industries surveyed include: urban environments, dryland farming, intensive livestock farming (both beef and lamb), irrigation agriculture, open cut and underground coal mining, and coal seam gas production. Daytime mobile methane surveys over a 2-year period show that at the landscape scale there is a high level of repeatability for the mole fraction of methane measured in the ground level atmosphere. Such consistency in the mole fraction of methane indicates that these data can be used as a proxy for flux. A scatter plot of the EDGAR emission gridmap Log[ton substance / 0.1 degree x 0.1 degree / year] versus the median mole fraction of methane / 0.1 degree x 0.1 degree in the ground level atmosphere highlights that the extent of elevated methane emissions associated with coal mining in the Hunter coalfields, which covers an area of 56 km by 24 km, has been under-represented in the EDGAR input data. Our results also show that methane emissions from country towns (population expansion of all forms of top-down emission estimates would result in reduced uncertainty in the global methane budget.

  15. Construction of mammographic examination process ontology using bottom-up hierarchical task analysis.

    Science.gov (United States)

    Yagahara, Ayako; Yokooka, Yuki; Jiang, Guoqian; Tsuji, Shintarou; Fukuda, Akihisa; Nishimoto, Naoki; Kurowarabi, Kunio; Ogasawara, Katsuhiko

    2018-01-10

    Describing complex mammography examination processes is important for improving the quality of mammograms. It is often difficult for experienced radiologic technologists to explain the process because their techniques depend on their experience and intuition. In our previous study, we analyzed the process using a new bottom-up hierarchical task analysis and identified key components of the process. Leveraging the results of the previous study, the purpose of this study was to construct a mammographic examination process ontology to formally describe the relationships between the process and image evaluation criteria to improve the quality of mammograms. First, we identified and created root classes: task, plan, and clinical image evaluation (CIE). Second, we described an "is-a" relation referring to the result of the previous study and the structure of the CIE. Third, the procedural steps in the ontology were described using the new properties: "isPerformedBefore," "isPerformedAfter," and "isPerformedAfterIfNecessary." Finally, the relationships between tasks and CIEs were described using the "isAffectedBy" property to represent the influence of the process on image quality. In total, there were 219 classes in the ontology. By introducing new properties related to the process flow, a sophisticated mammography examination process could be visualized. In relationships between tasks and CIEs, it became clear that the tasks affecting the evaluation criteria related to positioning were greater in number than those for image quality. We developed a mammographic examination process ontology that makes knowledge explicit for a comprehensive mammography process. Our research will support education and help promote knowledge sharing about mammography examination expertise.

  16. 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.

  17. Leaf LIMS: A Flexible Laboratory Information Management System with a Synthetic Biology Focus.

    Science.gov (United States)

    Craig, Thomas; Holland, Richard; D'Amore, Rosalinda; Johnson, James R; McCue, Hannah V; West, Anthony; Zulkower, Valentin; Tekotte, Hille; Cai, Yizhi; Swan, Daniel; Davey, Robert P; Hertz-Fowler, Christiane; Hall, Anthony; Caddick, Mark

    2017-12-15

    This paper presents Leaf LIMS, a flexible laboratory information management system (LIMS) designed to address the complexity of synthetic biology workflows. At the project's inception there was a lack of a LIMS designed specifically to address synthetic biology processes, with most systems focused on either next generation sequencing or biobanks and clinical sample handling. Leaf LIMS implements integrated project, item, and laboratory stock tracking, offering complete sample and construct genealogy, materials and lot tracking, and modular assay data capture. Hence, it enables highly configurable task-based workflows and supports data capture from project inception to completion. As such, in addition to it supporting synthetic biology it is ideal for many laboratory environments with multiple projects and users. The system is deployed as a web application through Docker and is provided under a permissive MIT license. It is freely available for download at https://leaflims.github.io .

  18. 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.

  19. 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.

  20. 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.

  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. Urban Biomining: Biological Extraction of Metals and Materials from Electronics Waste Using a Synthetic Biology Approach

    Science.gov (United States)

    Urbina-Navarrete, J.; Rothschild, L.

