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Sample records for synthetic genetic array

  1. Reporter-Based Synthetic Genetic Array Analysis: A Functional Genomics Approach for Investigating Transcript or Protein Abundance Using Fluorescent Proteins in Saccharomyces cerevisiae.

    Science.gov (United States)

    Göttert, Hendrikje; Mattiazzi Usaj, Mojca; Rosebrock, Adam P; Andrews, Brenda J

    2018-01-01

    Fluorescent reporter genes have long been used to quantify various cell features such as transcript and protein abundance. Here, we describe a method, reporter synthetic genetic array (R-SGA) analysis, which allows for the simultaneous quantification of any fluorescent protein readout in thousands of yeast strains using an automated pipeline. R-SGA combines a fluorescent reporter system with standard SGA analysis and can be used to examine any array-based strain collection available to the yeast community. This protocol describes the R-SGA methodology for screening different arrays of yeast mutants including the deletion collection, a collection of temperature-sensitive strains for the assessment of essential yeast genes and a collection of inducible overexpression strains. We also present an alternative pipeline for the analysis of R-SGA output strains using flow cytometry of cells in liquid culture. Data normalization for both pipelines is discussed.

  2. [Synthetic biology and rearrangements of microbial genetic material].

    Science.gov (United States)

    Liang, Quan-Feng; Wang, Qian; Qi, Qing-Sheng

    2011-10-01

    As an emerging discipline, synthetic biology has shown great scientific values and application prospects. Although there have been many reviews of various aspects on synthetic biology over the last years, this article, for the first time, attempted to discuss the relationship and difference between microbial genetics and synthetic biology. We summarized the recent development of synthetic biology in rearranging microbial genetic materials, including synthesis, design and reduction of genetic materials, standardization of genetic parts and modularization of genetic circuits. The relationship between synthetic biology and microbial genetic engineering was also discussed in the paper.

  3. Arrays of Synthetic Atoms: Nanocapacitor Batteries with Large Energy Density and Small Leak Currents

    Science.gov (United States)

    2017-11-28

    AFRL-RV-PS- AFRL-RV-PS- TR-2017-0169 TR-2017-0169 ARRAYS OF SYNTHETIC ATOMS: NANOCAPACITOR BATTERIES WITH LARGE ENERGY DENSITY AND SMALL LEAK...1-0247 Arrays of Synthetic Atoms: Nanocapacitor Batteries with Large Energy Density and Small Leak Currents 5b. GRANT NUMBER 5c. PROGRAM ELEMENT...large dielectric strength to a nanoscale rechargeable battery . We fabricated arrays of one-, two- and three-dimensional synthetic atoms and comparison

  4. Modularization of genetic elements promotes synthetic metabolic engineering.

    Science.gov (United States)

    Qi, Hao; Li, Bing-Zhi; Zhang, Wen-Qian; Liu, Duo; Yuan, Ying-Jin

    2015-11-15

    In the context of emerging synthetic biology, metabolic engineering is moving to the next stage powered by new technologies. Systematical modularization of genetic elements makes it more convenient to engineer biological systems for chemical production or other desired purposes. In the past few years, progresses were made in engineering metabolic pathway using synthetic biology tools. Here, we spotlighted the topic of implementation of modularized genetic elements in metabolic engineering. First, we overviewed the principle developed for modularizing genetic elements and then discussed how the genetic modules advanced metabolic engineering studies. Next, we picked up some milestones of engineered metabolic pathway achieved in the past few years. Last, we discussed the rapid raised synthetic biology field of "building a genome" and the potential in metabolic engineering. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Synthetic microfluidic paper: high surface area and high porosity polymer micropillar arrays.

    Science.gov (United States)

    Hansson, Jonas; Yasuga, Hiroki; Haraldsson, Tommy; van der Wijngaart, Wouter

    2016-01-21

    We introduce Synthetic Microfluidic Paper, a novel porous material for microfluidic applications that consists of an OSTE polymer that is photostructured in a well-controlled geometry of slanted and interlocked micropillars. We demonstrate the distinct benefits of Synthetic Microfluidic Paper over other porous microfluidic materials, such as nitrocellulose, traditional paper and straight micropillar arrays: in contrast to straight micropillar arrays, the geometry of Synthetic Microfluidic Paper was miniaturized without suffering capillary collapse during manufacturing and fluidic operation, resulting in a six-fold increased internal surface area and a three-fold increased porous fraction. Compared to commercial nitrocellulose materials for capillary assays, Synthetic Microfluidic Paper shows a wider range of capillary pumping speed and four times lower device-to-device variation. Compared to the surfaces of the other porous microfluidic materials that are modified by adsorption, Synthetic Microfluidic Paper contains free thiol groups and has been shown to be suitable for covalent surface chemistry, demonstrated here for increasing the material hydrophilicity. These results illustrate the potential of Synthetic Microfluidic Paper as a porous microfluidic material with improved performance characteristics, especially for bioassay applications such as diagnostic tests.

  6. Synthetic Genetic Targeting of Genome Instability in Cancer

    International Nuclear Information System (INIS)

    Sajesh, Babu V.; Guppy, Brent J.; McManus, Kirk J.

    2013-01-01

    Cancer is a leading cause of death throughout the World. A limitation of many current chemotherapeutic approaches is that their cytotoxic effects are not restricted to cancer cells, and adverse side effects can occur within normal tissues. Consequently, novel strategies are urgently needed to better target cancer cells. As we approach the era of personalized medicine, targeting the specific molecular defect(s) within a given patient’s tumor will become a more effective treatment strategy than traditional approaches that often target a given cancer type or sub-type. Synthetic genetic interactions are now being examined for their therapeutic potential and are designed to target the specific genetic and epigenetic phenomena associated with tumor formation, and thus are predicted to be highly selective. In general, two complementary approaches have been employed, including synthetic lethality and synthetic dosage lethality, to target aberrant expression and/or function associated with tumor suppressor genes and oncogenes, respectively. Here we discuss the concepts of synthetic lethality and synthetic dosage lethality, and explain three general experimental approaches designed to identify novel genetic interactors. We present examples and discuss the merits and caveats of each approach. Finally, we provide insight into the subsequent pre-clinical work required to validate novel candidate drug targets

  7. Three-dimensional real-time synthetic aperture imaging using a rotating phased array transducer

    DEFF Research Database (Denmark)

    Nikolov, Svetoslav; Dufait, Remi; Schoisswohl, Armin

    2002-01-01

    phased array, which is rotated over the volume of interest. The data is acquired using coded signals and synthetic transmit aperture imaging. Only one group of elements transmits at a time. The delays are set such as to form a cylindrical wave. The back-scattered signal carries information not only from......Current 3D real-time imaging is done either with sparse 2D arrays, or with mechanically moved phased arrays. The former results in a poor resolution and contrast due to a limited amount of elements. The latter has the disadvantage of low frame rates due to the sequential acquisition of the volume...... line-by-line and plane-by-plane. This paper describes an approach which combines mechanically moved phased array with synthetic transmit aperture imaging, resulting in high volume acquisition rates without a trade-off in image quality. The scan method uses a conventional fully populated 64 element...

  8. Rocking convex array used for 3D synthetic aperture focusing

    DEFF Research Database (Denmark)

    Andresen, Henrik; Nikolov, Svetoslav; Pedersen, M M

    2008-01-01

    Volumetric imaging can be performed using 1D arrays in combination with mechanical motion. Outside the elevation focus of the array, the resolution and contrast quickly degrade compared to the azimuth plane, because of the fixed transducer focus. The purpose of this paper is to use synthetic...... aperture focusing (SAF) for enhancing the elevation focusing for a convex rocking array, to obtain a more isotropic point spread function. This paper presents further development of the SAF method, which can be used with curved array combined with a rocking motion. The method uses a virtual source (VS...... Kretztechnik, Zipf, Austria). The array has an elevation focus at 60 mm of depth, and the angular rocking velocity is up to 140deg/s. The scan sequence uses an fprf of 4500 - 7000 Hz allowing up to 15 cm of penetration. The full width at half max (FWHM) and main-lobe to side-lobe ratio (MLSL) is used...

  9. Engineering genetic circuit interactions within and between synthetic minimal cells

    Science.gov (United States)

    Adamala, Katarzyna P.; Martin-Alarcon, Daniel A.; Guthrie-Honea, Katriona R.; Boyden, Edward S.

    2017-05-01

    Genetic circuits and reaction cascades are of great importance for synthetic biology, biochemistry and bioengineering. An open question is how to maximize the modularity of their design to enable the integration of different reaction networks and to optimize their scalability and flexibility. One option is encapsulation within liposomes, which enables chemical reactions to proceed in well-isolated environments. Here we adapt liposome encapsulation to enable the modular, controlled compartmentalization of genetic circuits and cascades. We demonstrate that it is possible to engineer genetic circuit-containing synthetic minimal cells (synells) to contain multiple-part genetic cascades, and that these cascades can be controlled by external signals as well as inter-liposomal communication without crosstalk. We also show that liposomes that contain different cascades can be fused in a controlled way so that the products of incompatible reactions can be brought together. Synells thus enable a more modular creation of synthetic biology cascades, an essential step towards their ultimate programmability.

  10. Three-Dimensional Synthetic Aperture Focusing Using a Rocking Convex Array Transducer

    DEFF Research Database (Denmark)

    Andresen, Henrik; Nikolov, Svetoslav; Pedersen, Mads Møller

    2010-01-01

    Volumetric imaging can be performed using 1-D arrays in combination with mechanical motion. Outside the elevation focus of the array, the resolution and contrast quickly degrade compared with the lateral plane, because of the fixed transducer focus. This paper shows the feasibility of using...... synthetic aperture focusing for enhancing the elevation focus for a convex rocking array. The method uses a virtual source (VS) for defocused multi-element transmit, and another VS in the elevation focus point. This allows a direct time-of-flight to be calculated for a given 3-D point. To avoid artifacts...... and increase SNR at the elevation VS, a plane-wave VS approach has been implemented. Simulations and measurements using an experimental scanner with a convex rocking array show an average improvement in resolution of 26% and 33%, respectively. This improvement is also seen in in vivo measurements...

  11. The population genetics of X-autosome synthetic lethals and steriles.

    Science.gov (United States)

    Lachance, Joseph; Johnson, Norman A; True, John R

    2011-11-01

    Epistatic interactions are widespread, and many of these interactions involve combinations of alleles at different loci that are deleterious when present in the same individual. The average genetic environment of sex-linked genes differs from that of autosomal genes, suggesting that the population genetics of interacting X-linked and autosomal alleles may be complex. Using both analytical theory and computer simulations, we analyzed the evolutionary trajectories and mutation-selection balance conditions for X-autosome synthetic lethals and steriles. Allele frequencies follow a set of fundamental trajectories, and incompatible alleles are able to segregate at much higher frequencies than single-locus expectations. Equilibria exist, and they can involve fixation of either autosomal or X-linked alleles. The exact equilibrium depends on whether synthetic alleles are dominant or recessive and whether fitness effects are seen in males, females, or both sexes. When single-locus fitness effects and synthetic incompatibilities are both present, population dynamics depend on the dominance of alleles and historical contingency (i.e., whether X-linked or autosomal mutations occur first). Recessive synthetic lethality can result in high-frequency X-linked alleles, and dominant synthetic lethality can result in high-frequency autosomal alleles. Many X-autosome incompatibilities in natural populations may be cryptic, appearing to be single-locus effects because one locus is fixed. We also discuss the implications of these findings with respect to standing genetic variation and the origins of Haldane's rule.

  12. Adaptive logical stochastic resonance in time-delayed synthetic genetic networks

    Science.gov (United States)

    Zhang, Lei; Zheng, Wenbin; Song, Aiguo

    2018-04-01

    In the paper, the concept of logical stochastic resonance is applied to implement logic operation and latch operation in time-delayed synthetic genetic networks derived from a bacteriophage λ. Clear logic operation and latch operation can be obtained when the network is tuned by modulated periodic force and time-delay. In contrast with the previous synthetic genetic networks based on logical stochastic resonance, the proposed system has two advantages. On one hand, adding modulated periodic force to the background noise can increase the length of the optimal noise plateau of obtaining desired logic response and make the system adapt to varying noise intensity. On the other hand, tuning time-delay can extend the optimal noise plateau to larger range. The result provides possible help for designing new genetic regulatory networks paradigm based on logical stochastic resonance.

  13. Cosmic non-TEM radiation and synthetic feed array sensor system in ASIC mixed signal technology

    Science.gov (United States)

    Centureli, F.; Scotti, G.; Tommasino, P.; Trifiletti, A.; Romano, F.; Cimmino, R.; Saitto, A.

    2014-08-01

    The paper deals with the opportunity to introduce "Not strictly TEM waves" Synthetic detection Method (NTSM), consisting in a Three Axis Digital Beam Processing (3ADBP), to enhance the performances of radio telescope and sensor systems. Current Radio Telescopes generally use the classic 3D "TEM waves" approximation Detection Method, which consists in a linear tomography process (Single or Dual axis beam forming processing) neglecting the small z component. The Synthetic FEED ARRAY three axis Sensor SYSTEM is an innovative technique using a synthetic detection of the generic "NOT strictly TEM Waves radiation coming from the Cosmo, which processes longitudinal component of Angular Momentum too. Than the simultaneous extraction from radiation of both the linear and quadratic information component, may reduce the complexity to reconstruct the Early Universe in the different requested scales. This next order approximation detection of the observed cosmologic processes, may improve the efficacy of the statistical numerical model used to elaborate the same information acquired. The present work focuses on detection of such waves at carrier frequencies in the bands ranging from LF to MMW. The work shows in further detail the new generation of on line programmable and reconfigurable Mixed Signal ASIC technology that made possible the innovative Synthetic Sensor. Furthermore the paper shows the ability of such technique to increase the Radio Telescope Array Antenna performances.

  14. 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.

  15. Synthetic alienation of microbial organisms by using genetic code engineering: Why and how?

    Science.gov (United States)

    Kubyshkin, Vladimir; Budisa, Nediljko

    2017-08-01

    The main goal of synthetic biology (SB) is the creation of biodiversity applicable for biotechnological needs, while xenobiology (XB) aims to expand the framework of natural chemistries with the non-natural building blocks in living cells to accomplish artificial biodiversity. Protein and proteome engineering, which overcome limitation of the canonical amino acid repertoire of 20 (+2) prescribed by the genetic code by using non-canonic amino acids (ncAAs), is one of the main focuses of XB research. Ideally, estranging the genetic code from its current form via systematic introduction of ncAAs should enable the development of bio-containment mechanisms in synthetic cells potentially endowing them with a "genetic firewall" i.e. orthogonality which prevents genetic information transfer to natural systems. Despite rapid progress over the past two decades, it is not yet possible to completely alienate an organism that would use and maintain different genetic code associations permanently. In order to engineer robust bio-contained life forms, the chemical logic behind the amino acid repertoire establishment should be considered. Starting from recent proposal of Hartman and Smith about the genetic code establishment in the RNA world, here the authors mapped possible biotechnological invasion points for engineering of bio-contained synthetic cells equipped with non-canonical functionalities. Copyright © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Real-time 3D imaging methods using 2D phased arrays based on synthetic focusing techniques.

    Science.gov (United States)

    Kim, Jung-Jun; Song, Tai-Kyong

    2008-07-01

    A fast 3D ultrasound imaging technique using a 2D phased array transducer based on the synthetic focusing method for nondestructive testing or medical imaging is proposed. In the proposed method, each column of a 2D array is fired successively to produce transverse fan beams focused at a fixed depth along a given longitudinal direction and the resulting pulse echoes are received at all elements of a 2D array used. After firing all column arrays, a frame of high-resolution image along a given longitudinal direction is obtained with dynamic focusing employed in the longitudinal direction on receive and in the transverse direction on both transmit and receive. The volume rate of the proposed method can be increased much higher than that of the conventional 2D array imaging by employing an efficient sparse array technique. A simple modification to the proposed method can further increase the volume scan rate significantly. The proposed methods are verified through computer simulations.

  17. Solving “Antenna Array Thinning Problem” Using Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    Rajashree Jain

    2012-01-01

    Full Text Available Thinning involves reducing total number of active elements in an antenna array without causing major degradation in system performance. Dynamic thinning is the process of achieving this under real-time conditions. It is required to find a strategic subset of antenna elements for thinning so as to have its optimum performance. From a mathematical perspective this is a nonlinear, multidimensional problem with multiple objectives and many constraints. Solution for such problem cannot be obtained by classical analytical techniques. It will be required to employ some type of search algorithm which can lead to a practical solution in an optimal. The present paper discusses an approach of using genetic algorithm for array thinning. After discussing the basic concept involving antenna array, array thinning, dynamic thinning, and application methodology, simulation results of applying the technique to linear and planar arrays are presented.

  18. A Unifying Mathematical Framework for Genetic Robustness, Environmental Robustness, Network Robustness and their Trade-offs on Phenotype Robustness in Biological Networks. Part III: Synthetic Gene Networks in Synthetic Biology

    Science.gov (United States)

    Chen, Bor-Sen; Lin, Ying-Po

    2013-01-01

    Robust stabilization and environmental disturbance attenuation are ubiquitous systematic properties that are observed in biological systems at many different levels. The underlying principles for robust stabilization and environmental disturbance attenuation are universal to both complex biological systems and sophisticated engineering systems. In many biological networks, network robustness should be large enough to confer: intrinsic robustness for tolerating intrinsic parameter fluctuations; genetic robustness for buffering genetic variations; and environmental robustness for resisting environmental disturbances. Network robustness is needed so phenotype stability of biological network can be maintained, guaranteeing phenotype robustness. Synthetic biology is foreseen to have important applications in biotechnology and medicine; it is expected to contribute significantly to a better understanding of functioning of complex biological systems. This paper presents a unifying mathematical framework for investigating the principles of both robust stabilization and environmental disturbance attenuation for synthetic gene networks in synthetic biology. Further, from the unifying mathematical framework, we found that the phenotype robustness criterion for synthetic gene networks is the following: if intrinsic robustness + genetic robustness + environmental robustness ≦ network robustness, then the phenotype robustness can be maintained in spite of intrinsic parameter fluctuations, genetic variations, and environmental disturbances. Therefore, the trade-offs between intrinsic robustness, genetic robustness, environmental robustness, and network robustness in synthetic biology can also be investigated through corresponding phenotype robustness criteria from the systematic point of view. Finally, a robust synthetic design that involves network evolution algorithms with desired behavior under intrinsic parameter fluctuations, genetic variations, and environmental

  19. 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.

  20. Alternative Watson-Crick Synthetic Genetic Systems.

    Science.gov (United States)

    Benner, Steven A; Karalkar, Nilesh B; Hoshika, Shuichi; Laos, Roberto; Shaw, Ryan W; Matsuura, Mariko; Fajardo, Diego; Moussatche, Patricia

    2016-11-01

    In its "grand challenge" format in chemistry, "synthesis" as an activity sets out a goal that is substantially beyond current theoretical and technological capabilities. In pursuit of this goal, scientists are forced across uncharted territory, where they must answer unscripted questions and solve unscripted problems, creating new theories and new technologies in ways that would not be created by hypothesis-directed research. Thus, synthesis drives discovery and paradigm changes in ways that analysis cannot. Described here are the products that have arisen so far through the pursuit of one grand challenge in synthetic biology: Recreate the genetics, catalysis, evolution, and adaptation that we value in life, but using genetic and catalytic biopolymers different from those that have been delivered to us by natural history on Earth. The outcomes in technology include new diagnostic tools that have helped personalize the care of hundreds of thousands of patients worldwide. In science, the effort has generated a fundamentally different view of DNA, RNA, and how they work. Copyright © 2016 Cold Spring Harbor Laboratory Press; all rights reserved.

  1. Genetic Diversity of Turf-Type Tall Fescue Using Diversity Arrays Technology

    Czech Academy of Sciences Publication Activity Database

    Baird, J. H.; Kopecký, David; Lukaszewski, A.J.; Green, R. J.; Bartoš, Jan; Doležel, Jaroslav

    2012-01-01

    Roč. 52, č. 1 (2012), s. 408-412 ISSN 0011-183X Institutional research plan: CEZ:AV0Z50380511 Keywords : Festuca arundinacea * Diversity Arrays Technology (DArT) * Low genetic polymorphism Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.513, year: 2012

  2. Biocontainment of genetically modified organisms by synthetic protein design

    Science.gov (United States)

    Mandell, Daniel J.; Lajoie, Marc J.; Mee, Michael T.; Takeuchi, Ryo; Kuznetsov, Gleb; Norville, Julie E.; Gregg, Christopher J.; Stoddard, Barry L.; Church, George M.

    2015-02-01

    Genetically modified organisms (GMOs) are increasingly deployed at large scales and in open environments. Genetic biocontainment strategies are needed to prevent unintended proliferation of GMOs in natural ecosystems. Existing biocontainment methods are insufficient because they impose evolutionary pressure on the organism to eject the safeguard by spontaneous mutagenesis or horizontal gene transfer, or because they can be circumvented by environmentally available compounds. Here we computationally redesign essential enzymes in the first organism possessing an altered genetic code (Escherichia coli strain C321.ΔA) to confer metabolic dependence on non-standard amino acids for survival. The resulting GMOs cannot metabolically bypass their biocontainment mechanisms using known environmental compounds, and they exhibit unprecedented resistance to evolutionary escape through mutagenesis and horizontal gene transfer. This work provides a foundation for safer GMOs that are isolated from natural ecosystems by a reliance on synthetic metabolites.

  3. Molecular analysis of genetic diversity in elite II synthetic hexaploid ...

    African Journals Online (AJOL)

    The present study was conducted to assess the genetic diversity of Elite-II synthetic hexaploid (SH) wheat by genome DNA fingerprinting as revealed by random amplified polymorphic DNA (RAPD) analysis. Ten decamer RAPD primers (OPG-1, OPG-2, OPG-3, OPG-4, OPG-5, OPA-3, OPA-4, OPA-5, OPA-8, and OPA-15) ...

  4. Oligonucleotide arrays vs. metaphase-comparative genomic hybridisation and BAC arrays for single-cell analysis: first applications to preimplantation genetic diagnosis for Robertsonian translocation carriers.

    Science.gov (United States)

    Ramos, Laia; del Rey, Javier; Daina, Gemma; García-Aragonés, Manel; Armengol, Lluís; Fernandez-Encinas, Alba; Parriego, Mònica; Boada, Montserrat; Martinez-Passarell, Olga; Martorell, Maria Rosa; Casagran, Oriol; Benet, Jordi; Navarro, Joaquima

    2014-01-01

    Comprehensive chromosome analysis techniques such as metaphase-Comparative Genomic Hybridisation (CGH) and array-CGH are available for single-cell analysis. However, while metaphase-CGH and BAC array-CGH have been widely used for Preimplantation Genetic Diagnosis, oligonucleotide array-CGH has not been used in an extensive way. A comparison between oligonucleotide array-CGH and metaphase-CGH has been performed analysing 15 single fibroblasts from aneuploid cell-lines and 18 single blastomeres from human cleavage-stage embryos. Afterwards, oligonucleotide array-CGH and BAC array-CGH were also compared analysing 16 single blastomeres from human cleavage-stage embryos. All three comprehensive analysis techniques provided broadly similar cytogenetic profiles; however, non-identical profiles appeared when extensive aneuploidies were present in a cell. Both array techniques provided an optimised analysis procedure and a higher resolution than metaphase-CGH. Moreover, oligonucleotide array-CGH was able to define extra segmental imbalances in 14.7% of the blastomeres and it better determined the specific unbalanced chromosome regions due to a higher resolution of the technique (≈ 20 kb). Applicability of oligonucleotide array-CGH for Preimplantation Genetic Diagnosis has been demonstrated in two cases of Robertsonian translocation carriers 45,XY,der(13;14)(q10;q10). Transfer of euploid embryos was performed in both cases and pregnancy was achieved by one of the couples. This is the first time that an oligonucleotide array-CGH approach has been successfully applied to Preimplantation Genetic Diagnosis for balanced chromosome rearrangement carriers.

  5. Oligonucleotide arrays vs. metaphase-comparative genomic hybridisation and BAC arrays for single-cell analysis: first applications to preimplantation genetic diagnosis for Robertsonian translocation carriers.

    Directory of Open Access Journals (Sweden)

    Laia Ramos

    Full Text Available Comprehensive chromosome analysis techniques such as metaphase-Comparative Genomic Hybridisation (CGH and array-CGH are available for single-cell analysis. However, while metaphase-CGH and BAC array-CGH have been widely used for Preimplantation Genetic Diagnosis, oligonucleotide array-CGH has not been used in an extensive way. A comparison between oligonucleotide array-CGH and metaphase-CGH has been performed analysing 15 single fibroblasts from aneuploid cell-lines and 18 single blastomeres from human cleavage-stage embryos. Afterwards, oligonucleotide array-CGH and BAC array-CGH were also compared analysing 16 single blastomeres from human cleavage-stage embryos. All three comprehensive analysis techniques provided broadly similar cytogenetic profiles; however, non-identical profiles appeared when extensive aneuploidies were present in a cell. Both array techniques provided an optimised analysis procedure and a higher resolution than metaphase-CGH. Moreover, oligonucleotide array-CGH was able to define extra segmental imbalances in 14.7% of the blastomeres and it better determined the specific unbalanced chromosome regions due to a higher resolution of the technique (≈ 20 kb. Applicability of oligonucleotide array-CGH for Preimplantation Genetic Diagnosis has been demonstrated in two cases of Robertsonian translocation carriers 45,XY,der(13;14(q10;q10. Transfer of euploid embryos was performed in both cases and pregnancy was achieved by one of the couples. This is the first time that an oligonucleotide array-CGH approach has been successfully applied to Preimplantation Genetic Diagnosis for balanced chromosome rearrangement carriers.

  6. Oligonucleotide Arrays vs. Metaphase-Comparative Genomic Hybridisation and BAC Arrays for Single-Cell Analysis: First Applications to Preimplantation Genetic Diagnosis for Robertsonian Translocation Carriers

    Science.gov (United States)

    Ramos, Laia; del Rey, Javier; Daina, Gemma; García-Aragonés, Manel; Armengol, Lluís; Fernandez-Encinas, Alba; Parriego, Mònica; Boada, Montserrat; Martinez-Passarell, Olga; Martorell, Maria Rosa; Casagran, Oriol; Benet, Jordi; Navarro, Joaquima

    2014-01-01

    Comprehensive chromosome analysis techniques such as metaphase-Comparative Genomic Hybridisation (CGH) and array-CGH are available for single-cell analysis. However, while metaphase-CGH and BAC array-CGH have been widely used for Preimplantation Genetic Diagnosis, oligonucleotide array-CGH has not been used in an extensive way. A comparison between oligonucleotide array-CGH and metaphase-CGH has been performed analysing 15 single fibroblasts from aneuploid cell-lines and 18 single blastomeres from human cleavage-stage embryos. Afterwards, oligonucleotide array-CGH and BAC array-CGH were also compared analysing 16 single blastomeres from human cleavage-stage embryos. All three comprehensive analysis techniques provided broadly similar cytogenetic profiles; however, non-identical profiles appeared when extensive aneuploidies were present in a cell. Both array techniques provided an optimised analysis procedure and a higher resolution than metaphase-CGH. Moreover, oligonucleotide array-CGH was able to define extra segmental imbalances in 14.7% of the blastomeres and it better determined the specific unbalanced chromosome regions due to a higher resolution of the technique (≈20 kb). Applicability of oligonucleotide array-CGH for Preimplantation Genetic Diagnosis has been demonstrated in two cases of Robertsonian translocation carriers 45,XY,der(13;14)(q10;q10). Transfer of euploid embryos was performed in both cases and pregnancy was achieved by one of the couples. This is the first time that an oligonucleotide array-CGH approach has been successfully applied to Preimplantation Genetic Diagnosis for balanced chromosome rearrangement carriers. PMID:25415307

  7. Persistency of Prediction Accuracy and Genetic Gain in Synthetic Populations Under Recurrent Genomic Selection

    Directory of Open Access Journals (Sweden)

    Dominik Müller

    2017-03-01

    Full Text Available Recurrent selection (RS has been used in plant breeding to successively improve synthetic and other multiparental populations. Synthetics are generated from a limited number of parents ( Np , but little is known about how Np affects genomic selection (GS in RS, especially the persistency of prediction accuracy (rg , g ^ and genetic gain. Synthetics were simulated by intermating Np= 2–32 parent lines from an ancestral population with short- or long-range linkage disequilibrium (LDA and subjected to multiple cycles of GS. We determined rg , g ^ and genetic gain across 30 cycles for different training set (TS sizes, marker densities, and generations of recombination before model training. Contributions to rg , g ^ and genetic gain from pedigree relationships, as well as from cosegregation and LDA between QTL and markers, were analyzed via four scenarios differing in (i the relatedness between TS and selection candidates and (ii whether selection was based on markers or pedigree records. Persistency of rg , g ^ was high for small Np , where predominantly cosegregation contributed to rg , g ^ , but also for large Np , where LDA replaced cosegregation as the dominant information source. Together with increasing genetic variance, this compensation resulted in relatively constant long- and short-term genetic gain for increasing Np > 4, given long-range LDA in the ancestral population. Although our scenarios suggest that information from pedigree relationships contributed to rg , g ^ for only very few generations in GS, we expect a longer contribution than in pedigree BLUP, because capturing Mendelian sampling by markers reduces selective pressure on pedigree relationships. Larger TS size (NTS and higher marker density improved persistency of rg , g ^ and hence genetic gain, but additional recombinations could not increase genetic gain.

  8. The Contribution of Genetic Recombination to CRISPR Array Evolution.

    Science.gov (United States)

    Kupczok, Anne; Landan, Giddy; Dagan, Tal

    2015-06-16

    CRISPR (clustered regularly interspaced short palindromic repeats) is a microbial immune system against foreign DNA. Recognition sequences (spacers) encoded within the CRISPR array mediate the immune reaction in a sequence-specific manner. The known mechanisms for the evolution of CRISPR arrays include spacer acquisition from foreign DNA elements at the time of invasion and array erosion through spacer deletion. Here, we consider the contribution of genetic recombination between homologous CRISPR arrays to the evolution of spacer repertoire. Acquisition of spacers from exogenic arrays via recombination may confer the recipient with immunity against unencountered antagonists. For this purpose, we develop a novel method for the detection of recombination in CRISPR arrays by modeling the spacer order in arrays from multiple strains from the same species. Because the evolutionary signal of spacer recombination may be similar to that of pervasive spacer deletions or independent spacer acquisition, our method entails a robustness analysis of the recombination inference by a statistical comparison to resampled and perturbed data sets. We analyze CRISPR data sets from four bacterial species: two Gammaproteobacteria species harboring CRISPR type I and two Streptococcus species harboring CRISPR type II loci. We find that CRISPR array evolution in Escherichia coli and Streptococcus agalactiae can be explained solely by vertical inheritance and differential spacer deletion. In Pseudomonas aeruginosa, we find an excess of single spacers potentially incorporated into the CRISPR locus during independent acquisition events. In Streptococcus thermophilus, evidence for spacer acquisition by recombination is present in 5 out of 70 strains. Genetic recombination has been proposed to accelerate adaptation by combining beneficial mutations that arose in independent lineages. However, for most species under study, we find that CRISPR evolution is shaped mainly by spacer acquisition and

  9. Computational Re-design of Synthetic Genetic Oscillators for Independent Amplitude and Frequency Modulation.

    Science.gov (United States)

    Tomazou, Marios; Barahona, Mauricio; Polizzi, Karen M; Stan, Guy-Bart

    2018-04-25

    To perform well in biotechnology applications, synthetic genetic oscillators must be engineered to allow independent modulation of amplitude and period. This need is currently unmet. Here, we demonstrate computationally how two classic genetic oscillators, the dual-feedback oscillator and the repressilator, can be re-designed to provide independent control of amplitude and period and improve tunability-that is, a broad dynamic range of periods and amplitudes accessible through the input "dials." Our approach decouples frequency and amplitude modulation by incorporating an orthogonal "sink module" where the key molecular species are channeled for enzymatic degradation. This sink module maintains fast oscillation cycles while alleviating the translational coupling between the oscillator's transcription factors and output. We characterize the behavior of our re-designed oscillators over a broad range of physiologically reasonable parameters, explain why this facilitates broader function and control, and provide general design principles for building synthetic genetic oscillators that are more precisely controllable. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  10. A semi-supervised learning approach to predict synthetic genetic interactions by combining functional and topological properties of functional gene network

    Directory of Open Access Journals (Sweden)

    Han Kyungsook

    2010-06-01

    Full Text Available Abstract Background Genetic interaction profiles are highly informative and helpful for understanding the functional linkages between genes, and therefore have been extensively exploited for annotating gene functions and dissecting specific pathway structures. However, our understanding is rather limited to the relationship between double concurrent perturbation and various higher level phenotypic changes, e.g. those in cells, tissues or organs. Modifier screens, such as synthetic genetic arrays (SGA can help us to understand the phenotype caused by combined gene mutations. Unfortunately, exhaustive tests on all possible combined mutations in any genome are vulnerable to combinatorial explosion and are infeasible either technically or financially. Therefore, an accurate computational approach to predict genetic interaction is highly desirable, and such methods have the potential of alleviating the bottleneck on experiment design. Results In this work, we introduce a computational systems biology approach for the accurate prediction of pairwise synthetic genetic interactions (SGI. First, a high-coverage and high-precision functional gene network (FGN is constructed by integrating protein-protein interaction (PPI, protein complex and gene expression data; then, a graph-based semi-supervised learning (SSL classifier is utilized to identify SGI, where the topological properties of protein pairs in weighted FGN is used as input features of the classifier. We compare the proposed SSL method with the state-of-the-art supervised classifier, the support vector machines (SVM, on a benchmark dataset in S. cerevisiae to validate our method's ability to distinguish synthetic genetic interactions from non-interaction gene pairs. Experimental results show that the proposed method can accurately predict genetic interactions in S. cerevisiae (with a sensitivity of 92% and specificity of 91%. Noticeably, the SSL method is more efficient than SVM, especially for

  11. Synthetic focused array of electrical prospecting using pole-pole array potential data; Sanjigen denki tansaho ni okeru nikyokuho den`i data wo mochiita denryu shusoku haichi no goseiho

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, K [Central Research Institute of Electric Power Industry, Tokyo (Japan)

    1997-10-22

    Various methods have been put into practice for the conventional two-dimensional pole configuration using a single line in three-dimensional electrical prospecting. Pole configuration effective for the three-dimensional exploration has not been investigated. This paper describes synthetic focused array using four pairs of guarded poles based on pole-pole array potential data in the case of arrangement of measuring points on a grid. Results of the numerical simulation are also described. For the focused array, laterolog of electrical logging is applied to the surface prospecting. Directivity can be given to the current from the main pole by controlling the current from guarded pole. It was found from the simulation that the resistivity anomaly is concentrated directly on the embedded ball for the focused array rather than for the pole-pole array. It was also found that two conductive balls can be clearly separated for the focused array rather than for the dipole-dipole array. Accordingly, it was considered that results approximating the original structures can be obtained by analyzing using the both arrays. 5 refs., 6 figs.

  12. Persistency of Prediction Accuracy and Genetic Gain in Synthetic Populations Under Recurrent Genomic Selection.

    Science.gov (United States)

    Müller, Dominik; Schopp, Pascal; Melchinger, Albrecht E

    2017-03-10

    Recurrent selection (RS) has been used in plant breeding to successively improve synthetic and other multiparental populations. Synthetics are generated from a limited number of parents [Formula: see text] but little is known about how [Formula: see text] affects genomic selection (GS) in RS, especially the persistency of prediction accuracy ([Formula: see text]) and genetic gain. Synthetics were simulated by intermating [Formula: see text]= 2-32 parent lines from an ancestral population with short- or long-range linkage disequilibrium ([Formula: see text]) and subjected to multiple cycles of GS. We determined [Formula: see text] and genetic gain across 30 cycles for different training set ( TS ) sizes, marker densities, and generations of recombination before model training. Contributions to [Formula: see text] and genetic gain from pedigree relationships, as well as from cosegregation and [Formula: see text] between QTL and markers, were analyzed via four scenarios differing in (i) the relatedness between TS and selection candidates and (ii) whether selection was based on markers or pedigree records. Persistency of [Formula: see text] was high for small [Formula: see text] where predominantly cosegregation contributed to [Formula: see text], but also for large [Formula: see text] where [Formula: see text] replaced cosegregation as the dominant information source. Together with increasing genetic variance, this compensation resulted in relatively constant long- and short-term genetic gain for increasing [Formula: see text] > 4, given long-range LD A in the ancestral population. Although our scenarios suggest that information from pedigree relationships contributed to [Formula: see text] for only very few generations in GS, we expect a longer contribution than in pedigree BLUP, because capturing Mendelian sampling by markers reduces selective pressure on pedigree relationships. Larger TS size ([Formula: see text]) and higher marker density improved persistency 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. GOLD MINERAL PROSPECTING USING PHASED ARRAY TYPE L-BAND SYNTHETIC APERTURE RADAR (PALSAR SATELLITE REMOTE SENSING DATA, CENTRAL GOLD BELT, MALAYSIA

    Directory of Open Access Journals (Sweden)

    A. Beiranvand Pour

    2016-06-01

    Full Text Available The Bentong-Raub Suture Zone (BRSZ of Peninsular Malaysia is one of the significant structural zones in Sundaland, Southeast Asia. It forms the boundary between the Gondwana-derived Sibumasu terrane in the west and Sukhothai arc in the east. The BRSZ is also genetically related to the sediment-hosted/orogenic gold deposits associated with the major lineaments and form-lines in the central gold belt Central Gold Belt of Peninsular Malaysia. In tropical environments, heavy tropical rainforest and intense weathering makes it impossible to map geological structures over long distances. Advances in remote sensing technology allow the application of Synthetic Aperture Radar (SAR data in geological structural analysis for tropical environments. In this investigation, the Phased Array type L-band Synthetic Aperture Radar (PALSAR satellite remote sensing data were used to analyse major geological structures in Peninsular Malaysia and provide detailed characterization of lineaments and form-lines in the BRSZ, as well as its implication for sediment-hosted/orogenic gold exploration in tropical environments. The major geological structure directions of the BRSZ are N-S, NNE-SSW, NE-SW and NW-SE, which derived from directional filtering analysis to PALSAR data. The pervasive array of N-S faults in the study area and surrounding terrain is mainly linked to the N-S trending of the Suture Zone. N-S striking lineaments are often cut by younger NE-SW and NW-SE-trending lineaments. Gold mineralized trends lineaments are associated with the intersection of N-S, NE-SW, NNW-SSE and ESE-WNW faults and curvilinear features in shearing and alteration zones. Lineament analysis on PALSAR satellite remote sensing data is a useful tool for detecting the boundary between the Gondwana-derived terranes and major geological features associated with suture zone especially for large inaccessible regions in tropical environments.

  15. Performance of Narrowband Signal Detection under Correlated Rayleigh Fading Based on Synthetic Array

    Directory of Open Access Journals (Sweden)

    Ali Broumandan

    2009-01-01

    design parameters of probability of detection (Pd and probability of false alarm (Pfa. An optimum detector based on Estimator-Correlator (EC is developed, and its performance is compared with that of suboptimal Equal-Gain (EG combiner in different channel correlation scenarios. It is shown that in moderate channel correlation scenarios the detection performance of EC and EG is identical. The sensitivity of the proposed method to knowledge of motion parameters is also investigated. An extensive set of measurements based on CDMA-2000 pilot signals using the static antenna and synthetic array are used to experimentally verify these theoretical findings.

  16. The control effect in a detached laminar boundary layer of an array of normal synthetic jets

    Science.gov (United States)

    Valenzuela Calva, Fernando; Avila Rodriguez, Ruben

    2016-11-01

    In this work, 3D numerical simulations of an array of three normal circular synthetic jets embedded in an attached laminar boundary layer that separates under the influence of an inclined flap are performed for flow separation control. At the beginning of the present study, three cases are used to validate the numerical simulation with data obtained from experiments. The experimental data is chosen based on the cases which presented higher repeatability and reliability. Simulations showed reasonable agreement when compared with experiments. The simulations are undertaken at three synthetic jet operating conditions, i.e. Case A: L = 2, VR = 0.32; Case B: L = 4, VR = 0.64 and Case C: L = 6, VR = 0.96. The vortical structures produced for each synthetic jet operating condition are hairpin vortices for Case A and tilted vortices for Case B and C, respectively. By examining the spatial wall shear stress variations, the effect on the boundary layer prior to separation of the middle synthetic jet is evaluated. For effective flow control, produced at a relatively low the finding from this study suggests that hairpin vortical structures are more desirable structures. Universidad Nacional Autonoma de Mexico.

  17. 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.

  18. Robust synchronization control scheme of a population of nonlinear stochastic synthetic genetic oscillators under intrinsic and extrinsic molecular noise via quorum sensing.

    Science.gov (United States)

    Chen, Bor-Sen; Hsu, Chih-Yuan

    2012-10-26

    Collective rhythms of gene regulatory networks have been a subject of considerable interest for biologists and theoreticians, in particular the synchronization of dynamic cells mediated by intercellular communication. Synchronization of a population of synthetic genetic oscillators is an important design in practical applications, because such a population distributed over different host cells needs to exploit molecular phenomena simultaneously in order to emerge a biological phenomenon. However, this synchronization may be corrupted by intrinsic kinetic parameter fluctuations and extrinsic environmental molecular noise. Therefore, robust synchronization is an important design topic in nonlinear stochastic coupled synthetic genetic oscillators with intrinsic kinetic parameter fluctuations and extrinsic molecular noise. Initially, the condition for robust synchronization of synthetic genetic oscillators was derived based on Hamilton Jacobi inequality (HJI). We found that if the synchronization robustness can confer enough intrinsic robustness to tolerate intrinsic parameter fluctuation and extrinsic robustness to filter the environmental noise, then robust synchronization of coupled synthetic genetic oscillators is guaranteed. If the synchronization robustness of a population of nonlinear stochastic coupled synthetic genetic oscillators distributed over different host cells could not be maintained, then robust synchronization could be enhanced by external control input through quorum sensing molecules. In order to simplify the analysis and design of robust synchronization of nonlinear stochastic synthetic genetic oscillators, the fuzzy interpolation method was employed to interpolate several local linear stochastic coupled systems to approximate the nonlinear stochastic coupled system so that the HJI-based synchronization design problem could be replaced by a simple linear matrix inequality (LMI)-based design problem, which could be solved with the help of LMI

  19. Design of Circularly-Polarised, Crossed Drooping Dipole, Phased Array Antenna Using Genetic Algorithm Optimisation

    DEFF Research Database (Denmark)

    Larsen, Niels Vesterdal

    2007-01-01

    A printed drooping dipole array is designed and constructed. The design is based on a genetic algorithm optimisation procedure used in conjunction with the software programme AWAS. By optimising the array G/T for specific combinations of scan angles and frequencies an optimum design is obtained...

  20. Comparison between fluorescent in-situ hybridisation and array comparative genomic hybridisation in preimplantation genetic diagnosis in translocation carriers.

    Science.gov (United States)

    Lee, Vivian C Y; Chow, Judy F C; Lau, Estella Y L; Yeung, William S B; Ho, P C; Ng, Ernest H Y

    2015-02-01

    To compare the pregnancy outcome of the fluorescent in-situ hybridisation and array comparative genomic hybridisation in preimplantation genetic diagnosis of translocation carriers. Historical cohort. A teaching hospital in Hong Kong. All preimplantation genetic diagnosis treatment cycles performed for translocation carriers from 2001 to 2013. Overall, 101 treatment cycles for preimplantation genetic diagnosis in translocation were included: 77 cycles for reciprocal translocation and 24 cycles for Robertsonian translocation. Fluorescent in-situ hybridisation and array comparative genomic hybridisation were used in 78 and 11 cycles, respectively. The ongoing pregnancy rate per initiated cycle after array comparative genomic hybridisation was significantly higher than that after fluorescent in-situ hybridisation in all translocation carriers (36.4% vs 9.0%; P=0.010). The miscarriage rate was comparable with both techniques. The testing method (array comparative genomic hybridisation or fluorescent in-situ hybridisation) was the only significant factor affecting the ongoing pregnancy rate after controlling for the women's age, type of translocation, and clinical information of the preimplantation genetic diagnosis cycles by logistic regression (odds ratio=1.875; P=0.023; 95% confidence interval, 1.090-3.226). This local retrospective study confirmed that comparative genomic hybridisation is associated with significantly higher pregnancy rates versus fluorescent in-situ hybridisation in translocation carriers. Array comparative genomic hybridisation should be the technique of choice in preimplantation genetic diagnosis cycles in translocation carriers.

  1. Sweet Spot Control of 1:2 Array Antenna using A Modified Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    Kyo-Hwan HYUN

    2007-10-01

    Full Text Available This paper presents a novel scheme that quickly searches for the sweet spot of 1:2 array antennas, and locks on to it for high-speed millimeter wavelength transmissions, when communications to another antenna array are disconnected. The proposed method utilizes a modified genetic algorithm, which selects a superior initial group through preprocessing in order to solve the local solution in a genetic algorithm. TDD (Time Division Duplex is utilized as the transfer method and data controller for the antenna. Once the initial communication is completed for the specific number of individuals, no longer antenna's data will be transmitted until each station processes GA in order to produce the next generation. After reproduction, individuals of the next generation become the data, and communication between each station is made again. The simulation results of 1:1, 1:2 array antennas, and experiment results of 1:1 array antenna confirmed the efficiency of the proposed method. The bit of gene is each 8bit, 16bit and 16bit split gene. 16bit split has similar performance as 16bit gene, but the gene of antenna is 8bit.

  2. Genetic interaction motif finding by expectation maximization – a novel statistical model for inferring gene modules from synthetic lethality

    Directory of Open Access Journals (Sweden)

    Ye Ping

    2005-12-01

    Full Text Available Abstract Background Synthetic lethality experiments identify pairs of genes with complementary function. More direct functional associations (for example greater probability of membership in a single protein complex may be inferred between genes that share synthetic lethal interaction partners than genes that are directly synthetic lethal. Probabilistic algorithms that identify gene modules based on motif discovery are highly appropriate for the analysis of synthetic lethal genetic interaction data and have great potential in integrative analysis of heterogeneous datasets. Results We have developed Genetic Interaction Motif Finding (GIMF, an algorithm for unsupervised motif discovery from synthetic lethal interaction data. Interaction motifs are characterized by position weight matrices and optimized through expectation maximization. Given a seed gene, GIMF performs a nonlinear transform on the input genetic interaction data and automatically assigns genes to the motif or non-motif category. We demonstrate the capacity to extract known and novel pathways for Saccharomyces cerevisiae (budding yeast. Annotations suggested for several uncharacterized genes are supported by recent experimental evidence. GIMF is efficient in computation, requires no training and automatically down-weights promiscuous genes with high degrees. Conclusion GIMF effectively identifies pathways from synthetic lethality data with several unique features. It is mostly suitable for building gene modules around seed genes. Optimal choice of one single model parameter allows construction of gene networks with different levels of confidence. The impact of hub genes the generic probabilistic framework of GIMF may be used to group other types of biological entities such as proteins based on stochastic motifs. Analysis of the strongest motifs discovered by the algorithm indicates that synthetic lethal interactions are depleted between genes within a motif, suggesting that synthetic

  3. Genetic diagnosis of familial hypercholesterolemia using a DNA-array based platform

    NARCIS (Netherlands)

    Alonso, Rodrigo; Defesche, Joep C.; Tejedor, Diego; Castillo, Sergio; Stef, Marianne; Mata, Nelva; Gomez-Enterria, Pilar; Martinez-Faedo, Ceferino; Forga, Lluis; Mata, Pedro

    2009-01-01

    The aim of this study was to validate the Lipochip genetic diagnostic platform by assessing effectiveness, sensitivity, specificity and costs for the identification of patients with familial hypercholesterolemia (FH) in Spain. This platform includes the use of a DNA micro array, the detection of

  4. An Optimal DEM Reconstruction Method for Linear Array Synthetic Aperture Radar Based on Variational Model

    Directory of Open Access Journals (Sweden)

    Shi Jun

    2015-02-01

    Full Text Available Downward-looking Linear Array Synthetic Aperture Radar (LASAR has many potential applications in the topographic mapping, disaster monitoring and reconnaissance applications, especially in the mountainous area. However, limited by the sizes of platforms, its resolution in the linear array direction is always far lower than those in the range and azimuth directions. This disadvantage leads to the blurring of Three-Dimensional (3D images in the linear array direction, and restricts the application of LASAR. To date, the research on 3D SAR image enhancement has focused on the sparse recovery technique. In this case, the one-to-one mapping of Digital Elevation Model (DEM brakes down. To overcome this, an optimal DEM reconstruction method for LASAR based on the variational model is discussed in an effort to optimize the DEM and the associated scattering coefficient map, and to minimize the Mean Square Error (MSE. Using simulation experiments, it is found that the variational model is more suitable for DEM enhancement applications to all kinds of terrains compared with the Orthogonal Matching Pursuit (OMPand Least Absolute Shrinkage and Selection Operator (LASSO methods.

  5. Diversity arrays technology (DArT) markers in apple for genetic linkage maps

    OpenAIRE

    Schouten, H.J.; Weg, van de, W.E.; Carling, J.; Khan, S.A.; McKay, S.J.; Kaauwen, van, M.P.W.

    2012-01-01

    Diversity Arrays Technology (DArT) provides a high-throughput whole-genome genotyping platform for the detection and scoring of hundreds of polymorphic loci without any need for prior sequence information. The work presented here details the development and performance of a DArT genotyping array for apple. This is the first paper on DArT in horticultural trees. Genetic mapping of DArT markers in two mapping populations and their integration with other marker types showed that DArT is a powerf...

  6. Diversity arrays technology (DArT) markers in apple for genetic linkage maps

    OpenAIRE

    Schouten, Henk J.; van de Weg, W. Eric; Carling, Jason; Khan, Sabaz Ali; McKay, Steven J.; van Kaauwen, Martijn P. W.; Wittenberg, Alexander H. J.; Koehorst-van Putten, Herma J. J.; Noordijk, Yolanda; Gao, Zhongshan; Rees, D. Jasper G.; Van Dyk, Maria M.; Jaccoud, Damian; Considine, Michael J.; Kilian, Andrzej

    2011-01-01

    Diversity Arrays Technology (DArT) provides a high-throughput whole-genome genotyping platform for the detection and scoring of hundreds of polymorphic loci without any need for prior sequence information. The work presented here details the development and performance of a DArT genotyping array for apple. This is the first paper on DArT in horticultural trees. Genetic mapping of DArT markers in two mapping populations and their integration with other marker types showed that DArT is a powerf...

  7. A novel method to design sparse linear arrays for ultrasonic phased array.

    Science.gov (United States)

    Yang, Ping; Chen, Bin; Shi, Ke-Ren

    2006-12-22

    In ultrasonic phased array testing, a sparse array can increase the resolution by enlarging the aperture without adding system complexity. Designing a sparse array involves choosing the best or a better configuration from a large number of candidate arrays. We firstly designed sparse arrays by using a genetic algorithm, but found that the arrays have poor performance and poor consistency. So, a method based on the Minimum Redundancy Linear Array was then adopted. Some elements are determined by the minimum-redundancy array firstly in order to ensure spatial resolution and then a genetic algorithm is used to optimize the remaining elements. Sparse arrays designed by this method have much better performance and consistency compared to the arrays designed only by a genetic algorithm. Both simulation and experiment confirm the effectiveness.

  8. Genetic control of mammalian T-cell proliferation with synthetic RNA regulatory systems

    OpenAIRE

    Chen, Yvonne Y.; Jensen, Michael C.; Smolke, Christina D.

    2010-01-01

    RNA molecules perform diverse regulatory functions in natural biological systems, and numerous synthetic RNA-based control devices that integrate sensing and gene-regulatory functions have been demonstrated, predominantly in bacteria and yeast. Despite potential advantages of RNA-based genetic control strategies in clinical applications, there has been limited success in extending engineered RNA devices to mammalian gene-expression control and no example of their application to functional res...

  9. 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.

  10. Genetic analysis of presbycusis by arrayed primer extension.

    Science.gov (United States)

    Rodriguez-Paris, Juan; Ballay, Charles; Inserra, Michelle; Stidham, Katrina; Colen, Tahl; Roberson, Joseph; Gardner, Phyllis; Schrijver, Iris

    2008-01-01

    Using the Hereditary Hearing Loss arrayed primer extension (APEX) array, which contains 198 mutations across 8 hearing loss-associated genes (GJB2, GJB6, GJB3, GJA1, SLC26A4, SLC26A5, 12S-rRNA, and tRNA Ser), we compared the frequency of sequence variants in 94 individuals with early presbycusis to 50 unaffected controls and aimed to identify possible genetic contributors. This cross-sectional study was performed at Stanford University with presbycusis samples from the California Ear Institute. The patients were between ages 20 and 65 yr, with adult-onset sensorineural hearing loss of unknown etiology, and carried a clinical diagnosis of early presbycusis. Exclusion criteria comprised known causes of hearing loss such as significant noise exposure, trauma, ototoxic medication, neoplasm, and congenital infection or syndrome, as well as congenital or pediatric onset. Sequence changes were identified in 11.7% and 10% of presbycusis and control alleles, respectively. Among the presbycusis group, these solely occurred within the GJB2 and SLC26A4 genes. Homozygous and compound heterozygous pathogenic mutations were exclusively seen in affected individuals. We were unable to detect a statistically significant difference between our control and affected populations regarding the frequency of sequence variants detected with the APEX array. Individuals who carry two mild mutations in the GJB2 gene possibly have an increased risk of developing early presbycusis.

  11. Genetic interaction network of the Saccharomyces cerevisiae type 1 phosphatase Glc7

    Directory of Open Access Journals (Sweden)

    Neszt Michael

    2008-07-01

    Full Text Available Abstract Background Protein kinases and phosphatases regulate protein phosphorylation, a critical means of modulating protein function, stability and localization. The identification of functional networks for protein phosphatases has been slow due to their redundant nature and the lack of large-scale analyses. We hypothesized that a genome-scale analysis of genetic interactions using the Synthetic Genetic Array could reveal protein phosphatase functional networks. We apply this approach to the conserved type 1 protein phosphatase Glc7, which regulates numerous cellular processes in budding yeast. Results We created a novel glc7 catalytic mutant (glc7-E101Q. Phenotypic analysis indicates that this novel allele exhibits slow growth and defects in glucose metabolism but normal cell cycle progression and chromosome segregation. This suggests that glc7-E101Q is a hypomorphic glc7 mutant. Synthetic Genetic Array analysis of glc7-E101Q revealed a broad network of 245 synthetic sick/lethal interactions reflecting that many processes are required when Glc7 function is compromised such as histone modification, chromosome segregation and cytokinesis, nutrient sensing and DNA damage. In addition, mitochondrial activity and inheritance and lipid metabolism were identified as new processes involved in buffering Glc7 function. An interaction network among 95 genes genetically interacting with GLC7 was constructed by integration of genetic and physical interaction data. The obtained network has a modular architecture, and the interconnection among the modules reflects the cooperation of the processes buffering Glc7 function. Conclusion We found 245 genes required for the normal growth of the glc7-E101Q mutant. Functional grouping of these genes and analysis of their physical and genetic interaction patterns bring new information on Glc7-regulated processes.

  12. 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.

  13. Fast and easy protocol for the purification of recombinant S-layer protein for synthetic biology applications

    KAUST Repository

    Norville, Julie E.

    2011-06-17

    A goal of synthetic biology is to make biological systems easier to engineer. One of the aims is to design, with nanometer-scale precision, biomaterials with well-defined properties. The surface-layer protein SbpA forms 2D arrays naturally on the cell surface of Lysinibacillus sphaericus, but also as the purified protein in solution upon the addition of divalent cations. The high propensity of SbpA to form crystalline arrays, which can be simply controlled by divalent cations, and the possibility to genetically alter the protein, make SbpA an attractive molecule for synthetic biology. To be a useful tool, however, it is important that a simple protocol can be used to produce recombinant wild-type and modified SbpA in large quantities and in a biologically active form. The present study addresses this requirement by introducing a mild and non-denaturing purification protocol to produce milligram quantities of recombinant, active SbpA.

  14. Laser-drilled micro-hole arrays on polyurethane synthetic leather for improvement of water vapor permeability

    International Nuclear Information System (INIS)

    Wu, Y.; Wang, A.H.; Zheng, R.R.; Tang, H.Q.; Qi, X.Y.; Ye, B.

    2014-01-01

    Three kinds of lasers at 1064, 532 and 355 nm wavelengths respectively were adopted to construct micro-hole arrays on polyurethane (PU) synthetic leather with an aim to improve water vapor permeability (WVP) of PU synthetic leather. The morphology of the laser-drilled micro-holes was observed to optimize laser parameters. The WVP and slit tear resistance of the laser-drilled leather were measured. Results show that the optimized pulse energy for the 1064, 532 and 355 nm lasers are 0.8, 1.1 and 0.26 mJ, respectively. The diameters of the micro-holes drilled with the optimized laser pulse energy were about 20, 15 and 10 μm, respectively. The depths of the micro-holes drilled with the optimized pulse energy were about 21, 60 and 69 μm, respectively. Compared with the untreated samples, the highest WVP growth ratio was 38.4%, 46.8% and 53.5% achieved by the 1064, 532 and 355 nm lasers, respectively. And the highest decreasing ratio of slit tear resistance was 11.1%, 14.8%, and 22.5% treated by the 1064, 532 and 355 nm lasers, respectively. Analysis of the interaction mechanism between laser beams at three kinds of laser wavelengths and the PU synthetic leather revealed that laser micro-drilling at 355 nm wavelength displayed both photochemical ablation and photothermal ablation, while laser micro-drilling at 1064 and 532 nm wavelengths leaded to photothermal ablation only.

  15. Laser-drilled micro-hole arrays on polyurethane synthetic leather for improvement of water vapor permeability

    Science.gov (United States)

    Wu, Y.; Wang, A. H.; Zheng, R. R.; Tang, H. Q.; Qi, X. Y.; Ye, B.

    2014-06-01

    Three kinds of lasers at 1064, 532 and 355 nm wavelengths respectively were adopted to construct micro-hole arrays on polyurethane (PU) synthetic leather with an aim to improve water vapor permeability (WVP) of PU synthetic leather. The morphology of the laser-drilled micro-holes was observed to optimize laser parameters. The WVP and slit tear resistance of the laser-drilled leather were measured. Results show that the optimized pulse energy for the 1064, 532 and 355 nm lasers are 0.8, 1.1 and 0.26 mJ, respectively. The diameters of the micro-holes drilled with the optimized laser pulse energy were about 20, 15 and 10 μm, respectively. The depths of the micro-holes drilled with the optimized pulse energy were about 21, 60 and 69 μm, respectively. Compared with the untreated samples, the highest WVP growth ratio was 38.4%, 46.8% and 53.5% achieved by the 1064, 532 and 355 nm lasers, respectively. And the highest decreasing ratio of slit tear resistance was 11.1%, 14.8%, and 22.5% treated by the 1064, 532 and 355 nm lasers, respectively. Analysis of the interaction mechanism between laser beams at three kinds of laser wavelengths and the PU synthetic leather revealed that laser micro-drilling at 355 nm wavelength displayed both photochemical ablation and photothermal ablation, while laser micro-drilling at 1064 and 532 nm wavelengths leaded to photothermal ablation only.

  16. Luminescence of two-dimensional ordered array of the ZnO quantum nanodots, obtained by means of the synthetic opal

    International Nuclear Information System (INIS)

    Gruzintsev, A.N.; Volkov, V.T.; Emelchenko, G.A.; Karpov, I.A.; Maslov, W.M.; Michailov, G.M.; Yakimov, E.E.

    2004-01-01

    The luminescence properties of ZnO films of different thickness obtained on a synthetic opal were investigated. Several narrow peaks in the exciton emission region related to the size quantum effect of the electron wave functions were detected. Two-dimensional ordered array of ZnO quantum dots formed inside the opal pores on the second sphere layer were found by the atomic force microscopy (AFM) and angle dependence of the luminescence spectra

  17. Quantification of within-sample genetic heterogeneity from SNP-array data

    DEFF Research Database (Denmark)

    Martinez, Pierre; Kimberley, Christopher; Birkbak, Nicolai Juul

    2017-01-01

    Intra-tumour genetic heterogeneity (ITH) fosters drug resistance and is a critical hurdle to clinical treatment. ITH can be well-measured using multi-region sampling but this is costly and challenging to implement. There is therefore a need for tools to estimate ITH in individual samples, using...... standard genomic data such as SNP-arrays, that could be implemented routinely. We designed two novel scores S and R, respectively based on the Shannon diversity index and Ripley's L statistic of spatial homogeneity, to quantify ITH in single SNP-array samples. We created in-silico and in-vitro mixtures...... sequencing data but heterogeneity in the fraction of tumour cells present across samples hampered accurate quantification. The prognostic potential of both scores was moderate but significantly predictive of survival in several tumour types (corrected p = 0.03). Our work thus shows how individual SNP...

  18. The OncoArray Consortium: a Network for Understanding the Genetic Architecture of Common Cancers

    Science.gov (United States)

    Amos, Christopher I.; Dennis, Joe; Wang, Zhaoming; Byun, Jinyoung; Schumacher, Fredrick R.; Gayther, Simon A.; Casey, Graham; Hunter, David J.; Sellers, Thomas A.; Gruber, Stephen B.; Dunning, Alison M.; Michailidou, Kyriaki; Fachal, Laura; Doheny, Kimberly; Spurdle, Amanda B.; Li, Yafang; Xiao, Xiangjun; Romm, Jane; Pugh, Elizabeth; Coetzee, Gerhard A.; Hazelett, Dennis J.; Bojesen, Stig E.; Caga-Anan, Charlisse; Haiman, Christopher A.; Kamal, Ahsan; Luccarini, Craig; Tessier, Daniel; Vincent, Daniel; Bacot, François; Van Den Berg, David J.; Nelson, Stefanie; Demetriades, Stephen; Goldgar, David E.; Couch, Fergus J.; Forman, Judith L.; Giles, Graham G.; Conti, David V.; Bickeböller, Heike; Risch, Angela; Waldenberger, Melanie; Brüske, Irene; Hicks, Belynda D.; Ling, Hua; McGuffog, Lesley; Lee, Andrew; Kuchenbaecker, Karoline B.; Soucy, Penny; Manz, Judith; Cunningham, Julie M.; Butterbach, Katja; Kote-Jarai, Zsofia; Kraft, Peter; FitzGerald, Liesel M.; Lindström, Sara; Adams, Marcia; McKay, James D.; Phelan, Catherine M.; Benlloch, Sara; Kelemen, Linda E.; Brennan, Paul; Riggan, Marjorie; O’Mara, Tracy A.; Shen, Hongbin; Shi, Yongyong; Thompson, Deborah J.; Goodman, Marc T.; Nielsen, Sune F.; Berchuck, Andrew; Laboissiere, Sylvie; Schmit, Stephanie L.; Shelford, Tameka; Edlund, Christopher K.; Taylor, Jack A.; Field, John K.; Park, Sue K.; Offit, Kenneth; Thomassen, Mads; Schmutzler, Rita; Ottini, Laura; Hung, Rayjean J.; Marchini, Jonathan; Al Olama, Ali Amin; Peters, Ulrike; Eeles, Rosalind A.; Seldin, Michael F.; Gillanders, Elizabeth; Seminara, Daniela; Antoniou, Antonis C.; Pharoah, Paul D.; Chenevix-Trench, Georgia; Chanock, Stephen J.; Simard, Jacques; Easton, Douglas F.