    2016-12-01

    End-of-life electronics waste (e-waste) containing toxic and valuable materials is a rapidly progressing human health and environmental issue. Using synthetic biology tools, we have developed a recycling method for e-waste. Our innovation is to use a recombinant version of a naturally-occurring silica-degrading enzyme to depolymerize the silica in metal- and glass- containing e-waste components, and subsequently, to use engineered bacterial surfaces to bind and separate metals from a solution. The bacteria with bound metals can then be used as "bio-ink" to print new circuits using a novel plasma jet electronics printing technology. Here, we present the results from our initial studies that focus on the specificity of metal-binding motifs for a cognate metal. The candidate motifs that show high affinity and specificity will be engineered into bacterial surfaces for downstream applications in biologically-mediated metal recycling. Since the chemistry and role of Cu in metalloproteins is relatively well-characterized, we are using Cu as a proxy to elucidate metal and biological ligand interactions with various metals in e-waste. We assess the binding parameters of 3 representative classes of Cu-binding motifs using isothermal titration calorimetry; 1) natural motifs found in metalloproteins, 2) consensus motifs, and 3) rationally designed peptides that are predicted, in silico, to bind Cu. Our results indicate that naturally-occurring motifs have relative high affinity and specificity for Cu (association constant for Cu Ka 104 M-1, Zn Ka 103 M-1) when competing ions are present in the aqueous milieu. However, motifs developed through rational design by applying quantum mechanical methods that take into account complexation energies of the elemental binding partners and molecular geometry of the cognate metal, not only show high affinity for the cognate metal (Cu Ka 106 M-1), but they show specificity and discrimination against other metal ions that would be

  3. 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...

  4. Synthetic Biology: A Bridge between Artificial and Natural Cells

    OpenAIRE

    Yunfeng Ding; Fan Wu; Cheemeng Tan

    2014-01-01

    Artificial cells are simple cell-like entities that possess certain properties of natural cells. In general, artificial cells are constructed using three parts: (1) biological membranes that serve as protective barriers, while allowing communication between the cells and the environment; (2) transcription and translation machinery that synthesize proteins based on genetic sequences; and (3) genetic modules that control the dynamics of the whole cell. Artificial cells are minimal and well-defi...

  5. 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. Copyright © 2014. Published by Elsevier Ltd.

  6. 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

  7. 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…

  8. Enhancing criterion-related validity through bottom-up contextualization of personality inventories: The construction of an ecological conscientiousness scale

    NARCIS (Netherlands)

    Marise Born; dr René Butter

    2011-01-01

    In this paper the concept of "ecological personality scales" is introduced. These are contextualized inventories with a high ecological validity. They are developed in a bottom-up or qualitative way and combine a relatively high trait specificity with a relatively high situational specificity. An

  9. Leadership for Quality University Teaching: How Bottom-Up Academic Insights Can Inform Top-Down Leadership

    Science.gov (United States)

    Scott, Donald E.; Scott, Shelleyann

    2016-01-01

    This paper presents the leadership implications from a study that explored how to increase the quality of teaching in a university thereby presenting data from the bottom up--the academic perspective--to inform leadership, policies, and academic development which generally flows from the top down. We report academics' perceptions of and…

  10. Balancing Top-Down, Bottom-Up, and Peer-to-Peer Approaches to Sustaining Distance Training

    Science.gov (United States)

    Dudink, Gertrude; Berge, Zane

    2006-01-01

    Many distance training case studies identify distance training leadership as bottom-up, whereas much of the literature suggests a need for strategic, top-down approaches. With change management as an overarching framework, approaches to sustaining distance training that originate at different levels of the organization are explored. Special…

  11. On the Temporal Relation of Top-Down and Bottom-Up Mechanisms during Guidance of Attention

    Science.gov (United States)

    Wykowska, Agnieszka; Schubo, Anna

    2010-01-01

    Two mechanisms are said to be responsible for guiding focal attention in visual selection: bottom-up, saliency-driven capture and top-down control. These mechanisms were examined with a paradigm that combined a visual search task with postdisplay probe detection. Two SOAs between the search display and probe onsets were introduced to investigate…

  12. An integrative top-down and bottom-up qualitative model construction framework for exploration of biochemical systems.

    Science.gov (United States)

    Wu, Zujian; Pang, Wei; Coghill, George M

    Computational modelling of biochemical systems based on top-down and bottom-up approaches has been well studied over the last decade. In this research, after illustrating how to generate atomic components by a set of given reactants and two user pre-defined component patterns, we propose an integrative top-down and bottom-up modelling approach for stepwise qualitative exploration of interactions among reactants in biochemical systems. Evolution strategy is applied to the top-down modelling approach to compose models, and simulated annealing is employed in the bottom-up modelling approach to explore potential interactions based on models constructed from the top-down modelling process. Both the top-down and bottom-up approaches support stepwise modular addition or subtraction for the model evolution. Experimental results indicate that our modelling approach is feasible to learn the relationships among biochemical reactants qualitatively. In addition, hidden reactants of the target biochemical system can be obtained by generating complex reactants in corresponding composed models. Moreover, qualitatively learned models with inferred reactants and alternative topologies can be used for further web-lab experimental investigations by biologists of interest, which may result in a better understanding of the system.