    2016-01-01

    Background Common cancers develop through a multistep process often including inherited susceptibility. Collaboration among multiple institutions, and funding from multiple sources, has allowed the development of an inexpensive genotyping microarray, the OncoArray. The array includes a genome-wide backbone, comprising 230,000 SNPs tagging most common genetic variants, together with dense mapping of known susceptibility regions, rare variants from sequencing experiments, pharmacogenetic markers and cancer related traits. Methods The OncoArray can be genotyped using a novel technology developed by Illumina to facilitate efficient genotyping. The consortium developed standard approaches for selecting SNPs for study, for quality control of markers and for ancestry analysis. The array was genotyped at selected sites and with prespecified replicate samples to permit evaluation of genotyping accuracy among centers and by ethnic background. Results The OncoArray consortium genotyped 447,705 samples. A total of 494,763 SNPs passed quality control steps with a sample success rate of 97% of the samples. Participating sites performed ancestry analysis using a common set of markers and a scoring algorithm based on principal components analysis. Conclusions Results from these analyses will enable researchers to identify new susceptibility loci, perform fine mapping of new or known loci associated with either single or multiple cancers, assess the degree of overlap in cancer causation and pleiotropic effects of loci that have been identified for disease-specific risk, and jointly model genetic, environmental and lifestyle related exposures. Impact Ongoing analyses will shed light on etiology and risk assessment for many types of cancer. PMID:27697780

  19. An Improved Chaos Genetic Algorithm for T-Shaped MIMO Radar Antenna Array Optimization

    Directory of Open Access Journals (Sweden)

    Xin Fu

    2014-01-01

    Full Text Available In view of the fact that the traditional genetic algorithm easily falls into local optimum in the late iterations, an improved chaos genetic algorithm employed chaos theory and genetic algorithm is presented to optimize the low side-lobe for T-shaped MIMO radar antenna array. The novel two-dimension Cat chaotic map has been put forward to produce its initial population, improving the diversity of individuals. The improved Tent map is presented for groups of individuals of a generation with chaos disturbance. Improved chaotic genetic algorithm optimization model is established. The algorithm presented in this paper not only improved the search precision, but also avoids effectively the problem of local convergence and prematurity. For MIMO radar, the improved chaos genetic algorithm proposed in this paper obtains lower side-lobe level through optimizing the exciting current amplitude. Simulation results show that the algorithm is feasible and effective. Its performance is superior to the traditional genetic algorithm.

  20. Synthetic biology and metabolic engineering.

    Science.gov (United States)

    Stephanopoulos, Gregory

    2012-11-16

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

  1. Loads Bias Genetic and Signaling Switches in Synthetic and Natural Systems

    Science.gov (United States)

    Medford, June; Prasad, Ashok

    2014-01-01

    Biological protein interactions networks such as signal transduction or gene transcription networks are often treated as modular, allowing motifs to be analyzed in isolation from the rest of the network. Modularity is also a key assumption in synthetic biology, where it is similarly expected that when network motifs are combined together, they do not lose their essential characteristics. However, the interactions that a network module has with downstream elements change the dynamical equations describing the upstream module and thus may change the dynamic and static properties of the upstream circuit even without explicit feedback. In this work we analyze the behavior of a ubiquitous motif in gene transcription and signal transduction circuits: the switch. We show that adding an additional downstream component to the simple genetic toggle switch changes its dynamical properties by changing the underlying potential energy landscape, and skewing it in favor of the unloaded side, and in some situations adding loads to the genetic switch can also abrogate bistable behavior. We find that an additional positive feedback motif found in naturally occurring toggle switches could tune the potential energy landscape in a desirable manner. We also analyze autocatalytic signal transduction switches and show that a ubiquitous positive feedback switch can lose its switch-like properties when connected to a downstream load. Our analysis underscores the necessity of incorporating the effects of downstream components when understanding the physics of biochemical network motifs, and raises the question as to how these effects are managed in real biological systems. This analysis is particularly important when scaling synthetic networks to more complex organisms. PMID:24676102

  2. Efficient synthesis of large-scale thinned arrays using a density-taper initialised genetic algorithm

    CSIR Research Space (South Africa)

    Du Plessis, WP

    2011-09-01

    Full Text Available The use of the density-taper approach to initialise a genetic algorithm is shown to give excellent results in the synthesis of thinned arrays. This approach is shown to give better SLL values more consistently than using random values and difference...

  3. Introduction to focus issue: quantitative approaches to genetic networks.

    Science.gov (United States)

    Albert, Réka; Collins, James J; Glass, Leon

    2013-06-01

    using field-programmable gate arrays. Mathematical analyses will be essential for understanding naturally occurring genetic networks in diverse organisms and for providing a foundation for the improved development of synthetic genetic networks.

  4. Radar techniques using array antennas

    CERN Document Server

    Wirth, Wulf-Dieter

    2013-01-01

    Radar Techniques Using Array Antennas is a thorough introduction to the possibilities of radar technology based on electronic steerable and active array antennas. Topics covered include array signal processing, array calibration, adaptive digital beamforming, adaptive monopulse, superresolution, pulse compression, sequential detection, target detection with long pulse series, space-time adaptive processing (STAP), moving target detection using synthetic aperture radar (SAR), target imaging, energy management and system parameter relations. The discussed methods are confirmed by simulation stud

  5. Detection of Defective Sensors in Phased Array Using Compressed Sensing and Hybrid Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    Shafqat Ullah Khan

    2016-01-01

    Full Text Available A compressed sensing based array diagnosis technique has been presented. This technique starts from collecting the measurements of the far-field pattern. The system linking the difference between the field measured using the healthy reference array and the field radiated by the array under test is solved using a genetic algorithm (GA, parallel coordinate descent (PCD algorithm, and then a hybridized GA with PCD algorithm. These algorithms are applied for fully and partially defective antenna arrays. The simulation results indicate that the proposed hybrid algorithm outperforms in terms of localization of element failure with a small number of measurements. In the proposed algorithm, the slow and early convergence of GA has been avoided by combining it with PCD algorithm. It has been shown that the hybrid GA-PCD algorithm provides an accurate diagnosis of fully and partially defective sensors as compared to GA or PCD alone. Different simulations have been provided to validate the performance of the designed algorithms in diversified scenarios.

  6. Diversity arrays technology (DArT) markers in apple for genetic linkage maps.

    Science.gov (United States)

    Schouten, Henk J; van de Weg, W Eric; Carling, Jason; Khan, Sabaz Ali; McKay, Steven J; van Kaauwen, Martijn P W; Wittenberg, Alexander H J; Koehorst-van Putten, Herma J J; Noordijk, Yolanda; Gao, Zhongshan; Rees, D Jasper G; Van Dyk, Maria M; Jaccoud, Damian; Considine, Michael J; Kilian, Andrzej

    2012-03-01

    Diversity Arrays Technology (DArT) provides a high-throughput whole-genome genotyping platform for the detection and scoring of hundreds of polymorphic loci without any need for prior sequence information. The work presented here details the development and performance of a DArT genotyping array for apple. This is the first paper on DArT in horticultural trees. Genetic mapping of DArT markers in two mapping populations and their integration with other marker types showed that DArT is a powerful high-throughput method for obtaining accurate and reproducible marker data, despite the low cost per data point. This method appears to be suitable for aligning the genetic maps of different segregating populations. The standard complexity reduction method, based on the methylation-sensitive PstI restriction enzyme, resulted in a high frequency of markers, although there was 52-54% redundancy due to the repeated sampling of highly similar sequences. Sequencing of the marker clones showed that they are significantly enriched for low-copy, genic regions. The genome coverage using the standard method was 55-76%. For improved genome coverage, an alternative complexity reduction method was examined, which resulted in less redundancy and additional segregating markers. The DArT markers proved to be of high quality and were very suitable for genetic mapping at low cost for the apple, providing moderate genome coverage. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11032-011-9579-5) contains supplementary material, which is available to authorized users.

  7. Rewiring protein synthesis: From natural to synthetic amino acids.

    Science.gov (United States)

    Fan, Yongqiang; Evans, Christopher R; Ling, Jiqiang

    2017-11-01

    The protein synthesis machinery uses 22 natural amino acids as building blocks that faithfully decode the genetic information. Such fidelity is controlled at multiple steps and can be compromised in nature and in the laboratory to rewire protein synthesis with natural and synthetic amino acids. This review summarizes the major quality control mechanisms during protein synthesis, including aminoacyl-tRNA synthetases, elongation factors, and the ribosome. We will discuss evolution and engineering of such components that allow incorporation of natural and synthetic amino acids at positions that deviate from the standard genetic code. The protein synthesis machinery is highly selective, yet not fixed, for the correct amino acids that match the mRNA codons. Ambiguous translation of a codon with multiple amino acids or complete reassignment of a codon with a synthetic amino acid diversifies the proteome. Expanding the genetic code with synthetic amino acids through rewiring protein synthesis has broad applications in synthetic biology and chemical biology. Biochemical, structural, and genetic studies of the translational quality control mechanisms are not only crucial to understand the physiological role of translational fidelity and evolution of the genetic code, but also enable us to better design biological parts to expand the proteomes of synthetic organisms. This article is part of a Special Issue entitled "Biochemistry of Synthetic Biology - Recent Developments" Guest Editor: Dr. Ilka Heinemann and Dr. Patrick O'Donoghue. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. TheCellMap.org: A Web-Accessible Database for Visualizing and Mining the Global Yeast Genetic Interaction Network.

    Science.gov (United States)

    Usaj, Matej; Tan, Yizhao; Wang, Wen; VanderSluis, Benjamin; Zou, Albert; Myers, Chad L; Costanzo, Michael; Andrews, Brenda; Boone, Charles

    2017-05-05

    Providing access to quantitative genomic data is key to ensure large-scale data validation and promote new discoveries. TheCellMap.org serves as a central repository for storing and analyzing quantitative genetic interaction data produced by genome-scale Synthetic Genetic Array (SGA) experiments with the budding yeast Saccharomyces cerevisiae In particular, TheCellMap.org allows users to easily access, visualize, explore, and functionally annotate genetic interactions, or to extract and reorganize subnetworks, using data-driven network layouts in an intuitive and interactive manner. Copyright © 2017 Usaj et al.

  9. A Synthetic Phased Array Surface Acoustic Wave Sensor for Quantifying Bolt Tension

    Directory of Open Access Journals (Sweden)

    Rasim Guldiken

    2012-09-01

    Full Text Available In this paper, we report our findings on implementing a synthetic phased array surface acoustic wave sensor to quantify bolt tension. Maintaining proper bolt tension is important in many fields such as for ensuring safe operation of civil infrastructures. Significant advantages of this relatively simple methodology is its capability to assess bolt tension without any contact with the bolt, thus enabling measurement at inaccessible locations, multiple bolt measurement capability at a time, not requiring data collection during the installation and no calibration requirements. We performed detailed experiments on a custom-built flexible bench-top experimental setup consisting of 1018 steel plate of 12.7 mm (½ in thickness, a 6.4 mm (¼ in grade 8 bolt and a stainless steel washer with 19 mm (¾ in of external diameter. Our results indicate that this method is not only capable of clearly distinguishing properly bolted joints from loosened joints but also capable of quantifying how loose the bolt actually is. We also conducted detailed signal-to-noise (SNR analysis and showed that the SNR value for the entire bolt tension range was sufficient for image reconstruction.

  10. 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.

  11. Rapid Characterization of Bacterial Electrogenicity Using a Single-Sheet Paper-Based Electrofluidic Array

    Directory of Open Access Journals (Sweden)

    Yang Gao

    2017-07-01

    Full Text Available Electrogenicity, or bacterial electron transfer capacity, is an important application which offers environmentally sustainable advances in the fields of biofuels, wastewater treatment, bioremediation, desalination, and biosensing. Significant boosts in this technology can be achieved with the growth of synthetic biology that manipulates microbial electron transfer pathways, thereby potentially significantly improving their electrogenic potential. There is currently a need for a high-throughput, rapid, and highly sensitive test array to evaluate the electrogenic properties of newly discovered and/or genetically engineered bacterial species. In this work, we report a single-sheet, paper-based electrofluidic (incorporating both electronic and fluidic structure screening platform for rapid, sensitive, and potentially high-throughput characterization of bacterial electrogenicity. This novel screening array uses (i a commercially available wax printer for hydrophobic wax patterning on a single sheet of paper and (ii water-dispersed electrically conducting polymer mixture, poly(3,4-ethylenedioxythiophene:polystyrene sulfonate, for full integration of electronic and fluidic components into the paper substrate. The engineered 3-D, microporous, hydrophilic, and conductive paper structure provides a large surface area for efficient electron transfer. This results in rapid and sensitive power assessment of electrogenic bacteria from a microliter sample volume. We validated the effectiveness of the sensor array using hypothesis-driven genetically modified Pseudomonas aeruginosa mutant strains. Within 20 min, we observed that the sensor platform successfully measured the electricity-generating capacities of five isogenic mutants of P. aeruginosa while distinguishing their differences from genetically unmodified bacteria.

  12. Synthetic Biology Parts for the Storage of Increased Genetic Information in Cells.

    Science.gov (United States)

    Morris, Sydney E; Feldman, Aaron W; Romesberg, Floyd E

    2017-10-20

    To bestow cells with novel forms and functions, the goal of synthetic biology, we have developed the unnatural nucleoside triphosphates dNaMTP and dTPT3TP, which form an unnatural base pair (UBP) and expand the genetic alphabet. While the UBP may be retained in the DNA of a living cell, its retention is sequence-dependent. We now report a steady-state kinetic characterization of the rate with which the Klenow fragment of E. coli DNA polymerase I synthesizes the UBP and its mispairs in a variety of sequence contexts. Correct UBP synthesis is as efficient as for a natural base pair, except in one sequence context, and in vitro performance is correlated with in vivo performance. The data elucidate the determinants of efficient UBP synthesis, show that the dNaM-dTPT3 UBP is the first generally recognized natural-like base pair, and importantly, demonstrate that dNaMTP and dTPT3TP are well optimized and standardized parts for the expansion of the genetic alphabet.

  13. Design and construction of "synthetic species".

    Directory of Open Access Journals (Sweden)

    Eduardo Moreno

    Full Text Available Synthetic biology is an area of biological research that combines science and engineering. Here, I merge the principles of synthetic biology and regulatory evolution to create a new species with a minimal set of known elements. Using preexisting transgenes and recessive mutations of Drosophila melanogaster, a transgenic population arises with small eyes and a different venation pattern that fulfils the criteria of a new species according to Mayr's Biological Species Concept. The population described here is the first transgenic organism that cannot hybridize with the original wild type population but remains fertile when crossed with other identical transgenic animals. I therefore propose the term "synthetic species" to distinguish it from "natural species", not only because it has been created by genetic manipulation, but also because it may never be able to survive outside the laboratory environment. The use of genetic engineering to design artificial species barriers could help us understand natural speciation and may have practical applications. For instance, the transition from transgenic organisms towards synthetic species could constitute a safety mechanism to avoid the hybridization of genetically modified animals with wild type populations, preserving biodiversity.

  14. pBAM1: an all-synthetic genetic tool for analysis and construction of complex bacterial phenotypes

    Directory of Open Access Journals (Sweden)

    Arévalo-Rodríguez Miguel

    2011-02-01

    Full Text Available Abstract Background Since publication in 1977 of plasmid pBR322, many breakthroughs in Biology have depended on increasingly sophisticated vector platforms for analysis and engineering of given bacterial strains. Although restriction sites impose a certain format in the procedures for assembling cloned genes, every attempt thus far to standardize vector architecture and nomenclature has ended up in failure. While this state of affairs may still be tolerable for traditional one-at-a-time studies of single genes, the onset of systems and synthetic biology calls for a simplification -along with an optimization- of the currently unwieldy pool of genetic tools. Results The functional DNA sequences present in the natural bacterial transposon Tn5 have been methodically edited and refactored for the production of a multi-purpose genetic tool named pBAM1, which allows a range of manipulations in the genome of Gram-negative bacteria. This all-synthetic construct enhances the power of mini-transposon vectors for either de-construction or re-construction of phenotypes á la carte by incorporating features inspired in systems engineering: modularity, re-usability, minimization, and compatibility with other genetic tools. pBAM1 bears an streamlined, restriction site-freed and narrow-host range replication frame bearing the sequences of R6K oriV, oriT and an ampicillin resistance marker. These go along with a business module that contains a host-independent and hyperactive transposition platform for in vivo or in vitro insertion of desired DNA into the genome of the target bacterium. All functional sequences were standardized for a straightforward replacement by equivalent counterparts, if required. pBAM1 can be delivered into recipient cells by either mating or electroporation, producing transposon insertion frequencies of 1.8 × 10-3 and 1.02 × 10-7, respectively in the soil bacterium Pseudomonas putida. Analyses of the resulting clones revealed a 100% of

  15. Dual-polarization, wideband microstrip antenna array for airborne C-band SAR

    DEFF Research Database (Denmark)

    Granholm, Johan; Skou, Niels

    2000-01-01

    The paper describes the development of a C-band, dual linear polarization wideband antenna array, for use in the next-generation of the Danish airborne polarimetric synthetic aperture radar (SAR) system. The array is made of probe-fed, stacked microstrip patches. The design and performance of the...... of the basic stacked patch element, operating from 4.9 GHz to 5.7 GHz, and a 2×2 element test array of these, are described.......The paper describes the development of a C-band, dual linear polarization wideband antenna array, for use in the next-generation of the Danish airborne polarimetric synthetic aperture radar (SAR) system. The array is made of probe-fed, stacked microstrip patches. The design and performance...

  16. Synchronous long-term oscillations in a synthetic gene circuit.

    Science.gov (United States)

    Potvin-Trottier, Laurent; Lord, Nathan D; Vinnicombe, Glenn; Paulsson, Johan

    2016-10-27

    Synthetically engineered genetic circuits can perform a wide variety of tasks but are generally less accurate than natural systems. Here we revisit the first synthetic genetic oscillator, the repressilator, and modify it using principles from stochastic chemistry in single cells. Specifically, we sought to reduce error propagation and information losses, not by adding control loops, but by simply removing existing features. We show that this modification created highly regular and robust oscillations. Furthermore, some streamlined circuits kept 14 generation periods over a range of growth conditions and kept phase for hundreds of generations in single cells, allowing cells in flasks and colonies to oscillate synchronously without any coupling between them. Our results suggest that even the simplest synthetic genetic networks can achieve a precision that rivals natural systems, and emphasize the importance of noise analyses for circuit design in synthetic biology.

  17. Diagnostics of the BIOMASS feed array prototype

    DEFF Research Database (Denmark)

    Cappellin, Cecilia; Pivnenko, Sergey; Pontoppidan, Kennie Nybo

    2013-01-01

    The 3D reconstruction algorithm is applied to the prototype feed array of the BIOMASS synthetic aperture radar, recently measured at the DTU-ESA Spherical Near-Field Antenna Test Facility in Denmark. Careful analysis of the measured feed array data has shown that the test support structure...

  18. DNA electrophoresis through microlithographic arrays

    International Nuclear Information System (INIS)

    Sevick, E.M.; Williams, D.R.M.

    1996-01-01

    Electrophoresis is one of the most widely used techniques in biochemistry and genetics for size-separating charged molecular chains such as DNA or synthetic polyelectrolytes. The separation is achieved by driving the chains through a gel with an external electric field. As a result of the field and the obstacles that the medium provides, the chains have different mobilities and are physically separated after a given process time. The macroscopically observed mobility scales inversely with chain size: small molecules move through the medium quickly while larger molecules move more slowly. However, electrophoresis remains a tool that has yet to be optimised for most efficient size separation of polyelectrolytes, particularly large polyelectrolytes, e.g. DNA in excess of 30-50 kbp. Microlithographic arrays etched with an ordered pattern of obstacles provide an attractive alternative to gel media and provide wider avenues for size separation of polyelectrolytes and promote a better understanding of the separation process. Its advantages over gels are (1) the ordered array is durable and can be re-used, (2) the array morphology is ordered and can be standardized for specific separation, and (3) calibration with a marker polyelectrolyte is not required as the array is reproduced to high precision. Most importantly, the array geometry can be graduated along the chip so as to expand the size-dependent regime over larger chain lengths and postpone saturation. In order to predict the effect of obstacles upon the chain-length dependence in mobility and hence, size separation, we study the dynamics of single chains using theory and simulation. We present recent work describing: 1) the release kinetics of a single DNA molecule hooked around a point, frictionless obstacle and in both weak and strong field limits, 2) the mobility of a chain impinging upon point obstacles in an ordered array of obstacles, demonstrating the wide range of interactions possible between the chain and

  19. 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.

  20. Design of sparse Halbach magnet arrays for portable MRI using a genetic algorithm.

    Science.gov (United States)

    Cooley, Clarissa Zimmerman; Haskell, Melissa W; Cauley, Stephen F; Sappo, Charlotte; Lapierre, Cristen D; Ha, Christopher G; Stockmann, Jason P; Wald, Lawrence L

    2018-01-01

    Permanent magnet arrays offer several attributes attractive for the development of a low-cost portable MRI scanner for brain imaging. They offer the potential for a relatively lightweight, low to mid-field system with no cryogenics, a small fringe field, and no electrical power requirements or heat dissipation needs. The cylindrical Halbach array, however, requires external shimming or mechanical adjustments to produce B 0 fields with standard MRI homogeneity levels (e.g., 0.1 ppm over FOV), particularly when constrained or truncated geometries are needed, such as a head-only magnet where the magnet length is constrained by the shoulders. For portable scanners using rotation of the magnet for spatial encoding with generalized projections, the spatial pattern of the field is important since it acts as the encoding field. In either a static or rotating magnet, it will be important to be able to optimize the field pattern of cylindrical Halbach arrays in a way that retains construction simplicity. To achieve this, we present a method for designing an optimized cylindrical Halbach magnet using the genetic algorithm to achieve either homogeneity (for standard MRI applications) or a favorable spatial encoding field pattern (for rotational spatial encoding applications). We compare the chosen designs against a standard, fully populated sparse Halbach design, and evaluate optimized spatial encoding fields using point-spread-function and image simulations. We validate the calculations by comparing to the measured field of a constructed magnet. The experimentally implemented design produced fields in good agreement with the predicted fields, and the genetic algorithm was successful in improving the chosen metrics. For the uniform target field, an order of magnitude homogeneity improvement was achieved compared to the un-optimized, fully populated design. For the rotational encoding design the resolution uniformity is improved by 95% compared to a uniformly populated design.

  1. Synthetic multicellular oscillatory systems: controlling protein dynamics with genetic circuits

    International Nuclear Information System (INIS)

    Koseska, Aneta; Volkov, Evgenii; Kurths, Juergen

    2011-01-01

    Synthetic biology is a relatively new research discipline that combines standard biology approaches with the constructive nature of engineering. Thus, recent efforts in the field of synthetic biology have given a perspective to consider cells as 'programmable matter'. Here, we address the possibility of using synthetic circuits to control protein dynamics. In particular, we show how intercellular communication and stochasticity can be used to manipulate the dynamical behavior of a population of coupled synthetic units and, in this manner, finely tune the expression of specific proteins of interest, e.g. in large bioreactors.

  2. 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.

  3. Comparison of Computational and Experimental Microphone Array Results for an 18%-Scale Aircraft Model

    Science.gov (United States)

    Lockard, David P.; Humphreys, William M.; Khorrami, Mehdi R.; Fares, Ehab; Casalino, Damiano; Ravetta, Patricio A.

    2015-01-01

    An 18%-scale, semi-span model is used as a platform for examining the efficacy of microphone array processing using synthetic data from numerical simulations. Two hybrid RANS/LES codes coupled with Ffowcs Williams-Hawkings solvers are used to calculate 97 microphone signals at the locations of an array employed in the NASA LaRC 14x22 tunnel. Conventional, DAMAS, and CLEAN-SC array processing is applied in an identical fashion to the experimental and computational results for three different configurations involving deploying and retracting the main landing gear and a part span flap. Despite the short time records of the numerical signals, the beamform maps are able to isolate the noise sources, and the appearance of the DAMAS synthetic array maps is generally better than those from the experimental data. The experimental CLEAN-SC maps are similar in quality to those from the simulations indicating that CLEAN-SC may have less sensitivity to background noise. The spectrum obtained from DAMAS processing of synthetic array data is nearly identical to the spectrum of the center microphone of the array, indicating that for this problem array processing of synthetic data does not improve spectral comparisons with experiment. However, the beamform maps do provide an additional means of comparison that can reveal differences that cannot be ascertained from spectra alone.

  4. A standard-enabled workflow for synthetic biology

    KAUST Repository

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

    2017-01-01

    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

  5. Freedom and Responsibility in Synthetic Genomics: The Synthetic Yeast Project.

    Science.gov (United States)

    Sliva, Anna; Yang, Huanming; Boeke, Jef D; Mathews, Debra J H

    2015-08-01

    First introduced in 2011, the Synthetic Yeast Genome (Sc2.0) PROJECT is a large international synthetic genomics project that will culminate in the first eukaryotic cell (Saccharomyces cerevisiae) with a fully synthetic genome. With collaborators from across the globe and from a range of institutions spanning from do-it-yourself biology (DIYbio) to commercial enterprises, it is important that all scientists working on this project are cognizant of the ethical and policy issues associated with this field of research and operate under a common set of principles. In this commentary, we survey the current ethics and regulatory landscape of synthetic biology and present the Sc2.0 Statement of Ethics and Governance to which all members of the project adhere. This statement focuses on four aspects of the Sc2.0 PROJECT: societal benefit, intellectual property, safety, and self-governance. We propose that such project-level agreements are an important, valuable, and flexible model of self-regulation for similar global, large-scale synthetic biology projects in order to maximize the benefits and minimize potential harms. Copyright © 2015 by the Genetics Society of America.

  6. Preimplantation genetic diagnosis and screening by array comparative genomic hybridisation: experience of more than 100 cases in a single centre.

    Science.gov (United States)

    Chow, J Fc; Yeung, W Sb; Lee, V Cy; Lau, E Yl; Ho, P C; Ng, E Hy

    2017-04-01

    Preimplantation genetic screening has been proposed to improve the in-vitro fertilisation outcome by screening for aneuploid embryos or blastocysts. This study aimed to report the outcome of 133 cycles of preimplantation genetic diagnosis and screening by array comparative genomic hybridisation. This study of case series was conducted in a tertiary assisted reproductive centre in Hong Kong. Patients who underwent preimplantation genetic diagnosis for chromosomal abnormalities or preimplantation genetic screening between 1 April 2012 and 30 June 2015 were included. They underwent in-vitro fertilisation and intracytoplasmic sperm injection. An embryo biopsy was performed on day-3 embryos and the blastomere was subject to array comparative genomic hybridisation. Embryos with normal copy numbers were replaced. The ongoing pregnancy rate, implantation rate, and miscarriage rate were studied. During the study period, 133 cycles of preimplantation genetic diagnosis for chromosomal abnormalities or preimplantation genetic screening were initiated in 94 patients. Overall, 112 cycles proceeded to embryo biopsy and 65 cycles had embryo transfer. The ongoing pregnancy rate per transfer cycle after preimplantation genetic screening was 50.0% and that after preimplantation genetic diagnosis was 34.9%. The implantation rates after preimplantation genetic screening and diagnosis were 45.7% and 41.1%, respectively and the miscarriage rates were 8.3% and 28.6%, respectively. There were 26 frozen-thawed embryo transfer cycles, in which vitrified and biopsied genetically transferrable embryos were replaced, resulting in an ongoing pregnancy rate of 36.4% in the screening group and 60.0% in the diagnosis group. The clinical outcomes of preimplantation genetic diagnosis and screening using comparative genomic hybridisation in our unit were comparable to those reported internationally. Genetically transferrable embryos replaced in a natural cycle may improve the ongoing pregnancy rate

  7. GENETIC VARIATION IN RED RASPBERRIES (RUBUS IDAEUS L.; ROSACEAE) FROM SITES DIFFERING IN ORGANIC POLLUTANTS COMPARED WITH SYNTHETIC TANDEM REPEAT DNA PROBES

    Science.gov (United States)

    Two synthetic tandem repetitive DNA probes were used to compare genetic variation at variable-number-tandem-repeat (VNTR) loci among Rubus idaeus L. var. strigosus (Michx.) Maxim. (Rosaceae) individuals sampled at eight sites contaminated by pollutants (N = 39) and eight adjacent...

  8. In-vivo evaluation of convex array synthetic aperture imaging

    DEFF Research Database (Denmark)

    Pedersen, Morten Høgholm; Gammelmark, Kim Løkke; Jensen, Jørgen Arendt

    2007-01-01

    This paper presents an in-vivo study of synthetic transmit aperture (STA) imaging in comparison to conventional imaging, evaluating whether STA imaging is feasible in-vivo, and whether the image quality obtained is comparable to traditional scanned imaging in terms of penetration depth, spatial...

  9. Genetic Algorithm with Maximum-Minimum Crossover (GA-MMC) Applied in Optimization of Radiation Pattern Control of Phased-Array Radars for Rocket Tracking Systems

    Science.gov (United States)

    Silva, Leonardo W. T.; Barros, Vitor F.; Silva, Sandro G.

    2014-01-01

    In launching operations, Rocket Tracking Systems (RTS) process the trajectory data obtained by radar sensors. In order to improve functionality and maintenance, radars can be upgraded by replacing antennas with parabolic reflectors (PRs) with phased arrays (PAs). These arrays enable the electronic control of the radiation pattern by adjusting the signal supplied to each radiating element. However, in projects of phased array radars (PARs), the modeling of the problem is subject to various combinations of excitation signals producing a complex optimization problem. In this case, it is possible to calculate the problem solutions with optimization methods such as genetic algorithms (GAs). For this, the Genetic Algorithm with Maximum-Minimum Crossover (GA-MMC) method was developed to control the radiation pattern of PAs. The GA-MMC uses a reconfigurable algorithm with multiple objectives, differentiated coding and a new crossover genetic operator. This operator has a different approach from the conventional one, because it performs the crossover of the fittest individuals with the least fit individuals in order to enhance the genetic diversity. Thus, GA-MMC was successful in more than 90% of the tests for each application, increased the fitness of the final population by more than 20% and reduced the premature convergence. PMID:25196013

  10. Real-time PCR array as a universal platform for the detection of genetically modified crops and its application in identifying unapproved genetically modified crops in Japan.

    Science.gov (United States)

    Mano, Junichi; Shigemitsu, Natsuki; Futo, Satoshi; Akiyama, Hiroshi; Teshima, Reiko; Hino, Akihiro; Furui, Satoshi; Kitta, Kazumi

    2009-01-14

    We developed a novel type of real-time polymerase chain reaction (PCR) array with TaqMan chemistry as a platform for the comprehensive and semiquantitative detection of genetically modified (GM) crops. Thirty primer-probe sets for the specific detection of GM lines, recombinant DNA (r-DNA) segments, endogenous reference genes, and donor organisms were synthesized, and a 96-well PCR plate was prepared with a different primer-probe in each well as the real-time PCR array. The specificity and sensitivity of the array were evaluated. A comparative analysis with the data and publicly available information on GM crops approved in Japan allowed us to assume the possibility of unapproved GM crop contamination. Furthermore, we designed a Microsoft Excel spreadsheet application, Unapproved GMO Checker version 2.01, which helps process all the data of real-time PCR arrays for the easy assumption of unapproved GM crop contamination. The spreadsheet is available free of charge at http://cse.naro.affrc.go.jp/jmano/index.html .

  11. 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.

  12. Synthetic Biology and Personalized Medicine

    Science.gov (United States)

    Jain, K.K.

    2013-01-01

    Synthetic biology, application of synthetic chemistry to biology, is a broad term that covers the engineering of biological systems with structures and functions not found in nature to process information, manipulate chemicals, produce energy, maintain cell environment and enhance human health. Synthetic biology devices contribute not only to improve our understanding of disease mechanisms, but also provide novel diagnostic tools. Methods based on synthetic biology enable the design of novel strategies for the treatment of cancer, immune diseases metabolic disorders and infectious diseases as well as the production of cheap drugs. The potential of synthetic genome, using an expanded genetic code that is designed for specific drug synthesis as well as delivery and activation of the drug in vivo by a pathological signal, was already pointed out during a lecture delivered at Kuwait University in 2005. Of two approaches to synthetic biology, top-down and bottom-up, the latter is more relevant to the development of personalized medicines as it provides more flexibility in constructing a partially synthetic cell from basic building blocks for a desired task. PMID:22907209

  13. Novel synthetic Medea selfish genetic elements drive population replacement in Drosophila; a theoretical exploration of Medea-dependent population suppression.

    Science.gov (United States)

    Akbari, Omar S; Chen, Chun-Hong; Marshall, John M; Huang, Haixia; Antoshechkin, Igor; Hay, Bruce A

    2014-12-19

    Insects act as vectors for diseases of plants, animals, and humans. Replacement of wild insect populations with genetically modified individuals unable to transmit disease provides a potentially self-perpetuating method of disease prevention. Population replacement requires a gene drive mechanism in order to spread linked genes mediating disease refractoriness through wild populations. We previously reported the creation of synthetic Medea selfish genetic elements able to drive population replacement in Drosophila. These elements use microRNA-mediated silencing of myd88, a maternally expressed gene required for embryonic dorso-ventral pattern formation, coupled with early zygotic expression of a rescuing transgene, to bring about gene drive. Medea elements that work through additional mechanisms are needed in order to be able to carry out cycles of population replacement and/or remove existing transgenes from the population, using second-generation elements that spread while driving first-generation elements out of the population. Here we report the synthesis and population genetic behavior of two new synthetic Medea elements that drive population replacement through manipulation of signaling pathways involved in cellular blastoderm formation or Notch signaling, demonstrating that in Drosophila Medea elements can be generated through manipulation of diverse signaling pathways. We also describe the mRNA and small RNA changes in ovaries and early embryos associated from Medea-bearing females. Finally, we use modeling to illustrate how Medea elements carrying genes that result in diapause-dependent female lethality could be used to bring about population suppression.

  14. Synthetic virus seeds for improved vaccine safety: Genetic reconstruction of poliovirus seeds for a PER.C6 cell based inactivated poliovirus vaccine.

    Science.gov (United States)

    Sanders, Barbara P; Edo-Matas, Diana; Papic, Natasa; Schuitemaker, Hanneke; Custers, Jerome H H V

    2015-10-13

    Safety of vaccines can be compromised by contamination with adventitious agents. One potential source of adventitious agents is a vaccine seed, typically derived from historic clinical isolates with poorly defined origins. Here we generated synthetic poliovirus seeds derived from chemically synthesized DNA plasmids encoding the sequence of wild-type poliovirus strains used in marketed inactivated poliovirus vaccines. The synthetic strains were phenotypically identical to wild-type polioviruses as shown by equivalent infectious titers in culture supernatant and antigenic content, even when infection cultures are scaled up to 10-25L bioreactors. Moreover, the synthetic seeds were genetically stable upon extended passaging on the PER.C6 cell culture platform. Use of synthetic seeds produced on the serum-free PER.C6 cell platform ensures a perfectly documented seed history and maximum control over starting materials. It provides an opportunity to maximize vaccine safety which increases the prospect of a vaccine end product that is free from adventitious agents. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Parameter Optimization of Multi-Element Synthetic Aperture Imaging Systems

    Directory of Open Access Journals (Sweden)

    Vera Behar

    2007-03-01

    Full Text Available In conventional ultrasound imaging systems with phased arrays, the further improvement of lateral resolution requires enlarging of the number of array elements that in turn increases both, the complexity and the cost, of imaging systems. Multi-element synthetic aperture focusing (MSAF systems are a very good alternative to conventional systems with phased arrays. The benefit of the synthetic aperture is in reduction of the system complexity, cost and acquisition time. In a MSAF system considered in the paper, a group of elements transmit and receive signals simultaneously, and the transmit beam is defocused to emulate a single element response. The echo received at each element of a receive sub-aperture is recorded in the computer memory. The process of transmission/reception is repeated for all positions of a transmit sub-aperture. All the data recordings associated with each corresponding pair "transmit-receive sub-aperture" are then focused synthetically producing a low-resolution image. The final high-resolution image is formed by summing of the all low-resolution images associated with transmit/receive sub-apertures. A problem of parameter optimization of a MSAF system is considered in this paper. The quality of imaging (lateral resolution and contrast is expressed in terms of the beam characteristics - beam width and side lobe level. The comparison between the MSAF system described in the paper and an equivalent conventional phased array system shows that the MSAF system acquires images of equivalent quality much faster using only a small part of the power per image.

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

    Science.gov (United States)

    Adams, Bryn L

    2016-12-16

    Escherichia coli (E. coli) has played a pivotal role in the development of genetics and molecular biology as scientific fields. It is therefore not surprising that synthetic biology (SB) was built upon E. coli and continues to dominate the field. However, scientific capabilities have advanced from simple gene mutations to the insertion of rationally designed, complex synthetic circuits and creation of entirely synthetic genomes. The point is rapidly approaching where E. coli is no longer an adequate host for the increasingly sophisticated genetic designs of SB. It is time to develop the next generation of SB chassis; robust organisms that can provide the advanced physiology novel synthetic circuits will require to move SB from the laboratory into fieldable technologies. This can be accomplished by developing chassis-specific genetic toolkits that are as extensive as those for E. coli. However, the holy grail of SB would be the development of a universal toolkit that can be ported into any chassis. This viewpoint article underscores the need for new bacterial chassis, as well as discusses some of the important considerations in their selection. It also highlights a few examples of robust, tractable bacterial species that can meet the demands of tomorrow's state-of-the-art in SB. Significant advances have been made in the first 15 years since this field has emerged. However, the advances over the next 15 years will occur not in laboratory organisms, but in fieldable species where the potential of SB can be fully realized in game changing technology.

  17. 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.

  18. Synthetic Biology Open Language (SBOL) Version 2.2.0.

    Science.gov (United States)

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

    2018-04-02

    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 2.2.0 of SBOL that builds upon version 2.1.0 published in last year's JIB special issue. In particular, SBOL 2.2.0 includes improved description and validation rules for genetic design provenance, an extension to support combinatorial genetic designs, a new class to add non-SBOL data as attachments, a new class for genetic design implementations, and a description of a methodology to describe the entire design-build-test-learn cycle within the SBOL data model.

  19. Synthetic Biology Open Language (SBOL) Version 2.2.0

    KAUST Repository

    Cox, Robert Sidney

    2018-04-04

    Synthetic biology builds upon the techniques and successes of genetics, molecular biology, and metabolic engineering by applying engineering principles to the design of biological systems. The field still faces substantial challenges, including long development times, high rates of failure, and poor reproducibility. One method to ameliorate these problems would be to improve the exchange of information about designed systems between laboratories. The synthetic biology open language (SBOL) has been developed as a standard to support the specification and exchange of biological design information in synthetic biology, filling a need not satisfied by other pre-existing standards. This document details version 2.2.0 of SBOL that builds upon version 2.1.0 published in last year\\'s JIB special issue. In particular, SBOL 2.2.0 includes improved description and validation rules for genetic design provenance, an extension to support combinatorial genetic designs, a new class to add non-SBOL data as attachments, a new class for genetic design implementations, and a description of a methodology to describe the entire design-build-test-learn cycle within the SBOL data model.

  20. Synthetic Biology Open Language (SBOL Version 2.2.0

    Directory of Open Access Journals (Sweden)

    Cox Robert Sidney

    2018-04-01

    Full Text Available 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 2.2.0 of SBOL that builds upon version 2.1.0 published in last year’s JIB special issue. In particular, SBOL 2.2.0 includes improved description and validation rules for genetic design provenance, an extension to support combinatorial genetic designs, a new class to add non-SBOL data as attachments, a new class for genetic design implementations, and a description of a methodology to describe the entire design-build-test-learn cycle within the SBOL data model.

  1. Synthetic Biology Open Language (SBOL) Version 2.2.0

    KAUST Repository

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

    2018-01-01

    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 2.2.0 of SBOL that builds upon version 2.1.0 published in last year's JIB special issue. In particular, SBOL 2.2.0 includes improved description and validation rules for genetic design provenance, an extension to support combinatorial genetic designs, a new class to add non-SBOL data as attachments, a new class for genetic design implementations, and a description of a methodology to describe the entire design-build-test-learn cycle within the SBOL data model.

  2. PHARUS : PHased ARray Universal SAR

    NARCIS (Netherlands)

    Paquay, M.H.A.; Vermeulen, B.C.B.; Koomen, P.J.; Hoogeboom, P.; Snoeij, P.; Pouwels, H.

    1996-01-01

    In the Netherlands, a polarimetric C-band aircraft SAR (Synthetic Aperture Radar) has been developed. The project is called PHARUS, an acronm for PHased ARray Universal SAR. This instrument serves remote sensing applications. The antenna system contains 48 active modules (expandable to 96). A module

  3. Assessment of genetic fidelity in Rauvolfia serpentina plantlets grown from synthetic (encapsulated) seeds following in vitro storage at 4 °C.

    Science.gov (United States)

    Faisal, Mohammad; Alatar, Abdulrahman A; Ahmad, Naseem; Anis, Mohammad; Hegazy, Ahmad K

    2012-05-03

    An efficient method was developed for plant regeneration and establishment from alginate encapsulated synthetic seeds of Rauvolfia serpentina. Synthetic seeds were produced using in vitro proliferated microshoots upon complexation of 3% sodium alginate prepared in Llyod and McCown woody plant medium (WPM) and 100 mM calcium chloride. Re-growth ability of encapsulated nodal segments was evaluated after storage at 4 °C for 0, 1, 2, 4, 6 and 8 weeks and compared with non-encapsulated buds. Effects of different media viz; Murashige and Skoog medium; Lloyd and McCown woody Plant medium, Gamborg’s B5 medium and Schenk and Hildebrandt medium was also investigated for conversion into plantlets. The maximum frequency of conversion into plantlets from encapsulated nodal segments stored at 4 °C for 4 weeks was achieved on woody plant medium supplement with 5.0 μM BA and 1.0 μM NAA. Rooting in plantlets was achieved in half-strength Murashige and Skoog liquid medium containing 0.5 μM indole-3-acetic acid (IAA) on filter paper bridges. Plantlets obtained from stored synseeds were hardened, established successfully ex vitro and were morphologically similar to each other as well as their mother plant. The genetic fidelity of Rauvolfia clones raised from synthetic seeds following four weeks of storage at 4 °C were assessed by using random amplified polymorphic DNA (RAPD) and inter-simple sequence repeat (ISSR) markers. All the RAPD and ISSR profiles from generated plantlets were monomorphic and comparable to the mother plant, which confirms the genetic stability among the clones. This synseed protocol could be useful for establishing a particular system for conservation, short-term storage and production of genetically identical and stable plants before it is released for commercial purposes.

  4. Quantum transport in coupled resonators enclosed synthetic magnetic flux

    International Nuclear Information System (INIS)

    Jin, L.

    2016-01-01

    Quantum transport properties are instrumental to understanding quantum coherent transport processes. Potential applications of quantum transport are widespread, in areas ranging from quantum information science to quantum engineering, and not restricted to quantum state transfer, control and manipulation. Here, we study light transport in a ring array of coupled resonators enclosed synthetic magnetic flux. The ring configuration, with an arbitrary number of resonators embedded, forms a two-arm Aharonov–Bohm interferometer. The influence of magnetic flux on light transport is investigated. Tuning the magnetic flux can lead to resonant transmission, while half-integer magnetic flux quantum leads to completely destructive interference and transmission zeros in an interferometer with two equal arms. -- Highlights: •The light transport is investigated through ring array of coupled resonators enclosed synthetic magnetic field. •Aharonov–Bohm ring interferometer of arbitrary configuration is investigated. •The half-integer magnetic flux quantum leads to destructive interference and transmission zeros for two-arm at equal length. •Complete transmission is available via tuning synthetic magnetic flux.

  5. Field computation for two-dimensional array transducers with limited diffraction array beams.

    Science.gov (United States)

    Lu, Jian-Yu; Cheng, Jiqi

    2005-10-01

    A method is developed for calculating fields produced with a two-dimensional (2D) array transducer. This method decomposes an arbitrary 2D aperture weighting function into a set of limited diffraction array beams. Using the analytical expressions of limited diffraction beams, arbitrary continuous wave (cw) or pulse wave (pw) fields of 2D arrays can be obtained with a simple superposition of these beams. In addition, this method can be simplified and applied to a 1D array transducer of a finite or infinite elevation height. For beams produced with axially symmetric aperture weighting functions, this method can be reduced to the Fourier-Bessel method studied previously where an annular array transducer can be used. The advantage of the method is that it is accurate and computationally efficient, especially in regions that are not far from the surface of the transducer (near field), where it is important for medical imaging. Both computer simulations and a synthetic array experiment are carried out to verify the method. Results (Bessel beam, focused Gaussian beam, X wave and asymmetric array beams) show that the method is accurate as compared to that using the Rayleigh-Sommerfeld diffraction formula and agrees well with the experiment.

  6. Volumetric real-time imaging using a CMUT ring array.

    Science.gov (United States)

    Choe, Jung Woo; Oralkan, Ömer; Nikoozadeh, Amin; Gencel, Mustafa; Stephens, Douglas N; O'Donnell, Matthew; Sahn, David J; Khuri-Yakub, Butrus T

    2012-06-01

    A ring array provides a very suitable geometry for forward-looking volumetric intracardiac and intravascular ultrasound imaging. We fabricated an annular 64-element capacitive micromachined ultrasonic transducer (CMUT) array featuring a 10-MHz operating frequency and a 1.27-mm outer radius. A custom software suite was developed to run on a PC-based imaging system for real-time imaging using this device. This paper presents simulated and experimental imaging results for the described CMUT ring array. Three different imaging methods--flash, classic phased array (CPA), and synthetic phased array (SPA)--were used in the study. For SPA imaging, two techniques to improve the image quality--Hadamard coding and aperture weighting--were also applied. The results show that SPA with Hadamard coding and aperture weighting is a good option for ring-array imaging. Compared with CPA, it achieves better image resolution and comparable signal-to-noise ratio at a much faster image acquisition rate. Using this method, a fast frame rate of up to 463 volumes per second is achievable if limited only by the ultrasound time of flight; with the described system we reconstructed three cross-sectional images in real-time at 10 frames per second, which was limited by the computation time in synthetic beamforming.

  7. Simultaneous determination of six synthetic phenolic antioxidants in edible oils using dispersive liquid-liquid microextraction followed by high-performance liquid chromatography with diode array detection.

    Science.gov (United States)

    Xu, Shuangjiao; Liu, Liangliang; Wang, Yanqin; Zhou, Dayun; Kuang, Meng; Fang, Dan; Yang, Weihua; Wei, Shoujun; Xiao, Aiping; Ma, Lei

    2016-08-01

    A simple, rapid, organic-solvent- and sample-saving pretreatment technique, called dispersive liquid-liquid microextraction, was developed for the determination of six synthetic phenolic antioxidants from edible oils before high-performance liquid chromatography with diode array detection. The entire procedure was composed of a two-step microextraction and a centrifugal process and could be finished in about 5 min, only consuming only 25 mg of sample and 1 mL of the organic solvent for each extraction. The influences of several important parameters on the microextraction efficiency were thoroughly investigated. Recovery assays for oil samples were spiked at three concentration levels, 50, 100 and 200 mg/kg, and provided recoveries in the 86.3-102.5% range with a relative standard deviation below 3.5%. The intra-day and inter-day precisions for the analysis were less than 3.8%. The proposed method was successfully applied for the determination of synthetic phenolic antioxidants in different oil samples, and satisfactory results were obtained. Thus, the developed method represents a viable alternative for the quality control of synthetic phenolic antioxidant concentrations in edible oils. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Mangrove vegetation structure in Southeast Brazil from phased array L-band synthetic aperture radar data

    Science.gov (United States)

    de Souza Pereira, Francisca Rocha; Kampel, Milton; Cunha-Lignon, Marilia

    2016-07-01

    The potential use of phased array type L-band synthetic aperture radar (PALSAR) data for discriminating distinct physiographic mangrove types with different forest structure developments in a subtropical mangrove forest located in Cananéia on the Southern coast of São Paulo, Brazil, is investigated. The basin and fringe physiographic types and the structural development of mangrove vegetation were identified with the application of the Kruskal-Wallis statistical test to the SAR backscatter values of 10 incoherent attributes. The best results to separate basin to fringe types were obtained using copolarized HH, cross-polarized HV, and the biomass index (BMI). Mangrove structural parameters were also estimated using multiple linear regressions. BMI and canopy structure index were used as explanatory variables for canopy height, mean height, and mean diameter at breast height regression models, with significant R2=0.69, 0.73, and 0.67, respectively. The current study indicates that SAR L-band images can be used as a tool to discriminate physiographic types and to characterize mangrove forests. The results are relevant considering the crescent availability of freely distributed SAR images that can be more utilized for analysis, monitoring, and conservation of the mangrove ecosystem.

  9. Novel Synthetic Medea selfish genetic elements drive population replacement in Drosophila, and a theoretical exploration of Medea-dependent population suppression

    Science.gov (United States)

    Akbari, Omar S.; Chen, Chun-Hong; Marshall, John M.; Huang, Haixia; Antoshechkin, Igor; Hay, Bruce A.

    2013-01-01

    Insects act as vectors for diseases of plants, animals and humans. Replacement of wild insect populations with genetically modified individuals unable to transmit disease provides a potentially self-perpetuating method of disease prevention. Population replacement requires a gene drive mechanism in order to spread linked genes mediating disease refractoriness through wild populations. We previously reported the creation of synthetic Medea selfish genetic elements able to drive population replacement in Drosophila. These elements use microRNA-mediated silencing of myd88, a maternally expressed gene required for embryonic dorso-ventral pattern formation, coupled with early zygotic expression of a rescuing transgene, to bring about gene drive. Medea elements that work through additional mechanisms are needed in order to be able to carry out cycles of population replacement and/or remove existing transgenes from the population, using second-generation elements that spread while driving first-generation elements out of the population. Here we report the synthesis and population genetic behavior of two new synthetic Medea elements that drive population replacement through manipulation of signaling pathways involved in cellular blastoderm formation or Notch signaling, demonstrating that in Drosophila Medea elements can be generated through manipulation of diverse signaling pathways. We also describe the mRNA and small RNA changes in ovaries and early embryos associated from Medea-bearing females. Finally, we use modeling to illustrate how Medea elements carrying genes that result in diapause-dependent female lethality could be used to bring about population suppression. PMID:23654248

  10. Approaches to chemical synthetic biology.

    Science.gov (United States)

    Chiarabelli, Cristiano; Stano, Pasquale; Anella, Fabrizio; Carrara, Paolo; Luisi, Pier Luigi

    2012-07-16

    Synthetic biology is first represented in terms of two complementary aspects, the bio-engineering one, based on the genetic manipulation of extant microbial forms in order to obtain forms of life which do not exist in nature; and the chemical synthetic biology, an approach mostly based on chemical manipulation for the laboratory synthesis of biological structures that do not exist in nature. The paper is mostly devoted to shortly review chemical synthetic biology projects currently carried out in our laboratory. In particular, we describe: the minimal cell project, then the "Never Born Proteins" and lastly the Never Born RNAs. We describe and critically analyze the main results, emphasizing the possible relevance of chemical synthetic biology for the progress in basic science and biotechnology. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  11. A Blueprint for a Synthetic Genetic Feedback Controller to Reprogram Cell Fate.

    Science.gov (United States)

    Del Vecchio, Domitilla; Abdallah, Hussein; Qian, Yili; Collins, James J

    2017-01-25

    To artificially reprogram cell fate, experimentalists manipulate the gene regulatory networks (GRNs) that maintain a cell's phenotype. In practice, reprogramming is often performed by constant overexpression of specific transcription factors (TFs). This process can be unreliable and inefficient. Here, we address this problem by introducing a new approach to reprogramming based on mathematical analysis. We demonstrate that reprogramming GRNs using constant overexpression may not succeed in general. Instead, we propose an alternative reprogramming strategy: a synthetic genetic feedback controller that dynamically steers the concentration of a GRN's key TFs to any desired value. The controller works by adjusting TF expression based on the discrepancy between desired and actual TF concentrations. Theory predicts that this reprogramming strategy is guaranteed to succeed, and its performance is independent of the GRN's structure and parameters, provided that feedback gain is sufficiently high. As a case study, we apply the controller to a model of induced pluripotency in stem cells. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Chunking of Large Multidimensional Arrays

    Energy Technology Data Exchange (ETDEWEB)

    Rotem, Doron; Otoo, Ekow J.; Seshadri, Sridhar

    2007-02-28

    Data intensive scientific computations as well on-lineanalytical processing applications as are done on very large datasetsthat are modeled as k-dimensional arrays. The storage organization ofsuch arrays on disks is done by partitioning the large global array intofixed size hyper-rectangular sub-arrays called chunks or tiles that formthe units of data transfer between disk and memory. Typical queriesinvolve the retrieval of sub-arrays in a manner that accesses all chunksthat overlap the query results. An important metric of the storageefficiency is the expected number of chunks retrieved over all suchqueries. The question that immediately arises is "what shapes of arraychunks give the minimum expected number of chunks over a query workload?"In this paper we develop two probabilistic mathematical models of theproblem and provide exact solutions using steepest descent and geometricprogramming methods. Experimental results, using synthetic workloads onreal life data sets, show that our chunking is much more efficient thanthe existing approximate solutions.

  13. 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.

  14. Synthetic Aperture Sequential Beamformation applied to medical imaging

    DEFF Research Database (Denmark)

    Hemmsen, Martin Christian; Hansen, Jens Munk; Jensen, Jørgen Arendt

    2012-01-01

    Synthetic Aperture Sequential Beamforming (SASB) is applied to medical ultrasound imaging using a multi element convex array transducer. The main motivation for SASB is to apply synthetic aperture techniques without the need for storing RF-data for a number of elements and hereby devise a system...... with a reduced system complexity. Using a 192 element, 3.5 MHz, λ-pitch transducer, it is demonstrated using tissue-phantom and wire-phantom measurements, how the speckle size and the detail resolution is improved compared to conventional imaging....

  15. SNP Arrays

    Directory of Open Access Journals (Sweden)

    Jari Louhelainen

    2016-10-01

    Full Text Available The papers published in this Special Issue “SNP arrays” (Single Nucleotide Polymorphism Arrays focus on several perspectives associated with arrays of this type. The range of papers vary from a case report to reviews, thereby targeting wider audiences working in this field. The research focus of SNP arrays is often human cancers but this Issue expands that focus to include areas such as rare conditions, animal breeding and bioinformatics tools. Given the limited scope, the spectrum of papers is nothing short of remarkable and even from a technical point of view these papers will contribute to the field at a general level. Three of the papers published in this Special Issue focus on the use of various SNP array approaches in the analysis of three different cancer types. Two of the papers concentrate on two very different rare conditions, applying the SNP arrays slightly differently. Finally, two other papers evaluate the use of the SNP arrays in the context of genetic analysis of livestock. The findings reported in these papers help to close gaps in the current literature and also to give guidelines for future applications of SNP arrays.

  16. Philosophy of Systems and Synthetic Biology

    DEFF Research Database (Denmark)

    Green, Sara

    2017-01-01

    This entry aims to clarify how systems and synthetic biology contribute to and extend discussions within philosophy of science. Unlike fields such as developmental biology or molecular biology, systems and synthetic biology are not easily demarcated by a focus on a specific subject area or level...... of organization. Rather, they are characterized by the development and application of mathematical, computational, and synthetic modeling strategies in response to complex problems and challenges within the life sciences. Proponents of systems and synthetic biology often stress the necessity of a perspective...... that goes beyond the scope of molecular biology and genetic engineering, respectively. With the emphasis on systems and interaction networks, the approaches explicitly engage in one of the oldest philosophical discussions on the relationship between parts and wholes, or between reductionism and holism...

  17. Synthetic Botany.

    Science.gov (United States)

    Boehm, Christian R; Pollak, Bernardo; Purswani, Nuri; Patron, Nicola; Haseloff, Jim

    2017-07-05

    Plants are attractive platforms for synthetic biology and metabolic engineering. Plants' modular and plastic body plans, capacity for photosynthesis, extensive secondary metabolism, and agronomic systems for large-scale production make them ideal targets for genetic reprogramming. However, efforts in this area have been constrained by slow growth, long life cycles, the requirement for specialized facilities, a paucity of efficient tools for genetic manipulation, and the complexity of multicellularity. There is a need for better experimental and theoretical frameworks to understand the way genetic networks, cellular populations, and tissue-wide physical processes interact at different scales. We highlight new approaches to the DNA-based manipulation of plants and the use of advanced quantitative imaging techniques in simple plant models such as Marchantia polymorpha. These offer the prospects of improved understanding of plant dynamics and new approaches to rational engineering of plant traits. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

  18. Molecular Cloning Designer Simulator (MCDS: All-in-one molecular cloning and genetic engineering design, simulation and management software for complex synthetic biology and metabolic engineering projects

    Directory of Open Access Journals (Sweden)

    Zhenyu Shi

    2016-12-01

    Full Text Available Molecular Cloning Designer Simulator (MCDS is a powerful new all-in-one cloning and genetic engineering design, simulation and management software platform developed for complex synthetic biology and metabolic engineering projects. In addition to standard functions, it has a number of features that are either unique, or are not found in combination in any one software package: (1 it has a novel interactive flow-chart user interface for complex multi-step processes, allowing an integrated overview of the whole project; (2 it can perform a user-defined workflow of cloning steps in a single execution of the software; (3 it can handle multiple types of genetic recombineering, a technique that is rapidly replacing classical cloning for many applications; (4 it includes experimental information to conveniently guide wet lab work; and (5 it can store results and comments to allow the tracking and management of the whole project in one platform. MCDS is freely available from https://mcds.codeplex.com. Keywords: BioCAD, Genetic engineering software, Molecular cloning software, Synthetic biology, Workflow simulation and management

  19. S-Layer Based Bio-Imprinting - Synthetic S-Layer Polymers

    Science.gov (United States)

    2015-07-09

    AFRL-OSR-VA-TR-2015-0161 S-Layer Based Bio- Imprinting - Synthetic S-Layer Polymers Dietmar Pum ZENTRUM FUER NANOBIOTECHNOLOGIE Final Report 07/09...COVERED (From - To)      01-06-2012 to 31-05-2015 4.  TITLE AND SUBTITLE S-Layer Based Bio- Imprinting - Synthetic S-Layer Polymers 5a.  CONTRACT...technology for the fabrication of nano patterned thin film imprints by using functional S-layer protein arrays as templates. The unique feature of

  20. 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

  1. Improved Alkane Production in Nitrogen-Fixing and Halotolerant Cyanobacteria via Abiotic Stresses and Genetic Manipulation of Alkane Synthetic Genes.

    Science.gov (United States)

    Kageyama, Hakuto; Waditee-Sirisattha, Rungaroon; Sirisattha, Sophon; Tanaka, Yoshito; Mahakhant, Aparat; Takabe, Teruhiro

    2015-07-01

    Cyanobacteria possess the unique capacity to produce alkane. In this study, effects of nitrogen deficiency and salt stress on biosynthesis of alkanes were investigated in three kinds of cyanobacteria. Intracellular alkane accumulation was increased in nitrogen-fixing cyanobacterium Anabaena sp. PCC7120, but decreased in non-diazotrophic cyanobacterium Synechococcus elongatus PCC7942 and constant in a halotolerant cyanobacterium Aphanothece halophytica under nitrogen-deficient condition. We also found that salt stress increased alkane accumulation in Anabaena sp. PCC7120 and A. halophytica. The expression levels of two alkane synthetic genes were not upregulated significantly under nitrogen deficiency or salt stress in Anabaena sp. PCC7120. The transformant Anabaena sp. PCC7120 cells with additional alkane synthetic gene set from A. halophytica increased intracellular alkane accumulation level compared to control cells. These results provide a prospect to improve bioproduction of alkanes in nitrogen-fixing halotolerant cyanobacteria via abiotic stresses and genetic engineering.

  2. Synthetic biology approaches: Towards sustainable exploitation of marine bioactive molecules.

    Science.gov (United States)

    Seghal Kiran, G; Ramasamy, Pasiyappazham; Sekar, Sivasankari; Ramu, Meenatchi; Hassan, Saqib; Ninawe, A S; Selvin, Joseph

    2018-06-01

    The discovery of genes responsible for the production of bioactive metabolites via metabolic pathways combined with the advances in synthetic biology tools, has allowed the establishment of numerous microbial cell factories, for instance the yeast cell factories, for the manufacture of highly useful metabolites from renewable biomass. Genome mining and metagenomics are two platforms provide base-line data for reconstruction of genomes and metabolomes which is based in the development of synthetic/semi-synthetic genomes for marine natural products discovery. Engineered biofilms are being innovated on synthetic biology platform using genetic circuits and cell signalling systems as represillators controlling biofilm formation. Recombineering is a process of homologous recombination mediated genetic engineering, includes insertion, deletion or modification of any sequence specifically. Although this discipline considered new to the scientific domain, this field has now developed as promising endeavor on the accomplishment of sustainable exploitation of marine natural products. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. Control theory meets synthetic biology.

    Science.gov (United States)

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

    2016-07-01

    The past several years have witnessed an increased presence of control theoretic concepts in synthetic biology. This review presents an organized summary of how these control design concepts have been applied to tackle a variety of problems faced when building synthetic biomolecular circuits in living cells. In particular, we describe success stories that demonstrate how simple or more elaborate control design methods can be used to make the behaviour of synthetic genetic circuits within a single cell or across a cell population more reliable, predictable and robust to perturbations. The description especially highlights technical challenges that uniquely arise from the need to implement control designs within a new hardware setting, along with implemented or proposed solutions. Some engineering solutions employing complex feedback control schemes are also described, which, however, still require a deeper theoretical analysis of stability, performance and robustness properties. Overall, this paper should help synthetic biologists become familiar with feedback control concepts as they can be used in their application area. At the same time, it should provide some domain knowledge to control theorists who wish to enter the rising and exciting field of synthetic biology. © 2016 The Author(s).

  4. Mammalian Synthetic Biology: Time for Big MACs.

    Science.gov (United States)

    Martella, Andrea; Pollard, Steven M; Dai, Junbiao; Cai, Yizhi

    2016-10-21

    The enabling technologies of synthetic biology are opening up new opportunities for engineering and enhancement of mammalian cells. This will stimulate diverse applications in many life science sectors such as regenerative medicine, development of biosensing cell lines, therapeutic protein production, and generation of new synthetic genetic regulatory circuits. Harnessing the full potential of these new engineering-based approaches requires the design and assembly of large DNA constructs-potentially up to chromosome scale-and the effective delivery of these large DNA payloads to the host cell. Random integration of large transgenes, encoding therapeutic proteins or genetic circuits into host chromosomes, has several drawbacks such as risks of insertional mutagenesis, lack of control over transgene copy-number and position-specific effects; these can compromise the intended functioning of genetic circuits. The development of a system orthogonal to the endogenous genome is therefore beneficial. Mammalian artificial chromosomes (MACs) are functional, add-on chromosomal elements, which behave as normal chromosomes-being replicating and portioned to daughter cells at each cell division. They are deployed as useful gene expression vectors as they remain independent from the host genome. MACs are maintained as a single-copy and can accommodate multiple gene expression cassettes of, in theory, unlimited DNA size (MACs up to 10 megabases have been constructed). MACs therefore enabled control over ectopic gene expression and represent an excellent platform to rapidly prototype and characterize novel synthetic gene circuits without recourse to engineering the host genome. This review describes the obstacles synthetic biologists face when working with mammalian systems and how the development of improved MACs can overcome these-particularly given the spectacular advances in DNA synthesis and assembly that are fuelling this research area.

  5. Cyanobacteria: photosynthetic factories combining biodiversity, radiation resistance, and genetics to facilitate drug discovery.

    Science.gov (United States)

    Cassier-Chauvat, Corinne; Dive, Vincent; Chauvat, Franck

    2017-02-01

    Cyanobacteria are ancient, abundant, and widely diverse photosynthetic prokaryotes, which are viewed as promising cell factories for the ecologically responsible production of chemicals. Natural cyanobacteria synthesize a vast array of biologically active (secondary) metabolites with great potential for human health, while a few genetic models can be engineered for the (low level) production of biofuels. Recently, genome sequencing and mining has revealed that natural cyanobacteria have the capacity to produce many more secondary metabolites than have been characterized. The corresponding panoply of enzymes (polyketide synthases and non-ribosomal peptide synthases) of interest for synthetic biology can still be increased through gene manipulations with the tools available for the few genetically manipulable strains. In this review, we propose to exploit the metabolic diversity and radiation resistance of cyanobacteria, and when required the genetics of model strains, for the production and radioactive ( 14 C) labeling of bioactive products, in order to facilitate the screening for new drugs.

  6. Linear Array Ultrasonic Transducers: Sensitivity and Resolution Study

    International Nuclear Information System (INIS)

    Kramb, V.A.

    2005-01-01

    The University of Dayton Research Institute (UDRI) under contract by the US Air Force has designed and integrated a fully automated inspection system for the inspection of turbine engines that incorporates linear phased array ultrasonic transducers. Phased array transducers have been successfully implemented into weld and turbine blade root inspections where the defect types are well known and characterized. Embedded defects in aerospace turbine engine components are less well defined, however. In order to determine the applicability of linear arrays to aerospace inspections the sensitivity of array transducers to embedded defects in engine materials must be characterized. In addition, the implementation of array transducers into legacy inspection procedures must take into account any differences in sensitivity between the array transducer and that of the single element transducer currently used. This paper discusses preliminary results in a study that compares the sensitivity of linear array and conventional single element transducers to synthetic hard alpha defects in a titanium alloy

  7. Application of Three Electrical Resistivity Arrays to Evaluate ...

    African Journals Online (AJOL)

    ADOWIE PERE

    shallow depth while Dipole-dipole is more susceptible to edge effect at deeper depth followed by the Pole-dipole array. 2D electrical resistivity field .... Data Processing: Both the apparent resistivity measurements for the synthetic and field data ...

  8. Establishment and application of a multiplex genetic mutation-detection method of lung cancer based on MassARRAY platform

    International Nuclear Information System (INIS)

    Tian, Hong-Xia; Zhang, Xu-Chao; Wang, Zhen; Chen, Jian-Guang; Chen, Shi-Liang; Guo, Wei-Bang; Wu, Yi-Long

    2016-01-01

    Objective: This study aims to establish a method for highly parallel multiplexed detection of genetic mutations in Chinese lung cancer samples through Agena iPLEX chemistry and matrix-assisted laser desorption ionization time-of-flight analysis on MassARRAY mass spectrometry platform. Methods: We reviewed the related literature and data on lung cancer treatments. We also identified 99 mutation hot spots in 13 target genes closely related to the pathogenesis, drug resistance, and metastasis of lung cancer. A total of 297 primers, composed of 99 paired forward and reverse amplification primers and 99 matched extension primers, were designed using Assay Design software. The detection method was established by analyzing eight cell lines and six lung cancer specimens. The proposed method was then validated through comparisons by using a LungCarta TM kit. The sensitivity and specificity of the proposed method were evaluated by directly sequencing EGFR and KRAS genes in 100 lung cancer cases. Results: The proposed method was able to detect multiplex genetic mutations in lung cancer cell lines. This finding was consistent with the observations on previously reported mutations. The proposed method can also detect such mutations in clinical lung cancer specimens. This result was consistent with the observations with LungCarta TM kit. However, an FGFR2 mutation was detected only through the proposed method. The measured sensitivity and specificity were 100% and 96.3%, respectively. Conclusions: The proposed MassARRAY technology-based multiplex method can detect genetic mutations in Chinese lung cancer patients. Therefore, the proposed method can be applied to detect mutations in other cancer tissues

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

    Science.gov (United States)

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

    2016-01-01

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

  10. Synthetic Phage for Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    So Young Yoo

    2014-01-01

    Full Text Available Controlling structural organization and signaling motif display is of great importance to design the functional tissue regenerating materials. Synthetic phage, genetically engineered M13 bacteriophage has been recently introduced as novel tissue regeneration materials to display a high density of cell-signaling peptides on their major coat proteins for tissue regeneration purposes. Structural advantages of their long-rod shape and monodispersity can be taken together to construct nanofibrous scaffolds which support cell proliferation and differentiation as well as direct orientation of their growth in two or three dimensions. This review demonstrated how functional synthetic phage is designed and subsequently utilized for tissue regeneration that offers potential cell therapy.

  11. Preimplantation genetic diagnosis for chromosomal rearrangements with the use of array comparative genomic hybridization at the blastocyst stage.

    Science.gov (United States)

    Christodoulou, Christodoulos; Dheedene, Annelies; Heindryckx, Björn; van Nieuwerburgh, Filip; Deforce, Dieter; De Sutter, Petra; Menten, Björn; Van den Abbeel, Etienne

    2017-01-01

    To establish the value of array comparative genomic hybridization (CGH) for preimplantation genetic diagnosis (PGD) in embryos of translocation carriers in combination with vitrification and frozen embryo transfer in nonstimulated cycles. Retrospective data analysis study. Academic centers for reproductive medicine and genetics. Thirty-four couples undergoing PGD for chromosomal rearrangements from October 2013 to December 2015. Trophectoderm biopsy at day 5 or day 6 of embryo development and subsequently whole genome amplification and array CGH were performed. This approach revealed a high occurrence of aneuploidies and structural rearrangements unrelated to the parental rearrangement. Nevertheless, we observed a benefit in pregnancy rates of these couples. We detected chromosomal abnormalities in 133/207 embryos (64.2% of successfully amplified), and 74 showed a normal microarray profile (35.7%). In 48 of the 133 abnormal embryos (36.1%), an unbalanced rearrangement originating from the parental translocation was identified. Interestingly, 34.6% of the abnormal embryos (46/133) harbored chromosome rearrangements that were not directly linked to the parental translocation in question. We also detected a combination of unbalanced parental-derived rearrangements and aneuploidies in 27 of the 133 abnormal embryos (20.3%). The use of trophectoderm biopsy at the blastocyst stage is less detrimental to the survival of the embryo and leads to a more reliable estimate of the genomic content of the embryo than cleavage-stage biopsy. In this small cohort PGD study, we describe the successful implementation of array CGH analysis of blastocysts in patients with a chromosomal rearrangement to identify euploid embryos for transfer. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  12. Systematic genetic array analysis links the Saccharomyces cerevisiae SAGA/SLIK and NuA4 component Tra1 to multiple cellular processes

    Directory of Open Access Journals (Sweden)

    Andrews Brenda

    2008-07-01

    Full Text Available Abstract Background Tra1 is an essential 437-kDa component of the Saccharomyces cerevisiae SAGA/SLIK and NuA4 histone acetyltransferase complexes. It is a member of a group of key signaling molecules that share a carboxyl-terminal domain related to phosphatidylinositol-3-kinase but unlike many family members, it lacks kinase activity. To identify genetic interactions for TRA1 and provide insight into its function we have performed a systematic genetic array analysis (SGA on tra1SRR3413, an allele that is defective in transcriptional regulation. Results The SGA analysis revealed 114 synthetic slow growth/lethal (SSL interactions for tra1SRR3413. The interacting genes are involved in a range of cellular processes including gene expression, mitochondrial function, and membrane sorting/protein trafficking. In addition many of the genes have roles in the cellular response to stress. A hierarchal cluster analysis revealed that the pattern of SSL interactions for tra1SRR3413 most closely resembles deletions of a group of regulatory GTPases required for membrane sorting/protein trafficking. Consistent with a role for Tra1 in cellular stress, the tra1SRR3413 strain was sensitive to rapamycin. In addition, calcofluor white sensitivity of the strain was enhanced by the protein kinase inhibitor staurosporine, a phenotype shared with the Ada components of the SAGA/SLIK complex. Through analysis of a GFP-Tra1 fusion we show that Tra1 is principally localized to the nucleus. Conclusion We have demonstrated a genetic association of Tra1 with nuclear, mitochondrial and membrane processes. The identity of the SSL genes also connects Tra1 with cellular stress, a result confirmed by the sensitivity of the tra1SRR3413 strain to a variety of stress conditions. Based upon the nuclear localization of GFP-Tra1 and the finding that deletion of the Ada components of the SAGA complex result in similar phenotypes as tra1SRR3413, we suggest that the effects of tra1SRR3413

  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. Riding Quality Model for Asphalt Pavement Monitoring Using Phase Array Type L-band Synthetic Aperture Radar (PALSAR

    Directory of Open Access Journals (Sweden)

    Kamiya Yoshikazu

    2010-11-01

    Full Text Available There are difficulties associated with near-real time or frequent pavement monitoring, because it is time consuming and costly. This study aimed to develop a binary logit model for the evaluation of highway riding quality, which could be used to monitor pavement conditions. The model was applied to investigate the influence of backscattering values of Phase Array type L-band Synthetic Aperture Radar (PALSAR. Training data obtained during 3–7 May 2007 was used in the development process, together with actual international roughness index (IRI values collected along a highway in Ayutthaya province, Thailand. The analysis showed that an increase in the backscattering value in the HH or the VV polarization indicated the poor condition of the pavement surface and, of the two, the HH polarization is more suitable for developing riding quality evaluation. The model developed was applied to analyze highway number 3467, to demonstrate its capability. It was found that the assessment accuracy of the prediction of the highway level of service was 97.00%. This is a preliminary study of the proposed technique and more intensive investigation must be carried out using ALOS/PALSAR images in various seasons.

  15. 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.

  16. Comparative study of single-nucleotide polymorphism array and next generation sequencing based strategies on triploid identification in preimplantation genetic diagnosis and screen.

    Science.gov (United States)

    Xu, Jiawei; Niu, Wenbin; Peng, Zhaofeng; Bao, Xiao; Zhang, Meixiang; Wang, Linlin; Du, Linqing; Zhang, Nan; Sun, Yingpu

    2016-12-06

    Triploidy occurred about 2-3% in human pregnancies and contributed to approximately 15% of chromosomally caused human early miscarriage. It is essential for preimplantation genetic diagnosis and screen to distinct triploidy sensitively. Here, we performed comparative investigations between MALBAC-NGS and MDA-SNP array sensitivity on triploidy detection. Self-correction and reference-correction algorism were used to analyze the NGS data. We identified 5 triploid embryos in 1198 embryos of 218 PGD and PGS cycles using MDA-SNP array, the rate of tripoidy was 4.17‰ in PGS and PGD patients. Our results indicated that the MDA-SNP array was sensitive to digyny and diandry triploidy, MALBAC-NGS combined with self and reference genome correction strategies analyze were not sensitive to detect triploidy. Our study demonstrated that triploidy occurred at 4.17‰ in PGD and PGS, MDA-SNP array could successfully identify triploidy in PGD and PGS and genomic DNA. MALBAC-NGS combined with self and reference genome correction strategies were not sensitive to triploidy.

  17. 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.

  18. Paper-based synthetic gene networks.

    Science.gov (United States)

    Pardee, Keith; Green, Alexander A; Ferrante, Tom; Cameron, D Ewen; DaleyKeyser, Ajay; Yin, Peng; Collins, James J

    2014-11-06

    Synthetic gene networks have wide-ranging uses in reprogramming and rewiring organisms. To date, there has not been a way to harness the vast potential of these networks beyond the constraints of a laboratory or in vivo environment. Here, we present an in vitro paper-based platform that provides an alternate, versatile venue for synthetic biologists to operate and a much-needed medium for the safe deployment of engineered gene circuits beyond the lab. Commercially available cell-free systems are freeze dried onto paper, enabling the inexpensive, sterile, and abiotic distribution of synthetic-biology-based technologies for the clinic, global health, industry, research, and education. For field use, we create circuits with colorimetric outputs for detection by eye and fabricate a low-cost, electronic optical interface. We demonstrate this technology with small-molecule and RNA actuation of genetic switches, rapid prototyping of complex gene circuits, and programmable in vitro diagnostics, including glucose sensors and strain-specific Ebola virus sensors.

  19. Paper-based Synthetic Gene Networks

    Science.gov (United States)

    Pardee, Keith; Green, Alexander A.; Ferrante, Tom; Cameron, D. Ewen; DaleyKeyser, Ajay; Yin, Peng; Collins, James J.

    2014-01-01

    Synthetic gene networks have wide-ranging uses in reprogramming and rewiring organisms. To date, there has not been a way to harness the vast potential of these networks beyond the constraints of a laboratory or in vivo environment. Here, we present an in vitro paper-based platform that provides a new venue for synthetic biologists to operate, and a much-needed medium for the safe deployment of engineered gene circuits beyond the lab. Commercially available cell-free systems are freeze-dried onto paper, enabling the inexpensive, sterile and abiotic distribution of synthetic biology-based technologies for the clinic, global health, industry, research and education. For field use, we create circuits with colorimetric outputs for detection by eye, and fabricate a low-cost, electronic optical interface. We demonstrate this technology with small molecule and RNA actuation of genetic switches, rapid prototyping of complex gene circuits, and programmable in vitro diagnostics, including glucose sensors and strain-specific Ebola virus sensors. PMID:25417167

  20. Synergistic Synthetic Biology: Units in Concert

    Science.gov (United States)

    Trosset, Jean-Yves; Carbonell, Pablo

    2013-01-01

    Synthetic biology aims at translating the methods and strategies from engineering into biology in order to streamline the design and construction of biological devices through standardized parts. Modular synthetic biology devices are designed by means of an adequate elimination of cross-talk that makes circuits orthogonal and specific. To that end, synthetic constructs need to be adequately optimized through in silico modeling by choosing the right complement of genetic parts and by experimental tuning through directed evolution and craftsmanship. In this review, we consider an additional and complementary tool available to the synthetic biologist for innovative design and successful construction of desired circuit functionalities: biological synergies. Synergy is a prevalent emergent property in biological systems that arises from the concerted action of multiple factors producing an amplification or cancelation effect compared with individual actions alone. Synergies appear in domains as diverse as those involved in chemical and protein activity, polypharmacology, and metabolic pathway complementarity. In conventional synthetic biology designs, synergistic cross-talk between parts and modules is generally attenuated in order to verify their orthogonality. Synergistic interactions, however, can induce emergent behavior that might prove useful for synthetic biology applications, like in functional circuit design, multi-drug treatment, or in sensing and delivery devices. Synergistic design principles are therefore complementary to those coming from orthogonal design and may provide added value to synthetic biology applications. The appropriate modeling, characterization, and design of synergies between biological parts and units will allow the discovery of yet unforeseeable, novel synthetic biology applications. PMID:25022769

  1. Synergistic Synthetic Biology: Units in Concert

    International Nuclear Information System (INIS)

    Trosset, Jean-Yves; Carbonell, Pablo

    2013-01-01

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

  2. 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.

  3. 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.

  4. The metabochip, a custom genotyping array for genetic studies of metabolic, cardiovascular, and anthropometric traits.

    Directory of Open Access Journals (Sweden)

    Benjamin F Voight

    Full Text Available Genome-wide association studies have identified hundreds of loci for type 2 diabetes, coronary artery disease and myocardial infarction, as well as for related traits such as body mass index, glucose and insulin levels, lipid levels, and blood pressure. These studies also have pointed to thousands of loci with promising but not yet compelling association evidence. To establish association at additional loci and to characterize the genome-wide significant loci by fine-mapping, we designed the "Metabochip," a custom genotyping array that assays nearly 200,000 SNP markers. Here, we describe the Metabochip and its component SNP sets, evaluate its performance in capturing variation across the allele-frequency spectrum, describe solutions to methodological challenges commonly encountered in its analysis, and evaluate its performance as a platform for genotype imputation. The metabochip achieves dramatic cost efficiencies compared to designing single-trait follow-up reagents, and provides the opportunity to compare results across a range of related traits. The metabochip and similar custom genotyping arrays offer a powerful and cost-effective approach to follow-up large-scale genotyping and sequencing studies and advance our understanding of the genetic basis of complex human diseases and traits.

  5. 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

  6. Synthesis of highly-ordered TiO2 nanotube arrays with tunable sizes

    Science.gov (United States)

    Wang, Xian; Zha, Chenyang; Ji, Cheng; Zhang, Xiaoyan; Shen, Liming; Wang, Yifeng; Gupta, Arunava; Yoriya, Sorachon; Bao, Ningzhong

    2014-09-01

    Vertically-oriented one-dimensional TiO2 nanotube (TNT) arrays have been fabricated by anodic oxidation using different electrolyte solvents, including ethylene glycol (EG), diethylene glycol (DEG), and dimethyl sulfoxide (DMSO), in the presence of hydrofluoric acid (HF) or ammonium fluoride (NH4F). The influence of synthetic conditions, including the nature of the electrolyte and anodization voltage, on nanotube microstructure has been systematically investigated. Highly-ordered TNTs with tube length of ˜0.5-26.7 μm, inner diameter of ˜13-201 nm, and outer diameter of ˜28-250 nm have been obtained. The conversion of as-prepared TNT arrays from amorphous phase to crystalline structure has been achieved by a post-synthetic annealing at 500 °C for 3 h in oxygen ambient. The TNT arrays with tunable sizes and structures are attractive for use as electrode materials in fabrication of thin film solar cells and highly active photocatalysts.

  7. Synthesis of highly-ordered TiO2 nanotube arrays with tunable sizes

    International Nuclear Information System (INIS)

    Wang, Xian; Zha, Chenyang; Ji, Cheng; Zhang, Xiaoyan; Shen, Liming; Wang, Yifeng; Bao, Ningzhong; Gupta, Arunava; Yoriya, Sorachon

    2014-01-01

    Vertically-oriented one-dimensional TiO 2 nanotube (TNT) arrays have been fabricated by anodic oxidation using different electrolyte solvents, including ethylene glycol (EG), diethylene glycol (DEG), and dimethyl sulfoxide (DMSO), in the presence of hydrofluoric acid (HF) or ammonium fluoride (NH 4 F). The influence of synthetic conditions, including the nature of the electrolyte and anodization voltage, on nanotube microstructure has been systematically investigated. Highly-ordered TNTs with tube length of ∼0.5–26.7 μm, inner diameter of ∼13–201 nm, and outer diameter of ∼28–250 nm have been obtained. The conversion of as-prepared TNT arrays from amorphous phase to crystalline structure has been achieved by a post-synthetic annealing at 500 °C for 3 h in oxygen ambient. The TNT arrays with tunable sizes and structures are attractive for use as electrode materials in fabrication of thin film solar cells and highly active photocatalysts. (paper)

  8. Cell-free protein synthesis enabled rapid prototyping for metabolic engineering and synthetic biology

    Directory of Open Access Journals (Sweden)

    Lihong Jiang

    2018-06-01

    Full Text Available Advances in metabolic engineering and synthetic biology have facilitated the manufacturing of many valuable-added compounds and commodity chemicals using microbial cell factories in the past decade. However, due to complexity of cellular metabolism, the optimization of metabolic pathways for maximal production represents a grand challenge and an unavoidable barrier for metabolic engineering. Recently, cell-free protein synthesis system (CFPS has been emerging as an enabling alternative to address challenges in biomanufacturing. This review summarizes the recent progresses of CFPS in rapid prototyping of biosynthetic pathways and genetic circuits (biosensors to speed up design-build-test (DBT cycles of metabolic engineering and synthetic biology. Keywords: Cell-free protein synthesis, Metabolic pathway optimization, Genetic circuits, Metabolic engineering, Synthetic biology

  9. 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.

  10. Synthetic genetic polymers capable of heredity and evolution

    DEFF Research Database (Denmark)

    Pinheiro, Vitor B; Taylor, Alexander I; Cozens, Christopher

    2012-01-01

    in and recovered from six alternative genetic polymers based on simple nucleic acid architectures not found in nature [xeno-nucleic acids (XNAs)]. We also select XNA aptamers, which bind their targets with high affinity and specificity, demonstrating that beyond heredity, specific XNAs have the capacity......Genetic information storage and processing rely on just two polymers, DNA and RNA, yet whether their role reflects evolutionary history or fundamental functional constraints is currently unknown. With the use of polymerase evolution and design, we show that genetic information can be stored...... for Darwinian evolution and folding into defined structures. Thus, heredity and evolution, two hallmarks of life, are not limited to DNA and RNA but are likely to be emergent properties of polymers capable of information storage....

  11. 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

  12. 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).

  13. Synthetic biology devices and circuits for RNA-based 'smart vaccines': a propositional review.

    Science.gov (United States)

    Andries, Oliwia; Kitada, Tasuku; Bodner, Katie; Sanders, Niek N; Weiss, Ron

    2015-02-01

    Nucleic acid vaccines have been gaining attention as an alternative to the standard attenuated pathogen or protein based vaccine. However, an unrealized advantage of using such DNA or RNA based vaccination modalities is the ability to program within these nucleic acids regulatory devices that would provide an immunologist with the power to control the production of antigens and adjuvants in a desirable manner by administering small molecule drugs as chemical triggers. Advances in synthetic biology have resulted in the creation of highly predictable and modular genetic parts and devices that can be composed into synthetic gene circuits with complex behaviors. With the recent advent of modified RNA gene delivery methods and developments in the RNA replicon platform, we foresee a future in which mammalian synthetic biologists will create genetic circuits encoded exclusively on RNA. Here, we review the current repertoire of devices used in RNA synthetic biology and propose how programmable 'smart vaccines' will revolutionize the field of RNA vaccination.

  14. Recent advances in preimplantation genetic diagnosis

    Directory of Open Access Journals (Sweden)

    Kahraman S

    2015-04-01

    Full Text Available Semra Kahraman, Çağri Beyazyürek, Hüseyin Avni Taç, Caroline Pirkevi, Murat Cetinkaya, Neşe Gülüm IVF and Reproductive Genetics Center, Istanbul Memorial Hospital, Istanbul, Turkey Abstract: Preimplantation genetic diagnosis (PGD is an important method for the identification chromosomal abnormalities and genes responsible for genetic defects in embryos that are created through in vitro fertilization before pregnancy. As the list of conditions and indications for PGD testing is continuing to extend enormously, novel in vitro fertilization techniques and newly established genetic analysis techniques have been implemented in clinical settings in the recent years. Blastocyst-stage biopsy, vitrification techniques, time-lapse imaging, whole-genome amplification, array-based diagnostic techniques, and next-generation sequencing techniques are promising techniques for the accurate diagnosis of diverse genetic conditions and also for the selection of the best embryo that has the highest implantation capacity. The timing and technique used for biopsy, the amplification techniques, the genetic diagnosis techniques, and appropriate genetic counseling play important roles in establishing a successful PGD. In this review, those key points of PGD will be reviewed in detail. Keywords: preimplantation genetic diagnosis, array comparative genomic hybridization, single-nucleotide polymorphism arrays, next-generation sequencing, monogenic disorders, aneuploidy testing 

  15. [Analysis of clinical outcomes of different embryo stage biopsy in array comparative genomic hybridization based preimplantation genetic diagnosis and screening].

    Science.gov (United States)

    Shen, J D; Wu, W; Shu, L; Cai, L L; Xie, J Z; Ma, L; Sun, X P; Cui, Y G; Liu, J Y

    2017-12-25

    Objective: To evaluate the efficiency of the application of array comparative genomic hybridization (array-CGH) in preimplantation genetic diagnosis or screening (PGD/PGS), and compare the clinical outcomes of different stage embryo biopsy. Methods: The outcomes of 381 PGD/PGS cycles referred in the First Affiliated Hospital of Nanjing Medical University from July 2011 to August 2015 were retrospectively analyzed. There were 320 PGD cycles with 156 cleavage-stage-biopsy cycles and 164 trophectoderm-biopsy cycles, 61 PGS cycles with 23 cleavage-stage-biopsy cycles and 38 trophectoderm-biopsy cycles. Chromosomal analysis was performed by array-CGH technology combined with whole genome amplification. Single embryo transfer was performed in all transfer cycles. Live birth rate was calculated as the main clinical outcomes. Results: The embryo diagnosis rate of PGD/PGS by array-CGH were 96.9%-99.1%. In PGD biopsy cycles, the live birth rate per embryo transfer cycle and live birth rate per embryo biopsy cycle were 50.0%(58/116) and 37.2%(58/156) in cleavage-stage-biopsy group, 67.5%(85/126) and 51.8%(85/164) in trophectoderm-biopsy group (both P 0.05). Conclusions: High diagnosis rate and idea live birth rate are achieved in PGD/PGS cycles based on array-CGH technology. The live birth rate of trophectoderm-biopsy group is significantly higher than that of cleavage-stage-biopsy group in PGD cycles; the efficiency of trophectoderm-biopsy is better.

  16. Synthetic Biology and the U.S. Biotechnology Regulatory System: Challenges and Options

    Energy Technology Data Exchange (ETDEWEB)

    Carter, Sarah R. [J. Craig Venter Inst., Rockville, MD (United States); Rodemeyer, Michael [Univ. of Virginia, Charlottesville, VA (United States); Garfinkel, Michele S. [EMBO, Heidelberg (Germany); Friedman, Robert M. [J. Craig Venter Inst., Rockville, MD (United States)

    2014-05-01

    Synthetic Biology and the U.S. Biotechnology Regulatory System: Challenges and Options Sarah R. Carter, Ph.D., J. Craig Venter Institute; Michael Rodemeyer, J.D., University of Virginia; Michele S. Garfinkel, Ph.D., EMBO; Robert M. Friedman, Ph.D., J. Craig Venter Institute In recent years, a range of genetic engineering techniques referred to as “synthetic biology” has significantly expanded the tool kit available to scientists and engineers, providing them with far greater capabilities to engineer organisms than previous techniques allowed. The field of synthetic biology includes the relatively new ability to synthesize long pieces of DNA from chemicals, as well as improved methods for genetic manipulation and design of genetic pathways to achieve more precise control of biological systems. These advances will help usher in a new generation of genetically engineered microbes, plants, and animals. The JCVI Policy Center team, along with researchers at the University of Virginia and EMBO, examined how well the current U.S. regulatory system for genetically engineered products will handle the near-term introduction of organisms engineered using synthetic biology. In particular, the focus was on those organisms intended to be used or grown directly in the environment, outside of a contained facility. The study concludes that the U.S. regulatory agencies have adequate legal authority to address most, but not all, potential environmental, health and safety concerns posed by these organisms. Such near-term products are likely to represent incremental changes rather than a marked departure from previous genetically engineered organisms. However, the study also identified two key challenges for the regulatory system, which are detailed in the report. First, USDA’s authority over genetically engineered plants depends on the use of an older engineering technique that is no longer necessary for many applications. The shift to synthetic biology and other newer genetic

  17. Strategy revealing phenotypic differences among synthetic oscillator designs.

    Science.gov (United States)

    Lomnitz, Jason G; Savageau, Michael A

    2014-09-19

    Considerable progress has been made in identifying and characterizing the component parts of genetic oscillators, which play central roles in all organisms. Nonlinear interaction among components is sufficiently complex that mathematical models are required to elucidate their elusive integrated behavior. Although natural and synthetic oscillators exhibit common architectures, there are numerous differences that are poorly understood. Utilizing synthetic biology to uncover basic principles of simpler circuits is a way to advance understanding of natural circadian clocks and rhythms. Following this strategy, we address the following questions: What are the implications of different architectures and molecular modes of transcriptional control for the phenotypic repertoire of genetic oscillators? Are there designs that are more realizable or robust? We compare synthetic oscillators involving one of three architectures and various combinations of the two modes of transcriptional control using a methodology that provides three innovations: a rigorous definition of phenotype, a procedure for deconstructing complex systems into qualitatively distinct phenotypes, and a graphical representation for illuminating the relationship between genotype, environment, and the qualitatively distinct phenotypes of a system. These methods provide a global perspective on the behavioral repertoire, facilitate comparisons of alternatives, and assist the rational design of synthetic gene circuitry. In particular, the results of their application here reveal distinctive phenotypes for several designs that have been studied experimentally as well as a best design among the alternatives that has yet to be constructed and tested.

  18. Arraying proteins by cell-free synthesis.

    Science.gov (United States)

    He, Mingyue; Wang, Ming-Wei

    2007-10-01

    Recent advances in life science have led to great motivation for the development of protein arrays to study functions of genome-encoded proteins. While traditional cell-based methods have been commonly used for generating protein arrays, they are usually a time-consuming process with a number of technical challenges. Cell-free protein synthesis offers an attractive system for making protein arrays, not only does it rapidly converts the genetic information into functional proteins without the need for DNA cloning, but also presents a flexible environment amenable to production of folded proteins or proteins with defined modifications. Recent advancements have made it possible to rapidly generate protein arrays from PCR DNA templates through parallel on-chip protein synthesis. This article reviews current cell-free protein array technologies and their proteomic applications.

  19. Genetic map of Triticum turgidum based on a hexaploid wheat population without genetic recombination for D genome

    Directory of Open Access Journals (Sweden)

    Zhang Li

    2012-08-01

    Full Text Available Abstract Background A synthetic doubled-haploid hexaploid wheat population, SynDH1, derived from the spontaneous chromosome doubling of triploid F1 hybrid plants obtained from the cross of hybrids Triticum turgidum ssp. durum line Langdon (LDN and ssp. turgidum line AS313, with Aegilops tauschii ssp. tauschii accession AS60, was previously constructed. SynDH1 is a tetraploidization-hexaploid doubled haploid (DH population because it contains recombinant A and B chromosomes from two different T. turgidum genotypes, while all the D chromosomes from Ae. tauschii are homogenous across the whole population. This paper reports the construction of a genetic map using this population. Results Of the 606 markers used to assemble the genetic map, 588 (97% were assigned to linkage groups. These included 513 Diversity Arrays Technology (DArT markers, 72 simple sequence repeat (SSR, one insertion site-based polymorphism (ISBP, and two high-molecular-weight glutenin subunit (HMW-GS markers. These markers were assigned to the 14 chromosomes, covering 2048.79 cM, with a mean distance of 3.48 cM between adjacent markers. This map showed good coverage of the A and B genome chromosomes, apart from 3A, 5A, 6A, and 4B. Compared with previously reported maps, most shared markers showed highly consistent orders. This map was successfully used to identify five quantitative trait loci (QTL, including two for spikelet number on chromosomes 7A and 5B, two for spike length on 7A and 3B, and one for 1000-grain weight on 4B. However, differences in crossability QTL between the two T. turgidum parents may explain the segregation distortion regions on chromosomes 1A, 3B, and 6B. Conclusions A genetic map of T. turgidum including 588 markers was constructed using a synthetic doubled haploid (SynDH hexaploid wheat population. Five QTLs for three agronomic traits were identified from this population. However, more markers are needed to increase the density and resolution of

  20. Genetic map of Triticum turgidum based on a hexaploid wheat population without genetic recombination for D genome.

    Science.gov (United States)

    Zhang, Li; Luo, Jiang-Tao; Hao, Ming; Zhang, Lian-Quan; Yuan, Zhong-Wei; Yan, Ze-Hong; Liu, Ya-Xi; Zhang, Bo; Liu, Bao-Long; Liu, Chun-Ji; Zhang, Huai-Gang; Zheng, You-Liang; Liu, Deng-Cai

    2012-08-13

    A synthetic doubled-haploid hexaploid wheat population, SynDH1, derived from the spontaneous chromosome doubling of triploid F1 hybrid plants obtained from the cross of hybrids Triticum turgidum ssp. durum line Langdon (LDN) and ssp. turgidum line AS313, with Aegilops tauschii ssp. tauschii accession AS60, was previously constructed. SynDH1 is a tetraploidization-hexaploid doubled haploid (DH) population because it contains recombinant A and B chromosomes from two different T. turgidum genotypes, while all the D chromosomes from Ae. tauschii are homogenous across the whole population. This paper reports the construction of a genetic map using this population. Of the 606 markers used to assemble the genetic map, 588 (97%) were assigned to linkage groups. These included 513 Diversity Arrays Technology (DArT) markers, 72 simple sequence repeat (SSR), one insertion site-based polymorphism (ISBP), and two high-molecular-weight glutenin subunit (HMW-GS) markers. These markers were assigned to the 14 chromosomes, covering 2048.79 cM, with a mean distance of 3.48 cM between adjacent markers. This map showed good coverage of the A and B genome chromosomes, apart from 3A, 5A, 6A, and 4B. Compared with previously reported maps, most shared markers showed highly consistent orders. This map was successfully used to identify five quantitative trait loci (QTL), including two for spikelet number on chromosomes 7A and 5B, two for spike length on 7A and 3B, and one for 1000-grain weight on 4B. However, differences in crossability QTL between the two T. turgidum parents may explain the segregation distortion regions on chromosomes 1A, 3B, and 6B. A genetic map of T. turgidum including 588 markers was constructed using a synthetic doubled haploid (SynDH) hexaploid wheat population. Five QTLs for three agronomic traits were identified from this population. However, more markers are needed to increase the density and resolution of this map in the future study.

  1. Archaeal extrachromosomal genetic elements

    DEFF Research Database (Denmark)

    Wang, Haina; Peng, Nan; Shah, Shiraz Ali

    2015-01-01

    SUMMARY: Research on archaeal extrachromosomal genetic elements (ECEs) has progressed rapidly in the past decade. To date, over 60 archaeal viruses and 60 plasmids have been isolated. These archaeal viruses exhibit an exceptional diversity in morphology, with a wide array of shapes, such as spind......SUMMARY: Research on archaeal extrachromosomal genetic elements (ECEs) has progressed rapidly in the past decade. To date, over 60 archaeal viruses and 60 plasmids have been isolated. These archaeal viruses exhibit an exceptional diversity in morphology, with a wide array of shapes...... on archaeal ECEs has just started to unravel the molecular biology of these genetic entities and their interactions with archaeal hosts, it is expected to accelerate in the next decade....

  2. BISRU: Synthetic Microbes for Moon, Mars and Beyond

    Science.gov (United States)

    Cumbers, J.; Rothchild, L.

    2010-04-01

    Synthetic biology and genomics will bring a new range of designer organisms into being and give us new tools for the manipulation and control of these organisms. BISRU or biological in situ resource utilization is the use of such genetically modified organisms in space.

  3. 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).

  4. Synthetic biology for microbial heavy metal biosensors.

    Science.gov (United States)

    Kim, Hyun Ju; Jeong, Haeyoung; Lee, Sang Jun

    2018-02-01

    Using recombinant DNA technology, various whole-cell biosensors have been developed for detection of environmental pollutants, including heavy metal ions. Whole-cell biosensors have several advantages: easy and inexpensive cultivation, multiple assays, and no requirement of any special techniques for analysis. In the era of synthetic biology, cutting-edge DNA sequencing and gene synthesis technologies have accelerated the development of cell-based biosensors. Here, we summarize current technological advances in whole-cell heavy metal biosensors, including the synthetic biological components (bioparts), sensing and reporter modules, genetic circuits, and chassis cells. We discuss several opportunities for improvement of synthetic cell-based biosensors. First, new functional modules must be discovered in genome databases, and this knowledge must be used to upgrade specific bioparts through molecular engineering. Second, modules must be assembled into functional biosystems in chassis cells. Third, heterogeneity of individual cells in the microbial population must be eliminated. In the perspectives, the development of whole-cell biosensors is also discussed in the aspects of cultivation methods and synthetic cells.

  5. 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).

  6. Biosynthesis of therapeutic natural products using synthetic biology.

    Science.gov (United States)

    Awan, Ali R; Shaw, William M; Ellis, Tom

    2016-10-01

    Natural products are a group of bioactive structurally diverse chemicals produced by microorganisms and plants. These molecules and their derivatives have contributed to over a third of the therapeutic drugs produced in the last century. However, over the last few decades traditional drug discovery pipelines from natural products have become far less productive and far more expensive. One recent development with promise to combat this trend is the application of synthetic biology to therapeutic natural product biosynthesis. Synthetic biology is a young discipline with roots in systems biology, genetic engineering, and metabolic engineering. In this review, we discuss the use of synthetic biology to engineer improved yields of existing therapeutic natural products. We further describe the use of synthetic biology to combine and express natural product biosynthetic genes in unprecedented ways, and how this holds promise for opening up completely new avenues for drug discovery and production. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Modular design of artificial tissue homeostasis: robust control through synthetic cellular heterogeneity.

    Directory of Open Access Journals (Sweden)

    Miles Miller

    Full Text Available Synthetic biology efforts have largely focused on small engineered gene networks, yet understanding how to integrate multiple synthetic modules and interface them with endogenous pathways remains a challenge. Here we present the design, system integration, and analysis of several large scale synthetic gene circuits for artificial tissue homeostasis. Diabetes therapy represents a possible application for engineered homeostasis, where genetically programmed stem cells maintain a steady population of β-cells despite continuous turnover. We develop a new iterative process that incorporates modular design principles with hierarchical performance optimization targeted for environments with uncertainty and incomplete information. We employ theoretical analysis and computational simulations of multicellular reaction/diffusion models to design and understand system behavior, and find that certain features often associated with robustness (e.g., multicellular synchronization and noise attenuation are actually detrimental for tissue homeostasis. We overcome these problems by engineering a new class of genetic modules for 'synthetic cellular heterogeneity' that function to generate beneficial population diversity. We design two such modules (an asynchronous genetic oscillator and a signaling throttle mechanism, demonstrate their capacity for enhancing robust control, and provide guidance for experimental implementation with various computational techniques. We found that designing modules for synthetic heterogeneity can be complex, and in general requires a framework for non-linear and multifactorial analysis. Consequently, we adapt a 'phenotypic sensitivity analysis' method to determine how functional module behaviors combine to achieve optimal system performance. We ultimately combine this analysis with Bayesian network inference to extract critical, causal relationships between a module's biochemical rate-constants, its high level functional behavior in

  8. Modular design of artificial tissue homeostasis: robust control through synthetic cellular heterogeneity.

    Science.gov (United States)

    Miller, Miles; Hafner, Marc; Sontag, Eduardo; Davidsohn, Noah; Subramanian, Sairam; Purnick, Priscilla E M; Lauffenburger, Douglas; Weiss, Ron

    2012-01-01

    Synthetic biology efforts have largely focused on small engineered gene networks, yet understanding how to integrate multiple synthetic modules and interface them with endogenous pathways remains a challenge. Here we present the design, system integration, and analysis of several large scale synthetic gene circuits for artificial tissue homeostasis. Diabetes therapy represents a possible application for engineered homeostasis, where genetically programmed stem cells maintain a steady population of β-cells despite continuous turnover. We develop a new iterative process that incorporates modular design principles with hierarchical performance optimization targeted for environments with uncertainty and incomplete information. We employ theoretical analysis and computational simulations of multicellular reaction/diffusion models to design and understand system behavior, and find that certain features often associated with robustness (e.g., multicellular synchronization and noise attenuation) are actually detrimental for tissue homeostasis. We overcome these problems by engineering a new class of genetic modules for 'synthetic cellular heterogeneity' that function to generate beneficial population diversity. We design two such modules (an asynchronous genetic oscillator and a signaling throttle mechanism), demonstrate their capacity for enhancing robust control, and provide guidance for experimental implementation with various computational techniques. We found that designing modules for synthetic heterogeneity can be complex, and in general requires a framework for non-linear and multifactorial analysis. Consequently, we adapt a 'phenotypic sensitivity analysis' method to determine how functional module behaviors combine to achieve optimal system performance. We ultimately combine this analysis with Bayesian network inference to extract critical, causal relationships between a module's biochemical rate-constants, its high level functional behavior in isolation, and

  9. Designing Uniquely Addressable Bio-orthogonal Synthetic Scaffolds for DNA and RNA Origami.

    Science.gov (United States)

    Kozyra, Jerzy; Ceccarelli, Alessandro; Torelli, Emanuela; Lopiccolo, Annunziata; Gu, Jing-Ying; Fellermann, Harold; Stimming, Ulrich; Krasnogor, Natalio

    2017-07-21

    Nanotechnology and synthetic biology are rapidly converging, with DNA origami being one of the leading bridging technologies. DNA origami was shown to work well in a wide array of biotic environments. However, the large majority of extant DNA origami scaffolds utilize bacteriophages or plasmid sequences thus severely limiting its future applicability as a bio-orthogonal nanotechnology platform. In this paper we present the design of biologically inert (i.e., "bio-orthogonal") origami scaffolds. The synthetic scaffolds have the additional advantage of being uniquely addressable (unlike biologically derived ones) and hence are better optimized for high-yield folding. We demonstrate our fully synthetic scaffold design with both DNA and RNA origamis and describe a protocol to produce these bio-orthogonal and uniquely addressable origami scaffolds.

  10. Simulation of Optical and Synthetic Imaging using Microwave Reflectometry

    International Nuclear Information System (INIS)

    Kramer, G.J.; Nazikian, R.; Valeo, E.

    2004-01-01

    Two-dimensional full-wave time-dependent simulations in full plasma geometry are presented which show that conventional reflectometry (without a lens) can be used to synthetically image density fluctuations in fusion plasmas under conditions where the parallel correlation length greatly exceeds the poloidal correlation length of the turbulence. The advantage of synthetic imaging is that the image can be produced without the need for a large lens of high optical quality, and each frequency that is launched can be independently imaged. A particularly simple arrangement, consisting of a single receiver located at the midpoint of a microwave beam propagating along the plasma midplane is shown to suffice for imaging purposes. However, as the ratio of the parallel to poloidal correlation length decreases, a poloidal array of receivers needs to be used to synthesize the image with high accuracy. Simulations using DIII-D relevant parameters show the similarity of synthetic and optical imaging in present-day experiments

  11. Simulation of Optical and Synthetic Imaging using Microwave Reflectometry

    Energy Technology Data Exchange (ETDEWEB)

    G.J. Kramer; R. Nazikian; E. Valeo

    2004-01-16

    Two-dimensional full-wave time-dependent simulations in full plasma geometry are presented which show that conventional reflectometry (without a lens) can be used to synthetically image density fluctuations in fusion plasmas under conditions where the parallel correlation length greatly exceeds the poloidal correlation length of the turbulence. The advantage of synthetic imaging is that the image can be produced without the need for a large lens of high optical quality, and each frequency that is launched can be independently imaged. A particularly simple arrangement, consisting of a single receiver located at the midpoint of a microwave beam propagating along the plasma midplane is shown to suffice for imaging purposes. However, as the ratio of the parallel to poloidal correlation length decreases, a poloidal array of receivers needs to be used to synthesize the image with high accuracy. Simulations using DIII-D relevant parameters show the similarity of synthetic and optical imaging in present-day experiments.

  12. 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.

  13. Improved Focusing Method for 3-D Imaging using Row–Column-Addressed 2-D Arrays

    DEFF Research Database (Denmark)

    Bouzari, Hamed; Engholm, Mathias; Stuart, Matthias Bo

    2017-01-01

    A row–column-addressed (RCA) 2-D array can be interpreted as two orthogonal 1-D arrays. By transmitting with row elements and receiving the echoes through column elements or vice versa, a rectilinear volume in front of the array can be beamformed. Since the transmit and receive 1-D arrays are ort...... measurements with a PZT λ/2-pitch 3 MHz 62+62 RCA 2-D transducer probe. A synthetic aperture imaging sequence with single element transmissions at a time, is designed for imaging down to 14 cm at a volume rate of 44 Hz....

  14. Evaluation of SNP Data from the Malus Infinium Array Identifies Challenges for Genetic Analysis of Complex Genomes of Polyploid Origin.

    Directory of Open Access Journals (Sweden)

    Michela Troggio

    Full Text Available High throughput arrays for the simultaneous genotyping of thousands of single-nucleotide polymorphisms (SNPs have made the rapid genetic characterisation of plant genomes and the development of saturated linkage maps a realistic prospect for many plant species of agronomic importance. However, the correct calling of SNP genotypes in divergent polyploid genomes using array technology can be problematic due to paralogy, and to divergence in probe sequences causing changes in probe binding efficiencies. An Illumina Infinium II whole-genome genotyping array was recently developed for the cultivated apple and used to develop a molecular linkage map for an apple rootstock progeny (M432, but a large proportion of segregating SNPs were not mapped in the progeny, due to unexpected genotype clustering patterns. To investigate the causes of this unexpected clustering we performed BLAST analysis of all probe sequences against the 'Golden Delicious' genome sequence and discovered evidence for paralogous annealing sites and probe sequence divergence for a high proportion of probes contained on the array. Following visual re-evaluation of the genotyping data generated for 8,788 SNPs for the M432 progeny using the array, we manually re-scored genotypes at 818 loci and mapped a further 797 markers to the M432 linkage map. The newly mapped markers included the majority of those that could not be mapped previously, as well as loci that were previously scored as monomorphic, but which segregated due to divergence leading to heterozygosity in probe annealing sites. An evaluation of the 8,788 probes in a diverse collection of Malus germplasm showed that more than half the probes returned genotype clustering patterns that were difficult or impossible to interpret reliably, highlighting implications for the use of the array in genome-wide association studies.

  15. 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.

  16. Exome Array Analysis of Nuclear Lens Opacity.

    Science.gov (United States)

    Loomis, Stephanie J; Klein, Alison P; Lee, Kristine E; Chen, Fei; Bomotti, Samantha; Truitt, Barbara; Iyengar, Sudha K; Klein, Ronald; Klein, Barbara E K; Duggal, Priya

    2018-06-01

    Nuclear cataract is the most common subtype of age-related cataract, the leading cause of blindness worldwide. It results from advanced nuclear sclerosis, or opacity in the center of the optic lens, and is affected by both genetic and environmental risk factors, including smoking. We sought to understand the genetic factors associated with nuclear sclerosis through interrogation of rare and low frequency coding variants using exome array data. We analyzed Illumina Human Exome Array data for 1,488 participants of European ancestry in the Beaver Dam Eye Study who were without cataract surgery for association with nuclear sclerosis grade, controlling for age and sex. We performed single-variant regression analysis for 32,138 variants with minor allele frequency (MAF) ≥0.003. In addition, gene-based analysis of 11,844 genes containing at least two variants with MAF nuclear sclerosis, the possible association with the RNF149 gene highlights a potential candidate gene for future studies that aim to understand the genetic architecture of nuclear sclerosis.

  17. High frame rate synthetic aperture duplex imaging

    DEFF Research Database (Denmark)

    Stuart, Matthias Bo; Tomov, Borislav Gueorguiev; Pihl, Michael Johannes

    2013-01-01

    aperture flow imaging as demonstrated in this paper. Synthetic aperture, directional beamforming, and cross-correlation are used to produce B-mode and vector velocity images at high frame rates. The frame rate equals the effective pulse repetition frequency of each imaging mode. Emissions for making the B...... estimation is −1.8% and the relative standard deviation 5.4%. The approach can thus estimate both high and low velocities with equal accuracy and thereby makes it possible to present vector flow images with a high dynamic range. Measurements are made using the SARUS research scanner, a linear array......Conventional color flow images are limited in velocity range and can either show the high velocities in systole or be optimized for the lower diastolic velocities. The full dynamics of the flow is, thus, hard to visualize. The dynamic range can be significantly increased by employing synthetic...

  18. Array-based techniques for fingerprinting medicinal herbs

    Directory of Open Access Journals (Sweden)

    Xue Charlie

    2011-05-01

    Full Text Available Abstract Poor quality control of medicinal herbs has led to instances of toxicity, poisoning and even deaths. The fundamental step in quality control of herbal medicine is accurate identification of herbs. Array-based techniques have recently been adapted to authenticate or identify herbal plants. This article reviews the current array-based techniques, eg oligonucleotides microarrays, gene-based probe microarrays, Suppression Subtractive Hybridization (SSH-based arrays, Diversity Array Technology (DArT and Subtracted Diversity Array (SDA. We further compare these techniques according to important parameters such as markers, polymorphism rates, restriction enzymes and sample type. The applicability of the array-based methods for fingerprinting depends on the availability of genomics and genetics of the species to be fingerprinted. For the species with few genome sequence information but high polymorphism rates, SDA techniques are particularly recommended because they require less labour and lower material cost.

  19. Visual detection of multiple genetically modified organisms in a capillary array.

    Science.gov (United States)

    Shao, Ning; Chen, Jianwei; Hu, Jiaying; Li, Rong; Zhang, Dabing; Guo, Shujuan; Hui, Junhou; Liu, Peng; Yang, Litao; Tao, Sheng-Ce

    2017-01-31

    There is an urgent need for rapid, low-cost multiplex methodologies for the monitoring of genetically modified organisms (GMOs). Here, we report a C[combining low line]apillary A[combining low line]rray-based L[combining low line]oop-mediated isothermal amplification for M[combining low line]ultiplex visual detection of nucleic acids (CALM) platform for the simple and rapid monitoring of GMOs. In CALM, loop-mediated isothermal amplification (LAMP) primer sets are pre-fixed to the inner surface of capillaries. The surface of the capillary array is hydrophobic while the capillaries are hydrophilic, enabling the simultaneous loading and separation of the LAMP reaction mixtures into each capillary by capillary forces. LAMP reactions in the capillaries are then performed in parallel, and the results are visually detected by illumination with a hand-held UV device. Using CALM, we successfully detected seven frequently used transgenic genes/elements and five plant endogenous reference genes with high specificity and sensitivity. Moreover, we found that measurements of real-world blind samples by CALM are consistent with results obtained by independent real-time PCRs. Thus, with an ability to detect multiple nucleic acids in a single easy-to-operate test, we believe that CALM will become a widely applied technology in GMO monitoring.

  20. [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.

  1. Preimplantation genetic diagnosis

    Directory of Open Access Journals (Sweden)

    Karin Writzl

    2013-02-01

    Conclusions: Over the last two decades, PGD has been shown to be a reliable and safe genetic test for couples who are at risk of a specific inher - ited disorder. For PGS, the results from several ongoing randomized controlled trials performed at different cell biopsy stage, using array-CGH and SNP array will provide the data needed to evaluate the clinical efficacy.

  2. 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...

  3. Synthetic biology in cell-based cancer immunotherapy.

    Science.gov (United States)

    Chakravarti, Deboki; Wong, Wilson W

    2015-08-01

    The adoptive transfer of genetically engineered T cells with cancer-targeting receptors has shown tremendous promise for eradicating tumors in clinical trials. This form of cellular immunotherapy presents a unique opportunity to incorporate advanced systems and synthetic biology approaches to create cancer therapeutics with novel functions. We first review the development of synthetic receptors, switches, and circuits to control the location, duration, and strength of T cell activity against tumors. In addition, we discuss the cellular engineering and genome editing of host cells (or the chassis) to improve the efficacy of cell-based cancer therapeutics, and to reduce the time and cost of manufacturing. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Genetic mapping using the Diversity Arrays Technology (DArT) : application and validation using the whole-genome sequences of Arabidopsis thaliana and the fungal wheat pathogen Mycosphaerella graminicola

    NARCIS (Netherlands)

    Wittenberg, A.H.J.

    2007-01-01

    Diversity Arrays Technology (DArT) is a microarray-based DNA marker technique for genome-wide discovery and genotyping of genetic variation. DArT allows simultaneous scoring of hundreds- to thousands of restriction site based polymorphisms between genotypes and does not require DNA sequence

  5. Sorting white blood cells in microfabricated arrays

    Science.gov (United States)

    Castelino, Judith Andrea Rose

    Fractionating white cells in microfabricated arrays presents the potential for detecting cells with abnormal adhesive or deformation properties. A possible application is separating nucleated fetal red blood cells from maternal blood. Since fetal cells are nucleated, it is possible to extract genetic information about the fetus from them. Separating fetal cells from maternal blood would provide a low cost noninvasive prenatal diagnosis for genetic defects, which is not currently available. We present results showing that fetal cells penetrate further into our microfabricated arrays than adult cells, and that it is possible to enrich the fetal cell fraction using the arrays. We discuss modifications to the array which would result in further enrichment. Fetal cells are less adhesive and more deformable than adult white cells. To determine which properties limit penetration, we compared the penetration of granulocytes and lymphocytes in arrays with different etch depths, constriction size, constriction frequency, and with different amounts of metabolic activity. The penetration of lymphocytes and granulocytes into constrained and unconstrained arrays differed qualitatively. In constrained arrays, the cells were activated by repeated shearing, and the number of cells stuck as a function of distance fell superexponentially. In unconstrained arrays the number of cells stuck fell slower than an exponential. We attribute this result to different subpopulations of cells with different sticking parameters. We determined that penetration in unconstrained arrays was limited by metabolic processes, and that when metabolic activity was reduced penetration was limited by deformability. Fetal cells also contain a different form of hemoglobin with a higher oxygen affinity than adult hemoglobin. Deoxygenated cells are paramagnetic and are attracted to high magnetic field gradients. We describe a device which can separate cells using 10 μm magnetic wires to deflect the paramagnetic

  6. A Synthetic Biology Framework for Programming Eukaryotic Transcription Functions

    Science.gov (United States)

    Khalil, Ahmad S.; Lu, Timothy K.; Bashor, Caleb J.; Ramirez, Cherie L.; Pyenson, Nora C.; Joung, J. Keith; Collins, James J.

    2013-01-01

    SUMMARY Eukaryotic transcription factors (TFs) perform complex and combinatorial functions within transcriptional networks. Here, we present a synthetic framework for systematically constructing eukaryotic transcription functions using artificial zinc fingers, modular DNA-binding domains found within many eukaryotic TFs. Utilizing this platform, we construct a library of orthogonal synthetic transcription factors (sTFs) and use these to wire synthetic transcriptional circuits in yeast. We engineer complex functions, such as tunable output strength and transcriptional cooperativity, by rationally adjusting a decomposed set of key component properties, e.g., DNA specificity, affinity, promoter design, protein-protein interactions. We show that subtle perturbations to these properties can transform an individual sTF between distinct roles (activator, cooperative factor, inhibitory factor) within a transcriptional complex, thus drastically altering the signal processing behavior of multi-input systems. This platform provides new genetic components for synthetic biology and enables bottom-up approaches to understanding the design principles of eukaryotic transcriptional complexes and networks. PMID:22863014

  7. Synthetic aperture integration (SAI) algorithm for SAR imaging

    Science.gov (United States)

    Chambers, David H; Mast, Jeffrey E; Paglieroni, David W; Beer, N. Reginald

    2013-07-09

    A method and system for detecting the presence of subsurface objects within a medium is provided. In some embodiments, the imaging and detection system operates in a multistatic mode to collect radar return signals generated by an array of transceiver antenna pairs that is positioned across the surface and that travels down the surface. The imaging and detection system pre-processes the return signal to suppress certain undesirable effects. The imaging and detection system then generates synthetic aperture radar images from real aperture radar images generated from the pre-processed return signal. The imaging and detection system then post-processes the synthetic aperture radar images to improve detection of subsurface objects. The imaging and detection system identifies peaks in the energy levels of the post-processed image frame, which indicates the presence of a subsurface object.

  8. Array-based genotyping and genetic dissimilarity analysis of a set of maize inbred lines belonging to different heterotic groups

    Directory of Open Access Journals (Sweden)

    Jambrović Antun

    2014-01-01

    Full Text Available Here we describe the results of the detailed array-based genotyping obtained by using the Illumina MaizeSNP50 BeadChip of eleven inbred lines belonging to different heterotic groups relevant for maize breeding in Southeast Europe - European Corn Belt. The objectives of this study were to assess the utility of the MaizeSNP50 BeadChip platform by determining its descriptive power and to assess genetic dissimilarity of the inbred lines. The distribution of the SNPs was found not completely uniform among chromosomes, but average call rate was very high (97.9% and number of polymorphic loci was 33200 out of 50074 SNPs with known mapping position indicating descriptive power of the MaizeSNP50 BeadChip. The dendrogram obtained from UPGMA cluster analysis as well as principal component analysis (PCA confirmed pedigree information, undoubtedly distinguishing lines according to their background in two population varieties of Reid Yellow Dent and Lancaster Sure Crop. Dissimilarity analysis showed that all of the inbred lines could be distinguished from each other. Whereas cluster analysis did not definitely differentiate Mo17 and Ohio inbred lines, PCA revealed clear genetic differences between them. The studied inbred lines were confirmed to be genetically diverse, representing a large proportion of the genetic variation occurring in two maize heterotic groups.

  9. Antiangiogenic effects of synthetic analogs of curcumin in vivo ...

    African Journals Online (AJOL)

    The active compound curcumin is isolated from the spice turmeric. Curcumin, curcuminoids and their synthetic analogs have been shown to inhibit the progression of cancer in animal models. In colon and skin carcinogenesis the genetic changes engross different genes, but curcumin is effective in preventing ...

  10. Preliminary In-Vivo Evaluation of Convex Array Synthetic Aperture Imaging

    DEFF Research Database (Denmark)

    Pedersen, Morten Høgholm; Gammelmark, Kim; Jensen, Jørgen Arendt

    2004-01-01

    of STA imaging in comparison to conventional imaging. The purpose is to evaluate whether STA imaging is feasible in-vivo. and whether the image quality obtained is comparable to traditional scanned imaging in terms of penetration depth, spatial resolution, contrast resolution, and artifacts. Acquisition...... was done using our RASMUS research scanner and a 5.5 MHz convex array transducer. STA imaging applies spherical wave emulation using multi-element subapertures and a 20 mus linear FM signal as excitation pulse. For conventional imaging a 64 element aperture was used in transmit and receive with a 1.5 cycle...

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

    Science.gov (United States)

    Knuuttila, Tarja; Loettgers, Andrea

    2013-06-01

    Synthetic biology is often understood in terms of the pursuit for well-characterized biological parts to create synthetic wholes. Accordingly, it has typically been conceived of as an engineering dominated and application oriented field. We argue that the relationship of synthetic biology to engineering is far more nuanced than that and involves a sophisticated epistemic dimension, as shown by the recent practice of synthetic modeling. Synthetic models are engineered genetic networks that are implanted in a natural cell environment. Their construction is typically combined with experiments on model organisms as well as mathematical modeling and simulation. What is especially interesting about this combinational modeling practice is that, apart from greater integration between these different epistemic activities, it has also led to the questioning of some central assumptions and notions on which synthetic biology is based. As a result synthetic biology is in the process of becoming more "biology inspired." Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. pyXSIM: Synthetic X-ray observations generator

    Science.gov (United States)

    ZuHone, John A.; Hallman, Eric. J.

    2016-08-01

    pyXSIM simulates X-ray observations from astrophysical sources. X-rays probe the high-energy universe, from hot galaxy clusters to compact objects such as neutron stars and black holes and many interesting sources in between. pyXSIM generates synthetic X-ray observations of these sources from a wide variety of models, whether from grid-based simulation codes such as FLASH (ascl:1010.082), Enzo (ascl:1010.072), and Athena (ascl:1010.014), to particle-based codes such as Gadget (ascl:0003.001) and AREPO, and even from datasets that have been created “by hand”, such as from NumPy arrays. pyXSIM can also manipulate the synthetic observations it produces in various ways and export the simulated X-ray events to other software packages to simulate the end products of specific X-ray observatories. pyXSIM is an implementation of the PHOX (ascl:1112.004) algorithm and was initially the photon_simulator analysis module in yt (ascl:1011.022); it is dependent on yt.

  13. Synthetic addiction extends the productive life time of engineered Escherichia coli populations

    DEFF Research Database (Denmark)

    Rugbjerg, Peter; Sarup-Lytzen, Kira; Nagy, Mariann

    2018-01-01

    range of genetic variants that disrupt the biosynthetic capacity of the engineered organism. Synthetic product addiction that couples high-yield production of a desired metabolite to expression of nonconditionally essential genes could offer a solution to this problem by selectively favoring cells...... with biosynthetic capacity in the population without constraining the medium. We constructed such synthetic product addiction by controlling the expression of two nonconditionally essential genes with a mevalonic acid biosensor. The product-addicted production organism retained high-yield mevalonic acid production...... through 95 generations of cultivation, corresponding to the number of cell generations required for >200-m3 industrial-scale production, at which time the nonaddicted strain completely abolished production. Using deep DNA sequencing, we find that the product-addicted populations do not accumulate genetic...