  13. A Clash of Bottom-Up and Top-Down Processes in Visual Search: The Reversed Letter Effect Revisited

    Science.gov (United States)

    Zhaoping, Li; Frith, Uta

    2011-01-01

    It is harder to find the letter "N" among its mirror reversals than vice versa, an inconvenient finding for bottom-up saliency accounts based on primary visual cortex (V1) mechanisms. However, in line with this account, we found that in dense search arrays, gaze first landed on either target equally fast. Remarkably, after first landing,…

  14. Two-dimensional combinatorial screening enables the bottom-up design of a microRNA-10b inhibitor.

    Science.gov (United States)

    Velagapudi, Sai Pradeep; Disney, Matthew D

    2014-03-21

    The RNA motifs that bind guanidinylated kanamycin A (G Kan A) and guanidinylated neomycin B (G Neo B) were identified via two-dimensional combinatorial screening (2DCS). The results of these studies enabled the "bottom-up" design of a small molecule inhibitor of oncogenic microRNA-10b.

  15. A critical role of temporoparietal junction in the integration of top-down and bottom-up attentional control.

    Science.gov (United States)

    Wu, Qiong; Chang, Chi-Fu; Xi, Sisi; Huang, I-Wen; Liu, Zuxiang; Juan, Chi-Hung; Wu, Yanhong; Fan, Jin

    2015-11-01

    Information processing can be biased toward behaviorally relevant and salient stimuli by top-down (goal-directed) and bottom-up (stimulus-driven) attentional control processes respectively. However, the neural basis underlying the integration of these processes is not well understood. We employed functional magnetic resonance imaging (fMRI) and transcranial direct-current stimulation (tDCS) in humans to examine the brain mechanisms underlying the interaction between these two processes. We manipulated the cognitive load involved in top-down processing and stimulus surprise involved in bottom-up processing in a factorial design by combining a majority function task and an oddball paradigm. We found that high cognitive load and high surprise level were associated with prolonged reaction time compared to low cognitive load and low surprise level, with a synergistic interaction effect, which was accompanied by a greater deactivation of bilateral temporoparietal junction (TPJ). In addition, the TPJ displayed negative functional connectivity with right middle occipital gyrus, which is involved in bottom-up processing (modulated by the interaction effect), and the right frontal eye field (FEF), which is involved in top-down control. The enhanced negative functional connectivity between the TPJ and right FEF was accompanied by a larger behavioral interaction effect across subjects. Application of cathodal tDCS over the right TPJ eliminated the interaction effect. These results suggest that the TPJ plays a critical role in processing bottom-up information for top-down control of attention. © 2015 Wiley Periodicals, Inc.

  16. Improving Reading Fluency and Comprehension in Adult ESL Learners Using Bottom-Up and Top-Down Vocabulary Training

    Science.gov (United States)

    Oliver, Rhonda; Young, Shahreen

    2016-01-01

    The current research examines the effect of two methods of vocabulary training on reading fluency and comprehension of adult English as second language (ESL) tertiary-bound students. The methods used were isolated vocabulary training (bottom-up reading) and vocabulary training in context (top-down reading). The current exploratory and…

  17. A comparative study of benchmarking approaches for non-domestic buildings: Part 2 – Bottom-up approach

    Directory of Open Access Journals (Sweden)

    Esfandiar Burman

    2014-12-01

    Full Text Available The bottom-up methods for energy benchmarking aim to derive a yardstick for energy performance based on a theoretical analysis of a building. While the top-down methods drive performance improvement by ranking a building against its peers, the bottom-up methods are focused on the building’s specific context. Consequently, the bottom-up methods can help identify how performance improvement could be materialised. These two complementary approaches can improve design practice and facilities’ management. Two bottom-up methods that could be used for energy benchmarking have been reviewed using UK schools as case studies: Building physics and aggregated end-use. The aim is to demonstrate how these methods could be used for benchmarking and identify their benefits and limitations. When all energy components are included in a model under expected operating conditions, the building physics method can be used to establish a baseline for energy performance. It is demonstrated that where this method is used under standardised operating conditions and is subject to minimum energy performance requirements, as prescribed by the Energy Performance of Buildings Directive (EPBD, it can be used to establish a benchmark for energy performance. It is also shown how aggregated end-use methods such as CIBSE TM22 can be used to define system level benchmarks, and identify the root causes for discrepancy between measured performance and design intent in a systematic way.

  18. 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

  19. Second Language Listening Instruction: Comparing a Strategies-Based Approach with an Interactive, Strategies/Bottom-Up Skills Approach

    Science.gov (United States)

    Yeldham, Michael

    2016-01-01

    This quasi-experimental study compared a strategies approach to second language listening instruction with an interactive approach, one combining a roughly equal balance of strategies and bottom-up skills. The participants were lower-intermediate-level Taiwanese university EFL learners, who were taught for 22 hours over one and a half semesters.…

  20. 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