  14. Synthetic biology, inspired by synthetic chemistry.

    Science.gov (United States)

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

    2012-07-16

    The topic synthetic biology appears still as an 'empty basket to be filled'. However, there is already plenty of claims and visions, as well as convincing research strategies about the theme of synthetic biology. First of all, synthetic biology seems to be about the engineering of biology - about bottom-up and top-down approaches, compromising complexity versus stability of artificial architectures, relevant in biology. Synthetic biology accounts for heterogeneous approaches towards minimal and even artificial life, the engineering of biochemical pathways on the organismic level, the modelling of molecular processes and finally, the combination of synthetic with nature-derived materials and architectural concepts, such as a cellular membrane. Still, synthetic biology is a discipline, which embraces interdisciplinary attempts in order to have a profound, scientific base to enable the re-design of nature and to compose architectures and processes with man-made matter. We like to give an overview about the developments in the field of synthetic biology, regarding polymer-based analogs of cellular membranes and what questions can be answered by applying synthetic polymer science towards the smallest unit in life, namely a cell. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  15. 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.

  16. Amplitude and Phase Calibration of an Dual Polarized Active Phased Array Antenna

    NARCIS (Netherlands)

    Vermeulen, B.C.B.; Paquay, M.H.A.; Koomen, P.J.; Hoogeboom, P.; Snoeij, P.; Pouwels, H.

    1996-01-01

    In the Netherlands, a Polarimetrie C-band aircraft SAR (Synthetic Aperture Radar) has been developed. The project is called PHARUS, an acronym for Phased Array Universal SAR. This instrument serves remote sensing applications. The antenna system contains 48 modules (expandable to 96). A module is

  17. Molecular analysis of genetic diversity in elite II synthetic hexaploid ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-07-20

    Jul 20, 2009 ... The presence of sufficient genetic diversity in the germplam is an important ..... Figure 1. PCR amplification profile of Elite-II SH Wheat using the primer OPG-2. .... genetic relationships among cowpea breeding lines and local.

  18. Evaluation of cytoplasmic genetic effects for production and ...

    African Journals Online (AJOL)

    uvp

    2014-12-03

    Dec 3, 2014 ... Cytoplasmic genetic effects are transmitted directly only from mother to offspring through mitochondrial DNA. Normal genetic .... inheritance in three synthetic lines of beef cattle differing in mature size. J. Anim. Sci. 69, 745.

  19. Research on High-Precision, Low Cost Piezoresistive MEMS-Array Pressure Transmitters Based on Genetic Wavelet Neural Networks for Meteorological Measurements

    Directory of Open Access Journals (Sweden)

    Jiahong Zhang

    2015-05-01

    Full Text Available This paper provides a novel and effective compensation method by improving the hardware design and software algorithm to achieve optimization of piezoresistive pressure sensors and corresponding measurement systems in order to measure pressure more accurately and stably, as well as to meet the application requirements of the meteorological industry. Specifically, GE NovaSensor MEMS piezoresistive pressure sensors within a thousandth of accuracy are selected to constitute an array. In the versatile compensation method, the hardware utilizes the array of MEMS pressure sensors to reduce random error caused by sensor creep, and the software adopts the data fusion technique based on the wavelet neural network (WNN which is improved by genetic algorithm (GA to analyze the data of sensors for the sake of obtaining accurate and complete information over the wide temperature and pressure ranges. The GA-WNN model is implemented in hardware by using the 32-bit STMicroelectronics (STM32 microcontroller combined with an embedded real-time operating system µC/OS-II to make the output of the array of MEMS sensors be a direct digital readout. The results of calibration and test experiments clearly show that the GA-WNN technique can be effectively applied to minimize the sensor errors due to the temperature drift, the hysteresis effect and the long-term drift because of aging and environmental changes. The maximum error of the low cost piezoresistive MEMS-array pressure transmitter proposed by us is within 0.04% of its full-scale value, and it can satisfy the meteorological pressure measurement.

  20. Preparing Synthetic Biology for the World

    Directory of Open Access Journals (Sweden)

    Gerd H.G. Moe-Behrens

    2013-01-01

    Full Text Available Synthetic Biology promises low-cost, exponentially scalable products and global health solutions in the form of self-replicating organisms, or living devices. As these promises are realized, proof-of-concept systems will gradually migrate from tightly regulated laboratory or industrial environments into private spaces as, for instance, probiotic health products, food, and even do-it-yourself bioengineered systems. What additional steps, if any, should be taken before releasing engineered self-replicating organisms into a broader user space? In this review, we explain how studies of genetically modified organisms lay groundwork for the future landscape of biosafety. Early in the design process, biological engineers are anticipating potential hazards and developing innovative tools to mitigate risk. Here, we survey lessons learned, ongoing efforts to engineer intrinsic biocontainment, and how different stakeholders in synthetic biology can act to accomplish best practices for biosafety.

  1. Breeding value of primary synthetic wheat genotypes for grain yield

    Science.gov (United States)

    To introduce new genetic diversity into the bread wheat gene pool from its progenitor, Aegilops tauschii (Coss.) Schmalh, 33 primary synthetic hexaploid wheat genotypes (SYN) were crossed to 20 spring bread wheat (BW) cultivars at the International Wheat and Maize Improvement Center. Modified single...

  2. Fast and easy protocol for the purification of recombinant S-layer protein for synthetic biology applications

    KAUST Repository

    Norville, Julie E.; Kelly, Deborah F.; Knight, Thomas F.; Belcher, Angela M.; Walz, Thomas

    2011-01-01

    A goal of synthetic biology is to make biological systems easier to engineer. One of the aims is to design, with nanometer-scale precision, biomaterials with well-defined properties. The surface-layer protein SbpA forms 2D arrays naturally

  3. Annotating novel genes by integrating synthetic lethals and genomic information

    Directory of Open Access Journals (Sweden)

    Faty Mahamadou

    2008-01-01

    Full Text Available Abstract Background Large scale screening for synthetic lethality serves as a common tool in yeast genetics to systematically search for genes that play a role in specific biological processes. Often the amounts of data resulting from a single large scale screen far exceed the capacities of experimental characterization of every identified target. Thus, there is need for computational tools that select promising candidate genes in order to reduce the number of follow-up experiments to a manageable size. Results We analyze synthetic lethality data for arp1 and jnm1, two spindle migration genes, in order to identify novel members in this process. To this end, we use an unsupervised statistical method that integrates additional information from biological data sources, such as gene expression, phenotypic profiling, RNA degradation and sequence similarity. Different from existing methods that require large amounts of synthetic lethal data, our method merely relies on synthetic lethality information from two single screens. Using a Multivariate Gaussian Mixture Model, we determine the best subset of features that assign the target genes to two groups. The approach identifies a small group of genes as candidates involved in spindle migration. Experimental testing confirms the majority of our candidates and we present she1 (YBL031W as a novel gene involved in spindle migration. We applied the statistical methodology also to TOR2 signaling as another example. Conclusion We demonstrate the general use of Multivariate Gaussian Mixture Modeling for selecting candidate genes for experimental characterization from synthetic lethality data sets. For the given example, integration of different data sources contributes to the identification of genetic interaction partners of arp1 and jnm1 that play a role in the same biological process.

  4. 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.

  5. SAQC: SNP Array Quality Control

    Directory of Open Access Journals (Sweden)

    Li Ling-Hui

    2011-04-01

    Full Text Available Abstract Background Genome-wide single-nucleotide polymorphism (SNP arrays containing hundreds of thousands of SNPs from the human genome have proven useful for studying important human genome questions. Data quality of SNP arrays plays a key role in the accuracy and precision of downstream data analyses. However, good indices for assessing data quality of SNP arrays have not yet been developed. Results We developed new quality indices to measure the quality of SNP arrays and/or DNA samples and investigated their statistical properties. The indices quantify a departure of estimated individual-level allele frequencies (AFs from expected frequencies via standardized distances. The proposed quality indices followed lognormal distributions in several large genomic studies that we empirically evaluated. AF reference data and quality index reference data for different SNP array platforms were established based on samples from various reference populations. Furthermore, a confidence interval method based on the underlying empirical distributions of quality indices was developed to identify poor-quality SNP arrays and/or DNA samples. Analyses of authentic biological data and simulated data show that this new method is sensitive and specific for the detection of poor-quality SNP arrays and/or DNA samples. Conclusions This study introduces new quality indices, establishes references for AFs and quality indices, and develops a detection method for poor-quality SNP arrays and/or DNA samples. We have developed a new computer program that utilizes these methods called SNP Array Quality Control (SAQC. SAQC software is written in R and R-GUI and was developed as a user-friendly tool for the visualization and evaluation of data quality of genome-wide SNP arrays. The program is available online (http://www.stat.sinica.edu.tw/hsinchou/genetics/quality/SAQC.htm.

  6. Synthetic LISA: Simulating time delay interferometry in a model LISA

    International Nuclear Information System (INIS)

    Vallisneri, Michele

    2005-01-01

    We report on three numerical experiments on the implementation of Time-Delay Interferometry (TDI) for LISA, performed with Synthetic LISA, a C++/Python package that we developed to simulate the LISA science process at the level of scientific and technical requirements. Specifically, we study the laser-noise residuals left by first-generation TDI when the LISA armlengths have a realistic time dependence; we characterize the armlength-measurement accuracies that are needed to have effective laser-noise cancellation in both first- and second-generation TDI; and we estimate the quantization and telemetry bitdepth needed for the phase measurements. Synthetic LISA generates synthetic time series of the LISA fundamental noises, as filtered through all the TDI observables; it also provides a streamlined module to compute the TDI responses to gravitational waves according to a full model of TDI, including the motion of the LISA array and the temporal and directional dependence of the armlengths. We discuss the theoretical model that underlies the simulation, its implementation, and its use in future investigations on system-characterization and data-analysis prototyping for LISA

  7. Diversity arrays technology (DArT) markers in apple for genetic linkage maps

    NARCIS (Netherlands)

    Schouten, H.J.; Weg, van de W.E.; Carling, J.; Khan, S.A.; McKay, S.J.; Kaauwen, van M.P.W.

    2012-01-01

    Diversity Arrays Technology (DArT) provides a high-throughput whole-genome genotyping platform for the detection and scoring of hundreds of polymorphic loci without any need for prior sequence information. The work presented here details the development and performance of a DArT genotyping array for

  8. Genetic Identity in Genebanks: Application of the SolCAP 12K SNP Array in Fingerprinting and Diversity Analysis in the Global In Trust Potato Collection.

    Science.gov (United States)

    Ellis, David; Chavez, Oswaldo; Coombs, Joseph J; Soto, Julian V; Gomez, Rene; Douches, David S; Panta, Ana; Silvestre, Rocio; Anglin, Noelle Lynette

    2018-05-24

    Breeders rely on genetic integrity of material from genebanks, however, mislabeling and errors in original data can occur. Paired samples of original material and their in vitro counterparts from 250 diverse potato landrace accessions from the International Potato Center (CIP), were fingerprinted using the Infinium 12K V2 Potato Array to confirm genetic identity and evaluate genetic diversity. Diploid, triploid, and tetraploid accessions were included representing seven cultivated potato taxa (Hawkes, 1990). Fingerprints between mother field plants and in vitro clones, were used to evaluate identity, relatedness, and ancestry. Clones of the same accession grouped together, however eleven (4.4%) accessions were mismatches genetically. SNP genotypes were used to construct a phylogeny to evaluate inter- and intraspecific relationships and population structure. Data suggests that the triploids evaluated are genetically similar. STRUCTURE analysis identified several putative hybrids and suggests six populations with significant gene flow between. This study provides a model for genetic identity of plant genetic resources collections as mistakes in conservation of these collections and in genebanks is a reality and confirmed identity is critical for breeders and other users of these collections, as well as for quality management programs and to provide insights into the diversity of the accessions evaluated.

  9. Synthetic biology approaches in drug discovery and pharmaceutical biotechnology.

    Science.gov (United States)

    Neumann, Heinz; Neumann-Staubitz, Petra

    2010-06-01

    Synthetic biology is the attempt to apply the concepts of engineering to biological systems with the aim to create organisms with new emergent properties. These organisms might have desirable novel biosynthetic capabilities, act as biosensors or help us to understand the intricacies of living systems. This approach has the potential to assist the discovery and production of pharmaceutical compounds at various stages. New sources of bioactive compounds can be created in the form of genetically encoded small molecule libraries. The recombination of individual parts has been employed to design proteins that act as biosensors, which could be used to identify and quantify molecules of interest. New biosynthetic pathways may be designed by stitching together enzymes with desired activities, and genetic code expansion can be used to introduce new functionalities into peptides and proteins to increase their chemical scope and biological stability. This review aims to give an insight into recently developed individual components and modules that might serve as parts in a synthetic biology approach to pharmaceutical biotechnology.

  10. Efficient engineering of marker-free synthetic allotetraploids of Saccharomyces.

    Science.gov (United States)

    Alexander, William G; Peris, David; Pfannenstiel, Brandon T; Opulente, Dana A; Kuang, Meihua; Hittinger, Chris Todd

    2016-04-01

    Saccharomyces interspecies hybrids are critical biocatalysts in the fermented beverage industry, including in the production of lager beers, Belgian ales, ciders, and cold-fermented wines. Current methods for making synthetic interspecies hybrids are cumbersome and/or require genome modifications. We have developed a simple, robust, and efficient method for generating allotetraploid strains of prototrophic Saccharomyces without sporulation or nuclear genome manipulation. S. cerevisiae×S. eubayanus, S. cerevisiae×S. kudriavzevii, and S. cerevisiae×S. uvarum designer hybrid strains were created as synthetic lager, Belgian, and cider strains, respectively. The ploidy and hybrid nature of the strains were confirmed using flow cytometry and PCR-RFLP analysis, respectively. This method provides an efficient means for producing novel synthetic hybrids for beverage and biofuel production, as well as for constructing tetraploids to be used for basic research in evolutionary genetics and genome stability. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Investigation of synthetic aperture methods in ultrasound surface imaging using elementary surface types.

    Science.gov (United States)

    Kerr, W; Pierce, S G; Rowe, P

    2016-12-01

    Synthetic aperture imaging methods have been employed widely in recent research in non-destructive testing (NDT), but uptake has been more limited in medical ultrasound imaging. Typically offering superior focussing power over more traditional phased array methods, these techniques have been employed in NDT applications to locate and characterise small defects within large samples, but have rarely been used to image surfaces. A desire to ultimately employ ultrasonic surface imaging for bone surface geometry measurement prior to surgical intervention motivates this research, and results are presented for initial laboratory trials of a surface reconstruction technique based on global thresholding of ultrasonic 3D point cloud data. In this study, representative geometry artefacts were imaged in the laboratory using two synthetic aperture techniques; the Total Focusing Method (TFM) and the Synthetic Aperture Focusing Technique (SAFT) employing full and narrow synthetic apertures, respectively. Three high precision metallic samples of known geometries (cuboid, sphere and cylinder) which featured a range of elementary surface primitives were imaged using a 5MHz, 128 element 1D phased array employing both SAFT and TFM approaches. The array was manipulated around the samples using a precision robotic positioning system, allowing for repeatable ultrasound derived 3D surface point clouds to be created. A global thresholding technique was then developed that allowed the extraction of the surface profiles, and these were compared with the known geometry samples to provide a quantitative measure of error of 3D surface reconstruction. The mean errors achieved with optimised SAFT imaging for the cuboidal, spherical and cylindrical samples were 1.3mm, 2.9mm and 2.0mm respectively, while those for TFM imaging were 3.7mm, 3.0mm and 3.1mm, respectively. These results were contrary to expectations given the higher information content associated with the TFM images. However, it was

  12. Tunable signal processing in synthetic MAP kinase cascades.

    Science.gov (United States)

    O'Shaughnessy, Ellen C; Palani, Santhosh; Collins, James J; Sarkar, Casim A

    2011-01-07

    The flexibility of MAPK cascade responses enables regulation of a vast array of cell fate decisions, but elucidating the mechanisms underlying this plasticity is difficult in endogenous signaling networks. We constructed insulated mammalian MAPK cascades in yeast to explore how intrinsic and extrinsic perturbations affect the flexibility of these synthetic signaling modules. Contrary to biphasic dependence on scaffold concentration, we observe monotonic decreases in signal strength as scaffold concentration increases. We find that augmenting the concentration of sequential kinases can enhance ultrasensitivity and lower the activation threshold. Further, integrating negative regulation and concentration variation can decouple ultrasensitivity and threshold from the strength of the response. Computational analyses show that cascading can generate ultrasensitivity and that natural cascades with different kinase concentrations are innately biased toward their distinct activation profiles. This work demonstrates that tunable signal processing is inherent to minimal MAPK modules and elucidates principles for rational design of synthetic signaling systems. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. RAPD and SSR based genetic diversity analysis of elite-2 set of ...

    African Journals Online (AJOL)

    Background: Synthetic hexaploid wheats are artificially reconstituted hexaploid wheats that possess high genetic variation which could be utilized for the development of new improved wheat varieties. One such group of synthetic wheats is called the Elite-II set of synthetic wheats that are derived from crossing durum wheat ...

  14. 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.

  15. Development and Applications of a High Throughput Genotyping Tool for Polyploid Crops: Single Nucleotide Polymorphism (SNP Array

    Directory of Open Access Journals (Sweden)

    Qian You

    2018-02-01

    Full Text Available Polypoid species play significant roles in agriculture and food production. Many crop species are polyploid, such as potato, wheat, strawberry, and sugarcane. Genotyping has been a daunting task for genetic studies of polyploid crops, which lags far behind the diploid crop species. Single nucleotide polymorphism (SNP array is considered to be one of, high-throughput, relatively cost-efficient and automated genotyping approaches. However, there are significant challenges for SNP identification in complex, polyploid genomes, which has seriously slowed SNP discovery and array development in polyploid species. Ploidy is a significant factor impacting SNP qualities and validation rates of SNP markers in SNP arrays, which has been proven to be a very important tool for genetic studies and molecular breeding. In this review, we (1 discussed the pros and cons of SNP array in general for high throughput genotyping, (2 presented the challenges of and solutions to SNP calling in polyploid species, (3 summarized the SNP selection criteria and considerations of SNP array design for polyploid species, (4 illustrated SNP array applications in several different polyploid crop species, then (5 discussed challenges, available software, and their accuracy comparisons for genotype calling based on SNP array data in polyploids, and finally (6 provided a series of SNP array design and genotype calling recommendations. This review presents a complete overview of SNP array development and applications in polypoid crops, which will benefit the research in molecular breeding and genetics of crops with complex genomes.

  16. Conserved molecular superlattices in a series of homologous synthetic mycobacterial cell-wall lipids forming interdigitated bilayers

    DEFF Research Database (Denmark)

    Martin-Bertelsen, Birte; Yaghmur, Anan; Franzyk, Henrik

    2016-01-01

    Synthetic analogues of the cell-wall lipid monomycoloyl glycerol (MMG) are promising as next-generation vaccine adjuvants. In the present study, the thermotropic phase behaviour of an array of synthetic MMG analogues was examined using simultaneous small- and wide-angle X-ray scattering under...... excess water conditions. The MMG analogues differed in the alkyl chain lengths and in the stereochemistry of the polar glycerol headgroup or of the lipid tails (native-like versus alternative compounds). All MMG analogues formed poorly hydrated lamellar phases at low temperatures and inverse hexagonal (H...

  17. Compact 1 × 2 and 2 × 2 Dual Polarized Series-Fed Antenna Array for X-Band Airborne Synthetic Aperture Radar Applications

    Directory of Open Access Journals (Sweden)

    Venkata Kishore Kothapudi

    2018-04-01

    Full Text Available In this paper, compact linear dual polarized series-fed 1 × 2 linear and 2 × 2 planar arrays antennas for airborne SAR applications are proposed. The proposed antenna design consists of a square radiating patch that is placed on top of the substrate, a quarter wave transformer and 50-Ω matched transformer. Matching between a radiating patch and the 50-Ω microstrip line is accomplished through a direct coupled-feed technique with the help of an impedance inverter (λ/4 impedance transformer placed at both horizontal and vertical planes, in the case of the 2 × 2 planar array. The overall size for the prototype-1 and prototype-2 fabricated antennas are 1.9305 × 0.9652 × 0.05106 λ03 and 1.9305 × 1.9305 × 0.05106 λ03, respectively. The fabricated structure has been tested, and the experimental results are similar to the simulated ones. The CST MWS simulated and vector network analyzer measured reflection coefficient (S11 results were compared, and they indicate that the proposed antenna prototype-1 yields the impedance bandwidth > 140 MHz (9.56–9.72 GHz defined by S11 140 MHz for all the individual ports. The surface currents and the E- and H-field distributions were studied for a better understanding of the polarization mechanism. The measured results of the proposed dual polarized antenna were in accordance with the simulated analysis and showed good performance of the S-parameters and radiation patterns (co-pol and cross-pol, gain, efficiency, front-to-back ratio, half-power beam width at the resonant frequency. With these features and its compact size, the proposed antenna will be suitable for X-band airborne synthetic aperture radar applications.

  18. Optimal Chunking of Large Multidimensional Arrays for Data Warehousing

    Energy Technology Data Exchange (ETDEWEB)

    Otoo, Ekow J; Otoo, Ekow J.; Rotem, Doron; Seshadri, Sridhar

    2008-02-15

    Very large multidimensional arrays are commonly used in data intensive scientific computations as well as on-line analytical processingapplications referred to as MOLAP. The storage organization of such arrays on disks is done by partitioning the large global array into fixed size sub-arrays called chunks or tiles that form the units of data transfer between disk and memory. Typical queries involve the retrieval of sub-arrays in a manner that access all chunks that overlap the query results. An important metric of the storage efficiency is the expected number of chunks retrieved over all such queries. The question that immediately arises is"what shapes of array chunks give the minimum expected number of chunks over a query workload?" The problem of optimal chunking was first introduced by Sarawagi and Stonebraker who gave an approximate solution. In this paper we develop exact mathematical models of the problem and provide exact solutions using steepest descent and geometric programming methods. Experimental results, using synthetic and real life workloads, show that our solutions are consistently within than 2.0percent of the true number of chunks retrieved for any number of dimensions. In contrast, the approximate solution of Sarawagi and Stonebraker can deviate considerably from the true result with increasing number of dimensions and also may lead to suboptimal chunk shapes.

  19. Genetic diversity of K-antigen gene clusters of Escherichia coli and their molecular typing using a suspension array.

    Science.gov (United States)

    Yang, Shuang; Xi, Daoyi; Jing, Fuyi; Kong, Deju; Wu, Junli; Feng, Lu; Cao, Boyang; Wang, Lei

    2018-04-01

    Capsular polysaccharides (CPSs), or K-antigens, are the major surface antigens of Escherichia coli. More than 80 serologically unique K-antigens are classified into 4 groups (Groups 1-4) of capsules. Groups 1 and 4 contain the Wzy-dependent polymerization pathway and the gene clusters are in the order galF to gnd; Groups 2 and 3 contain the ABC-transporter-dependent pathway and the gene clusters consist of 3 regions, regions 1, 2 and 3. Little is known about the variations among the gene clusters. In this study, 9 serotypes of K-antigen gene clusters (K2ab, K11, K20, K24, K38, K84, K92, K96, and K102) were sequenced and correlated with their CPS chemical structures. On the basis of sequence data, a K-antigen-specific suspension array that detects 10 distinct CPSs, including the above 9 CPSs plus K30, was developed. This is the first report to catalog the genetic features of E. coli K-antigen variations and to develop a suspension array for their molecular typing. The method has a number of advantages over traditional bacteriophage and serum agglutination methods and lays the foundation for straightforward identification and detection of additional K-antigens in the future.

  20. Assessment of Genetic Fidelity in Rauvolfia serpentina Plantlets Grown from Synthetic (Encapsulated Seeds Following in Vitro Storage at 4 °C

    Directory of Open Access Journals (Sweden)

    Mohammad Anis

    2012-05-01

    Full Text Available An efficient method was developed for plant regeneration and establishment from alginate encapsulated synthetic seeds of Rauvolfia serpentina. Synthetic seeds were produced using in vitro proliferated microshoots upon complexation of 3% sodium alginate prepared in Llyod and McCown woody plant medium (WPM and 100 mM calcium chloride. Re-growth ability of encapsulated nodal segments was evaluated after storage at 4 °C for 0, 1, 2, 4, 6 and 8 weeks and compared with non-encapsulated buds. Effects of different media viz; Murashige and Skoog medium; Lloyd and McCown woody Plant medium, Gamborg’s B5 medium and Schenk and Hildebrandt medium was also investigated for conversion into plantlets. The maximum frequency of conversion into plantlets from encapsulated nodal segments stored at 4 °C for 4 weeks was achieved on woody plant medium supplement with 5.0 μM BA and 1.0 μM NAA. Rooting in plantlets was achieved in half-strength Murashige and Skoog liquid medium containing 0.5 μM indole-3-acetic acid (IAA on filter paper bridges. Plantlets obtained from stored synseeds were hardened, established successfully ex vitro and were morphologically similar to each other as well as their mother plant. The genetic fidelity of Rauvolfia clones raised from synthetic seeds following four weeks of storage at 4 °C were assessed by using random amplified polymorphic DNA (RAPD and inter-simple sequence repeat (ISSR markers. All the RAPD and ISSR profiles from generated plantlets were monomorphic and comparable to the mother plant, which confirms the genetic stability among the clones. This synseed protocol could be useful for establishing a particular system for conservation, short-term storage and production of genetically identical and stable plants before it is released for commercial purposes.

  1. 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...

  2. New perspectives on preimplantation genetic diagnosis and preimplantation genetic screening

    Directory of Open Access Journals (Sweden)

    Chun-Kai Chen

    2014-06-01

    Full Text Available Preimplantation genetic diagnosis is a procedure that involves the removal of one or more nuclei from oocytes (a polar body or embryos (blastomeres or trophectoderm cells in order to test for problems in genome sequence or chromosomes of the embryo prior to implantation. It provides new hope of having unaffected children, as well as avoiding the necessity of terminating an affected pregnancy for genetic parents who carry an affected gene or have balanced chromosomal status. Polymerase chain reaction-based molecular techniques are the methods used to detect gene defects with a known sequence and X-linked diseases. The indication for using this approach has expanded for couples who are prevented from having babies because they carry a serious genetic disorder to couples with conditions that are not immediately life threatening, such as cancer predisposition genes and Huntington disease. In addition, fluorescent in situ hybridization (FISH has been widely applied for the detection of chromosome abnormalities. FISH allows the evaluation of many chromosomes at the same time, up to 15 chromosome pairs in a single cell. Preimplantation genetic screening, defined as a test that screens for aneuploidy, has been most commonly used in situations of advanced maternal age, a history of recurrent miscarriage, a history of repeated implantation failure, or a severe male factor. Unfortunately, randomized controlled trials have as yet shown no benefit with respect to preimplantation genetic screening using cleavage stage biopsy, which is probably attributable to the high levels of mosaicism at early cleavage stages and the limitations of FISH. Recently, two main types of array-based technology combined with whole genome amplification have been developed for use in preimplantation genetic diagnosis; these are comparative genomic hybridization and single nucleotide polymorphism-based arrays. Both allow the analysis of all chromosomes, and the latter also allows

  3. Chemical-genetic profile analysis in yeast suggests that a previously uncharacterized open reading frame, YBR261C, affects protein synthesis

    Directory of Open Access Journals (Sweden)

    Eroukova Veronika

    2008-12-01

    Full Text Available Abstract Background Functional genomics has received considerable attention in the post-genomic era, as it aims to identify function(s for different genes. One way to study gene function is to investigate the alterations in the responses of deletion mutants to different stimuli. Here we investigate the genetic profile of yeast non-essential gene deletion array (yGDA, ~4700 strains for increased sensitivity to paromomycin, which targets the process of protein synthesis. Results As expected, our analysis indicated that the majority of deletion strains (134 with increased sensitivity to paromomycin, are involved in protein biosynthesis. The remaining strains can be divided into smaller functional categories: metabolism (45, cellular component biogenesis and organization (28, DNA maintenance (21, transport (20, others (38 and unknown (39. These may represent minor cellular target sites (side-effects for paromomycin. They may also represent novel links to protein synthesis. One of these strains carries a deletion for a previously uncharacterized ORF, YBR261C, that we term TAE1 for Translation Associated Element 1. Our focused follow-up experiments indicated that deletion of TAE1 alters the ribosomal profile of the mutant cells. Also, gene deletion strain for TAE1 has defects in both translation efficiency and fidelity. Miniaturized synthetic genetic array analysis further indicates that TAE1 genetically interacts with 16 ribosomal protein genes. Phenotypic suppression analysis using TAE1 overexpression also links TAE1 to protein synthesis. Conclusion We show that a previously uncharacterized ORF, YBR261C, affects the process of protein synthesis and reaffirm that large-scale genetic profile analysis can be a useful tool to study novel gene function(s.

  4. Chemical-genetic profile analysis in yeast suggests that a previously uncharacterized open reading frame, YBR261C, affects protein synthesis.

    Science.gov (United States)

    Alamgir, Md; Eroukova, Veronika; Jessulat, Matthew; Xu, Jianhua; Golshani, Ashkan

    2008-12-03

    Functional genomics has received considerable attention in the post-genomic era, as it aims to identify function(s) for different genes. One way to study gene function is to investigate the alterations in the responses of deletion mutants to different stimuli. Here we investigate the genetic profile of yeast non-essential gene deletion array (yGDA, approximately 4700 strains) for increased sensitivity to paromomycin, which targets the process of protein synthesis. As expected, our analysis indicated that the majority of deletion strains (134) with increased sensitivity to paromomycin, are involved in protein biosynthesis. The remaining strains can be divided into smaller functional categories: metabolism (45), cellular component biogenesis and organization (28), DNA maintenance (21), transport (20), others (38) and unknown (39). These may represent minor cellular target sites (side-effects) for paromomycin. They may also represent novel links to protein synthesis. One of these strains carries a deletion for a previously uncharacterized ORF, YBR261C, that we term TAE1 for Translation Associated Element 1. Our focused follow-up experiments indicated that deletion of TAE1 alters the ribosomal profile of the mutant cells. Also, gene deletion strain for TAE1 has defects in both translation efficiency and fidelity. Miniaturized synthetic genetic array analysis further indicates that TAE1 genetically interacts with 16 ribosomal protein genes. Phenotypic suppression analysis using TAE1 overexpression also links TAE1 to protein synthesis. We show that a previously uncharacterized ORF, YBR261C, affects the process of protein synthesis and reaffirm that large-scale genetic profile analysis can be a useful tool to study novel gene function(s).

  5. A Parvovirus B19 synthetic genome: sequence features and functional competence.

    Science.gov (United States)

    Manaresi, Elisabetta; Conti, Ilaria; Bua, Gloria; Bonvicini, Francesca; Gallinella, Giorgio

    2017-08-01

    Central to genetic studies for Parvovirus B19 (B19V) is the availability of genomic clones that may possess functional competence and ability to generate infectious virus. In our study, we established a new model genetic system for Parvovirus B19. A synthetic approach was followed, by design of a reference genome sequence, by generation of a corresponding artificial construct and its molecular cloning in a complete and functional form, and by setup of an efficient strategy to generate infectious virus, via transfection in UT7/EpoS1 cells and amplification in erythroid progenitor cells. The synthetic genome was able to generate virus with biological properties paralleling those of native virus, its infectious activity being dependent on the preservation of self-complementarity and sequence heterogeneity within the terminal regions. A virus of defined genome sequence, obtained from controlled cell culture conditions, can constitute a reference tool for investigation of the structural and functional characteristics of the virus. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. SAFT-assisted sound beam focusing using phased arrays (PA-SAFT) for non-destructive evaluation

    Science.gov (United States)

    Nanekar, Paritosh; Kumar, Anish; Jayakumar, T.

    2015-04-01

    Focusing of sound has always been a subject of interest in ultrasonic non-destructive evaluation. An integrated approach to sound beam focusing using phased array and synthetic aperture focusing technique (PA-SAFT) has been developed in the authors' laboratory. The approach involves SAFT processing on ultrasonic B-scan image collected by a linear array transducer using a divergent sound beam. The objective is to achieve sound beam focusing using fewer elements than the ones required using conventional phased array. The effectiveness of the approach is demonstrated on aluminium blocks with artificial flaws and steel plate samples with embedded volumetric weld flaws, such as slag and clustered porosities. The results obtained by the PA-SAFT approach are found to be comparable to those obtained by conventional phased array and full matrix capture - total focusing method approaches.

  7. Parametric Beamformer for Synthetic Aperture Ultrasound Imaging

    DEFF Research Database (Denmark)

    Nikolov, Svetoslav; Tomov, Borislav Gueorguiev; Jensen, Jørgen Arendt

    2006-01-01

    . The beamformer consists of a number of identical beamforming blocks, each processing data from several channels and producing part of the image. A number of these blocks can be accommodated in a modern field-programmable gate array device (FPGA), and a whole synthetic aperture system can be implemented using...... with 255 levels. A beamforming block uses input data from 4 elements and produces a set of 10 lines. Linear interpolation is used to implement sub-sample delays. The VHDL code for the beamformer has been synthesized for a Xilinx V4FX100 speed grade 11 FPGA, where it can operate at a maximum clock frequency...

  8. Reverse engineering large-scale genetic networks: synthetic versus ...

    Indian Academy of Sciences (India)

    2010-04-19

    Apr 19, 2010 ... process computationally to describe the structure of the sys- tem and ... to the different mathematical formalisms used to model net-. Keywords. gene ..... All the algorithms were implemented in MATLAB 7.0 and run on all the 'gold ..... De Jong H. 2002 Medeling and simulation of genetic regulatory systems: a ...

  9. Genetic improvement of vegetables

    International Nuclear Information System (INIS)

    Jaramillo Vasquez, J.G.

    2001-01-01

    Some genetic bases of the improvement of vegetables are given. The objectives of the genetic improvement and the fundamental stages of this process are done. The sources of genetic variation are indicated and they are related the reproduction systems of the main horticultural species. It is analyzed the concept of genetic inheritance like base to determine the procedures more appropriate of improvement. The approaches are discussed, has more than enough phenotypic value, genetic action and genotypic variance; Equally the heredability concepts and value of improvement. The conventional methods of improvement are described, like they are: the introduction of species or varieties, the selection, the pure line, the pedigree method, the selection for families, the recurrent selection, the selection for unique seed, the haploids method, the selection for heterosis and the synthetic varieties

  10. In Vivo Real Time Volumetric Synthetic Aperture Ultrasound Imaging

    DEFF Research Database (Denmark)

    Bouzari, Hamed; Rasmussen, Morten Fischer; Brandt, Andreas Hjelm

    2015-01-01

    Synthetic aperture (SA) imaging can be used to achieve real-time volumetric ultrasound imaging using 2-D array transducers. The sensitivity of SA imaging is improved by maximizing the acoustic output, but one must consider the limitations of an ultrasound system, both technical and biological....... This paper investigates the in vivo applicability and sensitivity of volumetric SA imaging. Utilizing the transmit events to generate a set of virtual point sources, a frame rate of 25 Hz for a 90° x 90° field-of-view was achieved. Data were obtained using a 3.5 MHz 32 x 32 elements 2-D phased array...... transducer connected to the experimental scanner (SARUS). Proper scaling is applied to the excitation signal such that intensity levels are in compliance with the U.S. Food and Drug Administration regulations for in vivo ultrasound imaging. The measured Mechanical Index and spatial-peak- temporal...

  11. Natural - synthetic - artificial!

    DEFF Research Database (Denmark)

    Nielsen, Peter E

    2010-01-01

    The terms "natural," "synthetic" and "artificial" are discussed in relation to synthetic and artificial chromosomes and genomes, synthetic and artificial cells and artificial life.......The terms "natural," "synthetic" and "artificial" are discussed in relation to synthetic and artificial chromosomes and genomes, synthetic and artificial cells and artificial life....

  12. Side-Chain Supramolecular Polymers Employing Conformer Independent Triple Hydrogen Bonding Arrays

    OpenAIRE

    Gooch, Adam; Murphy, Natasha S.; Thomson, Neil H.; Wilson, Andrew J.

    2013-01-01

    Derivatives of thymine have been extensively used to promote supramolecular materials assembly. Such derivatives can be synthetically challenging to access and may be susceptible to degradation. The current article uses a conformer-independent acceptor-donor-acceptor array (ureidopyrimidine) which forms moderate affinity interactions with diamidopyridine derivatives to effect supramolecular blend formation between polystyrene and poly(methyl methacrylate) polymers obtained by RAFT which have ...

  13. The SBOL Stack: A Platform for Storing, Publishing, and Sharing Synthetic Biology Designs.

    Science.gov (United States)

    Madsen, Curtis; McLaughlin, James Alastair; Mısırlı, Göksel; Pocock, Matthew; Flanagan, Keith; Hallinan, Jennifer; Wipat, Anil

    2016-06-17

    Recently, synthetic biologists have developed the Synthetic Biology Open Language (SBOL), a data exchange standard for descriptions of genetic parts, devices, modules, and systems. The goals of this standard are to allow scientists to exchange designs of biological parts and systems, to facilitate the storage of genetic designs in repositories, and to facilitate the description of genetic designs in publications. In order to achieve these goals, the development of an infrastructure to store, retrieve, and exchange SBOL data is necessary. To address this problem, we have developed the SBOL Stack, a Resource Description Framework (RDF) database specifically designed for the storage, integration, and publication of SBOL data. This database allows users to define a library of synthetic parts and designs as a service, to share SBOL data with collaborators, and to store designs of biological systems locally. The database also allows external data sources to be integrated by mapping them to the SBOL data model. The SBOL Stack includes two Web interfaces: the SBOL Stack API and SynBioHub. While the former is designed for developers, the latter allows users to upload new SBOL biological designs, download SBOL documents, search by keyword, and visualize SBOL data. Since the SBOL Stack is based on semantic Web technology, the inherent distributed querying functionality of RDF databases can be used to allow different SBOL stack databases to be queried simultaneously, and therefore, data can be shared between different institutes, centers, or other users.

  14. Fine-mapping the HOXB region detects common variants tagging a rare coding allele: evidence for synthetic association in prostate cancer.

    Directory of Open Access Journals (Sweden)

    Edward J Saunders

    2014-02-01

    Full Text Available The HOXB13 gene has been implicated in prostate cancer (PrCa susceptibility. We performed a high resolution fine-mapping analysis to comprehensively evaluate the association between common genetic variation across the HOXB genetic locus at 17q21 and PrCa risk. This involved genotyping 700 SNPs using a custom Illumina iSelect array (iCOGS followed by imputation of 3195 SNPs in 20,440 PrCa cases and 21,469 controls in The PRACTICAL consortium. We identified a cluster of highly correlated common variants situated within or closely upstream of HOXB13 that were significantly associated with PrCa risk, described by rs117576373 (OR 1.30, P = 2.62×10(-14. Additional genotyping, conditional regression and haplotype analyses indicated that the newly identified common variants tag a rare, partially correlated coding variant in the HOXB13 gene (G84E, rs138213197, which has been identified recently as a moderate penetrance PrCa susceptibility allele. The potential for GWAS associations detected through common SNPs to be driven by rare causal variants with higher relative risks has long been proposed; however, to our knowledge this is the first experimental evidence for this phenomenon of synthetic association contributing to cancer susceptibility.

  15. The GenoChip: a new tool for genetic anthropology.

    Science.gov (United States)

    Elhaik, Eran; Greenspan, Elliott; Staats, Sean; Krahn, Thomas; Tyler-Smith, Chris; Xue, Yali; Tofanelli, Sergio; Francalacci, Paolo; Cucca, Francesco; Pagani, Luca; Jin, Li; Li, Hui; Schurr, Theodore G; Greenspan, Bennett; Spencer Wells, R

    2013-01-01

    The Genographic Project is an international effort aimed at charting human migratory history. The project is nonprofit and nonmedical, and, through its Legacy Fund, supports locally led efforts to preserve indigenous and traditional cultures. Although the first phase of the project was focused on uniparentally inherited markers on the Y-chromosome and mitochondrial DNA (mtDNA), the current phase focuses on markers from across the entire genome to obtain a more complete understanding of human genetic variation. Although many commercial arrays exist for genome-wide single-nucleotide polymorphism (SNP) genotyping, they were designed for medical genetic studies and contain medically related markers that are inappropriate for global population genetic studies. GenoChip, the Genographic Project's new genotyping array, was designed to resolve these issues and enable higher resolution research into outstanding questions in genetic anthropology. The GenoChip includes ancestry informative markers obtained for over 450 human populations, an ancient human (Saqqaq), and two archaic hominins (Neanderthal and Denisovan) and was designed to identify all known Y-chromosome and mtDNA haplogroups. The chip was carefully vetted to avoid inclusion of medically relevant markers. To demonstrate its capabilities, we compared the FST distributions of GenoChip SNPs to those of two commercial arrays. Although all arrays yielded similarly shaped (inverse J) FST distributions, the GenoChip autosomal and X-chromosomal distributions had the highest mean FST, attesting to its ability to discern subpopulations. The chip performances are illustrated in a principal component analysis for 14 worldwide populations. In summary, the GenoChip is a dedicated genotyping platform for genetic anthropology. With an unprecedented number of approximately 12,000 Y-chromosomal and approximately 3,300 mtDNA SNPs and over 130,000 autosomal and X-chromosomal SNPs without any known health, medical, or phenotypic

  16. The GenoChip: A New Tool for Genetic Anthropology

    Science.gov (United States)

    Elhaik, Eran; Greenspan, Elliott; Staats, Sean; Krahn, Thomas; Tyler-Smith, Chris; Xue, Yali; Tofanelli, Sergio; Francalacci, Paolo; Cucca, Francesco; Pagani, Luca; Jin, Li; Li, Hui; Schurr, Theodore G.; Greenspan, Bennett; Spencer Wells, R.

    2013-01-01

    The Genographic Project is an international effort aimed at charting human migratory history. The project is nonprofit and nonmedical, and, through its Legacy Fund, supports locally led efforts to preserve indigenous and traditional cultures. Although the first phase of the project was focused on uniparentally inherited markers on the Y-chromosome and mitochondrial DNA (mtDNA), the current phase focuses on markers from across the entire genome to obtain a more complete understanding of human genetic variation. Although many commercial arrays exist for genome-wide single-nucleotide polymorphism (SNP) genotyping, they were designed for medical genetic studies and contain medically related markers that are inappropriate for global population genetic studies. GenoChip, the Genographic Project’s new genotyping array, was designed to resolve these issues and enable higher resolution research into outstanding questions in genetic anthropology. The GenoChip includes ancestry informative markers obtained for over 450 human populations, an ancient human (Saqqaq), and two archaic hominins (Neanderthal and Denisovan) and was designed to identify all known Y-chromosome and mtDNA haplogroups. The chip was carefully vetted to avoid inclusion of medically relevant markers. To demonstrate its capabilities, we compared the FST distributions of GenoChip SNPs to those of two commercial arrays. Although all arrays yielded similarly shaped (inverse J) FST distributions, the GenoChip autosomal and X-chromosomal distributions had the highest mean FST, attesting to its ability to discern subpopulations. The chip performances are illustrated in a principal component analysis for 14 worldwide populations. In summary, the GenoChip is a dedicated genotyping platform for genetic anthropology. With an unprecedented number of approximately 12,000 Y-chromosomal and approximately 3,300 mtDNA SNPs and over 130,000 autosomal and X-chromosomal SNPs without any known health, medical, or phenotypic

  17. Avoiding pitfalls in molecular genetic testing: case studies of high-resolution array comparative genomic hybridization testing in the definitive diagnosis of Mowat-Wilson syndrome.

    Science.gov (United States)

    Kluk, Michael Joseph; An, Yu; James, Philip; Coulter, David; Harris, David; Wu, Bai-Lin; Shen, Yiping

    2011-05-01

    The molecular testing options available for the diagnosis of genetic disorders are numerous and include a variety of different assay platforms. The consultative input of molecular pathologists and cytogeneticists, working closely with the ordering clinicians, is often important for definitive diagnosis. Herein, we describe two patients who had long histories of unexplained signs and symptoms with a high clinical suspicion of an underlying genetic etiology. Initial molecular testing in both cases was negative, but the application of high-resolution array comparative genomic hybridization technology lead to definitive diagnosis in both cases. We summarize the clinical findings and molecular testing in each case, discuss the differential diagnoses, and review the clinical and pathological findings of Mowat-Wilson syndrome. This report highlights the importance for those involved in molecular testing to know the nature of the underlying genetic abnormalities associated with the suspected diagnosis, to recognize the limitations of each testing platform, and to persistently pursue repeat testing using high-resolution technologies when indicated. This concept is applicable to both germline and somatic molecular genetic testing. Copyright © 2011 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

  18. Experiential Engineering through iGEM--An Undergraduate Summer Competition in Synthetic Biology

    Science.gov (United States)

    Mitchell, Rudolph; Dori, Yehudit Judy; Kuldell, Natalie H.

    2011-01-01

    Unlike students in other engineering disciplines, undergraduates in biological engineering typically have limited opportunity to develop design competencies, and even fewer chances to implement their designed projects. The international Genetically Engineered Machines (iGEM) competition is a student Synthetic Biology competition that, in 2009,…

  19. How to turn a genetic circuit into a synthetic tunable oscillator, or a bistable switch.

    Directory of Open Access Journals (Sweden)

    Lucia Marucci

    2009-12-01

    Full Text Available Systems and Synthetic Biology use computational models of biological pathways in order to study in silico the behaviour of biological pathways. Mathematical models allow to verify biological hypotheses and to predict new possible dynamical behaviours. Here we use the tools of non-linear analysis to understand how to change the dynamics of the genes composing a novel synthetic network recently constructed in the yeast Saccharomyces cerevisiae for In-vivo Reverse-engineering and Modelling Assessment (IRMA. Guided by previous theoretical results that make the dynamics of a biological network depend on its topological properties, through the use of simulation and continuation techniques, we found that the network can be easily turned into a robust and tunable synthetic oscillator or a bistable switch. Our results provide guidelines to properly re-engineering in vivo the network in order to tune its dynamics.

  20. Synthetic lethality between gene defects affecting a single non-essential molecular pathway with reversible steps.

    Directory of Open Access Journals (Sweden)

    Andrei Zinovyev

    2013-04-01

    Full Text Available Systematic analysis of synthetic lethality (SL constitutes a critical tool for systems biology to decipher molecular pathways. The most accepted mechanistic explanation of SL is that the two genes function in parallel, mutually compensatory pathways, known as between-pathway SL. However, recent genome-wide analyses in yeast identified a significant number of within-pathway negative genetic interactions. The molecular mechanisms leading to within-pathway SL are not fully understood. Here, we propose a novel mechanism leading to within-pathway SL involving two genes functioning in a single non-essential pathway. This type of SL termed within-reversible-pathway SL involves reversible pathway steps, catalyzed by different enzymes in the forward and backward directions, and kinetic trapping of a potentially toxic intermediate. Experimental data with recombinational DNA repair genes validate the concept. Mathematical modeling recapitulates the possibility of kinetic trapping and revealed the potential contributions of synthetic, dosage-lethal interactions in such a genetic system as well as the possibility of within-pathway positive masking interactions. Analysis of yeast gene interaction and pathway data suggests broad applicability of this novel concept. These observations extend the canonical interpretation of synthetic-lethal or synthetic-sick interactions with direct implications to reconstruct molecular pathways and improve therapeutic approaches to diseases such as cancer.

  1. Genetic profiles of gastroesophageal cancer: combined analysis using expression array and tiling array--comparative genomic hybridization

    DEFF Research Database (Denmark)

    Isinger-Ekstrand, Anna; Johansson, Jan; Ohlsson, Mattias

    2010-01-01

    15, 13q34, and 12q13, whereas different profiles with gains at 5p15, 7p22, 2q35, and 13q34 characterized gastric cancers. CDK6 and EGFR were identified as putative target genes in cancers of the esophagus and the gastroesophageal junction, with upregulation in one quarter of the tumors. Gains......We aimed to characterize the genomic profiles of adenocarcinomas in the gastroesophageal junction in relation to cancers in the esophagus and the stomach. Profiles of gains/losses as well as gene expression profiles were obtained from 27 gastroesophageal adenocarcinomas by means of 32k high......-resolution array-based comparative genomic hybridization and 27k oligo gene expression arrays, and putative target genes were validated in an extended series. Adenocarcinomas in the distal esophagus and the gastroesophageal junction showed strong similarities with the most common gains at 20q13, 8q24, 1q21-23, 5p...

  2. Processing and display of medical three dimensional arrays of numerical data using octree encoding

    International Nuclear Information System (INIS)

    Amans, J.L.; Darier, P.

    1985-01-01

    Imaging modalities such as X-ray computerized Tomography (CT), Nuclear Medicine and Nuclear Magnetic Resonance can produce three-dimensional (3-D) arrays of numerical data of medical object internal structures. The analysis of 3-D data by synthetic generation of realistic images is an important area of computer graphics and imaging. We are currently developing experimental software that allows the analysis, processing and display of 3-D arrays of numerical data that are organized in a related hierarchical data structure using OCTREE (octal-tree) encoding technique based on a recursive subdivision of the data volume. The OCTREE encoding structure is an extension of the two-dimensional tree structure: the quadtree, developed for image processing applications. Before any operations, the 3-D array of data is OCTREE encoded, thereafter all processings are concerned with the encoded object. The elementary process for the elaboration of a synthetic image includes: conditioning the volume: volume partition (numerical and spatial segmentation), choice of the view-point..., two dimensional display, either by spatial integration (radiography) or by shaded surface representation. This paper introduces these different concepts and specifies the advantages of OCTREE encoding techniques in realizing these operations. Furthermore the application of the OCTREE encoding scheme to the display of 3-D medical volumes generated from multiple CT scans is presented

  3. Streptococcus pneumoniae Supragenome Hybridization Arrays for Profiling of Genetic Content and Gene Expression.

    Science.gov (United States)

    Kadam, Anagha; Janto, Benjamin; Eutsey, Rory; Earl, Joshua P; Powell, Evan; Dahlgren, Margaret E; Hu, Fen Z; Ehrlich, Garth D; Hiller, N Luisa

    2015-02-02

    There is extensive genomic diversity among Streptococcus pneumoniae isolates. Approximately half of the comprehensive set of genes in the species (the supragenome or pangenome) is present in all the isolates (core set), and the remaining is unevenly distributed among strains (distributed set). The Streptococcus pneumoniae Supragenome Hybridization (SpSGH) array provides coverage for an extensive set of genes and polymorphisms encountered within this species, capturing this genomic diversity. Further, the capture is quantitative. In this manner, the SpSGH array allows for both genomic and transcriptomic analyses of diverse S. pneumoniae isolates on a single platform. In this unit, we present the SpSGH array, and describe in detail its design and implementation for both genomic and transcriptomic analyses. The methodology can be applied to construction and modification of SpSGH array platforms, as well to other bacterial species as long as multiple whole-genome sequences are available that collectively capture the vast majority of the species supragenome. Copyright © 2015 John Wiley & Sons, Inc.

  4. Performance Evaluation of a Synthetic Aperture Real-Time Ultrasound System

    DEFF Research Database (Denmark)

    Stuart, Matthias Bo; Tomov, Borislav Gueorguiev; Jensen, Jørgen Arendt

    2011-01-01

    This paper evaluates the signal-to-noise ratio, the time stability, and the phase difference of the sampling in the experimental ultrasound scanner SARUS: A synthetic aperture, real-time ultrasound system. SARUS has 1024 independent transmit and receive channels and is capable of handling 2D probes...... arrays (FPGAs) making it very flexible and allowing implementation of other real-time ultrasound processing methods in the future. For conventional B-mode imaging, a penetration depth around 7 cm for a 7 MHz transducer is obtained (signal-tonoise ratio of 0 dB), which is comparable to commercial...... for 3D ultrasound imaging. It samples at 12 bits per sample and has a sampling rate of 70 MHz with the possibility of decimating the sampling frequency at the input. SARUS is capable of advanced real-time computations such as synthetic aperture imaging. The system is built using fieldprogrammable gate...

  5. Genetic alterations in syndromes with oral manifestations

    Directory of Open Access Journals (Sweden)

    Krishnamurthy Anuthama

    2013-01-01

    Full Text Available Ever since Gregor Johan Mendel proposed the law of inheritance, genetics has transcended the field of health and has entered all walks of life in its application. Thus, the gene is the pivoting factor for all happenings revolving around it. Knowledge of gene mapping in various diseases would be a valuable tool in prenatally diagnosing the condition and averting the future disability and stigma for the posterity. This article includes an array of genetically determined conditions in patients seen at our college out-patient department with complete manifestation, partial manifestation and array of manifestations not fitting into a particular syndrome.

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

    Science.gov (United States)

    Beach, Dale L; Alvarez, Consuelo J

    2015-12-01

    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 techniques, and information literacy. During the spring semesters of 2014 and 2015, the Synthetic Biology Laboratory Project was delivered to sophomore genetics courses. Using a cloning strategy based on standardized BioBrick genetic "parts," students construct a "reporter plasmid" expressing a reporter gene (GFP) controlled by a hybrid promoter regulated by the lac-repressor protein (lacI). In combination with a "sensor plasmid," the production of the reporter phenotype is inhibited in the presence of a target environmental agent, arabinose. When arabinose is absent, constitutive GFP expression makes cells glow green. But the presence of arabinose activates a second promoter (pBAD) to produce a lac-repressor protein that will inhibit GFP production. Student learning was assessed relative to five learning objectives, using a student survey administered at the beginning (pre-survey) and end (post-survey) of the course, and an additional 15 open-ended questions from five graded Progress Report assignments collected throughout the course. Students demonstrated significant learning gains (p Biology Laboratory Project enhanced their understanding of molecular genetics. The laboratory project is highly adaptable for both introductory and advanced courses.

  7. Quantitative genome-wide genetic interaction screens reveal global epistatic relationships of protein complexes in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Mohan Babu

    2014-02-01

    Full Text Available Large-scale proteomic analyses in Escherichia coli have documented the composition and physical relationships of multiprotein complexes, but not their functional organization into biological pathways and processes. Conversely, genetic interaction (GI screens can provide insights into the biological role(s of individual gene and higher order associations. Combining the information from both approaches should elucidate how complexes and pathways intersect functionally at a systems level. However, such integrative analysis has been hindered due to the lack of relevant GI data. Here we present a systematic, unbiased, and quantitative synthetic genetic array screen in E. coli describing the genetic dependencies and functional cross-talk among over 600,000 digenic mutant combinations. Combining this epistasis information with putative functional modules derived from previous proteomic data and genomic context-based methods revealed unexpected associations, including new components required for the biogenesis of iron-sulphur and ribosome integrity, and the interplay between molecular chaperones and proteases. We find that functionally-linked genes co-conserved among γ-proteobacteria are far more likely to have correlated GI profiles than genes with divergent patterns of evolution. Overall, examining bacterial GIs in the context of protein complexes provides avenues for a deeper mechanistic understanding of core microbial systems.

  8. Synthetic review on the genetic relatedness between North Africa ...

    African Journals Online (AJOL)

    ... genetic markers are associated with certain aspects of human culture like languages, ... In the Middle East, the predominant categories of Y chromosomes are ... less frequency than the Middle Eastern ones, showing an important paternal ...

  9. Acoustic field of focusing phased array probe and the scanning system

    International Nuclear Information System (INIS)

    Murai, J.; Miura, S.; Ida, T.; Shiraiwa, T.; Miya, T.

    1997-01-01

    Acoustic field of a point focusing cylindrical linear array probe, in which focusing in the axial direction of cylinder is done by the phased linear array and focusing in the orthogonal direction is done geometrically, was studied by numerical calculation and an optimum design of phased array probe for focusing has been obtained. In generally speaking, the beam width at focus point decreases with decrease of width of each transducer element and with increase of synthetic aperture made by total elements. If the number of total array elements excited as one pulse is limited, the above conditions are contradicted. Thus, an optimum element width exists for the best focusing. On the above consideration, we can get focusing ability of phased array nearly as same as geometrical focusing. A developed transducer is a linear array of polymer piezoelectric material of cylindrical shape, of which radius is from 50 mm to 75 mm. The frequency is 10 Mhz and the beam width of 0.5 mm (depending on aperture) in the orthogonal direction to the cylinder axis and 0.7 mm width in the cylinder axis (phased array focusing) have been obtained. A delay circuit for exciting the transducer was newly designed to give maximum performance to the array regarding to accuracy, stability, easy control and etc. A c-scan ultrasonic testing system equipped with this transducer has sixteen times inspection speed compared to the single probe instrument.

  10. VisBOL: Web-Based Tools for Synthetic Biology Design Visualization.

    Science.gov (United States)

    McLaughlin, James Alastair; Pocock, Matthew; Mısırlı, Göksel; Madsen, Curtis; Wipat, Anil

    2016-08-19

    VisBOL is a Web-based application that allows the rendering of genetic circuit designs, enabling synthetic biologists to visually convey designs in SBOL visual format. VisBOL designs can be exported to formats including PNG and SVG images to be embedded in Web pages, presentations and publications. The VisBOL tool enables the automated generation of visualizations from designs specified using the Synthetic Biology Open Language (SBOL) version 2.0, as well as a range of well-known bioinformatics formats including GenBank and Pigeoncad notation. VisBOL is provided both as a user accessible Web site and as an open-source (BSD) JavaScript library that can be used to embed diagrams within other content and software.

  11. Synthetic Brainbows

    KAUST Repository

    Wan, Y.

    2013-06-01

    Brainbow is a genetic engineering technique that randomly colorizes cells. Biological samples processed with this technique and imaged with confocal microscopy have distinctive colors for individual cells. Complex cellular structures can then be easily visualized. However, the complexity of the Brainbow technique limits its applications. In practice, most confocal microscopy scans use different florescence staining with typically at most three distinct cellular structures. These structures are often packed and obscure each other in rendered images making analysis difficult. In this paper, we leverage a process known as GPU framebuffer feedback loops to synthesize Brainbow-like images. In addition, we incorporate ID shuffing and Monte-Carlo sampling into our technique, so that it can be applied to single-channel confocal microscopy data. The synthesized Brainbow images are presented to domain experts with positive feedback. A user survey demonstrates that our synthetic Brainbow technique improves visualizations of volume data with complex structures for biologists.

  12. Processing And Display Of Medical Three Dimensional Arrays Of Numerical Data Using Octree Encoding

    Science.gov (United States)

    Amans, Jean-Louis; Darier, Pierre

    1986-05-01

    imaging modalities such as X-Ray computerized Tomography (CT), Nuclear Medecine and Nuclear Magnetic Resonance can produce three-dimensional (3-D) arrays of numerical data of medical object internal structures. The analysis of 3-D data by synthetic generation of realistic images is an important area of computer graphics and imaging.

  13. Definition of natural T cell antigens with mimicry epitopes obtained from dedicated synthetic peptide libraries.

    Science.gov (United States)

    Hiemstra, H S; van Veelen, P A; Schloot, N C; Geluk, A; van Meijgaarden, K E; Willemen, S J; Leunissen, J A; Benckhuijsen, W E; Amons, R; de Vries, R R; Roep, B O; Ottenhoff, T H; Drijfhout, J W

    1998-10-15

    Progress has recently been made in the use of synthetic peptide libraries for the identification of T cell-stimulating ligands. T cell epitopes identified from synthetic libraries are mimics of natural epitopes. Here we show how the mimicry epitopes obtained from synthetic peptide libraries enable unambiguous identification of natural T cell Ags. Synthetic peptide libraries were screened with Mycobacterium tuberculosis-reactive and -autoreactive T cell clones. In two cases, database homology searches with mimicry epitopes isolated from a dedicated synthetic peptide library allowed immediate identification of the natural antigenic protein. In two other cases, an amino acid pattern that reflected the epitope requirements of the T cell was determined by substitution and omission mixture analysis. Subsequently, the natural Ag was identified from databases using this refined pattern. This approach opens new perspectives for rapid and reliable Ag definition, representing a feasible alternative to the biochemical and genetic approaches described thus far.

  14. New perspectives on preimplantation genetic diagnosis and preimplantation genetic screening.

    Science.gov (United States)

    Chen, Chun-Kai; Yu, Hsing-Tse; Soong, Yung-Kuei; Lee, Chyi-Long

    2014-06-01

    Preimplantation genetic diagnosis is a procedure that involves the removal of one or more nuclei from oocytes (a polar body) or embryos (blastomeres or trophectoderm cells) in order to test for problems in genome sequence or chromosomes of the embryo prior to implantation. It provides new hope of having unaffected children, as well as avoiding the necessity of terminating an affected pregnancy for genetic parents who carry an affected gene or have balanced chromosomal status. Polymerase chain reaction-based molecular techniques are the methods used to detect gene defects with a known sequence and X-linked diseases. The indication for using this approach has expanded for couples who are prevented from having babies because they carry a serious genetic disorder to couples with conditions that are not immediately life threatening, such as cancer predisposition genes and Huntington disease. In addition, fluorescent in situ hybridization (FISH) has been widely applied for the detection of chromosome abnormalities. FISH allows the evaluation of many chromosomes at the same time, up to 15 chromosome pairs in a single cell. Preimplantation genetic screening, defined as a test that screens for aneuploidy, has been most commonly used in situations of advanced maternal age, a history of recurrent miscarriage, a history of repeated implantation failure, or a severe male factor. Unfortunately, randomized controlled trials have as yet shown no benefit with respect to preimplantation genetic screening using cleavage stage biopsy, which is probably attributable to the high levels of mosaicism at early cleavage stages and the limitations of FISH. Recently, two main types of array-based technology combined with whole genome amplification have been developed for use in preimplantation genetic diagnosis; these are comparative genomic hybridization and single nucleotide polymorphism-based arrays. Both allow the analysis of all chromosomes, and the latter also allows the haplotype of

  15. Adjuvants based on synthetic mycobacterial cord factor analogues: Biophysical properties of neat glycolipids and nano-self-assemblies with DDA

    DEFF Research Database (Denmark)

    Kallerup, Rie Selchau; Franzyk, Henrik; Schiøth, Mikkel Lohmann

    2017-01-01

    Synthetic mycobacterial cord factor analogues, e.g., trehalose 6,6'-dibehenate (TDB), are highly promising adjuvants due to their strong immunopotentiating capabilities, but their biophysical properties have remained poorly characterized. Here, we report the synthesis of an array of synthetic TDB...... trehalose mono- (TMX) and diester (TDX) analogues with symmetrically shortened acyl chains [denoted by X: arachidate (A), stearate (S), palmitate (P), myristate (Myr) and laurate (L)] and an analogue with a short hydrophilic polyethylene glycol (PEG) linker inserted between the trehalose headgroup of TDS...

  16. Phage Therapy in the Era of Synthetic Biology.

    Science.gov (United States)

    Barbu, E Magda; Cady, Kyle C; Hubby, Bolyn

    2016-10-03

    For more than a century, bacteriophage (or phage) research has enabled some of the most important discoveries in biological sciences and has equipped scientists with many of the molecular biology tools that have advanced our understanding of replication, maintenance, and expression of genetic material. Phages have also been recognized and exploited as natural antimicrobial agents and nanovectors for gene therapy, but their potential as therapeutics has not been fully exploited in Western medicine because of challenges such as narrow host range, bacterial resistance, and unique pharmacokinetics. However, increasing concern related to the emergence of bacteria resistant to multiple antibiotics has heightened interest in phage therapy and the development of strategies to overcome hurdles associated with bacteriophage therapeutics. Recent progress in sequencing technologies, DNA manipulation, and synthetic biology allowed scientists to refactor the entire bacterial genome of Mycoplasma mycoides, thereby creating the first synthetic cell. These new strategies for engineering genomes may have the potential to accelerate the construction of designer phage genomes with superior therapeutic potential. Here, we discuss the use of phage as therapeutics, as well as how synthetic biology can create bacteriophage with desirable attributes. Copyright © 2016 Cold Spring Harbor Laboratory Press; all rights reserved.

  17. Synthetic strategies for plant signalling studies: molecular toolbox and orthogonal platforms

    KAUST Repository

    Braguy, Justine

    2016-05-26

    Plants deploy a wide array of signalling networks integrating environmental cues with growth, defence and developmental responses. The high level of complexity, redundancy and connection between several pathways hampers a comprehensive understanding of involved functional and regulatory mechanisms. The implementation of synthetic biology approaches is revolutionizing experimental biology in prokaryotes, yeasts and animal systems and can likewise contribute to a new era in plant biology. This review gives an overview on synthetic biology approaches for the development and implementation of synthetic molecular tools and techniques to interrogate, understand and control signalling events in plants, ranging from strategies for the targeted manipulation of plant genomes up to the spatiotemporally resolved control of gene expression using optogenetic approaches. We also describe strategies based on the partial reconstruction of signalling pathways in orthogonal platforms, like yeast, animal and in vitro systems. This allows a targeted analysis of individual signalling hubs devoid of inter-connectivity with endogenous interacting components. Implementation of the interdisciplinary synthetic biology tools and strategies is not exempt of challenges and hardships but simultaneously most rewarding in terms of the advances in basic and applied research. As witnessed in other areas, these original theoretical-experimental avenues will lead to a breakthrough in the ability to study and comprehend plant signalling networks. This article is protected by copyright. All rights reserved.

  18. "What is this genetics, anyway?" Understandings of genetics, illness causality and inheritance among British Pakistani users of genetic services.

    Science.gov (United States)

    Shaw, Alison; Hurst, Jane A

    2008-08-01

    Misconceptions about basic genetic concepts and inheritance patterns may be widespread in the general population. This paper investigates understandings of genetics, illness causality and inheritance among British Pakistanis referred to a UK genetics clinic. During participant observation of genetics clinic consultations and semi-structured interviews in Urdu or English in respondents' homes, we identified an array of environmental, behavioral and spiritual understandings of the causes of medical and intellectual problems. Misconceptions about the location of genetic information in the body and of genetic mechanisms of inheritance were common, reflected the range of everyday theories observed for White British patients and included the belief that a child receives more genetic material from the father than the mother. Despite some participants' conversational use of genetic terminology, some patients had assimilated genetic information in ways that conflict with genetic theory with potentially serious clinical consequences. Additionally, skepticism of genetic theories of illness reflected a rejection of a dominant discourse of genetic risk that stigmatizes cousin marriages. Patients referred to genetics clinics may not easily surrender their lay or personal theories about the causes of their own or their child's condition and their understandings of genetic risk. Genetic counselors may need to identify, work with and at times challenge patients' understandings of illness causality and inheritance.

  19. 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.

  20. Resolution Enhancement Method Used for Force Sensing Resistor Array

    Directory of Open Access Journals (Sweden)

    Karen Flores De Jesus

    2015-01-01

    Full Text Available Tactile sensors are one of the major devices that enable robotic systems to interact with the surrounding environment. This research aims to propose a mathematical model to describe the behavior of a tactile sensor based on experimental and statistical analyses and moreover to develop a versatile algorithm that can be applied to different tactile sensor arrays to enhance the limited resolution. With the proposed algorithm, the resolution can be increased up to twenty times if multiple measurements are available. To verify if the proposed algorithm can be used for tactile sensor arrays that are used in robotic system, a 16×10 force sensing array (FSR is adopted. The acquired two-dimensional measurements were processed by a resolution enhancement method (REM to enhance the resolution, which can be used to improve the resolution for single image or multiple measurements. As a result, the resolution of the sensor is increased and it can be used as synthetic skin to identify accurate shapes of objects and applied forces.

  1. NORMAL NASAL GENE EXPRESSION LEVELS USING CDNA ARRAY TECHNOLOGY

    Science.gov (United States)

    Normal Nasal Gene Expression Levels Using cDNA Array Technology. The nasal epithelium is a target site for chemically-induced toxicity and carcinogenicity. To detect and analyze genetic events which contribute to nasal tumor development, we first defined the gene expressi...

  2. SOUND-SPEED TOMOGRAPHY USING FIRST-ARRIVAL TRANSMISSION ULTRASOUND FOR A RING ARRAY

    Energy Technology Data Exchange (ETDEWEB)

    HUANG, LIANJIE [Los Alamos National Laboratory; QUAN, YOULI [Los Alamos National Laboratory

    2007-01-31

    Sound-speed tomography images can be used for cancer detection and diagnosis. Tumors have generally higher sound speeds than the surrounding tissue. Quality and resolution of tomography images are primarily determined by the insonification/illumination aperture of ultrasound and the capability of the tomography method for accurately handling heterogeneous nature of the breast. We investigate the capability of an efficient time-of-flight tomography method using transmission ultrasound from a ring array for reconstructing sound-speed images of the breast. The method uses first arrival times of transmitted ultrasonic signals emerging from non-beamforming ultrasound transducers located around a ring. It properly accounts for ray bending within the breast by solving the eikonal equation using a finite-difference scheme. We test and validate the time-of-flight transmission tomography method using synthetic data for numerical breast phantoms containing various objects. In our simulation, the objects are immersed in water within a ring array. Two-dimensional synthetic data are generated using a finite-difference scheme to solve acoustic-wave equation in heterogeneous media. We study the reconstruction accuracy of the tomography method for objects with different sizes and shapes as well as different perturbations from the surrounding medium. In addition, we also address some specific data processing issues related to the tomography. Our tomography results demonstrate that the first-arrival transmission tomography method can accurately reconstruct objects larger than approximately five wavelengths of the incident ultrasound using a ring array.

  3. High-resolution imaging using a wideband MIMO radar system with two distributed arrays.

    Science.gov (United States)

    Wang, Dang-wei; Ma, Xiao-yan; Chen, A-Lei; Su, Yi

    2010-05-01

    Imaging a fast maneuvering target has been an active research area in past decades. Usually, an array antenna with multiple elements is implemented to avoid the motion compensations involved in the inverse synthetic aperture radar (ISAR) imaging. Nevertheless, there is a price dilemma due to the high level of hardware complexity compared to complex algorithm implemented in the ISAR imaging system with only one antenna. In this paper, a wideband multiple-input multiple-output (MIMO) radar system with two distributed arrays is proposed to reduce the hardware complexity of the system. Furthermore, the system model, the equivalent array production method and the imaging procedure are presented. As compared with the classical real aperture radar (RAR) imaging system, there is a very important contribution in our method that the lower hardware complexity can be involved in the imaging system since many additive virtual array elements can be obtained. Numerical simulations are provided for testing our system and imaging method.

  4. Molecular Cloning Designer Simulator (MCDS): All-in-one molecular cloning and genetic engineering design, simulation and management software for complex synthetic biology and metabolic engineering projects.

    Science.gov (United States)

    Shi, Zhenyu; Vickers, Claudia E

    2016-12-01

    Molecular Cloning Designer Simulator (MCDS) is a powerful new all-in-one cloning and genetic engineering design, simulation and management software platform developed for complex synthetic biology and metabolic engineering projects. In addition to standard functions, it has a number of features that are either unique, or are not found in combination in any one software package: (1) it has a novel interactive flow-chart user interface for complex multi-step processes, allowing an integrated overview of the whole project; (2) it can perform a user-defined workflow of cloning steps in a single execution of the software; (3) it can handle multiple types of genetic recombineering, a technique that is rapidly replacing classical cloning for many applications; (4) it includes experimental information to conveniently guide wet lab work; and (5) it can store results and comments to allow the tracking and management of the whole project in one platform. MCDS is freely available from https://mcds.codeplex.com.

  5. Synthetic Cannabinoids

    Directory of Open Access Journals (Sweden)

    Aslihan Okan Ibiloglu

    2017-09-01

    Full Text Available Synthetic cannabinoids which is a subgroup of cannabinoids are commonly used for recreational drug use throughout the whole world. Although both marijuana and synthetic cannabinoids stimulate the same receptors, cannabinoid receptor 1 (CB1 and cannabinoid receptor 2 (CB2, studies have shown that synthetic cannabinoids are much more potent than marijuana. The longer use of synthetic cannabinoids can cause severe physical and psychological symptoms that might even result in death, similar to many known illicit drugs. Main treatment options mostly involve symptom management and supportive care. The aim of this article is to discuss clinical and pharmacological properties of the increasingly used synthetic cannabinoids. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2017; 9(3.000: 317-328

  6. Making a chocolate chip: development and evaluation of a 6K SNP array for Theobroma cacao.

    Science.gov (United States)

    Livingstone, Donald; Royaert, Stefan; Stack, Conrad; Mockaitis, Keithanne; May, Greg; Farmer, Andrew; Saski, Christopher; Schnell, Ray; Kuhn, David; Motamayor, Juan Carlos

    2015-08-01

    Theobroma cacao, the key ingredient in chocolate production, is one of the world's most important tree fruit crops, with ∼4,000,000 metric tons produced across 50 countries. To move towards gene discovery and marker-assisted breeding in cacao, a single-nucleotide polymorphism (SNP) identification project was undertaken using RNAseq data from 16 diverse cacao cultivars. RNA sequences were aligned to the assembled transcriptome of the cultivar Matina 1-6, and 330,000 SNPs within coding regions were identified. From these SNPs, a subset of 6,000 high-quality SNPs were selected for inclusion on an Illumina Infinium SNP array: the Cacao6kSNP array. Using Cacao6KSNP array data from over 1,000 cacao samples, we demonstrate that our custom array produces a saturated genetic map and can be used to distinguish among even closely related genotypes. Our study enhances and expands the genetic resources available to the cacao research community, and provides the genome-scale set of tools that are critical for advancing breeding with molecular markers in an agricultural species with high genetic diversity. © The Author 2015. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.

  7. Development of recombinant antigen array for simultaneous detection of viral antibodies.

    Directory of Open Access Journals (Sweden)

    Yi Liu

    Full Text Available Protein microarrays have been developed to study antibody reactivity against a large number of antigens, demonstrating extensive perspective for clinical application. We developed a viral antigen array by spotting four recombinant antigens and synthetic peptide, including glycoprotein G of herpes simplex virus (HSV type 1 and 2, phosphoprotein 150 of cytomegalovirus (CMV, Rubella virus (RV core plus glycoprotein E1 and E2 as well as a E1 peptide with the optimal concentrations on activated glass slides to simultaneously detect IgG and IgM against HSV1, HSV2, CMV and RV in clinical specimens of sera and cerebrospinal fluids (CSFs. The positive reference sera were initially used to measure the sensitivity and specificity of the array with the optimal conditions. Then clinical specimens of 144 sera and 93 CSFs were tested for IgG and IgM antibodies directed against HSV1, HSV2, CMV and RV by the antigen array. Specificity of the antigen array for viral antibodies detection was satisfying compared to commercial ELISA kits but sensitivity of the array varied relying on quality and antigenic epitopes of the spotting antigens. In short, the recombinant antigen array has potential to simultaneous detect multiple viral antibodies using minute amount (3 µl of samples, which holds the particularly advantage to detect viral antibodies in clinical CSFs being suspicious of neonatal meningitis and encephalitis.

  8. Directional synthetic aperture flow imaging using a dual stage beamformer approach

    DEFF Research Database (Denmark)

    Li, Ye; Jensen, Jørgen Arendt

    2011-01-01

    . The new method has been studied using the Field II simulations and experimental flow rig measurements. A linear array transducer with 7 MHz center frequency is used, and 64 elements are active to transmit and receive signals. The data is processed in two stages. The first stage has a fixed focus point......A new method for directional synthetic aperture flow imaging using a dual stage beamformer approach is presented. The velocity estimation is angle independent and the amount of calculations is reduced compared to full synthetic aperture, but still maintains all the advantages at the same time....... In the second stage, focal points are considered as virtual sources and data is beamformed along the flow direction. Then the velocities are estimated by finding the spatial shift between two signals. In the experimental measurements the angle between the transmit beam and flow vessel was 70 and a laminar flow...

  9. Non-invasive preimplantation genetic screening using array comparative genomic hybridization on spent culture media: a proof-of-concept pilot study.

    Science.gov (United States)

    Feichtinger, Michael; Vaccari, Enrico; Carli, Luca; Wallner, Elisabeth; Mädel, Ulrike; Figl, Katharina; Palini, Simone; Feichtinger, Wilfried

    2017-06-01

    The aim of this pilot study was to assess if array comparative genomic hybridization (aCGH), non-invasive preimplantation genetic screening (PGS) on blastocyst culture media is feasible. Therefore, aCGH analysis was carried out on 22 spent blastocyst culture media samples after polar body PGS because of advanced maternal age. All oocytes were fertilized by intracytoplasmic sperm injection and all embryos underwent assisted hatching. Concordance of polar body analysis and culture media genetic results was assessed. Thirteen out of 18 samples (72.2%) revealed general concordance of ploidy status (euploid or aneuploid). At least one chromosomal aberration was found concordant in 10 out of 15 embryos found to be aneuploid by both polar body and culture media analysis. Overall, 17 out of 35 (48.6%) single chromosomal aneuploidies were concordant between the culture media and polar body analysis. By analysing negative controls (oocytes with fertilization failure), notable maternal contamination was observed. Therefore, non-invasive PGS could serve as a second matrix after polar body or cleavage stage PGS; however, in euploid results, maternal contamination needs to be considered and results interpreted with caution. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  10. SA-SSR: a suffix array-based algorithm for exhaustive and efficient SSR discovery in large genetic sequences.

    Science.gov (United States)

    Pickett, B D; Karlinsey, S M; Penrod, C E; Cormier, M J; Ebbert, M T W; Shiozawa, D K; Whipple, C J; Ridge, P G

    2016-09-01

    Simple Sequence Repeats (SSRs) are used to address a variety of research questions in a variety of fields (e.g. population genetics, phylogenetics, forensics, etc.), due to their high mutability within and between species. Here, we present an innovative algorithm, SA-SSR, based on suffix and longest common prefix arrays for efficiently detecting SSRs in large sets of sequences. Existing SSR detection applications are hampered by one or more limitations (i.e. speed, accuracy, ease-of-use, etc.). Our algorithm addresses these challenges while being the most comprehensive and correct SSR detection software available. SA-SSR is 100% accurate and detected >1000 more SSRs than the second best algorithm, while offering greater control to the user than any existing software. SA-SSR is freely available at http://github.com/ridgelab/SA-SSR CONTACT: perry.ridge@byu.edu Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.

  11. High resolution three-dimensional robotic synthetic tracked aperture ultrasound imaging: feasibility study

    Science.gov (United States)

    Zhang, Haichong K.; Fang, Ting Yun; Finocchi, Rodolfo; Boctor, Emad M.

    2017-03-01

    Three dimensional (3D) ultrasound imaging is becoming a standard mode for medical ultrasound diagnoses. Conventional 3D ultrasound imaging is mostly scanned either by using a two dimensional matrix array or by motorizing a one dimensional array in the elevation direction. However, the former system is not widely assessable due to its cost, and the latter one has limited resolution and field-of-view in the elevation axis. Here, we propose a 3D ultrasound imaging system based on the synthetic tracked aperture approach, in which a robotic arm is used to provide accurate tracking and motion. While the ultrasound probe is moved by a robotic arm, each probe position is tracked and can be used to reconstruct a wider field-of-view as there are no physical barriers that restrict the elevational scanning. At the same time, synthetic aperture beamforming provides a better resolution in the elevation axis. To synthesize the elevational information, the single focal point is regarded as the virtual element, and forward and backward delay-andsum are applied to the radio-frequency (RF) data collected through the volume. The concept is experimentally validated using a general ultrasound phantom, and the elevational resolution improvement of 2.54 and 2.13 times was measured at the target depths of 20 mm and 110 mm, respectively.

  12. [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.

  13. 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).

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

    Czech Academy of Sciences Publication Activity Database

    Hlavová, Monika; Turóczy, Zoltán; Bišová, Kateřina

    2015-01-01

    Roč. 33, č. 6 (2015), s. 1194-1203 ISSN 0734-9750 R&D Projects: GA MŠk EE2.3.30.0059; GA MŠk ED2.1.00/03.0110 Institutional support: RVO:61388971 Keywords : Microalgae * Genetics * Mutagenesis Subject RIV: EE - Microbiology, Virology Impact factor: 9.848, year: 2015

  15. Synthetic constructs in/for the environment: managing the interplay between natural and engineered Biology.

    Science.gov (United States)

    Schmidt, Markus; de Lorenzo, Víctor

    2012-07-16

    The plausible release of deeply engineered or even entirely synthetic/artificial microorganisms raises the issue of their intentional (e.g. bioremediation) or accidental interaction with the Environment. Containment systems designed in the 1980s-1990s for limiting the spread of genetically engineered bacteria and their recombinant traits are still applicable to contemporary Synthetic Biology constructs. Yet, the ease of DNA synthesis and the uncertainty on how non-natural properties and strains could interplay with the existing biological word poses yet again the challenge of designing safe and efficacious firewalls to curtail possible interactions. Such barriers may include xeno-nucleic acids (XNAs) instead of DNA as information-bearing molecules, rewriting the genetic code to make it non-understandable by the existing gene expression machineries, and/or making growth dependent on xenobiotic chemicals. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  16. Reprint of Design of synthetic microbial communities for biotechnological production processes.

    Science.gov (United States)

    Jagmann, Nina; Philipp, Bodo

    2014-12-20

    In their natural habitats microorganisms live in multi-species communities, in which the community members exhibit complex metabolic interactions. In contrast, biotechnological production processes catalyzed by microorganisms are usually carried out with single strains in pure cultures. A number of production processes, however, may be more efficiently catalyzed by the concerted action of microbial communities. This review will give an overview of organismic interactions between microbial cells and of biotechnological applications of microbial communities. It focuses on synthetic microbial communities that consist of microorganisms that have been genetically engineered. Design principles for such synthetic communities will be exemplified based on plausible scenarios for biotechnological production processes. These design principles comprise interspecific metabolic interactions via cross-feeding, regulation by interspecific signaling processes via metabolites and autoinducing signal molecules, and spatial structuring of synthetic microbial communities. In particular, the implementation of metabolic interdependencies, of positive feedback regulation and of inducible cell aggregation and biofilm formation will be outlined. Synthetic microbial communities constitute a viable extension of the biotechnological application of metabolically engineered single strains and enlarge the scope of microbial production processes. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. "Knight in shining armour" or "Frankenstein's creation"? The coverage of synthetic biology in German-language media.

    Science.gov (United States)

    Gschmeidler, Brigitte; Seiringer, Alexandra

    2012-02-01

    Although still a side issue in the German-language media, attention towards synthetic biology has risen clearly during the last years, in line with the first applications being presented. This paper presents findings from a content analysis of synthetic biology coverage in German-language media over the years 2004-2009. In the media, synthetic biology is not clearly separated from gene technology. News value is attributed to established categories such as persons and events. Many metaphors and analogies used in describing gene technology can also be found in the coverage of synthetic biology; however, engineering metaphors are more prominent. In addition, playfulness constitutes an aspect rarely found in genetic engineering coverage. Overall, the picture emerging is ambivalent, which leaves prospects for the further development of public debate ambiguous.

  18. Processing and display of three-dimensional arrays of numerical data using octree encoding

    International Nuclear Information System (INIS)

    Amans, J.L.; Antoine, M.; Darier, P.

    1986-04-01

    The analysis of three-dimensional (3-D) arrays of numerical data from medical, industrial or scientific imaging, by synthetic generation of realistic images, has been widely developed. The Octree encoding, that organizes the volume data in a hierarchical tree structure, has some interesting features for 3-D arrays of data processing. The Octree encoding method, based on the recursive subdivision of a 3-D array, is an extension of the Quadtree encoding in the two-dimensional plane. We have developed a software package to validate the basic Octree encoding methodology for some manipulation and display operations of volume data. The contribution introduces the technique we have used (called ''overlay technique'') to make the projection operation of an Octree on a Quadtree encoded image plane. The application of this technique to the hidden surface display is presented [fr

  19. Recent advances of molecular toolbox construction expand Pichia pastoris in synthetic biology applications.

    Science.gov (United States)

    Kang, Zhen; Huang, Hao; Zhang, Yunfeng; Du, Guocheng; Chen, Jian

    2017-01-01

    Pichia pastoris: (reclassified as Komagataella phaffii), a methylotrophic yeast strain has been widely used for heterologous protein production because of its unique advantages, such as readily achievable high-density fermentation, tractable genetic modifications and typical eukaryotic post-translational modifications. More recently, P. pastoris as a metabolic pathway engineering platform has also gained much attention. In this mini-review, we addressed recent advances of molecular toolboxes, including synthetic promoters, signal peptides, and genome engineering tools that established for P. pastoris. Furthermore, the applications of P. pastoris towards synthetic biology were also discussed and prospected especially in the context of genome-scale metabolic pathway analysis.

  20. The first genetic map of pigeon pea based on diversity arrays ...

    Indian Academy of Sciences (India)

    2016-08-26

    Aug 26, 2016 ... a total of 554 diversity arrays technology (DArT) markers showed ... EH Graham Centre for Agricultural Innovation (NSW Department of Industry and ... India; Theme-Comparative and Applied Genomics, Generation Challenge ...

  1. Complex and unexpected dynamics in simple genetic regulatory networks

    Science.gov (United States)

    Borg, Yanika; Ullner, Ekkehard; Alagha, Afnan; Alsaedi, Ahmed; Nesbeth, Darren; Zaikin, Alexey

    2014-03-01

    One aim of synthetic biology is to construct increasingly complex genetic networks from interconnected simpler ones to address challenges in medicine and biotechnology. However, as systems increase in size and complexity, emergent properties lead to unexpected and complex dynamics due to nonlinear and nonequilibrium properties from component interactions. We focus on four different studies of biological systems which exhibit complex and unexpected dynamics. Using simple synthetic genetic networks, small and large populations of phase-coupled quorum sensing repressilators, Goodwin oscillators, and bistable switches, we review how coupled and stochastic components can result in clustering, chaos, noise-induced coherence and speed-dependent decision making. A system of repressilators exhibits oscillations, limit cycles, steady states or chaos depending on the nature and strength of the coupling mechanism. In large repressilator networks, rich dynamics can also be exhibited, such as clustering and chaos. In populations of Goodwin oscillators, noise can induce coherent oscillations. In bistable systems, the speed with which incoming external signals reach steady state can bias the network towards particular attractors. These studies showcase the range of dynamical behavior that simple synthetic genetic networks can exhibit. In addition, they demonstrate the ability of mathematical modeling to analyze nonlinearity and inhomogeneity within these systems.

  2. Development and validation of a high density SNP genotyping array for Atlantic salmon (Salmo salar)

    Science.gov (United States)

    2014-01-01

    Background Dense single nucleotide polymorphism (SNP) genotyping arrays provide extensive information on polymorphic variation across the genome of species of interest. Such information can be used in studies of the genetic architecture of quantitative traits and to improve the accuracy of selection in breeding programs. In Atlantic salmon (Salmo salar), these goals are currently hampered by the lack of a high-density SNP genotyping platform. Therefore, the aim of the study was to develop and test a dense Atlantic salmon SNP array. Results SNP discovery was performed using extensive deep sequencing of Reduced Representation (RR-Seq), Restriction site-Associated DNA (RAD-Seq) and mRNA (RNA-Seq) libraries derived from farmed and wild Atlantic salmon samples (n = 283) resulting in the discovery of > 400 K putative SNPs. An Affymetrix Axiom® myDesign Custom Array was created and tested on samples of animals of wild and farmed origin (n = 96) revealing a total of 132,033 polymorphic SNPs with high call rate, good cluster separation on the array and stable Mendelian inheritance in our sample. At least 38% of these SNPs are from transcribed genomic regions and therefore more likely to include functional variants. Linkage analysis utilising the lack of male recombination in salmonids allowed the mapping of 40,214 SNPs distributed across all 29 pairs of chromosomes, highlighting the extensive genome-wide coverage of the SNPs. An identity-by-state clustering analysis revealed that the array can clearly distinguish between fish of different origins, within and between farmed and wild populations. Finally, Y-chromosome-specific probes included on the array provide an accurate molecular genetic test for sex. Conclusions This manuscript describes the first high-density SNP genotyping array for Atlantic salmon. This array will be publicly available and is likely to be used as a platform for high-resolution genetics research into traits of evolutionary and economic importance in

  3. Precision control of recombinant gene transcription for CHO cell synthetic biology.

    Science.gov (United States)

    Brown, Adam J; James, David C

    2016-01-01

    The next generation of mammalian cell factories for biopharmaceutical production will be genetically engineered to possess both generic and product-specific manufacturing capabilities that may not exist naturally. Introduction of entirely new combinations of synthetic functions (e.g. novel metabolic or stress-response pathways), and retro-engineering of existing functional cell modules will drive disruptive change in cellular manufacturing performance. However, before we can apply the core concepts underpinning synthetic biology (design, build, test) to CHO cell engineering we must first develop practical and robust enabling technologies. Fundamentally, we will require the ability to precisely control the relative stoichiometry of numerous functional components we simultaneously introduce into the host cell factory. In this review we discuss how this can be achieved by design of engineered promoters that enable concerted control of recombinant gene transcription. We describe the specific mechanisms of transcriptional regulation that affect promoter function during bioproduction processes, and detail the highly-specific promoter design criteria that are required in the context of CHO cell engineering. The relative applicability of diverse promoter development strategies are discussed, including re-engineering of natural sequences, design of synthetic transcription factor-based systems, and construction of synthetic promoters. This review highlights the potential of promoter engineering to achieve precision transcriptional control for CHO cell synthetic biology. Copyright © 2015. Published by Elsevier Inc.

  4. Novel applications of array comparative genomic hybridization in molecular diagnostics.

    Science.gov (United States)

    Cheung, Sau W; Bi, Weimin

    2018-05-31

    In 2004, the implementation of array comparative genomic hybridization (array comparative genome hybridization [CGH]) into clinical practice marked a new milestone for genetic diagnosis. Array CGH and single-nucleotide polymorphism (SNP) arrays enable genome-wide detection of copy number changes in a high resolution, and therefore microarray has been recognized as the first-tier test for patients with intellectual disability or multiple congenital anomalies, and has also been applied prenatally for detection of clinically relevant copy number variations in the fetus. Area covered: In this review, the authors summarize the evolution of array CGH technology from their diagnostic laboratory, highlighting exonic SNP arrays developed in the past decade which detect small intragenic copy number changes as well as large DNA segments for the region of heterozygosity. The applications of array CGH to human diseases with different modes of inheritance with the emphasis on autosomal recessive disorders are discussed. Expert commentary: An exonic array is a powerful and most efficient clinical tool in detecting genome wide small copy number variants in both dominant and recessive disorders. However, whole-genome sequencing may become the single integrated platform for detection of copy number changes, single-nucleotide changes as well as balanced chromosomal rearrangements in the near future.

  5. From Nature to the Lab: Establishing Drosophila Resources for Evolutionary Genetics

    Directory of Open Access Journals (Sweden)

    Vítor G. Faria

    2017-06-01

    Full Text Available In recent years important tools have been developed in Drosophila to capture with the greatest possible accuracy the variation found in nature. Efforts, such as the Drosophila melanogaster Genetic Reference Panel (DGRP or the Drosophila Synthetic Population Resource (DSPR allied to the advances in whole-genome sequencing and analysis have propelled to unprecedented level our capacity to dissect the genotype-phenotype map. However, several practical problems arise upstream of these analyses starting with the collection and identification of wild specimens. These problems are dealt with in different ways by each researcher generating solutions not necessarily compatible across laboratories. Here, we provide a systematic coverage of every phase of this process based on our experience, and suggest procedures to maximize and share the generated resources potentiating future applications. We propose a detailed pipeline to guide researchers from collection in the wild to the development of a large array of molecular and genetic resources. We designed a multiplex-PCR that distinguishes sister species D. melanogaster and D. simulans and is diagnostic of the presence/absence of Wolbachia infection. These procedures may extend to other cryptic species pairs and endosymbionts. We developed a standardized protocol to create, replicate and maintain isofemale lines and outbred populations. Finally, we explore the potential of outbred populations across several applications from experimental evolution, to introgression of transgenic constructs or mutant alleles, and genomic analyses. We hope to contribute to the success in developing Drosophila resources for evolutionary genetics studies and facilitate exchanges across laboratories based on a common set of procedures.

  6. Synthetic Biology and Metabolic Engineering Approaches and Its Impact on Non-Conventional Yeast and Biofuel Production

    Energy Technology Data Exchange (ETDEWEB)

    Madhavan, Aravind [Biotechnology Division, National Institute for Interdisciplinary Science and Technology, Council of Scientific and Industrial Research, Trivandrum (India); Rajiv Gandhi Centre for Biotechnology, Trivandrum (India); Jose, Anju Alphonsa; Binod, Parameswaran; Sindhu, Raveendran, E-mail: sindhurgcb@gmail.com; Sukumaran, Rajeev K. [Biotechnology Division, National Institute for Interdisciplinary Science and Technology, Council of Scientific and Industrial Research, Trivandrum (India); Pandey, Ashok [Biotechnology Division, National Institute for Interdisciplinary Science and Technology, Council of Scientific and Industrial Research, Trivandrum (India); Center for Innovative and Applied Bioprocessing, Mohali, Punjab (India); Castro, Galliano Eulogio [Dpt. Ingeniería Química, Ambiental y de los Materiales Edificio, Universidad de Jaén, Jaén (Spain)

    2017-04-25

    The increasing fossil fuel scarcity has led to an urgent need to develop alternative fuels. Currently microorganisms have been extensively used for the production of first-generation biofuels from lignocellulosic biomass. Yeast is the efficient producer of bioethanol among all existing biofuels option. Tools of synthetic biology have revolutionized the field of microbial cell factories especially in the case of ethanol and fatty acid production. Most of the synthetic biology tools have been developed for the industrial workhorse Saccharomyces cerevisiae. The non-conventional yeast systems have several beneficial traits like ethanol tolerance, thermotolerance, inhibitor tolerance, genetic diversity, etc., and synthetic biology have the power to expand these traits. Currently, synthetic biology is slowly widening to the non-conventional yeasts like Hansenula polymorpha, Kluyveromyces lactis, Pichia pastoris, and Yarrowia lipolytica. Herein, we review the basic synthetic biology tools that can apply to non-conventional yeasts. Furthermore, we discuss the recent advances employed to develop efficient biofuel-producing non-conventional yeast strains by metabolic engineering and synthetic biology with recent examples. Looking forward, future synthetic engineering tools’ development and application should focus on unexplored non-conventional yeast species.

  7. Synthetic Biology and Metabolic Engineering Approaches and Its Impact on Non-Conventional Yeast and Biofuel Production

    Directory of Open Access Journals (Sweden)

    Raveendran Sindhu

    2017-04-01

    Full Text Available The increasing fossil fuel scarcity has led to an urgent need to develop alternative fuels. Currently microorganisms have been extensively used for the production of first-generation biofuels from lignocellulosic biomass. Yeast is the efficient producer of bioethanol among all existing biofuels option. Tools of synthetic biology have revolutionized the field of microbial cell factories especially in the case of ethanol and fatty acid production. Most of the synthetic biology tools have been developed for the industrial workhorse Saccharomyces cerevisiae. The non-conventional yeast systems have several beneficial traits like ethanol tolerance, thermotolerance, inhibitor tolerance, genetic diversity, etc., and synthetic biology have the power to expand these traits. Currently, synthetic biology is slowly widening to the non-conventional yeasts like Hansenula polymorpha, Kluyveromyces lactis, Pichia pastoris, and Yarrowia lipolytica. Herein, we review the basic synthetic biology tools that can apply to non-conventional yeasts. Furthermore, we discuss the recent advances employed to develop efficient biofuel-producing non-conventional yeast strains by metabolic engineering and synthetic biology with recent examples. Looking forward, future synthetic engineering tools’ development and application should focus on unexplored non-conventional yeast species.

  8. Synthetic Biology and Metabolic Engineering Approaches and Its Impact on Non-Conventional Yeast and Biofuel Production

    International Nuclear Information System (INIS)

    Madhavan, Aravind; Jose, Anju Alphonsa; Binod, Parameswaran; Sindhu, Raveendran; Sukumaran, Rajeev K.; Pandey, Ashok; Castro, Galliano Eulogio

    2017-01-01

    The increasing fossil fuel scarcity has led to an urgent need to develop alternative fuels. Currently microorganisms have been extensively used for the production of first-generation biofuels from lignocellulosic biomass. Yeast is the efficient producer of bioethanol among all existing biofuels option. Tools of synthetic biology have revolutionized the field of microbial cell factories especially in the case of ethanol and fatty acid production. Most of the synthetic biology tools have been developed for the industrial workhorse Saccharomyces cerevisiae. The non-conventional yeast systems have several beneficial traits like ethanol tolerance, thermotolerance, inhibitor tolerance, genetic diversity, etc., and synthetic biology have the power to expand these traits. Currently, synthetic biology is slowly widening to the non-conventional yeasts like Hansenula polymorpha, Kluyveromyces lactis, Pichia pastoris, and Yarrowia lipolytica. Herein, we review the basic synthetic biology tools that can apply to non-conventional yeasts. Furthermore, we discuss the recent advances employed to develop efficient biofuel-producing non-conventional yeast strains by metabolic engineering and synthetic biology with recent examples. Looking forward, future synthetic engineering tools’ development and application should focus on unexplored non-conventional yeast species.

  9. Genetic Constructor: An Online DNA Design Platform.

    Science.gov (United States)

    Bates, Maxwell; Lachoff, Joe; Meech, Duncan; Zulkower, Valentin; Moisy, Anaïs; Luo, Yisha; Tekotte, Hille; Franziska Scheitz, Cornelia Johanna; Khilari, Rupal; Mazzoldi, Florencio; Chandran, Deepak; Groban, Eli

    2017-12-15

    Genetic Constructor is a cloud Computer Aided Design (CAD) application developed to support synthetic biologists from design intent through DNA fabrication and experiment iteration. The platform allows users to design, manage, and navigate complex DNA constructs and libraries, using a new visual language that focuses on functional parts abstracted from sequence. Features like combinatorial libraries and automated primer design allow the user to separate design from construction by focusing on functional intent, and design constraints aid iterative refinement of designs. A plugin architecture enables contributions from scientists and coders to leverage existing powerful software and connect to DNA foundries. The software is easily accessible and platform agnostic, free for academics, and available in an open-source community edition. Genetic Constructor seeks to democratize DNA design, manufacture, and access to tools and services from the synthetic biology community.

  10. Tissue Harmonic Synthetic Aperture Ultrasound Imaging

    DEFF Research Database (Denmark)

    Hemmsen, Martin Christian; Rasmussen, Joachim; Jensen, Jørgen Arendt

    2014-01-01

    Synthetic aperture sequential beamforming (SASB) and tissue har- monic imaging (THI) are combined to improve the image quality of medical ultrasound imaging. The technique is evaluated in a compar- ative study against dynamic receive focusing (DRF). The objective is to investigate if SASB combined...... with THI improves the image qual- ity compared to DRF-THI. The major benet of SASB is a reduced bandwidth between the probe and processing unit. A BK Medical 2202 Ultraview ultrasound scanner was used to acquire beamformed RF data for oine evaluation. The acquisition was made interleaved between methods......, and data were recorded with and without pulse inversion for tissue harmonic imaging. Data were acquired using a Sound Technol- ogy 192 element convex array transducer from both a wire phantom and a tissue mimicking phantom to investigate spatial resolution and pen- etration. In-vivo scans were also...

  11. High-density polymer microarrays: identifying synthetic polymers that control human embryonic stem cell growth.

    Science.gov (United States)

    Hansen, Anne; Mjoseng, Heidi K; Zhang, Rong; Kalloudis, Michail; Koutsos, Vasileios; de Sousa, Paul A; Bradley, Mark

    2014-06-01

    The fabrication of high-density polymer microarray is described, allowing the simultaneous and efficient evaluation of more than 7000 different polymers in a single-cellular-based screen. These high-density polymer arrays are applied in the search for synthetic substrates for hESCs culture. Up-scaling of the identified hit polymers enables long-term cellular cultivation and promoted successful stem-cell maintenance. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Preimplantation genetic screening.

    Science.gov (United States)

    Harper, Joyce C

    2018-03-01

    Preimplantation genetic diagnosis was first successfully performed in 1989 as an alternative to prenatal diagnosis for couples at risk of transmitting a genetic or chromosomal abnormality, such as cystic fibrosis, to their child. From embryos generated in vitro, biopsied cells are genetically tested. From the mid-1990s, this technology has been employed as an embryo selection tool for patients undergoing in vitro fertilisation, screening as many chromosomes as possible, in the hope that selecting chromosomally normal embryos will lead to higher implantation and decreased miscarriage rates. This procedure, preimplantation genetic screening, was initially performed using fluorescent in situ hybridisation, but 11 randomised controlled trials of screening using this technique showed no improvement in in vitro fertilisation delivery rates. Progress in genetic testing has led to the introduction of array comparative genomic hybridisation, quantitative polymerase chain reaction, and next generation sequencing for preimplantation genetic screening, and three small randomised controlled trials of preimplantation genetic screening using these new techniques indicate a modest benefit. Other trials are still in progress but, regardless of their results, preimplantation genetic screening is now being offered globally. In the near future, it is likely that sequencing will be used to screen the full genetic code of the embryo.

  13. Array-CGH Analysis in a Cohort of Phenotypically Well-Characterized Individuals with "Essential" Autism Spectrum Disorders

    Science.gov (United States)

    Napoli, Eleonora; Russo, Serena; Casula, Laura; Alesi, Viola; Amendola, Filomena Alessandra; Angioni, Adriano; Novelli, Antonio; Valeri, Giovanni; Menghini, Deny; Vicari, Stefano

    2018-01-01

    Copy-number variants (CNVs) are associated with susceptibility to autism spectrum disorder (ASD). To detect the presence of CNVs, we conducted an array-comparative genomic hybridization (array-CGH) analysis in 133 children with "essential" ASD phenotype. Genetic analyses documented that 12 children had causative CNVs (C-CNVs), 29…

  14. 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.

  15. Transcription control engineering and applications in synthetic biology.

    Science.gov (United States)

    Engstrom, Michael D; Pfleger, Brian F

    2017-09-01

    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. Properties of alternative microbial hosts used in synthetic biology: towards the design of a modular chassis

    Science.gov (United States)

    Kim, Juhyun; Salvador, Manuel; Saunders, Elizabeth; González, Jaime; Avignone-Rossa, Claudio

    2016-01-01

    The chassis is the cellular host used as a recipient of engineered biological systems in synthetic biology. They are required to propagate the genetic information and to express the genes encoded in it. Despite being an essential element for the appropriate function of genetic circuits, the chassis is rarely considered in their design phase. Consequently, the circuits are transferred to model organisms commonly used in the laboratory, such as Escherichia coli, that may be suboptimal for a required function. In this review, we discuss some of the properties desirable in a versatile chassis and summarize some examples of alternative hosts for synthetic biology amenable for engineering. These properties include a suitable life style, a robust cell wall, good knowledge of its regulatory network as well as of the interplay of the host components with the exogenous circuits, and the possibility of developing whole-cell models and tuneable metabolic fluxes that could allow a better distribution of cellular resources (metabolites, ATP, nucleotides, amino acids, transcriptional and translational machinery). We highlight Pseudomonas putida, widely used in many different biotechnological applications as a prominent organism for synthetic biology due to its metabolic diversity, robustness and ease of manipulation. PMID:27903818

  17. Two-dimensional Fast ESPRIT Algorithm for Linear Array SAR Imaging

    Directory of Open Access Journals (Sweden)

    Zhao Yi-chao

    2015-10-01

    Full Text Available The linear array Synthetic Aperture Radar (SAR system is a popular research tool, because it can realize three-dimensional imaging. However, owning to limitations of the aircraft platform and actual conditions, resolution improvement is difficult in cross-track and along-track directions. In this study, a twodimensional fast Estimation of Signal Parameters by Rotational Invariance Technique (ESPRIT algorithm for linear array SAR imaging is proposed to overcome these limitations. This approach combines the Gerschgorin disks method and the ESPRIT algorithm to estimate the positions of scatterers in cross and along-rack directions. Moreover, the reflectivity of scatterers is obtained by a modified pairing method based on “region growing”, replacing the least-squares method. The simulation results demonstrate the applicability of the algorithm with high resolution, quick calculation, and good real-time response.

  18. Extended lanthanide-transition metal arrays with cyanide bridges: syntheses, structures, and catalytic applications

    International Nuclear Information System (INIS)

    Liu Shengming; Poplaukhin, Pavel; Ding Errun; Plecnik, Christine E.; Chen Xuenian; Keane, Mark A.; Shore, Sheldon G.

    2006-01-01

    Systematic synthetic procedures produced several different structural types of extended lanthanide-transition metal (group 10) complexes with cyanide bridges. Of these, one-dimensional ladder arrays containing a Yb-Pd combination have been converted to bimetallic heterogeneous catalysts on an oxide (SiO 2 ) surface that is more effective than supported Pd alone. Two lanthanide-Cu(I) complexes have been prepared. One type, an inclusion complex consists of lanthanide(III) cations encapsulated in the pockets of a three-dimensional anionic array that contains Cu(I)-CN-Cu(I) bridges. The second type, an extended layer complex, consists of joined five-membered rings in a 'tile-like' pattern with Ln-CN-Cu and Cu-CN-Cu bridges

  19. Design of synthetic biological logic circuits based on evolutionary algorithm.

    Science.gov (United States)

    Chuang, Chia-Hua; Lin, Chun-Liang; Chang, Yen-Chang; Jennawasin, Tanagorn; Chen, Po-Kuei

    2013-08-01

    The construction of an artificial biological logic circuit using systematic strategy is recognised as one of the most important topics for the development of synthetic biology. In this study, a real-structured genetic algorithm (RSGA), which combines general advantages of the traditional real genetic algorithm with those of the structured genetic algorithm, is proposed to deal with the biological logic circuit design problem. A general model with the cis-regulatory input function and appropriate promoter activity functions is proposed to synthesise a wide variety of fundamental logic gates such as NOT, Buffer, AND, OR, NAND, NOR and XOR. The results obtained can be extended to synthesise advanced combinational and sequential logic circuits by topologically distinct connections. The resulting optimal design of these logic gates and circuits are established via the RSGA. The in silico computer-based modelling technology has been verified showing its great advantages in the purpose.

  20. MIDAS: A Modular DNA Assembly System for Synthetic Biology.

    Science.gov (United States)

    van Dolleweerd, Craig J; Kessans, Sarah A; Van de Bittner, Kyle C; Bustamante, Leyla Y; Bundela, Rudranuj; Scott, Barry; Nicholson, Matthew J; Parker, Emily J

    2018-04-20

    A modular and hierarchical DNA assembly platform for synthetic biology based on Golden Gate (Type IIS restriction enzyme) cloning is described. This enabling technology, termed MIDAS (for Modular Idempotent DNA Assembly System), can be used to precisely assemble multiple DNA fragments in a single reaction using a standardized assembly design. It can be used to build genes from libraries of sequence-verified, reusable parts and to assemble multiple genes in a single vector, with full user control over gene order and orientation, as well as control of the direction of growth (polarity) of the multigene assembly, a feature that allows genes to be nested between other genes or genetic elements. We describe the detailed design and use of MIDAS, exemplified by the reconstruction, in the filamentous fungus Penicillium paxilli, of the metabolic pathway for production of paspaline and paxilline, key intermediates in the biosynthesis of a range of indole diterpenes-a class of secondary metabolites produced by several species of filamentous fungi. MIDAS was used to efficiently assemble a 25.2 kb plasmid from 21 different modules (seven genes, each composed of three basic parts). By using a parts library-based system for construction of complex assemblies, and a unique set of vectors, MIDAS can provide a flexible route to assembling tailored combinations of genes and other genetic elements, thereby supporting synthetic biology applications in a wide range of expression hosts.

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

    Science.gov (United States)

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

    2016-06-17

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

  2. Journal of Genetics | Indian Academy of Sciences

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Genetics. Azubel Ramírez-Velazco. Articles written in Journal of Genetics. Volume 93 Issue 3 December 2014 pp 869-873 Research Note. De novo dir dup/del of 18q characterized by SNP arrays and FISH in a girl child with mixed phenotypes · Carlos Córdova-Fletes Enrique Sáinz-González ...

  3. Array capabilities and future arrays

    International Nuclear Information System (INIS)

    Radford, D.

    1993-01-01

    Early results from the new third-generation instruments GAMMASPHERE and EUROGAM are confirming the expectation that such arrays will have a revolutionary effect on the field of high-spin nuclear structure. When completed, GAMMASHPERE will have a resolving power am order of magnitude greater that of the best second-generation arrays. When combined with other instruments such as particle-detector arrays and fragment mass analysers, the capabilites of the arrays for the study of more exotic nuclei will be further enhanced. In order to better understand the limitations of these instruments, and to design improved future detector systems, it is important to have some intelligible and reliable calculation for the relative resolving power of different instrument designs. The derivation of such a figure of merit will be briefly presented, and the relative sensitivities of arrays currently proposed or under construction presented. The design of TRIGAM, a new third-generation array proposed for Chalk River, will also be discussed. It is instructive to consider how far arrays of Compton-suppressed Ge detectors could be taken. For example, it will be shown that an idealised open-quote perfectclose quotes third-generation array of 1000 detectors has a sensitivity an order of magnitude higher again than that of GAMMASPHERE. Less conventional options for new arrays will also be explored

  4. Large-Aperture Membrane Active Phased-Array Antennas

    Science.gov (United States)

    Karasik, Boris; McGrath, William; Leduc, Henry

    2009-01-01

    Large-aperture phased-array microwave antennas supported by membranes are being developed for use in spaceborne interferometric synthetic aperture radar systems. There may also be terrestrial uses for such antennas supported on stationary membranes, large balloons, and blimps. These antennas are expected to have areal mass densities of about 2 kg/sq m, satisfying a need for lightweight alternatives to conventional rigid phased-array antennas, which have typical areal mass densities between 8 and 15 kg/sq m. The differences in areal mass densities translate to substantial differences in total mass in contemplated applications involving aperture areas as large as 400 sq m. A membrane phased-array antenna includes patch antenna elements in a repeating pattern. All previously reported membrane antennas were passive antennas; this is the first active membrane antenna that includes transmitting/receiving (T/R) electronic circuits as integral parts. Other integral parts of the antenna include a network of radio-frequency (RF) feed lines (more specifically, a corporate feed network) and of bias and control lines, all in the form of flexible copper strip conductors on flexible polymeric membranes. Each unit cell of a prototype antenna (see Figure 1) contains a patch antenna element and a compact T/R module that is compatible with flexible membrane circuitry. There are two membrane layers separated by a 12.7-mm air gap. Each membrane layer is made from a commercially available flexible circuit material that, as supplied, comprises a 127-micron-thick polyimide dielectric layer clad on both sides with 17.5-micron-thick copper layers. The copper layers are patterned into RF, bias, and control conductors. The T/R module is located on the back side of the ground plane and is RF-coupled to the patch element via a slot. The T/R module is a hybrid multilayer module assembled and packaged independently and attached to the membrane array. At the time of reporting the information for

  5. A reconfigurable NAND/NOR genetic logic gate.

    Science.gov (United States)

    Goñi-Moreno, Angel; Amos, Martyn

    2012-09-18

    Engineering genetic Boolean logic circuits is a major research theme of synthetic biology. By altering or introducing connections between genetic components, novel regulatory networks are built in order to mimic the behaviour of electronic devices such as logic gates. While electronics is a highly standardized science, genetic logic is still in its infancy, with few agreed standards. In this paper we focus on the interpretation of logical values in terms of molecular concentrations. We describe the results of computational investigations of a novel circuit that is able to trigger specific differential responses depending on the input standard used. The circuit can therefore be dynamically reconfigured (without modification) to serve as both a NAND/NOR logic gate. This multi-functional behaviour is achieved by a) varying the meanings of inputs, and b) using branch predictions (as in computer science) to display a constrained output. A thorough computational study is performed, which provides valuable insights for the future laboratory validation. The simulations focus on both single-cell and population behaviours. The latter give particular insights into the spatial behaviour of our engineered cells on a surface with a non-homogeneous distribution of inputs. We present a dynamically-reconfigurable NAND/NOR genetic logic circuit that can be switched between modes of operation via a simple shift in input signal concentration. The circuit addresses important issues in genetic logic that will have significance for more complex synthetic biology applications.

  6. Genetic analyses of agronomic and seed quality traits of synthetic ...

    Indian Academy of Sciences (India)

    As for protein content, similar results were found in the F2 plants and their maternal parents. ... doubled haploid; genetic analysis; gene interaction; agronomic traits; seed ..... Han J. Q. and Liu H. L. 1993 Principal component analysis for main.

  7. Photolithographic Synthesis of High-Density DNA and RNA Arrays on Flexible, Transparent, and Easily Subdivided Plastic Substrates.

    Science.gov (United States)

    Holden, Matthew T; Carter, Matthew C D; Wu, Cheng-Hsien; Wolfer, Jamison; Codner, Eric; Sussman, Michael R; Lynn, David M; Smith, Lloyd M

    2015-11-17

    The photolithographic fabrication of high-density DNA and RNA arrays on flexible and transparent plastic substrates is reported. The substrates are thin sheets of poly(ethylene terephthalate) (PET) coated with cross-linked polymer multilayers that present hydroxyl groups suitable for conventional phosphoramidite-based nucleic acid synthesis. We demonstrate that by modifying array synthesis procedures to accommodate the physical and chemical properties of these materials, it is possible to synthesize plastic-backed oligonucleotide arrays with feature sizes as small as 14 μm × 14 μm and feature densities in excess of 125 000/cm(2), similar to specifications attainable using rigid substrates such as glass or glassy carbon. These plastic-backed arrays are tolerant to a wide range of hybridization temperatures, and improved synthetic procedures are described that enable the fabrication of arrays with sequences up to 50 nucleotides in length. These arrays hybridize with S/N ratios comparable to those fabricated on otherwise identical arrays prepared on glass or glassy carbon. This platform supports the enzymatic synthesis of RNA arrays and proof-of-concept experiments are presented showing that the arrays can be readily subdivided into smaller arrays (or "millichips") using common laboratory-scale laser cutting tools. These results expand the utility of oligonucleotide arrays fabricated on plastic substrates and open the door to new applications for these important bioanalytical tools.

  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. Synthetic biology for manufacturing chemicals: constraints drive the use of non-conventional microbial platforms.

    Science.gov (United States)

    Czajka, Jeffrey; Wang, Qinhong; Wang, Yechun; Tang, Yinjie J

    2017-10-01

    Genetically modified microbes have had much industrial success producing protein-based products (such as antibodies and enzymes). However, engineering microbial workhorses for biomanufacturing of commodity compounds remains challenging. First, microbes cannot afford burdens with both overexpression of multiple enzymes and metabolite drainage for product synthesis. Second, synthetic circuits and introduced heterologous pathways are not yet as "robust and reliable" as native pathways due to hosts' innate regulations, especially under suboptimal fermentation conditions. Third, engineered enzymes may lack channeling capabilities for cascade-like transport of metabolites to overcome diffusion barriers or to avoid intermediate toxicity in the cytoplasmic environment. Fourth, moving engineered hosts from laboratory to industry is unreliable because genetic mutations and non-genetic cell-to-cell variations impair the large-scale fermentation outcomes. Therefore, synthetic biology strains often have unsatisfactory industrial performance (titer/yield/productivity). To overcome these problems, many different species are being explored for their metabolic strengths that can be leveraged to synthesize specific compounds. Here, we provide examples of non-conventional and genetically amenable species for industrial manufacturing, including the following: Corynebacterium glutamicum for its TCA cycle-derived biosynthesis, Yarrowia lipolytica for its biosynthesis of fatty acids and carotenoids, cyanobacteria for photosynthetic production from its sugar phosphate pathways, and Rhodococcus for its ability to biotransform recalcitrant feedstock. Finally, we discuss emerging technologies (e.g., genome-to-phenome mapping, single cell methods, and knowledge engineering) that may facilitate the development of novel cell factories.

  10. Determination of synthetic colorants and natural carmine in wines

    Directory of Open Access Journals (Sweden)

    S. Virtanen

    1999-09-01

    Full Text Available Methods were developed for the determination of synthetic colorants and natural carmine (E120 in wines. The synthetic colorants studied were tartrazine (E102, quinoline yellow (E104, sunset yellow (E110, azo ruby (E122, amaranth (E123, ponceau 4R (E124, and erythrosine (E127. The colorants were extracted using solid-phase extraction (SPE with NH2 cartridges. The extracted colorants were then analysed by high-performance liquid chromatography (HPLC. The compounds were identified by comparing the spectrum of extract with spectra in a UV-vis spectral library of known food colorants. The detection limits in red wine ranged from 0.1 mg/l to 0.2 mg/l. Diode array detection and library search makes the method very effective in identifying forbidden colorants in wines. SPE is sufficiently effective in separating and concentrating colorants from wine. The effect of added colorants, e.g. azo ruby (E122, amaranth (E123 and tartrazine (E102 on the UV-vis spectra of red and white wines were studied. The added colorants could be identified in this way but not as accurately as by the HPLC method.

  11. Libraries of Synthetic TALE-Activated Promoters: Methods and Applications.

    Science.gov (United States)

    Schreiber, T; Tissier, A

    2016-01-01

    The discovery of proteins with programmable DNA-binding specificities triggered a whole array of applications in synthetic biology, including genome editing, regulation of transcription, and epigenetic modifications. Among those, transcription activator-like effectors (TALEs) due to their natural function as transcription regulators, are especially well-suited for the development of orthogonal systems for the control of gene expression. We describe here the construction and testing of libraries of synthetic TALE-activated promoters which are under the control of a single TALE with a given DNA-binding specificity. These libraries consist of a fixed DNA-binding element for the TALE, a TATA box, and variable sequences of 19 bases upstream and 43 bases downstream of the DNA-binding element. These libraries were cloned using a Golden Gate cloning strategy making them usable as standard parts in a modular cloning system. The broad range of promoter activities detected and the versatility of these promoter libraries make them valuable tools for applications in the fine-tuning of expression in metabolic engineering projects or in the design and implementation of regulatory circuits. © 2016 Elsevier Inc. All rights reserved.

  12. DNA Array-Based Gene Profiling

    Science.gov (United States)

    Mocellin, Simone; Provenzano, Maurizio; Rossi, Carlo Riccardo; Pilati, Pierluigi; Nitti, Donato; Lise, Mario

    2005-01-01

    Cancer is a heterogeneous disease in most respects, including its cellularity, different genetic alterations, and diverse clinical behaviors. Traditional molecular analyses are reductionist, assessing only 1 or a few genes at a time, thus working with a biologic model too specific and limited to confront a process whose clinical outcome is likely to be governed by the combined influence of many genes. The potential of functional genomics is enormous, because for each experiment, thousands of relevant observations can be made simultaneously. Accordingly, DNA array, like other high-throughput technologies, might catalyze and ultimately accelerate the development of knowledge in tumor cell biology. Although in its infancy, the implementation of DNA array technology in cancer research has already provided investigators with novel data and intriguing new hypotheses on the molecular cascade leading to carcinogenesis, tumor aggressiveness, and sensitivity to antiblastic agents. Given the revolutionary implications that the use of this technology might have in the clinical management of patients with cancer, principles of DNA array-based tumor gene profiling need to be clearly understood for the data to be correctly interpreted and appreciated. In the present work, we discuss the technical features characterizing this powerful laboratory tool and review the applications so far described in the field of oncology. PMID:15621987

  13. Comparison of Wenner and dipole–dipole arrays in the study of an underground three-dimensional cavity

    International Nuclear Information System (INIS)

    Neyamadpour, Ahmad; Wan Abdullah, W A T; Taib, Samsudin; Neyamadpour, Behrang

    2010-01-01

    The objective of this paper was to compare Wenner and dipole–dipole configurations in delineating an underground cavity at a site near the University of Malaya, Malaysia. A three-dimensional electrical resistivity imaging survey was carried out along seven parallel lines using Wenner and dipole–dipole arrays. A three-dimensional least-squares algorithm, based on the robust inversion method, was used in the inversion of the apparent resistivity data. In the inverted model, both the horizontal and vertical extents of the anomalous zones were displayed. Results indicate the superiority of the Wenner array over the dipole–dipole array for determining the vertical distribution of the subsurface resistivity, although the dipole–dipole array produced a better lateral extent of the subsurface features. The results show that the three-dimensional electrical resistivity imaging survey using both the Wenner and dipole–dipole arrays, in combination with an appropriate three-dimensional inversion method and synthetic model analysis, can be highly useful for engineering and environmental applications, especially for underground three-dimensional cavity detection

  14. 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.

  15. Designing synthetic biology.

    Science.gov (United States)

    Agapakis, Christina M

    2014-03-21

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

  16. Multilayer mirror and foil filter AXUV diode arrays on CDX-U spherical torus

    International Nuclear Information System (INIS)

    Soukhanovskii, V. A.; Stutman, D.; Iovea, M.; Finkenthal, M.; Moos, H. W.; Munsat, T.; Jones, B.; Hoffman, D.; Kaita, R.; Majeski, R.

    2001-01-01

    Recent upgrades to CDX-U spherical torus diagnostics include two 10-channel AXUV diode arrays. The multilayer mirror (MLM) array measures the λ150 O VI brightness profile in the poloidal plane using the Mo/B 4 C synthetic multilayer structures as dispersive elements. The foil filter array has a tangential view and is equipped with interchangeable clear aperture, beryllium and titanium filters. This allows measurements of radiated power, O VI or C V radial distributions, respectively. The O VI and C V emissivity and the radiated power profiles are highly peaked. A Neoclassical impurity accumulation mechanism is considered as an explanation. For radiated power measurements in the T e ≤100 eV plasmas, photon energy dependent corrections must be used in order to account for nonlinear AXUV sensitivity in the range E phot ≤20 eV. The arrays are also used for characterization of resistive MHD phenomena, such as the low m modes, saw-tooth oscillations and internal reconnection events. Based on the successful operation of the diagnostics, a new ultra soft x-ray multilayer mirror diode AXUV diode array monitoring the 34 Aa emissivity distribution of C VI will be built and installed on the National Spherical Torus Experiment

  17. Accuracy of Genomic Prediction in Synthetic Populations Depending on the Number of Parents, Relatedness, and Ancestral Linkage Disequilibrium.

    Science.gov (United States)

    Schopp, Pascal; Müller, Dominik; Technow, Frank; Melchinger, Albrecht E

    2017-01-01

    Synthetics play an important role in quantitative genetic research and plant breeding, but few studies have investigated the application of genomic prediction (GP) to these populations. Synthetics are generated by intermating a small number of parents ([Formula: see text] and thereby possess unique genetic properties, which make them especially suited for systematic investigations of factors contributing to the accuracy of GP. We generated synthetics in silico from [Formula: see text]2 to 32 maize (Zea mays L.) lines taken from an ancestral population with either short- or long-range linkage disequilibrium (LD). In eight scenarios differing in relatedness of the training and prediction sets and in the types of data used to calculate the relationship matrix (QTL, SNPs, tag markers, and pedigree), we investigated the prediction accuracy (PA) of Genomic best linear unbiased prediction (GBLUP) and analyzed contributions from pedigree relationships captured by SNP markers, as well as from cosegregation and ancestral LD between QTL and SNPs. The effects of training set size [Formula: see text] and marker density were also studied. Sampling few parents ([Formula: see text]) generates substantial sample LD that carries over into synthetics through cosegregation of alleles at linked loci. For fixed [Formula: see text], [Formula: see text] influences PA most strongly. If the training and prediction set are related, using [Formula: see text] parents yields high PA regardless of ancestral LD because SNPs capture pedigree relationships and Mendelian sampling through cosegregation. As [Formula: see text] increases, ancestral LD contributes more information, while other factors contribute less due to lower frequencies of closely related individuals. For unrelated prediction sets, only ancestral LD contributes information and accuracies were poor and highly variable for [Formula: see text] due to large sample LD. For large [Formula: see text], achieving moderate accuracy requires

  18. A platform for rapid prototyping of synthetic gene networks in mammalian cells

    Science.gov (United States)

    Duportet, Xavier; Wroblewska, Liliana; Guye, Patrick; Li, Yinqing; Eyquem, Justin; Rieders, Julianne; Rimchala, Tharathorn; Batt, Gregory; Weiss, Ron

    2014-01-01

    Mammalian synthetic biology may provide novel therapeutic strategies, help decipher new paths for drug discovery and facilitate synthesis of valuable molecules. Yet, our capacity to genetically program cells is currently hampered by the lack of efficient approaches to streamline the design, construction and screening of synthetic gene networks. To address this problem, here we present a framework for modular and combinatorial assembly of functional (multi)gene expression vectors and their efficient and specific targeted integration into a well-defined chromosomal context in mammalian cells. We demonstrate the potential of this framework by assembling and integrating different functional mammalian regulatory networks including the largest gene circuit built and chromosomally integrated to date (6 transcription units, 27kb) encoding an inducible memory device. Using a library of 18 different circuits as a proof of concept, we also demonstrate that our method enables one-pot/single-flask chromosomal integration and screening of circuit libraries. This rapid and powerful prototyping platform is well suited for comparative studies of genetic regulatory elements, genes and multi-gene circuits as well as facile development of libraries of isogenic engineered cell lines. PMID:25378321

  19. Decomposing Additive Genetic Variance Revealed Novel Insights into Trait Evolution in Synthetic Hexaploid Wheat

    Directory of Open Access Journals (Sweden)

    Abdulqader Jighly

    2018-02-01

    Full Text Available Whole genome duplication (WGD is an evolutionary phenomenon, which causes significant changes to genomic structure and trait architecture. In recent years, a number of studies decomposed the additive genetic variance explained by different sets of variants. However, they investigated diploid populations only and none of the studies examined any polyploid organism. In this research, we extended the application of this approach to polyploids, to differentiate the additive variance explained by the three subgenomes and seven sets of homoeologous chromosomes in synthetic allohexaploid wheat (SHW to gain a better understanding of trait evolution after WGD. Our SHW population was generated by crossing improved durum parents (Triticum turgidum; 2n = 4x = 28, AABB subgenomes with the progenitor species Aegilops tauschii (syn Ae. squarrosa, T. tauschii; 2n = 2x = 14, DD subgenome. The population was phenotyped for 10 fungal/nematode resistance traits as well as two abiotic stresses. We showed that the wild D subgenome dominated the additive effect and this dominance affected the A more than the B subgenome. We provide evidence that this dominance was not inflated by population structure, relatedness among individuals or by longer linkage disequilibrium blocks observed in the D subgenome within the population used for this study. The cumulative size of the three homoeologs of the seven chromosomal groups showed a weak but significant positive correlation with their cumulative explained additive variance. Furthermore, an average of 69% for each chromosomal group's cumulative additive variance came from one homoeolog that had the highest explained variance within the group across all 12 traits. We hypothesize that structural and functional changes during diploidization may explain chromosomal group relations as allopolyploids keep balanced dosage for many genes. Our results contribute to a better understanding of trait evolution mechanisms in polyploidy

  20. Parametric Study of Synthetic-Jet-Based Flow Control on a Vertical Tail Model

    Science.gov (United States)

    Monastero, Marianne; Lindstrom, Annika; Beyar, Michael; Amitay, Michael

    2015-11-01

    Separation control over the rudder of the vertical tail of a commercial airplane using synthetic-jet-based flow control can lead to a reduction in tail size, with an associated decrease in drag and increase in fuel savings. A parametric, experimental study was undertaken using an array of finite span synthetic jets to investigate the sensitivity of the enhanced vertical tail side force to jet parameters, such as jet spanwise spacing and jet momentum coefficient. A generic wind tunnel model was designed and fabricated to fundamentally study the effects of the jet parameters at varying rudder deflection and model sideslip angles. Wind tunnel results obtained from pressure measurements and tuft flow visualization in the Rensselaer Polytechnic Subsonic Wind Tunnel show a decrease in separation severity and increase in model performance in comparison to the baseline, non-actuated case. The sensitivity to various parameters will be presented.

  1. A synthetic system links FeFe-hydrogenases to essential E. coli sulfur metabolism

    Directory of Open Access Journals (Sweden)

    Grandl Gerald

    2011-05-01

    Full Text Available Abstract Background FeFe-hydrogenases are the most active class of H2-producing enzymes known in nature and may have important applications in clean H2 energy production. Many potential uses are currently complicated by a crucial weakness: the active sites of all known FeFe-hydrogenases are irreversibly inactivated by O2. Results We have developed a synthetic metabolic pathway in E. coli that links FeFe-hydrogenase activity to the production of the essential amino acid cysteine. Our design includes a complementary host strain whose endogenous redox pool is insulated from the synthetic metabolic pathway. Host viability on a selective medium requires hydrogenase expression, and moderate O2 levels eliminate growth. This pathway forms the basis for a genetic selection for O2 tolerance. Genetically selected hydrogenases did not show improved stability in O2 and in many cases had lost H2 production activity. The isolated mutations cluster significantly on charged surface residues, suggesting the evolution of binding surfaces that may accelerate hydrogenase electron transfer. Conclusions Rational design can optimize a fully heterologous three-component pathway to provide an essential metabolic flux while remaining insulated from the endogenous redox pool. We have developed a number of convenient in vivo assays to aid in the engineering of synthetic H2 metabolism. Our results also indicate a H2-independent redox activity in three different FeFe-hydrogenases, with implications for the future directed evolution of H2-activating catalysts.

  2. The need for additional genetic markers for MDS stratification: what does the future hold for prognostication?

    Science.gov (United States)

    Otrock, Zaher K.; Tiu, Ramon V.; Maciejewski, Jaroslaw P.; Sekeres, Mikkael A.

    2013-01-01

    Myelodysplastic syndromes (MDS) constitute a heterogeneous group of clonal hematopoietic disorders. Metaphase cytogenetics (MC) has been the gold standard for genetic testing in MDS, but it can detect clonal cytogenetic abnormalities in only 50% of cases. New karyotyping tests include fluorescence in situ hybridization (FISH), array-based comparative genomic hybridization (aCGH), and single nucleotide polymorphism arrays (SNP-A). These techniques have increased the detected genetic abnormalities in MDS, many of which confer prognostic significance to overall and leukemia-free survival. This has eventually increased our understanding of MDS genetics. With the help of new technologies, we anticipate that the existing prognostic scoring systems will incorporate mutational data into their parameters. This review discusses the progress in MDS diagnosis through the use of array-based technologies. We also discuss the recently investigated genetic mutation in MDS, and revisit the MDS classification and prognostic scoring systems. PMID:23373781

  3. CRISPR/Cas9 gene drives in genetically variable and nonrandomly mating wild populations.

    Science.gov (United States)

    Drury, Douglas W; Dapper, Amy L; Siniard, Dylan J; Zentner, Gabriel E; Wade, Michael J

    2017-05-01

    Synthetic gene drives based on CRISPR/Cas9 have the potential to control, alter, or suppress populations of crop pests and disease vectors, but it is unclear how they will function in wild populations. Using genetic data from four populations of the flour beetle Tribolium castaneum , we show that most populations harbor genetic variants in Cas9 target sites, some of which would render them immune to drive (ITD). We show that even a rare ITD allele can reduce or eliminate the efficacy of a CRISPR/Cas9-based synthetic gene drive. This effect is equivalent to and accentuated by mild inbreeding, which is a characteristic of many disease-vectoring arthropods. We conclude that designing such drives will require characterization of genetic variability and the mating system within and among targeted populations.

  4. Heat and mass transfer caused by a laminar channel flow equipped with a synthetic jet array

    Czech Academy of Sciences Publication Activity Database

    Trávníček, Zdeněk; Dančová, Petra; Kordík, Jozef; Vít, Tomáš; Pavelka, Miroslav

    2011-01-01

    Roč. 2, č. 4 (2011), 041006-041006 ISSN 1948-5085 R&D Projects: GA AV ČR(CZ) IAA200760801; GA ČR(CZ) GA101/09/1959 Institutional research plan: CEZ:AV0Z20760514 Keywords : synthetic jet * flow control * naphthalene sublimation Subject RIV: BK - Fluid Dynamics http://scitation.aip.org/getabs/servlet/GetabsServlet?prog=normal&id=JTSEBV000002000004041006000001&idtype=cvips&gifs=yes

  5. Parametric analyses for synthetic jet control on separation and stall over rotor airfoil

    Directory of Open Access Journals (Sweden)

    Zhao Guoqing

    2014-10-01

    Full Text Available Numerical simulations are performed to investigate the effects of synthetic jet control on separation and stall over rotor airfoils. The preconditioned and unsteady Reynolds-averaged Navier–Stokes equations coupled with a k − ω shear stream transport turbulence model are employed to accomplish the flowfield simulation of rotor airfoils under jet control. Additionally, a velocity boundary condition modeled by a sinusoidal function is developed to fulfill the perturbation effect of periodic jets. The validity of the present CFD procedure is evaluated by the simulated results of an isolated synthetic jet and the jet control case for airfoil NACA0015. Then, parametric analyses are conducted specifically for an OA213 rotor airfoil to investigate the effects of jet parameters (forcing frequency, jet location and momentum coefficient, jet direction, and distribution of jet arrays on the control effect of the aerodynamic characteristics of a rotor airfoil. Preliminary results indicate that the efficiency of jet control can be improved with specific frequencies (the best lift-drag ratio at F+ = 2.0 and jet angles (40° or 75° when the jets are located near the separation point of the rotor airfoil. Furthermore, as a result of a suitable combination of jet arrays, the lift coefficient of the airfoil can be improved by nearly 100%, and the corresponding drag coefficient decreased by 26.5% in comparison with the single point control case.

  6. An Extended Two-Phase Method for Accessing Sections of Out-of-Core Arrays

    Directory of Open Access Journals (Sweden)

    Rajeev Thakur

    1996-01-01

    Full Text Available A number of applications on parallel computers deal with very large data sets that cannot fit in main memory. In such applications, data must be stored in files on disks and fetched into memory during program execution. Parallel programs with large out-of-core arrays stored in files must read/write smaller sections of the arrays from/to files. In this article, we describe a method for accessing sections of out-of-core arrays efficiently. Our method, the extended two-phase method, uses collective l/O: Processors cooperate to combine several l/O requests into fewer larger granularity requests, to reorder requests so that the file is accessed in proper sequence, and to eliminate simultaneous l/O requests for the same data. In addition, the l/O workload is divided among processors dynamically, depending on the access requests. We present performance results obtained from two real out-of-core parallel applications – matrix multiplication and a Laplace's equation solver – and several synthetic access patterns, all on the Intel Touchstone Delta. These results indicate that the extended two-phase method significantly outperformed a direct (noncollective method for accessing out-of-core array sections.

  7. Improving the Image Quality of Synthetic Transmit Aperture Ultrasound Images - Achieving Real-Time In-Vivo Imaging

    DEFF Research Database (Denmark)

    Gammelmark, Kim

    in-vivo experiments, showed, that TMS imaging can increase the SNR by as much as 17 dB compared to the traditional imaging techniques, which improves the in-vivo image quality to a highly competitive level. An in-vivo evaluation of convex array TMS imaging for abdominal imaging applications......-vivo imaging, and that the obtained image quality is highly competitive with the techniques applied in current medical ultrasound scanners. Hereby, the goals of the PhD have been successfully achieved.......Synthetic transmit aperture (STA) imaging has the potential to increase the image quality of medical ultrasound images beyond the levels obtained by conventional imaging techniques (linear, phased, and convex array imaging). Currently, however, in-vivo applications of STA imaging is limited...

  8. Freedom and Responsibility in Synthetic Genomics: The Synthetic Yeast Project

    OpenAIRE

    Sliva, Anna; Yang, Huanming; Boeke, Jef D.; Mathews, Debra J. H.

    2015-01-01

    First introduced in 2011, the Synthetic Yeast Genome (Sc2.0) Project is a large international synthetic genomics project that will culminate in the first eukaryotic cell (Saccharomyces cerevisiae) with a fully synthetic genome. With collaborators from across the globe and from a range of institutions spanning from do-it-yourself biology (DIYbio) to commercial enterprises, it is important that all scientists working on this project are cognizant of the ethical and policy issues associated with...

  9. Accurate 3D reconstruction of bony surfaces using ultrasonic synthetic aperture techniques for robotic knee arthroplasty.

    Science.gov (United States)

    Kerr, William; Rowe, Philip; Pierce, Stephen Gareth

    2017-06-01

    Robotically guided knee arthroplasty systems generally require an individualized, preoperative 3D model of the knee joint. This is typically measured using Computed Tomography (CT) which provides the required accuracy for preoperative surgical intervention planning. Ultrasound imaging presents an attractive alternative to CT, allowing for reductions in cost and the elimination of doses of ionizing radiation, whilst maintaining the accuracy of the 3D model reconstruction of the joint. Traditional phased array ultrasound imaging methods, however, are susceptible to poor resolution and signal to noise ratios (SNR). Alleviating these weaknesses by offering superior focusing power, synthetic aperture methods have been investigated extensively within ultrasonic non-destructive testing. Despite this, they have yet to be fully exploited in medical imaging. In this paper, the ability of a robotic deployed ultrasound imaging system based on synthetic aperture methods to accurately reconstruct bony surfaces is investigated. Employing the Total Focussing Method (TFM) and the Synthetic Aperture Focussing Technique (SAFT), two samples were imaged which were representative of the bones of the knee joint: a human-shaped, composite distal femur and a bovine distal femur. Data were captured using a 5MHz, 128 element 1D phased array, which was manipulated around the samples using a robotic positioning system. Three dimensional surface reconstructions were then produced and compared with reference models measured using a precision laser scanner. Mean errors of 0.82mm and 0.88mm were obtained for the composite and bovine samples, respectively, thus demonstrating the feasibility of the approach to deliver the sub-millimetre accuracy required for the application. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  10. Characterization of Thermal Stability of Synthetic and Semi-Synthetic Engine Oils

    Directory of Open Access Journals (Sweden)

    Anand Kumar Tripathi

    2015-03-01

    Full Text Available Engine oils undergo oxidative degradation and wears out during service. Hence it is important to characterize ageing of engine oils at different simulated conditions to evaluate the performance of existing oils and also design new formulations. This work focuses on characterizing the thermo-oxidative degradation of synthetic and semi-synthetic engine oils aged at 120, 149 and 200 °C. Apparent activation energy of decomposition of aged oils evaluated using the isoconversional Kissinger-Akahira-Sunose technique was used as a thermal stability marker. The temporal variation of stability at different ageing temperatures was corroborated with kinematic viscosity, oxidation, sulfation and nitration indices, total base number, antiwear additive content and molecular structure of the organic species present in the oils. At the lowest temperature employed, synthetic oil underwent higher rate of oxidation, while semi-synthetic oil was stable for longer time periods. At higher temperatures, the initial rate of change of average apparent activation energy of synthetic oil correlated well with a similar variation in oxidation number. A mixture of long chain linear, branched, and cyclic hydrocarbons were observed when semi-synthetic oil was degraded at higher temperatures.

  11. Element sharing in interleaved antenna arrays

    CSIR Research Space (South Africa)

    Du Plessis, WP

    2012-03-01

    Full Text Available , there is a large variation in the results for a small number of shared elements which reduces as the number of times the GA is run increases. Taken together, these points suggest that the GA implemented here does not provide consistently good results when... levels in linear arrays,? IEEE Antennas Wirel. Propag. Lett., vol. 9, pp. 771?774, 2010. [11] D. E. Goldberg, Genetic algorithms in search, optimization, and machine learning. Addison-Wesley, 1989. [12] T. Blickle and L. Thiele, ?A comparison...

  12. Delay-independent stability of genetic regulatory networks.

    Science.gov (United States)

    Wu, Fang-Xiang

    2011-11-01

    Genetic regulatory networks can be described by nonlinear differential equations with time delays. In this paper, we study both locally and globally delay-independent stability of genetic regulatory networks, taking messenger ribonucleic acid alternative splicing into consideration. Based on nonnegative matrix theory, we first develop necessary and sufficient conditions for locally delay-independent stability of genetic regulatory networks with multiple time delays. Compared to the previous results, these conditions are easy to verify. Then we develop sufficient conditions for global delay-independent stability for genetic regulatory networks. Compared to the previous results, this sufficient condition is less conservative. To illustrate theorems developed in this paper, we analyze delay-independent stability of two genetic regulatory networks: a real-life repressilatory network with three genes and three proteins, and a synthetic gene regulatory network with five genes and seven proteins. The simulation results show that the theorems developed in this paper can effectively determine the delay-independent stability of genetic regulatory networks.

  13. TARSyn: Tunable Antibiotic Resistance Devices Enabling Bacterial Synthetic Evolution and Protein Production

    DEFF Research Database (Denmark)

    Rennig, Maja; Martinez, Virginia; Mirzadeh, Kiavash

    2018-01-01

    Evolution can be harnessed to optimize synthetic biology designs. A prominent example is recombinant protein production-a dominating theme in biotechnology for more than three decades. Typically, a protein coding sequence (cds) is recombined with genetic elements, such as promoters, ribosome...... and allows expression levels in large clone libraries to be probed using a simple cell survival assay on the respective antibiotic. The power of the approach is demonstrated by substantially increasing production of two commercially interesting proteins, a Nanobody and an Affibody. The method is a simple......-level expression-an example of synthetic evolution. However, manual screening limits the ability to assay expression levels of all putative sequences in the libraries. Here we have solved this bottleneck by designing a collection of translational coupling devices based on a RNA secondary structure. Exchange...

  14. Recovery and evolutionary analysis of complete integron gene cassette arrays from Vibrio

    Directory of Open Access Journals (Sweden)

    Gillings Michael R

    2006-01-01

    Full Text Available Abstract Background Integrons are genetic elements capable of the acquisition, rearrangement and expression of genes contained in gene cassettes. Gene cassettes generally consist of a promoterless gene associated with a recombination site known as a 59-base element (59-be. Multiple insertion events can lead to the assembly of large integron-associated cassette arrays. The most striking examples are found in Vibrio, where such cassette arrays are widespread and can range from 30 kb to 150 kb. Besides those found in completely sequenced genomes, no such array has yet been recovered in its entirety. We describe an approach to systematically isolate, sequence and annotate large integron gene cassette arrays from bacterial strains. Results The complete Vibrio sp. DAT722 integron cassette array was determined through the streamlined approach described here. To place it in an evolutionary context, we compare the DAT722 array to known vibrio arrays and performed phylogenetic analyses for all of its components (integrase, 59-be sites, gene cassette encoded genes. It differs extensively in terms of genomic context as well as gene cassette content and organization. The phylogenetic tree of the 59-be sites collectively found in the Vibrio gene cassette pool suggests frequent transfer of cassettes within and between Vibrio species, with slower transfer rates between more phylogenetically distant relatives. We also identify multiple cases where non-integron chromosomal genes seem to have been assembled into gene cassettes and others where cassettes have been inserted into chromosomal locations outside integrons. Conclusion Our systematic approach greatly facilitates the isolation and annotation of large integrons gene cassette arrays. Comparative analysis of the Vibrio sp. DAT722 integron obtained through this approach to those found in other vibrios confirms the role of this genetic element in promoting lateral gene transfer and suggests a high rate of gene

  15. Improvements in the UT Inspection of vessel nozzles. Array application

    International Nuclear Information System (INIS)

    Tanarro, A.; Garcia, A.; Izquierdo, J.

    1998-01-01

    Automatic ultrasonic inspection of certain components in nuclear power plants, together with problems related to access of same, result in other difficulties due to the complexity of their geometry and the apparent orientation of possible defects. Array technology, recently developed on the basis of the theoretical principals of phased array technique, has meant that it is now possible to advance in the characterisation, localisation, and sizing of the defects in these components. This has been possible thanks to the discovery of synthetic materials which have allowed us to design and manufacture a new group of ultrasonic transducers. To these we may add new developments in electronics and computer sciences which have facilitated the building of high-powered control systems. This report discusses the work carried out by Tecnatom and Iberdrola in the field of automatic ultrasonic inspection of the vessel nozzles by means of array technology in the BWR at the Cofrentes Nuclear Power Station. The aims of this work were: - To facilitate the detection, characterisation, sizing and positioning of defects - To simplify and improve ultrasonic inspection in order to reduce acquisition times and the cost of same In order to achieve these results the following items were developed: - New array transducers were designed and manufactured - A new data acquisition system was developed - New programs for analysing data and for simulating ultrasonic testing was developed - The results have been validated in mock up. (Author)

  16. Passive synthetic aperture sonar techniques in combination with tow ship noise canceling: application to a triplet towed array

    NARCIS (Netherlands)

    Colin, M.E.G.D.; Groen, J.

    2002-01-01

    An important issue in research on passive ASW operations is improvement in signal-to-noise ratio (SNR) and bearing resolution for targets emitting low frequency signals. One of the techniques believed to improve these characteristics is Synthetic Aperture Sonar (SAS). The method is based on the

  17. Manipulation of Turbulent Boundary Layers Using Synthetic Jets

    Science.gov (United States)

    Berger, Zachary; Gomit, Guillaume; Lavoie, Philippe; Ganapathisubramani, Bharath

    2015-11-01

    This work focuses on the application of active flow control, in the form of synthetic jet actuators, of turbulent boundary layers. An array of 2 synthetic jets are oriented in the spanwise direction and located approximately 2.7 meters downstream from the leading edge of a flat plate. Actuation is applied perpendicular to the surface of the flat plate with varying blowing ratios and reduced frequencies (open-loop). Two-component large window particle image velocimetry (PIV) was performed at the University of Southampton, in the streamwise-wall-normal plane. Complementary stereo PIV measurements were performed at the University of Toronto Institute for Aerospace Studies (UTIAS), in the spanwise-wall-normal plane. The freestream Reynolds number is 3x104, based on the boundary layer thickness. The skin friction Reynolds number is 1,200 based on the skin friction velocity. The experiments at Southampton allow for the observation of the control effects as the flow propagates downstream. The experiments at UTIAS allow for the observation of the streamwise vorticity induced from the actuation. Overall the two experiments provide a 3D representation of the flow field with respect to actuation effects. The current work focuses on the comparison of the two experiments, as well as the effects of varying blowing ratios and reduced frequencies on the turbulent boundary layer. Funded Supported by Airbus.

  18. Synthetic biology to access and expand nature’s chemical diversity

    Science.gov (United States)

    Smanski, Michael J.; Zhou, Hui; Claesen, Jan; Shen, Ben; Fischbach, Michael; Voigt, Christopher A.

    2016-01-01

    Bacterial genomes encode the biosynthetic potential to produce hundreds of thousands of complex molecules with diverse applications, from medicine to agriculture and materials. Economically accessing the potential encoded within sequenced genomes promises to reinvigorate waning drug discovery pipelines and provide novel routes to intricate chemicals. This is a tremendous undertaking, as the pathways often comprise dozens of genes spanning as much as 100+ kiliobases of DNA, are controlled by complex regulatory networks, and the most interesting molecules are made by non-model organisms. Advances in synthetic biology address these issues, including DNA construction technologies, genetic parts for precision expression control, synthetic regulatory circuits, computer aided design, and multiplexed genome engineering. Collectively, these technologies are moving towards an era when chemicals can be accessed en mass based on sequence information alone. This will enable the harnessing of metagenomic data and massive strain banks for high-throughput molecular discovery and, ultimately, the ability to forward design pathways to complex chemicals not found in nature. PMID:26876034

  19. 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.

  20. Preimplantation genetic diagnosis associated to Duchenne muscular dystrophy.

    Science.gov (United States)

    Bianco, Bianca; Christofolini, Denise Maria; Conceição, Gabriel Seixas; Barbosa, Caio Parente

    2017-01-01

    Duchenne muscular dystrophy is the most common muscle disease found in male children. Currently, there is no effective therapy available for Duchenne muscular dystrophy patients. Therefore, it is essential to make a prenatal diagnosis and provide genetic counseling to reduce the birth of such boys. We report a case of preimplantation genetic diagnosis associated with Duchenne muscular dystrophy. The couple E.P.R., 38-year-old, symptomatic patient heterozygous for a 2 to 47 exon deletion mutation in DMD gene and G.T.S., 39-year-old, sought genetic counseling about preimplantation genetic diagnosis process. They have had a 6-year-old son who died due to Duchenne muscular dystrophy complications. The couple underwent four cycles of intracytoplasmic sperm injection (ICSI) and eight embryos biopsies were analyzed by polymerase chain reaction (PCR) for specific mutation analysis, followed by microarray-based comparative genomic hybridisation (array CGH) for aneuploidy analysis. Preimplantation genetic diagnosis revealed that two embryos had inherited the maternal DMD gene mutation, one embryo had a chromosomal alteration and five embryos were normal. One blastocyst was transferred and resulted in successful pregnancy. The other embryos remain vitrified. We concluded that embryo analysis using associated techniques of PCR and array CGH seems to be safe for embryo selection in cases of X-linked disorders, such as Duchenne muscular dystrophy.

  1. DNA suspension arrays: silencing discrete artifacts for high-sensitivity applications.

    Directory of Open Access Journals (Sweden)

    Matthew S Lalonde

    2010-11-01

    Full Text Available Detection of low frequency single nucleotide polymorphisms (SNPs has important implications in early screening for tumorgenesis, genetic disorders and pathogen drug resistance. Nucleic acid arrays are a powerful tool for genome-scale SNP analysis, but detection of low-frequency SNPs in a mixed population on an array is problematic. We demonstrate a model assay for HIV-1 drug resistance mutations, wherein ligase discrimination products are collected on a suspension array. In developing this system, we discovered that signal from multiple polymorphisms was obscured by two discrete hybridization artifacts. Specifically: 1 tethering of unligated probes on the template DNA elicited false signal and 2 unpredictable probe secondary structures impaired probe capture and suppressed legitimate signal from the array. Two sets of oligonucleotides were used to disrupt these structures; one to displace unligated reporter labels from the bead-bound species and another to occupy sequences which interfered with array hybridization. This artifact silencing system resulted in a mean 21-fold increased sensitivity for 29 minority variants of 17 codons in our model assay for mutations most commonly associated with HIV-1 drug resistance. Furthermore, since the artifacts we characterized are not unique to our system, their specific inhibition might improve the quality of data from solid-state microarrays as well as from the growing number of multiple analyte suspension arrays relying on sequence-specific nucleic acid target capture.

  2. A Porous Perchlorate-Doped Polypyrrole Nanocoating on Nickel Nanotube Arrays for Stable Wide-Potential-Window Supercapacitors.

    Science.gov (United States)

    Chen, Gao-Feng; Li, Xian-Xia; Zhang, Li-Yi; Li, Nan; Ma, Tian Yi; Liu, Zhao-Qing

    2016-09-01

    A bottom-up synthetic strategy is developed to fabricate a highly porous wave-superposed perchlorate-doped polypyrrole nanocoating on nickel nanotube arrays. The delicate nanostructure and the unique surface chemistry synergistically endow the obtained electrode with revealable pseudocapacitance, large operating potential window, and excellent cycling stability, which are highly promising for both asymmetric and symmetric supercapacitors. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Synthetic genome engineering forging new frontiers for wine yeast.

    Science.gov (United States)

    Pretorius, Isak S

    2017-02-01

    Over the past 15 years, the seismic shifts caused by the convergence of biomolecular, chemical, physical, mathematical, and computational sciences alongside cutting-edge developments in information technology and engineering have erupted into a new field of scientific endeavor dubbed Synthetic Biology. Recent rapid advances in high-throughput DNA sequencing and DNA synthesis techniques are enabling the design and construction of new biological parts (genes), devices (gene networks) and modules (biosynthetic pathways), and the redesign of biological systems (cells and organisms) for useful purposes. In 2014, the budding yeast Saccharomyces cerevisiae became the first eukaryotic cell to be equipped with a fully functional synthetic chromosome. This was achieved following the synthesis of the first viral (poliovirus in 2002 and bacteriophage Phi-X174 in 2003) and bacterial (Mycoplasma genitalium in 2008 and Mycoplasma mycoides in 2010) genomes, and less than two decades after revealing the full genome sequence of a laboratory (S288c in 1996) and wine (AWRI1631 in 2008) yeast strain. A large international project - the Synthetic Yeast Genome (Sc2.0) Project - is now underway to synthesize all 16 chromosomes (∼12 Mb carrying ∼6000 genes) of the sequenced S288c laboratory strain by 2018. If successful, S. cerevisiae will become the first eukaryote to cross the horizon of in silico design of complex cells through de novo synthesis, reshuffling, and editing of genomes. In the meantime, yeasts are being used as cell factories for the semi-synthetic production of high-value compounds, such as the potent antimalarial artemisinin, and food ingredients, such as resveratrol, vanillin, stevia, nootkatone, and saffron. As a continuum of previously genetically engineered industrially important yeast strains, precision genome engineering is bound to also impact the study and development of wine yeast strains supercharged with synthetic DNA. The first taste of what the future

  4. Locating non-volcanic tremor along the San Andreas Fault using a multiple array source imaging technique

    Science.gov (United States)

    Ryberg, T.; Haberland, C.H.; Fuis, G.S.; Ellsworth, W.L.; Shelly, D.R.

    2010-01-01

    Non-volcanic tremor (NVT) has been observed at several subduction zones and at the San Andreas Fault (SAF). Tremor locations are commonly derived by cross-correlating envelope-transformed seismic traces in combination with source-scanning techniques. Recently, they have also been located by using relative relocations with master events, that is low-frequency earthquakes that are part of the tremor; locations are derived by conventional traveltime-based methods. Here we present a method to locate the sources of NVT using an imaging approach for multiple array data. The performance of the method is checked with synthetic tests and the relocation of earthquakes. We also applied the method to tremor occurring near Cholame, California. A set of small-aperture arrays (i.e. an array consisting of arrays) installed around Cholame provided the data set for this study. We observed several tremor episodes and located tremor sources in the vicinity of SAF. During individual tremor episodes, we observed a systematic change of source location, indicating rapid migration of the tremor source along SAF. ?? 2010 The Authors Geophysical Journal International ?? 2010 RAS.

  5. Revision of an automated microseismic location algorithm for DAS - 3C geophone hybrid array

    Science.gov (United States)

    Mizuno, T.; LeCalvez, J.; Raymer, D.

    2017-12-01

    Application of distributed acoustic sensing (DAS) has been studied in several areas in seismology. One of the areas is microseismic reservoir monitoring (e.g., Molteni et al., 2017, First Break). Considering the present limitations of DAS, which include relatively low signal-to-noise ratio (SNR) and no 3C polarization measurements, a DAS - 3C geophone hybrid array is a practical option when using a single monitoring well. Considering the large volume of data from distributed sensing, microseismic event detection and location using a source scanning type algorithm is a reasonable choice, especially for real-time monitoring. The algorithm must handle both strain rate along the borehole axis for DAS and particle velocity for 3C geophones. Only a small quantity of large SNR events will be detected throughout a large aperture encompassing the hybrid array; therefore, the aperture is to be optimized dynamically to eliminate noisy channels for a majority of events. For such hybrid array, coalescence microseismic mapping (CMM) (Drew et al., 2005, SPE) was revised. CMM forms a likelihood function of location of event and its origin time. At each receiver, a time function of event arrival likelihood is inferred using an SNR function, and it is migrated to time and space to determine hypocenter and origin time likelihood. This algorithm was revised to dynamically optimize such a hybrid array by identifying receivers where a microseismic signal is possibly detected and using only those receivers to compute the likelihood function. Currently, peak SNR is used to select receivers. To prevent false results due to small aperture, a minimum aperture threshold is employed. The algorithm refines location likelihood using 3C geophone polarization. We tested this algorithm using a ray-based synthetic dataset. Leaney (2014, PhD thesis, UBC) is used to compute particle velocity at receivers. Strain rate along the borehole axis is computed from particle velocity as DAS microseismic

  6. Genetically transformed tobacco plants expressing synthetic EPSPS gene confer tolerance against glyphosate herbicide.

    Science.gov (United States)

    Imran, Muhammad; Asad, Shaheen; Barboza, Andre Luiz; Galeano, Esteban; Carrer, Helaine; Mukhtar, Zahid

    2017-04-01

    Glyphosate quashes the synthesis of 5-enolpyruvylshikimate-3- phosphate synthase (EPSPS) enzyme which intercedes the functioning of shikimate pathway for the production of aromatic amino acids. Herbicide resistant crops are developed using glyphosate insensitive EPSPS gene isolated from Agrobacterium sp. strain CP4, which give farmers a sustainable weed control option. Intentions behind this study were to design and characterize the synthetic herbicide resistant CP4 - EPSPS gene in a model plant system and check the effectiveness of transformed tobacco against application of glyphosate. Putative transgenic plants were obtained from independent transformation events, and stable plant transformation, transgene expression and integration were demonstrated respectively by PCR, qRT-PCR and Southern hybridization. Gene transcript level and gene copy number (1-4) varied among the tested transgenic tobacco lines. Herbicide assays showed that transgenic plants were resistant to glyphosate after 12 days of spraying with glyphosate, and EPSPS activity remained at sufficient level to withstand the spray at 1000 ppm of the chemical. T 1 plants analyzed through immunoblot strips and PCR showed that the gene was being translated into protein and transmitted to the next generation successfully. This codon optimized synthetic CP4 - EPSPS gene is functionally equivalent to the gene for glyphosate resistance available in the commercial crops and hence we recommend this gene for transformation into commercial crops.

  7. Evaluation of Bovine High-Density SNP Genotyping Array in Indigenous Dairy Cattle Breeds.

    Science.gov (United States)

    Dash, S; Singh, A; Bhatia, A K; Jayakumar, S; Sharma, A; Singh, S; Ganguly, I; Dixit, S P

    2018-04-03

    In total 52 samples of Sahiwal ( 19 ), Tharparkar ( 17 ), and Gir ( 16 ) were genotyped by using BovineHD SNP chip to analyze minor allele frequency (MAF), genetic diversity, and linkage disequilibrium among these cattle. The common SNPs of BovineHD and 54K SNP Chips were also extracted and evaluated for their performance. Only 40%-50% SNPs of these arrays was found informative for genetic analysis in these cattle breeds. The overall mean of MAF for SNPs of BovineHD SNPChip was 0.248 ± 0.006, 0.241 ± 0.007, and 0.242 ± 0.009 in Sahiwal, Tharparkar and Gir, respectively, while that for 54K SNPs was on lower side. The average Reynold's genetic distance between breeds ranged from 0.042 to 0.055 based on BovineHD Beadchip, and from 0.052 to 0.084 based on 54K SNP Chip. The estimates of genetic diversity based on HD and 54K chips were almost same and, hence, low density chip seems to be good enough to decipher genetic diversity of these cattle breeds. The linkage disequilibrium started decaying (r 2  < 0.2) at 140 kb inter-marker distance and, hence, a 20K low density customized SNP array from HD chip could be designed for genomic selection in these cattle else the 54K Bead Chip as such will be useful.

  8. Transferrin-derived synthetic peptide induces highly conserved pro-inflammatory responses of macrophages.

    Science.gov (United States)

    Haddad, George; Belosevic, Miodrag

    2009-02-01

    We examined the induction of macrophage pro-inflammatory responses by transferrin-derived synthetic peptide originally identified following digestion of transferrin from different species (murine, bovine, human N-lobe and goldfish) using elastase. The mass spectrometry analysis of elastase-digested murine transferrin identified a 31 amino acid peptide located in the N2 sub-domain of the transferrin N-lobe, that we named TMAP. TMAP was synthetically produced and shown to induce a number of pro-inflammatory genes by quantitative PCR. TMAP induced chemotaxis, a potent nitric oxide response, and TNF-alpha secretion in different macrophage populations; P338D1 macrophage-like cells, mouse peritoneal macrophages, mouse bone marrow-derived macrophages (BMDM) and goldfish macrophages. The treatment of BMDM cultures with TMAP stimulated the production of nine cytokines and chemokines (IL-6, MCP-5, MIP-1 alpha, MIP-1 gamma, MIP-2, GCSF, KC, VEGF, and RANTES) that was measured using cytokine antibody array and confirmed by Western blot. Our results indicate that transferrin-derived peptide, TMAP, is an immunomodulating molecule capable of inducing pro-inflammatory responses in lower and higher vertebrates.

  9. Spatially Defined Oligonucleotide Arrays. Technical Report for Phase II; FINAL

    International Nuclear Information System (INIS)

    None

    2000-01-01

    The goal of the Human Genome Project is to sequence all 3 billion base pairs of the human genome. Progress in this has been rapid; GenBank(reg s ign) finished 1994 with 286 million bases of sequence and grew by 2470 in the first quarter of 1995. The challenge to the scientific community is to understand the biological relevance of this genetic information. In most cases the sequence being generated for any single region of the genome represents the genotype of a single individual. A complete understanding of the function of specific genes and other regions of the genome and their role in human disease and development will only become apparent when the sequence of many more individuals is known. Access to genetic information is ultimately limited by the ability to screen DNA sequence. Although the pioneering sequencing methods of Sanger et al. (15) and Maxam and Gilbert (11) have become standard in virtually all molecular biology laboratories, the basic protocols remain largely unchanged. The throughput of this sequencing technology is now becoming the rate-limiting step in both large-scale sequencing projects such as the Human Genome Project and the subsequent efforts to understand genetic diversity. This has inspired the development of advanced DNA sequencing technologies (9), Incremental improvements to Sanger sequencing have been made in DNA labeling and detection. High-speed electrophoresis methods using ultrathin gels or capillary arrays are now being more widely employed. However, these methods are throughput-limited by their sequential nature and the speed and resolution of separations. This limitation will become more pronounced as the need to rapidly screen newly discovered genes for biologically relevant polymorphisms increases. An alternative to gel-based sequencing is to use high-density oligonucleotide probe arrays. Oligonucleotide probe arrays display specific oligonucleotide probes at precise locations in a high density, information-rich format (5

  10. A genetic assessment of the English bulldog

    OpenAIRE

    Pedersen, Niels C.; Pooch, Ashley S.; Liu, Hongwei

    2016-01-01

    Background This study examines genetic diversity among 102 registered English Bulldogs used for breeding based on maternal and paternal haplotypes, allele frequencies in 33 highly polymorphic short tandem repeat (STR) loci on 25 chromosomes, STR-linked dog leukocyte antigen (DLA) class I and II haplotypes, and the number and size of genome-wide runs of homozygosity (ROH) determined from high density SNP arrays. The objective was to assess whether the breed retains enough genetic diversity to ...

  11. 基于超声阵列传感器与遗传MUSIC的局放源波达方向估计%Source DOA Estimation Based on Ultrasonic Array Sensor and Genetic MUSIC

    Institute of Scientific and Technical Information of China (English)

    侯姗姗; 谢庆; 廖峰; 纪巍

    2014-01-01

    基于超声阵列传感器的局放源波达方向估计是局部放电准确定位的基础。传统MUSIC测向算法的精度和搜索成功率较低,据此提出一种基于超声阵列传感器与遗传MUSIC算法的局放源波达方向估计新方法。遗传MUSIC算法利用空间谱估计公式构造适应度函数,基于遗传迭代搜索的思想对方位角进行谱峰搜索,以获得全局最优解。通过建立信号模型、阵列模型开展了大量仿真实验,并采用寻优精度、搜索成功率和搜索时间等三个指标为依据,对经典MUSIC和遗传MUSIC的测向结果进行对比。结果表明,基于遗传MUSIC算法提高了搜索成功率,绝对精度相较传统MUSIC算法误差减小0.3°,可以获得更高精度的局放源波达方向角。%Partial discharge direction of arrival ( DOA) estimation based on ultrasonic array sensor is the basis for ac-curate positioning of the partial discharge. Considering the problem of low precision and searching success rate of tra-ditional MUSIC direction finding algorithm, the paper presents a new method based on ultrasonic array sensor and ge-netic MUSIC algorithm for partial discharge DOA estimation. The genetic MUSIC algorithm constructs fitness function with spatial spectrum estimation, and searches spectral peak of the azimuth based on the idea of genetic iterative searching for global optimal solution. This paper carried out a large number of simulation experiments through the es-tablishment of signal model and array model, then uses three indicators of searching precision, searching success rate and searching time as the basis to compare the direction finding results of classical MUSIC and genetic MUSIC. Re-sults show that compared with traditional MUSIC algorithm, the genetic MUSIC based algorithm improves the searching success rate and reduces the error by 0. 3° in absolute precision, therefore obtains higher accuracy of partial discharge DOA angle.

  12. A 34K SNP genotyping array for Populus trichocarpa: design, application to the study of natural populations and transferability to other Populus species.

    Science.gov (United States)

    Geraldes, A; Difazio, S P; Slavov, G T; Ranjan, P; Muchero, W; Hannemann, J; Gunter, L E; Wymore, A M; Grassa, C J; Farzaneh, N; Porth, I; McKown, A D; Skyba, O; Li, E; Fujita, M; Klápště, J; Martin, J; Schackwitz, W; Pennacchio, C; Rokhsar, D; Friedmann, M C; Wasteneys, G O; Guy, R D; El-Kassaby, Y A; Mansfield, S D; Cronk, Q C B; Ehlting, J; Douglas, C J; Tuskan, G A

    2013-03-01

    Genetic mapping of quantitative traits requires genotypic data for large numbers of markers in many individuals. For such studies, the use of large single nucleotide polymorphism (SNP) genotyping arrays still offers the most cost-effective solution. Herein we report on the design and performance of a SNP genotyping array for Populus trichocarpa (black cottonwood). This genotyping array was designed with SNPs pre-ascertained in 34 wild accessions covering most of the species latitudinal range. We adopted a candidate gene approach to the array design that resulted in the selection of 34 131 SNPs, the majority of which are located in, or within 2 kb of, 3543 candidate genes. A subset of the SNPs on the array (539) was selected based on patterns of variation among the SNP discovery accessions. We show that more than 95% of the loci produce high quality genotypes and that the genotyping error rate for these is likely below 2%. We demonstrate that even among small numbers of samples (n = 10) from local populations over 84% of loci are polymorphic. We also tested the applicability of the array to other species in the genus and found that the number of polymorphic loci decreases rapidly with genetic distance, with the largest numbers detected in other species in section Tacamahaca. Finally, we provide evidence for the utility of the array to address evolutionary questions such as intraspecific studies of genetic differentiation, species assignment and the detection of natural hybrids. © 2013 Blackwell Publishing Ltd.

  13. Genetic programming applied to RFI mitigation in radio astronomy

    Science.gov (United States)

    Staats, K.

    2016-12-01

    Genetic Programming is a type of machine learning that employs a stochastic search of a solutions space, genetic operators, a fitness function, and multiple generations of evolved programs to resolve a user-defined task, such as the classification of data. At the time of this research, the application of machine learning to radio astronomy was relatively new, with a limited number of publications on the subject. Genetic Programming had never been applied, and as such, was a novel approach to this challenging arena. Foundational to this body of research, the application Karoo GP was developed in the programming language Python following the fundamentals of tree-based Genetic Programming described in "A Field Guide to Genetic Programming" by Poli, et al. Karoo GP was tasked with the classification of data points as signal or radio frequency interference (RFI) generated by instruments and machinery which makes challenging astronomers' ability to discern the desired targets. The training data was derived from the output of an observation run of the KAT-7 radio telescope array built by the South African Square Kilometre Array (SKA-SA). Karoo GP, kNN, and SVM were comparatively employed, the outcome of which provided noteworthy correlations between input parameters, the complexity of the evolved hypotheses, and performance of raw data versus engineered features. This dissertation includes description of novel approaches to GP, such as upper and lower limits to the size of syntax trees, an auto-scaling multiclass classifier, and a Numpy array element manager. In addition to the research conducted at the SKA-SA, it is described how Karoo GP was applied to fine-tuning parameters of a weather prediction model at the South African Astronomical Observatory (SAAO), to glitch classification at the Laser Interferometer Gravitational-wave Observatory (LIGO), and to astro-particle physics at The Ohio State University.

  14. Ischemic stroke after use of the synthetic marijuana "spice".

    Science.gov (United States)

    Freeman, Melissa J; Rose, David Z; Myers, Martin A; Gooch, Clifton L; Bozeman, Andrea C; Burgin, W Scott

    2013-12-10

    To report and associate acute cerebral infarctions in 2 young, previously healthy siblings with use of the street drug known as "spice" (a synthetic marijuana product, also known as "K2"), which they independently smoked before experiencing acute embolic-appearing ischemic strokes. We present history, physical examination, laboratory data, cerebrovascular imaging, echocardiogram, ECG, and hospital course of these patients. We found that in both siblings spice was obtained from the same source. The drug was found to contain the schedule I synthetic cannabinoid JWH-018. Full stroke workup was unrevealing of a stroke etiology; urine drug screen was positive for marijuana. We found that our 2 patients who smoked the street drug spice had a temporal association with symptoms of acute cerebral infarction. This association may be confounded by contaminants in the product consumed (i.e., marijuana or an unidentified toxin) or by an unknown genetic mechanism. The imaging of both patients suggests an embolic etiology, which is consistent with reports of serious adverse cardiac events with spice use, including tachyarrhythmias and myocardial infarctions.

  15. Insulated transcriptional elements enable precise design of genetic circuits.

    Science.gov (United States)

    Zong, Yeqing; Zhang, Haoqian M; Lyu, Cheng; Ji, Xiangyu; Hou, Junran; Guo, Xian; Ouyang, Qi; Lou, Chunbo

    2017-07-03

    Rational engineering of biological systems is often complicated by the complex but unwanted interactions between cellular components at multiple levels. Here we address this issue at the level of prokaryotic transcription by insulating minimal promoters and operators to prevent their interaction and enable the biophysical modeling of synthetic transcription without free parameters. This approach allows genetic circuit design with extraordinary precision and diversity, and consequently simplifies the design-build-test-learn cycle of circuit engineering to a mix-and-match workflow. As a demonstration, combinatorial promoters encoding NOT-gate functions were designed from scratch with mean errors of 96% using our insulated transcription elements. Furthermore, four-node transcriptional networks with incoherent feed-forward loops that execute stripe-forming functions were obtained without any trial-and-error work. This insulation-based engineering strategy improves the resolution of genetic circuit technology and provides a simple approach for designing genetic circuits for systems and synthetic biology.Unwanted interactions between cellular components can complicate rational engineering of biological systems. Here the authors design insulated minimal promoters and operators that enable biophysical modeling of bacterial transcription without free parameters for precise circuit design.

  16. Novel genetic diversity of the alien D-genome synthetic hexaploid wheat (2n=6x=42, Aabbdd) germplasm for various phenology traits

    International Nuclear Information System (INIS)

    Masood, R.M.; Bibi, K.; Jamil, M.

    2016-01-01

    The current study evaluates genetic penetrance and expressivity of an alien genome introgression in a set of 117 primary synthetic hexaploid wheat (SHW) accessions. These SHW have originated from durum wheat /accessions with three sets of durum wheat cultivars ALTAR 84, D67.2 and CERCETA as the female and diverse Ae. tauschii accessions as the pollen parents. Diversity of the 12 important traits (Growth habit, pigmentation, chlorophyll content, leaf area index, crop digital ground cover, awn size, awn length, and several seed digital imaging parameters)revealed significant variation for the respective traits, leading to the conclusion that Ae. tauschii accessions have tremendous diversity than the durum controls. Further, the value deviations within each attribute had a range of being lower or higher than their durum wheat female parents and these observations allowed us to use the variations as selective sieves and narrow down the desirable SHW that would be advantageous to exploit for wheat breeding and cultivar improvement programs. Selections were made and a group of 41SHW accessions were identified that will after an intermediate DNA diversity evaluation form a crisper final set for user friendly utilization. The range of selections shows multiple trait advantages for exploitation in both irrigated and rain-fed conditions. This pivotal study sets the foundation to better define the D genome SHW for efficient utilization in future research investigations. Our results have implications in widening the genetic base of hexaploid bread wheat and may facilitate the development of agronomically desirable wheat cultivars. (author)

  17. Characterization of a Wheat Breeders' Array suitable for high-throughput SNP genotyping of global accessions of hexaploid bread wheat (Triticum aestivum).

    Science.gov (United States)

    Allen, Alexandra M; Winfield, Mark O; Burridge, Amanda J; Downie, Rowena C; Benbow, Harriet R; Barker, Gary L A; Wilkinson, Paul A; Coghill, Jane; Waterfall, Christy; Davassi, Alessandro; Scopes, Geoff; Pirani, Ali; Webster, Teresa; Brew, Fiona; Bloor, Claire; Griffiths, Simon; Bentley, Alison R; Alda, Mark; Jack, Peter; Phillips, Andrew L; Edwards, Keith J

    2017-03-01

    Targeted selection and inbreeding have resulted in a lack of genetic diversity in elite hexaploid bread wheat accessions. Reduced diversity can be a limiting factor in the breeding of high yielding varieties and crucially can mean reduced resilience in the face of changing climate and resource pressures. Recent technological advances have enabled the development of molecular markers for use in the assessment and utilization of genetic diversity in hexaploid wheat. Starting with a large collection of 819 571 previously characterized wheat markers, here we describe the identification of 35 143 single nucleotide polymorphism-based markers, which are highly suited to the genotyping of elite hexaploid wheat accessions. To assess their suitability, the markers have been validated using a commercial high-density Affymetrix Axiom ® genotyping array (the Wheat Breeders' Array), in a high-throughput 384 microplate configuration, to characterize a diverse global collection of wheat accessions including landraces and elite lines derived from commercial breeding communities. We demonstrate that the Wheat Breeders' Array is also suitable for generating high-density genetic maps of previously uncharacterized populations and for characterizing novel genetic diversity produced by mutagenesis. To facilitate the use of the array by the wheat community, the markers, the associated sequence and the genotype information have been made available through the interactive web site 'CerealsDB'. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  18. Inversion of ground-motion data from a seismometer array for rotation using a modification of Jaeger's method

    Science.gov (United States)

    Chi, Wu-Cheng; Lee, W.H.K.; Aston, J.A.D.; Lin, C.J.; Liu, C.-C.

    2011-01-01

    We develop a new way to invert 2D translational waveforms using Jaeger's (1969) formula to derive rotational ground motions about one axis and estimate the errors in them using techniques from statistical multivariate analysis. This procedure can be used to derive rotational ground motions and strains using arrayed translational data, thus providing an efficient way to calibrate the performance of rotational sensors. This approach does not require a priori information about the noise level of the translational data and elastic properties of the media. This new procedure also provides estimates of the standard deviations of the derived rotations and strains. In this study, we validated this code using synthetic translational waveforms from a seismic array. The results after the inversion of the synthetics for rotations were almost identical with the results derived using a well-tested inversion procedure by Spudich and Fletcher (2009). This new 2D procedure can be applied three times to obtain the full, three-component rotations. Additional modifications can be implemented to the code in the future to study different features of the rotational ground motions and strains induced by the passage of seismic waves.

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

    Science.gov (United States)

    Hodgman, C Eric; Jewett, Michael C

    2012-05-01

    Cell-free synthetic biology is emerging as a powerful approach aimed to understand, harness, and expand the capabilities of natural biological systems without using intact cells. Cell-free systems bypass cell walls and remove genetic regulation to enable direct access to the inner workings of the cell. The unprecedented level of control and freedom of design, relative to in vivo systems, has inspired the rapid development of engineering foundations for cell-free systems in recent years. These efforts have led to programmed circuits, spatially organized pathways, co-activated catalytic ensembles, rational optimization of synthetic multi-enzyme pathways, and linear scalability from the micro-liter to the 100-liter scale. It is now clear that cell-free systems offer a versatile test-bed for understanding why nature's designs work the way they do and also for enabling biosynthetic routes to novel chemicals, sustainable fuels, and new classes of tunable materials. While challenges remain, the emergence of cell-free systems is poised to open the way to novel products that until now have been impractical, if not impossible, to produce by other means. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. Synthetic environments

    Science.gov (United States)

    Lukes, George E.; Cain, Joel M.

    1996-02-01

    The Advanced Distributed Simulation (ADS) Synthetic Environments Program seeks to create robust virtual worlds from operational terrain and environmental data sources of sufficient fidelity and currency to interact with the real world. While some applications can be met by direct exploitation of standard digital terrain data, more demanding applications -- particularly those support operations 'close to the ground' -- are well-served by emerging capabilities for 'value-adding' by the user working with controlled imagery. For users to rigorously refine and exploit controlled imagery within functionally different workstations they must have a shared framework to allow interoperability within and between these environments in terms of passing image and object coordinates and other information using a variety of validated sensor models. The Synthetic Environments Program is now being expanded to address rapid construction of virtual worlds with research initiatives in digital mapping, softcopy workstations, and cartographic image understanding. The Synthetic Environments Program is also participating in a joint initiative for a sensor model applications programer's interface (API) to ensure that a common controlled imagery exploitation framework is available to all researchers, developers and users. This presentation provides an introduction to ADS and the associated requirements for synthetic environments to support synthetic theaters of war. It provides a technical rationale for exploring applications of image understanding technology to automated cartography in support of ADS and related programs benefitting from automated analysis of mapping, earth resources and reconnaissance imagery. And it provides an overview and status of the joint initiative for a sensor model API.

  1. Effective elastic modulus of isolated gecko setal arrays.

    Science.gov (United States)

    Autumn, K; Majidi, C; Groff, R E; Dittmore, A; Fearing, R

    2006-09-01

    Conventional pressure sensitive adhesives (PSAs) are fabricated from soft viscoelastic materials that satisfy Dahlquist's criterion for tack with a Young's modulus (E) of 100 kPa or less at room temperature and 1 Hz. In contrast, the adhesive on the toes of geckos is made of beta-keratin, a stiff material with E at least four orders of magnitude greater than the upper limit of Dahlquist's criterion. Therefore, one would not expect a beta-keratin structure to function as a PSA by deforming readily to make intimate molecular contact with a variety of surface profiles. However, since the gecko adhesive is a microstructure in the form of an array of millions of high aspect ratio shafts (setae), the effective elastic modulus (E(eff)) is much lower than E of bulk beta-keratin. In the first test of the E(eff) of a gecko setal adhesive, we measured the forces resulting from deformation of isolated arrays of tokay gecko (Gekko gecko) setae during vertical compression, and during tangential compression at angles of +45 degrees and -45 degrees . We tested the hypothesis that E(eff) of gecko setae falls within Dahlquist's criterion for tack, and evaluated the validity of a model of setae as cantilever beams. Highly linear forces of deformation under all compression conditions support the cantilever model. E(eff) of setal arrays during vertical and +45 degrees compression (along the natural path of drag of the setae) were 83+/-4.0 kPa and 86+/-4.4 kPa (means +/- s.e.m.), respectively. Consistent with the predictions of the cantilever model, setae became significantly stiffer when compressed against the natural path of drag: E(eff) during -45 degrees compression was 110+/-4.7 kPa. Unlike synthetic PSAs, setal arrays act as Hookean elastic solids; setal arrays function as a bed of springs with a directional stiffness, assisting alignment of the adhesive spatular tips with the contact surface during shear loading.

  2. Identifying tagging SNPs for African specific genetic variation from the African Diaspora Genome.

    Science.gov (United States)

    Johnston, Henry Richard; Hu, Yi-Juan; Gao, Jingjing; O'Connor, Timothy D; Abecasis, Gonçalo R; Wojcik, Genevieve L; Gignoux, Christopher R; Gourraud, Pierre-Antoine; Lizee, Antoine; Hansen, Mark; Genuario, Rob; Bullis, Dave; Lawley, Cindy; Kenny, Eimear E; Bustamante, Carlos; Beaty, Terri H; Mathias, Rasika A; Barnes, Kathleen C; Qin, Zhaohui S

    2017-04-21

    A primary goal of The Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA) is to develop an 'African Diaspora Power Chip' (ADPC), a genotyping array consisting of tagging SNPs, useful in comprehensively identifying African specific genetic variation. This array is designed based on the novel variation identified in 642 CAAPA samples of African ancestry with high coverage whole genome sequence data (~30× depth). This novel variation extends the pattern of variation catalogued in the 1000 Genomes and Exome Sequencing Projects to a spectrum of populations representing the wide range of West African genomic diversity. These individuals from CAAPA also comprise a large swath of the African Diaspora population and incorporate historical genetic diversity covering nearly the entire Atlantic coast of the Americas. Here we show the results of designing and producing such a microchip array. This novel array covers African specific variation far better than other commercially available arrays, and will enable better GWAS analyses for researchers with individuals of African descent in their study populations. A recent study cataloging variation in continental African populations suggests this type of African-specific genotyping array is both necessary and valuable for facilitating large-scale GWAS in populations of African ancestry.

  3. Development and Evaluation of a Barley 50k iSelect SNP Array

    Directory of Open Access Journals (Sweden)

    Micha M. Bayer

    2017-10-01

    Full Text Available High-throughput genotyping arrays continue to be an attractive, cost-effective alternative to sequencing based approaches. We have developed a new 50k Illumina Infinium iSelect genotyping array for barley, a cereal crop species of major international importance. The majority of SNPs on the array have been extracted from variants called in exome capture data of a wide range of European barley germplasm. We used the recently published barley pseudomolecule assembly to map the exome capture data, which allowed us to generate markers with accurate physical positions and detailed gene annotation. Markers from an existing and widely used barley 9k Infinium iSelect array were carried over onto the 50k chip for backward compatibility. The array design featured 49,267 SNP markers that converted into 44,040 working assays, of which 43,461 were scorable in GenomeStudio. Of the working assays, 6,251 are from the 9k iSelect platform. We validated the SNPs by comparing the genotype calls from the new array to legacy datasets. Rates of agreement averaged 98.1 and 93.9% respectively for the legacy 9k iSelect SNP set (Comadran et al., 2012 and the exome capture SNPs. To test the utility of the 50k chip for genetic mapping, we genotyped a segregating population derived from a Golden Promise × Morex cross (Liu et al., 2014 and mapped over 14,000 SNPs to genetic positions which showed a near exact correspondence to their known physical positions. Manual adjustment of the cluster files used by the interpreting software for genotype scoring improved results substantially, but migration of cluster files between sites led to a deterioration of results, suggesting that local adjustment of cluster files is required on a site-per-site basis. Information relating to the markers on the chip is available online at https://ics.hutton.ac.uk/50k.

  4. Array CGH analysis of a cohort of Russian patients with intellectual disability.

    Science.gov (United States)

    Kashevarova, Anna A; Nazarenko, Lyudmila P; Skryabin, Nikolay A; Salyukova, Olga A; Chechetkina, Nataliya N; Tolmacheva, Ekaterina N; Sazhenova, Elena A; Magini, Pamela; Graziano, Claudio; Romeo, Giovanni; Kučinskas, Vaidutis; Lebedev, Igor N

    2014-02-15

    The use of array comparative genomic hybridization (array CGH) as a diagnostic tool in molecular genetics has facilitated the identification of many new microdeletion/microduplication syndromes (MMSs). Furthermore, this method has allowed for the identification of copy number variations (CNVs) whose pathogenic role has yet to be uncovered. Here, we report on our application of array CGH for the identification of pathogenic CNVs in 79 Russian children with intellectual disability (ID). Twenty-six pathogenic or likely pathogenic changes in copy number were detected in 22 patients (28%): 8 CNVs corresponded to known MMSs, and 17 were not associated with previously described syndromes. In this report, we describe our findings and comment on genes potentially associated with ID that are located within the CNV regions. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Rapid and accurate synthesis of TALE genes from synthetic oligonucleotides.

    Science.gov (United States)

    Wang, Fenghua; Zhang, Hefei; Gao, Jingxia; Chen, Fengjiao; Chen, Sijie; Zhang, Cuizhen; Peng, Gang

    2016-01-01

    Custom synthesis of transcription activator-like effector (TALE) genes has relied upon plasmid libraries of pre-fabricated TALE-repeat monomers or oligomers. Here we describe a novel synthesis method that directly incorporates annealed synthetic oligonucleotides into the TALE-repeat units. Our approach utilizes iterative sets of oligonucleotides and a translational frame check strategy to ensure the high efficiency and accuracy of TALE-gene synthesis. TALE arrays of more than 20 repeats can be constructed, and the majority of the synthesized constructs have perfect sequences. In addition, this novel oligonucleotide-based method can readily accommodate design changes to the TALE repeats. We demonstrated an increased gene targeting efficiency against a genomic site containing a potentially methylated cytosine by incorporating non-conventional repeat variable di-residue (RVD) sequences.

  6. Assessing the monitoring performance using a synthetic microseismic catalogue for hydraulic fracturing

    Science.gov (United States)

    Ángel López Comino, José; Kriegerowski, Marius; Cesca, Simone; Dahm, Torsten; Mirek, Janusz; Lasocki, Stanislaw

    2016-04-01

    Hydraulic fracturing is considered among the human operations which could induce or trigger seismicity or microseismic activity. The influence of hydraulic fracturing operations is typically expected in terms of weak magnitude events. However, the sensitivity of the rock mass to trigger seismicity varies significantly for different sites and cannot be easily predicted prior to operations. In order to assess the sensitivity of microseismity to hydraulic fracturing operations, we perform a seismic monitoring at a shale gas exploration/exploitation site in the central-western part of the Peribaltic synclise at Pomerania (Poland). The monitoring will be continued before, during and after the termination of hydraulic fracturing operations. The fracking operations are planned in April 2016 at a depth 4000 m. A specific network setup has been installed since summer 2015, including a distributed network of broadband stations and three small-scale arrays. The network covers a region of 60 km2. The aperture of small scale arrays is between 450 and 950 m. So far no fracturing operations have been performed, but seismic data can already be used to assess the seismic noise and background microseismicity, and to investigate and assess the detection performance of our monitoring setup. Here we adopt a recently developed tool to generate a synthetic catalogue and waveform dataset, which realistically account for the expected microseismicity. Synthetic waveforms are generated for a local crustal model, considering a realistic distribution of hypocenters, magnitudes, moment tensors, and source durations. Noise free synthetic seismograms are superposed to real noise traces, to reproduce true monitoring conditions at the different station locations. We estimate the detection probability for different magnitudes, source-receiver distances, and noise conditions. This information is used to estimate the magnitude of completeness at the depth of the hydraulic fracturing horizontal wells

  7. Precise Time-of-Flight Calculation For 3-D Synthetic Aperture Focusing

    DEFF Research Database (Denmark)

    Andresen, Henrik; Nikolov, Svetoslav; Jensen, Jørgen Arendt

    2009-01-01

    in elevation can be achieved by applying synthetic aperture (SA) focusing to the beamformed in-plane RF-data. The proposed method uses a virtual source (VS) placed at the elevation focus for postbeamforming. This has previously been done in two steps, in plane focusing followed by SA post-focusing in elevation......, because of a lack of a simple expression for the exact time of flight (ToF). This paper presents a new method for calculating the ToF for a 3D case in a single step using a linear array. This method is more flexible than the previously proposed method and is able to beamform a fewer number of points much...

  8. Development of synthetic selfish elements based on modular nucleases in Drosophila melanogaster

    OpenAIRE

    Simoni, A; Siniscalchi, C; Chan, Y-S; Huen, DS; Russell, S; Windbichler, N; Crisanti, A

    2014-01-01

    Selfish genes are DNA elements that increase their rate of genetic transmission at the expense of other genes in the genome and can therefore quickly spread within a population. It has been suggested that selfish elements could be exploited to modify the genome of entire populations for medical and ecological applications. Here we report that transcription activator-like effector nuclease (TALEN) and zinc finger nuclease (ZFN) can be engineered into site-specific synthetic selfish elements (S...

  9. 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.

  10. Maize Genetic Resources Collections – Utilizing a Treasure Trove

    Science.gov (United States)

    The maize genetic resource collection managed by the USDA-ARS's National Plant Germplasm System is heavily utilized by researchers and educators. A collection of landraces, inbred lines from public and private sector sources, synthetics and key populations, it serves both as a living snapshot of th...

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

    Science.gov (United States)

    Ciechonska, Marta; Grob, Alice; Isalan, Mark

    2016-04-18

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

  12. Focal plane array with modular pixel array components for scalability

    Science.gov (United States)

    Kay, Randolph R; Campbell, David V; Shinde, Subhash L; Rienstra, Jeffrey L; Serkland, Darwin K; Holmes, Michael L

    2014-12-09

    A modular, scalable focal plane array is provided as an array of integrated circuit dice, wherein each die includes a given amount of modular pixel array circuitry. The array of dice effectively multiplies the amount of modular pixel array circuitry to produce a larger pixel array without increasing die size. Desired pixel pitch across the enlarged pixel array is preserved by forming die stacks with each pixel array circuitry die stacked on a separate die that contains the corresponding signal processing circuitry. Techniques for die stack interconnections and die stack placement are implemented to ensure that the desired pixel pitch is preserved across the enlarged pixel array.

  13. Developing high coercivity in large diameter cobalt nanowire arrays

    Science.gov (United States)

    Montazer, A. H.; Ramazani, A.; Almasi Kashi, M.; Zavašnik, J.

    2016-11-01

    Regardless of the synthetic method, developing high magnetic coercivity in ferromagnetic nanowires (NWs) with large diameters has been a challenge over the past two decades. Here, we report on the synthesis of highly coercive cobalt NW arrays with diameters of 65 and 80 nm, which are embedded in porous anodic alumina templates with high-aspect-ratio pores. Using a modified electrochemical deposition method enabled us to reach room temperature coercivity and remanent ratio up to 3000 Oe and 0.70, respectively, for highly crystalline as-synthesized hcp cobalt NW arrays with a length of 8 μm. The first-order reversal curve (FORC) analysis showed the presence of both soft and hard magnetic phases along the length of the resulting NWs. To develop higher coercive fields, the length of the NWs was then gradually reduced in order from bottom to top, thereby reaching NW sections governed by the hard phase. Consequently, this resulted in record high coercivities of 4200 and 3850 Oe at NW diameters of 65 and 80 nm, respectively. In this case, the FORC diagrams confirmed a significant reduction in interactions between the magnetic phases of the remaining sections of NWs. At this stage, x-ray diffraction (XRD) and dark-field transmission electron microscopy analyses indicated the formation of highly crystalline bamboo-like sections along the [0 0 2] direction during a progressive pulse-controlled electrochemical growth of NW arrays under optimized parameters. Our results both provide new insights into the growth process, crystalline characteristics and magnetic phases along the length of large diameter NW arrays and, furthermore, develop the performance of pure 3d transition magnetic NWs.

  14. A living foundry for Synthetic Biological Materials: A synthetic biology roadmap to new advanced materials

    Directory of Open Access Journals (Sweden)

    Rosalind A. Le Feuvre

    2018-06-01

    Full Text Available Society is on the cusp of harnessing recent advances in synthetic biology to discover new bio-based products and routes to their affordable and sustainable manufacture. This is no more evident than in the discovery and manufacture of Synthetic Biological Materials, where synthetic biology has the capacity to usher in a new Materials from Biology era that will revolutionise the discovery and manufacture of innovative synthetic biological materials. These will encompass novel, smart, functionalised and hybrid materials for diverse applications whose discovery and routes to bio-production will be stimulated by the fusion of new technologies positioned across physical, digital and biological spheres. This article, which developed from an international workshop held in Manchester, United Kingdom, in 2017 [1], sets out to identify opportunities in the new materials from biology era. It considers requirements, early understanding and foresight of the challenges faced in delivering a Discovery to Manufacturing Pipeline for synthetic biological materials using synthetic biology approaches. This challenge spans the complete production cycle from intelligent and predictive design, fabrication, evaluation and production of synthetic biological materials to new ways of bringing these products to market. Pathway opportunities are identified that will help foster expertise sharing and infrastructure development to accelerate the delivery of a new generation of synthetic biological materials and the leveraging of existing investments in synthetic biology and advanced materials research to achieve this goal. Keywords: Synthetic biology, Materials, Biological materials, Biomaterials, Advanced materials

  15. Timed arrays wideband and time varying antenna arrays

    CERN Document Server

    Haupt, Randy L

    2015-01-01

    Introduces timed arrays and design approaches to meet the new high performance standards The author concentrates on any aspect of an antenna array that must be viewed from a time perspective. The first chapters briefly introduce antenna arrays and explain the difference between phased and timed arrays. Since timed arrays are designed for realistic time-varying signals and scenarios, the book also reviews wideband signals, baseband and passband RF signals, polarization and signal bandwidth. Other topics covered include time domain, mutual coupling, wideband elements, and dispersion. The auth

  16. Mapping DNA damage-dependent genetic interactions in yeast via party mating and barcode fusion genetics.

    Science.gov (United States)

    Díaz-Mejía, J Javier; Celaj, Albi; Mellor, Joseph C; Coté, Atina; Balint, Attila; Ho, Brandon; Bansal, Pritpal; Shaeri, Fatemeh; Gebbia, Marinella; Weile, Jochen; Verby, Marta; Karkhanina, Anna; Zhang, YiFan; Wong, Cassandra; Rich, Justin; Prendergast, D'Arcy; Gupta, Gaurav; Öztürk, Sedide; Durocher, Daniel; Brown, Grant W; Roth, Frederick P

    2018-05-28

    Condition-dependent genetic interactions can reveal functional relationships between genes that are not evident under standard culture conditions. State-of-the-art yeast genetic interaction mapping, which relies on robotic manipulation of arrays of double-mutant strains, does not scale readily to multi-condition studies. Here, we describe barcode fusion genetics to map genetic interactions (BFG-GI), by which double-mutant strains generated via en masse "party" mating can also be monitored en masse for growth to detect genetic interactions. By using site-specific recombination to fuse two DNA barcodes, each representing a specific gene deletion, BFG-GI enables multiplexed quantitative tracking of double mutants via next-generation sequencing. We applied BFG-GI to a matrix of DNA repair genes under nine different conditions, including methyl methanesulfonate (MMS), 4-nitroquinoline 1-oxide (4NQO), bleomycin, zeocin, and three other DNA-damaging environments. BFG-GI recapitulated known genetic interactions and yielded new condition-dependent genetic interactions. We validated and further explored a subnetwork of condition-dependent genetic interactions involving MAG1 , SLX4, and genes encoding the Shu complex, and inferred that loss of the Shu complex leads to an increase in the activation of the checkpoint protein kinase Rad53. © 2018 The Authors. Published under the terms of the CC BY 4.0 license.

  17. Synthetic tracked aperture ultrasound imaging: design, simulation, and experimental evaluation.

    Science.gov (United States)

    Zhang, Haichong K; Cheng, Alexis; Bottenus, Nick; Guo, Xiaoyu; Trahey, Gregg E; Boctor, Emad M

    2016-04-01

    Ultrasonography is a widely used imaging modality to visualize anatomical structures due to its low cost and ease of use; however, it is challenging to acquire acceptable image quality in deep tissue. Synthetic aperture (SA) is a technique used to increase image resolution by synthesizing information from multiple subapertures, but the resolution improvement is limited by the physical size of the array transducer. With a large F-number, it is difficult to achieve high resolution in deep regions without extending the effective aperture size. We propose a method to extend the available aperture size for SA-called synthetic tracked aperture ultrasound (STRATUS) imaging-by sweeping an ultrasound transducer while tracking its orientation and location. Tracking information of the ultrasound probe is used to synthesize the signals received at different positions. Considering the practical implementation, we estimated the effect of tracking and ultrasound calibration error to the quality of the final beamformed image through simulation. In addition, to experimentally validate this approach, a 6 degree-of-freedom robot arm was used as a mechanical tracker to hold an ultrasound transducer and to apply in-plane lateral translational motion. Results indicate that STRATUS imaging with robotic tracking has the potential to improve ultrasound image quality.

  18. An Experimental Study on Active Flow Control Using Synthetic Jet Actuators over S809 Airfoil

    International Nuclear Information System (INIS)

    Gul, M; Uzol, O; Akmandor, I S

    2014-01-01

    This study investigates the effect of periodic excitation from individually controlled synthetic jet actuators on the dynamics of the flow within the separation and re-attachment regions of the boundary layer over the suction surface of a 2D model wing that has S809 airfoil profile. Experiments are performed in METUWIND's C3 open-loop suction type wind tunnel that has a 1 m × 1 m cross-section test section. The synthetic jet array on the wing consists of three individually controlled actuators driven by piezoelectric diaphragms located at 28% chord location near the mid-span of the wing. In the first part of the study, surface pressure, Constant Temperature Anemometry (CTA) and Particle Image Velocimetry (PIV) measurements are performed over the suction surface of the airfoil to determine the size and characteristics of the separated shear layer and the re-attachment region, i.e. the laminar separation bubble, at 2.3x10 5 Reynolds number at zero angle of attack and with no flow control as a baseline case. For the controlled case, CTA measurements are carried out under the same inlet conditions at various streamwise locations along the suction surface of the airfoil to investigate the effect of the synthetic jet on the boundary layer properties. During the controlled case experiments, the synthetic jet actuators are driven with a sinusoidal frequency of 1.45 kHz and 300Vp-p. Results of this study show that periodic excitation from the synthetic jet actuators eliminates the laminar separation bubble formed over the suction surface of the airfoil at 2.3x10 5 Reynolds number at zero angle of attack

  19. Synthetic biological networks

    International Nuclear Information System (INIS)

    Archer, Eric; Süel, Gürol M

    2013-01-01

    Despite their obvious relationship and overlap, the field of physics is blessed with many insightful laws, while such laws are sadly absent in biology. Here we aim to discuss how the rise of a more recent field known as synthetic biology may allow us to more directly test hypotheses regarding the possible design principles of natural biological networks and systems. In particular, this review focuses on synthetic gene regulatory networks engineered to perform specific functions or exhibit particular dynamic behaviors. Advances in synthetic biology may set the stage to uncover the relationship of potential biological principles to those developed in physics. (review article)

  20. Open-array analysis of genetic variants in Egyptian patients with ...

    African Journals Online (AJOL)

    Background: Diabetes mellitus is considered a major public health problem worldwide. Susceptibility to diabetes is influenced by both genetic and environmental determinants. Aims/hypothesis: The aim of the present study was to test for 16 independent single nucleotide polymorphisms (SNPs) in established Type 2 ...

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

    Science.gov (United States)

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

    2016-07-01

    The Green Revolution has fuelled an exponential growth in human population since the mid-20th century. Due to population growth, food and energy demands will soon surpass supply capabilities. To overcome these impending problems, significant improvements in genetic engineering will be needed to complement breeding efforts in order to accelerate the improvement of agronomical traits. The new field of plant synthetic biology has emerged in recent years and is expected to support rapid, precise, and robust engineering of plants. 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 on traits related to lignocellulose, oil, and soluble sugars. Ultimately, progress and innovation in these fields may facilitate the development of beneficial traits in crop plants to meet society's bioenergy needs. © 2016 The Authors. The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.

  2. Monitoring performance for hydraulic fracturing using synthetic microseismic catalogue at the Wysin site (Poland)

    Science.gov (United States)

    Ángel López Comino, José; Cesca, Simone; Kriegerowski, Marius; Heimann, Sebastian; Dahm, Torsten; Mirek, Janusz; Lasocky, Stanislaw

    2017-04-01

    Previous analysis to assess the monitoring performance of a dedicated seismic network are always useful to determine its capability of detecting, locating and characterizing target seismicity. This work focuses on a hydrofracking experiment in Poland, which is monitored in the framework of the SHEER (SHale gas Exploration and Exploitation induced Risks) EU project. The seismic installation is located near Wysin (Poland), in the central-western part of the Peribaltic synclise at Pomerania. The network setup includes a distributed network of six broadband stations, three shallow borehole stations and three small-scale arrays. We assess the monitoring performance prior operations, using synthetic seismograms. Realistic full waveform are generated and combined with real noise before fracking operations, to produce either event based or continuous synthetic waveforms. Background seismicity is modelled by double couple (DC) focal mechanisms. Non-DC sources resemble induced tensile fractures opening in the direction of the minimal compressive stress and closing in the same direction after the injection. Microseismic sources are combined with a realistic crustal model, distribution of hypocenters, magnitudes and source durations. The network detection performance is then assessed in terms of Magnitude of Completeness (Mc) through two different techniques: i) using an amplitude threshold approach, taking into account a station dependent noise level and different values of signal-to-noise ratio (SNR) and ii) through the application of an automatic detection algorithm to the continuous synthetic dataset. In the first case, we compare the maximal amplitude of noise free synthetic waveforms with the different noise levels. Imposing the simultaneous detection at e.g. 4 stations for a robust detection, the Mc is assessed and can be adjusted by empirical relationships for different SNR values. We find that different source mechanisms have different detection threshold. The

  3. ArrayBridge: Interweaving declarative array processing with high-performance computing

    Energy Technology Data Exchange (ETDEWEB)

    Xing, Haoyuan [The Ohio State Univ., Columbus, OH (United States); Floratos, Sofoklis [The Ohio State Univ., Columbus, OH (United States); Blanas, Spyros [The Ohio State Univ., Columbus, OH (United States); Byna, Suren [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Prabhat, Prabhat [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Wu, Kesheng [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Brown, Paul [Paradigm4, Inc., Waltham, MA (United States)

    2017-05-04

    Scientists are increasingly turning to datacenter-scale computers to produce and analyze massive arrays. Despite decades of database research that extols the virtues of declarative query processing, scientists still write, debug and parallelize imperative HPC kernels even for the most mundane queries. This impedance mismatch has been partly attributed to the cumbersome data loading process; in response, the database community has proposed in situ mechanisms to access data in scientific file formats. Scientists, however, desire more than a passive access method that reads arrays from files. This paper describes ArrayBridge, a bi-directional array view mechanism for scientific file formats, that aims to make declarative array manipulations interoperable with imperative file-centric analyses. Our prototype implementation of ArrayBridge uses HDF5 as the underlying array storage library and seamlessly integrates into the SciDB open-source array database system. In addition to fast querying over external array objects, ArrayBridge produces arrays in the HDF5 file format just as easily as it can read from it. ArrayBridge also supports time travel queries from imperative kernels through the unmodified HDF5 API, and automatically deduplicates between array versions for space efficiency. Our extensive performance evaluation in NERSC, a large-scale scientific computing facility, shows that ArrayBridge exhibits statistically indistinguishable performance and I/O scalability to the native SciDB storage engine.

  4. Open questions in origin of life: experimental studies on the origin of nucleic acids and proteins with specific and functional sequences by a chemical synthetic biology approach

    DEFF Research Database (Denmark)

    Adamala, K.; Anella, F.; Wieczorek, R.

    2014-01-01

    sequences among a vast array of possible ones, the huge "sequence space", leading to the question "why these macromolecules, and not the others?" We have recently addressed these questions by using a chemical synthetic biology approach. In particular, we have tested the catalytic activity of small peptides...

  5. Development and validation of a 20K single nucleotide polymorphism (SNP) whole genome genotyping array for apple (Malus × domestica Borkh).

    Science.gov (United States)

    Bianco, Luca; Cestaro, Alessandro; Sargent, Daniel James; Banchi, Elisa; Derdak, Sophia; Di Guardo, Mario; Salvi, Silvio; Jansen, Johannes; Viola, Roberto; Gut, Ivo; Laurens, Francois; Chagné, David; Velasco, Riccardo; van de Weg, Eric; Troggio, Michela

    2014-01-01

    High-density SNP arrays for genome-wide assessment of allelic variation have made high resolution genetic characterization of crop germplasm feasible. A medium density array for apple, the IRSC 8K SNP array, has been successfully developed and used for screens of bi-parental populations. However, the number of robust and well-distributed markers contained on this array was not sufficient to perform genome-wide association analyses in wider germplasm sets, or Pedigree-Based Analysis at high precision, because of rapid decay of linkage disequilibrium. We describe the development of an Illumina Infinium array targeting 20K SNPs. The SNPs were predicted from re-sequencing data derived from the genomes of 13 Malus × domestica apple cultivars and one accession belonging to a crab apple species (M. micromalus). A pipeline for SNP selection was devised that avoided the pitfalls associated with the inclusion of paralogous sequence variants, supported the construction of robust multi-allelic SNP haploblocks and selected up to 11 entries within narrow genomic regions of ±5 kb, termed focal points (FPs). Broad genome coverage was attained by placing FPs at 1 cM intervals on a consensus genetic map, complementing them with FPs to enrich the ends of each of the chromosomes, and by bridging physical intervals greater than 400 Kbps. The selection also included ∼3.7K validated SNPs from the IRSC 8K array. The array has already been used in other studies where ∼15.8K SNP markers were mapped with an average of ∼6.8K SNPs per full-sib family. The newly developed array with its high density of polymorphic validated SNPs is expected to be of great utility for Pedigree-Based Analysis and Genomic Selection. It will also be a valuable tool to help dissect the genetic mechanisms controlling important fruit quality traits, and to aid the identification of marker-trait associations suitable for the application of Marker Assisted Selection in apple breeding programs.

  6. Development and validation of a 20K single nucleotide polymorphism (SNP whole genome genotyping array for apple (Malus × domestica Borkh.

    Directory of Open Access Journals (Sweden)

    Luca Bianco

    Full Text Available High-density SNP arrays for genome-wide assessment of allelic variation have made high resolution genetic characterization of crop germplasm feasible. A medium density array for apple, the IRSC 8K SNP array, has been successfully developed and used for screens of bi-parental populations. However, the number of robust and well-distributed markers contained on this array was not sufficient to perform genome-wide association analyses in wider germplasm sets, or Pedigree-Based Analysis at high precision, because of rapid decay of linkage disequilibrium. We describe the development of an Illumina Infinium array targeting 20K SNPs. The SNPs were predicted from re-sequencing data derived from the genomes of 13 Malus × domestica apple cultivars and one accession belonging to a crab apple species (M. micromalus. A pipeline for SNP selection was devised that avoided the pitfalls associated with the inclusion of paralogous sequence variants, supported the construction of robust multi-allelic SNP haploblocks and selected up to 11 entries within narrow genomic regions of ±5 kb, termed focal points (FPs. Broad genome coverage was attained by placing FPs at 1 cM intervals on a consensus genetic map, complementing them with FPs to enrich the ends of each of the chromosomes, and by bridging physical intervals greater than 400 Kbps. The selection also included ∼3.7K validated SNPs from the IRSC 8K array. The array has already been used in other studies where ∼15.8K SNP markers were mapped with an average of ∼6.8K SNPs per full-sib family. The newly developed array with its high density of polymorphic validated SNPs is expected to be of great utility for Pedigree-Based Analysis and Genomic Selection. It will also be a valuable tool to help dissect the genetic mechanisms controlling important fruit quality traits, and to aid the identification of marker-trait associations suitable for the application of Marker Assisted Selection in apple breeding programs.

  7. Development and Validation of a 20K Single Nucleotide Polymorphism (SNP) Whole Genome Genotyping Array for Apple (Malus × domestica Borkh)

    Science.gov (United States)

    Bianco, Luca; Cestaro, Alessandro; Sargent, Daniel James; Banchi, Elisa; Derdak, Sophia; Di Guardo, Mario; Salvi, Silvio; Jansen, Johannes; Viola, Roberto; Gut, Ivo; Laurens, Francois; Chagné, David; Velasco, Riccardo; van de Weg, Eric; Troggio, Michela

    2014-01-01

    High-density SNP arrays for genome-wide assessment of allelic variation have made high resolution genetic characterization of crop germplasm feasible. A medium density array for apple, the IRSC 8K SNP array, has been successfully developed and used for screens of bi-parental populations. However, the number of robust and well-distributed markers contained on this array was not sufficient to perform genome-wide association analyses in wider germplasm sets, or Pedigree-Based Analysis at high precision, because of rapid decay of linkage disequilibrium. We describe the development of an Illumina Infinium array targeting 20K SNPs. The SNPs were predicted from re-sequencing data derived from the genomes of 13 Malus × domestica apple cultivars and one accession belonging to a crab apple species (M. micromalus). A pipeline for SNP selection was devised that avoided the pitfalls associated with the inclusion of paralogous sequence variants, supported the construction of robust multi-allelic SNP haploblocks and selected up to 11 entries within narrow genomic regions of ±5 kb, termed focal points (FPs). Broad genome coverage was attained by placing FPs at 1 cM intervals on a consensus genetic map, complementing them with FPs to enrich the ends of each of the chromosomes, and by bridging physical intervals greater than 400 Kbps. The selection also included ∼3.7K validated SNPs from the IRSC 8K array. The array has already been used in other studies where ∼15.8K SNP markers were mapped with an average of ∼6.8K SNPs per full-sib family. The newly developed array with its high density of polymorphic validated SNPs is expected to be of great utility for Pedigree-Based Analysis and Genomic Selection. It will also be a valuable tool to help dissect the genetic mechanisms controlling important fruit quality traits, and to aid the identification of marker-trait associations suitable for the application of Marker Assisted Selection in apple breeding programs. PMID:25303088

  8. A living foundry for Synthetic Biological Materials: A synthetic biology roadmap to new advanced materials.

    Science.gov (United States)

    Le Feuvre, Rosalind A; Scrutton, Nigel S

    2018-06-01

    Society is on the cusp of harnessing recent advances in synthetic biology to discover new bio-based products and routes to their affordable and sustainable manufacture. This is no more evident than in the discovery and manufacture of Synthetic Biological Materials , where synthetic biology has the capacity to usher in a new Materials from Biology era that will revolutionise the discovery and manufacture of innovative synthetic biological materials. These will encompass novel, smart, functionalised and hybrid materials for diverse applications whose discovery and routes to bio-production will be stimulated by the fusion of new technologies positioned across physical, digital and biological spheres. This article, which developed from an international workshop held in Manchester, United Kingdom, in 2017 [1], sets out to identify opportunities in the new materials from biology era. It considers requirements, early understanding and foresight of the challenges faced in delivering a Discovery to Manufacturing Pipeline for synthetic biological materials using synthetic biology approaches. This challenge spans the complete production cycle from intelligent and predictive design, fabrication, evaluation and production of synthetic biological materials to new ways of bringing these products to market. Pathway opportunities are identified that will help foster expertise sharing and infrastructure development to accelerate the delivery of a new generation of synthetic biological materials and the leveraging of existing investments in synthetic biology and advanced materials research to achieve this goal.

  9. 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.

  10. Phenotype in patients with intellectual disability and pathological results in array CGH.

    Science.gov (United States)

    Caballero Pérez, V; López Pisón, F J; Miramar Gallart, M D; González Álvarez, A; García Jiménez, M C; García Iñiguez, J P; Orden Rueda, C; Gil Hernández, I; Fuertes Rodrigo, C; Fernando Martínez, R; Rodríguez Valle, A; Alcaine Villarroya, M J

    Global developmental delay (GDD) and intellectual disability (ID) are frequent reasons for consultation in paediatric neurology departments. Nowadays, array comparative genomic hybridisation (array-CGH) is one of the most widely used techniques for diagnosing these disorders. Our purpose was to determine the phenotypic features associated with pathological results in this genetic test. We conducted a blind study of the epidemiological, clinical, anthropometric, and morphological features of 80 patients with unexplained ID to determine which features were associated with pathological results in array-CGH. Pathological results were found in 27.5% of the patients. Factors associated with pathological results in array-CGH were a family history of GDD/ID (OR = 12.1), congenital malformations (OR = 5.33), having more than 3 facial dysmorphic features (OR = 20.9), and hypotonia (OR = 3.25). Our findings are consistent with those reported by other published series. We therefore conclude that the probability of having pathological results in array-CGH increases with the presence of any of the features mentioned above in patients with ID/GDD. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  11. Multispecies genetic objectives in spatial conservation planning.

    Science.gov (United States)

    Nielsen, Erica S; Beger, Maria; Henriques, Romina; Selkoe, Kimberly A; von der Heyden, Sophie

    2017-08-01

    Growing threats to biodiversity and global alteration of habitats and species distributions make it increasingly necessary to consider evolutionary patterns in conservation decision making. Yet, there is no clear-cut guidance on how genetic features can be incorporated into conservation-planning processes, despite multiple molecular markers and several genetic metrics for each marker type to choose from. Genetic patterns differ between species, but the potential tradeoffs among genetic objectives for multiple species in conservation planning are currently understudied. We compared spatial conservation prioritizations derived from 2 metrics of genetic diversity (nucleotide and haplotype diversity) and 2 metrics of genetic isolation (private haplotypes and local genetic differentiation) in mitochondrial DNA of 5 marine species. We compared outcomes of conservation plans based only on habitat representation with plans based on genetic data and habitat representation. Fewer priority areas were selected for conservation plans based solely on habitat representation than on plans that included habitat and genetic data. All 4 genetic metrics selected approximately similar conservation-priority areas, which is likely a result of prioritizing genetic patterns across a genetically diverse array of species. Largely, our results suggest that multispecies genetic conservation objectives are vital to creating protected-area networks that appropriately preserve community-level evolutionary patterns. © 2016 Society for Conservation Biology.

  12. Genetic testing in the workplace: the employer's coin toss.

    Science.gov (United States)

    French, Samantha

    2002-09-05

    A toss of the coin by the modern-day employer reveals two options regarding genetic testing in the workplace. The employer may choose to take advantage of increasingly precise, available, and affordable genetic testing in order to ascertain the genetic characteristics--and deficiencies--of its employees. This outcome exposes the employer to a vast array of potential litigation and liability relating to the Americans with Disabilities Act, the Fourth Amendment, Title VII of the Civil Rights Act, and state legislation designed to protect genetic privacy. Alternatively, the employer may neglect to indulge in this trend of genetic testing and may face liability for employer negligence, violations of federal legislation such as OSHA regulations, and increased costs associated with insuring the health of genetically endangered employees. In the rapidly developing universe of genetic intelligence, the employer is faced with a staggering dilemma.

  13. Preimplantation genetic diagnosis to improve pregnancy outcomes in subfertility.

    Science.gov (United States)

    Simpson, Joe Leigh

    2012-12-01

    Pre-implantation genetic diagnosis provides prenatal genetic diagnosis before implantation, thus allowing detection of chromosomal abnormalities and their exclusion from embryo transfer in assisted reproductive technologies. Polar body, blastomere or trophectoderm can each be used to obtain requisite genetic or embryonic DNA. Pre-implantation genetic diagnosis for excluding unbalanced translocations is well accepted, and pre-implantation genetic diagnosis aneuploidy testing to avoid repeated pregnancy losses in couples having recurrent aneuploidy is efficacious in reducing miscarriages. Controversy remains about whether pre-implantation genetic diagnosis aneuploidy testing improves take home pregnancy rates, for which reason adherence to specific indications is recommended while the issue is being adjudicated. Current recommendations are for obligatory 24 chromosome testing, most readily using array comparative genome hybridisation. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. 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.

  15. Genetic Engineering In BioButanol Production And Tolerance

    Directory of Open Access Journals (Sweden)

    Ashok Rao

    Full Text Available ABSTRACT 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. Higher-chain alcohols possess chemical properties that are more similar to gasoline. Ethanol and butanol are two products which are used as biofuel. Butanol production was more concerned than ethanol because of its high octane number. Unfortunately, these alcohols are not produced efficiently in natural microorganisms, and thus economical production in industrial volumes remains a challenge. The synthetic biology, however, offers additional tools to engineer synthetic pathways in user-friendly hosts to help increase titers and productivity of bio-butanol. Knock out and over-expression of genes is the major approaches towards genetic manipulation and metabolic engineering of microbes. Yet there are TargeTron Technology, Antisense RNA and CRISPR technology has a vital role in genome manipulation of C.acetobutylicum. This review concentrates on the recent developments for efficient production of butanol and butanol tolerance by various genetically engineered microbes.

  16. Tracking the emergence of synthetic biology.

    Science.gov (United States)

    Shapira, Philip; Kwon, Seokbeom; Youtie, Jan

    2017-01-01

    Synthetic biology is an emerging domain that combines biological and engineering concepts and which has seen rapid growth in research, innovation, and policy interest in recent years. This paper contributes to efforts to delineate this emerging domain by presenting a newly constructed bibliometric definition of synthetic biology. Our approach is dimensioned from a core set of papers in synthetic biology, using procedures to obtain benchmark synthetic biology publication records, extract keywords from these benchmark records, and refine the keywords, supplemented with articles published in dedicated synthetic biology journals. We compare our search strategy with other recent bibliometric approaches to define synthetic biology, using a common source of publication data for the period from 2000 to 2015. The paper details the rapid growth and international spread of research in synthetic biology in recent years, demonstrates that diverse research disciplines are contributing to the multidisciplinary development of synthetic biology research, and visualizes this by profiling synthetic biology research on the map of science. We further show the roles of a relatively concentrated set of research sponsors in funding the growth and trajectories of synthetic biology. In addition to discussing these analyses, the paper notes limitations and suggests lines for further work.

  17. Printability of Synthetic Papers by Electrophotography

    Directory of Open Access Journals (Sweden)

    Rozália Szentgyörgyvölgyi

    2010-04-01

    Full Text Available This paper deals with the printability of synthetic papers by the electrophotography technique. Prints of cmyk colour fields from 20% to 100% raster tone values were printed on three types of synthetic papers (one film synthetic paper and two fiber synthetic papers. The investigation of the appearance included densitometric measurement of the cmyk prints. The results have shown differences in the optical density and optical tone value between cmyk prints made on various synthetic papers. The highest optical density and the increase of the optical tone value were observed on the film synthetic paper, where cmyk prints were more saturated. The highest abrasion resistance of cmyk prints was obtained from the fibre synthetic paper.

  18. Layout Optimisation of Wave Energy Converter Arrays

    DEFF Research Database (Denmark)

    Ruiz, Pau Mercadé; Nava, Vincenzo; Topper, Mathew B. R.

    2017-01-01

    This paper proposes an optimisation strategy for the layout design of wave energy converter (WEC) arrays. Optimal layouts are sought so as to maximise the absorbed power given a minimum q-factor, the minimum distance between WECs, and an area of deployment. To guarantee an efficient optimisation......, a four-parameter layout description is proposed. Three different optimisation algorithms are further compared in terms of performance and computational cost. These are the covariance matrix adaptation evolution strategy (CMA), a genetic algorithm (GA) and the glowworm swarm optimisation (GSO) algorithm...

  19. Highly reproducible and sensitive silver nanorod array for the rapid detection of Allura Red in candy

    Science.gov (United States)

    Yao, Yue; Wang, Wen; Tian, Kangzhen; Ingram, Whitney Marvella; Cheng, Jie; Qu, Lulu; Li, Haitao; Han, Caiqin

    2018-04-01

    Allura Red (AR) is a highly stable synthetic red azo dye, which is widely used in the food industry to dye food and increase its attraction to consumers. However, the excessive consumption of AR can result in adverse health effects to humans. Therefore, a highly reproducible silver nanorod (AgNR) array was developed for surface enhanced Raman scattering (SERS) detection of AR in candy. The relative standard deviation (RSD) of AgNR substrate obtained from the same batch and different batches were 5.7% and 11.0%, respectively, demonstrating the high reproducibility. Using these highly reproducible AgNR arrays as the SERS substrates, AR was detected successfully, and its characteristic peaks were assigned by the density function theory (DFT) calculation. The limit of detection (LOD) of AR was determined to be 0.05 mg/L with a wide linear range of 0.8-100 mg/L. Furthermore, the AgNR SERS arrays can detect AR directly in different candy samples within 3 min without any complicated pretreatment. These results suggest the AgNR array can be used for rapid and qualitative SERS detection of AR, holding a great promise for expanding SERS application in food safety control field.

  20. Ischemic stroke after use of the synthetic marijuana “spice”

    Science.gov (United States)

    Freeman, Melissa J.; Rose, David Z.; Myers, Martin A.; Gooch, Clifton L.; Bozeman, Andrea C.

    2013-01-01

    Objectives: To report and associate acute cerebral infarctions in 2 young, previously healthy siblings with use of the street drug known as “spice” (a synthetic marijuana product, also known as “K2”), which they independently smoked before experiencing acute embolic-appearing ischemic strokes. Methods: We present history, physical examination, laboratory data, cerebrovascular imaging, echocardiogram, ECG, and hospital course of these patients. Results: We found that in both siblings spice was obtained from the same source. The drug was found to contain the schedule I synthetic cannabinoid JWH-018. Full stroke workup was unrevealing of a stroke etiology; urine drug screen was positive for marijuana. Conclusions: We found that our 2 patients who smoked the street drug spice had a temporal association with symptoms of acute cerebral infarction. This association may be confounded by contaminants in the product consumed (i.e., marijuana or an unidentified toxin) or by an unknown genetic mechanism. The imaging of both patients suggests an embolic etiology, which is consistent with reports of serious adverse cardiac events with spice use, including tachyarrhythmias and myocardial infarctions. PMID:24212384

  1. Bacteriophage-based synthetic biology for the study of infectious diseases

    Science.gov (United States)

    Lu, Timothy K.

    2014-01-01

    Since their discovery, bacteriophages have contributed enormously to our understanding of molecular biology as model systems. Furthermore, bacteriophages have provided many tools that have advanced the fields of genetic engineering and synthetic biology. Here, we discuss bacteriophage-based technologies and their application to the study of infectious diseases. New strategies for engineering genomes have the potential to accelerate the design of novel phages as therapies, diagnostics, and tools. Though almost a century has elapsed since their discovery, bacteriophages continue to have a major impact on modern biological sciences, especially with the growth of multidrug-resistant bacteria and interest in the microbiome. PMID:24997401

  2. Fiber-array based optogenetic prosthetic system for stimulation therapy

    Science.gov (United States)

    Gu, Ling; Cote, Chris; Tejeda, Hector; Mohanty, Samarendra

    2012-02-01

    Recent advent of optogenetics has enabled activation of genetically-targeted neuronal cells using low intensity blue light with high temporal precision. Since blue light is attenuated rapidly due to scattering and absorption in neural tissue, optogenetic treatment of neurological disorders may require stimulation of specific cell types in multiple regions of the brain. Further, restoration of certain neural functions (vision, and auditory etc) requires accurate spatio-temporal stimulation patterns rather than just precise temporal stimulation. In order to activate multiple regions of the central nervous system in 3D, here, we report development of an optogenetic prosthetic comprising of array of fibers coupled to independently-controllable LEDs. This design avoids direct contact of LEDs with the brain tissue and thus does not require electrical and heat isolation, which can non-specifically stimulate and damage the local brain regions. The intensity, frequency, and duty cycle of light pulses from each fiber in the array was controlled independently using an inhouse developed LabView based program interfaced with a microcontroller driving the individual LEDs. While the temporal profile of the light pulses was controlled by varying the current driving the LED, the beam profile emanating from each fiber tip could be sculpted by microfabrication of the fiber tip. The fiber array was used to stimulate neurons, expressing channelrhodopsin-2, in different locations within the brain or retina. Control of neural activity in the mice cortex, using the fiber-array based prosthetic, is evaluated from recordings made with multi-electrode array (MEA). We also report construction of a μLED array based prosthetic for spatio-temporal stimulation of cortex.

  3. Evolvable synthetic neural system

    Science.gov (United States)

    Curtis, Steven A. (Inventor)

    2009-01-01

    An evolvable synthetic neural system includes an evolvable neural interface operably coupled to at least one neural basis function. Each neural basis function includes an evolvable neural interface operably coupled to a heuristic neural system to perform high-level functions and an autonomic neural system to perform low-level functions. In some embodiments, the evolvable synthetic neural system is operably coupled to one or more evolvable synthetic neural systems in a hierarchy.

  4. Synthetic Training Data Generation for Activity Monitoring and Behavior Analysis

    Science.gov (United States)

    Monekosso, Dorothy; Remagnino, Paolo

    This paper describes a data generator that produces synthetic data to simulate observations from an array of environment monitoring sensors. The overall goal of our work is to monitor the well-being of one occupant in a home. Sensors are embedded in a smart home to unobtrusively record environmental parameters. Based on the sensor observations, behavior analysis and modeling are performed. However behavior analysis and modeling require large data sets to be collected over long periods of time to achieve the level of accuracy expected. A data generator - was developed based on initial data i.e. data collected over periods lasting weeks to facilitate concurrent data collection and development of algorithms. The data generator is based on statistical inference techniques. Variation is introduced into the data using perturbation models.

  5. Shared genetics underlying epidemiological association between endometriosis and ovarian cancer

    DEFF Research Database (Denmark)

    Lu, Yi; Cuellar-Partida, Gabriel; Painter, Jodie N

    2015-01-01

    Epidemiological studies have demonstrated associations between endometriosis and certain histotypes of ovarian cancer, including clear cell, low-grade serous and endometrioid carcinomas. We aimed to determine whether the observed associations might be due to shared genetic aetiology. To address...... this, we used two endometriosis datasets genotyped on common arrays with full-genome coverage (3194 cases and 7060 controls) and a large ovarian cancer dataset genotyped on the customized Illumina Infinium iSelect (iCOGS) arrays (10 065 cases and 21 663 controls). Previous work has suggested...... that a large number of genetic variants contribute to endometriosis and ovarian cancer (all histotypes combined) susceptibility. Here, using the iCOGS data, we confirmed polygenic architecture for most histotypes of ovarian cancer. This led us to evaluate if the polygenic effects are shared across diseases. We...

  6. 2D Doppler backscattering using synthetic aperture microwave imaging of MAST edge plasmas

    Science.gov (United States)

    Thomas, D. A.; Brunner, K. J.; Freethy, S. J.; Huang, B. K.; Shevchenko, V. F.; Vann, R. G. L.

    2016-02-01

    Doppler backscattering (DBS) is already established as a powerful diagnostic; its extension to 2D enables imaging of turbulence characteristics from an extended region of the cut-off surface. The Synthetic Aperture Microwave Imaging (SAMI) diagnostic has conducted proof-of-principle 2D DBS experiments of MAST edge plasma. SAMI actively probes the plasma edge using a wide (±40° vertical and horizontal) and tuneable (10-34.5 GHz) beam. The Doppler backscattered signal is digitised in vector form using an array of eight Vivaldi PCB antennas. This allows the receiving array to be focused in any direction within the field of view simultaneously to an angular range of 6-24° FWHM at 10-34.5 GHz. This capability is unique to SAMI and is a novel way of conducting DBS experiments. In this paper the feasibility of conducting 2D DBS experiments is explored. Initial observations of phenomena previously measured by conventional DBS experiments are presented; such as momentum injection from neutral beams and an abrupt change in power and turbulence velocity coinciding with the onset of H-mode. In addition, being able to carry out 2D DBS imaging allows a measurement of magnetic pitch angle to be made; preliminary results are presented. Capabilities gained through steering a beam using a phased array and the limitations of this technique are discussed.

  7. Molecular identification of common Salmonella serovars using multiplex DNA sensor-based suspension array.

    Science.gov (United States)

    Aydin, Muhsin; Carter-Conger, Jacqueline; Gao, Ning; Gilmore, David F; Ricke, Steven C; Ahn, Soohyoun

    2018-04-01

    Salmonella is one of major foodborne pathogens and the leading cause of foodborne illness-related hospitalizations and deaths. It is critical to develop a sensitive and rapid detection assay that can identify Salmonella to ensure food safety. In this study, a DNA sensor-based suspension array system of high multiplexing ability was developed to identify eight Salmonella serovars commonly associated with foodborne outbreaks to the serotype level. Each DNA sensor was prepared by activating pre-encoded microspheres with oligonucleotide probes that are targeting virulence genes and serovar-specific regions. The mixture of 12 different types of DNA sensors were loaded into a 96-well microplate and used as a 12-plex DNA sensor array platform. DNA isolated from Salmonella was amplified by multiplex polymerase chain reaction (mPCR), and the presence of Salmonella was determined by reading fluorescent signals from hybridization between probes on DNA sensors and fluorescently labeled target DNA using the Bio-Plex® system. The developed multiplex array was able to detect synthetic DNA at the concentration as low as 100 fM and various Salmonella serovars as low as 100 CFU/mL within 1 h post-PCR. Sensitivity of this assay was further improved to 1 CFU/mL with 6-h enrichment. The array system also correctly and specifically identified serotype of tested Salmonella strains without any cross-reactivity with other common foodborne pathogens. Our results indicate the developed DNA sensor suspension array can be a rapid and reliable high-throughput method for simultaneous detection and molecular identification of common Salmonella serotypes.

  8. Association between genetic subgroups of pancreatic ductal adenocarcinoma defined by high density 500 K SNP-arrays and tumor histopathology.

    Directory of Open Access Journals (Sweden)

    María Laura Gutiérrez

    Full Text Available The specific genes and genetic pathways associated with pancreatic ductal adenocarcinoma are still largely unknown partially due to the low resolution of the techniques applied so far to their study. Here we used high-density 500 K single nucleotide polymorphism (SNP-arrays to define those chromosomal regions which most commonly harbour copy number (CN alterations and loss of heterozygozity (LOH in a series of 20 PDAC tumors and we correlated the corresponding genetic profiles with the most relevant clinical and histopathological features of the disease. Overall our results showed that primary PDAC frequently display (>70% extensive gains of chromosomes 1q, 7q, 8q and 20q, together with losses of chromosomes 1p, 9p, 12q, 17p and 18q, such chromosomal regions harboring multiple cancer- and PDAC-associated genes. Interestingly, these alterations clustered into two distinct genetic profiles characterized by gains of the 2q14.2, 3q22.1, 5q32, 10q26.13, 10q26.3, 11q13.1, 11q13.3, 11q13.4, 16q24.1, 16q24.3, 22q13.1, 22q13.31 and 22q13.32 chromosomal regions (group 1; n = 9 versus gains at 1q21.1 and losses of the 1p36.11, 6q25.2, 9p22.1, 9p24.3, 17p13.3 and Xp22.33 chromosomal regions (group 2; n = 11. From the clinical and histopathological point of view, group 1 cases were associated with smaller and well/moderately-differentiated grade I/II PDAC tumors, whereas and group 2 PDAC displayed a larger size and they mainly consisted of poorly-differentiated grade III carcinomas. These findings confirm the cytogenetic complexity and heterozygozity of PDAC and provide evidence for the association between tumor cytogenetics and its histopathological features. In addition, we also show that the altered regions identified harbor multiple cancer associate genes that deserve further investigation to determine their relevance in the pathogenesis of PDAC.

  9. Synthetic Cathinones ("Bath Salts")

    Science.gov (United States)

    ... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

  10. Application of chemical arrays in screening elastase inhibitors.

    Science.gov (United States)

    Gao, Feng; Du, Guan-Hua

    2006-06-01

    Protein chip technology provides a new and useful tool for high-throughput screening of drugs because of its high performance and low sample consumption. In order to screen elastase inhibitors on a large scale, we designed a composite microarray integrating enzyme chip containing chemical arrays on glass slides to screen for enzymatic inhibitors. The composite microarray includes an active proteinase film, screened chemical arrays distributed on the film, and substrate microarrays to demonstrate change of color. The detection principle is that elastase hydrolyzes synthetic colorless substrates and turns them into yellow products. Because yellow is difficult to detect, bromochlorophenol blue (BPB) was added into substrate solutions to facilitate the detection process. After the enzyme had catalyzed reactions for 2 h, effects of samples on enzymatic activity could be determined by detecting color change of the spots. When chemical samples inhibited enzymatic activity, substrates were blue instead of yellow products. If the enzyme retained its activity, the yellow color of the products combined with blue of BPB to make the spots green. Chromogenic differences demonstrated whether chemicals inhibited enzymatic activity or not. In this assay, 11,680 compounds were screened, and two valuable chemical hits were identified, which demonstrates that this assay is effective, sensitive and applicable for high-throughput screening (HTS).

  11. Pattern Nulling of Linear Antenna Arrays Using Backtracking Search Optimization Algorithm

    Directory of Open Access Journals (Sweden)

    Kerim Guney

    2015-01-01

    Full Text Available An evolutionary method based on backtracking search optimization algorithm (BSA is proposed for linear antenna array pattern synthesis with prescribed nulls at interference directions. Pattern nulling is obtained by controlling only the amplitude, position, and phase of the antenna array elements. BSA is an innovative metaheuristic technique based on an iterative process. Various numerical examples of linear array patterns with the prescribed single, multiple, and wide nulls are given to illustrate the performance and flexibility of BSA. The results obtained by BSA are compared with the results of the following seventeen algorithms: particle swarm optimization (PSO, genetic algorithm (GA, modified touring ant colony algorithm (MTACO, quadratic programming method (QPM, bacterial foraging algorithm (BFA, bees algorithm (BA, clonal selection algorithm (CLONALG, plant growth simulation algorithm (PGSA, tabu search algorithm (TSA, memetic algorithm (MA, nondominated sorting GA-2 (NSGA-2, multiobjective differential evolution (MODE, decomposition with differential evolution (MOEA/D-DE, comprehensive learning PSO (CLPSO, harmony search algorithm (HSA, seeker optimization algorithm (SOA, and mean variance mapping optimization (MVMO. The simulation results show that the linear antenna array synthesis using BSA provides low side-lobe levels and deep null levels.

  12. New designer drugs (synthetic cannabinoids and synthetic cathinones): review of literature.

    Science.gov (United States)

    Cottencin, Olivier; Rolland, Benjamin; Karila, Laurent

    2014-01-01

    New designer drugs (synthetic cannabinoids and synthetic cathinones) are new "legal highs" that are sold online for recreational public or private use. Synthetic cannabinoids are psychoactive herbal and chemical products that mimic the effects of cannabis when used. These drugs are available on the Internet or in head shops as incense or air fresheners to circumvent the law. Cathinone is a naturally occurring beta-ketone amphetamine analog found in the leaves of the Catha edulis plant. Synthetic cathinones are phenylalkylamine derivatives that may possess amphetamine-like properties. These drugs are sold online as bath salts. Designer drugs are often labeled as "not for human consumption" to circumvent drug abuse legislation. The absence of legal risks, the ease of obtaining these drugs, the moderate cost, and the availability via the Internet are the main features that attract users, but the number of intoxicated people presenting with emergencies is increasing. There is evidence that negative health and social consequences may affect recreational and chronic users. The addictive potential of designer drugs is not negligible.

  13. Rewiring cells: synthetic biology as a tool to interrogate the organizational principles of living systems.

    Science.gov (United States)

    Bashor, Caleb J; Horwitz, Andrew A; Peisajovich, Sergio G; Lim, Wendell A

    2010-01-01

    The living cell is an incredibly complex entity, and the goal of predictively and quantitatively understanding its function is one of the next great challenges in biology. Much of what we know about the cell concerns its constituent parts, but to a great extent we have yet to decode how these parts are organized to yield complex physiological function. Classically, we have learned about the organization of cellular networks by disrupting them through genetic or chemical means. The emerging discipline of synthetic biology offers an additional, powerful approach to study systems. By rearranging the parts that comprise existing networks, we can gain valuable insight into the hierarchical logic of the networks and identify the modular building blocks that evolution uses to generate innovative function. In addition, by building minimal toy networks, one can systematically explore the relationship between network structure and function. Here, we outline recent work that uses synthetic biology approaches to investigate the organization and function of cellular networks, and describe a vision for a synthetic biology toolkit that could be used to interrogate the design principles of diverse systems.

  14. Current status of synthetic epikeratoplasty.

    Science.gov (United States)

    Thompson, K P; Hanna, K; Waring, G O; Gipson, I; Liu, Y; Gailitis, R P; Johnson-Wint, B; Green, K

    1991-01-01

    Many of the deficiencies with human tissue epikeratoplasty might be improved by the use of a suitable synthetic lenticule. Potential biomaterials for epikeratoplasty include collagen (types I, III, or IV), collagen-hydrogel copolymers, bioactive synthetics, and coated hydrogels. The biomaterial must be engineered to achieve strict specifications of optical clarity, support of epithelial migration and adhesion, permeability to solutes, and stability to corneal proteases. Attaching synthetic lenticules to the cornea without cutting Bowman's layer by adhesives, laser welding, or direct adhesion may also improve the efficacy of synthetic epikeratoplasty.

  15. Tissue Harmonic Synthetic Aperture Imaging

    DEFF Research Database (Denmark)

    Rasmussen, Joachim

    The main purpose of this PhD project is to develop an ultrasonic method for tissue harmonic synthetic aperture imaging. The motivation is to advance the field of synthetic aperture imaging in ultrasound, which has shown great potentials in the clinic. Suggestions for synthetic aperture tissue...... system complexity compared to conventional synthetic aperture techniques. In this project, SASB is sought combined with a pulse inversion technique for 2nd harmonic tissue harmonic imaging. The advantages in tissue harmonic imaging (THI) are expected to further improve the image quality of SASB...

  16. Life after the synthetic cell

    DEFF Research Database (Denmark)

    Rasmussen, Steen

    2010-01-01

    Nature asked eight synthetic-biology experts about the implications for science and society of the “synthetic cell” made by the J. Craig Venter Institute (JCVI). The institute's team assembled, modified and implanted a synthesized genome into a DNA-free bacterial shell to make a self-replicating ......Nature asked eight synthetic-biology experts about the implications for science and society of the “synthetic cell” made by the J. Craig Venter Institute (JCVI). The institute's team assembled, modified and implanted a synthesized genome into a DNA-free bacterial shell to make a self...

  17. Efficient Analysis of Systems Biology Markup Language Models of Cellular Populations Using Arrays.

    Science.gov (United States)

    Watanabe, Leandro; Myers, Chris J

    2016-08-19

    The Systems Biology Markup Language (SBML) has been widely used for modeling biological systems. Although SBML has been successful in representing a wide variety of biochemical models, the core standard lacks the structure for representing large complex regular systems in a standard way, such as whole-cell and cellular population models. These models require a large number of variables to represent certain aspects of these types of models, such as the chromosome in the whole-cell model and the many identical cell models in a cellular population. While SBML core is not designed to handle these types of models efficiently, the proposed SBML arrays package can represent such regular structures more easily. However, in order to take full advantage of the package, analysis needs to be aware of the arrays structure. When expanding the array constructs within a model, some of the advantages of using arrays are lost. This paper describes a more efficient way to simulate arrayed models. To illustrate the proposed method, this paper uses a population of repressilator and genetic toggle switch circuits as examples. Results show that there are memory benefits using this approach with a modest cost in runtime.

  18. 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.

  19. Profile of genetic disorders prevalent in northeast region of Cairo ...

    African Journals Online (AJOL)

    Rabah M. Shawky

    2012-02-04

    Feb 4, 2012 ... syndromes, multiple genetic disorders in the same individual or same family and homozygosity ...... array of hereditary eye disorders has been identified. These in- ..... of ED, decreased sweating was present in 92%, dry skin in.

  20. Optimization of modal filters based on arrays of piezoelectric sensors

    International Nuclear Information System (INIS)

    Pagani, Carlos C Jr; Trindade, Marcelo A

    2009-01-01

    Modal filters may be obtained by a properly designed weighted sum of the output signals of an array of sensors distributed on the host structure. Although several research groups have been interested in techniques for designing and implementing modal filters based on a given array of sensors, the effect of the array topology on the effectiveness of the modal filter has received much less attention. In particular, it is known that some parameters, such as size, shape and location of a sensor, are very important in determining the observability of a vibration mode. Hence, this paper presents a methodology for the topological optimization of an array of sensors in order to maximize the effectiveness of a set of selected modal filters. This is done using a genetic algorithm optimization technique for the selection of 12 piezoceramic sensors from an array of 36 piezoceramic sensors regularly distributed on an aluminum plate, which maximize the filtering performance, over a given frequency range, of a set of modal filters, each one aiming to isolate one of the first vibration modes. The vectors of the weighting coefficients for each modal filter are evaluated using QR decomposition of the complex frequency response function matrix. Results show that the array topology is not very important for lower frequencies but it greatly affects the filter effectiveness for higher frequencies. Therefore, it is possible to improve the effectiveness and frequency range of a set of modal filters by optimizing the topology of an array of sensors. Indeed, using 12 properly located piezoceramic sensors bonded on an aluminum plate it is shown that the frequency range of a set of modal filters may be enlarged by 25–50%

  1. 3D-QSAR Investigation of Synthetic Antioxidant Chromone Derivatives by Molecular Field Analysis

    Directory of Open Access Journals (Sweden)

    Jiraporn Ungwitayatorn

    2008-02-01

    Full Text Available A series of 7-hydroxy, 8-hydroxy and 7,8-dihydroxy synthetic chromone derivatives was evaluated for their DPPH free radical scavenging activities. A training set of 30 synthetic chromone derivatives was subject to three-dimensional quantitative structure-activity relationship (3D-QSAR studies using molecular field analysis (MFA. The substitutional requirements for favorable antioxidant activity were investigated and a predictive model that could be used for the design of novel antioxidants was derived. Regression analysis was carried out using genetic partial least squares (G/PLS method. A highly predictive and statistically significant model was generated. The predictive ability of the developed model was assessed using a test set of 5 compounds (r2pred = 0.924. The analyzed MFA model demonstrated a good fit, having r2 value of 0.868 and crossvalidated coefficient r2cv value of 0.771.

  2. Biologically-inspired synthetic dry adhesives for wall-climbing robots

    Science.gov (United States)

    Murphy, Michael P.

    Animals such as insects, spiders, and lizards are capable of clinging to and climbing on a variety of surfaces, from rough stone to smooth silicon. Hairy microscale arrays of structures on their feet conform to surface roughness to create millions of points of contact, creating a large overall contact area. Weak intermolecular forces (van der Waals forces) between each fiber tip and the surface sum to large overall forces due to the high number of contacts. In this work we present the fabrication, characterization, and demonstration of synthetic polyurethane fibrillar adhesives inspired by these animals. Angled polymer micro-fiber arrays are fabricated and characterized. A tip modification technique is presented which enables fabrication of fibers with flat mushroom shaped tips which greatly increase the adhesion of the fibers, up to 5N/cm 2 (normal direction), and with a magnitude within the range of geckos (10 N/cm2) in the shear direction on smooth surfaces. We present a fabrication technique to create fibers with angled flat mushroom-shaped tips which replicate the directional characteristics of geckos, gripping in one direction (within the range of gecko adhesion) and releasing easily in the other. Multilevel hierarchical structures with specialized tips for roughness adaptation are also presented. Fiber hierarchies from the millimeter scale to the sub-micron scale are demonstrated, including three-level fiber fabrication with specialized tips. Hierarchical structures demonstrate up to 5 times the adhesion of an unstructured sample, and requiring up to 10 times the detachment energy. Finally, an agile, wireless, palm-sized wall climbing robot which uses the synthetic fibrillar dry adhesives to climb is presented. Waalbot , named after the van der Waals forces it uses to climb, exploits the attachment and detachment characteristics of the developed dry adhesives, capabilities include climbing smooth surfaces such as glass in any orientation on any surface slope

  3. Microlens array processor with programmable weight mask and direct optical input

    Science.gov (United States)

    Schmid, Volker R.; Lueder, Ernst H.; Bader, Gerhard; Maier, Gert; Siegordner, Jochen

    1999-03-01

    We present an optical feature extraction system with a microlens array processor. The system is suitable for online implementation of a variety of transforms such as the Walsh transform and DCT. Operating with incoherent light, our processor accepts direct optical input. Employing a sandwich- like architecture, we obtain a very compact design of the optical system. The key elements of the microlens array processor are a square array of 15 X 15 spherical microlenses on acrylic substrate and a spatial light modulator as transmissive mask. The light distribution behind the mask is imaged onto the pixels of a customized a-Si image sensor with adjustable gain. We obtain one output sample for each microlens image and its corresponding weight mask area as summation of the transmitted intensity within one sensor pixel. The resulting architecture is very compact and robust like a conventional camera lens while incorporating a high degree of parallelism. We successfully demonstrate a Walsh transform into the spatial frequency domain as well as the implementation of a discrete cosine transform with digitized gray values. We provide results showing the transformation performance for both synthetic image patterns and images of natural texture samples. The extracted frequency features are suitable for neural classification of the input image. Other transforms and correlations can be implemented in real-time allowing adaptive optical signal processing.

  4. A comparison between genotyping-by-sequencing and array-based scoring of SNPs for genomic prediction accuracy in winter wheat.

    Science.gov (United States)

    Elbasyoni, Ibrahim S; Lorenz, A J; Guttieri, M; Frels, K; Baenziger, P S; Poland, J; Akhunov, E

    2018-05-01

    The utilization of DNA molecular markers in plant breeding to maximize selection response via marker-assisted selection (MAS) and genomic selection (GS) has revolutionized plant breeding. A key factor affecting GS applicability is the choice of molecular marker platform. Genotyping-by-sequencing scored SNPs (GBS-scored SNPs) provides a large number of markers, albeit with high rates of missing data. Array scored SNPs are of high quality, but the cost per sample is substantially higher. The objectives of this study were 1) compare GBS-scored SNPs, and array scored SNPs for genomic selection applications, and 2) compare estimates of genomic kinship and population structure calculated using the two marker platforms. SNPs were compared in a diversity panel consisting of 299 hard winter wheat (Triticum aestivum L.) accessions that were part of a multi-year, multi-environments association mapping study. The panel was phenotyped in Ithaca, Nebraska for heading date, plant height, days to physiological maturity and grain yield in 2012 and 2013. The panel was genotyped using GBS-scored SNPs, and array scored SNPs. Results indicate that GBS-scored SNPs is comparable to or better than Array-scored SNPs for genomic prediction application. Both platforms identified the same genetic patterns in the panel where 90% of the lines were classified to common genetic groups. Overall, we concluded that GBS-scored SNPs have the potential to be the marker platform of choice for genetic diversity and genomic selection in winter wheat. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. A Parasitic Array Receiver for ISAR Imaging of Ship Targets Using a Coastal Radar

    Directory of Open Access Journals (Sweden)

    Fabrizio Santi

    2016-01-01

    Full Text Available The detection and identification of ship targets navigating in coastal areas are essential in order to prevent maritime accidents and to take countermeasures against illegal activities. Usually, coastal radar systems are employed for the detection of vessels, whereas noncooperative ship targets as well as ships not equipped with AIS transponders can be identified by means of dedicated active radar imaging system by means of ISAR processing. In this work, we define a parasitic array receiver for ISAR imaging purposes based on the signal transmitted by an opportunistic coastal radar over its successive scans. In order to obtain the proper cross-range resolution, the physical aperture provided by the array is combined with the synthetic aperture provided by the target motion. By properly designing the array of passive devices, the system is able to correctly observe the signal reflected from the ships over successive scans of the coastal radar. Specifically, the upper bounded interelement spacing provides a correct angular sampling accordingly to the Nyquist theorem and the lower bounded number of elements of the array ensures the continuity of the observation during multiple scans. An ad hoc focusing technique has been then proposed to provide the ISAR images of the ships. Simulated analysis proved the effectiveness of the proposed system to provide top-view images of ship targets suitable for ATR procedures.

  6. [60 years of medical genetics in Israel].

    Science.gov (United States)

    Shalev, Stavit A; Borochowitz, Zvi U; Zlotogora, Joel

    2010-02-01

    The principle deeds of genetics in Israel consist of a wide array of disciplines including agriculture, nutrients, biotechnology, pharmacology and pharmacogenetics, pertaining to criminal as well as medical aspects. In the scope of this state of the art historical review, the authors emphasize the medical issues. The initial stimulus for genetic studies and medical awareness among the various ethnic populations in Israel was the immigration, in the early 1950s, of over a million Jewish immigrants from more than 100 countries from all continents. It was soon recognized that frequencies of genetic diseases differed markedly among the various communities, serving as a trigger for studying and managing these populations. In this state of the art historical review, particular emphasize was given to the historical events concerning genetics in the land of Israel, as well as in the state of Israel. Highlights of genetic diversity of the various ethnic and sub-populations are added, along with the advances and major achievements of the human genetics discipline in the state of Israel.

  7. Creating biological nanomaterials using synthetic biology

    International Nuclear Information System (INIS)

    Rice, MaryJoe K; Ruder, Warren C

    2014-01-01

    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. (review)

  8. 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.

  9. Synthetic Defects for Vibrothermography

    Science.gov (United States)

    Renshaw, Jeremy; Holland, Stephen D.; Thompson, R. Bruce; Eisenmann, David J.

    2010-02-01

    Synthetic defects are an important tool used for characterizing the performance of nondestructive evaluation techniques. Viscous material-filled synthetic defects were developed for use in vibrothermography (also known as sonic IR) as a tool to improve inspection accuracy and reliability. This paper describes how the heat-generation response of these VMF synthetic defects is similar to the response of real defects. It also shows how VMF defects can be applied to improve inspection accuracy for complex industrial parts and presents a study of their application in an aircraft engine stator vane.

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

    Science.gov (United States)

    Roehner, Nicholas; Myers, Chris J

    2014-02-21

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

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

    Science.gov (United States)

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

    2014-06-01

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

  12. Potencial genético de um sintético de milho de grãos duros para formação de híbridos Genetic potential of a flint maize synthetic for hybrid production

    Directory of Open Access Journals (Sweden)

    Elto Eugenio Gomes e Gama

    2003-08-01

    Full Text Available O objetivo deste estudo foi determinar através das estimativas de parâmetros genéticos o potencial de um sintético de milho de grãos duros e de ciclo semiprecoce, para a formação de híbridos e/ou melhoramento intrapopulacional. Foram utilizadas 142 progênies endogâmicas S2 do Sin EEL Flint, em cruzamentos topcrosses com um Sintético heteroticamente contrastante. Essas progênies topcrosses foram avaliadas utilizando-se o delineamento em látice simples 12 x 12, e em dois locais de teste. Os maiores valores médios para PED foram observados para os topcrosses n.º 101 (12069kg ha-1 e nº 72 (11068Kg ha-1, tendo o primeiro apresentado comportamento específico para Londrina, e o segunda demonstrado comportamento superior nos dois ambientes. Os valores das estimativas dos parâmetros estudados foram semelhantes aos encontrados em alguns estudos conduzidos em condições tropicais. O grupo de progênies S2 da Sin EEL Flint conduziu a valores médios de , CVg e h² similares aos encontrados na literatura para outros genótipos. Observa-se que esse Sintético possui suficiente variabilidade genética e potencial para extração de linhagens para formação de híbridos e como germoplasma em programas de melhoramento.The objective of this study was to determine the genetic potential of a semi-early maize synthetic with flint type kernel (Sin EEL Flint. The estimation of genetic parameters was obtained with S2 progenies, and the performance of the progenies in hybrid combinations were evaluated. One hundred fourty-two S2 progenies of Sin EEL Flint were used. They were obtained by top crossings with a contrasting heterotic synthetic of dent type kernel. These topcross progenies were tested in a lattice design 12 x 12 with two replications in two locations, Sete Lagoas and Londrina. The selected topcross nº 101, with specific adaptation for Londrina. and nº72, being adapted to both locations, were the best yieldings (PED with 12069Kg ha-1 and

  13. Application of the micro-array comparative genomic hybridization technology in preimplantation genetic diagnosis%Array-CGH技术在胚胎植入前遗传学诊断中的应用进展

    Institute of Scientific and Technical Information of China (English)

    韩丹; 陈大蔚; 曹云霞; 周平

    2015-01-01

    As a new kind high-throughput genomics technology, micro array-based comparative genomic hybridization (aCGH) has brought the huge change for molecular biology and medical research. Because of the detection range covers the whole genome, high efficiency, easy operation etc, aCGH has been widely used in many areas of human genetic disease diagnosis, tumor genomics, systems biology and prenatal diagnosis. Human preimplantation genetic diagnosis (PGD) is an important part of assisted reproductive technology, with the development of molecular genetics technology, its application range is continuously widening. Based on aCGH technology in PGD for embryonic whole genome screening for aneuploidy and structural abnormalities, human PGD/human preimplantation genetic screening (PGS) implantation rate and clinical pregnancy rate have improved significantly. In this article, we discussed the advantages, disadvantages and prospects of aCGH in prenatal diagnosis.%微阵列比较基因组杂交(aCGH)作为一种新兴的高通量检测技术,给分子生物学及医学研究带来了巨大变化,因其检测范围覆盖全基因组、高效率、操作简便等特点,在人类遗传疾病诊断,肿瘤基因组学,系统生物学研究及产前诊断中已有了广泛应用。植入前遗传学诊断(PGD)是辅助生殖技术的重要组成部分,随着分子遗传学技术的发展,其应用范围也不断拓宽。基于aCGH技术在PGD中对胚胎全染色体组非整倍体及结构异常的筛查,PGD/植入前遗传学筛查(PGS)胚胎植入率和临床妊娠率均有显著提高,本文就aCGH技术在胚胎植入前遗传学诊断中的应用进行综述。

  14. Cu-implanted ZnO nanorods array film: An aqueous synthetic approach

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Ajaya Kumar, E-mail: ajayaksingh_au@yahoo.co.in [Department of Chemistry, Govt. VYT PG. Autonomous College Durg, Chhattisgarh (India); Thool, Gautam Sheel [Department of Chemistry, Govt. VYT PG. Autonomous College Durg, Chhattisgarh (India); Singh, R.S. [Department of Physics, Govt. D.T. College, Utai, Durg, Chhattisgarh (India); Singh, Surya Prakash, E-mail: spsingh@iict.res.in [Inorganic and Physical Chemistry Division, CSIR-Indian Institute of Chemical Technology, Uppal road, Tarnaka, Hyderabad 500007 (India)

    2015-01-05

    Highlights: • Cu doped ZnO nanorods were synthesized using low temperature aqueous solution method. • We demonstrated the capping action of TEA via theoretical simulation. • Raman analysis revealed the presence of tensile strain in Cu doped ZnO nanorods. • Growth rate was found to be high in Cu doped ZnO nanorods. - Abstract: Pure and Cu doped ZnO nanorods array are synthesized via two step chemical bath deposition method. The seed layer is prepared by successive ionic layer adsorption reaction (SILAR) method. The synthesized materials have been systematically characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray (EDAX), Raman spectroscopy, Fourier transform infrared (FTIR) spectroscopy and photoluminescence (PL) spectroscopy. SEM pictures show the existence of vertically well aligned hexagonal ZnO nanorods. EDAX spectrum confirms the presence of Cu in ZnO nanorods. High intense peak of (0 0 2) plane and E{sub 2}{sup high} mode for XRD and Raman spectrum respectively, suggest the ZnO nanorods are adopted c-axis orientation perpendicular to substrate. XRD and Raman analysis shows the presence of tensile strain in Cu doped ZnO nanorods. Effect of Cu doping on lattice constants, unit cell volume and Zn–O bond length of ZnO nanorods have also been studied. Room temperature PL measurement exhibits two luminescence bands in the spectra i.e. UV emission centered at 3.215 eV and a broad visible band. Theoretical investigation for capping action of triethanolamine is done by Hartree–Fock (HF) method with 3-21G basis set using Gaussian 09 program package.

  15. TMTI Task 1.6 Genetic Engineering Methods and Detection

    Energy Technology Data Exchange (ETDEWEB)

    Slezak, T; Lenhoff, R; Allen, J; Borucki, M; Vitalis, E; Gardner, S

    2009-12-04

    A large number of GE techniques can be adapted from other microorganisms to biothreat bacteria and viruses. Detection of GE in a microorganism increases in difficulty as the size of the genetic change decreases. In addition to the size of the engineered change, the consensus genomic sequence of the microorganism can impact the difficulty of detecting an engineered change in genomes that are highly variable from strain to strain. This problem will require comprehensive databases of whole genome sequences for more genetically variable biothreat bacteria and viruses. Preliminary work with microarrays for detecting synthetic elements or virulence genes and analytic bioinformatic approaches for whole genome sequence comparison to detect genetic engineering show promise for attacking this difficult problem but a large amount of future work remains.

  16. Synthetic Jet Interactions with Flows of Varying Separation Severity and Spanwise Flow Magnitude

    Science.gov (United States)

    Monastero, Marianne; Lindstrom, Annika; Amitay, Michael

    2017-11-01

    Flow physics associated with the interactions of synthetic jet actuators with a highly three-dimensional separated flow over a flapped airfoil were investigated experimentally and analyzed using stereo particle image velocimetry (SPIV) and surface pressure data. Increased understanding of active flow control devices in flows which are representative of airplane wings or tails can lead to actuator placement (i.e., chordwise location, spanwise spacing) with the greatest beneficial effect on performance. An array of discrete synthetic jets was located just upstream of the control surface hingeline and operated at a blowing ratio of 1 and non-dimensional frequency of 48. Detailed flowfield measurements over the control surface were conducted, where the airfoil's sweep angle and the control surface deflection angle were fixed at 20°. Focus was placed on the local and global flowfields as spanwise actuator spacing was varied. Moreover, surface pressure measurement for several sweep angles, control surface deflection angles, and angles of attack were also performed. Actuation resulted in an overall separation reduction and a dependence of local flowfield details (i.e. separation severity, spanwise flow magnitude, flow structures, and jet trajectory) on spanwise jet spacing. The Boeing Company.

  17. A Canadian refiner's perspective of synthetic crudes

    International Nuclear Information System (INIS)

    Halford, T.L.; McIntosh, A.P.; Rasmussen

    1997-01-01

    Some of the factors affecting a refiner's choice of crude oil include refinery hardware, particularly gas oil crackers, products slate and product specifications, crude availability, relative crude price and crude quality. An overview of synthetic crude, the use of synthetic crude combined with other crudes and a comparison of synthetic crude with conventional crude oil was given. The two main users of synthetic crude are basically two groups of refiners, those large groups who use synthetic crude combined with other crudes, and a smaller group who run synthetic crude on specially designed units as a sole feed. The effects of changes in fuel legislation were reviewed. It was predicted that the changes will have a mixed impact on the value of synthetic crude, but low sulphur diesel regulations and gasoline sulphur regulations will make current synthetic crudes attractive. The big future change with a negative impact will be diesel cetane increases to reduce engine emissions. This will reduce synthetic crude attractiveness due to distillate yields and quality and high gas oil yields. Similarly, any legislation limiting aromatics in diesel fuel will also make synthetic crudes less attractive. Problems experienced by refiners with hardware dedicated to synthetic crude (salt, naphthenic acid, fouling, quality variations) were also reviewed. 3 tabs

  18. A SNP Genotyping Array for Hexaploid Oat

    Directory of Open Access Journals (Sweden)

    Nicholas A. Tinker

    2014-11-01

    Full Text Available Recognizing a need in cultivated hexaploid oat ( L. for a reliable set of reference single nucleotide polymorphisms (SNPs, we have developed a 6000 (6K BeadChip design containing 257 Infinium I and 5486 Infinium II designs corresponding to 5743 SNPs. Of those, 4975 SNPs yielded successful assays after array manufacturing. These SNPs were discovered based on a variety of bioinformatics pipelines in complementary DNA (cDNA and genomic DNA originating from 20 or more diverse oat cultivars. The array was validated in 1100 samples from six recombinant inbred line (RIL mapping populations and sets of diverse oat cultivars and breeding lines, and provided approximately 3500 discernible Mendelian polymorphisms. Here, we present an annotation of these SNPs, including methods of discovery, gene identification and orthology, population-genetic characteristics, and tentative positions on an oat consensus map. We also evaluate a new cluster-based method of calling SNPs. The SNP design sequences are made publicly available, and the full SNP genotyping platform is available for commercial purchase from an independent third party.

  19. Discovery of gigantic molecular nanostructures using a flow reaction array as a search engine.

    Science.gov (United States)

    Zang, Hong-Ying; de la Oliva, Andreu Ruiz; Miras, Haralampos N; Long, De-Liang; McBurney, Roy T; Cronin, Leroy

    2014-04-28

    The discovery of gigantic molecular nanostructures like coordination and polyoxometalate clusters is extremely time-consuming since a vast combinatorial space needs to be searched, and even a systematic and exhaustive exploration of the available synthetic parameters relies on a great deal of serendipity. Here we present a synthetic methodology that combines a flow reaction array and algorithmic control to give a chemical 'real-space' search engine leading to the discovery and isolation of a range of new molecular nanoclusters based on [Mo(2)O(2)S(2)](2+)-based building blocks with either fourfold (C4) or fivefold (C5) symmetry templates and linkers. This engine leads us to isolate six new nanoscale cluster compounds: 1, {Mo(10)(C5)}; 2, {Mo(14)(C4)4(C5)2}; 3, {Mo(60)(C4)10}; 4, {Mo(48)(C4)6}; 5, {Mo(34)(C4)4}; 6, {Mo(18)(C4)9}; in only 200 automated experiments from a parameter space spanning ~5 million possible combinations.

  20. Growth-rate-dependent dynamics of a bacterial genetic oscillator

    Science.gov (United States)

    Osella, Matteo; Lagomarsino, Marco Cosentino

    2013-01-01

    Gene networks exhibiting oscillatory dynamics are widespread in biology. The minimal regulatory designs giving rise to oscillations have been implemented synthetically and studied by mathematical modeling. However, most of the available analyses generally neglect the coupling of regulatory circuits with the cellular “chassis” in which the circuits are embedded. For example, the intracellular macromolecular composition of fast-growing bacteria changes with growth rate. As a consequence, important parameters of gene expression, such as ribosome concentration or cell volume, are growth-rate dependent, ultimately coupling the dynamics of genetic circuits with cell physiology. This work addresses the effects of growth rate on the dynamics of a paradigmatic example of genetic oscillator, the repressilator. Making use of empirical growth-rate dependencies of parameters in bacteria, we show that the repressilator dynamics can switch between oscillations and convergence to a fixed point depending on the cellular state of growth, and thus on the nutrients it is fed. The physical support of the circuit (type of plasmid or gene positions on the chromosome) also plays an important role in determining the oscillation stability and the growth-rate dependence of period and amplitude. This analysis has potential application in the field of synthetic biology, and suggests that the coupling between endogenous genetic oscillators and cell physiology can have substantial consequences for their functionality.

  1. Aquaculture genomics, genetics and breeding in the United States: Current status, challenges, and priorities for future research

    Science.gov (United States)

    Advancing the production efficiency and profitability of aquaculture is dependent upon the ability to utilize a diverse array of genetic resources. The ultimate goals of aquaculture genomics, genetics and breeding research are to enhance aquaculture production efficiency, sustainability, product qua...

  2. Flexible Supercapacitors Based on Polyaniline Arrays Coated Graphene Aerogel Electrodes.

    Science.gov (United States)

    Yang, Yu; Xi, Yunlong; Li, Junzhi; Wei, Guodong; Klyui, N I; Han, Wei

    2017-12-01

    Flexible supercapacitors(SCs) made by reduced graphene oxide (rGO)-based aerogel usually suffer from the low energy density, short cycle life and bad flexibility. In this study, a new, synthetic strategy was developed for enhancing the electrochemical performances of rGO aerogel-based supercapacitor via electrodeposition polyaniline arrays on the prepared ultralight rGO aerogel. The novel hybrid composites with coated polyaniline (PANI) arrays growing on the rGO surface can take full advantage of the rich open-pore and excellent conductivity of the crosslinking framework structure of 3D rGO aerogel and high capacitance contribution from the PANI. The obtained hybrid composites exhibit excellent electrochemical performance with a specific capacitance of 432 F g -1 at the current density of 1 A g -1 , robust cycling stability to maintain 85% after 10,000 charge/discharge cycles and high energy density of 25 W h kg -1 . Furthermore, the flexible all-solid-state supercapacitor have superior flexibility and outstanding stability under different bending states from the straight state to the 90° status. The high-performance flexible all-solid-state SCs together with the lighting tests demonstrate it possible for applications in portable electronics.

  3. 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

  4. Resiliency to Victimization: The Role of Genetic Factors

    Science.gov (United States)

    Beaver, Kevin M.; Mancini, Christina; DeLisi, Matt; Vaughn, Michael G.

    2011-01-01

    There is a burgeoning line of criminological research examining the genetic underpinnings to a wide array of antisocial phenotypes. From this perspective, genes are typically viewed as risk factors that increase the odds of various maladaptive behaviors. However, genes can also have protective effects that insulate against the deleterious effects…

  5. 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.

  6. Geo synthetic-reinforced Pavement systems

    International Nuclear Information System (INIS)

    Zornberg, J. G.

    2014-01-01

    Geo synthetics have been used as reinforcement inclusions to improve pavement performance. while there are clear field evidence of the benefit of using geo synthetic reinforcements, the specific conditions or mechanisms that govern the reinforcement of pavements are, at best, unclear and have remained largely unmeasured. Significant research has been recently conducted with the objectives of: (i) determining the relevant properties of geo synthetics that contribute to the enhanced performance of pavement systems, (ii) developing appropriate analytical, laboratory and field methods capable of quantifying the pavement performance, and (iii) enabling the prediction of pavement performance as a function of the properties of the various types of geo synthetics. (Author)

  7. Methods and Tools for the Analysis, Verification and Synthesis of Genetic Logic Circuits,

    DEFF Research Database (Denmark)

    Baig, Hasan

    2017-01-01

    . This usually requires simulating the mathematical models of these genetic circuits and perceive whether or not the circuit behaves appropriately. Furthermore, synthetic biology utilizes the concepts from electronic design automation (EDA) of abstraction and automated construction to generate genetic circuits...... that the proposed approach is effective to determine the variation in the behavior of genetic circuits when the circuit’s parameters are changed. In addition, the thesis also attempts to propose a synthesis and technology mapping tool, called GeneTech, for genetic circuits. It allows users to construct a genetic...... important design characteristics. This thesis also introduces an automated approach to analyze the behavior of genetic logic circuits from the simulation data. With this capability, the boolean logic of complex genetic circuits can be analyzed and/or verified automatically. It is also shown in this thesis...

  8. A circular aperture array for ultrasonic tomography and quantitative NDE

    Energy Technology Data Exchange (ETDEWEB)

    Nielsen, S A

    1998-08-01

    The main topics of this thesis are ultrasonic tomography and ultrasonic determination of elastic stiffness constants. Both issues are based on a synthetic array with transducer elements distributed uniformly along a circular aperture, i.e., a circular aperture array. The issues are treated both theoretically and experimentally by broadband pulse techniques. Ultrasonic tomography, UCT, from a circular aperture is a relatively new imaging technique in Non-destructive Evaluation (NDE) to acquire cross sectional images in bulk materials. A filtered back-projection algorithm is used to reconstruct images in four different experiments and results of attenuation, velocity and reflection tomograms in Plexiglas of AlSi-alloy cylinders are presented. Two kinds of ultrasonic tomography are introduced: bistatic and monostatic imaging. Both techniques are verified experimentally by Plexiglas cylinders. Different reconstruction artifacts are discussed and theoretical resolution constraints are discussed for various configurations of the circular aperture array. The monostatic technique is used in volumetric imaging. In the experimental verification artificial and real discontinuities in a cylindrical AlSi-alloy are compared with similar discontinuities in a Plexiglas specimen. Finally, some limitations to UCT are discussed. The circular aperture array is used to determine five independent elastic stiffness constants of a unidirectional glass/PET (Poly Ethylene Teraphtalate) laminate. Energy flux propagation and attenuation of ultrasonic waves are considered and velocity surfaces are calculated for different planes of interest. Relations between elastic stiffness constants and engineering constants (i.e., Young`s moduli, shear moduli and Poisson`s ratios) are discussed for an orthotropic composite. Six micromechanical theories are reviewed, and expressions predicting the elastic engineering constants are evaluated. The micromechanical predicted elastic stiffness constants for the

  9. Comparing genetic variants detected in the 1000 genomes project ...

    Indian Academy of Sciences (India)

    Single-nucleotide polymorphisms (SNPs) determined based on SNP arrays from the international HapMap consortium (HapMap) and the genetic variants detected in the 1000 genomes project (1KGP) can serve as two references for genomewide association studies (GWAS). We conducted comparative analyses to provide ...

  10. Models for synthetic biology.

    Science.gov (United States)

    Kaznessis, Yiannis N

    2007-11-06

    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.

  11. A Spaceborne Synthetic Aperture Radar Partial Fixed-Point Imaging System Using a Field- Programmable Gate Array-Application-Specific Integrated Circuit Hybrid Heterogeneous Parallel Acceleration Technique.

    Science.gov (United States)

    Yang, Chen; Li, Bingyi; Chen, Liang; Wei, Chunpeng; Xie, Yizhuang; Chen, He; Yu, Wenyue

    2017-06-24

    With the development of satellite load technology and very large scale integrated (VLSI) circuit technology, onboard real-time synthetic aperture radar (SAR) imaging systems have become a solution for allowing rapid response to disasters. A key goal of the onboard SAR imaging system design is to achieve high real-time processing performance with severe size, weight, and power consumption constraints. In this paper, we analyse the computational burden of the commonly used chirp scaling (CS) SAR imaging algorithm. To reduce the system hardware cost, we propose a partial fixed-point processing scheme. The fast Fourier transform (FFT), which is the most computation-sensitive operation in the CS algorithm, is processed with fixed-point, while other operations are processed with single precision floating-point. With the proposed fixed-point processing error propagation model, the fixed-point processing word length is determined. The fidelity and accuracy relative to conventional ground-based software processors is verified by evaluating both the point target imaging quality and the actual scene imaging quality. As a proof of concept, a field- programmable gate array-application-specific integrated circuit (FPGA-ASIC) hybrid heterogeneous parallel accelerating architecture is designed and realized. The customized fixed-point FFT is implemented using the 130 nm complementary metal oxide semiconductor (CMOS) technology as a co-processor of the Xilinx xc6vlx760t FPGA. A single processing board requires 12 s and consumes 21 W to focus a 50-km swath width, 5-m resolution stripmap SAR raw data with a granularity of 16,384 × 16,384.

  12. Estimating receiver functions on dense arrays: application to the IRIS Community Wavefield Experiment in Oklahoma

    Science.gov (United States)

    Zhong, M.; Zhan, Z.

    2017-12-01

    Receiver functions (RF) estimated on dense arrays have been widely used for studies of Earth structures at different scales. However, there are still challenges in estimating and interpreting RF images due to non-uniqueness of deconvolution, noise in data, and lack of uncertainty. Here, we develop a dense-array-based RF method towards robust and high-resolution RF images. We cast RF images as the models in a sparsity-promoted inverse problem, in which waveforms from multiple events recorded by neighboring stations are jointly inverted. We use the Neighborhood Algorithm to find the optimal model (i.e., RF image) as well as an ensemble of models for further uncertainty quantification. Synthetic tests and application to the IRIS Community Wavefield Experiment in Oklahoma demonstrate that the new method is able to deal with challenging dataset, retrieve reliable high-resolution RF images, and provide realistic uncertainty estimates.

  13. Improvement of resolution in full-view linear-array photoacoustic computed tomography using a novel adaptive weighting method

    Science.gov (United States)

    Omidi, Parsa; Diop, Mamadou; Carson, Jeffrey; Nasiriavanaki, Mohammadreza

    2017-03-01

    Linear-array-based photoacoustic computed tomography is a popular methodology for deep and high resolution imaging. However, issues such as phase aberration, side-lobe effects, and propagation limitations deteriorate the resolution. The effect of phase aberration due to acoustic attenuation and constant assumption of the speed of sound (SoS) can be reduced by applying an adaptive weighting method such as the coherence factor (CF). Utilizing an adaptive beamforming algorithm such as the minimum variance (MV) can improve the resolution at the focal point by eliminating the side-lobes. Moreover, invisibility of directional objects emitting parallel to the detection plane, such as vessels and other absorbing structures stretched in the direction perpendicular to the detection plane can degrade resolution. In this study, we propose a full-view array level weighting algorithm in which different weighs are assigned to different positions of the linear array based on an orientation algorithm which uses the histogram of oriented gradient (HOG). Simulation results obtained from a synthetic phantom show the superior performance of the proposed method over the existing reconstruction methods.

  14. Genetic diversity of carotenoid-rich bananas evaluated by Diversity Arrays Technology (DArT

    Directory of Open Access Journals (Sweden)

    Edson P. Amorim

    2009-01-01

    Full Text Available The aim of this work was to evaluate the carotenoid content and genetic variability of banana accessions from the Musa germplasm collection held at Embrapa Cassava and Tropical Fruits, Brazil. Forty-two samples were analyzed, including 21 diploids, 19 triploids and two tetraploids. The carotenoid content was analyzed spectrophotometrically and genetic variability was estimated using 653 DArT markers. The average carotenoid content was 4.73 µg.g-1, and ranged from 1.06 µg.g-1 for the triploid Nanica (Cavendish group to 19.24 µg.g-1 for the triploid Saney. The diploids Modok Gier and NBA-14 and the triploid Saney had a carotenoid content that was, respectively, 7-fold, 6-fold and 9-fold greater than that of cultivars from the Cavendish group (2.19 µg.g-1. The mean similarity among the 42 accessions was 0.63 (range: 0.24 to 1.00. DArT analysis revealed extensive genetic variability in accessions from the Embrapa Musa germplasm bank.

  15. Recoding aminoacyl-tRNA synthetases for synthetic biology by rational protein-RNA engineering.

    Science.gov (United States)

    Hadd, Andrew; Perona, John J

    2014-12-19

    We have taken a rational approach to redesigning the amino acid binding and aminoacyl-tRNA pairing specificities of bacterial glutaminyl-tRNA synthetase. The four-stage engineering incorporates generalizable design principles and improves the pairing efficiency of noncognate glutamate with tRNA(Gln) by over 10(5)-fold compared to the wild-type enzyme. Better optimized designs of the protein-RNA complex include substantial reengineering of the globular core region of the tRNA, demonstrating a role for specific tRNA nucleotides in specifying the identity of the genetically encoded amino acid. Principles emerging from this engineering effort open new prospects for combining rational and genetic selection approaches to design novel aminoacyl-tRNA synthetases that ligate noncanonical amino acids onto tRNAs. This will facilitate reconstruction of the cellular translation apparatus for applications in synthetic biology.

  16. Three Women Scientists and Their Role in the History of Genetics.

    Science.gov (United States)

    Venville, Grady; Milne, Catherine

    1999-01-01

    Draws on an array of historical documents to delve into the history of genetics and the lives and scientific accomplishments of female geneticists that include Nettie Stevens, Rosalind Franklin, and Barbara McClintock. (Contains 20 references.) (Author/WRM)

  17. Statistics for Learning Genetics

    Science.gov (United States)

    Charles, Abigail Sheena

    , although the necessity for infusing these quantitative subjects with genetics and, overall, the biological sciences is growing (topics including synthetic biology, molecular systems biology and phylogenetics) there remains little time in the semester to be dedicated to the consolidation of learning and understanding.

  18. Yeast synthetic biology for the production of recombinant therapeutic proteins.

    Science.gov (United States)

    Kim, Hyunah; Yoo, Su Jin; Kang, Hyun Ah

    2015-02-01

    The production of recombinant therapeutic proteins is one of the fast-growing areas of molecular medicine and currently plays an important role in treatment of several diseases. Yeasts are unicellular eukaryotic microbial host cells that offer unique advantages in producing biopharmaceutical proteins. Yeasts are capable of robust growth on simple media, readily accommodate genetic modifications, and incorporate typical eukaryotic post-translational modifications. Saccharomyces cerevisiae is a traditional baker's yeast that has been used as a major host for the production of biopharmaceuticals; however, several nonconventional yeast species including Hansenula polymorpha, Pichia pastoris, and Yarrowia lipolytica have gained increasing attention as alternative hosts for the industrial production of recombinant proteins. In this review, we address the established and emerging genetic tools and host strains suitable for recombinant protein production in various yeast expression systems, particularly focusing on current efforts toward synthetic biology approaches in developing yeast cell factories for the production of therapeutic recombinant proteins. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.

  19. Genetic activity of plant growth regulators, cartolin and benzilandenin, under ionizing radiation

    International Nuclear Information System (INIS)

    Vilenskij, E.P.

    1987-01-01

    Protective effects of a new cytokinin-type growth regulator cartolin (CRT) are established on a genetic test system of waxy-changes in pollen barley grains under acute irradiation of growing plants. It is shown that the CRT effect is similar to that of synthetic cytokinin benziladenin

  20. Comparison between different encoding schemes for synthetic aperture imaging

    DEFF Research Database (Denmark)

    Nikolov, Svetoslav; Jensen, Jørgen Arendt

    2002-01-01

    and spatio-temporal encoding was investigated. Experiments on wire phantom in water were carried out to quantify the gain from the different encodings. The gain in SNR using an FM modulated pulse is 12 dB. The penetration depth of the images was studied using tissue mimicking phantom with frequency dependent......Synthetic transmit aperture ultrasound (STAU) imaging can create images with as low as 2 emissions, making it attractive for 3D real-time imaging. Two are the major problems to be solved: (1) complexity of the hardware involved, and (2) poor image quality due to low signal to noise ratio (SNR). We...... attenuation of 0.5 dB/(cm MHz). The combination of spatial and temporal encoding have highest penetration depth. Images to a depth of 110 mm, can successfully be made with contrast resolution comparable to that of a linear array image. The in-vivo scans show that the motion artifacts do not significantly...

  1. Coupling in reflector arrays

    DEFF Research Database (Denmark)

    Appel-Hansen, Jørgen

    1968-01-01

    In order to reduce the space occupied by a reflector array, it is desirable to arrange the array antennas as close to each other as possible; however, in this case coupling between the array antennas will reduce the reflecting properties of the reflector array. The purpose of the present communic......In order to reduce the space occupied by a reflector array, it is desirable to arrange the array antennas as close to each other as possible; however, in this case coupling between the array antennas will reduce the reflecting properties of the reflector array. The purpose of the present...

  2. Meeting Report: Synthetic Biology Jamboree for Undergraduates

    Science.gov (United States)

    Campbell, A. Malcolm

    2005-01-01

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

  3. 21 CFR 73.1200 - Synthetic iron oxide.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Synthetic iron oxide. 73.1200 Section 73.1200 Food... COLOR ADDITIVES EXEMPT FROM CERTIFICATION Drugs § 73.1200 Synthetic iron oxide. (a) Identity. (1) The color additive synthetic iron oxide consists of any one or any combination of synthetically prepared...

  4. 21 CFR 73.200 - Synthetic iron oxide.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Synthetic iron oxide. 73.200 Section 73.200 Food... COLOR ADDITIVES EXEMPT FROM CERTIFICATION Foods § 73.200 Synthetic iron oxide. (a) Identity. (1) The color additive synthetic iron oxide consists of any one or any combination of synthetically prepared...

  5. 21 CFR 172.888 - Synthetic petroleum wax.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Synthetic petroleum wax. 172.888 Section 172.888... CONSUMPTION Multipurpose Additives § 172.888 Synthetic petroleum wax. Synthetic petroleum wax may be safely used in or on foods in accordance with the following conditions: (a) Synthetic petroleum wax is a...

  6. Biochips Containing Arrays of Carbon-Nanotube Electrodes

    Science.gov (United States)

    Li, Jun; Meyyappan, M.; Koehne, Jessica; Cassell, Alan; Chen, Hua

    2008-01-01

    Biochips containing arrays of nanoelectrodes based on multiwalled carbon nanotubes (MWCNTs) are being developed as means of ultrasensitive electrochemical detection of specific deoxyribonucleic acid (DNA) and messenger ribonucleic acid (mRNA) biomarkers for purposes of medical diagnosis and bioenvironmental monitoring. In mass production, these biochips could be relatively inexpensive (hence, disposable). These biochips would be integrated with computer-controlled microfluidic and microelectronic devices in automated hand-held and bench-top instruments that could be used to perform rapid in vitro genetic analyses with simplified preparation of samples. Carbon nanotubes are attractive for use as nanoelectrodes for detection of biomolecules because of their nanoscale dimensions and their chemical properties.

  7. 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.

  8. A model for improving microbial biofuel production using a synthetic feedback loop

    Energy Technology Data Exchange (ETDEWEB)

    Dunlop, Mary; Keasling, Jay; Mukhopadhyay, Aindrila

    2011-07-14

    Cells use feedback to implement a diverse range of regulatory functions. Building synthetic feedback control systems may yield insight into the roles that feedback can play in regulation since it can be introduced independently of native regulation, and alternative control architectures can be compared. We propose a model for microbial biofuel production where a synthetic control system is used to increase cell viability and biofuel yields. Although microbes can be engineered to produce biofuels, the fuels are often toxic to cell growth, creating a negative feedback loop that limits biofuel production. These toxic effects may be mitigated by expressing efflux pumps that export biofuel from the cell. We developed a model for cell growth and biofuel production and used it to compare several genetic control strategies for their ability to improve biofuel yields. We show that controlling efflux pump expression directly with a biofuel-responsive promoter is a straight forward way of improving biofuel production. In addition, a feed forward loop controller is shown to be versatile at dealing with uncertainty in biofuel production rates.

  9. Role of Synthetic and Dimensional Synthetic Organic Chemistry in Block Copolymer Micelle Nanosensor Engineering

    DEFF Research Database (Denmark)

    Ek, Pramod Kumar

    This thesis investigated the role of amphiphilic triblock copolymer micelle nanomaterials in nanosensors, with emphasis on the synthesis of micelle particle sensors. The thesis is focused on the role of synthetic and dimensional synthetic organic chemistry in amphiphilic triblock core-shellcorona...

  10. Genetic profiles distinguish different types of hereditary ovarian cancer

    DEFF Research Database (Denmark)

    Domanska, Katarina; Malander, Susanne; Staaf, Johan

    2010-01-01

    (HBOC) syndrome and the hereditary non-polyposis colorectal cancer (HNPCC) syndrome. Genome-wide array comparative genomic hybridization was applied to 12 HBOC associated tumors with BRCA1 mutations and 8 HNPCC associated tumors with mismatch repair gene mutations with 24 sporadic ovarian cancers......Heredity represents the strongest risk factor for ovarian cancer with disease predisposing mutations identified in 15% of the tumors. With the aim to identify genetic classifiers for hereditary ovarian cancer, we profiled hereditary ovarian cancers linked to the hereditary breast and ovarian cancer...... that HBOC and HNPCC associated ovarian cancer develop along distinct genetic pathways and genetic profiles can thus be applied to distinguish between different types of hereditary ovarian cancer....

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

    DEFF Research Database (Denmark)

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

    of genotype-to-phenotype. To achieve this, we have developed orthologous protein prediction software that utilizes genus-wide genetic diversity. The approach is optimized for large data sets, based on BLASTp considering protein identity and alignment coverage, and clustering using single linkage of bi......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......-directional hits. The result is orthologous protein families describing the genomic and functional features of individual species, clades and the core/pan genome of Aspergillus; and applicable to genotype-to-phenotype analyses in other microbial genera....

  12. Word selection affects perceptions of synthetic biology

    Directory of Open Access Journals (Sweden)

    Tonidandel Scott

    2011-07-01

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

  13. Oligonucleotide array discovery of polymorphisms in cultivated tomato (Solanum lycopersicum L. reveals patterns of SNP variation associated with breeding

    Directory of Open Access Journals (Sweden)

    Zhu Tong

    2009-10-01

    Full Text Available Abstract Background Cultivated tomato (Solanum lycopersicum L. has narrow genetic diversity that makes it difficult to identify polymorphisms between elite germplasm. We explored array-based single feature polymorphism (SFP discovery as a high-throughput approach for marker development in cultivated tomato. Results Three varieties, FL7600 (fresh-market, OH9242 (processing, and PI114490 (cherry were used as a source of genomic DNA for hybridization to oligonucleotide arrays. Identification of SFPs was based on outlier detection using regression analysis of normalized hybridization data within a probe set for each gene. A subset of 189 putative SFPs was sequenced for validation. The rate of validation depended on the desired level of significance (α used to define the confidence interval (CI, and ranged from 76% for polymorphisms identified at α ≤ 10-6 to 60% for those identified at α ≤ 10-2. Validation percentage reached a plateau between α ≤ 10-4 and α ≤ 10-7, but failure to identify known SFPs (Type II error increased dramatically at α ≤ 10-6. Trough sequence validation, we identified 279 SNPs and 27 InDels in 111 loci. Sixty loci contained ≥ 2 SNPs per locus. We used a subset of validated SNPs for genetic diversity analysis of 92 tomato varieties and accessions. Pairwise estimation of θ (Fst suggested significant differentiation between collections of fresh-market, processing, vintage, Latin American (landrace, and S. pimpinellifolium accessions. The fresh-market and processing groups displayed high genetic diversity relative to vintage and landrace groups. Furthermore, the patterns of SNP variation indicated that domestication and early breeding practices have led to progressive genetic bottlenecks while modern breeding practices have reintroduced genetic variation into the crop from wild species. Finally, we examined the ratio of non-synonymous (Ka to synonymous substitutions (Ks for 20 loci with multiple SNPs (≥ 4 per

  14. Non-destructive ultrasonic techniques for classifying and reconstructing defects; ALOK, phased arrays, holography-SAFT

    International Nuclear Information System (INIS)

    Hoeller, P.; Schmitz, V.; Mueller, W.; Gebhardt, W.; Barbian, O.A.

    1983-01-01

    The only way to achieve ultrasonic testing methods capable of reconstructing defects or inhomogeneities is to measure those data that are related to the geometry of the reflector. These are phase and time-of-flight as a function of the locus of incidence. For this purpose several synthetic aperture methods have been developed in recent years by our institute: ALOK and phased arrays as searching and analysing systems, especially for in-service inspection of nuclear power plants; and holography and SAFT as analysing systems. Their ability to detect, localize, classify and reconstruct defects is discussed. (author)

  15. Metformin is synthetically lethal with glucose withdrawal in cancer cells.

    Science.gov (United States)

    Menendez, Javier A; Oliveras-Ferraros, Cristina; Cufí, Sílvia; Corominas-Faja, Bruna; Joven, Jorge; Martin-Castillo, Begoña; Vazquez-Martin, Alejandro

    2012-08-01

    Glucose deprivation is a distinctive feature of the tumor microecosystem caused by the imbalance between poor supply and an extraordinarily high consumption rate. The metabolic reprogramming from mitochondrial respiration to aerobic glycolysis in cancer cells (the "Warburg effect") is linked to oncogenic transformation in a manner that frequently implies the inactivation of metabolic checkpoints such as the energy rheostat AMP-activated protein kinase (AMPK). Because the concept of synthetic lethality in oncology can be applied not only to genetic and epigenetic intrinsic differences between normal and cancer cells but also to extrinsic ones such as altered microenvironment, we recently hypothesized that stress-energy mimickers such as the AMPK agonist metformin should produce metabolic synthetic lethality in a glucose-starved cell culture milieu imitating the adverse tumor growth conditions in vivo. Under standard high-glucose conditions, metformin supplementation mostly caused cell cycle arrest without signs of apoptotic cell death. Under glucose withdrawal stress, metformin supplementation circumvented the ability of oncogenes (e.g., HER2) to protect breast cancer cells from glucose-deprivation apoptosis. Significantly, representative cell models of breast cancer heterogeneity underwent massive apoptosis (by >90% in some cases) when glucose-starved cell cultures were supplemented with metformin. Our current findings may uncover crucial issues regarding the cell-autonomous metformin's anti-cancer actions: (1) The offently claimed clinically irrelevant, non-physiological concentrations needed to observe the metformin's anti-cancer effects in vitro merely underlie the artifactual interference of erroneous glucose-rich experimental conditions that poorly reflect glucose-starved in vivo conditions; (2) the preferential killing of cancer stem cells (CSC) by metformin may simply expose the best-case scenario for its synthetically lethal activity because an increased

  16. Air data system optimization using a genetic algorithm

    Science.gov (United States)

    Deshpande, Samir M.; Kumar, Renjith R.; Seywald, Hans; Siemers, Paul M., III

    1992-01-01

    An optimization method for flush-orifice air data system design has been developed using the Genetic Algorithm approach. The optimization of the orifice array minimizes the effect of normally distributed random noise in the pressure readings on the calculation of air data parameters, namely, angle of attack, sideslip angle and freestream dynamic pressure. The optimization method is applied to the design of Pressure Distribution/Air Data System experiment (PD/ADS) proposed for inclusion in the Aeroassist Flight Experiment (AFE). Results obtained by the Genetic Algorithm method are compared to the results obtained by conventional gradient search method.

  17. Directed genetic modification of African horse sickness virus by reverse genetics

    Directory of Open Access Journals (Sweden)

    Elaine Vermaak

    2015-07-01

    Full Text Available African horse sickness virus (AHSV, a member of the Orbivirus genus in the family Reoviridae, is an arthropod-transmitted pathogen that causes a devastating disease in horses with a mortality rate greater than 90%. Fundamental research on AHSV and the development of safe, efficacious vaccines could benefit greatly from an uncomplicated genetic modification method to generate recombinant AHSV. We demonstrate that infectious AHSV can be recovered by transfection of permissive mammalian cells with transcripts derived in vitro from purified AHSV core particles. These findings were expanded to establish a genetic modification system for AHSV that is based on transfection of the cells with a mixture of purified core transcripts and a synthetic T7 transcript. This approach was applied successfully to recover a directed cross-serotype reassortant AHSV and to introduce a marker sequence into the viral genome. The ability to manipulate the AHSV genome and engineer specific mutants will increase understanding of AHSV replication and pathogenicity, as well as provide a tool for generating designer vaccine strains.

  18. Synthetic Biology for Specialty Chemicals.

    Science.gov (United States)

    Markham, Kelly A; Alper, Hal S

    2015-01-01

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

  19. Mammalian synthetic biology: emerging medical applications.

    Science.gov (United States)

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

    2015-05-06

    In this review, we discuss new emerging medical applications of the rapidly evolving field of mammalian synthetic biology. We start with simple mammalian synthetic biological components and move towards more complex and therapy-oriented gene circuits. A comprehensive list of ON-OFF switches, categorized into transcriptional, post-transcriptional, translational and post-translational, is presented in the first sections. Subsequently, Boolean logic gates, synthetic mammalian oscillators and toggle switches will be described. Several synthetic gene networks are further reviewed in the medical applications section, including cancer therapy gene circuits, immuno-regulatory networks, among others. The final sections focus on the applicability of synthetic gene networks to drug discovery, drug delivery, receptor-activating gene circuits and mammalian biomanufacturing processes. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  20. Concurrent array-based queue

    Science.gov (United States)

    Heidelberger, Philip; Steinmacher-Burow, Burkhard

    2015-01-06

    According to one embodiment, a method for implementing an array-based queue in memory of a memory system that includes a controller includes configuring, in the memory, metadata of the array-based queue. The configuring comprises defining, in metadata, an array start location in the memory for the array-based queue, defining, in the metadata, an array size for the array-based queue, defining, in the metadata, a queue top for the array-based queue and defining, in the metadata, a queue bottom for the array-based queue. The method also includes the controller serving a request for an operation on the queue, the request providing the location in the memory of the metadata of the queue.

  1. Protease-sensitive synthetic prions.

    Directory of Open Access Journals (Sweden)

    David W Colby

    2010-01-01

    Full Text Available Prions arise when the cellular prion protein (PrP(C undergoes a self-propagating conformational change; the resulting infectious conformer is designated PrP(Sc. Frequently, PrP(Sc is protease-resistant but protease-sensitive (s prions have been isolated in humans and other animals. We report here that protease-sensitive, synthetic prions were generated in vitro during polymerization of recombinant (rec PrP into amyloid fibers. In 22 independent experiments, recPrP amyloid preparations, but not recPrP monomers or oligomers, transmitted disease to transgenic mice (n = 164, denoted Tg9949 mice, that overexpress N-terminally truncated PrP. Tg9949 control mice (n = 174 did not spontaneously generate prions although they were prone to late-onset spontaneous neurological dysfunction. When synthetic prion isolates from infected Tg9949 mice were serially transmitted in the same line of mice, they exhibited sPrP(Sc and caused neurodegeneration. Interestingly, these protease-sensitive prions did not shorten the life span of Tg9949 mice despite causing extensive neurodegeneration. We inoculated three synthetic prion isolates into Tg4053 mice that overexpress full-length PrP; Tg4053 mice are not prone to developing spontaneous neurological dysfunction. The synthetic prion isolates caused disease in 600-750 days in Tg4053 mice, which exhibited sPrP(Sc. These novel synthetic prions demonstrate that conformational changes in wild-type PrP can produce mouse prions composed exclusively of sPrP(Sc.

  2. Single-Crystalline Ultrathin Nickel Nanosheets Array from In Situ Topotactic Reduction for Active and Stable Electrocatalysis.

    Science.gov (United States)

    Kuang, Yun; Feng, Guang; Li, Pengsong; Bi, Yongmin; Li, Yaping; Sun, Xiaoming

    2016-01-11

    Simultaneously synthesizing and structuring atomically thick or ultrathin 2D non-precious metal nanocrystal may offer a new class of materials to replace the state-of-art noble-metal electrocatalysts; however, the synthetic strategy is the bottleneck which should be urgently solved. Here we report the synthesis of an ultrathin nickel nanosheet array (Ni-NSA) through in situ topotactic reduction from Ni(OH)2 array precursors. The Ni nanosheets showed a single-crystalline lamellar structure with only ten atomic layers in thickness and an exposed (111) facet. Combined with a superaerophobic (low bubble adhesive) arrayed structure the Ni-NSAs exhibited a dramatic enhancement on both activity and stability towards the hydrazine-oxidation reaction (HzOR) relative to platinum. Furthermore, the partial oxidization of Ni-NSAs in ambient atmosphere resulted in effective water-splitting electrocatalysts for the hydrogen-evolution reaction (HER). © 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

  3. Variance decomposition of protein profiles from antibody arrays using a longitudinal twin model

    Directory of Open Access Journals (Sweden)

    Kato Bernet S

    2011-11-01

    Full Text Available Abstract Background The advent of affinity-based proteomics technologies for global protein profiling provides the prospect of finding new molecular biomarkers for common, multifactorial disorders. The molecular phenotypes obtained from studies on such platforms are driven by multiple sources, including genetic, environmental, and experimental components. In characterizing the contribution of different sources of variation to the measured phenotypes, the aim is to facilitate the design and interpretation of future biomedical studies employing exploratory and multiplexed technologies. Thus, biometrical genetic modelling of twin or other family data can be used to decompose the variation underlying a phenotype into biological and experimental components. Results Using antibody suspension bead arrays and antibodies from the Human Protein Atlas, we study unfractionated serum from a longitudinal study on 154 twins. In this study, we provide a detailed description of how the variation in a molecular phenotype in terms of protein profile can be decomposed into familial i.e. genetic and common environmental; individual environmental, short-term biological and experimental components. The results show that across 69 antibodies analyzed in the study, the median proportion of the total variation explained by familial sources is 12% (IQR 1-22%, and the median proportion of the total variation attributable to experimental sources is 63% (IQR 53-72%. Conclusion The variability analysis of antibody arrays highlights the importance to consider variability components and their relative contributions when designing and evaluating studies for biomarker discoveries with exploratory, high-throughput and multiplexed methods.

  4. BAC CGH-array identified specific small-scale genomic imbalances in diploid DMBA-induced rat mammary tumors

    International Nuclear Information System (INIS)

    Samuelson, Emma; Karlsson, Sara; Partheen, Karolina; Nilsson, Staffan; Szpirer, Claude; Behboudi, Afrouz

    2012-01-01

    Development of breast cancer is a multistage process influenced by hormonal and environmental factors as well as by genetic background. The search for genes underlying this malignancy has recently been highly productive, but the etiology behind this complex disease is still not understood. In studies using animal cancer models, heterogeneity of the genetic background and environmental factors is reduced and thus analysis and identification of genetic aberrations in tumors may become easier. To identify chromosomal regions potentially involved in the initiation and progression of mammary cancer, in the present work we subjected a subset of experimental mammary tumors to cytogenetic and molecular genetic analysis. Mammary tumors were induced with DMBA (7,12-dimethylbenz[a]anthrazene) in female rats from the susceptible SPRD-Cu3 strain and from crosses and backcrosses between this strain and the resistant WKY strain. We first produced a general overview of chromosomal aberrations in the tumors using conventional kartyotyping (G-banding) and Comparative Genome Hybridization (CGH) analyses. Particular chromosomal changes were then analyzed in more details using an in-house developed BAC (bacterial artificial chromosome) CGH-array platform. Tumors appeared to be diploid by conventional karyotyping, however several sub-microscopic chromosome gains or losses in the tumor material were identified by BAC CGH-array analysis. An oncogenetic tree analysis based on the BAC CGH-array data suggested gain of rat chromosome (RNO) band 12q11, loss of RNO5q32 or RNO6q21 as the earliest events in the development of these mammary tumors. Some of the identified changes appear to be more specific for DMBA-induced mammary tumors and some are similar to those previously reported in ACI rat model for estradiol-induced mammary tumors. The later group of changes is more interesting, since they may represent anomalies that involve genes with a critical role in mammary tumor development. Genetic

  5. 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.

  6. Development and implementation of a highly-multiplexed SNP array for genetic mapping in maritime pine and comparative mapping with loblolly pine

    Directory of Open Access Journals (Sweden)

    Garnier-Géré Pauline

    2011-07-01

    Full Text Available Abstract Background Single nucleotide polymorphisms (SNPs are the most abundant source of genetic variation among individuals of a species. New genotyping technologies allow examining hundreds to thousands of SNPs in a single reaction for a wide range of applications such as genetic diversity analysis, linkage mapping, fine QTL mapping, association studies, marker-assisted or genome-wide selection. In this paper, we evaluated the potential of highly-multiplexed SNP genotyping for genetic mapping in maritime pine (Pinus pinaster Ait., the main conifer used for commercial plantation in southwestern Europe. Results We designed a custom GoldenGate assay for 1,536 SNPs detected through the resequencing of gene fragments (707 in vitro SNPs/Indels and from Sanger-derived Expressed Sequenced Tags assembled into a unigene set (829 in silico SNPs/Indels. Offspring from three-generation outbred (G2 and inbred (F2 pedigrees were genotyped. The success rate of the assay was 63.6% and 74.8% for in silico and in vitro SNPs, respectively. A genotyping error rate of 0.4% was further estimated from segregating data of SNPs belonging to the same gene. Overall, 394 SNPs were available for mapping. A total of 287 SNPs were integrated with previously mapped markers in the G2 parental maps, while 179 SNPs were localized on the map generated from the analysis of the F2 progeny. Based on 98 markers segregating in both pedigrees, we were able to generate a consensus map comprising 357 SNPs from 292 different loci. Finally, the analysis of sequence homology between mapped markers and their orthologs in a Pinus taeda linkage map, made it possible to align the 12 linkage groups of both species. Conclusions Our results show that the GoldenGate assay can be used successfully for high-throughput SNP genotyping in maritime pine, a conifer species that has a genome seven times the size of the human genome. This SNP-array will be extended thanks to recent sequencing effort using

  7. Programmable cellular arrays. Faults testing and correcting in cellular arrays

    International Nuclear Information System (INIS)

    Cercel, L.

    1978-03-01

    A review of some recent researches about programmable cellular arrays in computing and digital processing of information systems is presented, and includes both combinational and sequential arrays, with full arbitrary behaviour, or which can realize better implementations of specialized blocks as: arithmetic units, counters, comparators, control systems, memory blocks, etc. Also, the paper presents applications of cellular arrays in microprogramming, in implementing of a specialized computer for matrix operations, in modeling of universal computing systems. The last section deals with problems of fault testing and correcting in cellular arrays. (author)

  8. [Clinical genealogical and molecular genetic study of patients with mental retardation].

    Science.gov (United States)

    Hryshchenko, N V; B'ichkova, A M; Lyvshyts, A B; Kravchenko, S A; Pampukha, V N; Solov'ev, A A; Kucherenko, A M; Tatarskiĭ, P F; Afanas'eva, N A; Dubrovskaia, E V; Patskun, Ie Y; Zymak-Zakutnaia, N O; Nykytchina, T V; Lohysh, S Iu; Lyvshyts, L A

    2012-01-01

    The results of clinical, genealogical, cytogenetic and molecular genetic studies of 113 patients from 96 families with different forms of mental retardation from Ukraine are presented. This study was held as part of the CHERISH project of the 7-th Framework Program. The aim of the project is to improve diagnostics of mental retardation in children in Eastern Europe and Central Asia through detailed analysis of known chromosomal and gene's aberrations and to find the new gene-candidates that cause mental retardation. All patients have normal chromosome number (46XY or 46XX). The cases with fragile-X syndrome were eliminated using molecular genetic methods. Genome rearrangements were found among 28 patients using cytogenetic analysis, multiplex ligation-dependent probe amplification (MLPA analysis) ofsubtelomeric regions and array-based comparative genomic hybridisation (array CGH screening). In 10 cases known pathogenic CNV's were identified, 11 cases are unknown aberrations; their pathogenicity is being determined. The rest cases are known nonpathogenic gene rearrangements. Obtained results show the strong genetic heterogeneity of hereditary forms of mental retardation. The further studies will allow to identificate genes candidates and certain mutations in these genes that may be associated with this pathology.

  9. Construction of new synthetic biology tools for the control of gene expression in the cyanobacterium Synechococcus sp. strain PCC 7002.

    Science.gov (United States)

    Zess, Erin K; Begemann, Matthew B; Pfleger, Brian F

    2016-02-01

    Predictive control of gene expression is an essential tool for developing synthetic biological systems. The current toolbox for controlling gene expression in cyanobacteria is a barrier to more in-depth genetic analysis and manipulation. Towards relieving this bottleneck, this work describes the use of synthetic biology to construct an anhydrotetracycline-based induction system and adapt a trans-acting small RNA (sRNA) system for use in the cyanobacterium Synechococcus sp. strain PCC 7002. An anhydrotetracycline-inducible promoter was developed to maximize intrinsic strength and dynamic range. The resulting construct, PEZtet , exhibited tight repression and a maximum 32-fold induction upon addition of anhydrotetracycline. Additionally, a sRNA system based on the Escherichia coli IS10 RNA-IN/OUT regulator was adapted for use in Synechococcus sp. strain PCC 7002. This system exhibited 70% attenuation of target gene expression, providing a demonstration of the use of sRNAs for differential gene expression in cyanobacteria. These systems were combined to produce an inducible sRNA system, which demonstrated 59% attenuation of target gene expression. Lastly, the role of Hfq, a critical component of sRNA systems in E. coli, was investigated. Genetic studies showed that the Hfq homolog in Synechococcus sp. strain PCC 7002 did not impact repression by the engineered sRNA system. In summary, this work describes new synthetic biology tools that can be applied to physiological studies, metabolic engineering, or sRNA platforms in Synechococcus sp. strain PCC 7002. © 2015 Wiley Periodicals, Inc.

  10. Teaching Synthetic Biology, Bioinformatics and Engineering to Undergraduates: The Interdisciplinary Build-a-Genome Course

    Science.gov (United States)

    Dymond, Jessica S.; Scheifele, Lisa Z.; Richardson, Sarah; Lee, Pablo; Chandrasegaran, Srinivasan; Bader, Joel S.; Boeke, Jef D.

    2009-01-01

    A major challenge in undergraduate life science curricula is the continual evaluation and development of courses that reflect the constantly shifting face of contemporary biological research. Synthetic biology offers an excellent framework within which students may participate in cutting-edge interdisciplinary research and is therefore an attractive addition to the undergraduate biology curriculum. This new discipline offers the promise of a deeper understanding of gene function, gene order, and chromosome structure through the de novo synthesis of genetic information, much as synthetic approaches informed organic chemistry. While considerable progress has been achieved in the synthesis of entire viral and prokaryotic genomes, fabrication of eukaryotic genomes requires synthesis on a scale that is orders of magnitude higher. These high-throughput but labor-intensive projects serve as an ideal way to introduce undergraduates to hands-on synthetic biology research. We are pursuing synthesis of Saccharomyces cerevisiae chromosomes in an undergraduate laboratory setting, the Build-a-Genome course, thereby exposing students to the engineering of biology on a genomewide scale while focusing on a limited region of the genome. A synthetic chromosome III sequence was designed, ordered from commercial suppliers in the form of oligonucleotides, and subsequently assembled by students into ∼750-bp fragments. Once trained in assembly of such DNA “building blocks” by PCR, the students accomplish high-yield gene synthesis, becoming not only technically proficient but also constructively critical and capable of adapting their protocols as independent researchers. Regular “lab meeting” sessions help prepare them for future roles in laboratory science. PMID:19015540

  11. Genetic algorithms applied to nuclear reactor design optimization

    International Nuclear Information System (INIS)

    Pereira, C.M.N.A.; Schirru, R.; Martinez, A.S.

    2000-01-01

    A genetic algorithm is a powerful search technique that simulates natural evolution in order to fit a population of computational structures to the solution of an optimization problem. This technique presents several advantages over classical ones such as linear programming based techniques, often used in nuclear engineering optimization problems. However, genetic algorithms demand some extra computational cost. Nowadays, due to the fast computers available, the use of genetic algorithms has increased and its practical application has become a reality. In nuclear engineering there are many difficult optimization problems related to nuclear reactor design. Genetic algorithm is a suitable technique to face such kind of problems. This chapter presents applications of genetic algorithms for nuclear reactor core design optimization. A genetic algorithm has been designed to optimize the nuclear reactor cell parameters, such as array pitch, isotopic enrichment, dimensions and cells materials. Some advantages of this genetic algorithm implementation over a classical method based on linear programming are revealed through the application of both techniques to a simple optimization problem. In order to emphasize the suitability of genetic algorithms for design optimization, the technique was successfully applied to a more complex problem, where the classical method is not suitable. Results and comments about the applications are also presented. (orig.)

  12. Synthetic Aperture Sequential Beamforming

    DEFF Research Database (Denmark)

    Kortbek, Jacob; Jensen, Jørgen Arendt; Gammelmark, Kim Løkke

    2008-01-01

    A synthetic aperture focusing (SAF) technique denoted Synthetic Aperture Sequential Beamforming (SASB) suitable for 2D and 3D imaging is presented. The technique differ from prior art of SAF in the sense that SAF is performed on pre-beamformed data contrary to channel data. The objective is to im......A synthetic aperture focusing (SAF) technique denoted Synthetic Aperture Sequential Beamforming (SASB) suitable for 2D and 3D imaging is presented. The technique differ from prior art of SAF in the sense that SAF is performed on pre-beamformed data contrary to channel data. The objective...... is to improve and obtain a more range independent lateral resolution compared to conventional dynamic receive focusing (DRF) without compromising frame rate. SASB is a two-stage procedure using two separate beamformers. First a set of Bmode image lines using a single focal point in both transmit and receive...... is stored. The second stage applies the focused image lines from the first stage as input data. The SASB method has been investigated using simulations in Field II and by off-line processing of data acquired with a commercial scanner. The performance of SASB with a static image object is compared with DRF...

  13. Towards a synthetic chloroplast.

    Directory of Open Access Journals (Sweden)

    Christina M Agapakis

    2011-04-01

    Full Text Available The evolution of eukaryotic cells is widely agreed to have proceeded through a series of endosymbiotic events between larger cells and proteobacteria or cyanobacteria, leading to the formation of mitochondria or chloroplasts, respectively. Engineered endosymbiotic relationships between different species of cells are a valuable tool for synthetic biology, where engineered pathways based on two species could take advantage of the unique abilities of each mutualistic partner.We explored the possibility of using the photosynthetic bacterium Synechococcus elongatus PCC 7942 as a platform for studying evolutionary dynamics and for designing two-species synthetic biological systems. We observed that the cyanobacteria were relatively harmless to eukaryotic host cells compared to Escherichia coli when injected into the embryos of zebrafish, Danio rerio, or taken up by mammalian macrophages. In addition, when engineered with invasin from Yersinia pestis and listeriolysin O from Listeria monocytogenes, S. elongatus was able to invade cultured mammalian cells and divide inside macrophages.Our results show that it is possible to engineer photosynthetic bacteria to invade the cytoplasm of mammalian cells for further engineering and applications in synthetic biology. Engineered invasive but non-pathogenic or immunogenic photosynthetic bacteria have great potential as synthetic biological devices.

  14. Whole genome DNA copy number changes identified by high density oligonucleotide arrays

    Directory of Open Access Journals (Sweden)

    Huang Jing

    2004-05-01

    Full Text Available Abstract Changes in DNA copy number are one of the hallmarks of the genetic instability common to most human cancers. Previous micro-array-based methods have been used to identify chromosomal gains and losses; however, they are unable to genotype alleles at the level of single nucleotide polymorphisms (SNPs. Here we describe a novel algorithm that uses a recently developed high-density oligonucleotide array-based SNP genotyping method, whole genome sampling analysis (WGSA, to identify genome-wide chromosomal gains and losses at high resolution. WGSA simultaneously genotypes over 10,000 SNPs by allele-specific hybridisation to perfect match (PM and mismatch (MM probes synthesised on a single array. The copy number algorithm jointly uses PM intensity and discrimination ratios between paired PM and MM intensity values to identify and estimate genetic copy number changes. Values from an experimental sample are compared with SNP-specific distributions derived from a reference set containing over 100 normal individuals to gain statistical power. Genomic regions with statistically significant copy number changes can be identified using both single point analysis and contiguous point analysis of SNP intensities. We identified multiple regions of amplification and deletion using a panel of human breast cancer cell lines. We verified these results using an independent method based on quantitative polymerase chain reaction and found that our approach is both sensitive and specific and can tolerate samples which contain a mixture of both tumour and normal DNA. In addition, by using known allele frequencies from the reference set, statistically significant genomic intervals can be identified containing contiguous stretches of homozygous markers, potentially allowing the detection of regions undergoing loss of heterozygosity (LOH without the need for a matched normal control sample. The coupling of LOH analysis, via SNP genotyping, with copy number

  15. Discovery of novel variants in genotyping arrays improves genotype retention and reduces ascertainment bias

    Directory of Open Access Journals (Sweden)

    Didion John P

    2012-01-01

    Full Text Available Abstract Background High-density genotyping arrays that measure hybridization of genomic DNA fragments to allele-specific oligonucleotide probes are widely used to genotype single nucleotide polymorphisms (SNPs in genetic studies, including human genome-wide association studies. Hybridization intensities are converted to genotype calls by clustering algorithms that assign each sample to a genotype class at each SNP. Data for SNP probes that do not conform to the expected pattern of clustering are often discarded, contributing to ascertainment bias and resulting in lost information - as much as 50% in a recent genome-wide association study in dogs. Results We identified atypical patterns of hybridization intensities that were highly reproducible and demonstrated that these patterns represent genetic variants that were not accounted for in the design of the array platform. We characterized variable intensity oligonucleotide (VINO probes that display such patterns and are found in all hybridization-based genotyping platforms, including those developed for human, dog, cattle, and mouse. When recognized and properly interpreted, VINOs recovered a substantial fraction of discarded probes and counteracted SNP ascertainment bias. We developed software (MouseDivGeno that identifies VINOs and improves the accuracy of genotype calling. MouseDivGeno produced highly concordant genotype calls when compared with other methods but it uniquely identified more than 786000 VINOs in 351 mouse samples. We used whole-genome sequence from 14 mouse strains to confirm the presence of novel variants explaining 28000 VINOs in those strains. We also identified VINOs in human HapMap 3 samples, many of which were specific to an African population. Incorporating VINOs in phylogenetic analyses substantially improved the accuracy of a Mus species tree and local haplotype assignment in laboratory mouse strains. Conclusion The problems of ascertainment bias and missing

  16. Array measurements of long-period microtremors in southwestern Kanto plain, Japan; Kanto heiya nanseibu ni okeru yaya choshuki bido no array kansoku

    Energy Technology Data Exchange (ETDEWEB)

    Yamanaka, H; Sato, H; Kurita, K; Seo, K [Tokyo Institute of Technology, Tokyo (Japan)

    1997-05-27

    Array measurements of long-period microtremors were carried out in the southwestern part of Kanto Plain, Japan, to obtain S-wave velocity structures in sedimentary beds as fundamental data for estimating long-term strong ground motion in Kanto Plain. The major component in a long-term seismic motion observed in Kanto Plain is the surface wave. According to the result of observations on Love wave by Kinoshita et al, the wavelengths of the surface waves of a long-term cycle are 10 to 20 km. Therefore, if an array observation is to be performed at intervals of about two wavelengths, about 40 points will be required to cover the entire Kanto plain. The final phase velocity is decided by averaging phase velocities of each cycle obtained for each data set. The acquired phase velocities are analyzed inversely by using a genetic algorithm to derive the S-wave velocities at each observation point. The present microtremor array observation has used 13 points in the southwestern part of Kanto Plain to acquire S-wave velocity (Vs) distribution in sedimentary beds. It was made clear that beds with Vs of 1.0 km/s and Vs of 1.5 km/s exist in this area between the surface bed and the seismic foundation with Vs of about 3 km/s. 10 refs., 10 figs., 1 tab.

  17. Synthetic Biology: Advancing Biological Frontiers by Building Synthetic Systems

    OpenAIRE

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

    2012-01-01

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

  18. 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.

  19. Induction and transmission of tolerance to the synthetic pesticide emamectin benzoate in field and laboratory populations of diamondback moth.

    Science.gov (United States)

    Rahman, M M; Baker, G; Powis, K J; Roush, R T; Schmidt, O

    2010-08-01

    Field surveys of pest insect pest populations in agroecosystems reveal low but significant levels of tolerance to synthetic and biological pesticides but fail to uncover resistance alleles in test crosses. To study the potential of inducible mechanisms to generate tolerance to synthetic pesticides, we performed baseline susceptibility studies in field and laboratory populations of diamondback moth, Plutella xylostella (L.), to commercial formulations of emamectin benzoate. Pesticide exposure in the field caused elevated levels of tolerance, which decreased in field-collected populations after maintaining insects with pesticide-free diet in the laboratory. Because no significant resistance alleles were identified in back-crossed individuals, the observed increase in tolerance was probably not based on preexisting recessive resistance mechanisms in the population. Instead, the genetic analysis after five and 12 generations is compatible with a transient up-regulation of an immune and metabolic status in tolerant insects that can be transmitted to offspring by a maternal effect. Although the epigenetic effects contributed to incremental increases in tolerance in the first five generations, other resistance mechanisms that are transmitted genetically predominate after 12 generations of increased exposure to the pesticide.

  20. Synthetic biology routes to bio-artificial intelligence

    Science.gov (United States)

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

    2016-01-01

    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). PMID:27903825